Coagulation/ FIbrinolysis Flashcards
List 4 anticoagulant properties of endothelium
- secretion of: (prostacyclin, nitric oxide, heparin sulfate, TFPI, TPA)
- smooth surface
- Protein C receptors = inactivates Va and VIIIa
- Thrombomodulin expression = inactivates thrombin
Prostacyclin function
PLT inhibitor
NOTE: anticoagulant secretion by endothelium
Nitric oxide function
Vascular relaxing (dilation)
NOTE: anticoagulant secretion by endothelium
Heparin sulfate function
anticoagulant secretion by endothelium
TFPI function
Tissue Factor Pathway Inhibitor: suppresses extrinsic pathway
NOTE: anticoagulant secretion by endothelium
Thrombomodulin source + function
- inactivates thrombin
- an anticoagulant secretion by endothelium
Role of WVF in primary hemostasis
Why is vit K needed by coagulation factors ?
What initiates primary hemostasis ?
vascular damage = procoagulant factors released from vessel cells, exposed collagen promotes procoagulants to begin primary hemostasis
List 5 pro-coagulant properties of damaged vasculature
- endothelial cells secrete vWF + up-regulate PLT receptors
- exposed collagen = binds vWF and PLTs
- vasoconstriction (smooth muscles contract)
- PLTs release factors (prostaglandins + prostacyclin)
- smooth muscle contain TF = activates FVII
Describe Adhesion stage of platelet plug
- reversible; PLTs BIND VESSEL WALL
a. MINOR injury = PLTs bind to collagen via GPIa/IIa, GP IV, and GP VI
b. MAJOR injury = PLTs also bind vWFv via GPIb/IX/V receptors before binding wall
Bernard Soulier
GPIb deficiency
- affects adhesion in PLT plug for MAJOR injuries
VonWillebrand Disease
vWF deficiency
- affects adhesion in PLT plug for MAJOR injuries
Describe Aggregation stage of platelet plug
- reversible OR irreversible (TXA2 and ADP)
- PLTs bind other PLTs
- ADP released during PLT adhesion = exposes fibrinogen receptors on PLTs (GPIIb/IIIa integrin) and P-selectin
- PLTs aggregate using fibrinogen and Ca2+
Glanzmann’s Thrombasthenia
GPIIb/IIIa deficiency
- affects aggregation in PLT plug
- reduced fibrinogen receptors on PLTs
Describe Granule Secretion stage of platelet plug
- simultaneously during adhesion/ aggregation
a. ALPHA granules = via SCC system
- PF4
- B thrombomodulin
- PDGF, endothelial GF, Transforming GF
- Factors V, XI, vWF, fibrinogen
b. DENSE = via exocytosis
- ADP/ ATP
- Ca2+, Mg2+
- serotonin
SSC = surface-connected canalicular
Describe Formation/ Function of Thromboxane A2 in a platelet plug
PF3 = PLT phospholipids
- during PLT activation = converted to arachidonic acid = thromboxane A2
- thromboxane A2 = triggers more Ca2+ release = promotes PLT aggregation and vasoconstriction = coagulation
What blocks cyclooxygenase and prevents thromboxane A2 production ?
ASPIRIN leads to impaired PLT function
What is TF and where is it found ?
a transmembrane protein in the endothelium
What are coagulation factors ? Where are they made ?
proteins synthesized by the liver
Define zyomgen
Inactive form of enzymes (coagulation factors)
Define serine protease
enzymes that cleave proteins = must be activated to participate in reaction ie. IIa/ prothrombin
Define cofactor
a substance (other than the substrate) whose presence is essential for the activity of an enzyme
Which coagulation factors are serine proteases ?
Kallikrein
IIa (prothrombin)
VIIa
IXa
Xa
XIa
XIIa
Plasmin
Protein C
Which coagulation factors are cofactors ?
FV and FVIII
Which clotting factors are vit-K dependent ? What is the function of vit K in the synthesis of these factors ?
II/ prothrombin, VII, IX, X (2790) & Protein C/ S/ Z:
- vit K catalyses carboxylation of terminal glutamic acids
- carboxyl group binds Ca2+ = allows binding of PF3