Anticoagulant Related Intracerebral Hemorrhage Management

see also Intracerebral Hemorrhage Treatment.

Patients with minor and moderate associated bleeding can be treated with supportive care and general hemostatic measures. Nonspecific reversal agents (eg, prothrombin complex concentrate, activated prothrombin complex concentrate) are of unproven benefit, carry a risk of thrombosis, and should be reserved for severe bleeding. Specific reversal agents, such as idarucizumab (a monoclonal antibody fragment that binds dabigatran) and andexanet alfa (a recombinant factor Xa variant that binds factor Xa inhibitors but lacks coagulant activity), are in clinical development ¹⁾.

The management of intracerebral hemorrhage and anticoagulation must be initiated simultaneously with diagnosis, treatment, and disposition.

They require urgent correction of their coagulopathy to prevent hemorrhage expansion, limit tissue damage, and facilitate surgical intervention as necessary.

Advances such as newer laboratory testing and rapid computed tomography for diagnosis, blood pressure reduction to reduce hematoma expansion, and new anticoagulant reversal agents may allow for improved outcomes. Management of intracranial pressure is particularly important in anticoagulated patients, as is identifying patients who may benefit from rapid neurosurgical intervention and/or emergent transport to facilities capable of managing this disease ²⁾.

After such an event, it is unclear whether anticoagulant therapy should be resumed. Such a decision hinges upon the assessment of the competing risks of haematoma growth or recurrent ICH and thromboembolic events. ICH location and the risk for ischaemic cerebrovascular event seem to be the key factors that lead to risk/benefit balance of restarting anticoagulation after ICH.

Patients with deep hemispheric ICH and a baseline risk of ischemic stroke >6.5% per year, that corresponds to CHADS2≥ 4 or CHA2DS2-VASc ≥ 5, may receive net benefit from restarting anticoagulation. To date, a reasonable recommendation regarding time to resumption of anticoagulation therapy would be after 10 weeks. Available data regarding the role of magnetic resonance imaging in assessing the risks of both ICH and warfarin-related ICH do not support the use of this test for excluding anticoagulation in patients with atrial fibrillation ³⁾.

While oral anticoagulation (OAC) is universally indicated for patients with mechanical heart valves (MHVs), OAC resumption following anticoagulant-associated intracerebral hemorrhage (ICH) is an area of uncertainty.

A cross-sectional survey was disseminated to North American members of the American Association of Neurological Surgeons and the International Society for Thrombosis and Haemostasis. Demographic factors, as well as a clinical scenario with 14 modifiable clinical risk factors were included in the survey.

504 physicians completed the survey (response rate 34.3%). Majority of participants were affiliated with academic centres, and managed ≤10 ICH patients with MHV per year. There was wide distribution in response in optimal timing for OAC resumption following an ICH: 59% and 60% preferred to re-start OAC between 3 and 14 days following the hemorrhagic event (median of 6-7 days). Smaller hemorrhages (<30cm2). CHADS2 score ≥2, concomitant venous thromboembolism, mitral valve prosthesis, caged-ball valves and multiple valves prompted earlier OAC resumption.

Wide variation in the current practice of neurosurgeons and thrombosis specialists exist when they encounter patients with ICH and MHV, though decisions were influenced by patient- and valve-related factors. As our observed variation likely reflects the immense gap in current evidence, prospective randomized trials in this population are therefore urgently needed ⁴⁾.

A total of 942 (44%) patients with ICH took antithrombotic drugs at hospital admission (no difference between cohorts). Antithrombotic drugs were restarted in 96 (20%) of the 469 survivors who had taken antithrombotic drugs for secondary prevention or atrial fibrillation, but this proportion differed when stratified by the cohort of origin (Lille, 18%; Utrecht, 45%; Lothian, 15%; CROMIS-2 ICH, 11%; Amsterdam, 20%; P<0.001) and by type of antithrombotic drug pre-ICH (14% in patients with previous antiplatelet drugs versus 26% in patients with previous vitamin K antagonists and 41% in patients with both drugs; P<0.001). We did not find other consistent, independent associations with restarting antithrombotic drugs.

The variation in clinical practice and lack of consistent associations with restarting antithrombotic drugs after ICH reflect current knowledge and support the need for randomized controlled trials to resolve this dilemma ⁵⁾.

In 27 patients with cardiac diseases, anticoagulants were stopped as soon as the diagnosis of intracranial hemorrhage was established by computed tomographic scan.

Mechanical valve prosthesis patients, who required intensive long-term anticoagulant therapy, constituted the majority of the series (74.1%). Intraoperative hemostasis was brought under control despite low thrombotest values (13%-68%) at the time of surgery except for the acute subdural hematoma (SDH) patients with cerebral contusion. Early resumption of anticoagulant therapy (within 3 days) did not cause intracranial rebleeding in any operative patient. All the chronic SDH patients and some of the subcortical hematoma patients had a good outcome. All three patients with acute SDH and contusion, however, had a fatal outcome because of intracranial rebleeding within a short period of time or ineffective intraoperative hemostasis.

The patients with anticoagulant-related intracranial hemorrhage may undergo surgery with thrombotest values approximately between 20% and 60%, and anticoagulants can be resumed after an interval of 3 days. Aggressive surgery should particularly be performed in patients with anticoagulation-related chronic SDH or subcortical hemorrhage, as in the cases of anticoagulant-unrelated intracranial hemorrhage ⁶⁾.