Haemostasis in cerebrospinal fluid. Basic concept of antifibrinolytic therapy of subarachnoid haemorrhage.
Among the reasons for intensified research into the CSF haemostatic pathway were the clinical case reports stating that special importance must be attached to the CSF for the high incidence of rebleeding and the intraoperative haemorrhage rate in SAH patients, which, among other things, may be regarded as the reasons for mortality. Extensive analyses of the coagulation and fibrinolysis enzyme systems were carried out and constitute the basic concept for the conservative AFT aiming at restoring to normal haemostasis and wound healing which had been disturbed by local fibrinolytic activity in the area of operation or trauma. The programme of investigation, first served as basic research and was then directed towards the clinical situation for recording the partly contradictory or still unknown haemostasis values in the CSF. This necessitated that the immunochemical, enzymatic, enzymatic-fluorometric, biophysical and chromogenic substrate methods should be adapted to low quantities of protein for the quantitative determination of activators, inhibitors, zymogens, enzymes, the fibrin substrate and its degradation products. The results obtained with the prospective series of tests applying selective methods with objective data recording confirm the operating hypothesis that, on principle, a distinction must be made between the proteins of normal CSF in cases of intact BBB and the pathological protein patterns, not typical of CSF, caused by disturbances of permeation. The CSF space, therefore, must be regarded as a compartment largely insulated by the BBB. That is why the unqualified interpretation is wrong, when it states that the CSF, in general, shows a fibrinolytic activity, no matter whether the CSF is formed under physiological or pathological conditions, or whether it represents a mixture of blood and CSF. CSF formed when the BBB is normal has no fibrinolytic activity. The plasminogen activator antigen always present in CSF does not become effective because the quantity of plasminogen in CSF is well below normal for the measurable fibrinolytic activity. In the case of diseases accompanied by disturbance of the BBB, the proteins of the fibrinolytic system in the CSF increasingly penetrate in proportion to the disturbance of BBB, and thus enable the CSF to some extent to become a fibrinolytically active fluid. A temporarily limited breakdown of the BBB in the case of bleeding into the CSF space permits the unhampered transfer of all the factors required for the fibrinolytic system, as well as the inhibitors.(ABSTRACT TRUNCATED AT 400 WORDS)
D000933:Antifibrinolytic Agents / Q000627:therapeutic use*; D001777:Blood Coagulation; D001812:Blood-Brain Barrier; D002555:Cerebrospinal Fluid / Q000502:physiology*; D002556:Cerebrospinal Fluid Proteins / Q000032:analysis; D005342:Fibrinolysis; D006487:Hemostasis; D006801:Humans; D013345:Subarachnoid Hemorrhage / Q000097:blood / Q000134:cerebrospinal fluid / Q000188:drug therapy*
D000933:Antifibrinolytic Agents; D002556:Cerebrospinal Fluid Proteins