Platelets and Coagulation

Primary hemostatic/platelet plug Coagulation

o Is a process and is a property of plasma, alone o Process by which soluble fibrinogen can transform into

insoluble fibrin strandso A cascade of enzymatic reactions o Fibrinogen (soluble in the plasma) is produced by the liver o How does the cardiovascular system keep blood in a liquid

form? Endothelial cell can release NO, PGI2

(prostacyclin), ADP dephosphotase – they are anti-platelet agents

Platelet receptor must be in the active state 2-3 microns – size of platelet 8-10 days – lifespan of platelet 7-8 micros size of RBC

o Heparan sulfate – expressed by endothelial cells; hooked with ATIII (produced by the liver); AT3III – becomes active and will cut down the thrombin molecules and can also inactivate Xa and destroy IXa

o Thrombomodulin – modulates the functions of thrombin; thrombin activates protein C and (will digest Va and VIIIa)

o Tissue plasminogen activator –produces by healthy endothelium; activates plasminogen into plasmin

o Plasmin – will digest the fibrin into fibrin degradation products (Thus the endothelium has the power to destroy the fibrin)

Steps to prevent the bleeding

1. Vasoconstriction – early response; vasoconstrictors are released because of damaged sensory endings

2. Myogenic constriction – injured smooth muscle 3. Endothelial cells – normally releases vasodilators (PGI2 and

NO); so when injured, produces endothelin and causes muscle contraction (blood loss prevention)

o Von Willebrand factor – sticky glue; there are special type of receptors on the platelet; receptor is known as GPIb

Platelet Adhesion o Process wherein platelet stick to non-platelet surface

Platelet Activation o In the platelet membrane, phospholipases enzyme are

activated → arachidonic acid → TXA2 (vasoconstrictor and platelet aggregator)

o Aspirin inhibits cyclooxygenase (converts AA to TXA2) in the platelet

o When GPIb receptors are activated, platelets release o Platelets have granules – alpha and delta (Serotonin, ADP,

and calcium) Serotonin – vasoconstriction ADP – platelet activating Calcium – hold the coagulation factors tightly on

the phospholipid membrane o Vitamin K important for glycosylation o Alpha granules contain coagulation factors, fibrinogen,

platelet derived growth factors o ADP and TXA2 attracts more platelets o Initial/ primary platelet plug is formed after platelet

aggregation Platelet Aggregation

Secondary Hemostatic/platelet plug

Intrinsic pathway Extrinsic pathway -leads to coagulation without addition of any external substance-when blood comes in touch with the injured endothelial cell-factor XII → factor XIIa → factor XI → Factor XIa → factor IX → factor IXa (PL, calcium, factor VIII) → factor Xa (PL, calcium, factor V)→ converts prothrombin (factor II) to thrombin → convert fibrinogen to fibrin monomers -thrombin also activates factor XIII (fibrin stimulating factor) → factor XIIIa (for cross linking of monomers) – secondary hemostatic plug

-activated by tissue factors -tissue factors activate factor VII → factor VIIa → can also activate factor IX and X -more rapid

Clot – outside cardiovascular system Thrombus – within CV Embolus – travelling thrombus