MHD: Normal Hemostasis Flashcards
What is the major event of normal hemostasis?
The formation of a hemostatic plug when blood vessels are ruptured or injured
What is abnormal hemostasis?
Pathological activation of clotting factors leading to formation of a clot when there are no ruptured vessels.
Hemostasis depends on interactions between what 3 entities?
Blood vessel wall
Platelets
Coagulation and fibrinolytic systems
What is the first step of primary hemostasis?
Vasoconstriction occurs reflexively in order to try to minimize blood loss
What is the vasoconstrictive agent involved with the first step of primary hemostasis?
Endothelin, released by the endothelial cells near the site of injury
After vasoconstriction, what are the next steps of primary hemostasis?
Platelet adherence to newly exposed collagen
Activation: degranulation release of ADP, TXA2, 5HT
Aggregation: degranulation recruits additional platelets to form hemostatic plug
What are the two types of platelet granules?
Light granules (Alpha): contain proteins including PF4, PDGF Dense granules (Beta): contain ADP, Ca2+, histamine, 5HT, and Epi
What is the general function of primary hemostasis? What about secondary hemostasis?
Primary Places Plug
Secondary Stabilizes
What factor is released to initiate secondary hemostasis?
Tissue factor released from the endothelial cells at the site of injury
What two events occur simultaneously during secondary hemostasis?
Release of tissue factor
Coagulation proteins form complexes on platelet surface
What is the product of the coagulation cascade?
Thrombin is formed, which then converts fibrinogen to fibrin
What process forms the stabilized permanent hemostatic plug?
Fibrin polymerization
Cross linking of fibrin forms a stable platelet t-thrombin plug
Describe the cells contained in the permanent hemostatic plug.
RBCs and WBCs become trapped in the plug in addition to the platelets that make up the majority of the plug
What two outcomes of hemostasis are controlled by the endothelium?
Normally, endothelium has an antithrombotic effect
If there is injury to the endothelium, then there is a prothrombotic effect
Describe the antiplatelet effect of the endothelium
Prevents contact between collagen and platelets/coagulation proteins
Secretion of prostacyclin and nitric oxide
Describe the anticoagulant effect of the endothelium
Endothelial membranes express antithrombin (heparin cofactor) and thrombomodulin. Thrombomodulin combines with thrombin to activate protein C Protein S (cofactor for C) is also secreted
Describe the fibrinolytic effect of the endothelium
The endothelial cells secrete plasminogen activators (t-PA) which converts plasminogen to plasmin, thus promoting fibrinolysis
What factors of the clotting pathway are degraded by activated protein C?
Va and VIIIa
Describe the prothrombotic effect of the endothelium
Following injury, endothelia secrete von Willebrand factor (VWF), which allows platelets to attach to newly exposed collagen
What 3 molecules are released by endothelia for during the prothrombotic response to injury?
VWF
Tissue factor
Cytokines