Fibrinolysis in subarachnoid haemorrhage.

RECURRENT subarrachnoid haemorrhage from intrachanial aneurysms most commonly occurs during the 2nd, 3rd and 4th weeks after the initial ictus, and after 8 weeks the recurrence rate, approaching 50% in untreated cases, falls sharply (Hamby, 1948; Walton, 1952; Holmes, 1957; McKissoch, Paine & Walshe, 1958). For those patients having no surgery who survive 6 weeks after subarachnoid haemorrhage, the chances of surviving 1 year or longer are 82% (Locksley, 1966). The anatomical pattern of saccular aneurysm is too often repeated, at each of the common sites, for any one to be recognized as more vulnerable to recurrent bleeding than others. Mechanical factors such as the size of aneurysm, streaming, or width and configuration of the neck, do not in general influence the recurrence rate; and our attention is necessarily directed towards variations in the natural physico-chemical processes believed first to seal, and then to repair, a rent in a blood vessel. The primary sealing of the hole in an aneurysm wall by a platelet plug, at first permeable to red cells, may be assumed responsible for the initial stemming of the leak within, say, 4 min. Cells infiltrate the plug and the complex process of building a clot commences. What happens to this clot during the next 8 weeks determines whether the patient suflers recurrent haemorrhage. In about half such patients the seal remains viable; good firm adherent clot becomes organized, and the repair may last for many years. In a conservatively treated series of cases there must be a very fine dividing-line between the mechanism of blood clotting in these patients, and in the other 50% whose aneurysms bleed again within a few weeks. This does not mean that there is any recognizable abnormality in the maturation of the clot in those cases that bleed again. Clotting and bleeding times in both groups are within normal limits; but the balance is so delicate that either variations within the norm are decisive, or some other factor is operative in the maturation of clot, which we have not been able to measure sufficiently accurately. Platelet adhesiveness, blood viscosity, local fibrinogen concentration, fibrinolysis-any or all of these may be relevant. It seems certain, however, that there is both continual building up and absorption of clot going on simultaneously-the laying down of fibrin and formed elements on the one hand, and fibrinolysis with digestion on the other. Perhaps one of these processes ceases too soon, or another too late. Hellem (1960) says that 'the fact that Factor R is inactivated in plasma (in vitro and probably in vivo) may, with the fibrinolytic system, explain why a thrombus does not grow indefinitely'. Two considerations prompted the investigation in this paper: in the first place the development of accurate methods of fibrinolysis assay in vitro, and secondly the marketing of epsilon aminocaproic acid (EACA), known to inhibit fibrinolysis and almost harmless when given orally. Between November 1963 and March 1965 assay of plasminogen activator and of fibrinogen was performed in 109 cases of subarachnoid haemorrhage admitted to the South East Regional Neurosurgical Centre. A clinical trial of the effects of administering EACA was continued until the end of the year.