Towards rational treatments in subarachnoid haemorrhage

This thesis investigates two equivocal treatment strategies in subarachnoid haemorrhage (SAH). The first is administration of tranexamic acid (TXA), previously shown to have no beneficial effect on the clinical outcome. In three studies we investigate whether TXA is beneficial in a subgroup of patients (patients with a proven ruptured aneurysm; using different timing intervals from ictus to TXA treatment; good-grade and poor-grade aneurysmal SAH). None of the subgroup analyses shows a beneficial effect of TXA on clinical outcome. The second strategy is hypertension-induction, a non-evidence-based, though worldwide applied, treatment of delayed cerebral ischemia (DCI). The results show that hypertension-induction more frequently leads to clinical improvement on day one after DCI, however, improvement rates were similar on day five, due to spontaneous reversal of DCI-symptoms in patients treated without hypertension-induction. Clinical outcome also did not differ between both groups after three or six months. Part two focuses on biomarkers of DCI. An extensive literature review resulted in a selection of seven promising biomarkers of clinical DCI (haptoglobin polymorphism 2-1 and 2-2, ADAMTS13, neutrophil/lymphocyte ratio, P-selectin and von Willebrand Factor in blood; and F2-isoprostane in urine), and one biomarker of radiological DCI (lactate/pyruvate ratio in microdialysate). The combination of a review on viscoelastic testing in SAH patients and our prospective study on rotational thromboelastometry (ROTEM) in aneurysmal SAH showed that hypercoagulability, as detected by ROTEM, has good predictive test characteristics for DCI and excellent predictive test characteristics for poor clinical outcome. Lastly, we show that platelet RNA profiles significantly differ between patients with and without radiological DCI, and selected a radiological DCI-specific 13 platelet RNA panel, which was already apparent within the first 24 hours after SAH.