Hemostasis

Hemostasis and coagulation disorders

haemostasis

= the biochemical process that opposes blood loss, while contributing to maintaining the fluidity of the circulatory flow

 The physiological processes involved in hemostasis are interdependent and follow one another quickly.

Phases of hemostasis

1. Vascular phase => the first to intervene in the physiological process of hemostasis - involves a reflex vasoconstriction, insufficient, however, to stop the bleeding, if the vessels exceed certain dimensions.

2. Platelet phase => consists in the adhesion of platelets to the surface of the damaged vessel in several successive layers until the formation of platelet thrombus.

o Platelets:

• Fragments from megakaryocytes, with no. Between 150,000-400,000 / mmc.

• They intervene in adhesion (when we have vasoconstriction they adhere to the vascular breach => when a breach is made positive electrical charges accumulate which attract platelets with negative charge => GP1B, 23BA favors adhesion), aggregation (favored by thromboxane A2 and ADP) and secretion (they release serotonin, thromboxane A2 etc => the white thrombus is formed => with the formation of the white thrombus the primary hemostasis ends).

3. Coagulation

= an enzymatic process during which soluble fibrinogen is transformed into insoluble fibrin.

- can be triggered by an intrinsic or extrinsic mechanism.

a. The extrinsic mechanism

 The fascular wall releases FT (tissue factor) => under the action of FT, FVII becomes FVIIa => FVIIa + Ca2 +, PL forms the activation complex of FX through the extrinsic mechanism.

b. The intrinsic mechanism

 Triggers when blood comes in contact with a rough surface

 Participates in FXII, HMWK (high molecular weight kininogen), and prekalikrein, the result of the contact phase is the activation of FXIa.

 Under the action of FXIa FIX is activated => the conversion complex of FX formed by intrinsic mechanism is composed of: FVIII, Ixa, Ca2 + PL.

c. The common way of activating coagulation

X FXa, having as PV cofactor, in the presence of Ca2 + and PL, converts prothrombin to thrombin.

 Under the action of thrombin fibrinogen becomes fibrin monomer => fibrin polymer => under the action of FXIII it becomes insoluble fibrin. => Red thrombus => stable, stops bleeding.

 Coagulation inhibitors (examples): antirombin III, heparin cofactor II, protein C system, inhibitor of the extrinsic mechanism of coagulation activation.

4. Fibrinolysis

= the process of enzymatic decomposition of fibrin.

- The fibrinolytic system has a structure similar to that of the coagulation system

 Plasminogen can be activated in plasmin by an extrinsic and intrinsic mechanism.

a. The extrinsic mechanism

- is triggered by: the tissue activator released by the vascular endothelium; urokinase (found in urine, plasma, semen, vagina, gastric juice, etc.); streptokinase (of bacterial origin - strong plasminogen activator).

b. The intrinsic mechanism

- triggered by FXII activation

- plasmin digests fibrin => resumption of blood flow.

I. Vascular abnormalities (vasculopathies)

a) Vasculopathies by hypersensitivity

• Purple Schonlein-Henoch

o It is based on a mechanism of hypersensitivity mediated by circulating immune complexes, formed in the conditions of excess Ag (microbes, viruses, food, etc.) or the immune complexes are formed locally in the vessel walls.

o Due to the structure of the CIC or as a consequence of a deficit in the capture of macrophages, they persist in circulation, they are deposited in the vessel walls.

a CIC deposited in the walls activates the complementary system, which releases the mediators of inflammation and thus weakens the vascular walls.

b) Vasculopathies by altering the structure of the vessels and perivascular tissues

• Render-Osler disease

o It is the consequence of a hypolplasia of the vascular environment, which contributes to the formation of dilations in the subpapillary venous network

o Vascular ecstasy occurs in the form of red spots, nodules with increased fragility that break easily, causing bleeding.

• Scurvy

o Occurs due to severe cattle deficiency. C.

o There is a conjunctival hypoplasia, which is manifested by gingival or skin hemorrhage.

o Absent vit. C leads to lack of hydroxyproline => no collagen is formed => tissue. Conj. Perivascular is no longer airtight => bleeding occurs