Lecture 20: Fibronolysis And Disorders Of Hemostasis Flashcards
Indicate the role of calcium in hemostasis
-Represents Factor IV in clotting cascade
-Calcium ions are required for all steps that require
the vitamin K dependent clotting factors II, VII, IX
and X
Note:
• PLASMA: has all coagulation factors
• SERUM: supernatant obtained after clotting (contains no
coagulation factors)
Discuss the role of vitamin K in the post-translational modification of clotting factors
-Vitamin K is required for the hepatic synthesis of
Prothrombin (Factor II), VII, IX, X, Proteins C and S
-Vitamin K is the co-enzyme needed for the y-carboxylation of glutamic acid residues of these proteins –> Change helps clotting process
(Note: Warfin inhibits Vit K (VKOR) –> Problems w clotting)
Predict the clinical manifestations in a patient with vitamin K deficiency
-Will have problems clotting or delayed clotting
Can check for deficiency w:
1) INR (Prothrombin time)
2) Factor VII (Extrinsic pathway) –> Factor most sensitive to Vit K
Describe the Fibrinolysis pathway and it’s steps
1) Clot begins to develop and inactive plasminogen goes in clot
(Activators: TPA, Urokinase, Streptokinase)
2) Active Plasmin (Proteolytic)
(Inhibitor: Antiplasmin)
3) Fibrin degradation Products (FDP) D-Dimers–> Clots broken up and size decreases
(FYI: Elevated D-dimers= clot breaking out at a rapid rate –> -Elevated =deep vein thrombosis
-highly elevated= high risk of Pulmonary embolism)
Indicate the role of aspirin, warfarin, streptokinase and heparin as anticoagulant agents
Aspirin:
-Inhibits COX –> Inhibits formation thromboxane (TXA2)
Warfarin:
-Blocks vitamin K epoxide reductase (VKOR) –> Inhibits mature Vit K synthesis
Strepokinase:
-Thrombolytic agent; plasminogen activator; converts plasminogen to plasmin enabling the dissolution of clots
Heparin:
-Activates antithrombin III and inactivates thrombin
Discuss the biochemical basis and laboratory findings in the following disorders of hemostasis: Hemophilia (A and B), thrombocytopenia, von Willebrand Disease, Bernard-Soulier Syndrome, Glanzmann thrombasthenia
1) Hemophilia (A and B):
-Labs:
NO PROB W BLEEDING TIME
Prolonged APTT (Intrinsic pathway),
Factor VIII low =Type A, Factor IX low = Type B
(Whichever one it is will have a lower level in their factor)
2) von Willebrand Disease Biochemical basis: -Defect in platelet plug formation -Labs: PROLONGED bleeding time, Prolonged APTT, Low vWF Low levels of Factor VIII Test: RIstocetin assay will come back abnormal
3) Bernard-Soulier Syndrome (GP1b defect) -Labs: Increased bleeding time Platelet count normal
4)Glanzmann thrombasthenia (Gp11b/111a defect) -Labs: Increased bleeding time Platelet count normal
5) Thrombocytopenia
-Labs:
Increased bleeding time
Low platelet count
Discuss the regulation of coagulation and fibrinolysis.
Outline the role of PGI2, antithrombin III, proteins C and S, and plasmin
Control factors:
1) Continuous blood flow
2) Endothelia = anti-thrombotic
3) Fibrinolysis
Anti-Coagulant factors:
1) PGI2 (prostacyclin) and NO
- Released by endothelium
- PGI2 increases cAMP
2) Antithrombin III
- Binds and inactivates thrombin IIa and Xa
3) Protein C and S
- Require Vit K for y-carboxylation
- Inactivate Va and VIIIa of coagulation cascade
4) Plasmin
- Degrades cross-linked fibrin (Fibrinolysis) releasing fibrin degradation products such as D-dimers
Name the factors measured by these tests:
1) Prothrombin time (PT) or International normalized ratio (INR)
2) Activated Partial thromboplastin time
(APTT/ aPTT/ PTT)
PT = Extrinsic Pathway • Tissue factor • Factor VII (Exclusive to Ex) • Factor V (Both) • Factor X (Both) • Prothrombin (Both) • Fibrinogen (Both)
APTT = Intrinsic Pathway • Factor VIII (Exclusive to In) • Factor IX (Exclusive to In) • Factor XI (Exclusive to In) • Factor XII (Exclusive to In) • Factor V (Both) • Factor X (Both) • Prothrombin (Both) • Fibrinogen (Both)
What does the platelet plug formation?
1) vWF
2) Platelet glycoproteins:
- GPIA
- GPIB
- GPIIB/IIIA
- fibrinogen)
