Hemostasis Flashcards
Primary Hemostasis
rapid vasoconstriction and formation of the platelet plug minimizing blood loss after injury
Secondary Hemostasis
An explosive, localized increase in thrombin generation and fibrin clot formation that anchors and stabilizes the platelet plug
2 Functions of Thrombin
Potent platelet activator
Converts soluble fibrinogen to insoluble fibrin clot
Plasmin
a protease that gradually breaks down the fibrin clot
converted from plasminogen
3 Prothrombotic Components
Platelets/von Willebrand Factor (primary platelet plug)
Coagulation Cascade
Fibrinolysis inhibitors
3 Antithrombotic Components
Endothelium
Fibrinolysis (plasmin)
Coagulation inhibitors
What occurs in Adhesion phase of primary hemostasis?
mediated by the binding of the platelet glycoprotein Ib-V-IX complex to vWF
platelets then activated by a variety of agonists (thrombin, collagen, ADP, etc.)
What occurs in Aggregation phase of primary hemostasis?
cross-linking of activated platelets primarily mediated by fibrinogen binding to activated glycoprotein IIb/IIIa complex
What occurs in Secretion phase of primary hemostasis?
platelet granules release substances that recruit/activate additional platelets
Normal range of platelets in blood
150,000-400,000/microL
What occurs when a platelet is activated?
- shape change
- conformational activation of the Gp IIb/IIIa complex
- granule release
- eventually thrombus retraction
Describe Thrombopoietin (TPO)
controls the production of platelets
negative feedback, platelets bind to TPO
If more TPO is unbound, will signal to make more platelets
Describe platelet storage
about 30% of circulating platelets are sequestered in the spleen (reserve force)
spleen also removed platelets from blood after 7-10 days
Two major functions of von Willebrand Factor
- the major carrier protein for factor VIII (significantly prolongs the plasma half-life for this factor)
- vWF mediates platelet tethering and adhesion
what receptor on platelets does vWF bind to?
Gp Ib-V-IX
Function of ADAMTS13
cleaves partially unfolded ultra-large vWF multimers that have bound to platelets into smaller, less sticky multimers
-if there is an inherited or acquired deficiency in ADAMTS13, large vWF-platelet aggregates can form in the circulation and occlude small blood vessels (occurs in thrombotic thrombocytopenic purpura (TPP))
What characterizes von Willebrand Disease?
mutations in the vWF gene that impairs multimer formation, or that lead to excessive cleavage of multimers by ADAMTS13 that can lead to bleeding disorder
2 strong platelet agonists
- Collagen (extracellular matrix)
- Thrombin (generated by TF exposure at site of injury)
4 weak platelet agonists
- Epinephrine
- ADP
- Serotonin
- Thromboxane A2 (produced from platelet arachidonic acid via COX-1 pathway)
Important step for platelet aggregation
conformational change in the Gp IIb/IIIa receptor that allows the receptor to bind fibrinogen (glues platelets together)
Phosphatidylserine exposure on outer platelet membrane leads to?
assembly of the membrane-bound coagulation enzyme complexes IXa-VIIIa, Xa-Va
Another name for Thrombin and its function in cascade?
Factor IIa, serine protease that converts fibrinogen to fibrin
Two arms of the coagulation cascade
Intrinsic and Extrinsic
Which lab test measures the Extrinsic pathway?
Prothrombin time (PT)
Which lab test measures the Intrinsic pathway?
activated partial thromboplastin time (aPTT)
Remember this about the intrinsic and extrinsic pathway separation.
useful for lab testing but not for describing the response in vivo
Vitamin K dependent proteases
II (prothrombin), VIIa, IXa, Xa, Protein C
Function of factor XIII
activated by thrombin and crosslinks fibrin to stabilize the thrombus
List the cofactors in cascade
Tissue factor (TF), factor V, factor VIII, protein S
