Hemostasis and Thrombosis Flashcards
What is hemostasis?
Maintenance of clot-free blood within the vascular system while allowing for the formation of a solid plug of blood under conditions of vessel wall injury (ie. thrombosis)
What are the “key players” in hemostasis?
- Vascular endothelium
- Platelets
- Coagulation system
What are some anti-platelet effects of intact endothelium?
- Insulate platelets from subendothelial collagen
- Prostacyclin (PGI2) synthesis
- ADPase synthesis
- Nitric oxide synthesis
What is the function of prostacyclin (PGI2)?
Inhibits platelet aggregation
What is the function of ADPase?
ADP activates platelets, increased ADP leads to less ATP, platelet aggregation is inhibited
What is the function of nitric oxide?
Vasodilation and inhibits platelet aggregation
The intrinsic pathway with CF XII and the extrinsic pathway with tissue factor join in the common pathway to make…
fibrin which allows for clot
Does ADP or ATP activate platelets?
ADP (not ATP)
What is an anti-coagulant effect of intact endothelium?
Heparin-like molecule synthesis
Heparin-like molecule synthesis activates…
anti-thrombin III (degrades thrombin)
Without thrombin, fibrinogen cannot join with it to form…
fibrin
Normally, thrombin and fibrinogen form…
fibrin
Normally, plasminogen and tPA will form…
plasmin
Normally, fibrin and plasmin form…
fibrin split products
Without plasmin or fibrin, what cannot be formed?
Fibrin split products
What is a fibrinolytic property of intact endothelium?
Tissue plasminogen activator (tPA) synthesis
What is the function of tPA?
Converts plasminogen to plasmin (plasmin degrades fibrin)
What are some pro-thrombotic properties of damaged endothelium?
- von Willebrand’s factor synthesis
- Tissue factor synthesis
- Platelet activating factor (PAF)
- tPA inhibitor synthesis
What is tPAi?
Tissue plasminogen activator inhibitor
von Willebrand’s factor is essential for…
platelet adhesion
What is the significance of tissue factor synthesis?
Glycoprotein activates coagulation system
What are considered the “brick” of a thrombus?
Platelets
What is secreted by platelets when they are activated?
- Thromboxane (TXA2)
- ADP
- Factor V
- Factor VIII
- Calcium
Activated platelets bind to…
exposed collagen (vWF)
Activated platelets are involved in initiation of…
coagulation cascade (role of calcium and phospholipid complex)
A temporary “plug” of platelets becomes definitive with…
formation of fibrin from thrombin (leads to fused mass of platelets)
What activates the coagulation system?
Factor XII or tissue factor
What is the end product of the coagulation system?
Formation of fibrin monomers
What is the “cement” of a thrombus?
Fibrin
Is thrombosis normal or pathological?
Pathological
What is thrombosis?
An aggregate of platelets, fibrin, and blood cells within the non-interrupted vascular system (clot should not be there)
Thrombus is adherent to…
the vascular endothelium
Where may thrombosis arise?
Arterial or venous circulation
Surgery anywhere increases the risk of…
deep vein thrombosis
What are the predisposing factors to arterial thrombi?
Virchow’s triad:
* Damage to endothelium
* Alterations in blood flow
* Increased coagulability of blood
Which aspect of Virchow’s triad is most predisposing to arterial thrombi?
Damage to endothelium
What are three types of damage to endothelium?
- Ischemic damage to endocardium
- Valvular damage
- Free-radical induced damage
What are some causes of free-radical induced damage?
- Hemodynamic stress (increased blood pressure)
- Radiation
- Trauma
- Chemicals
- Microbes
Alterations in normal blood flow refer to…
role of stasis and turbulence
What are the alterations in normal blood flow when endothelium is physically damaged?
- Disrupts laminar flow
- Prevents renal clearance of coagulation proteins
- Slows flow of anticoagulants to site of injury
What is Leiden Factor V?
What does its defect lead to?
A coagulant protein
Factor V can’t shut off coagulation leading to increased risk of thrombosis
What are causes of increased coagulability of blood?
- Genetic defect in anticoagulant proteins or coagulant proteins Leiden factor V
- Inherited hypercoagulability
What is the most common genetic hypercoagulability disorder?
Activated protein C resistance
APC resistance accounts for up to 65% of patients with…
venous thrombosis
What is activated protein C resistance?
A point mutation in the factor V gene (factor V Leiden) renders it resistant to inhibition by APC (can’t turn off coagulation)
What is the effect of homocysteine?
What gene prevents metabolization of homocysteine?
Homocysteine produces free radicals in the blood
MTHFR gene: can’t metabolize homocysteine
When a patient has the MTHFR gene and can’t metabolize homocysteine, what is the effect?
Inherited hypercoagulability
How does neoplasia lead to hypercoagulability?
Releases procoagulants
What is the effect of polycythemia vera leading to hypercoagulability?
Increased RBC and viscosity
How does smoking lead to hypercoagulability?
Free radical damage to endothelium
How does obesity lead to hypercoagulability?
Increased fat increases viscosity
