Hemostasis Flashcards
List synonyms for von Willebrand factor, and describe where it is produced and released
Von Willebrand factor (AKA VIII:vWF, VIII:v, or VIII:R) is produced and released by the endothelial cells. It is released when there is damage to the endothelium and the subendothelium layer of the blood vessel is exposed. VIII:vWF anchors to the platelets on one end, and to the collagen receptor of the damaged tissue on the other.
VIII:vWF promotes platelet adhesion
Describe Von Willbrand’s Disease and how it is treated
Von Willebrands disease is the most common inherited coagulation defect. The most common form is characterized by insufficient production of vWF by endothelial cells. Less commonly due to abnormal binding to platelet receptors. First line of TX is DDAVP (0.3mcg/kg IV) effective in 80% of cases. Causes release of vWF from endothelial cells. If necessary DDAVP should be followed by:
Cryoprecipitate (contains: Factor VIII, factor I-fibrinogen, and factor XIII)
Humate-P (Purified factor VIII)
Describe the steps of Hemostasis
- Primary hemostasis (PLT plug “white plug”)
- Secondary hemostasis (coagulation “red thrombus”)
- Anticoagulation
- Fibrinolysis
Describe the steps in Primary Hemostasis
- Adhesion of PLTs to dammaged vascular wall, via vWF
- Activation of PLTs requires thrombin (IIa)
- Aggregation of PLTs, requires ADP and thromboxane A2
- Production of fibrin, requires extrinsic, intrinsic, and final common pathways coagulation factors
What is the mechanism of PLT adhesion
VWF is released when there is damage to the endothelium, and the subendothelium layer of the blood vessel is exposed. VIII:vWF anchors to the platelets on one end, and to the collagen receptor of the damaged tissue on the other.
What is the mechanism of PLT activation?
Prothrombi-II gets activated to Thrombin-IIa which binds on the suface of the PLT causing the PLT to change shape. The activated PLT synthesizes and releases Thromboxane A2 and ADP
What is the mechanism PLT aggregation?
Thromboxane A2 and ADP uncover fibrinogen receptors on the PLT. Fibrinogen attaches to its receptors, thereby linking the PLTs to each other. At this point, the clot is still water soluble and friable
What is the mechanism of antiplatelet action of asprin and NSAIDs?
Asprin and NSAIDs prevent PLT aggregation by interfering with the synthesis of thromboxane A2 by interfering with the activity of cyclo-oygenase (COX). ASA irreversibly inhibits PLTs while NSAIDsinhibit for 24-48hrs
Thrombin-IIa activates the PLT
What are the anti-ADP agents ?
Plavix (clopidegrel): Inhibts ADP for the life of the PLT
Ticlopidine (Ticlid): Inhibts ADP
What are the fribrinogen receptors, and what are the anti-fibrinogen receptor agents?
The fibrinogen receptors are GPIIb/IIa.
Anti-fibrinogen receptor agents are:
Eptifibatine (Integrilin), Abciximad (ReoPro), Tirofiban (Aggrastat)
These agents work by “capping” the fibrinogen receptors preventing PLT linking and aggregation
What coagulation factors are dependent on vitamin K?
Prothrombin-II, VII, IX, and X
What coagulation factors are produced in the liver?
What factors are not?
Factors produced by the liver:
Fibrinogen-I, Prothrobin-II, V, VII, VIII:C, IX, X, XI, XII, Fibrin-stabilizing Factor XIII
Factors NOT produced by liver:
VIII:vWB, Tissue Factor-III (Thromboplastin), and calcium-IV
Discuss Hemophilia A and Hemophila B and their treatment
Hemophilia A results from factor VIII:C defficiency and is the second most common coagulation disorder 1 in 1000 male births. Sex-linked recessive. Tx with cryoprecipitate Or FFP, however concentrate factor VIII is preferred.
Hemophila B (Christmas disease) is a deficiency in factor IX tx with replacement
Describe the action of activated antithrombin III
Activated antithrombin III predominantly attaches to thrombin-II and Xa and factors IX XI XII to a lesser degree, removing them from circulation.
Acquired antithrombin deficiency is found in cirrhosis of the liver, and in nephrotic syndrome
Antithrombin deficiency is the most common reason for heparin resistance
Discuss the pharmacology of heparin
Heparin binds to antithrombin III and potentates it’s action by 1000-10000. Therefore heparin interferes with the intrinsic and common pathways.
aPPT is prolonged by heparin
