Lecture 27: Hemostasis Flashcards
What is another name for platelets?
Thrombocytes
From where are platelets derived?
Megakaryoctyes
What are platelets’ three simples to create a plug?
- Adhesion
- Activation
- Aggregation
What controls the process of platelet production?
Thrombopoietin: stimulates platelet production
- If too many platelets, TPO decreases
- If too few platelets, TPO increases
What produces thrombopoietin?
Liver
Kidney
Where does thrombopoietin bind?
c-MPL (CD-100) receptor
-found on megakaryocytes and platelets
What is hemostasis?
Preventing and stopping bleeding
-keep blood within a damaged blood vessel
What are the four basic steps of hemostasis?
- Vascular spasm (contraction)
- Formation of platelet plug
- Formation of blood clot
- Repair of damage
Why is vasospasm important in hemostasis?
Disrupts blood flow and prevent further blood loss
How does vasospasm occur in hemostasis?
- Myogenic contraction
- Platelet factors: serotonin, thromboxane A2 promote vasoconstriction
- Release of molecules from endothelial cells
- Neural reflex for spasm to occur
Where do platelets attach to on an injured blood vessel?
Negative charges on collagen and laminin
What specific receptors allow platelets to adhere to each other and the endothelial cells?
Von Willebrand Factor (vWF)
Collagen (Gp Ia/IIa)
What is released from dense granules in platelets when they are activated?
ATP and ADP
Serotonin
Calcium
What is released from α granules in platelets when they are activated?
Growth factors
Von Willebrand Factor (vWF)
Factor V
Fibrinogen
What factors from platelets promote aggregation?
ADP
Serotonin
Thromboxane A2
What is the role of fibrinogen?
When it is activated as fibrin, it helps form platelet plug
How does aspirin work?
Inhibits clotting by reducing release of thromboxane A2 from platelets
How does Plavix (clopidogrel) work?
Inhibits P2Y12 receptors to prevent further platelet activation and aggregation
What activates fibrinogen?
Thrombin (activated form of pro-thrombin)
What is the role of platelet derived growth factor?
Stimulates fibroblasts to grow into the damaged area and differentiate into smooth muscle
How are clots removed?
Plasmin: lysis fibrin and fibrinogen
What limits clotting?
Fibrin: inhibits thrombin
Prostacyclin: limits platelet aggregation
Antithrombin II: anticoagulant
Heparin: anti-thrombin from mast cells
What are some hallmarks of the extrinsic pathway?
Activated by external trauma and prevents blood to escape vascular system
-Factor VII
What are some hallmarks of the intrinsic pathway?
Activated by internal trauma, platelets, exposed endothelium
-Factors XII, XI, IX, VIII
What are some hallmarks of the common pathway?
Finish pathway of clot producition
-Factors I, II, V, X
What factors do Vitamin K antagonists affect?
Factors II, VII, IX, X
-cofactor for the synthesis of these
What do Vitamin K antagonists do?
Prevents blood clots
What is the difference between primary and secondary hemostasis?
Primary has a weaker platelet plug
Secondary has strong plug with fibrin mesh
What factors does thrombin activate?
- Fibrinogen –> Fibrin
- Factor XIII –> Factor XIIIa
- Factor VIII –> Factor VIIIa
- Factor V –> Factor Va
What factor allows fibrin to cross link?
Factor XIIIa
What are the two types of oral anticoagulants?
Hydroxycoumarins (Warfarin/Coumadin) and Indanediones
-Vitamin K antagonists
What does warfarin target?
Vitamin K epoxide reductase
-prevents reduction of Vitamin K after its oxidized
Which is more potent: R-Warfarin or S-Warfarin?
S-warfarin
What are the roles of Protein C and S?
Anti-coagulants
- inactivates Factor Va and VIIIa
- Protein C promotes plasmin by inhibiting its inhibitor
In Hemophilia A, what factor is deficient or absent?
Factor VIII
In Hemophilia B, what factor is deficient or absent?
Factor IX
What does prothrombin time (PT) evaluate?
Extrinsic Coagulation Pathway
- Factors I, II, V, VII, and X
- normal: 12-13 sec
What does partial thromboplastin time (PTT) evaluate?
Intrinsic and Common Clotting Pathway
- Factors XII, XI, IX, VIII, X, V, II, I
- normal: 30-50 sec
If PT is prolonged and PTT is normal, what can that mean?
Liver disease
-something wrong with Factor VII
If PTT is prolonged and PT is normal, what can that mean?
Issue with a intrinsic pathway factor of vWF disease
If both PT and PTT are prolonged, what can that mean?
- Issue with common pathway factors
- Warfarin overdose
- Severe liver disease
