Blood Coagulation II

Question 1

describe the role of vitamin K and γ-Carboxylation

Answer 1

• vitamin K is required for the hepatic synthesis of prothrombin (factor II), VII, IX, X, protieins C and S
  
  • vitamin K is the coenzyme for the γ-carboxylase
• γ-carboxylation allows Ca binding to clotting factors
• INR (prothrombin time, extrinsic pathway) is a sensitive indicator of vitamin K deficiency
  
  • factor VII levels are most sensitive to vitamin K

Question 2

describe fibrinolysis - dissolution of the fibrin clot (tertiary hemostasis)

Answer 2

• inactive plasminogen gets incorporated into the developing clot
• inactive plasminogen can become activated by tissue plasminogen activator, urokinase or streptokinase
• active plasmin is proteolytic and degrades fibrin

Question 3

levels of what get raised during dissolution of the fibrin clot?

Answer 3

• fibrin degradation products and D-dimer levels are raised in patients with DVT

Question 4

name anti-coagulant factors

Answer 4

• antithrombin III
  
  • binds to and inhibits factor X, thrombin (II) and other activated clotting factors
  • Heparin (GAG) acts by activating this factor and preventing coagulation
• protein C and S (also require vit. K for γ-carboxylation)
  
  • protein C is activated by the binding of thrombomodulin to thrombin
    
    • protein S is a cofactor for protein C
  • proteins C and S act together to inactivate cofactors V and VIII of the coagulation cascade

Question 5

describe action of aspirin

Answer 5

• prevents the formation of thromboxane in platelets
  
  • action of aspirin on platelets is permanent since it is an irreversible inhibitor of COX

Question 6

describe action of heparin

Answer 6

• heparin activates antithrombin III and inactivates thrombin (anti-coagulant)

Question 7

describe the action of Warfarin

Answer 7

• blocks epoxide reductase in liver and prevents the regeneration of the active form of vit. K
  
  • this inhibits the action of γ-carboxylase and therefore the synthesis of clotting factors II (prothrombin), VII, IX and X

Question 8

describe the action of streptokinase

Answer 8

• streptokianse is a plasminogen activator that converts plasminogen to plasmin, enabling the dissolution of clots

Question 9

describe bleeding time (BT)

Answer 9

• BT is an indicator of platelet plug formation (primary hemostasis)
• indicator of:
  
  • low platelet count
  • vWF deficiency
  • platelet receptor defects

Question 10

describe clotting time

Answer 10

• time taken for the formation of the stable fibrin
• prolonged clotting time indicates defects in the coagulation pathway (secondary hemostasis)

Question 11

contrast PT/INR vs aPTT

Answer 11

• PT/INR tests the extrinsic pathway
• aPTT tests the intrinsic pathway

Question 12

describe the ristocetin cofactor assay

Answer 12

• it is typically used in von Willebrand disease
  
  • there is reduced platelet aggregation in patients with von Willebrand disease
• flow cytometry is used to identify the platelet glycoprotein defects

Question 13

describe Hemophilia A and B

Answer 13

• inherited coagulation disorder – defect in the intrinsic coagulation pathway
  
  • ​inherited in an X-linked recessive manner
• Hemophilia A: factor VIII deficiency
• Hemophilia B: factor IX deficiency
• increased aPTT for both

Question 14

contrast diseases involved in increased bleeding time and increased clotting time

Answer 14

• clotting pathway
  
  • Hemophilia A and B
• platelet plug formation
  
  • VW disease
  • platelet defects
    
    • Bernard Soulier syndrome
    • Glanzmann thrombasthenia
    • thrombocytopenia

Question 15

describe von Willibrand disease

Answer 15

• most common inherited bleeding disorder due to deficiency of vWF
• defect in platelet plug formation
• instability of factor VIII
• bleeding time: prolonged
• aPTT: prolonged

Question 16

describe disorders of hemostasis due to platelet defects

Answer 16

• these disorders have an increased bleeding time and platelet aggregation tests are abnormal
  
  • patients with thrombocytopenia have increased bleeding time and low platelet counts
• if platelet count is normal, flow cytometry is performed to identify platelet receptor defects
  
  • GPIb: Bernard Soulier syndrome
  • GPIIb/IIIa: Glanzmann thrombasthenia