Hemodynamic Disorders (4) - Hemostasis, section 2 Flashcards
Hemostasis
Formation of a blood clot to stop blood flow
What are the 4 steps to Hemostasis
- Arterial Vasoconstriction
- Primary Hemostasis - platelet plug
- Secondary Hemostasis - fibrin deposition
- Clot stabilization and resorption
What causes vasoconstriction?
Endothelin
What are the 3 steps of platelets during primary hemostasis?
- Adhesion
- Activation
- Aggregation
What molecule on the subendeothelial surface is involved with platelet adhesion?
Von Willebrand Factor (vWF)
What molecule on the platelet surface is involved with platelet adhesion?
GP1b
What binds to what for platelet adhesion during primary hemostasis?
GP1b binds to Von Willebrand Factor
What molecule activates platelets during primary hemostasis?
Thrombin
Platelet activation involves 3 structural changes. Describe those.
- Conformational change of the platelet (increased surface area) and GP2b-3a (concave)
- Negatively charged platelet surface
Platelet activation involves release of 2 types of granules. What are those?
Dense granules
Alpha granules
Platelet activation causes release of granules from the platelet. What molecule release causes more platelet activation?
ADP
Platelet activation causes release of granules from the platelet. What molecule release causes platelet aggregation?
Thromboxane A2
What does Aspirin inhibit?
Thromboxane A2 - Platelet aggregation during primary hemostasis
For platelet aggregation, what receptor on the platelet is involved?
GP2b-3a
For platelet aggregation, what binds to GP2b-3a?
Fibrinogen
Fibrinogen binding to GP2b-3a allows for?
Cross linking of platelets and forms platelet plug
What is contained in endothelial cells and is a source of von willebrand factor?
Weibel Palade Bodies
Where does von willebrand factor come from?
Weibel Palade Bodies in the endothelial cells
Von willebrand factor disease
Lack of von willebrand factor
- Trouble with platelet adhesion
Bernard Soulier Syndrome
Lack of GP1b
- Trouble with platelet adhesion
How do platelets appear with Bernard Soulier Syndrome?
GIANT
Glanzmann Thrombasthenia
Lack of GP2b-3a
- Trouble with platelet aggregation
Thrombocytopenia
LOW platelets (less than 50K)
What occurs during secondary hemostasis?
Fibrin deposition and coagulation cascade
= clot stabilization
Describe the Intrinsic pathway of secondary hemostasis
Factor XII
Factor XI
Factor IX + Factor VIII
- Common pathway
Describe the Extrinsic pathway of secondary hemostasis
Tissue factor + Factor VII
- Common pathway
Describe the Common pathway of secondary hemostasis
Factors IX, VIII, VII activate Factors X and V Factor II (thrombin) Fibrinogen activated to Fibrin = stable clot
What measures the Extrinsic pathway
PT (prothrombin time)
What measures the Intrinsic pathway
aPTT
PT test
Tissue factor + blood
- A clot should form in less than 14 seconds
aPTT test
Negative surface calcium + blood
- A clot should form in less than 45 seconds
Anti - Hemophilic A factor
Factor VIII
Vitamin K dependent factors require?
Calcium
What are the Vitamin K dependent factors?
2, 7, 9, 10
Main activities of thrombin?
Activate platelets
Stabilize fibrin
Coumadin (warfarin) inhibits?
Vitamin K - cannot activate factors 2, 7, 9, 10
The _____ can regulate clot formation and dissolution
Endothelium
What 3 things can the Endothelium produce to INHIBIT platelets?
- Adenosine DisphophatASE - blocks ADP which activates platelets
- NO
- Prostacyclins
What can the Endothelium produce to break down fibrin?
Tissue Plasminogen Activator (t-PA)
How does Tissue Plasminogen Activator (t-PA) break down fibrin?
It activates Plasmin!
Plasmin then breaks apart Fibrin and degrades the clot
Cascade of events of the fibrinolytic activity of the Endothelium
- Endothelium produces t-PA
- t-PA activates Plasmin
- Plasmin breaks Fibrin apart and degrades clot
What inhibits plasmin?
Alpha2 - antiplasmin – keeps clot stable
What receptors on the endothelium can bind Thrombin and exert anti-coagulation effects?
Thrombomodulin
Once Thrombomodulin binds Thrombin, then what happens?
Activates protein C and S which INHIBIT factors 5 and 8
= Anticoagulation
Heparin-like molecules on the endothelial surface activate _____ which inhibits ______
Antithrombin III
Thombin
Small bleeds (petechiae and purpura) are due to defects in?
Primary hemostasis
How do defects in primary hemostasis present?
Nosebleeds
Excessive menstruation
GI bleeds
Bleeds in joints (hemarthrosis) are due to defects in?
Secondary hemostasis
Secondary hemostasis defects cause?
Bleeds in joints (hemarthrosis)
Generalized defects of small vessels cause?
Eccyhmoses