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What are the 3 initial responses to vascular injury?
- 1) vasoconstriction
- 2) thrombin generation
- 3) platelet adhesion
Draw Coagulation cascade (p. 5)
- 1) X
- 2) V
- 3) Ca
- 4) platelet factor 3
- 5) prothrombin
- 6) forms on platelets
- 7) catalyzes the formation of thrombin
What is the convergence point of both intrinsic and extrinsic pathways?
What inhibits factor X
Tissue factor pathway inhibitor
What combines with platelets to form platelet plug --> hemostasis
What helps crosslink fibrin?
- 1) key to coagulation
- 2) converts fibrinogen to fibrin and fibrin split products
- 3) activates factors V and VIII
- 4) activates platelets
Anticoagulation (to follow)
- 1) key to anticoagulation
- 2) binds and inhibits thrombin
- 3) inhibits factors IX, X, XI
- 4) Heparin binds AT-III
- Protein C
- 1) vitamin K dependent
- 2) degrades factors V and VIII
- 3) degrades fibrinogen
- Protein S
- 1) vitamin K dependent
- 2) protein C co-factor
- Tissue Plasminogen Activator:
- 1- released from endothelium
- 2- converts plasminogen to plasmin
- 1- degrades factors V and VIII, fibrinogen, and fibrin--> lose platelet plug
- Alpha-2 antiplasmin-
- natural inhibitor of plasmin, released from endothelium
Which factor has the shortest half-life?
Factors V and VIII:
- 1) labile factors
- 2) activity lost in stored blood
- 3) activity not lost in FFP
What is the only factor not synthesized in the liver
VIII, only factor not synthesized in liver (synthesized in endothelium)
What are the vitamin K- dependent factors?
II, VII, IX, and X; protein C + S
How long does it take for vitamin k to take effect?
takes 6 hours
How long does it take for FFP to take effect?
effect is immediate, lasts for 6 hours
Whats the name for factor II?
Normal half-life of:
- RBC: 120 days
- Platelets: 7 days
- PMNs: 1-2 days
- 1) PGI2
- 2) from endothelium
- 3) decreases platelet aggregation and promotes vasodilation (antagonistic to TXA2)
- 1) TXA2
- 2) from platelets
- 3) increases platelet aggregation and promotes vasoconstriction
- 4) triggers release of calcium in platelets --> exposes GpIIb/IIIa and causes platelet-to-platelet binding, platelet-to-collagen binding
- 5) activates PIP system to further increase calcium
contains highest concentration of VWF and VIII; used in von willibrand's disease and hemophilia A (factor VIII deficiency), also contains fibrinogen
has high levels of all factors (including labile factors V and VIII), protein C, protein S, and AT-III
DDAVP and conjugated estrogens
causes release of VIII and vWF from endothelium
What does PT measure?
- 1) PT- measures II, V, VII, and X; fibrinogen
- 2) Best for synthetic liver activity
What does PTT measure?
PTT- measures most factors except VII and XIII (thus does not pick up factor VII deficiency); also measures fibrinogen
What range should PTT be if you want anticoagulation?
PTT 60-90 sec for anticoagulation
- 1) activated clotting time
- 2) want ACT 150-200 sec for routine anticoagulation, 460 sec for cardiopulmonary bypass
What INR ranges are a contraindication for procedures?
INR >1.5- relative contraindication to performing surgical procedures
INR >1.3- relative contraindication to central line placement, percutaneous needle biopsies, and eye surgery
What is the most common cause of surgical bleeding?
Von Willebrand's disease
- 1) most common congenital bleeding disorder2) types I and II are autosomal dominant; type III is autosomal recessive3) vWF links GpIb receptor on platelets to collagen4) PT normal, PTT can be normal or abnormal5) have long bleeding time (ristocetin test)
- 6) type I is most common (70% of cases) and often only has mild symptoms
- 7) Type III causes most severe bleeding
- 8) Type I and III- reduced quantity of circulating vWF
- Tx: recombinant VIII:vWF, DDAVP, cryoprecipitate, conjugated estrogens
- 9) Type II- defect in vWF molecule itself, have enough vWF but does not work well
- Tx: recombinant VIII: vWF, cryoprecipitate