Hematology (Pathophysiology)

Question 1

An autosomal dominant inherited disorder in which membrane proteins (band 3, ankyrin, and spectrin) are defected. This causes poor linkage of RBC cytoskeleton to lipid bilayer leading to continuous loss of RBC lipid bilayer. This culminates to spherical shaped RBCs that have high osmotic fragility. These RBCs get caught in the spleen and are hemolyzed leading to anemia.

Answer 1

Hereditary Spherocytosis (HS).

Question 2

An ACQUIRED disorder in which the gene encoding for GPI-linked proteins CD 55 and 59 are defective. This makes RBCs more susceptible to lysis from complement. This causes intravascular hemolytic anemia!

Answer 2

Paroxysmal Nocturnal Hemoglobinuria (PNH).

Question 3

An x-linked inherited disorder in which the gene for G6PD is mutated. This leads to low levels of G6PD and subsequent low generation of reduced glutathione (an important anti-oxidant) in RBCs increasing their susceptibility to oxidative damage (H2O2). The damage will lead to formation of Heinz-bodies leading to intra and extravascular hemolyisis of RBCs.

Answer 3

G6PD Deficiency.

Question 4

Acquired disorder in which at low temperatures IgM binds RBCs leading to extravascular hemolysis in the liver or intravascular hemolysis if MAC is formed.

Answer 4

Cold Agglutinin Autoimmune Hemolytic Anemia

Question 5

Acquired disorder in which at warm temperatures IgG binds RBCs leading to extravascular hemolysis in the liver/spleen.

Answer 5

Warm Agglutinin Autoimmune Hemolytic Anemia.

Question 6

Ingestion of lead can block heme ring synthesis via inhibition of aminolevulinate dehydratase and ferrochelatase. This will cause ineffective erythropoesis.

Answer 6

Lead poisoning induced anemia.

Question 7

A clotting disorder in which bacteria release a toxin (ie. shiga toxin from E.coli) that damages endothelial cells (especially that of the kidney). This leads to secretion of cytokines to promote clotting and vasoconstriction. RBC’s are destroyed (intravascular) as they try passing through the “minefield.” (This happens more in the kidney for HUS).

Answer 7

Hemolytic Uremic Syndrome.

Question 8

An autosomal recessive inherited disorder in which there is a deficiency of the ADAMTS13 enzyme. This leads to accumulation of vWF on the surface of endothelium causing increased platelet adhesion and microthrombosis resulting in RBCs getting lysed as the go through the “minefield.” (intravascular hemolysis)

Answer 8

Thrombotic Thrombocytopenic Purpura.

Question 9

Low protein S will decrease the inhibition of the clotting cascade (factor 5 won’t be cut). This will lead to excess clotting and eventual necrosis.

Answer 9

Protein S Deficiency.

Question 10

Enterocytes in the terminal ileum are damaged, preventing effective absorption of Vit B12. This can lead to Megaloblastic anemia.

Answer 10

Crohn’s Disease

Question 11

Autoimmune disease that increases the risk of thrombosis as a result of procoagulatory antibodies directed against phospholipids found in cell membranes. In vitro the antibodies act as an anticoagulant (prolongs aPTT) in vivo it acts as a procoagulant (shortens aPTT)

Answer 11

Lupus Anticoagulants Syndrome

Question 12

An acquired BLEEDING disorder in which immunoglobulins coat platelets (via platelet GIIb/IIIa receptors) leading to rapid destruction by macrophages (in spleen and liver). Has a childhood (viral-induced; acute) and adult (true autoimmunity; chronic) form.

Answer 12

Immune Thrombocytopenic Purpura (ITP).

Question 13

A rare autosomal-recessive BLEEDING disorder caused by a deficiency of platelet GPIIb/IIIa receptor. This deficiency leads to ineffective platelet aggregation by preventing platelet plug stabilization by fibrin! (Poor Clotting)

Answer 13

Glanzmann’s Thrombasthenia.

Question 14

An autosomal recessive BLEEDING disorder in which a defect in the GIb-V-IX receptor of platelets, prevents platelet adhesion to the subendothelium. (Poor Clotting)

Answer 14

Bernard-Soulier syndrome.

Question 15

Bleeding disorder due to drugs that inhibit platelet function. (ie. aspirin, clopidrogel, etc)

Answer 15

Drug-induced platelet dysfunction.

Question 16

A an autosomal dominant (variable penetrance) inherited BLEEDING disorder in which the patient is lacking in the number or quality of vWF. There are also low levels of factor VIII. (Poor Clotting)

Answer 16

Von Willebrand Disease (vWD).

Question 17

An X-linked BLEEDING disorder in which there is a clotting factor deficiency of either factor VIII(8) or IX(9) (<30%).

A is more common than B.

Answer 17

Hemophilia

Question 18

Lack of a certain vitamin leading to decrease in Factors; II(2), VII(7), IX(9), X(10) and decrease in proteins C and S.

Answer 18

Vitamin K Deficiency

Question 19

Increased exposure to tissue factor (ie. From diffuse endothelial injury) leads to dysregulated/unorganized activation of clotting and fibrinolytic systems with rapid formation and lysis of fibrin.

Answer 19

Disseminated Intravascular Coagulation (DIC).

Question 20

Hemophilia C is a deficiency of which clotting factor? Can it affect females?

Answer 20

Factor XI (11). 
It can effect females (autosomal recessive inheritance), but is not common in the US.

Question 21

A clot/thrombus (fibrin-rich) will form within the venous system. The clot can break off, travel through the vessels, and lead to vessel occlusion; possibly pulmonary embolism (fatal). This will cause edema, swelling, etc.

Answer 21

Venous Thromboembolism (VTE).

Question 22

Hereditary Hemoglobinopathy in which RBCs take on a “sickle” shape when deoxygenated due to defective beta Hemoglobin genes.

Answer 22

Sickle Cell Anemia.

Question 23

An autosomal dominant inherited blood-clotting disorder in a mutation of the blood’s clotting factor 5, making it more resistant to inactivation by (activated) protein C (& cofactor S) which leads to a hypercoaguable state —> Clot formation.

Answer 23

Factor V(5) Leiden.

Question 24

Anemia caused by chronic disease states leading to prolonged inflammation which impairs Iron metabolism leading to ↓ RBC production (cytokines and dysregulated iron homeostasis) and ↓ lifespan (toxins).

Inflammation → IL-6 → ↑ Hepcidin → ↓ Iron absorption

Answer 24

Anemia of Chronic Disease/Inflammation.

Question 25

PF4 receptor on heparin binds Antibody which leads to platelet activation as well as platelet sequestration (decreased platelet count)

Answer 25

Heparin Induced Thrombocytopenia (HIT)