Flashcards in Hemostasis Deck (54):
What are the 3 major components of the hemostatic system?
1. Blood Vessel Wall
3. Coagulation and Fibrinolytic Systems
Normal hemostasis is the complex process by which ruptured vessels undergo changes which prevent blood loss.
Abnormal hemostasis, thrombosis, is the process by which blood forms a clot within intact blood vessels (vessels which have not ruptured).
Abnormal hemostasis is a pathologic process that represents the activation of the clotting system when there are no ruptured vessels.
What is the purpose of hemostasis in injury?
Prevent excessive blood loss
What are the steps of the hemostatic response?
2. Primary Hemostasis
3. Secondary Hemostasis
4. Formation of platelet-thrombin plug
What is the role of vasoconstriction in hemostasis?
It occurs immediately and briefly through reflex neurogenic mechanisms and may mediate humoral factors released from endothelium such as endothelin and serves to reduce blood loss.
The injury damages endothelial cells and exposes subendothelial collagen. Platelets quickly adhere to the collagen and become activated.
The platelets change in shape and release chemicals such as ADP, thromboxane A2 and serotonin which recruit additional platelets to the site of injury and promote aggregates to form, resulting in a hemostatic plug.
Tissue factor is released at the site of injury from the endothelial cells which combine with platelet factors to initiate the plasma coagulation cascade ultimately forming thrombin.
The coagulation proteins form complexes on the platelet surface utilizing the phospholipids of the platelet membrane.
What is the function of thrombin?
Converts fibrinogen into fibrin
Detached blood clot traveling through the blood vessels and it can lodge in certain organs and cause ischemia
What are the two pathways in the role of the endothelium?
1. Antithrombotic effect (normal state).
2. Prothrombotic effect (response to injured endothelium).
What are parts of the antithrombotic effect of the endothelium?
Antiplatelet and Anticoagulant and Fibrinolytic
Intact endothelium prevents platelets and coagulation proteins from coming into contact with subendothelial collagen. Normal endothelial cells secrete prostacyclin and nitric oxide that prevent platelet aggregation.
Antithrombin inhibits thrombin formation and thrombomodulin binds thrombin to activate protein C as an anticoagulant.
The endothelium also secretes plasminogen activators (tPA) which promote fibrinolysis. Plasminogen is converted to plasmin and dissolves the clot.
What is the mechanism of the prothrombic effect of the endothelium?
As injury occurs, it will secrete von Willebrand factor, a protein, which forms a molecular bridge between platelets and sub endothelial collagen. It also synthesizes and secretes tissue factor, which activates the extrinsic sequence of the coagulation cascade.
What is the function of tissue factor?
It promotes the generation of thrombin and formation of a clot.
Platelets are discoid, anuclear cells which play a major role in hemostasis.
How do platelets attach to sub endothelial proteins?
How do platelets inter-adhere?
Light Granule Platelets (alpha)
Contain fibrinogen, fibronectin, coagulation factors V and VIII, platelet factor 4 (heparin- binding chemokine) and growth factors, PDGF (platelet derived growth factor) and TGF (transforming growth factor beta).
Dark Granule Platelets (beta)
Contain ADP, ATP, ionized calcium, histamine, serotonin and epinephrine.
What is the function of serotonin?
What are the three reactions of platelets with vessel injury?
Adhesion - Platlets
Glycoprotein receptor (GP Ib) on the platelets attach to the von Willebrand factor which in turn attaches to collagen.
Adhesion is a critical reaction because it prevents the blood flow from dislodging the adherent platelets and unplugging the defect in the vessel wall.
What is the function of GP Ib?
Attachment of the platelet to vWF
What is the function of GP IIb and IIIa?
Attachment of platelets to each other
Disease with vWF deficiency
von Willebrand Disease
Disease with GP Ib deficiency
Disease with GP IIb and IIIa deficiency
Activation - Platelets
Activation of platelets is initiated by molecules binding with platelet membrane GP IIb/IIIa receptors. This leads to the release of coagulation factors, ADP, calcium and thromboxane A2.
Aggregation - Platelets
Secretions recruit and aggregate platelets with the aggregation resulting in the release of serotonin and thromboxane A2 by platelet granules causing vasoconstriction of the vessel, decreasing the size of injury, reducing blood flow and the likelihood of the plug detaching from the vessel wall.
What is the function of fibrin?
Fibrin surrounds and structurally holds platelets in a secondary (irreversible) hemostatic plug.
What stabilizes fibrin?
The fibrin clot is stabilized by a transamidase enzyme (XIIIa) and TAFIa.
What is the test for the Intrinsic Pathway function?
What is the test for the Extrinsic Pathway function?
XIIa leads to XIa activation which leads into X being activated to Xa which converts prothrombin to thrombin
Tissue damage leads to the release of tissue factor which activates VII to form the tissue factor-VIIa complex which will activate X to Xa which converts prothrombin to thrombin.
Conversion of X to Xa will lead to prothrombin conversion to thrombin
What are the factors that are part of the prothrombin group?
Factors II, VII, IX and X (2, 7, 9, 10)
All of these proteins contain gamma - carboxy glutamic acid which is needed for the binding of calcium.
What are some inhibitors of the coagulatory system?
Tissue Factor Pathway Inhibitor (TFPI)
Heparin Cofactor II
Antithrombin III function
Antithrombin is a plasma inhibitor which also mediates the anticoagulant actions of heparin.
Tissue Factor Pathway Inhibitor (TFPI) function
Heparin cofactor II is a weak inhibitor of thrombin.
Heparin Cofactor II function
Tissue factor pathway inhibitor is a potent inhibitor of tissue factor.
What is the function of the fibrinolytic system?
The fibrinolytic system is a network of enzymes that are responsible for the dissolution of a formed clot.
Splits up fibrin
What are the inhibitors of the fibrinolytic system?
- Plasminogen activator inhibitor (PAI)
- Thrombin activatable fibrinolytic inhibitor (TAFI)
What is Virchow's Triad?
1. Endothelial Injury
3. Abnormal Blood Flow
All lead to thrombosis
What is primary fibrinolysis?
The body's regular response to break up blood clots
What is secondary fibrinolysis?
Usage of medication to break up clots
What are some conditions that cause high risk for thrombosis?
What are some conditions that cause medium risk for thrombosis?