Term
|
Definition
Mediterranean populations (and blacks.)
MAJOR - homozygous beta0 or beta0-beta+. HbF is predominant (Alpha2,Gamma2)
Crew cut skull look on x-ray, chipmunk faces from marrow expansion. Severe anemia, jaundice, hepatosplenomegaly, bone changes, growth retardation, iron overload (--> cardiac, liver, endocrine failure).
Treat with transfusions long term. Danger of iron overload (hemosiderosis).
MINOR - beta+-normal heterozygote. Elevated HbF and HbA2. Targeting and basophilic stipling of red blood cells in peripheral smear. Diagnose by elevated HbA2 on electrophoresis (over 3.5%)
Normally asymptomatic, mild microcytic anemia.
NO Treatment, danger of iron overload.
Pathogenesis:
Mutation in beta globin gene - splicing or promoter region. There are 2 beta globin genes. Mutations can be beta+, producing some beta globulins, or beta0, no synthesis. |
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Term
|
Definition
Asian and African populations.
Mutation of alpha globin gene (chromosome 16). There are 4 genes.
HbBarts - Hydrops fetalis, all 4 are mutated. 4 gamma units is predominant.
HbH disease - 3 are mutated. 4 beta units is predominant. Hemolytic anemia from excess beta-chain inclusions causing macrophage destruction.
Alpha-thalassemia trait - 2 are mutated. Mild anemia, elevated RBC count. 5-10% of hemoglobin is HbBarts at birth.
Tx: DO NOT GIVE IRON, danger of overload. no treatment.
Single mutation = asymptomatic. |
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Term
|
Definition
Heme synthesis defect
photosensitivity, abdominal pain, neuro
ACUTE INTERMITTENT
red wine urine
polyneuropathy
painful abdomen
accum uroporphyrine (urine), ALA, porphobilinogen
defect in porphobilinogen deaminase
CUTANEA TARDA
most common
photosensitivity - blistering
defect in uroporphyrinogen decarboxylase
accum uroporphyrin |
|
|
Term
|
Definition
1. Metabolic disorder
Pregnancy
Renal Failure (lack EPO, so no RBC production)
2. Endocrine deficiency
Androgen deficiency (to stim EPO)
Adrenal failure (cortisol stims stem cells)
Hypothyroidism (BMR)
3. Marrow Replacement
4. Marrow Failure
Aplastic anemia
Leukemia
5. Anemia of Chronic Disease
Increased RBC destruction |
|
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Term
Anemia from renal disease
Pathophys. |
|
Definition
reduced EPO production and shortened RBC lifespan
details:
Kidney peritubular capillary cells produce EPO in response to hypoxia. EPO is needed for RBC differentiation.
RBCs lifespan shortens because the kidney can't clear toxic metabolites as efficiently.
Uremia inhibits platelet functions and causes blood loss. |
|
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Term
Anemia of Chronic Inflammation.
Pathophys. |
|
Definition
1. Normocytic while bone marrow is trying to replace RBCs
2. Microcytic once iron stores are mismanaged and marrow can't keep up replacing RBCs
*Inflammation drives hepcidin expression --> blocks iron release from macrophages (because this is where it is sequestered to keep away from bacteria, which thrive off iron). Ferritin increases to store more and more iron in macrophages. Low Erythropoietin. Messed up iron cycle wastes iron.
Caused by Rheumatoid arthritis, TB infection, alcoholism, malignancy, etc |
|
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Term
|
Definition
1. High Retic Count
2. Increased RBC membranes
Liver disease (dyslipidemia)
Obstructive jaundice
Post splenectomy (lack processing)
Drugs: 5-FU, AZT, hydroxygurea
3. Hypothyroidism
4. Megaloblastic anemia
Vit B12 deficiency
Folic Acid deficiency
Chemotherapeutics that interfere with DNA synthesis (Methotrexate)
Myelodysplastic syndrome (abn stem cells)
Hereditary defects |
|
|
Term
|
Definition
A Macrocytic Anemia
Presentation:
Hypersegmented neutrophils (over 5)
Glossitis
Jaundice - Pale yellow skin
Elevated plasma homocysteine --> thrombosis risk
Elevated MCV
Marrow nuclei are large and lacy chromatin (immature) = macro-ovalocytes
Angular Stomatitis
Etiology:
Impaired DNA synthesis - Nucleus doesn't mature quickly enough. Ineffective erythropoiesis. Pancytopenia (all blood cell lines reduced).
Caused by Deficiency in Vit B12, Folic Acid, Chemotherapeutics like Methotrexate, Myelodysplastic syndromes, Hereditary defects |
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Term
|
Definition
A Macrocytic Megaloblastic anemia that causes impaired DNA synthesis.
Presentation:
like B12 deficiency but without neurologic symptoms: glossitis, weakness, fatigue, dyspnea, paresthesias, edema, pallor/jaundice, smooth tongue.
Pathogenesis:
Folate deficiency causes impaired DNA synthesis AND increases serum homocysteine, which damages endothelial cells leading to thrombosis.
Labs:
RBC folate is the best indicator of folate stores.
Normal urine methylmalonic acid (vs. elevated in vit B12 deficiency)
Etiology:
Usually due to dietary deficiency (fresh fruits/vege's! be a vegan). Need 50 microg/day, diet usually 700 but only absorb 10%.
- dietary deficiency (alcoholics, poor)
- increased requirements (pregnant, dialysis, hemolysis, chronic infection)
- malabsorption (small bowel disease, dilantin and estrogens in OCPs inhibit deconjugation needed for absorption, alcohol inhibits folate absorption and folate release from the liver wher eit is stored)
- deficient interconversion (liver disease, B12 deficiency, methotrexate, trimethoprim, dilantin)
Tx:
Oral monoglutamic folic acid. |
|
|
Term
| Vit B12 deficiency anemia |
|
Definition
A Macrocytic Megaloblastic Anemia that causes impaired DNA syntehsis AND impaired myelin production.
More common in blood group A.
Presentation:
nonspecific symptoms like jaundice, edema, pallor, dyspnea, atrophic tongue, paresthesias
AND neurologic symptoms
-Peripheral neuropathy (sensorimotor)
- Posterior column fail (vibration and proprioception)
- Lateral corticospinal (spasticity)
- Dorsal spinocerebellar (ataxia)
- Dementia
Labs:
Most sensitive test is elevated methylmalonic acid.
Peripheral blood has pancytopenia, oval macrocytes (enlarged egg shaped RBCs due to DNA maturation failure), hypersegmented neutrophils (over 5 lobes)
Etiology:
Usually Malabsorption from Pernicious anemia (lack intrinsic factor due to atrophic gastritis)
- has to be more than just a dietary deficiency because dietary requrements are so low (*except vegans)
- parietal cell damage (produce IF to absorb vit B12)
- bacterial overgrowth competes for B12
- fish tapeworms (Diphyllobothrium latum)
hereditary
-IF problem, receptor for IF problem
-Transcobalmin tranport protein (TCII) mutation
Pathogenesis:
Vit B12 is needed early in the DNA synthesis pathway, converting homocystine to methionine. Methionine is needed both for DNA synth and for myelin production.
Tx:
Vit B12 intramuscular injection.
Folate alone will help the anemia but will not fix the neurologic problems!! |
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Term
|
Definition
A Macrocytic Megaoloblastic Anemia of Vit B12 deficiency due to Intrinsic Factor deficiency secondary to atrophic gastritis.
Pathogenesis:
A type II hypersensitivity reaction.
Autoantibodies that block IF, can destroy parietal cells, can be against proton pump in parietal cells, can prevent VitB12-IF binding, etc. Elevates Gastrin. Increases risk of Gastric adenocarcinoma.
Causes Vit B12 deficiency which leads to impaired DNA synthesis AND impaired myelin production.
Presentation:
** achlorydria, autoantibodies, chronic atrophic gastritis (vs. other vit B 12 deficiencies)
nonspecific symptoms like jaundice, edema, pallor, dyspnea, atrophic smooth sore tongue, paresthesias
AND neurologic symptoms like decreased vibratory and positional sensation (posterior column), spasticity (lateral corticospinal tract), ataxia (dorsal spinocerebellar tract), peripheral neuropathy |
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|
Term
Ddx of Microcytic Anemia
key features. |
|
Definition
CLITS
Chronic Inflammation
Lead poisoning
Iron deficiency
Thalassemias
Sideroblastic anemias
It is a problem with hemoglobin synthesis.
MCV<80
low retic
hypochromic smear
from reduced hemoglobin synthesis |
|
|
Term
|
Definition
Presentation:
Pica and koilonychia (spoon nails) are specific but not common. Nonspecific glossitis, angular stomatitis (irritation in corners of lips), tachycardia, pallor, dyspnea, fatigue, weakness.
May see Plummer-Vinson Syndrome (achlorydia, esophageal web, glossitis, koilonychia, due to chronic iron def anemia)
Toddlers 1-2 years old and menstruating females.
Causes:
Blood loss - hookworm infestation, PUD, gastritis (NSAIDs), Meckel's diverticulum, menorrhagia, polps / colorectal cancer
Increased use - pregnancy/lactation, infants (for tissue growth)
Decreased intake - premature birth, low meat diet
Decreased absorption - Celiac sprue, gastric surgery (lack acid to help absorption)
Intravascular hemolysis
Signs before true anemia:
1. absent iron stores
2. low serum ferritin
3. low serum iron
4. high TIBC
5. low iron saturation
6. normocytic anemia
7. microcytic anemia
hypochromic RBCs on peripheral smear
Labs:
low Retic, MCV, MCHC, serum iron, serum ferritin, % transferrin saturation. Normal leukocytes. High serum FEP (free erythrocyte protoporphyrin) because no iron to bind protoporphyrin to make heme. Erythroid hyperplasia in marrow.
Tx: Give iron 100-200mg/day for 6 months (oral ferrous sulfate). At 1 week see reticulocytes, at 2 week see increased hemoglobin, both halfway to normal at 1 month, normal at 2 months.
Daily requirements: 1 mg (2mg if menstruating, 3-4 mg if pregnant). Diet usually is 10 mg, absorb 5-10%.
Bleeding: lose .5mg of iron per ml of blood lost. |
|
|
Term
Differentiate Iron deficiency anemia and Anemia of Chronic Inflammation based on:
Serum iron, ferritin, transferrin (unbound), Transferrin saturation, bone marrow iron storage. |
|
Definition
Both Microcytic Anemias (though Chronic inflammation can initially cause normocytic anemia).
Serum iron - low in both
Serum ferritin - high in Inflammation, low in Iron Def
Transferrin (unbound) - low in Inflammation, high in Iron Def
Transferrin saturation - low in both
Bone marrow iron storage - high in Inflammation, low in Iron Def |
|
|
Term
Differentiate Sideroblastic Anemia from Thalassemias based on:
Serum iron, ferritin, transferrin (unbound), Transferrin saturation, bone marrow iron storage. |
|
Definition
Both are Microcytic Anemias.
Sideroblastic Anemia is defective heme synthesis, resulting in characteristic signet ring cells in the marrow (premature RBCs packed with iron).
Thalassemias are defective globin synthesis.
Serum iron - both high (Th. can be normal)
Serum ferritin - both high (Th. can be normal)
Transferrin (unbound) - both normal
Transferrin saturation - both 30-100%
Bone marrow iron storage - both high |
|
|
Term
|
Definition
Triad:
Iron deficiency anemia (chronic)
Esophageal web
Atrophic glossitis
Koilonychia (spoon nails)
Achlorydria (no acid in stomach, decreases iron absorption because acid is needed to free elemental iron from food)
A possible presentation of chronic Iron deficiency anemia. |
|
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Term
|
Definition
An alpha thalassemia where all 4 genes are mutated on chromosome 16. No functional alpha globin is produced.
Causes Hydrops fetalis.
Predominant hemoglobin has 4 gamma units. |
|
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Term
|
Definition
An alpha-thalassemia where 3 of the 4 genes on chromosome 16 are mutated.
Predominnat hemoglobin is 4 beta units.
Presents with hemolytic anemia. |
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Term
|
Definition
A microcytic anemia due to defective heme synthesis in the mitochondria.
"Signet rings" - Iron accumulates in mitochondria of developing RBCs, forming signet ring cells in the marrow.
Labs: high serum iron, normal TIBC, high serum ferritin.
Etiology:
-*chronic alcoholism is the most common because alcohol is a mitochondrial toxin
-lead poisoning is most common cause in children 1-5
-chronic inflammation, leukemia
-drugs (isoniazid, pyrazinamide, chloramphenicol) Isoniazid therpay causes Vitamin B6 deficiency, which is needed in the RDS of heme synthesis (with delta-aminolevulinic acid synthase)
-Inherited mutation. (common= Xlinked delta-aminolevulinic acid synthase gene)
Tx:
Primary (Inherited X linked esp) - high dose pyridoxine alone or with folic acid
Secondary - remove cause. |
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Term
| Anemia from Lead poisoning |
|
Definition
A microcytic anemia where reduced heme synthesis is caused by lead inhibiting ferrochelatase and ALA dehydratase.
Basophilic stippling in RBCs from aggregating ribosomes because lead also inhibits rRNA degradation. |
|
|
Term
|
Definition
History:
Works with house paint, car batteries and radiator repair mechanics, ammunition factory, pottery glazes, or children in inner cities who eat lead-based paint (age 1-5)
Presentation: "LEADS"
LEAD LINES: (Burton's lines on gingivae, and in ephiphyses of long bones)
ENCEPHALOPATHY and ERYTHROCYTE basophilic stipping
ABDOMINAL collic and sideroblastic ANEMIA
DROPS (wrist and food drop)
Pathogenesis:
Lead denatures enzymes:
- Ferrochelatase (last step of heme synthesis, binding protoporphyrin to iron), therefore increase FEP
- ALA dehydratase (step 2 of heme synthesis) --> build up of delta-ALA which damages neurons and causes cerebral edema and demyelination --> food drop, encephalopathy
- Ribonuclease (which breaks down old rRNA, so they persist and clump in teh RBC --> basophilic stippling)
Tx: chelation therapy
DIMERCAPROL and EDTA for treatment
SUCCIMER for kids.
**Lead the only heavy metal that can deposit in epiphyses |
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Term
|
Definition
A normocytic anemia.
Presentation:
fatigue, pallor, purpura, mucosal bleeding, petechiae, infeciton
Pancytopenia, normal cell morphology, hypocellular bone marrow with fatty infiltration.
Etiology:
--Radiation/drugs (benzene, chloramphenicol, alkylating agetns)
--Viral agents (parvovirus B19, EBV, HIV, HCV)
--Fanconi's anemia (inherited DNA repair defect)
--Idiopathic, can be immune mediated
Treatment:
Remove cause, immunosuprression (cyclosporine, antithymocyte globulin), allogeneic bone marrow transplant, transfusion, G-CSF, MG-CSF |
|
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Term
|
Definition
A genetic Aplastic Anemia.
Ashkenazi Jews and Afrikaners (South Africa)
A genetic defect in DNA repair. Cancer is very common, especially acute myelogenous leukemia. Bone marrow failure by age 40.
congenital defects, commonly short stature, abnormalities of the skin, arms, head, eyes, kidneys, and ears, and developmental disabilities.
Only real treatment is bone marrow transplant.
* not the same as Fanconi's syndrome! |
|
|
Term
List most common causes of iron deficiency of anemia in the following:
Very young children (age 1-2)
Children
Adult Men under 50
Adult Women under 50
Adults over 50 |
|
Definition
Very young children - inadequate intake
Children - Meckel's diverticulum causing GI blood loss
Adult Men under 50 - PUD
Adult Women under 50 - Menorrhagia
Adults over 50 - Polyps/ colorectal cancer |
|
|
Term
Anemia of Chronic Inflammation.
Labs. |
|
Definition
| Serum Iron is low, but Serum ferritin is high, Transferrin (unbound) is low, and bone marrow iron storage is high because iron is there just mis-cycled, high FEP (high protoporphyrin). |
|
|
Term
GVHD
Graft Versus Host Disease |
|
Definition
Immunocompetent graft (includes blood products) attacks recipient.
Fatal in 80% of cases.
*Use gamma irradiation of blood products to prevent CD8 T cells from proliferating to reduce GVHD in anyone who is at risk.
At risk:
-immunodeficient patients
-newborns (esp with erythroblastosis fetalis or premature)
-anyone who has received intrauterine transfusions, hematopoietic stem cells, blood products from relatives, HLA-selected homozygous platelets
-solid tumors treated with cytotoxic agents
-hematological malignancies
-recipient donor pairs from genetically homogenous population |
|
|
Term
Non-megaloblastic Macrocytic Anemia
Traits and Ddx |
|
Definition
Traits:
No hypersegmented neutrophils
Normal Leukocytes and platelets
No glossitis
Ddx:
Liver disease from alcohol excess is most common cause.
1. High Retic Count
2. Increased RBC membranes
Liver disease (dyslipidemia)
Obstructive jaundice
Post splenectomy (lack processing)
3. Hypothyroidism
drugs like 5-FU, AZT, hydroxyurea |
|
|
Term
| Non-megaloblastic Macrocytic Anemia due to Alcohol Liver disease |
|
Definition
Non-megaloblastic Macrocytic Anemia
Traits:
Target cells on peripheral smear. (Thin, round, macrocytic) - due to excess cholesterol in membrane.
Tx:
Abstain from alcohol.... |
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|
Term
Transfusion reactions:
Acute Hemolytic Transfusion Reaction |
|
Definition
Presentation:
Fever, chills, hypotension, back pain, pain at infusion site, nausea/vomiting, DIC, hemoglobinuria.
About:
When you give someone blood products they are not compatable with (cerical error).
Fatality rate > 10%
Tx:
Stop transfusion.
Flush with IVF.
Monitor DIC and renal failure. |
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Term
Transfusion reactions:
Febrile Reaction |
|
Definition
Presentation:
Over 1 degree C increase in temperature.
About:
One of the most common transfustion reactions.
Due to cytokine release from WBC in transfusion, or Ab to WBC, or bacterial contamination.
This is nonhemolytic, and can be difficult to distinguish from Acute Hemolytic Transfusion Reaction.
Tx:
Prevent by Pre-storage leukoreduction. |
|
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Term
Transfusion reactions:
"Septic Reaction" |
|
Definition
About:
Due to bacterial contamination of blood unit.
Platelet units - common issue (stored at room temp)
RBC units - Yersinia enterocolitica, citrobacter, E. coli.
Can be deadly.
Tx:
Stop transfusion. |
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|
Term
Transfusion reactions:
Urticarial Reaction |
|
Definition
Presentation:
Rash/itching.
About:
Occurs in 3% of transfusions.
Because recipient is previously sensitized to a soluble allergen in the donor unit.
Tx:
Stop transfusion and give antihistamines.
You can restart the transfusion later! |
|
|
Term
Transfusion reactions:
Anaphylactic Reaction |
|
Definition
Presentation:
Hypotension, chills, fever, dyspnea/bronchospasm, nausea/vomiting, diarrhea, urticaria
About:
Allergic reaction.
Tx:
Stop transfusion
Give antihistamine, epinephrine, steroids
Future transfusions - wash products, premedicate, use blood from IgA deficient donors |
|
|
Term
Transfusion reactions:
TRALI (Transfusion Related Acute Lung Injury) |
|
Definition
Presentation:
Hypotension. Acute onset noncardiogenic pulmonary edema within 6 hrs of transfusion. Respiratory insufficiency, fever/chills, bilateral infiltrates on CXR.
Common after FFP transfusions.
About:
Most common cause of transfusion related fatalities in US.
Looks like ARDS but resolves in 48 hrs.
Caused by anti-HLA/anti-neutrophil antibodies attacking WBCs.
Tx:
Supportive care and ventilation. Not Diuretics!
Preventation: FFP donors are only men, not women, because if they are pregnaant they get exposed to fetal blood and can develop these anti-WBC antibodies. |
|
|
Term
Transfusion reactions:
TACO (Transfusion associated circulatory overload) |
|
Definition
Presentation:
Hypertension. Dyspnea, orthopnea, peripheral edema.
About:
You fluid overloaded the patient. Most common in pts who have cardiopulmonary problems.
Tx:
Diuretics. (Lasix)
In future, transfuse smaller volumes at slower rates. |
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|
Term
Transfusion reactions:
Iron overload |
|
Definition
Presentation:
Liver, cardiac, endocrine problems.
About:
A unit of RBCs is 200mg of iron. Iron overloaded after 10 transfusion because we hold onto iron.
Tx:
Chelation with Desferal, Exjade, or phlebotomy. |
|
|
Term
|
Definition
High retic count > 75000
Corrected retic > 3%
High non-conjugated (indirect) bilirubin
High LDH (lactic dehydrogenase, in RBCs)
Low haptoglobins (binds free hemoglobin, now all occupied) - esp in intravascular
Usually normocytic MCV = 80-94
*though intravascular may lead to microcytic
Hemosiderosis - systemic iron deposition
Increase urine urobilinogen |
|
|
Term
| Alloimmune hemolytic anemia |
|
Definition
An immune hemolytic anemia where an immunologically incompatible RBC is destroyed by the body's immune system (as in mismatched ABO for transfusion).
Amnestic response: 6-8 days (if antibodies already exist)
New response: 9-11 days |
|
|
Term
Autoimmune hemolytic anemia
Cold antibody |
|
Definition
IgM binds to RBCs at extremities (lower temperature), which are then destroyed in the liver and intravascularly. Linked to Mycoplasma pneumoniae.
Etiology:
Infectious disease (mononucleosis, Mycoplasma pneumoniae)
Lymphoproliferative disease
Idiopathic
Tx:
NOT responsive to steriods
NOT responsive to splenectomy |
|
|
Term
Autoimmune hemolytic anemia
Paroxysmal cold hemoglobinuria |
|
Definition
| Like Cold antibody autoimmune hemolytic anemia, but it is IgG not IgM attacking the RBCs at the extremities. |
|
|
Term
Autoimmune hemolytic anemia
Warm antibody |
|
Definition
Hemolytic anemia with spherocytosis (due to membrane loss) and positive direct Coombs test.
The most common immune hemolytic anemia.
Pathogenesis:
IgG binds to RBCs, which will then be destroyed in the spleen. This can happen anywhere in the body, not just the extremities.
Etiology:
Idopathic
Lymphoproliferative
Autoimmune (SLE, Hodgkin ds, non-Hodgkin lymphomas)
Infection
Tx:
Steriod
Splenectomy |
|
|
Term
Drug induced hemolytic anemia
Hapten-penicillin type
and
Innocent bystander type
and
Autoimmune Aldomet type |
|
Definition
Hapten-penicillin type:
Penicillin, cephalosporin, cephtriaxone, etc
An antibody forms against a drug, like penicillin, that is bound to the RBC membrane. This brings the antibody and RBC in close contact, and the RBC gets destroyed.
IgG usually
Innocent bystander type:
Common
Sulfonamides, Quinidine, Phenothiazines
"autoimmune drive-by lysing"
Immune complexes form with a drug, and this complex occasionally sticks to the RBCs and destroys them.
Autoimmune Aldomet:
antibody against Rh locus |
|
|
Term
Erythroblastosis Fetalis
(Autoimmune Hemolytic Anemia) |
|
Definition
Hemolysis in newborns because mother's antibodies attack fetal RBCs usually due to the Rh locus. Mother is Rh- baby is Rh+. Mom makes anti-RH IgG, which can cross the placenta. Prevented by giving mom Rhogam.
anti-AB antibodies don't cross placenta because they are IgM.
Complications:
Kernicterus - stained basal ganglia CNS with unconjugated bilirubin. This causes neurologic damage.
Hyrops fetalis - fetal heart failure with massive edema.
Direct Coombs tests positive on cord blood.
Treatment:
Prevention by giving mother anti-Rh antibody (anti-D IgG) to remove Rh-positive cells from maternal circulation. |
|
|
Term
| Paroxysmal nocturnal hemoglobinuria |
|
Definition
intrinsic hemolytic normocytic anemia with intravascular hemolysis.
Characterized by episodes of significant increase in intensity of hemolysis with macroscopic hemoglobinuria
bloody urine
abdominal pain
smooth muscle dystonias
fatigue
Pathogenesis:
GPI anchor dysfunction can't hold DAF (decay accelerating factor) to RBCs, which normally gets rid of the complement that deposits there overnight while your oxygen saturation is lower.
Diagnosis:
CD59-negative RBCs.
High urine hemosiderin.
Treatment:
Eculizumab - a humanized monoclonal antibody against terminal complement protein C5 |
|
|
Term
Non-immune mediated
acquired hemolytic anemia.
List causes. |
|
Definition
Hypersplenism.
Hypophosphatemia.
Lipid abnormalities.
Infectious agents. (Malaria (Plasmodia falciparum.)
Fragmentation hemolytic anemia.
- Macroangiopathic (heart valve)
- Microangiopathic (DIC, HUS, TTP, HELLP)
- Hemangiomas
- Disseminated Carcinoma
- Malignant HTN or Pulmonary HTN |
|
|
Term
Microangiopathic anemia.
(Fragmentation hemolytic anemia)
List causes.
What do you see on peripheral smear? |
|
Definition
See schistocytes (helmet cells) on peripheral smear.
Due to mechanical destruction
DIC,
vasculitis,
hemolytic uremic syndrome,
eclampsia,
TTP (thrombotic thrombocytopenic purpura)
HUS (Hemolytic uremic syndrome) |
|
|
Term
Macroangiopathic anemia.
(Fragmentation hemolytic anemia)
List causes. |
|
Definition
| RBCs lyse due to valvular defects (stenosis) and valvular prostheses |
|
|
Term
|
Definition
Can cause Non-immune mediated, microangiopathic, Acquired Hemolytic anemia
Severe preeclampsia with:
hemolysis (elevated LDH)
elevated liver enzymes (elevated AST)
low platelets
Multiparous slightly older women with peak frequency 27-37 weeks gestation
Treatment:
Delivery
Steroids
Platelet transfusion |
|
|
Term
TTP
Thrombotic thrombocytopenic purpura |
|
Definition
Can cause Non-immune mediated, microangiopathic, Acquired Hemolytic anemia
Pentad:
- Thrombocytopenia (low platelet count), leading to bruising or purpura
- Microangiopathic hemolytic anemia (anemia, jaundice and a blood film featuring evidence of mechanical fragmentation of red blood cells)
- Neurologic symptoms (fluctuating), such as hallucinations, bizarre behavior, altered mental status, stroke or headaches
- Kidney failure
- Fever
Pathogenesis:
Red blood cells passing the microscopic clots are subjected to shear stress which damages their membranes, leading to intravascular hemolysis and schistocyte formation. Reduced blood flow due to thrombosis and cellular injury results in end organ damage. On a continuum with HUS.
Treatment:
LDH used to monitor disease activity
Plasmapheresis - an exchange transfusion involving removal of the patient's blood plasma through apheresis and replacement with donor plasma |
|
|
Term
HUS
Hemolytic uremic syndrome |
|
Definition
Most common cause of acute renal failure in kids because it causes clotting around glomeruli.
Usually children (6mo-4y) after infectious bloody diarrhea from E.coli shiga toxin who present with the triad of:
- intravascular hemolysis
- thrombocytopenia
- acute renal failure
Can cause Non-immune mediated, microangiopathic, Acquired Hemolytic anemia
Very difficult to distinguish from TTP (thrombotic thrombocytopenic purpura).
Treatment:
ONLY supportive therapy.
Eculizumab |
|
|
Term
|
Definition
An inherited Extravascular hemolytic anemia due to membrane abnormality.
Presentation:
Splenomegally
Howell-Jolly bodies after splenectomy.
Spherical cells on peripheral smear, lacking central pallor and usually slightly smaller and hyperchromatic.
Complications:
Aplastic crisis (sudden drop in retics) in presence of viral infection, especially parvovirus B19.
Pathogenesis:
AD inheritance.
A mutation in a component of RBC cytoskeleton, usually ankyrin.
The membranes bud off very easily leading to spherical RBCs.
Mis-shapen RBCs get trapped and killed in the spleen.
Dx:
increased osmotic fragility- very senstivie to hypotonic solution.
Treatment:
Splenectomy |
|
|
Term
| Hereditary Elliptocytosis |
|
Definition
An inherited hemolytic anemia due to membrane abnormality.
AD inheritance.
Oval RBCs.
Hemolytic anemia * but not necessarily
Splenomegaly.
** often does not cause anemia
** When severe, this is called pyropoikilocytosis.
Diagnosis:
Peripheral smear with more than 20% OF RBCs shaped elliptically.
Pathogenesis:
A mutation in a component of RBC cytoskeleton, usually spectrin. |
|
|
Term
| Pyruvate kindase deficiency. |
|
Definition
An inherited Extravascular hemolytic anemia. RBCs are rigid.
Presentation:
hemolytic anemia in newborn.
Chronic sustained anemia.
AR inheritance. |
|
|
Term
|
Definition
An inherited Intravascular hemolytic anemia.
Presentation:
Back pain
Hemoglobinuria a few days after back pain
Episodic
Triggers: Sulfa drugs, anti-malarials, anti-helminthics, infections, fava beans (in Mediterranean type)!
More common in African Americans and Mediterraneans.
"bite cells" and "Heinz bodies" and "blister cells" on peripheral smear
Pathogenesis:
X-linked inheritance.
Lack G6PD therefore reduced glutatione (an antioxidant that deals with free radicals/ peroxide in cells). No NADPH therefore no reducing capacity.
RBC is susceptible to oxidant stress, and can form blister cells (compete precipitation of hemoglobin --> halo of cytososl).
Heinz bodies form = cellular inclusions in RBCs from aggregates of denatured Hb. These make the RBC less squishy. They get "bitten" when they try to get through the spleen. |
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Term
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Definition
An inherited Extravascular hemolytic anemia due to abnormal hemoglobin: a hemoglobinopathy.
Presentation:
More common in African Americans.
Does not present at birth due to HbF.
Howell Jolly bodies.
Salmonella osteomyelitis.
Vaso-occlusive pain crises.
Vessel occlusion:
Stroke, tissue infarction, episodic pain, skin ulcerations esp at lower extremities.
Bone pain from vascular necrosis of bone especially at head of femur and humerus.
Spleen:
Worse infections by encapsulated bacteria (eg. Strep pneumonia) that need to be cleared by the spleen.
Howell-Jolly bodies
Kidney:
Sickle nephropathy (tubular damage, kills glomeruli and vasa recta, renal papillary necrosis) --> dehydrate easily.
Blood cells:
"crew cut" skull x-ray from marrow expansion
Aplastic crisis from parvovirus B19
Pathogenesis:
Beta6, substition glutamic acid --> valine.
This makes the beta chain more hyrophobic, allowing it to aggregate, stimulated by
- deoxygenation
- acidity
- high Hb concentration
- high temperature.
Aggregation into long fibers causes sickling. Sickled cells have a lifespan of 12-30 days instead of 120 days.
Sickled cells obstruct blood vessels.
Spleen becomes non-functional early in life.
Encapsulated bacteria that need to be cleared by the spleen aren't cleared and cause worse infections.
Treatment:
hydroxyurea to increase HbF
Bone marrow transplant |
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Term
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Definition
An inherited Inravascular hemolytic anemia due to abnormal hemoglobin: a hemoglobinopathy.
Presentation:
More common in African American population. Often asymptomatic. Mild hemolytic anemia with prominent splenomegaly, target cells.
Can have HbSC disease which is similar to sickle cell but milder.
Pathogenesis:
Beta chain of hemoglobin at position 6, substition glutamic acid --> lysine. |
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Term
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Definition
History:
wet hay/wood
PMH:
Poor mucuous clearance (CF)
Emphysema
Sarcoidosis
Complications:
Likes to grow in blood vessels and then colonize brain.
Diagnosis:
CT: Halo-nodular infiltrate, ground glass, eventually air-crescent sign
Treatment:
Voriconazole, opt with Echinocandin |
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Term
| Zygomycosis / Mucormycosis Infection |
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Definition
High mortality, low incidence, rapid dz
Presentation:
Rhinocerebral - nasal congestion, pain behind eye, exophthalmos, altered mental status
or
Pulmonary - SOB, fever, non-productive cough, pleuritic chest pain
PMH:
Neutropenia
Immunocompromised
Diabetes poorly controlled, esp DKA
Initial infection:
spores inhaled, germinate in mucosa and invade, causing tissue necrosis
Diagnosis:
Few hyphae, must look closely
MRI: opaque sinuses
CT: edema and opacity behind eye, dense infiltrates in lung
Treatment:
Amphotericin B
Posaconazole |
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Term
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Definition
Naturally inhabits our intestines, typical of critically ill pts and those after GI surgery
Presentation:
Infection of operative site
UTI
Pneumonia
Mucocutaneous - thrush, esophagitis, diaper rash, vaginitis, folliculitis, angular chelitis
Blood stream - shock, sepsis
PMH:
Neutropenia
Indwelling central venous catheter
hemodialysis
diabetes
Neonate or >65
use of broad spectrum antibiotics
Diagnosis:
culture
Glucan test (antigen)
Multiple abscesses on imaging.
Treatment:
amphotericin B or fluconazole only if symptomatic or immunocompromised
Treatment:
Systemic - Echinocandins
Mucocutaneous - Topical azole or fluconazole |
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