Term
| What is the differential diagnosis for a macrocytic anemia with high reticulocyte absolute reticuloyte count? |
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Definition
| hemorrhage, hemolysis, recently treated B12, folate deficiency |
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Term
| If a patient has a macrocytic anemia, low absolute retic count, and round macrocytes with no hypersegmentation of polys, then the ddx includes... |
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Definition
| EtOH, liver, myelodysplasia, hypothyroidism and other non megaloblastic causes |
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Term
| What are the "big three" labs you should get to differentiate between intra and extravascular hemolysis? |
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Definition
| serum haptoglobin, LDH, and indirect bili |
|
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Term
| What aspect of the RBC is abnormal in patients with paroxysmal nocturnal hemoglobinuria? |
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Definition
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Term
| What does the PBS of hereditary spherocytosis look like? |
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Definition
| lots of spherocytes usually with polychromatocphilic RBCs |
|
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Term
| What race is predisposed to hereditary spherocytosis? |
|
Definition
|
|
Term
| What is the inheritance pattern of hereditary spherocytosis? |
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Definition
|
|
Term
| How can you correct the hemolytic process of hereditary spherocytosis? |
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Definition
|
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Term
| What part of the RBC emembrane is defective in hereditary spherocytosis? |
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Definition
| although a spectrin deficiency is seen in nearly all HS patients, the most common principle defect is an abnormality of the membrane ankyrin. Defects in band 3 (AE1) proteins are also common |
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Term
| What type of hemolysis is characterized by an abnormal permeability to sodium d/t membrane defect and dysfunctional Na/K ATPase pump? |
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Definition
|
|
Term
| A verticle defect in RBC membrane leads to what type of RBC morphology? |
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Definition
|
|
Term
| What does the CBC of HS show? |
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Definition
| variable MCV, increased MCH and MCHC (increased MCHC is characteristic), RDW may be increased |
|
|
Term
| What lab studies should you get for hereditary spherocytosis? |
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Definition
| negative anti-globulin (coomb's) test, Osmotic fagility test, and flow cytometric detection of band 3 |
|
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Term
| A positive osmotic fagility test means that... |
|
Definition
| there is asignificant number of spherocytes |
|
|
Term
| What is the clinical presentation of hereditary spherocytosis? |
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Definition
| chronic hemolysis, jaundice, splenomegaly. Can be asymptomatic to severe anemia (neonatal jaundice or aplastic crisis d/t parvovirus infection), increased incidence of gall stones |
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Term
| How do you make the diagnosis of hereditary elliptocytosis on PBS? |
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Definition
| >25% of RBCs are elliptocytes; fewer than 25% may be seen in Fe deficiency, megaloblastic anemia, myelodysplasia, and myelophthisis |
|
|
Term
| What is the inheritance pattern of hereditary elliptocytosis? |
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Definition
|
|
Term
| What genetic mutation causes hereditary elliptocytosis? |
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Definition
| lots of different ones; MCly abnormalities of spectrins, result in their inability to form multimers, non anemic |
|
|
Term
| What is thetreatment for hereditary elliptocytosis? |
|
Definition
| splenectomy in symptomatic patients |
|
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Term
| Horizontal defects in RBC cell membranes leads to what morphology? |
|
Definition
|
|
Term
| What is the inheritance pattern of hereditary pyropoikilocytosis? |
|
Definition
|
|
Term
| What is the mutation in hereditary pyropoikilocytosis? |
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Definition
| its a subtype of hereditary elliptocytosis with a spectrin deficiency combined with a spectrin defect |
|
|
Term
| Red cells that bud and fragment at lower temperatures (45) compared to normal RBCs (49) is indicative of what disorder? |
|
Definition
| hereditary pyropoikilocytosis |
|
|
Term
| How do you tell the difference between hereditary pyropoikilocytosis from MAHA on PBS? |
|
Definition
| hereditary pyropoikilocytosis does not have thrombocytopenia |
|
|
Term
| In what patient population is hereditary pyropoikilocytosis most often seen? |
|
Definition
| neonates; may be transient |
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|
Term
| What is the inheritance pattern of hereditary stomatocytosis? |
|
Definition
| usually autosomal dominant |
|
|
Term
| What are the characteristics of heterozygotes vs homozygotes of hereditary stomatocytosis? |
|
Definition
hetero= no anemia, 1-25% stomatocytes in blood
homo= mild to moderate anemia, 1/3 of cells are stomatocytes |
|
|
Term
| What is the MC mutation that causes hereditary stomatocytosis? |
|
Definition
| abnormal stomatin protein causing the membrane to be abnormally permeable to sodium and potassium |
|
|
Term
| Therapeutic splenectomy should be avoided for which herditary hemolytic disease? |
|
Definition
| hereditary stomatocytosis; splenectomy in these patients is associated with thrombosis (DVT, PE, etc.) |
|
|
Term
| What is the MCV of patients with hereditary stomatocytosis? |
|
Definition
|
|
Term
| What causes paroxysmal nocturnal hemoglobinuria? |
|
Definition
| acquired intrinsic stem cell defect (acquired membrane defect) in which the cell can no longer syntehsize the glycosyl-phosphatidyl inositol (GPT). Over time, the clone expands to dominate the RBC population and variable proportions of WBCs and platelets (megs) |
|
|
Term
| What proteins bind to glycosyl-phosphatidyl inositol anchor? |
|
Definition
| DAF (CD55) and MIRL (CD59) and C8 binding protein |
|
|
Term
| What is teh typical patient population of PNH? |
|
Definition
|
|
Term
| What are the symptoms of PNH? |
|
Definition
| abdominal pain, back pain, headaches, esophageal spasms, usually at night or in AM. Impotence concomitant with hemoglobinuria |
|
|
Term
|
Definition
| infection, surgery, contrast dyes, or severe exercise |
|
|
Term
| Pts with PNH have an increased risk of developing... |
|
Definition
| aplastic anemia or acute myelogenous leukemia |
|
|
Term
| What are the two characteristic modes of PNH clinical presentation? |
|
Definition
| hemolytic anemia (cola urine, increased retic, LDH and decreased serum haptoglobin) OR thrombotic event |
|
|
Term
| Where are common sites of PNH thrombosis? |
|
Definition
| Budd-Chiari syndrome (hepatic thrombosis), abdominal vein thrombosis may lead to bowel infarction; cerebral thrombosis, commonly with sagittal vein; dermal thromboses produces raised, painful, red nodules that may lead to necrosis |
|
|
Term
| What are the features of PNH on peripheral smear? |
|
Definition
| some polychromasia; usually normocytic but may be hypochromic (iron loss in urine) |
|
|
Term
| What are the CBC abnormalities of PHN? |
|
Definition
| neutropenia in 3/5 and thrombocytopenia in 2/3, i.e. pancytopenia common |
|
|
Term
| T/F Hemosiderinuria is almost always present in PNH. |
|
Definition
|
|
Term
| What percent of people with PNH have nocturnal hemoglobinuria? |
|
Definition
| <25% (b/c respiratory acidosis may enhance complement but urine concentration also contributes) |
|
|
Term
|
Definition
Currently: flow cytometry with monoclonal antibodies against CD 55 (DAF) and CD59 (MIRL), FLAER
previously: sugar water test and Ham test (acidified serum test) |
|
|
Term
| What is the inheritance pattern of G6PD deficiency? |
|
Definition
|
|
Term
| What races are typical of G-6-PD deficiency? |
|
Definition
| kurdish jews, blacks, middle easterners, and asians |
|
|
Term
| Describe the biochemical abnormality of G6PD deficiency. |
|
Definition
| no G6PD so NADP can't become NADPH to form GSSG and GSH to neutralize hydrogen peroxide. Increased H2O2 oxidezes Hb which precipitates as Heinz bodies |
|
|
Term
| What is the LDH, haptoglobin, and indirect bilirubin of G6PD deficiency? |
|
Definition
| increased serum LDH, decreased haptoglobin, increased indirect bilirubin |
|
|
Term
| What are the characteristics of the G6PD PBS? |
|
Definition
| normocytic anemia with bite cells |
|
|
Term
| What specific labs should you get for G6PD deficiency? |
|
Definition
| supravital stain (for heinz bodies), flourescent screening test for G6PD activity (detects formation of NADPH), RBC quantitative G6PD assay |
|
|
Term
| What are the different G6PD deficiency variants? |
|
Definition
A and B= normal variants
A-= african american type
MED = mediterranean type |
|
|
Term
| Describe the AA variant of G6PD. |
|
Definition
| half life is moderately reduced; episodic type of hemolytic anemia that occurs after exposure to oxidant streses. younger RBCs are at normal levels because they are resistant to hemolysis but older RBCs can hemolyze |
|
|
Term
| Describe the mediterranean variant of G6PD. |
|
Definition
| severe, chronic hemolytic anemia; even reticulocytes have low enzymes and hemolyze |
|
|
Term
| What are the oxidant stresses inducing hemolysis in patients with G6PD? |
|
Definition
| infection (most common), drugs (primaquine, dapsone, sulfonamides), fava beans (mainly in Mediterranean variant) |
|
|
Term
| What is the inheritance pattern of pyruvate kinase deficiency? |
|
Definition
|
|
Term
| What kind of hemolysis takes place in pyruvate kinase deficiency? |
|
Definition
|
|
Term
| What are the symptoms of pyruvate kinase deficiency? |
|
Definition
| mild to moderately severe hemolytic anemia, splenomegally |
|
|
Term
| What is the treatment for pyruvate kinase deficiency? |
|
Definition
| splenectomy is indicated in cases requiring transfusion |
|
|
Term
| What type of inherited anemia may not have notable RBC abnormalities until after splenectomy? |
|
Definition
| pyruvate kinase deficiency |
|
|
Term
| What is the biochemical pathway that is disturbed in pyruvate kinase deficiency? |
|
Definition
| Normally PK converts phosphoenolpyruvate to pyruvate leading to a net gain of 2 ATP. Chronic lack of ATP causes membrane damage and dehydration of the RBC |
|
|
Term
| Describe the PBS of a pyruvate kinase def. |
|
Definition
| normocytic anemia, RBC polychromasia, anisopoikilocytosis with echinocytes and NRBCs |
|
|
Term
| What is the confirmatory test for a pyruvate kinase deficiency anemia? |
|
Definition
|
|
Term
| What are nonimmunologic causes of extrinsic hemolytic anemias? |
|
Definition
| chemicals (drugs, venoms), physical agents (heat, trauma, MAHA), infectious agents (malaria, clostridia) |
|
|
Term
| What infectious agents cause extrinsic hemolytic anemia? |
|
Definition
| malaria, bartonella, babesiosis |
|
|
Term
| What is red cell fragmentation syndrome? |
|
Definition
| schistocytes and irregularly contracted cells (triangular or helmet cells) |
|
|
Term
| What does malaria look like on PBS? |
|
Definition
|
|
Term
| What does Babesia look like on PBS? |
|
Definition
|
|
Term
| Where is babesia/what spreads it? |
|
Definition
| vector-borne illness transmitted by lxodes ticks in the northeast US |
|
|
Term
| Causes of red cell fragmentation syndrome can be classified into what two broad categories? |
|
Definition
| cardiac valve replacement and surgica repair of septal defects with plastic patch (MACROangiopathic hemolytic anemia) and microangiopathic hemolytic anemia |
|
|
Term
| What causes Microangiopathic hemolytic anemia? |
|
Definition
| TTP, HUS, DIC, HELLP syndrome, malignant hypertension, disseminated carcinoma |
|
|
Term
| What does HELLP syndrome stand for? |
|
Definition
| hemolysis, high liver enzymes, low platelets |
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