Hematology and Oncology - Physiology

Question 1

Blood groups

• A
• B
• AB
• O
• Antibodies
• Incompatible blood transfusions can cause…

Answer 1

• A
  
  • A antigen on RBC surface and anti-B antibody in plasma.
• B
  
  • B antigen on RBC surface and anti-A antibody in plasma.
• AB
  
  • A and B antigens on RBC surface
  • No antibodies in plasma
  • “Universal recipient” of RBCs, “universal donor” of plasma.
• O
  
  • Neither A nor B antigen on RBC surface
  • Both antibodies in plasma
  • “Universal donor” of RBCs, “universal recipient” of plasma.
• Antibodies
  
  • Anti-A and anti-B antibodies—IgM (do not cross placenta)
  • Anti-Rh—IgG (cross placenta).
• Incompatible blood transfusions can cause immunologic response, hemolysis, renal failure, shock, and death

Question 2

Blood groups

• Rh
• Rh treatment

Answer 2

• Rh
  
  • Rh antigen on RBC surface.
  • Rh- mothers exposed to fetal Rh+ blood (often during delivery) may make anti-Rh IgG.
  • In subsequent pregnancies, anti-Rh IgG crosses the placenta, causing hemolytic disease of the newborn (erythroblastosis fetalis) in the next fetus that is Rh+.
• Rh treatment
  
  • Rho(D) immune globulin for mother during every pregnancy to prevent initial sensitization of Rh- mother to Rh antigen.

Question 3

Coagulation, complement, and kinin pathways (377)

• Hemophilia A
• Hemophilia B

Answer 3

• Hemophilia A
  
  • Deficiency of factor VIII.
• Hemophilia B
  
  • Deficiency of factor IX.

Question 4

Coagulation cascade components:
Procoagulation

• Warfarin
• Neonates
• Vitamin K deficiency
• vWF
• Oxidized vitamin K pathway

Answer 4

• Warfarin inhibits the enzyme vitamin K epoxide reductase.
• Neonates lack enteric bacteria, which produce vitamin K.
• Vitamin K deficiency: decreased synthesis of factors II, VII, IX, X, protein C, protein S.
• vWF carries/protects VIII.
• Oxidized vitamin K
  
  • –> [epoxide reductase]
  • –> reduced vitamin K
  • –> [(acts as cofactor)]
  • –> II, VII, IX, X, C, S: precursors –> mature

Question 5

Coagulation cascade components:
Anticoagulation

• Antithrombin
• Heparin
• Principal targets of antithrombin
• Factor V Leiden mutation
• tPA
• Protein C pathway
• Plasminogen pathway

Answer 5

• Antithrombin inhibits activated forms of factors II, VII, IX, X, XI, XII.
• Heparin enhances the activity of antithrombin.
• Principal targets of antithrombin: thrombin and factor Xa.
• Factor V Leiden mutation produces a factor V resistant to inhibition by activated protein C.
• tPA is used clinically as a thrombolytic.
• Protein C
  
  • –> [thrombin-thrombomodulin complex (endothelial cells)]
  • –> activated protein C
  • –> [protein S]
  • –> cleaves and inactivates Va, VIIIa
• Plasminogen
  
  • –> [tPA]
  • –> plasmin
  • –> fibronolysis
    
    • Cleavage of fibrin mesh
    • Destruction of coagulation factors

Question 6

Platelet plug formation (primary hemostasis) (378)

• Injury
• Adhesion
• Activation
• Aggregation

Answer 6

• Injury
  
  • vWF binds to exposed collagen upon endothelial damage
• Adhesion
  
  • Platelets bind vWF via GpIb receptor at the site of injury only (specific)
  • Platelets release ADP and Ca2+ (necessary for coagulation cascade)
  • ADP helps platelets adhere to endothelium
• Activation
  
  • ADP binding to receptor induces GpIIb/IIIa expression at platelet surface
• Aggregation
  
  • Fibrinogen binds GpIIb/IIIa receptors and links platelets
  • Balance between…
    
    • Pro-aggregation factors
      
      • TXA2 (released by platelets)
      • Decreased blood flow
      • Increased platelet aggregation
    • Anti-aggregation factors
      
      • PGI2 and NO (released by endothelial cells)
      • Increased blood flow
      • Decreased platelet aggregation
  • Temporary plug stops bleeding

Question 7

Thrombogenesis (379)

• Definition
• Aspirin
• Ticlopidine and clopidogrel
• Abciximab
• Ristocetin
• Useful for diagnosis

Answer 7

• Definition
  
  • Formation of insoluble fibrin mesh.
• Aspirin
  
  • Inhibits cyclooxygenase (TXA2 synthesis).
• Ticlopidine and clopidogrel
  
  • Inhibit ADP-induced expression of GpIIb/IIIa.
• Abciximab
  
  • Inhibits GpIIb/IIIa directly.
• Ristocetin
  
  • Activates vWF to bind to GpIb.
• Useful for diagnosis
  
  • Normal platelet aggregation response is not seen in von Willebrand disease.

Question 8

Erythrocyte sedimentation rate

• Acute-phase reactants
• Increased ESR Ž–>
• Decreased ESR –>

Answer 8

• Acute-phase reactants in plasma (e.g., fibrinogen) can cause RBC aggregation, thereby increasing RBC sedimentation rate (RBC aggregates have a higher density than plasma).
• Increased ESR Ž–> infections, autoimmune diseases (e.g., SLE, rheumatoid arthritis, temporal arteritis), malignant neoplasms, GI disease (ulcerative colitis), pregnancy.
• Decreased ESR –>Ž polycythemia, sickle cell anemia, CHF, microcytosis, hypofibrinogenemia.