HEMOSTASIS

A i.e. Antithrombin III

A i.e. Platelet adhesion to exposed endothelium B i.e. Clot retraction C i.e. Activation of prothrombinase complex

Role of Platelets in Hemostasis

–                       VasoconstrictionQ d/t release of TXA₂ and serotonin

–                       Adherence : The glycoprotein of cell membrane platelet cause adherence to exposed endothelium (but repulses to normal endothelium)

–                       Platelet plug formation closing small vascular holes

–                       Conversion of prothrombin to thrombin: Activation of prothrombinase complex+2 (consisting of platelet anionic phospholipids Ca++, factor Va, factor Xa and prothrombin) on the surface of activated platelet lit conversion of prothrombin into thrombin

–                       Stabilization of fibrin: Fibrin stabilization factor released from platelet cause stablization of fibrin (Polymerization of fibrin)

–                       Thrombin causes conversion of fibrinogen to fibrin

–                       Fibrinous organization of blood clot d/t growth factors secreted by platelet

–                       Clot retraction & contraction d/t contractile proteins actin, myosin and thrombosthenin

Ans. is None

o All the processes from vosoconstriction to dissolution of clot are the part of hemostasis.

Ans. is ‘d’ i.e., Vascular endothelium is smooth and coated with glycocalyx

“The luminal surface of the endothelium is relatively smooth and the membrane is coated by a prominent Glycocalyx. The glycocalyx is highly charged, polysaccharide rich felt of glycorprotein anchored to the cell membrane. Because of the high charge density, the glycocalyx may contribute to the non-thrombogenic properties of the surface of the intact endothelium.” – Grays

Endothelium and hemostasis

o Endothelial cells modulate several aspects of hemostasis.

o On one hand, endothelial cells promote blood fluidity by antithrombotic properties.

o On the other hand, endothelial cells exhibit procoagulant activity after injury to arrest bleeding.

A. Antithrombotic properties

o Under most circumstances, endothelial cells maintain fluidity of blood : ‑

1. Antiplatelet effects

o Intact endothelium prevents contact of platelets to highly thrombogenic subendothelial ECM (especially collegen).

o Endothelium secretes PGI₂ & NO, both are inhibitors of platelets aggregation.

o Endothelial cells have ADPase that degrades ADP, a potent stimulator of platelets.

1. Anticoagulant effect

o Endothelium has membrane bound heparin-like molecule that binds with antithrombin III and inactivates factor II (thrombin), IX, X, XI, XII.

o Endothelium also produces thrombomodulin that binds to thrombin converting it from a procoagulant to antigoagulant capable of activating protein C. Protein ‘C’ with the help of protein ‘,V’ as a cofactor, causes proteolytic cleavage of factor V & VIII.

o Endothelium produces tissue factor pathway inhibitor that inactivates tissue factors – factor VII & X.

1. Fibrinolytic effect

o Endothelial cells synthesize tissue-type plasminogen activator (I-PA) that converts plasminogen to plasmin and plasmin then dissolves clot by breaking fibrin.

B. Prothrombotic property

o After injury to endothelium, it becomes prothrombotic by following effects.

I .Platelet effects

o Endothelial cell injury exposes highly thrombogenic subendothelial ECM, which allows platelets to adhere to the collegen of ECM.

o This effects is due to increased production of Von-Willebrond factor by endothelium, an essential cofactor for platelet binding to collegen.

1. Procoagulant effect

o Endothelial cells synthesize tissue factor (factor that activates extrinsic pathway of coagulation).

1. Antifibrinolytic effect

o Endothelial cells secrete inhibitors of plasminogen activator (PAls) that inhibitors the action of plasminogen activator —> Plasmin is not produced from plasminogen No fibrinolysis.

Ans is ‘c’ i.e., Cerebral microcirculation

‘All endothelial cells except those in the cerebral microcirculation produce thrombomodulin, a thrombin protein, and express it on their surface’ – Ganong

Ans. is ‘d’ i.e., The complex removes thrombin and also activates protein kinase ‘C’ which inactivates factors V & VIII

Ans. is ‘a’ i.e., Vascular endothelium

Ans. is ‘a’ i.e., Direct presure over the wound

Ans. is ‘d’ i.e., Bradykinin

Factors promoting platelet aggregation : ADP, TXA, epinephrine, serotonin, vWF, fibrinogen, collagen, immune complex, thrombin, thrombospondin.

Factors inhibiting platelet aggregation: PGIr, NO, endothelin, bradykinin.