Vascular-platelet haemostasis, blood coagulation and fibrinolysis regulation.

 

There exist 4 levels of haemostatic system regulation.

Molecular level – supposes haemostatic equillibrium supporting for factors influencing on vascular-platelet haemostasis, blood coagulation and fibrinolysis. Factor excessment appearing in organism due to one or other reason must be liquidated in short time as soon as possible. Such equillibrium is constantly supported between prostacycline and thromboxanes, procoagulants and anticoagulants, plasminogen activators and inhibitors. Cellular receptors existance to many blood coagulation factors underlies haemostatic equillibrium in haemostatic system at molecular level. Receptors to coagulation and fibrinolysis factors coming off cells (“swimming” receptors) acquire new features becoming natural anticoagulants, plasmine inhibitors and plasminogene activator. Regulational molecular level may be realized with immune system by means of antibodies to activated coagulation and fibrinolysis factors – II_a, X_a, tissular palsminogene activator and others- formation. There is genetic control under factors production providing blood clot forming and dissolving.

Cellular level. In circulation constant coagulational and fibrinolytic factors consumption occurs that must obviousely lead to their concentration restoration. This process must be caused by either activated factors or their metabolic products. If it is really so, cells must have receptors to indicated substances. Such receptors were found on many cells to thrombine, kallikrein, plasminogene activator, plasmine, FDP and others. Cellular level is also provided by “near-wall” fibrinolysis occuring at fibrine accumulation on vascular wall endothelium.

Organic level- determine haemostatic system optimal existential conditions in circulation different regions. Vascular-platelet and coagulational haemostasis and fibrinolysis mosaic is expressed due to this level. Our chair collaborators scientifical works for last years have proved that blood while passing through one or other organs (for example, brain, extremities muscles, kidneys) is satiated with additional haemocoagulational and fibrinolytical factors which may be synthesized in these organs. Moreover, we (V.P.Mischenko, I.V.Mischenko, E.V.Tkachenko, E.A.Tkach, O.V.Kokovskaya, J.M.Grishko and students of different departments and courses which are members of our chair student’s scientific society) demonstrate that blood outflowing from these organs on the right and on the left has different coagulative and fibrinolytic features. It was the base to consider that in animal and human organism there is haemostatic and fibrinolytic process asymmetry. Such asymmetry was found by us in different laboratory animals (hens, rats, rabbits, guinea pigs, cats) and human beings.

Nervous-humoral regulation controls haemostasis state from molecular till organ level, providing reactions integrity at organism level. It is realized mainly through vegetative nervous system sympathetic and parasympathetic parts.

First of all, one should mention that there exists cortical (conditioned-reflectory) haemostatic system regulation. There some scientific data indicating on the possibility to determine conditioned reflexes both to the acceleration and especially to blood coagulation retardation up to bleedings (bleedy tears, haemorrhagias in places analogous to wounds places, caused at Christ crucifixion et al.).

CNS separate structures (cerebellum, thalamus, hypothalamus) participate in regulation both of activation and inhibition of haemostasis system functionning. As it was proved (B.I.Kuznic, V.P.Mischenko, L.L.Goncharenko. D.S.Zazykina) hypersympathicotony (acute haemorrhagia, hypoxy, stress, intensive muscular activity, adrenaline and noradrenaline introduction) causes blood coagulation acceleration and fibrinolysis enforcement. It is linked not only with Hageman’s factor activation but also with thromboplastine, tissular plasminogene activator releasing from vascular wall. But the most interesting is the fact that at hyperparasympathicotony (vagus irritation, acetylcholine and pilocarpine introduction) we observe coagulation acceleration and fibrinolysis too. Under this conditions thromboplastine and tissular plasminogene activator releasing from vascular wall occurs too. Moreover, drugs vasoconstrictors and vasodilatators by their nature cause similar answer from blood coagulation and fibrinolysis - thromboplastine and tissular plasminogene activator releasing. It testifies that vascular wall is blood coagulation and fibrinolysis efferent regulator!

Haemostasis regulationhumoral mechanism - is hormones, mediators, vitamines and other substances action.

Hormones of suprarenal glands (corticosteroids, adrenaline), hypophysis (ACTH, STH), thyroid (thyroxine), parathyroid (parathormone) and other glands mainly activate blood coagulation, although everything depends on their dosage.

Mediators – noradrenaline, acetylcholine and others mainly activate blood coagulation too.

Vitamines have different influence on haemostasis process.

Vitamine “A” - inhibits coagulation and activates fibrinolysis.

Vitamine “E” – accelerates blood coagulation and suppresses fibrinolysis.

Vitamine “PP” (nicotinic acid) – accelerates coagulation and increases fibrinolysis.

Vitamine “B₁₂” – accelerates coagulation and suppresses fibrinolysis.

Vitamine “C’ - enforces blood coagulation.

But at the same time doctor should remember that this vitamines effect on haemocoagulation depends on their dosage. These data are quite important because vitamines and hormones usage is widely-spread.

Hypercoagulation occurs mainly due to time shortening mainly of the first haemocoagulation stage. That’s why hypercoagulation reasons are quite different and depend on many coagulation factors located in plasma, formed elements and tissues. Hypercoagulation reasons:

1) Hypercoagulation occurs at blood coagulation factors (especially I, VIII and IX) excessment). It may be observed at:

· muscular activity;

· emotions;

· pain;

· hyperadrenalinaemia;

· in pregnant women.

3) Thrombocytosis.

4) Erythrocytosis.

5) Erythrocytic haemolysis:

· burns;

· haemolytic states;

· toxic animals bites;

· blood haemotransfusions.

6) Some leukosis forms.

7) Any tissular injuries.

But hypercoagulation may transforms into hypocoagulation, which is secondary under natural conditions and is caused by thrombocytes and plasma coagulation factors consumption as well as secondary anticoagulants formation. Primary hypocoagulation reasons are following:

1) blood coagulation congenital disorders:

· haemophilia;

· thrombocytopathies (Glanzman’s disease et al.);

2) autoimmune hypocoagulation accompanied by bleedings.

In clinics often secondary hypocoagulation of coagulational character is observed, for instance in cource of disseminated intravascular syndrom (DIS-syndrom) development. This phenomenon is occured at many diseases, it’s non-specific, universal and almost catastrophic. Letality at its acute formes reaches 30-60 per cent in adults and up to 90 per cent in new-borns.

Pathogenesis. Disseminated blood coagulation with multiple clots and formed elements aggregates forming in circulation which lead to blood circulation disorders. Possible result: dystrophic changes in tissues and organs where it occurs.

In course of this syndrom development everything is originated from blood coagulation activating, i.e. hypercoagulation (possible reasons of which – see above). Its determining doesn’t require special conditions because one can see it at blood taking: blood is coagulated in neadle, in test-tube with stabilizator. This is the first sign of DIS – syndrom. The reaction main reason – tissular injury and destruction. It results in thromboplastine big amounts coming into circulation and rapid thrombine formation.

Thrombocytopenia increases at the second stage, blood coagulation part is consumped to clots formation. This is the phase of different-dimensioned changes: laboratory analizes testify that one tests tell about hypercoagualtion, others – about hypocoagulation and the third ones are normal. Such contradictory picture is a distinguishing feature of DIS-syndrom.

Third stage - hypocoagulational; clots are formed badly or are not formed; thrombocytopenia is enforced. Haemorrhagical stage of DIS-syndrom is very dangerous, but is is not always accompanied by it. Sometimes bleedness may have local, for example organic character. Common bleedness is characterized by appearence of cruises great amount, haemorrhagias, haematomas and different bleedings (nasal, pulmonal, stomach-intestinal et al.).

On its freaquency DIS-syndrom is developed in target-organs in such an order (sequence): lungs, kidneys, liver, alimentary tract, brain.

Fighting with DIS-syndrom is rather complicated.

There exist blood coagulation disorders and DIS-syndrom preventive physiologic methods: healthy life style:

· constant (regular) physical training (in trained organism anticoagulants and fibrinolysis activators content is always bigger);

· individual restricted feeding (better - according to your blood group). Animal products especially rich in fats will enforce blood coagulation reactions.

Live generousely, with taste, according to needs individual to your blood – and all problems will be over!

Lecture 19.