Term
| What is the approximate distribution of WBC types in the serum by percentage? |
|
Definition
Neutrophils Like Making Everything Better
1) Neutrophils (57-67%)
2) Lymphocytes (23-33%)
3) Monocytes (including lymphocytes, 3-7%)
4) Eosinophils (1-3%)
5) Basophils (0-1%) |
|
|
Term
Which type of WBC is described by each of the following?
1) Acute inflammatory response cell containing large lysosome granules with hydrolytic enzymes, lysozyme, myeloperoxidase and lactoferrin (binds iron).
2. CD14+, long-lived cells that lie resident in tissues and are activated by IFN-y
3. Cells with "frosted glass" cytoplasm and "kidney shaped nuclei" that differentiate into macrophages in tissues
4. Cells with bi-lobate nuclei packed with large granules containing histaminase and arylsulfatase, that defend against helminthic infections (major basic protein)
5. Rare cells with bi-lobate nuclei that mediate allergic reactions, releasing heparin, histamine, vasoactive amines, and leukotrienes (LTD) |
|
Definition
Page 373
1) Neutrophil
- MPO produces hypochlorous acid from Cl- and H2O2 in respiratory birst
- Lactoferrin binds iron to prevent growth of phagocytosed bacteria and fungi
2) Macrophages- phagocytose bacteria, cell debris and senescent RBCs
3) Monocytes in the blood
4) Eosinophils
- Phagocytose antigen-antibody complexes (type III)
- Produce histaminase and arylsulfatase (limit mast cell effect)
- Defend against helminthes (major basic protein)
5) Basophils (stain with Basic stains) |
|
|
Term
Which of the following is NOT a major cause of eosinophilia
1) Hay fever
2) Hodgkin's lymphoma
3) Churg-Strauss syndrome
4) Hemolytic anemia
5) PCN allergy |
|
Definition
4
Causes of Eosinophilia- NAACP
1) Neoplastic (Hodgkin's and some non-hodkin's lymphoma)
2) Asthma
3) Allergic process (drugs or dermatitis)
4) Collagen vascular disease
5) Parasites (invasive) |
|
|
Term
Which type of blood cell is described by each of the following?
1. Anucleate, biconcave discs with membranes that contain chloride-bicarbonate antiporters, which enable CO2 elimination from the lungs
2. Small cytoplasmic fragments that are derived from megakaryocytes and stored in the spleen, containing dense (ADP and calcium) and alpha granules (vWF and fibrinogen)
3. Cells found in tissues, producing and release histamine, heparin and eosinophil chemotactic factors in response to IgE binding
4. Round, densely staining nuclei with small, pale cytoplasm
5. Cells with eccentric, "clock-face" nuclei, abundant RER and well-developed golgi apparatus. |
|
Definition
1) Erythrocytes
2) Platelets
3) Mast cells (type 1 hypersensitivity)
4) Lymphocytes (B- CD19+CD20+, and T cells- CD3, CD4, CD8)
5) Plasma cell (antigen-specific antibody producers) |
|
|
Term
| What are the major types of Leukocytes in the blood and tissue? |
|
Definition
CBC normally 4,000-10,000 WBC
1) Granulocytes
- Basophils (bilobate)
- Eosinophils (bilobate)
- Neutrophils (multilobate)
2) Mononuclear cells
- Monocytes
- Lymphocytes |
|
|
Term
| What neutrophil abnormality should you look for in vitamin B12/folate deficiency? |
|
Definition
|
|
Term
Describe the formation of a primary hemostastic plug, following vessel injury.
What diagnostic tests should be used to evaluate primary hemostasis? |
|
Definition
Platelet plug-
1) diagnostically- think about platelet count, bleeding time and rCoF (vWF test)
2) Damaged vessels expose collagen fibrils and platelets adhere with Gp1b via vWF that is produced in alpha granules.
- Platelets then produce ADP (dense granules) and TXA2, leading to vasoconstriction and aggregation.
- Release reaction occurs (ADP, TXA2, 5-HT and Calcium), leading to agglutination, and primary plug is overlaid by fibrinogen (produced by alpha-granules)
- Primary plug is stabilized by factor XIII and Thrombasthenin |
|
|
Term
| How long to platelets live vs. RBCs? |
|
Definition
1) RBCs normally live 120 days before being phagocytes by splenic macrophages and broken down into heme and protoporphyrin.
2) Platelets live 8-10 days. |
|
|
Term
| Where to RBCs derive energy from? |
|
Definition
Glucose!
1) 90% from anaerobic glycolysis/lactate production
2) 10% by HMP shunt |
|
|
Term
What do each of the following terms mean in reference to RBCs?
1) Anisocytosis
2) Poikilocytosis
3) Reticulocyte |
|
Definition
1) Varying size
2) Varying shape
3) Immature erythrocytes (erythrocytosis= polycythemia) |
|
|
Term
| What are the major causes of Polycythemia? |
|
Definition
1) Relative polycythemia from cellular dehydration
2) Absolute, appropriate polycythemia from hypoxia
- examples include lung disease, tetralogy of fallot, high altitude
3) Absolute, inappropriate
- Polycythemia rubra vera (hyperviscosity, hypervolemia, hyperhistaminemia, hyperuricemia)
- Ectopic production of EPO from tumor |
|
|
Term
| What are the primary products of activated mast cells in an allergic reaction? |
|
Definition
Activated B cells become IgE-producing plasma cells and IgE molecules bind mast cell-Fc receptors in tissues
1) Degranulation products
- Histamine
- Heparin
- 5-HT
2) Late response
- thromboxane
- prostaglandin D2
- leukotriene C4
- platelet-activating factor
- eosinophil chemotactic factor |
|
|
Term
| Where do mature B cells migrate to from the bone marrow? |
|
Definition
Peripheral lymphoid tissues where they encounter antigens and become plasma cells (also function as APCs with MHC-II)
1) Follicles of LN
2) White pulp of spleen
3) Unencapsulated lymphoid tissue (GALT or MALT) |
|
|
Term
Which of the following statements regarding blood groups is INCORRECT?
1. Individuals with type A blood cannot receive transfusions from individuals with type B blood
2. Type AB individuals can receive blood from any other type
3. Type O individuals can only receive type AB blood
4. Type A individuals produce anti-B antibodies
5. Type O mothers should not be worried about immunlogic injury to her type A fetus. |
|
Definition
3.
Type O blood means that the individual has antibodies against A and B. They can GIVE to anyone, but only receive from O.
anti-Rh-IgG crosses the placenta but anti-AB IgM DOES NOT |
|
|
Term
| Why might a an Rh- pregnant woman be given Rho(D)-IG (Rhogam) during her first delivery? |
|
Definition
If her fetus is Rh+, she will develop anti-Rh IG that can cross the placenta curing subsequent pregnancies and produce hemolytic disease of the newborn (Erythroblastosis fetalis).
Remember, this is different with anti-AB antibodies. Anti-Rh-IgG crosses the placenta but anti-AB IgM DOES NOT |
|
|
Term
Which of the following is NOT a likely result of incompatible blood transfusions?
1. Hemolysis
2. Shock
3. Renal failure
4. Neoplasm
5. Immunological response |
|
Definition
4.
Immunological, Shock, Renal failure and Hemolysis are all characteristic |
|
|
Term
Which coagulation disorder is described by each of the following and what PTT/APTT changes would you expect in each?
1) Decreased synthesis of factors II, VII, IX, X, protein C and protein S
2. Factor IX deficiency
3. Factor VIII deficiency |
|
Definition
1) Vitamin K deficiency
- Both intrinsic (IX) and extrinsic (VII) factors so both APTT and PTT would be prolonged.
- Similar to effect of Warfarin, which is monitored by PTT
2) Hemophilia B (20%)
- Factor VIII is intrinsic pathway, so APTT would prolonged and PTT would be normal
3) Hemophilia A (80%)
- Factor IX is also intrinsic, so APTT would be prolonged and PTT would be normal. |
|
|
Term
| Describe the extrinsic and intrinsic coagulation pathways. |
|
Definition
1) Intrinsic (Contact activation of XII by collagen, basement membrane and activated platelets)
- XII...XI....IX...VIII....X.....V....II....I
2) Extrinsic (Activated by TF/thromboplastin released by vessel endothelial cells.
- VII/TF....X....V....II...I |
|
|
Term
| How can the coagulation cascade activate the complement system? |
|
Definition
1) Activated F XII in the intrinsic pathway activates Prokallikrein to Kallikrein
2) Kallikrein activates plasminogen to plasmin (fibrinolytic), which activates C3 to C3a (as well as producing fibrin degradation products and D-dimers) |
|
|
Term
| How does the Kinin system relate the the coagulation cascade? |
|
Definition
1) XIIa in intrinsic activates this system of serine proteases (Kallikrein from Prokallikrein)
2) Kallikrein activates the fibrinolytic (plasmin) system and activates Bradykinin from HMWK.
3) Bradykinin (inhibited by ACE) acts as a vasodilator, increasing vessel permeability and pain sensation as well. |
|
|
Term
| How does Warfarin act as an anti-coagulant, how is it monitored and when/why can it cause skin necrosis? |
|
Definition
1) Inhibits Epoxide reductase, which is responsible for vitamin K activation (co-factor is activation of F II, VII, IX, X, C, S)
2) Monitored by PT (extrinsic pathway) vs. PTT for heparin
3) If patients has protein C/S deficiency, further deficiency can cause necrosis. |
|
|
Term
| How does Heparin act as an anti-coagulant, how is it monitored and what are the benefits of its use? |
|
Definition
1) Binds and activates AT-III, which inhibits II, VII, IX, X, XI and XII
2) monitored by PTT (intrinsic) vs. PT for warfarin
3) Does not cross the placenta, so it is safe during pregnancy. |
|
|
Term
| Why do Factor V Leiden mutations cause thrombosis? |
|
Definition
1) A factor V is produced that is resistant to activated Protein C-mediated inhibition, so the common coagulation pathway proceeds unrelentingly
**Protein C is activated by thrombomodulin, a vitamin-K-dependent enzyme which is released from endothelial cells**
2) |
|
|
Term
| Why does vitamin K deficiency interfere with factor V cleavage? |
|
Definition
1) Factor Va (as well as VIIIa) is inhibited by activated Protein C
2) Protein C is activated by thrombomodulin, a vitamin-K-dependent enzyme which is released from endothelial cells (a reaction facilitated by protein S) |
|
|
Term
How might each of the following actions alter platelet plug formation?
1) VWD
2) Glanzmann's thrombasthenia
3) Bernard Soulier Syndrome
4) Abcixumab addition
5) Aspirin
6) Clopidogrel/Ticlopidine |
|
Definition
1) Without vWF, platelets cannot adhere to sites of vessel injury, because they cannot bind to GP1b (adhesion)
2) Without GPIIb/IIIa, fibrinogen cannot bind and link platelets together (aggregation)
3) Without GP1b, vWF on platelets cannot bind to site of vessel injury (adhesion)
4) GPIIb/IIIa inhibitor that functions the same as Glanzmann's
5) Aspirin inhibits platelet COX, preventing TXA2 synthesis, tipping the balance towards vasodilation and decreased platelet aggregation (PGI2 and NO from endothelial cells)
6) Prevents ADP-induced GpIIb/IIIa expression (similar to Abcixumab)
Platelet plug formation occurs in the following manner
1) Vessel injury: vWF binding to exposed collagen
2) Adhesion: Platelets bind vWF via GP1b at site of injury
3) Platelets release ADP and Ca2+ (necessary for coagulation)
4) ADP facilitates adhesion and induces GpIIb/IIIa expression at platelet surface
5) Aggregation: Fibrinogen binds GpIIb/IIIa receptors and links platelets (promoted by TXA2 from platelets and inhibited by PGI2 and NO from endothelial cells)
6) Temporary plug forms and bleeding stops. |
|
|
Term
| What important compounds are released from vascular endothelial cells during thrombogenesis? |
|
Definition
1) Thromboplastin (TF): released at time of vessel injury, binds and activates VII in extrinsic pathway
2) vWF (also produced by platelets) binds Gp1b in platelet adhesion
3) tPA for fibrinolysis
4) PGI2 and NO (vasodilation and decreased platelet aggregation) to counteract TXA2 released from platelets |
|
|
Term
What is the importance of AA metabolism in platelets and endothelial cells during thrombogenesis?
What is the effect of adding aspirin to the mix? |
|
Definition
1) In platelets, AA becomes TXA2, which is important for vasoconstriction, bronchostriction and platelet aggregation
2) In endothelial cells, AA becomes PGI2, which opposes TXA2
3) Aspirin inhibits pCOX >>>eCOX, leading to a vasodilatory, anti-aggregation effect (BLEEDING). |
|
|
Term
How do Clopidogrel/Ticlopidine influence thrombogenesis?
How does their action relate to that of Abcixumab? |
|
Definition
1) Irreversibly Inhibit ADP binding to receptor on platelets, inhibition GpIIb/IIIa insertion into platelet membrane.
2) Without GpIIb/IIIa. fibrinogen cannot bind and link platelets (no aggregation).
3) Abcixumab has a similar effect, but directly inhibits GpIIb/IIIa |
|
|
Term
| What is the meaning of a high/low ESR? |
|
Definition
Acute phase reactants in plasma (fibrinogen from platelets) cause RBC aggregation, increasing the ESR.
1) High ESR suggests infection, inflammation (temporal arteritis, polymyalgia rheumatica), malignant neoplasms, GI disease (UC) or pregnancy.
2) Low ESR are found in Polycythemia, sickle cell anemia, CHF, microcytosis and hypofibrinogenemia |
|
|
Term
Which of the following would NOT cause an elevated ESR?
1) URI
2) Temporal/Giant cell arteritis
3) Ulcerative colitis
4) Polycythemia
5) Pregnancy
6) Multiple myeloma |
|
Definition
4- Polycythemia rubra vera actually causes a decreased ESR (JAK2 mutation, myeloroliferative disorder of marrow with hyperviscosity, hypervolemia, hyperuricemia and hyperhistaminemia)
Other causes of decreased ESR include CHF, Sickle cell anemia, microcytosis and hypofibrinogenemia |
|
|
Term
What type of condition(s) is associated with each of the following RBC forms?
1) Acanthocyte (spur cell)
2) Basophilic stippling
3) Bite cells
4) Macro-ovalocyte
5) Ringed sideroblasts
6) Eliptocyte |
|
Definition
1) Liver disease, Abetalipoproteinemia)
2) Thallassemia, Anemia of chronic disease, Iron deficiency, Lead poisoning (BASte the ox TAIL)
3) G6PD deficiency (no protection from oxidative damage by glutathione)
4) Megaloblastic anemia (B12/folic acid or drugs) or Marrow failure
5) Microcytic, sideroblastic anemia
6) Hereditary Eliptocyte (no spectrin) |
|
|
Term
What type of condition(s) is associated with each of the following RBC forms?
1) Schistocyte (helmet cell)
2) Spherocyte
3) Teardrop cell
4) Target cell
5) Schistocyte (helmet cell) |
|
Definition
1) MAHA, HUS, TTP, DIC, Traumatic hemolysis
2) Hereditary spherocytosis, autoimmune hemolysis
3) Bone marrow infiltration (myelofibrosis)
4) "HALT" said the hunger to his target
- HbC disease
- Asplenia
- Liver disease
- Thalassemia
5) DIC, TTP/HUS, MAHA, Traumatic hemolysis |
|
|
Term
Why might you discover Heinz bodies on a peripheral smear?
What about Howell-Jolly bodies? |
|
Definition
1) Heinz bodies indicate oxidation of iron from ferrous to ferric form that is producing denatured hemoglobin precipitation and damage to RBC membrane.
Heinz bodies lead to Bite cells (G6PD deficiency and Alpha thalasemia)
2) Howell-Jolly bodies are basophillic nuclear remnants found in RBCs
HJB= Functional hyposplenia/asplenia (Sickle Cell disease) |
|
|
Term
Patient is lightheaded and dizzy.
You order blood work at discover MCV of 90
What is on your differential? |
|
Definition
MCV 80-100 is normocytic.
1) Non-hemolytic
- ACD (may progress to microcytic)
- Aplastic anemia
- Kidney disease
2a) Hemolytic- Extrinsic (splenic macrophages)
- Autoimmune (spherocytes)
- MiHI
- MAHA (Schistocytes-helmet cells)
- Infections
2b) Hemolytic intrinsic
- RBC membrane defect (spherocytosis)
- Enzyme deficiency (G6PD, PK) (bite cells)
- HbC (target cells)
- Sickle cell anemia (sickle cells)
- PNH (DAF deficiency so compliment-mediated destruction) |
|
|
Term
Which of the following cells would not appear in a normocytic, hemolytic anemia?
1. Spherocytes
2. Sickle cells
3. Schistocytes (helmet cells)
4. Bite cells
5. Ringed sideroblasts |
|
Definition
5- Ringed siderobloasts are found in sideroblastic anemia, a microcytic anemia
1) Spherocytes could be due to hereditary membrane defect (intrinsic hemolytic) or autoimmune hemolytic anemia (extrinsic)
2) Sickle cells are found in SCD (intrinsic hemolytic)
3) Schistocytes are found in MAHA, which occurs in DIC/HUS/TTP (extrinsic hemolytic)
4) Bite cells are associated with intrinsic RBC enzyme deficiency in G6PD (also see heinz bodies because of precipitated HB due to iron oxidation). |
|
|
Term
Which of the following would NOT produce a normocytic, extrinsic hemolytic anemia?
1. Sickle cell
2. MAHA
3. MIHA
4. Autoimmune
5. Infections |
|
Definition
|
|
Term
Which of the following should not be on your differential for an anemia with an MCV of 72?
1. Iron deficiency
2. Thalassemia
3. Aplastic anemia
4. Anemia of chronic disease
5. Lead poisoning
6. Sideroblastic anemia |
|
Definition
3. Aplastic anemia produces a NORMOcytic (80-100) anemia
**ACD may start normocytic, but will become microcytic)
Microcytic
- Thalassemia (target cells)
- Iron (most common)
- Sideroblastic (ringed sideroblasts)
- ACD
- Lead poisoning (basophilic stippling) |
|
|
Term
Which of the following should not be on your differential for an anemia with an MCV of 112?
1. Folate deficiency
2. B12 deficiency
3. Alcoholism
4. Iron deficiency
5. Liver disease
6. Hypothyroidism |
|
Definition
4- Iron deficiency is class microcytic
Megaloblastic
- B12/Folate: would show hyper-segmented PMNs and Macro-ovalocytes
Non-Megaloblastic
- Liver, Hypothyroid, Reticulocytosis, Drugs |
|
|
Term
What type of anemia is produced in each of the following conditions?
1) HbC disease
2) Reticulocytosis
3) Thalassemia
4) Anemia of chronic disease
5) TTP
6) Aplastic anemia |
|
Definition
1) Intrinsic, hemolytic, normocytic
- see Target cells
2) Non-megaloblastic, macrocytic anemia
3) Microcytic anemia
- see Target cells and/or basophilic stippling
4) Normocytic progressing to microcytic
5) MAHA procues extrinsic, hemolytic, normocytic anemia - see Schistocytes/helmet cells
6) Non-hemolytic, normocytic anemia |
|
|
Term
Which of the following is not a common cause of Iron deficiency?
1) GI bleeding
2) Radiation
3) Menorrhagia
4) Malnutrition
5) Pregnancy
6) Celiac disease |
|
Definition
Microcytic, hypochromic anemia
2: Radiation is a common cause of aplastic anemia, but not iron deficiency specifically.
Chronic bleeding (Menorrhagia, Gi bleeding), malabsorption (celiac), malnutrition and increased demand (pregnancy) are all possible. |
|
|
Term
Patient presents complaining of weakness and difficulty swallowing.
Bloodwork comes back and reveals a hypo-chromic, microcytic anemia.
On PE, you discover a small and inflamed tongue.
What is the treatment of this condition? |
|
Definition
Plummer-Vinson syndrome manifestation of Iron-deficiency anemia.
Triad= Iron deficiency anemia, atrophic glossitis, esophageal web (causing dysphagia)
- Cause unknown, but can be pre-malignant (squamous cell carcinoma), so give them iron supplementation and dilate with upper endoscopy, if necessary. |
|
|
Term
Why might you see peripheral blood smear with small, hypochromic red cells of varying sizes and shapes with target cells?
What is the pathophysiological basis and patient population effected? |
|
Definition
Beta thalasemia!
Point mutations in splice sites and promotor sequences of B-globin gene in Mediterranean (Greek and Italians)
Target Cells= HALT (HbC, Asplenia, Liver disease, Thalassemia) |
|
|
Term
| What populations are differentially affected by alpha and beta thalassemia, respectively? |
|
Definition
1) Alpha thalassemia occurs in Asians and Africans
- Gene mutations/deletions
2) Beta thalassemia occurs in Mediterranean (Greek and Italian)
- Point mutations in splice sites and/or promotor regions |
|
|
Term
| What are the major variants of Alpha thalassemia? |
|
Definition
AR conditions with 2 alpha globin genes (4 alleles) that produce hypochromic, microcytic anemia in Africans and Asian populations.
Look for target cells, heinz bodies and basophillic stippling.
1) 4 gene mutation= Hb Barts (y4)- incompatible with life causing Hydropis fetalis (fluid collection and edema in 2 body compartments)
2) 3 gene mutation= HbH disease (b4)- abnormal oxygen-dissociated curves
3) 1-2 gene mutation: no significant anemia |
|
|
Term
| What are the major variants of beta thalassemia? |
|
Definition
AR point mutations in splice sites/promotor sequences of beta globin genes producing hypochromic, mycrocytic anemia in Mediterranean population with increased HbF (a2y2)
1) B-thalassemia minor (heterozygote)
- B-chain underproduced and usually asymptomatic
- Diagnosed by electrophoresis (increased HbA2 >3.5%)
2) Major (homozygote)
- Beta chain absent producing severe anemia (need transfusion (secondary hemochromatosis))
- Marrow expansion ("crew cut" on skull x-ray with skeletal deformities and chipmunk facies) |
|
|
Term
| Why might a patient have a skull X-ray without a fracture, but a "crew cut" appearance? |
|
Definition
| B-thalassemia or HbS/B-thalassemia heterozygote (moderate sickle cell disease depending on amount of B globin production) |
|
|
Term
2 year old boy presents with strange lines on their gingiva and complains of abdominal colic.
On PE, you discover a wrist and foot drop and order some blood work, which a hypochromic, microcytic anemia.
What other blood findings would you expect to find and what is the underlying pathophysiology? |
|
Definition
Lead Poisoning
- Lead Lines (Burton's lines) on gingiva
- Encephalopathy with wrist/foot drops
- Abdominal colic.
1) Blood findings include Basophilic stipling and Ringed sideroblasts (Sideroblastic anemia).
2) Lead inhibits ferrochelatase and ALA dehydratase, decreasing Heme synthesis.
- Also inhibits rRNA degradation (basophilic stipling)
Treat it with EDTA and Dimercaprol, or Succimer for kids. |
|
|
Term
| How do you treat a patient who suffers from abdominal colic, foot/wrist drop and strange "lines" on their gingiva and bony epipheses? |
|
Definition
Abdominal Colic+ Drogs+ Burton's lines= Lead poisoning.
- EDTA, Dimercaprol are first line
- Succimer for kids
Lead inhibits
- Ferrochelatase (protoporphyrin to Heme in mitochondria)
- ALA dehydratase (porphobilinogen from two molecules of aminolevulinic acid)
- rRNA degredation |
|
|
Term
| How does lead produce sideroblastic anemia with basophilic stippling? |
|
Definition
Treat with EDTA, Dimercaprol and Succimer (kids)
Lead inhibits
1) Ferrochelatase
- protoporphyrin to Heme in mitochondria
2) ALA dehydratase (porphobilinogen from two molecules of aminolevulinic acid)
3) rRNA degradation |
|
|
Term
| What are the hereditary and secondary causes of the form of anemia that exhibits increased total Fe, normal TIBC and increased ferritin? |
|
Definition
Sideroblastic anemia (iron deficient would have increased TIBC. Treat it with Pyridoxine therapy
Form of hypochromic, microcytic anemia with ringed sideroblasts (iron-laden mitochondria)
1) Hereditary
- X-linked defect in delta-aminolevulnic acid synthase gene (protophorphyrin-heme synthesis)
2) Acquired
- Alcohol
- Lead toxicity |
|
|
Term
Which of the following treatments is appropriate for hereditary Sideroblastic anemia?
1) EDTA
2) Pyridoxine
3) Iron
4) Hydroxyurea |
|
Definition
2- Vitamin B6 will improve low heme level from X-linked deficit in delta-aminolevulinic acid synthase gene
1) EDTA would treat lead toxicity if it were causing sideroblastic anemia
2) Iron would be for iron deficiency
3) Hydroxyurea for symptomatic treatment of SCD and |
|
|
Term
Which of the following macrocytic anemias is associated with each of the following characteristics?
1) Hypersegmented PMNs with glossitis, increased homocysteine and normal MMA
2) Macrocytosis and bone marrow suppression with normal B12/folate levels
3) Hyper-segmented PMNs, glossitis, increased homocysteine and MMA |
|
Definition
1) Folate deficiency
- Malnutrition (alcohol), Malabsorption, Impaired metabolism (MTX, Bactrim), increased requirement (hemolytic anemia and pregnancy)
2) Nonmegaloblastic macrocytic anemia
- Could be liver disease
- hypothyroidism
- drugs (5-FU, AXST, hydroxyurea)
- alcoholism
- reticulocytosis
- congenital defects in purine/pyrimidine metabolism
3) B12 deficiency
- Intake (vegan)
- Malabsorption (crohn's)
- Pernicious anemia
- Diphyllobothrium latum (fish tapeworm) |
|
|
Term
Which of the following is NOT associated with B12 deficient anemia?
1) Peripheral neuropathy
2) Spasticity
3) Abnormal vibration sense
4) Dementia
5) Diplopia |
|
Definition
Diplopia is not characteristic. Remember, Always give B12 before folate, because folate will correct anemia without preventing NEURO
B12 deficiency causes subacute combined degeneration of spinal chord (B12 role in fatty acid pathways and myelination)
1) Peripheral neuropathy with sensorimotor dysfunction
2) Posterior columns (vibration/proprioception
3) Lateral corticospinal (spasticity)
4) Dementia |
|
|
Term
Patient has a normocytic anemia with decreased haptoglobin levels, elevated LDH and hemoglobinuria.
What is on your differential and how might you distinguish between these options? |
|
Definition
Low hapto, high LDH and Hgb in urine in context of normocytic anemia= Intravascular hemolytic anemia
1) PNH= increased urine hemosiderin
2) G6PD deficiency= bite cells
3) MAHA
4) Mechanical destruction due to prosthetic valve or aortic stenosis |
|
|
Term
Patient has a normocytic anemia with elevated LDH and jaundice
What is on your differential and how might you distinguish between these options? |
|
Definition
Normocytic anemia with increased LDH and jaundice (UCB) suggests extravascular hemolytic anemia, where macrophages in the spleen are clearing RBCs.
1) Hereditary spherocytosis (intrinsic)= spherocytosis without antibodies
2) PK deficiency
3) Sickle cell anemia (intrinsic)= sickle cells |
|
|
Term
Which anemia is characterized by each of the following?
1) High Fe, normal TIBC and high ferritin
2) Low Fe, low TIBC and high ferritin
3) Low Fe, high TIBC, low ferritin |
|
Definition
1) Sideroblastic anemia- microcytic anemia due to X-linked delta-aminolevulinic acid synthase gene defect or secondary to Lead or alcohol.
2) Normo/microcytic anemia due to inflammation and increased hepcidin release
- Iron is stuck in macrophages and bound to transferritin
- Hepcidin binds ferroprotein on intestinal mucosal cells and macrophages and inhibits iron transport, preventing its release from macrophages.
3) Microcytic anemia due to iron deficiency
- Transferritin has open space without the iron to fill it |
|
|
Term
| What is the pathophysiogical basis of the 3 primary causes of non-hemolytic, normocytic anemia? |
|
Definition
1) ACD
- Inflammation increases hepcidin released from liver
- Hepcidin binds ferroportin on intestinal mucosal cells and macrophages, inhibiting iron transport
2) Aplastic anemia
- Destruction of myeloid stem cells due to a) Radiation/drugs, b) viral agents, c) Fanconi's anemia or d) Idiopathic/immune following hepatitis
3) Kidney disease
- Decreased EPO leads to decreased hematopoiesis |
|
|
Term
Which of the following is not a known cause of Aplastic anemia?
1) Parvovirus B19
2) Benzene
3) Radiation
4) DNA repair defect
5) Mycobacterial infection |
|
Definition
5
Normocytic, non-hemolytic anemia due to failure or destruction of myeloid stem cells due to
1) Radiation and drugs (benzene, chloramphenicol, alkylating agents, antimetabolites)
2) Viral agents (parvovirus B19, EBV, HIV, HCV)
3) Fanconi's anemia (DNA repair defect)
4) Immune mediated reaction, often following acute hepatitis |
|
|
Term
| How can radiation-induced pancytopenia presenting with fatigue, malaise, pallor, purpura and mucosal bleeding be treated? |
|
Definition
Patient with Aplastic anemia due to destruction of myeloid stem cells in bone marrow (normocytic, non-hemolytic anemia).
1) Withdraw offending agent
2) Immunosuppression (ATG, cyclosporine)
3) Allogeneic BMT
4) RBC and platelet transfusion
5) G-CSF or GM-CSF |
|
|
Term
What is the pathophysiological deficit associated with each of the following findings in a patient with intrinsic hemolytic anemia?
1) Splenomegaly, aplastic crisis and positive osmotic fragility test
2) Back pain and hemoglobinuria with Heinz bodies and Bite cells in smear.
3) Hemolytic anemia in a newborn
4) Target cells in patient with HbSC genotype
5) Increased hemosiderin and complicated by thrombosis |
|
Definition
1) Hereditary spherocytosis (Extravascular)
- Defect in membrane proteins like spectrin and ankyrin) with premature removal in spleen
- Less membrane causes small and round RBCs with no central pallor (increased MCHC and RDW)
2) G6PD deficiency (intravascular)
- Defect decreases glutathione, increased RBC susceptibility to oxidant stress
- Hemolytic anemia following stress (sulfa drugs, infections, fava beans)
3) PK deficiency (Extravascular)
- AR defect leading to decreased ATP and rigid RBCs removed in the spleen
4) HbC defect (glutamic acid-to-lysine mutation at position 6 in chain)
5) PNH (Intravascular)
- Increased complement-mediated RBC lysis (impaired synthesis of GPI anchor/DAF in RBC membrane) |
|
|
Term
| What are the major complications associated with homozygous sickle cell disease? |
|
Definition
Point mutation in B chain (glutamic acid for valine at position 6) causing an intrinsic, extravascular hemolytic anemia. Treat it with hydroxyurea (HbF) and BMT
1) Aplastic crisis (due to parvovirus B19)
2) Autosplenectomy (risk of encapsulated infections from S. pneumoniae, H. influenzae and N. meningiditis)
- Howell-Jolly Bodies
3) Splenic sequestration crisis
4) Salmonella osteomyelitis
5) Painful crisis (vaso-occlusive): dactylitis, acute chest syndrome
6) Renal papillary necrosis (due to low O2 in papilla) and microhematuria (medullary infarcts) |
|
|
Term
| What is the pathogenesis of SCD and how is it treated? |
|
Definition
HbS point mutation (G6V in beta globin chain)
1) Low O2 or dehydration ppt sickling (deoxygenated HbS polymerizes), resulting in anemia and veno-occlusive crisis (dactilitis)
**newborns initially asymptomatic because of HbF until 6 months**
2) Treat with hydroxyurea (HbF) and BMT |
|
|
Term
True or False:
Sickle cell trait is rare among americans |
|
Definition
False!
8% of AA individuals have trait, because of malaria resistance. |
|
|
Term
| Why due patients with SCD and beta thalassemia have "crew cut" skull X rays? |
|
Definition
Marrow expansion from increased erythropoiesis.
NOT alpha-thalassemia and NOT a fracture |
|
|
Term
Which of the following is NOT a complication of homozygous SCD?
1) Osteomyelitis from shigella toxin
2) Increased risk against H. influenza infection
3) Splenic sequestration crisis
4) Aplastic crisis from parvovirus B19
5) Dactilitis
6) Renal papillary necrosis |
|
Definition
1- It is SALMONELLA, which is taken up by splenic macrophages, which are disturbed by autosplenectomy.
2. H. influenza, S. pneumonia and N. meningititis because of autosplenectomy (encapsulated bacteria)
3. Extravascular hemolysis
4. Viral infection
5. Veno-oclusive syndrome (also acute chest syndrome)
6. Due to low O2 in papilla (also see microhematuria because of medullary infarcts) |
|
|
Term
What is the pathophysiological deficit associated with each of the following findings in a patient with extrinsic, hemolytic, normocytic anemia?
1. Acute anemia seen in CLL, Mycoplasma pneumonia infection or infectious mononucleosis
2. Chronic anemia seen in SLE, CLL or with certain drugs like alpha-methyldopa
3. Schistocytes on blood smear |
|
Definition
1) Cold Agglutinin (IgM attacks RBCs) autoimmune hemolytic anemia
2) Warm Agglutinin (IgG attacks RBCs) autoimmune hemolytic anemia
**autoimmune seen in Erythroblastosis fetalis with Rh incompatibility**
3) MAHA or Prosthetic valve
- RBCs damaged when passing through obstructed or narrowed vessel lumen (seen in DIC, HUS, TTP, SLE and malignant hypertension)
**Infections can also cause extrinsic hemolytic anemias** |
|
|
Term
| How are autoimmune hemolytic anemias diagnosed? |
|
Definition
Can be Cold (acute IgM- CLL, Mycoplasma pneumonia, EBV) or Warm (chronic IgG- CLL, SLE)
Coomb's tests
1) Direct Coomb's- anti-Ig antibody added to patient's RBCs
- They agglutinate if RBCs are coated with Ig
**Diagnose AHA**
2) Indirect- Normal RBCs added to patients serum
- They agglutinate if serum has anti-RBC surface Ig
**Used for pre-natal identification of Rh-/Rh+ mismatch** |
|
|
Term
What type of anemia is described by each of the following lab values?
Serum Iron, TIBC, Ferritin, % Saturation (serum Fe/TIBC)
1. Decreased, Increased, Decreased, Very low
2) Decreased, Decreased, Increased, Variable
3) Increased, Decreased, Increased, Very High
4) Normal, Increased, Normal, Decreased
5) Increased, Decreased, Normal, Increased |
|
Definition
1) Iron deficiency
2) ACD
3) Hemochromatosis
4) Pregnancy/OCP use
5) Lead poisoning |
|
|
Term
| Why is TIBC thought be low in ACD? |
|
Definition
Body adapted a system in which iron is stored within cells of the body to prevent pathogens from acquiring circulating iron.
1) Liver makes more Hepcidin, which stops iron transport out of macrophages and across small intestine is duodenum
2) less iron is available to break down by infection. |
|
|
Term
| What steps of Heme biosynthesis take place in the mitochondria, and which take place in the cytoplasm? |
|
Definition
Protoporphyrin + Iron= Heme
1) Mitochondria
- Glycine and Succinyl-CoA combine to form d-aminolevulinic acid via dALA-synthase (RLS!)
2) Cytoplasm
- Aminolevulinic acid is dehydrated to Porphobilinogen by d-ALA dehydratase
- Porphobilinogen is deaminated to Hydroxymethylbilane by Porphobilinogen deaminase
- Porphobilinogen becom Uroporphyrinogen III, which is Decarboxylated to Coproporphyrinogen III by Uroporphyrinogen decarboxylase
3) Mitochondria
- Coproporphyrinogen III becomes Protoporphyrin, and Iron is added by Ferrochelatase to make Heme. |
|
|
Term
Which of the following enzymes controls the rate limiting step of Heme synthesis?
1) Ferrochelatase in the mitochondria
2) d-ALA dehydratase in the cytpoplasm
3) d-ALA synthase in the mitochondria
4) Uroporphyrinogen decarboxylase in the cytoplasm
5) Porphobilinogen deaminase in the cytoplasm |
|
Definition
3- dALA synthease converts glycine + succinyl-CoA to dALA in the mitochondria (B6 cofactor required).
ALA-synthease activity increases when heme is Low
This enzyme is rate-limiting and is defective in X-linked Sideroblastic anemia, a hypochromic, microcytic anemia that presents with ringed sideroblasts in the peripheral blood (iron-laidened macrophages). |
|
|
Term
Which enzyme(s) involved in heme synthesis is affected by each of the following diseases?
1) Lead poisoning
2) Sideroblastic anemia (X-linked)
3) Acute intermittent porphyria
4) Porphyria cutanea tarda |
|
Definition
1) Lead Poisoning (microcytic anemia)
- dALA dehydratase, which produces Porphobilinogen from d-ALA in the cytoplasm
- Ferrochelatase, which converts Protoporphryin and Fe2+ to Heme in the mitochondria
2) Sideroblastic anemia
- d-ALA synthease (RLS), which converts glycine and sCoA to d-ALA in the mitochondria (B6 dependent reaction)
3) Porphobilinogen deaminase
- Produces Hydroxymethylbilane from Porphobilinogen in the cytoplasm
4) Uroporphyrinogen decarboxylase
- Converts Uroporphyrinogen II to Coproporphyrinogen III in the Cytoplasm (final cytoplasmic step) |
|
|
Term
Which disease of Heme synthesis presents in each of the following ways?
1) Microcytic anemia, with GI and Kidney disease, as well as CNS symptoms
2) Painful abdomen with "red-wine" colored urine, Polyneuropathy and Psychological disturbances
3) Blistering cutaneous photosensitivity |
|
Definition
1) Lead poisoning
- Defective ferrochelatase and ALA dehydratase
- Accumulation of Protoporphyrin (blood)
2) Acute intermittent porphyria (Symptoms triggered by drugs)
- Defective Porphobilinogen deaminase (aka uroporphyrinogen-I-synthase)
- Accumulation of Porphobilinogen, d-ALA and Uroporphyrin (urine)
3) Porphyria cutanea tarda (most common)
- Defective Uroporphyrinogen decarboxylase
- Accumulated Uroporphyrin (tea-colored urine) |
|
|
Term
| What are the common exposures to lead toxicity in kids and adults and what neurological symptoms do they produce? |
|
Definition
Lead poisoning= Defective Ferrochelatase and ALA dehydratase, wich accumulation of Protoporphyrin (blood)
1) Kids get mental deterioration from lead-based paints
2) Adults get headache, memory loss and demyelination from battery/ammunition/radiation exposure.
**Both get microcytic anemia, with GI and Kidney disease** |
|
|
Term
Patient presents complaining of abdominal pain and severe mood swings. They are also having tingling sensations in their fingers and toes.
They urinate in a cup and you notice that the urine is "red wine" colored.
What is likely going on, and could you confirm and how would you treat? |
|
Definition
Abdominal Pain, Polyneuropathy, Psychological disturbances and red-wine urine= Acute intermittent Porphyria, likely exacerbated by drug use.
1) Defective Porphobilinogen deaminase (cytoplasmic enzyme in heme synthesis)
2) Look for elevated Porphobilinogen, d-ALA and Uroporphyrin (urine)
3) Give glucose and heme, which inhibit ALA synthase |
|
|
Term
Patient presents blood work reveals elevated Fe2+, normal TIBC and elevated ferritin.
How might you treat them and why? |
|
Definition
Sounds like Sideroblastic (microcytic anemia) due to defective ALA-synthase, a mitochondrial enzyme that regulates the RLS of heme synthesis.
Give them B6 supplementation, because ALA-synthase uses B6 as a cofactor to produce d-ALA from glycine and succinyl CoA |
|
|
Term
Which disease of heme synthesis affects each of the following enzymes and what are the notable clinical symptoms?
1) d-ALA dehydratase
2) Ferrochelatase
3) d-ALA synthase
4) Uroporphyrinogen decarboxylase
5) Porphobilinogen deaminase |
|
Definition
1) Lead poisoning- Micryocytic anemia, GI and Kidney disease and CNS disturbances.
- Treat with Dimercaprol and EDTA, or Succimer in kids.
2) Lead poisoning again
3) Sideroblastic anemia- microcytic anemia with normal TIBC and elevated Fe 2+ and ferritin- Treat with B6
4) Porphyria cutanea tarda- tea-colored urine with blistering cutaneous photosensitivity (most common porphyria).
5) Acute intermittent porphyria (triggered by drugs)- Red-wine urine, Painful abdomen, psych disturbance, polyneuropathy.
- Treat with glucose and heme (inhibits ALA synthase in mitochondria) |
|
|
Term
| Which disorder(s) of coagulation might presents with a prolonged PTT, but normal PT? What about Prolonged PTT and PT? |
|
Definition
PT= extrinsic (VII)
PTT= intrinsic (XII, XI, IX, VIII)
1) Prolonged PTT and normal PT
- Hemophilia A (VIII) or B (IX)- Hemarthroses and easy bruising
2) Prolonged PTT and prolonged PT
- Vitamin K deficiency (II, VII, IX, X, C, S)
- |
|
|
Term
| What are the possible causes of an elevated bleeding time (BT) in the absence of coagulation defects, and what are the classic clinical symptoms? |
|
Definition
Platelet disorder (quantitative or qualitative) presents with micro-hemorrhage: mucous membrane bleeding, epistaxis, petechiae, purpura.
1) Bernard Soulier- defect in GP1b (defective platelet-to-collagen adhesion)
2) Glanzmann's thrombasthenia- defect in GPIIb/IIIa (defective plug formation because fibrinogen cannot cross-link)
3) Idiopathic TP-decreased platelet survival because of anti-GpIIb/IIIa antibodies
- Labs show increased megakaryocytes
4) TTP- decreased platelet survival time
- Deficient ADAMTS 13 (vWF MMP) leading to vWF multimers, which increase aggregation and cause thrombosis
- Labs show schistocytes and increased LDH |
|
|
Term
45 year old patient presents complaining of recurrent bloody noses and small bruises on their legs and thighs.
You run some blood work and discover that their platelet count is low and their bleeding time is prolonged. PT and PTT are normal.
What is on your differential? |
|
Definition
Symptoms are primary hemostasis (platelet issue), with normal coagulation (PT and PTT).
Since PC is low, Glanzmann's thrombasthenia is ruled out (GPIIb/IIIa).
Low PC and high BT leave 3 major options.
1) Bernard-Soulier- defect in Gb1b (platelet adhesion)
- congenital and more commonly early presentation
2) ITP- decreased platelet survival because anti-GpIIb/IIIa antibodies
- would see elevated megakaryocyte levels
3) TTP
- Deficient ADAMTS 13 (vWF MMP) leads to vWF multimer buildup, platelet aggregation and thrombosis
- Would see fever, CNS, renal, TP and MAHA |
|
|
Term
| What is the pathogenesis/treatment of the most common inherited bleeding disorder? |
|
Definition
Autosomal Dominant- VWD (can be quantitative, qualitative or severe).
Would see elevated BT, normal PC and perhaps elevated PTT if severe (VIII is carried by vWF)
1) Decreased vWF inhibits platelet adhesion to vessel wall collagen
2) Treat with DDAVP (desmopressin) to increase vWF release from weiber palladine bodies in endothelium. |
|
|
Term
What are the major causes of the mixed bleeding/coagulation disorder that is characterized by
- decreased PC, increased BT, increased PT and increased PTT
- increased D-dimer
- decreased fibrinogen, factors V and VIII |
|
Definition
DIC- widespread activation of clotting leads to deficiency of clotting factors, which creates bleeding state.
See schistocytes because of thrombosis and split products because of clot breakdown.
STOP Making New Thrombi
1) Sepsis
2) Trauma
3) Obstetric complications
4) Pancreatitis
5) Malignancy
6) Nephrotic syndrome
7) Transfusion |
|
|
Term
Which of the following is unlikely to cause an elevated D-dimer with elevated BT, decreased fibrinogen and factors V and VIII?
1) Trauma
2) Sepsis
3) Cirrhosis
4) Obstetric complications
5) Nephrotic syndrome
6) Transfusion |
|
Definition
DIC is not associated with Cirrhosis particularly.
STOP Making New Thrombi
Sepsis, Trauma, Obstetric complications, Pancreatitis, Malignancy, Nephrotic syndrome, Transfusion |
|
|
Term
Which hereditary thrombosis syndrome is described by each of the following?
1) Production of mutant factor V that cannot be degraded by protein C
2) Reduced increase in PTT after heparin addition
3) Overactivity of V and VIII, with risk of skin necrosis with hemorrhage following warfarin addition
4) Mutuation in 3' UTR associated with venous clots |
|
Definition
1) Factor V Leiden (most common)
2) AT-III deficiency- AT-III is activated by heparin, which should increase PTT (monitor of heparin activity)
3) Protein C/S deficiency (activated by vitamin-K-dependent thrombomodulin enzyme.
4) Prothrombin variant (2nd most common) |
|
|
Term
Why might you give each of the following types of blood transfusion therapy?
1) Packed RBCs
2) Platelets
3) FFP
4) Cryoprecipitate |
|
Definition
1) Acute blood loss, severe anemia
- Increases Hb and O2 carrying capacity
2) Stop significant bleeding (TP, qualitative platelet defect)
- Increase PC (given in "6pack" for therapeutic effect)
3) DIC, cirrhosis, warfarin over anti-coagulation
- Increase coagulation factor levels by 20%
4) Abnormal fibrinogen or factor VIII or XIII defect |
|
|
Term
Which of the following is not a major risk associated with blood transfusions?
1) Infection
2) B12 toxicity
3) Iron overload
4) Hypocalcemia
5) Hyperkalemia
6) Immune reaction |
|
Definition
2- This is not a thing
1) Infection risk is low, but important
3) Iron overload does occur
4) Hypocalcemia because citrate is a calcium chelator
5) Hyperkalemia because RBCs may lyse in old blood units
6) Immune rejection is type match is off |
|
|
Term
| How does a "leukemoid reaction" differ from leukemia? |
|
Definition
| A leukemoid reaction is an increase in WBC count with a left shift (80% bands) and increased leukocyte alkaline phosphatase, usually due to INFECTION. |
|
|
Term
Which of the following is NOT a correct description of Hodgkin's Lymphoma?
1) Presence of Reed-Sterberg cells
2) Associated with HIV
3) Constitutional signs/symptoms of low-grade fever, night sweats and weight loss
4) Localized, mediastinal lymphadenoapthy
5) EBV association |
|
Definition
2- HIV and immunosuppression is associated with NHL
- Low-grade fever, weight loss and night sweats are characteristic, with localized, single group of affected mediastinal nodes and RS cells.
- HL prognosis is predicted by Staging and number of lymphocyte/RS cells (higher RS:lymphocyte ratio is poor prognosis)
- 50% HL is associated with EBV, with bimodal distribution of young and old.
- More common in men, except for nodular sclerosis type |
|
|
Term
True or False:
CD30+, CD15+ cells arising from B cells are necessary for the diagnosis of Hodgkin's lymphoma. |
|
Definition
True! These are Reed-Sternberg cells ("owl eyes")
Necessary, but NOT sufficient. Variants include lacunar cells in nodular sclerosis (women) variant) |
|
|
Term
What type of Hodgkin's lymphoma is characteristic of each of the following demographics?
1) Young women and young Men
2) Men < 35
3) Older males with disseminated disease
3) Men with numerous RS cells |
|
Definition
1) Nodular sclerosis (65-75%)
- Collagen binding and lacunar RS cells
- High Lymphocyte:RS ratio and good prognosis
2) Lymphocyte predominant (6%)
- High lymphocyte:RS ratio and good prognosis
3) Lymphocyte depleted (rare)
- Low lymphocyte:RS ratio and poor prognosis
4) Mixed cellularity (25%)
- Intermediate Lymphocyte:RS ratio and intermediate prognosis |
|
|
Term
Which form of NHL is described by each of the following?
1) "Starry-sky" appearance on pathology (sheets of lymphocytes and interspersed macrophages) associated with EBV and t(8:14) of c-myc gene to Ig gene
2) Most common form of adult NHL, usually of B-cell origin, but can be mature T-cell origin (20%)
3) CD5+ cells with t(11:14) translocation resulting in deactivation of cyclin D regulatory gene- common in older males
4) Caused by HTLV-1 in adults and associated with aggressive, cutaneous lesions in Japan, West Africa and Caribbean
5) Indolent course with t(14:18) of bcl-2- common in adults
6) Indolent course in adults with CD4+ cells and cutaneous patches/nodules |
|
Definition
1) Burkitt's lymphoma (adolescents or young adults)
- B-cell lymphoma associated with jaw lesion in endemic form in Africa and pelvis/abdomen lesions in sporadic form
2) Diffuse large B-cell lymphoma
- Usually older, but 20% younger
3) Mantle cell lymphoma
- B cell lymphoma of older males with poor prognosis
4) Adult T-cell lymphoma
5) Follicular lymphoma
- B cell lymphoma with bcl-2-inhibition of apoptosis
- Difficult to cure
6) Mycosis fungoides/Sezary syndrome (mature T-cell neoplasm) |
|
|
Term
Which lymphoma is associated with each of the following genetic translocations?
1) t(11;14) of cyclin D1 regulatory gene
2) t(8:14) of c-myc to heavy-chain Ig gene
3) t(14:18) of bcl-2 expression |
|
Definition
1) Mantle Cell Lymphoma (B cell)
- CD5+, found in older males and poor prognosis
2) Burkitt's lymphoma (B cell)
- "starry sky" with lymphocyte sheet/intermittent phage
- EBV association and jaw lesion in African population
- Young adults/children
3) Follicular Lymphoma (B cell)
- Difficult to cure with indolent course in adults |
|
|
Term
Which of the following is NOT characteristic of the most common primary tumor of the bone marrow in the elderly (>40-50)?
1) Renal insufficiency
2) Pulmonary fibrosis
3) Bone lytic lesions
4) Anemia
5) Hypercalcemia |
|
Definition
2- PF is not associated with Multiple Myeloma
CRAB (hyperCalcemia, Renal, Anemia, Bone lytic lesion)
MM has monoclonal plasma cell neoplasm ("fried-egg") arising in the bone marrow and producing large amounts of IgG (55%) or IgA (25%).
Monoclonal M protein spike for Multiple Myeloma |
|
|
Term
55 year old male presents with severe back pain and fatigue.
You run some labs and discover he is anemic, his urinary Cr is high and he is hypercalcemic. You order a CXR, and discover bone lytic lesions.
What might you expect to see on a blood smear? |
|
Definition
Elderly male with lytic lesions/back pain, hypercalcemia, renal insufficiency and anemia suggests multiple myeloma.
CRAB (hyperCalcemia, Renal insufficiency, Anemia, Bone lytic)
- Smear will show 1) Numerous plasma cells (clock-face chromatin) and 2) Intra-cytoplasmic inclusions containing Ig.
- Rouleaux formation (RBC stacked like poler chips) is also common |
|
|
Term
Which of the following is NOT associated with multiple myeloma?
1) Increased susceptibility to infection
2) Howell-Jolly bodies
3) Rouleaux formation on blood smear
4) Bence Jones protein in urine
5) Primary amyloidosis
6) M spike on protein electrophoresis |
|
Definition
2- HJ bodies are characteristic of autosplenectomy (SCD) or spleen removal.
Individuals with MM get
- infections
- stacked RBCs on smear (Rouleaux)
- BJ protein (Ig light chains) in urine
- M spike on electrophoresis
- Amyloidosis |
|
|
Term
| How can Waldenstrom's macroglobulinemia be distinguished from Multiple Myeloma? |
|
Definition
Protein electrophoresis.
1) WM
- M spike is IgM and there will be hyperviscosity and NO BONE LESIONS
2) MM
- M spike is IgG (55%) or IgA (25%) and you will see Bone lesions.
- CRAB (hyperCalcemia, renal, anemia, bone lesions) |
|
|
Term
| What might you call a monoclonal plasma cell expansion without evidence of bone lesions, back pain, anemia or renal insufficiency? |
|
Definition
MGUS- Monoclonal gammopathy of undetermined significance
- Looks like Multiple myeloma, but without symptoms. |
|
|
Term
What are the most common leukemias in each of the following demographics?
1) Age > 15 years
2) Age 30-60
3) Age 60
4) Age > 60 |
|
Definition
1) ALL
- bone marrow involvement in childhood or mediastinal mass in adolescent males
- Bone marrow replaced by TdT+ (pre-T and pre-B), CALLA+, lymphoblasts
2) CML
- Philadelphia chromosome (t[9;22], bcr-abl) with myeloid stem cell proliferation
- Can transform to AML or ALL in "blast crisis"
- Responds to Imatinib (inhibits bcr-abl TK)
3) AML
- Aur rods with circulating myeloblasts on peripheral smear (watch out for DIC)
- t(15;17), M3 AML subtype responds to all-trans retinoid acid (vitamin A), which induces myeloblast differentiation
4) Small LL/CLL
- Asymptomatic with "smudge cells" in peripheral smear
- Warm antibody (IgG) HA
- SLL is same as CLL, except CLL has increased peripheral blood lymphocyosis |
|
|
Term
| Which leukemia is effectively treated with all-trans retinoid acid? |
|
Definition
t(15;17), M3 subtype of AML (usually 60 year old)
- Vitamin A form increases myeolblast differentiation
- Look for aur rods and watch out for DIC. |
|
|
Term
Which leukemia is associated with each of the following translocations?
1) t(15;17)
2) t(9;22), bcr-abl
3) t(12;21) |
|
Definition
1) M3 subtype of AML (60 year olds) treated with all-trans-RA to induce myeloblast differentiation
2) Philadelphia chromosome of CML (30-60 years old) treated with Imatinib to inhibit TK activity
3) Form of ALL (age < 15) associated with better prognosis |
|
|
Term
| What are "auer bodies" and why are they clinically important? |
|
Definition
1) Peroxidase-positive cytoplasmic inclusions in granulocytes and myeloblasts that serve as a marker for Acute Promyelocytic Leukemia (M3 AML)
2) Treatment with all-trans RA can release Auer rods and cause DIC! |
|
|
Term
What disorder is associated with each of the following translocations?
1) t(9;22) bcr-abl
2) t(8;14) c-myc
3) t(14;18) bcl-2
4) t(15;17)
5) t(11;22)
6) t(11;14) cyclin D |
|
Definition
1) Philadelphia chromosome of CML- Imitanib treat
2) Burkitt's lymphoma- Starry sky and EBV
3) Follicular lymphoma- hard to treat
4) M3 AML- treat with all-trans RA and watch for DIC
5) Ewing's sarcoma- malignant bone tumor
6) Mantle cell lymphoma- B cell, CD5+ poor prognosis |
|
|
Term
| What hematological disease is associated with S-100 and CD1a expression, as well as "tennis racket" granules on EM? |
|
Definition
Birbeck granules are seen in Langerhan Cell Histiocytosis (LCH), which is a proliferative disorder of immature dendritic cells, which cannot efficiency stimulate T lymphocytes.
- Multi-system disease with unclear etiology. |
|
|
Term
Which chronic myeloproliferative disorder is described by each of the following?
1) RBC (+), WBC (+), Platelet (+), JAK2 mutation (+)
2) RBC (_), WBC (_), Platelet (+), JAK2 mutation (+ 1/2)
3) RBC (-), WBC (variable), Platelet (variable), JAK2 (+ 1/2)
4) RBC (-), WBC (+), Platelet (+), JAK2 (-) |
|
Definition
1) Polycythemia rubra vera
- Hyperviscosity, hypervolemia, hyperuricemia, hyperhistinemia
- Abnormal clone of HSC sensitive to growth factors
2) Essential thrombocytosis (Polycythemia specific for megakaryocytes)
3) Myelofibrosis
- Fibrotic obliteration of marrow with "teardrop cells"
4) CML
- bcr-abl transformation leds to increased cell division and inhibited apoptosis. |
|
|
Term
What type of Polycythemia is described by each of the following?
1) Decreased plasma volume with normal RBC mass and O2 saturation
2) Normal plasma volume with increased RBC mass and decreased O2 saturation
3) Normal plasma volume with increased RBC mass and normal O2 saturation
4) Increased plasma volume, highly increased RCB mass and normal O2 saturation |
|
Definition
1) Relative (dehydration)
2) Appropriate absolute (hypoxia from lung disease, altitude or TOF). EPO would be high
3) Inappropriate absolute due to RCC, Wilm's tumor, cyst, HCC, hydronephrosis (ectopic EPO)
4) Rubra vera (hypervolemia, hyperviscosity, hyperuricemia, hyperhistaminemia) |
|
|
Term
| What are the major myeloproliferative disorders? |
|
Definition
1) Polycythemia vera
2) Essential thrombocytosis
3) Myelofibrosis
4) CML |
|
|
Term
| Why might you put a patient on Heparin and what is its mechanism of action and possible toxicity profile? |
|
Definition
1) Mechanism
- Cofactor for activation of AT-III, decreasing thrombin and factor Xa
2) Clinical Use- Immediate anti-coagulation (IV)
- PE, stroke, ACS, MI, DVT.
- monitored by PTT and reversed with protamine sulfate
(+ charged molecule that binds and inactivates)
3) Toxicity
- Bleeding, HIT, osteoporosis, drug-drug interactions
**LMW heparin can be given sub-q without monitoring, has longer half life and acts more specifically on Xa, but cannot be reversed easily** |
|
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Term
| What are the benefits/drawbacks of using low MW heparin instead of un-fractioned heparin? |
|
Definition
Both can be given safely during pregnancy and for immediate anti-coagulation of DVT/PE, MI, stroke, ACS
1) Benefits of Low MW
- more specific for Xa (no HIT unless previous h/x)
- has a longer half life
- given sub-q without monitoring
2) Drawbacks
- Not easily reversible like UFH, which can be reversed with protamine sulfate (+ charged molecule) |
|
|
Term
| What is the underlying mechanism of heparin-induced thrombocytopenia? |
|
Definition
Less likely with LMW heparin, unless there is a previous h/x
1) Heparin binds platelet factor 4 and causes antibody production
2) Antibodies bind to and activate platelets leading to thei clearance and resulting in thrombocytopenic, hypercoagulable state. |
|
|
Term
| Why might you prescribe Lepirudin or Bivalirudin and how do these agents work? |
|
Definition
Anti-coagulants in place of heparin in case of HIT for immediate anti-coagulation (DVT/PE, ACS, MI)
Direct thrombin inhibitors derived from yeast. |
|
|
Term
| Why might you put a patient on Warfarin and what is its mechanism of action and possible toxicity profile? |
|
Definition
Monitored by PT/INR (extrinsic pathway) and reversed with vitamin K or rapidly with FFP.
1) Mechanism
- Inhibits epoxide reductase, the enzyme responsible for vitamin K activation (you get no II, VII, IX, X, C or S)
2) Clinical use
- Chronic anticoagulation (Post STEMI, venous thromboembolism prophylaxis)
- NOT in pregnancy/crosses placenta
3) Toxicity
- Bleeding, teratogen, skin/tissue necrosis (C/S deficiency), drug-drug interactions (CYP metabolism) |
|
|
Term
Which of the following is NOT a side effect of Heparin use?
1) Bleeding
2) Osteoporosis
3) Teratogenicity
4) Thrombotic Thrombocytopenia
5) Drug-drug interactions |
|
Definition
| 3- Heparin, unlike Warfarin/Coumadin does NOT cross the placenta and can be safely used in pregnancy |
|
|
Term
| How can Warfarin and Heparin administration be reversed in the case of overdose? What about tPA? |
|
Definition
1) Heparin: Protamine sulfate (+ charged molecule)
**hard to reverse low MW version, with Xa specificity
2) Warfarin/Coumadin: IV Vitamin K or FFP (if emergent)
3) tPA is reversed with aminocaproic acid (inhibits plasminogen activation) |
|
|
Term
What are the major differences between heparin and warfarin in terms of the following.
1) Structure
2) Administration
3) Site of action
4) Mechanism of action
5) Duration of action
6) In vitro activity
7) Monitoring |
|
Definition
1) Large anionic, acidic polymer (H) vs. small lipid-soluble molecule (W)
2) Parenteral (IV/SC- H) vs. Oral (W)
3) Blood (H) vs. Liver (W)
4) Activates AT-III decreasing IIa and Xs (H) vs. Impairs epoxide reductase (W)
5) Acute/hours (H) vs. chronic/days (W)
6) Yes (H) vs. No (W)
7) PTT (H) vs PT/INR (W) |
|
|
Term
| What are the major available thrombolytic agents and how do they function, how are they used and what is their toxicity? |
|
Definition
Streptokinase, Urokinase, tPA (altepase), APSAC (anistreplase)
1) Mechanism
- Directly or indirectly aid conversion of plasminogen to plasmin, which cleaves thrombin and fibrin clots
- increase PT and PTT, without change in PC
2) Early MI, early ischemic stroke
3) Bleeding, recent surgery, severe hypertension
- Reverse with aminocaproic acid |
|
|
Term
| What are the major available platelet inhibitors and how do they work? |
|
Definition
1) ASA- acetylate and irreversibly inhibit COX1/2 in platelets to prevent AA conversion to TXA2
- increase BT, but no change in PT/PTT
2) Clopidogrel, Ticlopidine
- Inhibit platelet activation by blocking ADP receptors (inhibit fibrinogen binding by preventing glycoprotein IIb/IIIa expression)
3) Cilostazol, Dipyrimadole
- PDEIII inhibitor that increases cAMP in platelets and inhibits their activation
4) Abciximab
- Monoclonal antibody against GpIIb/IIIa on activated platelets, preventing aggregation via fibrin cross-linking |
|
|
Term
What are the clinical uses/toxicities of the drugs with the following mechanisms of action?
1) Monoclonal antibody against GpIIb/IIIa
2) Inhibitor of ADP-receptor on platelets
3) Irreversible inhibition of COX1/2 in platelets
4) PDEIII inhibitor, increasing cAMP in platelets and preventing activation. |
|
Definition
1) Abcixumab
- Use for ACS and percutaneous transluminal coronary angioplasty (PTCA)
- Bleeding, TP
2) Clopidogrel and Ticlopidine
- Use in ACS, coronary stenting and to prevent stroke recurrence.
- Neutropenia (ticlopidine)
3) ASA
- Antipyretic, analgesic, anti-inflammatory, anti-coagulation prophylaxis.
- GI ulcers, bleeding, hyperventilation, Reye's syndrome, tinnitus
4) Cilostazol, Dipyridamole
- Intermittent claudication, coronary vasodilation, prevention of stroke/TIA (with ASA), angina prophylaxis
- Nausea, headache, facial flushing, hypotension, abdominal pain |
|
|
Term
What part of the cell cycle is inhibited by each of the following Cancer drugs?
1) Vinca alkaloids and Taxols
2) Bleomycin
3) Etoposide
4) Antimetabolites |
|
Definition
1) M phase- Microtubule inhibitors
2) G2 (synthesis of components for mitosis)
3) S and G2
4) G1 (synthesis of components for DNA synthesis |
|
|
Term
Which anti-neoplastic drugs inhibit each of the following aspects of cellular function?
1) Nucleotide synthesis
2) DNA
3) Cellular Division |
|
Definition
1) Nucleotide synthesis
- Thymidine synthesis inhibitor (MTX and 5-FU)
- Purine synthesis inhibitor (6-MP)
2) DNA
- DNA cross-link (Alkylating agents and Cysplatin)
- DNA intercalators (Dactinomycin, doxorubicin)
- Topoisomerase II inhibitor (Etoposide)
3) Cell division
- Inhibit microtubule formation (Vinca alkaloids)
- Inhibit microtubule disassembly (Paclita |
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|
Term
What is the clinical use of each of the following drugs (mechanism described).
1) Folic acid analog that inhibits Dihydrofolate reductase, leading to decreased dTMP, decrease DNA and decreased protein synthesis.
2) Pyrimidine analog that is activated to a compound that covalently complexes folic acid and inhibits thymidylate synthase (decreasing dTMP, DNA and protein)
3) Purine analog (thiol) that is activated by HGPRTase and decreases de novo purine synthesis
4) Pyrimidine anlog that inhibits DNA polymerase |
|
Definition
These are all anti-metabolite drugs that are S-phase specific!
1) MTX
- Cancer: Luekemias, Lymphomas, Sarcomas
- Other: Abortion, Ectopic pregnancy, RA and Psoriasis
2) 5-FU activated to 5F-dUMP
- Cancer: Colon and other solid tumors, basal cell carcinoma (topical)
- Synergy with MTX
3) 6-MP
- Cancer: Leukemia, lymphoma (NOT CLL or Hodgkin's)
- 6-TG works the same way and is used to treat ALL
4) Cytarabine (ara-C)
- Cancer: AML, ALL, high-grade NHL |
|
|
Term
| How can you reverse the action of MTX or 5-FU in cancer treatment? |
|
Definition
1) MTX- Myelosuppression reversed by Leucovorin (folinic acid)
- Folic acid analog that inhibits DHFR
- Also causes macrovesicular fatty change in liver, mucositis and birth defects.
2) 5-FU- Myelosuppression reversed with Thymidine
- Pyrimidine analog that is activated to 5F-dUMP, complexes with folic acid and inhibits thymidyalte synthase
- Also causes photosensitivity |
|
|
Term
Which of the following is NOT a side effect of MTX use?
1) Mucositis
2) Birth defects
3) Thrombocytopenia
4) Myelosuppression
5) Macrovesicular fatty change of liver |
|
Definition
3- TP is a side effect of Cytarabine use (ara-C)
MTX is folic acid analog that inhibits DHFR in treatment of leukemia/lymphoma, abortion and autoimmune MSK disorders.
1) Myelosuppression (reversed by leucovirin)
2) Macrovesicular fatty change
3) Mucositis
4) Teratogenic |
|
|
Term
Which of the following regarding 5-FU is FALSE?
1) Pyrimidine analog
2) Myelosuppression rescued with leucovirin
3) Inhibits thymidylate synthase
4) must be bioactivated for action
5) complexes with folic acid
6) causes photosensitivity |
|
Definition
2- It causes myelosuppression and photosensitivity, and is rescued with thymidine
MTX (another anti-metabolic drug) is rescued with leucovirin)
5-FU is pyrimidine analog activated to 5F-dUMP, complexes with folic acid and inhibits thymidylate synthase, preventing dTMP production and decreasing DNA/protein synthesis.
5-FU is useful for solid tumors and basal cell carcinoma (topical)- works synergistically with MTX |
|
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Term
Which of the following regarding 6-Mercatpopurine is FALSE?
1) Anti-metabolite drug that has S-phase-specific action
2) Purine (thiol) analog that inhibits de novo purine synthesis
3) Must be activated by HGPRTase
4) Toxic to the bone marrow, GI and Liver
5) Can be given with allopurinol |
|
Definition
5) 6-MP is metabolized by xanthine oxidase, and therefore exhibits GREATER toxicity when given with allopurinol (unlike its sister compound, 6-TG, which is used to treat ALL).
6-MP IS a purine (thiol) analog that is activated by HGPRTase, inhibits de novo purine synthesis and is used to treat leukemia/lymphoma (NOT CLL or Hodgkin's) |
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Term
Which of the following statements regarding Cytarabine is FALSE?
1) Anti-metabolite agent used to treat AML, ALL and high grade NHL
2) Pyrimidine analog that inhibits DNA polymerase
3) Can cause leukopenia, TP and megaloblastic anemia
4) Can cause macrovesicular fatty change in liver and myeolsuppression.
5) S-phase specific action |
|
Definition
4- This toxicity profile describes MTX, another anti-metabolite agent that inhibits DHFR and inhibits dTMP, DNA and protein synthesis (Myelosuppression with MTX is reversed by leucovirin)
All anti-metabolites act in the S-phase, and Cytarabine is a pyrimidine analog that inhibits DNA polymerase in the treatment of ALL, AML and high grade NHL |
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Term
Which of the following drugs is should not be given with allopurinol?
1) MTX
2) 6-TG
3) 6-MP
4) 5-FU
5) ara-C |
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Definition
| 3) 6-MP (purine/thiol analog that inhibits de novo purine synthesis) is metabolized by Xanthine oxidase (which is inhibited by Allopurinol). |
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Term
| What are the major available anti-tumor antibiotics/mechanisms of action? |
|
Definition
1) Dactinomycin (ACTinomycin D)
- Intercalates with DNA and used for childhood tumors (Wilm's, Ewing's sarcoma, Rhabomyosarcoma)
2) Doxorubicin (Adriamycin) and Daunorubicin
- Generates free radical and non-covalently interacts with DNA (breaks and inhibits replication)
- Used for Hodgkin's lymphoma, myeloma and sarcoma
3) Bleomycin
- Induces free radical formation and DNA breakage (G2 action)
4) Etoposide (VP-16) and Teniposide
- Inhibits topoisomerase II (increases DNA degradation and acts on S/G2 phases) |
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Term
What are the clinical uses of each of the drug mechanisms/toxicities described below
1) Intercalates with DNA and causes myelosuppression
2) Intercalates with DNA, produces free radicals and causes Cardiotoxicity
3) Induces free radical formation, causing DNA breaks and inhibiting G2 phase, with pulmonary fibrosis and skin changes, but minimal myelosuppression
4) Inhibits topoisomerase II, increasing DNA degradation (S/G2 phases) and associated with myelosuppression, GI irritation and alopecia |
|
Definition
All are anti-tumor antibiotics
1) Dactinomycin (ACTinomycin D)
- Used in childhood tumors (Wilm's, Ewing's sarcoma, Rhabdomyosarcoma)
2) Doxorubicin (Adriamycin) or Daunorubicin
- Hodgkin's lymphomas, as well as myeloma, sarcoma and solid tumors (breast, ovary and lung)
- Cardiotoxicity prevented with Dexrazoxane (iron chelating)
3) Bleomycin
- Testicular caner and Hodgkin's lymphoma
4) Etoposide (VP-16) or Teniposide
- Small cell carcinoma of lung and prostate, as well as testicular carcinoma |
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Term
What drug is associated with each of the following?
1) Cardiotoxicity reversible with Dexrazoxane (iron chelation)
2) Treatment of childhood tumors like Wilm's tumor
3) Associated with pulmonary fibrosis, skin changes and minimal myelosuppression, in the treatment of Hodgkin's lymphoma and testicular cancer
4) Treats small cell carcinoma of lung and prostate, but causes myelosuppression, GI irritation and alopecia |
|
Definition
All are anti-tumor antibiotics
1) Doxorubicin (Adriamycin) and Daunorubucin treats Hodgkin;s lymphomas, myelomas, sarcomas and solid tumors, but cause dilated cardiomyopathy, allopecia and myelosuppresion.
2) Dactinomycin (ACTinomycin A)- associated with myelosuppresion
3) Bleomycin- induces free radical generation and DNA breakage (S/G2 phase)
4) Etoposide (VP-16)- Topoisomerase II inhibitor |
|
|
Term
| What are the major available alkylating agents/mechanisms of action? |
|
Definition
DNA cross-linkers
1) Cyclophosphamide, Ifosamide
- Covalently X-link DNA at guanine N-7 (must be bioactivated in liver)
2) Nitrosoureas (Carmustine, lomustine, semustine, streptozocin)
- Must be bioactivated and cross BBB (CNS toxicity- ataxia and dizziness)
3) Busulfan
- Alkylates DNA |
|
|
Term
Which of the following drugs is associated with each of the following?
1) Pulmonary fibrosis and hyper-pigmentation during CML treatment or when ablating bone marrow prior to transplant
2) Dizziness and ataxia during treatment of glioblastoma multiform |
|
Definition
|
|
Term
| Which anti-cancer drug is associated with hemorrhagic cystitis and myelosuppresion during treatment of NHL? |
|
Definition
Alkylating agents, Cyclophosphamide and Isofamide
Prevent partially with Mesna, which has a thiol group that binds toxic metabolite of cyclophosphamide. |
|
|
Term
| What are the major available microtubule inhibitors/mechanisms of action? |
|
Definition
Microtubule inhibitors (vinca alkaloids and Taxols) act on M phase
1) Vincristine, vinblastine
- Alkaloids that bind tubulin and block polymerization, preventing spindle formation
- Used in Hodgkin's lymphoma, Wilms tumor, choriocarcinoma and ALL
2) PacliTAXel andTAXols
- Hyperstabalize polymerized microtubules to prevent spindle breakdown (anaphase cannot occur)
- Used in ovarian/breast cancer
- watch out for myelosuppression and hypersensitivity |
|
|
Term
| Which microtubule inhibitors are associated with bone marrow suppression, paralytic ileus and neurotoxicity? |
|
Definition
Vincristine and Vinblastine (alkaloids that prevent microtubule polymerization in M phase).
Used to treat Hodgkin's lymphoma, Wilm's tumor, Choriocarcinoma and ALL |
|
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Term
| Why might you prescribe Paclitaxel and how does it work? |
|
Definition
Anti-microtubule agent used in ovarian and breast carcinomas.
1) Hyper-stabilize polymerized microtubules in M phase (prevent anaphase)
2) Myelosuppression and hypersensitivity is issue |
|
|
Term
When might you use each of the following chemotherapy compounds?
1) Cysplatin, carboplatin
2) Hydroxyurea
3) Prednisone
4) Tamoxifen, raloxifene |
|
Definition
1) Cross-linkes DNA
- Testicular, bladder, ovary and lung cancer
2) Inhibits ribonucleatide reductase, inhibiting DNA Synthesis (S phase)
- Melanoma, CML, and SCD
3) Trigger apoptosis and may act on non-dividing cells
- Used in CLL, Hodgkin's (MOPP regimen) and autoimmune disease
4) SERMs- receptor antagonists in breast and agonists in bone. Block binding of estrogen to estrogen receptor-positive cells.
- Used in breast cancer and to prevent osteoporosis |
|
|
Term
Which chemotherapy agent is described by each of the following? What is its clinical use?
1) Inhibits ribonucleotide reductase and causes Bone marrow suppression and GI upset
2) Triggers apoptosis and causes cushing-like symptoms, including immunosuppression, cataracts, acne, osteoporosis and hypertension.
3) Cross-links DNA and causes nephrotoxicity and acoustic nerve damage
4) Activates estrogen receptors in bone and inhibits them in breast |
|
Definition
1) Hyoxyurea- CML, SCD and melanoma
2) Prednisone- CLL and Hodgkins lymphoma (part of MOPP regimen)
3) Cysplatin, Carboplatin- testicular, bladder, ovary and lung cancer
- prevented nephrotoxicity by adding amifostine/free radical scaveneer and chloride diuresis
4) Tamoxifen, raloxifen- Breast cancer and osteoporosis |
|
|
Term
| Why is tamoxifen use in treating breast cancer associated with increased risk of endometrial cancer, while raloxifene is not? |
|
Definition
Only tamoxifen exerts partial agonist effects on endometrial tissue and causes "hot flashes".
Both compounds are SERMS that inhibit estrogen receptor in breast and activate it in bone. |
|
|
Term
| How can you prevent nephrotoxcity when using Cysplatin to treat ovarian cancer? |
|
Definition
| Give amifostine (free radical scavenger) and chloride diuresis |
|
|
Term
How do each of the following antibodies work to treat cancer?
1) Trastuzumab (Herceptin)
2) Imatinib (Gleevec)
3) Rituximab |
|
Definition
1) Monoclonal antibody against HER-2 (erb-B2), a tyrosine kinase over-expressed in certain breast cancers.
- Treat metastatic breast cancer but watch cardiotoxicity
2) Philadelphia chromosome bcr-abl TK inhibitor used to treat CML and GI stromal tumors
- watch out for fluid retention
3) Monoclonal antibody against CD20 (B cell neoplasms), used in NHL and RA (with MTX) |
|
|
Term
What are the common chemotoxicities associated with each of the following agents?
1) Cisplatin/Carboplatin
2) Vincristine
3) Bleomycin
4) Doxorubicin
5) Cyclophosphamide
6) 5-FU
7) 6-MP
8) MTX |
|
Definition
1) Nephrotoxicity and acoustic nerve damage
2) Anti-microtubule (polymerization inhibition)- peripheral neuropathy
3) Antibiotic- Pulmonary fibrosis (also Bulsulfan)
4) Antibiotic- Cardiotoxicity
5) Alkylating agent- hemorrhagic cystitis (mesna)
6) Anti-metabolite- myelosuppresion (thymidine)
7) Anti-metabolite- myelosuppression
8) Anti-metabolite- myelosuppression (leucovirin) |
|
|
Term
True or False:
The first presentation of iron deficiency anemia is a microcytic, hypochromic anemia? |
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Definition
False. All the labs come first.
Serum ferritin is first, followed by serum iron, increased TIBC, decreased saturation. |
|
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Term
What are the most common causes of iron deficiency anemia in children, adult males, women <50 and adults > 50
. What is the most common reason for failure to treat iron deficiency anemia? |
|
Definition
1) Children- Mecke;s diverticulum
Adult males- PUD
Adult women- Menorrhagia
Older adults- Polyps/colorectal cancer (positive blood in stool)
2) Most commonly compliance issue, but can also be blood loss or absorption issue |
|
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Term
What is the most common anemia of hospitalized patients?
What about alcoholics? Patients with cancer? |
|
Definition
All are ACD- microcytic, hypochromic anemia due to increased hepcidin levels and iron getting stuck in marrow macrophages.
Iron enters macrophages, but never comes out! |
|
|
Term
| How do you treat each of the microcytic anemias? |
|
Definition
1) Iron deficiency- Ferrous sulfate PO
2) ACD- treat underlying disease, and may give EPO
3) Thalassemia- No treatment
4) Sideroblastic anemia- B6
5) Lead poisoning- EDTA, Dimercaperol, Succimer |
|
|
Term
| Describe the 4 major forms of alpha thalassemia. |
|
Definition
4 alpha genes
1) 1 deletion has no manifestation
2) 2 deletions produces "trait" with mild anemia
- Blacks have on different chromosomes
- Asians have both on same chromosome
3) 3 deletions produces HbH disease (4 beta chains)
- Severe hemolytic anemia
4) 4 deletions produces Hb Bart (4 gamma chains)
- Death |
|
|
Term
| What might be on your differential if increased HbA2 and HbF are detected on protein electrophoresis during a workup for microcytic anemia? |
|
Definition
Beta thalassemia. HbA2 uses 2 delta-chains and HbF uses 2 y-chains. HbA is decreased because beta is missing.
Would expect severe hemolytic anemia with jaundice and ineffective erythrppoiesis
If its B-Thal major (Cooleys' with B0/B0) you will need long-term transfusions, with a danger of hemosiderosis. |
|
|
Term
| What might be on your differential if increased HbA2 and HbF are detected on protein electrophoresis during a workup for microcytic anemia? |
|
Definition
Beta thalassemia. HbA2 uses 2 delta-chains and HbF uses 2 y-chains. HbA is decreased because beta is missing.
Would expect severe hemolytic anemia with jaundice and ineffective erythrppoiesis
If its B-Thal major (Cooleys' with B0/B0) you will need long-term transfusions, with a danger of hemosiderosis. |
|
|
Term
Which of the following is not a known cause of sideroblastic anemia?
1) Chronic alcoholism
2) Pyridoxine deficiency from isoniazid treatment of TB
3) Defect in ferrochelatase
4) Folic acid deficiency
5) X-linked recessive defect in ALA-synthase |
|
Definition
4- This would produce a completely different (macrocytic) anemia
Sideroblastic anemia is caused by alcohol, lead (ferrochelatase), B6 deficiency and hereditary/ALA-synthase |
|
|
Term
Why might each of the following cause macrocytic anemia due to B12 deficiency?
1) Vegan diet
2) Malnutrition
3) Pernicious anemia
4) Chrohn's disease/Celiac disease
5) Bacterial overgrowth
6) Chronic pancreatitis
8) Pregnancy |
|
Definition
Pernicious Anemia is most common
1) Not enough intake
2) Elderly, same issue as 1
3) Autoimmune destruction of parietal cells (no IF or HCl)
- B12-IF complex cannot be reabsorbed in illeum and B12 cannot be released from protein in stomach by HCl
4) Terminal illeal disease (no B12-IF reabsorption)
5) Bacteria use it!
6) No pancreatic enzymes to release B12 from R-binders in duodenum
7) Over-utilization (more likely in vegan)
- B12 is ingested (meat, eggs, dairy) and released from dietary protein by Pepsin (HCl from parietal cells converts pepsin from pepsinogen)
- Free B12 binds R-binders (synthesized in salivary gland) in stomach, which are then cleaved by pancreatic enzymes in the duodenum
- B12 then binds IF (from parietal cells) and is absorbed in terminal ileum, binds to transcobalamin II and is secreted into the plasma
- Goes to metabolically active cells of the liver. |
|
|
Term
| What kind of anemia might you have from damage to the duodenum, jejunum and illeum, respectively? |
|
Definition
1) Duodenum is where iron goes in. You might also have problem with B12, because it binds R-binders here (Mixed anemia)
2) Folate deficiency
3) B12 deficiency |
|
|
Term
True or False:
Folate stores are used up more quickly that B12 stores? |
|
Definition
| True- Only 3-4 month supply in liver, vs. years of B12 in marrow macrophages |
|
|
Term
Which of the following drugs does NOT cause folate deficiency?
1) Phenytoin
2) 5-FU
3) 6-MP
4) MTX
5) Alcohol |
|
Definition
3) 6-MP, a purine analog.
1) Phenytoin (inhibits intestinal conjugase, which makes monoglutamate form that can be absorbed)
2) 5-FU is pyrimidine analog that is activated to 5F-UMP, complexes with folic acid and inhibits thymidilate synthase (dUMP to dTMP)
4) MTX and Bactrim inhibit DHFR, the enzyme responsible for converting dyhydrofolate to tetrahydrofolate.
5) Alcohol and oral contraceptives Inhibit folate release from liver |
|
|
Term
| How do B12 and folic acid interact with one another? |
|
Definition
1) B12 removes methyl group from methyl-THF (circulating form after absorption of monoglutamate form)
2) Methyl-B12 transfers methyl group to homocysteine to make methionine
**look for elevated homocysteine in either deficiency**
3) Thymidylate synthase uses THF to convert dUMP to dTMP (5-FU inhibition), and THF is replenished by DHFR (MTX and Bactrim inhibition)
4) B12 is also co-factor for methylmalonyl CoA mutase, so you see increased MMA in B12 deficiency as well. |
|
|
Term
Which of the following is NOT associated with B12 deficiency anemia?
1) Achloridia from hypergastrinemia
2) Prolonged PPi use
3) Decreased vibratory sensation and proprioception
4) Muscle spasticity and ataxia
5) Normal urine methylmalonic acid
6) Hypersegmented neutrophils |
|
Definition
5- This would be seen in FOLIC ACID deficiency, megaloblastic anemia
Elevated homocysteine (no methyl transfer to make methionine) and MMA (no MMCoA reductase to make succinyl CoA from MMA).
1) no gastric acid, so no breakdown of B12 in diet to bind R-binders
2) Pernicious anemia attacks parietal cells (no IF or HCl)
3 & 4) Neuro from SCD of spinal chord (dorsal columns, lateral corticospinal tracts and spinocerebellar tract) |
|
|
Term
| What are the possible causes of normocytic anemia with corrected reticulocyte count <3%? |
|
Definition
1) Acute blood loss (wait 5-7 days for response)
2) Early iron deficiency
3) Aplastic anemia (antigenic alteration of myeloid cells and T-cell attack)
4) Chronic renal failure (loss of EPO)
5) Malignancy (ACD) |
|
|
Term
| What is the pathogenesis/treatment of the heriditary disorders of RBC shape and what type of anemia do they produce? |
|
Definition
An extravascular, instrinsic hemolyic anemia (normocytic)
1) Autosomal dominants disorders with defective Ankyrin (spherocytosis) and Spectrin band 4.1 (eliptocytosis)
2) Treat with splenectomy (look out for encapsulated- N. meningiditis, H. influenza, S. pneumoniae) |
|
|
Term
Which of the following causes an intrinsic, intravascular hemolytic anemia
1) HbS homozygote
2) Mutation in Ankyrin protein
3) Acquired defect in decay accelerating factor
4) IgG-mediated hemolysis |
|
Definition
3- Paroxysmal nocturnal hemoglobinuria (lack of DAF prevents de-stabalization of C3 and C5 convertase, so you get complement-mediated lysis and intravascular hemolysis). Causes episodic pancytopenia
1) SCD is intrinsic, extravascular
2) Hereditary spherocytosis is intrinsic, extravascular
4) Warm immune hemolytic anemia is extrinsic, extravascular. |
|
|
Term
| What are the major types of immune hemolytic anemia? |
|
Definition
normocytic, hemolytic anemia with spherocytes (IgG) from splenic removal
1) Autoimmune (most common
C3b (extravascular) and C5-C9 (intravascular))
- Warm IgG (70%)- primary or secondary (SLE)
- Cold IgM (30%)- primary or secondary (EBV, Myco)
2) Drug-induced
3) Alloimmune |
|
|
Term
| What are the primary causes of micro- and macro-angiopathic hemolytic anemia? |
|
Definition
Both cause intravascular, extrinsic hemolytic anemia (hemoglobinuria)
1) Micro- microcirculatory defects causes RBC fragmentation (schistocytes)
- TTP, HUS, DIC
2) Macro- valvular defect (aortic stenosis) |
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Term
True or False:
The most common cause of hemolytic anemia is Plasmodium faciparum. |
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Definition
False! Most lethal, but P. vivax is most common.
- Female anopheles mospquito transmits plasmodia to humans where intra-erithrocytic parasites cause extravascular hemolysis
.
- Prevent with Chloroquine (or atovaquone-proguanil for resistant) and treat with Cloroquine |
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Term
Which of the following is NOT a cause of eosinophelia (>700 cells/ml3)?
1) Strongyloidiasis
2) Pinworm
3) Polyarteritis nodosa
4) Hay fever
5) Bronchial asthma |
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Definition
2- Pinworm (and adult ascarisis) are NOT invasive helminthes, so they do not cause eosinophilia
Eosinophlia
1) Type-1 hypersensitivity (Bronchial asthma, PCN, hay fever)
2) Invasive helminthes (Strongyloides, hookworm)
3) Polyarteritis nodosa
4) Lack of sequestration in LN (hypocortisolism) |
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Term
| What are the most common causes of lymphocytosis? |
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Definition
>4000 in adults and >8000 kids
1) Viral- CMV, EBV
2) Bacterial- Whooping cough
3) Drugs- Phenytoin
4) Graves disease (autoimmune hyperthyroidism) |
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Term
17 year old male presents with fatigue, exudative tonsilitis, hepatosplenomegally and generalized, painful lymphadenopathy.
What should you expect in laboratory analysis?
How do you make the diagnosis? |
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Definition
EBV infection- infects CD21+ B cells and lies dormant.
1) Look for abnormal lymphocytes (T cells reacting to viral B cell antigens) and lymphocytosis
2) Screen with Heterophil test (anti-horse) for IgM and confirm later with Anti-Epstein Barr nuclear antigen (EBNA) test |
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Term
What are the most characteristic leukemias of each of the following age groups?
1) <14
2) 15-39
3) 40-60
4) >60 |
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Definition
CLL is MOST common overall
1) ALL- CNS and testicular involvement (12:21 are protective)
2) AML (auer rods and M3 (15:17)W\ subtype for all-trans RA)
3) AML or CML (philadelphia chromosome 9:21, bcr-abl)
4) CLL |
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Term
25 year old patient presents with fever, fatigue and hepatosplenomegaly, as well as generalized painless lymphadenopathy.
They are thrombocytopenic and have had blood in their stool.
What is most likely going on? |
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Definition
Symptoms fit acute lymphoma/leukemia and age fits AML.
Look for auer bodies on smear and significant blasts.
AML is most severe survival (21% at 5 years) |
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Term
Why do you see each of the following in a patient with increased RBC mass, normal SaO2, splenomegaly and absolute leukocytosis.
1) Itching after a shower
2) Gout
3) Thrombosis
4) Impaired CNS circulation
5) Ruddy face
6) Hepatosplenomegaly |
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Definition
Polycythemia vera (chronic myeloproliferative)- treat with phlebotomy +/- hydroxyurea
1) Hyperhistaminemia- also see PUD
2) Hyperuricemia from increased purine breakdown
3) Hyperviscosity related to RBC count
4) Hyperviscosity
5) Vessel congestion
6) Work on high RBC mass |
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Term
| What are the 4 forms of chronic myeloproliferative disorders and what are their treatments? |
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Definition
1,3 and 4 may have JAK2 mutations on 9p
1) P. vera: phlebotomy +/- hydroxyurea
2) CML: Imatinib mesylate for bcr;abl 9:22
3) Myelofibrosis and metaplasia: Hydroxyurea and IFN-a
4) Essential thrombocythemia
- Hydroxyurea |
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Term
| What is the most likely explanation for a 75 year old male with pancytopenia and hyper-cellular marrow? Why might you be especially worried? |
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Definition
Myelodysplastic syndrome
>30% progress to acute leukemia! |
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Term
| What is the major concern for a 25 year old women with t(15:17) acute leukemia? How can you treat? |
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Definition
AML worry is DIC
Treat with all-trans RA
Otherwise:
1) Induction- ara-C and Daunorubicin
2) Consolidation; aggressive chemo w or w/o radiation
3) Maintenance: ara-C |
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Term
| What is the treatment protocol for the luekemia that presents in young children with TdT+ CD10+ clonal cells and a t(12:21)? |
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Definition
Germinal center B cell ALL with protective translocation
1) Induction: vincristine, prednisone, L-asparaginase
2) Consolidate: aggressive chemo w or w/o radiation
3) Maintenance: MTX and 6-MP
BMT is also an option |
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Term
| What are the pertinent clinical and laboratory findings associated with the ONLY leukemia without lymphadenopathy? |
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Definition
Hairy Cell Leukemia (B cell in middle-aged men)
- Treat with purine analogs
- Positive TRAP stain
1) Splenomegaly (site of proliferation)
2) Absence of lymphadenopathy
3) Hepatomegaly (20%)
4) Autoimmune vasculitis/arthritis
Pancytopenia and Leukemic cells with hair-like projections. |
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Term
| What type of leukemia presents with skin infiltration and lytic bone lesions with hypercalcemia in an adult male? |
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Definition
Adult T cell leukemia from HTLV-1
CD4+ TdT- |
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Term
Which B-cell NHL form is associated with each of the following?
1. Patients >60 with generalized lymphadenopathy and peripheral blood lymphoma cells
2) Children with jaw cancer associated with EBV and t (8:14) of cMYC
3) Germinal center disease is children and elderly
4) Low-grade malignant lymphoma of stomach deriving from MALT, associated with H. pylori
5) Adults with generalized lymphadenopathy and bone marrow involvement- associated with t(14:18) bcl-2 |
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Definition
1) CLL- would be SLL if confined to LN (most common overall)
2) African Burkitt's lymphoma (starry sky)
3) Diffuse large B-cell lymphoma
4) Extra-nodal marginal zone lymphoma
5) Follicular lymphoma |
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Term
| What are 2 major lysosomal storage diseases that can cause splenomegaly? |
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Definition
1) Gaucher's disease
- Deficiency of glucocerebrosidase, with lysosomal accumulation of glucocerebroside
- see "fibrillary" macrophages
2) Niemann-Pick
- Deficiency of sphingomyelinase, with accumulation of sphingomyelin
- Macrophages have "soap bubble" appearance |
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Term
| What are the primary causes of splenomegaly? |
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Definition
1) Autoimmune
- SLE, ITP, anemia
2) Infection
- EBV (antigenic stimulation of T cells)
3) Parasites
- Malaria
4) Lysosomal storage
- Niemann-pick= sphingomyelinase deficiency with soap bubble macrophages
- Gouchet's= glucocerebrosidase deficiency with fibrillary macrophages |
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Term
| What is the genetic inheritance of the group of coagulation disorders that present with prolonged PTT and normal PT? |
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Definition
| Hemophilia A (VIII) and B (IX) are X-linked recessive conditions with finding of late re-bleading, hemarthrosis and deep muscular bleeding. |
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Term
Which of the following is not characteristic of VWD?
1) Autosomal dominant inheritance
2) Associated with MVP, Marfan's syndrome and Andiodysplasia
3) Primarily found in Mediterranean population.
4) Decreased VIII
5) Treated with DAVP (desmopressin)
6) Abnormal rCOF assay |
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Definition
3- This population is affected by Beta Thalassemia, but not particularly associated with AD VWD
rCOF assay measures vWF activity and DAVP gets vWF out of weiber palladine bodies in endothelial cells |
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Term
Which of the following is NOT a common cause of vitamin K deficiency?
1) Celiac sprue
2) Prolonged treatment with antibiotics
3) Heparin treatement
4) Cirrhosis
5) Warfarin treatment |
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Definition
3- Heparin binds and activates AT-III, which inhibits VIII, IX, XI, XII and II, enzymes that are activated by vitamin K, but not vitamin K itself (monitored by PTT).
1) Decreased small bowel reabsorption of fat-soluble vitamins
2) Bacterial colonization is key for synthesis
4) Decreased activation because there is less epoxide reductase
5) Inhibition of epoxide reductase |
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Term
| Why is DIC considered a "thrombohemorrhagic disorder"? |
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Definition
There is bleeding from consumption of coagulation factors. You need to treat underlying condition and transfuse to replete factors!
In cases of sepsis (E. coli), disseminated malignancy (AML- M3), crush injuries, rattlesnake venom), the coagulation cascade is activated and fibrin thrombi develop in microcirculation. There is also secondary activation of the fibrinolytic system, which is why you can diagnose with D-dimer and/or fibrin breakdown products. |
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Term
| How do you treat a patient who recently had open heart surgery, has a + FDP and a -D dimer? |
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Definition
Primary fibrinolysis= Aminocaproic acid
D-dimer is negative because there are no fibrin thrombi (unlike DIC) |
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Term
| What are the primary "acquired thrombosis syndromes"? |
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Definition
1) Antiphospholipid syndrome (APLS)
- Anticardiolipin (false positive syphilis)
- Lupus anti-coagulant (prolonged PTT without mixing correction)
- Anti-beta 2 glycoprotein
2) Post-operative state with stasis
3) Malignancy
4) Folate/B12 deficiency
- homocysteinuria
5) OCPs
6) Hyper-viscosity (P. vera and Waldenstrom's macroglobulinemia) |
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Term
| What are the components of a standard "cross match" for a blood donation? |
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Definition
1) ABO group and Rh type
2) Antibody screen for atypical antibodies (indirect)
3) Direct Coomb's for atypical IgG antibodies on patient RBC
4) Major crossmatch (antibodies against foreign antigens on donor cells) |
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Term
| What are the 3 possible transfusion reactions that can occur with blood donation? |
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Definition
1) Allergic
- Type 1 IgE-mediated against proteins in donor blood
- Urticaria with pruritis, fever, tachycardia, anaphylaxis (IgA)
2) Febrile
- Recipient has anti-HLA antibodies against donor (type II)
- Fever, chills, headache, flushing= give anti-pyretic
3) Acute hemolytic transfusion reactions (HTR)= RARE
- Fever, back pain and hypotension, with worry of DIC
- Extravascular- atypical antibody reaction (IgG)
- Intravascular- ABO incompatibility (type II-IgM)
- Generally in context of multiple transfusions with atypical antibody development in memory B cells |
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Term
| What is the pathogenesis of ABO-type and Rh-type Hemolytic disease of the newborn? |
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Definition
Both cause extravascular hemolytic anemia
1) ABO
- Mother is group O (anti A/B IgG) and fetus is A or B
- IgG antibodies cross placenta, fetal splenic macrophages phagocytose IgG-bound RBCs and UCB from infant is disposed by mother's liver
- Look for anemia, positive direct Coomb's and Spherocytes
2) Rh
- Mom is Rh (-) and first baby is Rh (+)
- Mom develops anti-D IgG that crosses placenta and attacks Rh (+) fetus
- Can cause hydropis fetalis and high output cardiac failure.
- Prevent by giving mother anti-D globulin, which will NOT pass the placenta, but that will prevent sensitization. |
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Term
| Why might you use blue flourescent light or sunlight to treat a case of jaundice in the newborn? |
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Definition
| Convert free, insoluble bilirubin in skin to water-soluble dipyrrole |
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