Investigation of Haemostasis.

HHHHaemostasis is the arrest of blood loss from damaged vessels. TTTThe haemostatic mechanisms have two primary functions: To ensure that circulating blood remains fluid while in the vascular bed. And to arrest bleeding at the site of an injured blood vessel.

TTTTo fulfill that: BBBBlood must be fluid MMMMust coagulate (clot) at appropriate time Rapid Localized Reversible

The normal haemeostasis depends on a delicate balance and complex interaction between at least five components: PPPPlatelet. BBBBlood vessels. PPPPlasma coagulation proteins. 4444+5. Inhibitors and the fibrinolytic system.

Vascular haemostasis.

HHHHumans have evolved an intricate hemostatic system that is designed to maintain blood in a fluid state under physiologic conditions, but that is primed to react to vascular injury in an explosive manner to stem blood loss by sealing the defect in the vessel wall. TTTThe blood cell wall has three layers: intima, media and adventitia. TTTThe intima consists of the endothelium and subendothelial connective tissue and is separated from the media by the elastic lamina interna. EEEEndothelium cells form a continuous monolayer lining all blood vessels.

 T T T The function and the structure of these cells are vary according their location in the vascular tree, but they are all share three important characteristics: TTTThey are "non thrombogenic" that is do not react with plasma or the cellular elements of the blood. TTTThey play an active role in supplying nutrients to the subendothelial structures. AAAAnd act as a barrier to macromolecules and particles matter circulating in the blood stream. TTTThe intact vessel wall has an important role in preventing haemostasis.

EEEEndothelial cells produce: PPPProstacyclin, which causes vasodilatation and inhibits platelets aggregation. PPPProtein C (PC) activator (Thrombomodulin), which inhibits coagulation. AAAAnd tissue plasminogen activator (TPA) which activates fibrinolysis.

Endothelial cell function 1: TTTThe luminal surface of the endothelial cell is covered by Glycocalyx coat. IIIIt contains heparin sulphate and other substances which are capable of activating antithrombin III, an important inhibitor of coagulation enzymes. BBBBeneath the glycocalyx, there is a trilaminar membrane containing ADPase, an enzyme which degrades ADP which is a potent platelets agonist. TTTThe endothelial cells can also generate angiotensin II, a local vasoconstrictor.

Endothelial cell function 2: TTTThrombin generated at the site of the injury is rapidly bound to a specific cofactor of the endothelial cell, Thrombomodulin. When bound this protein, thrombin can activate the protein C system to degrade and inhibit factor Va and VIIIa. TTTThrombin can also stimulate the endothelial cells to produce plasminogen activator. FFFFinally, the endothelial cells produces von Willebrand factor (vWF), essential for platelets adhesion to the subendothelium. vWF is secreted partly into the circulation and partially towards the subendothelial matrix.

The subendothelium: TTTThe subendothelium is consists of connective tissues composed of collagen, elastic tissues, proteoglycans, fibronectin and vWF. AAAAfter endothelial damage has taken place, components of subendothelium are exposed and platelets adhere to various elements collagen of basement membrane and micofibrils. TTTThe adhesion of platelets is regulated by specific properties of the platelet membranes and biochemical characteristics of the subendothelial structures. OOOOther factors, such as plasma concentration of vWF and the characteristics of the blood flow also effect adhesion.

Vasoconstriction: VVVVessels with muscular coat contract following injury, thus assisting haemostatic plug formation by reducing the blood flow. VVVVasoconstriction occurs, however, even in the microcirculation in vessels without smooth muscle cells. EEEEndothelial cells can themselves produce vasoconstrictors such as angiotensin II; in addition, activated platelets produce prostaglandins (TXA2) with vasoconstricting properties.

Investigation of the Disorders of Vascular Haemostasis: TTTThe disorder this part may be due to increase permeability, reduction of vessels strength and failure to contract in injury. AAAAn accurate history and careful clinical examination are almost always the keystone of diagnosis. TTTTests of defective vascular function are difficult to perform and interpret. TTTTests of capillary resistance are of limited value. IIIIn some cases skin biopsy with specific staining or even biochemical analysis of the micro-sample may be helpful. TTTThe bleeding time test is normal and the other tests of haemostasis are also normal.

Capillary fragility (resistance) test: TTTThis test is used to determine the presence of vascular disorder, a circle 2.5 cm in diameter, the upper edge of which is 4 cm below the crease of the elbow, is drawn on the inner aspect of the forearm, pressure midway between the systolic and diastolic blood pressure is applied using sphygmomanometer above the elbow for 15 minutes, and a count of p p p p p eeee tttt eeee cccc hhhh iiii aaaa eeeewithin the circle is made: 10, normal; 10–20, marginal; more than 20, abnormal.