Emerging treatments

Surgical techniques

Post hoc subgroup analyses of the STICH (Surgical Trial in Intracerebral Haemorrhage) trial suggested a benefit for resection of haematomas <1 cm from the brain surface and possible harm from resection for patients in coma (Glasgow Coma Scale ≤8).[102] Some data support the possibility of a good outcome with early resection (<12 hours), despite a possible higher rate of recurrent bleeding.[23]​ Extensive research is being done to assess the benefit of haematoma drainage through minimally invasive surgery. An extensive meta-analysis showed that patients with supratentorial intracerebral haemorrhage (ICH) may benefit from minimally invasive draining techniques, especially when suffering superficial 25 mL to 40 mL haematomas.[103] The phase 2, randomised, controlled, open-label MISTIE trial showed that minimally invasive surgery plus alteplase appears to be safe in patients with ICH; however, increased asymptomatic bleeding was a major finding.[104] The STICH II trial confirmed that early surgery of superficial haemorrhage may offer a small survival advantage, especially in the non-comatose group of patients that present with or progress to a decreased level of consciousness (Glasgow Coma Score 9 -12).[105] The ICES study also showed that early intraoperative stereotactic computed tomography (CT)-guided endoscopic surgery is a safe and effective method to remove acute ICHs.[106] The use of recombinant tissue plasminogen activator (r-TPA) has been shown to accelerate resolution of intraventricular haemorrhage.[107]

Recombinant coagulation factor Xa (andexanet alfa)

A recombinant modified human factor Xa decoy protein that binds factor Xa inhibitors, resulting in decreased anti-Xa activity and thrombin generation. In the UK, andexanet alfa is recommended only in research for reversing anticoagulation from apixaban or rivaroxaban in adults with life-threatening or uncontrolled intracranial haemorrhage, in the form of an ongoing randomised trial mandated by the regulator.[108]​ There is an ongoing trial, which aims to determine the efficacy and safety of andexanet alfa compared to usual care in patients presenting with acute intracranial haemorrhage within 6 hours of symptom onset and within 15 hours of taking an oral factor Xa inhibitor.[109]

Haemostatic therapy

Treatment with recombinant activated factor VII prevented haematoma growth but failed to improve clinical outcomes in a phase III trial.[21] Future trials may investigate whether recombinant activated factor VII is more effective in selected patient subgroups. Additional basic research has been performed on cilostazol (a phosphodiesterase-3 inhibitor) to prevent intravenous tissue plasminogen activator-associated haemorrhagic transformation and warfarin-induced haemorrhage. Cilostazol has been shown to have protective properties on endothelial cells, vascular smooth muscle cells, and the blood-brain barrier, yet clinical trials are needed to investigate if such properties would be of benefit in haemorrhagic stroke or prevention of haematoma expansion.[110][111][112]​​

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