Antifibrinolytic treatment in aneurysmal subarachnoid hemorrhage

"It is perhaps no wonder that young doctors, nurtured in an aura of basic science, turn vvistfully back to the laboratory where a neat and aesthetically satisf) • ing experiment can be performed, even though the result is of no obvious benefit to the medical practice for which they have been trained." ].E. Lennard-Janes (176) aan mUn ouders aan de nagedachtenis van Spuistraat 70 Some parts of this thesis were adapted for articles that have been or will be published.-Vermeulen M, Muizelaar JP: Do antifibrinolytic agents prevent rebleeding after rupture of a cerebral aneurysm? A review. Spectrophotometric analysis of CSF after subarachnoid hemorrage: Limitations in the diagnosis of rebleeding. Causes of acute deterioration in patients with a ruptured intracranial aneurysm. A prospective study with serial CT scanning. Antifibrinolytic treatment in subarachnoid hemorrhage: A multicenter, double-blind, placebo-controlled trial. Degradation products of Fibrin/Fibrinogen in the CSF after subarach-noid hemorrhage: A result of protein leakage rather than local fibrinolytic activity. General introduction 7 Chapter I Current knowledge of subarachnoid hemorrhage and antifibrinolytic therapy 9 Part 1: Aneurysmal subarachnoid hemorrhage 9 Part 2: Fibrinolysis and antifibrinolytic treatment 14 Part 3: Fibrinolysis after subarachnoid hemorrhage 19 Part 4: Methods for the clinical assessment of antifibrinolytic treatment in subarachnoid hemorrhage 21 Part 5: Previous clinical studies on the effectiveness of antifibri-nolytic treatment in subarachnoid hemorrhage 29 Chapter II Degradation products of fibrin and fibrinogen in the cerebrospinal fluid after subarachnoid hembrrhage: A result of protein leakage rather than local fibrinolytic activity 35 Chapter III The diagnosis of rebleeding from the cerebrospinal fluid: Comparison of serial spectrophotometry of the CSF and serial computed tomography of the brain 43 Chapter IV The diagnosis of rebleeding on clinical grounds: serial computed tomography and episodes of acute clinical deterioration 49 Chapter V Antifibrinolytic treatment in subarachnoid hemorrhage: A multi-center, double-blind, placebo-controlled trial in 479 patients 59 General summary 73 Samenvatting 76 References 80 Acknowledgements 87 Curriculum Vitae 88 7 GENERAL INTRODUCTION Since 1967 antifibrinolytic agents have been used in patients with a subarachnoid hemorrhage (SAH) from a ruptured intracranial aneurysm. Despite many studies on this subject, it is still not clear whether these patients benefit from this treatment. The aim of this study is to elucidate and to solve this controversy. Chapter I gives a detailed outline of the problem. Aneurysmal subarachnoid hemorrhage is a serious condition with an incidence of 10-20 per 100,000 population per year. One of the …