24. Clotting Cascade Flashcards
In the extrinsic pathway- Tissue factor, which is released by endothelium after tissue damage, interacts with what which triggers the clotting/coagulation cascade?
Interacts with factor VII (7) allowing it to come in contact with factor III to produce VIIa
Factor III, VIIa, and Ca2+ bind to factor X, activating factor X to Xa which will?
feed the common pathway which is Xa with Va and Ca2+ avticates II (prothrombin) to become IIa(thrombin). IIa, I (fibrinogen) and Ca, activate Ia (fibrin) which with activated XIIIa (13a) crosslinks fibrin
In the intrinsic pathway, factor XII is activated by negative platelet and HMWK to form XIIa. This activates XIa which activates IXa. IXa then does what?
Factor VIII to VIIIa activated via IIa (thrombin), which with IXa and Ca form the tenase complex. Tenase converts factor X to Xa, which goes to common pathway
PPT or partial prothrombin time is the time is takes from?
(intrinsic pathway) XII to fibrin clot usually 20-35 seconds
PT or prothrombin time is the time is takes for?
extrinsic pathway to make fibrin clot usually 10-13 seconds
Warfarin decreases vitamin K which is needed to activate Factor II, VII, IX, and X. What changes when someone is on warfarin and is taken off 48 hours before- establishing a normal PT?
The time required for full expression of Factor II, VII, IX, and X along with Protein C and S
What are the shortest half life and longest halflifes of vitamin K dependent factors?
Factor VII : 4-6 hours shortest
Protein C: 7 hours- shorter
Factor II: 60 h LONGEST
Factor X: 40-60h
The extrinsic pathway is quicker than intrinsic, activated by external traumaand involves factor VII, while the intrinsic pathway? (3)
Is slower than extrinsic
activated by trauma inside and platelets
involves factors XII, XI, IX, VIII
What does the common pathway share?
Factors I, II, V, and X
The key difference between primary and secondary hemostasis is that primary hemostasis makes a weak platelet plug at the injury site, while secondary hemostasis?
makes is strong by generating a fibrin mesh on it
Thrombin activates XIII to XIIIa and fibrinogen to fibrin + Ca allows fibrin crosslinkning. What are the 3 other important roles of thrombin?
Activates itself from prothrombin to thrombin
Activates platelets
Activates Factors V and VIII to Va and VIIIa
Vitamin K is needed for long term control over INR. To activate Vit K, the first step uses 2,3 epoxide reductase to convert vitamin K to its quinone form. What is the second step?
Quinone reductase reduces the quinone form of Vit K to active form Vitamin K quinol form
BOTH of these steps (MAINLY epoxide reductase) can be blocked by Warfarin
Warfarin works by decreasing the activity of Vit K dependent epoxide reductase, lengthening the time to form a clot. Vitamin K is a cofactor in synthesizing what factors?
Factors II, VII, IX, X and proteins C and S
Once VitK is in the active quinol form, it reacts with 10+ glutamyl carboxyglutamate, to activate the factors. What is the main used of vitamin K?
to help patients with over coagulation
Warfarin has both S/R diastereomers. What is most effective and by how much, what does it activate?
S warfarin is more activate than R warfarin, 2-5 times more active, activating cytochrome P2C9 (CYP2C9)
Orally ingested warfarin is completely absorbed and has peak plasma concentrations at 3 hours. What is important to remember about interactions with warfarin?
There are many drug, food, and environmental, herbal interactions associated with warfarin
Protein C and S inactivate Factor Va and VIIIa to limit thrombin. A genetic deficiency in protein C causes?
a significantly increased risk of venous thrombosis d/t increased coagulation
Hemophilia A also called factor VIII deficiency is a genetic disorder caused by missing or defective factor VIII (8). This is usually passed down from parents to children, with 1/3 being from a spontaneous mutation. What happens when there is no factor VIII?
No factor 8 will lead to no intrinsic activation of factor X, with little to none X, there will be no clotting cascade- BLEED FOREVER
PT measures extrinsic pathway with a normal time of 12-13 seconds. What factors are associated with extrinsic?
VII 7
PTT measures intrinsic pathway with a normal time of 30-50 seconds. What factors are associated with intrinsic?
XII, XI, IX, VIII (12,11,9,8)
What is the INR? (internation reference tissue factor)
Ratio of patient’s prothrombin time to a normal sample, raised to the power of ISI value (internation sensistivity index) for the analytical system being used
By looking at PT and PTT, a practitioner can gain clues as to what bleeding disorder may be present. If PT is prolonged and PTT is normal. What could this clue to?
Liver disease, decreased VitK, decreased factor VII
If a patient has recurrent DVT but PTT, PT and thrombin times are normal, what can be the cause?
Deficiency of Protein S (Protein C) becuase they cause anticoagulation
