Hemostasis Flashcards
Healthy blood vessels - prevent clotting
- Prostacyclin
- Nitric oxide
- Tunica intima: smooth flow and barrier between collagen and pro-coagulant proteins
- Smooth internal surface: endothelium, subendothelium, internal elastic lamina
Damaged blood vessels - promote clotting
- Vascular spasm (vasoconstriction)
- Collagen fibers exposed
- vWF secreted by endothelium –> bind PTL and collagen
- Tissue factor from subendothelium –> Coagulation cascade
Platelets granules
- Alpha granules (large protein): vWF, fibrinogen, albumin, PF4, Factor V, Factor VIII, Proteins S
- Delta granules (small molecular): Calcium, ADP/ATP, serotonin
Primary hemostasis
- Vessel injury
- Adhesion
- Aggregation
- Activation (Platelet)
Adhesion of PTL
Platelet binds to
- Collagen via GP1a receptor
- vWF via GP1b/IX/V (vWF links PTL & collagen/endothelial cell)
Aggregation of PTL
Platelet binds to fibrinogen via PTL receptor: GPIIb/IIIa
Requires Ca
Activation of (more) PTL
- TXA2 (thromboxane A2) bind to TXA2 receptor: get more Ca from bone, increases receptor GPIIb/IIIa
- ADP binds to P2Y12 receptor: active more PTL, change PTL shapes, form more TXA2
- Thrombin (factor II): initiate intracellular signal events
PTL aggregometry
- ADP and collagen: via GPIIb/IIIa
- Ristocetin: via vWF
- Arachidonic acid: via COX/endoperoxidase/TXA2 stimulation
Mechanism of aspirin
- Aspirin irreversibly block the COX enzyme
- Low dose: inhibit COX-1 –> reduce TXA2 –> reduce aggregation
- High dose: inhibit COX-2 –> reduce prostacyclin –> increase blood clot
Secondary hemostasis
Fibrin clot is formed
Extrinsic + Intrinsic + Common
Factors involved in 2nd hemostasis
Extrinsic: TF –> VIIa
Intrinsic: XII –> XI –> IXa + VIIIa
Both ways activate X –> Xa
Common:
1. Xa + V –> activate Prothrombin to Thrombin (IIa)
2. Thrombin activate Fibrinogen to Fibrin (Ia)
Enzymatic coagulation factors
II, VII, IX, X, XI
Usually inactive and must be activated
Non-enzymatic coagulation factors
TF, V, VII
Zymogens
Inactive enzymes circulated in the bloodstream
Become serine proteases when activated
Clot forming
- Thrombin converts solube fibrinogen to insolube fibrin
- Link with PTL via GPIIb/IIIa
- Factor XIIIa cross-link fibrin
- Level of fibrinogen in blood: 200-400 mg/dL
PT test (Prothrombin time)
- Measure extrinsic pathway
- Measure 3 of 4 vit K dependent factors (II, VII, X)
- Add: pt’s plasma, TF, Ca
- PT prolong with: warfarin, deficiency of factor: I, II, V, VII, X; liver disease, some antibiotics
aPTT test (Activated partial thromboplastin time)
- Measure intrinsic pathway
- Add: Activator (surface), Ca, pt’s plasma, phospholipids
- Prolong with: All factors (except VII, XIII), presence of inhibitors for VIII and IX, some drugs (heparin, anticoagulant)
Hemophilia
- Genetic disorders on X chromosome
- Hemophilia A: factor 8
- Hemophilia B: factor 9
- Bleeding from mild to severe
Vitamin K dependent factors
II, VII, IX, X
Protein S, C
Thrombophilia
Imbalance in naturally occurring clot factors
Protein C and S
Activated Protein C: inhibits V and VIII –> inhibits clotting cascade
Protein S: cofactor for protein C
Factor V Leiden
The point mutation in factor V –> Protein C unable to bind –> Super active –> More clot
Heparin - Anticoagulant drugs
- Blood thinner
- Given IV
- Can be produced by basophils and mast cells
- Treat and prevent vein thrombosis, pulmonary embolism
6 functions of thrombin
- Activating V
- Activating VIII
- Activating XI
- Activating XIII for cross-link
- Combine with thrombomodulin to activate protein C
- Activate TAFI to suppress fibrinolysis
