Abstract

Introduction: Arterial and venous thromboembolic events, including stroke and myocardial infarction, are a leading cause of morbidity and mortality in the United States. Anticoagulation therapies including but not limited to vitamin K anticoagulant (VKA) and direct oral anticoagulants (DOACs) are critical in preventing such morbidity and/or mortality. Adversely, studies have shown an increased risk of bleeding associated with anticoagulation. For instance, there is a two-fivefold increase risk of intracranial hemorrhage (ICH) with warfarin use. On the other hand, 6.5% to 19.6% of all strokes result in ICH which increases mortality. For patients who were on anticoagulation prior to ICH, there seems to be no consensus on the appropriate timing to resume anticoagulation if at all. Most reported observational studies reveal that the decision on whether and when to resume anticoagulation is based on several clinical factors, such as the size and location of the ICH, the recurrence rate of the particular type of ICH, the underlying indication for anticoagulation and social factors. We performed a single institutional analysis on the correlation of anticoagulation resumption with subsequent risk of ICH recurrence and/or thromboembolism

Method: We retrospectively reviewed medical records of 600 adults [mean age 69 (22-79)] at Beaumont Hospital, an academic community center from May 2015 to May 2016 with confirmed ICH, of which 125 patients were on prior anticoagulation. Our aim was to determine whether there is correlation between timing of re-institution of anticoagulant post ICH and eventual outcome with regards to recurrent ICH and/or thrombosis. We also compared outcome in patients on VKA to those on DOACs. Statistical analysis was performed by an independent investigator.

Results: Demographic distribution of studied patients were 97(77.6%) white, 10 (8.0%) African Americans and 18 (14.4%) others. Among these patients, 75 (60.0%) were on VKA, 18 (14.4%) on Enoxaparin, 26(20.8%) were on one of the DOACs, and 6(4.8%) were on unknown anticoagulant prior to intracranial hemorrhage (ICH) (Table 1). Although anticoagulation was not reinstituted in 71(56.8%) patients following ICH; 5 (4.0%) patients had anticoagulant restarted within 7 days of diagnosis of ICH; 27 (21.6%) patients were restarted between 7-30days and 18 (14.4%) patients were restarted after 30 days. All patients restarted within 7 days of diagnosis were on warfarin due to severe cardiac dysfunction requiring mechanical valves. Using SAS System for Windows version 9.3, statistical analysis was performed on 32 (25.6%) patients who restarted on anticoagulation within 30 days of initial diagnosis to determine the risk of recurrent ICH or thromboembolism. Results showed that 11 (37.5%) patients had recurrent ICH when anticoagulation was restarted within 14 days from initial diagnosis. Of these, 2 (6.25%) patients were on DOACs (specifically, rivaroxaban) while 9 (28.1%) patients were on VKA. Within 30 days of initial ICH diagnosis, 19 (15.2%) patients developed thrombosis. Of those, 16 (12.8%) patients were restarted more than twenty-one days from initial diagnosis; 3 (2.4%) were restarted between fourteen and twenty-one days post diagnosis. Subgroup analysis of the thrombosis arm revealed that 2 (10.5%) were restarted on rivaroxaban while 17 (89.5%) were restarted on VKA. Forty-one (32.8%) patients were alive within the studied time period and the outcome of 28 (22.4%) patients could not be ascertained from our database.

Conclusion: Given the rising national trend on the use of anticoagulants for various medical necessities, it is imperative that a safe and efficient process be devised on reinstitution of anticoagulation post ICH. Although our study represents a single institutional analysis, it concurs with recent studies that early resumption of anticoagulant following stable ICH is associated with lower thromboembolic events and similar risk of ICH recurrence. Our study further reveals that the risk of recurrent ICH and/or thromboembolism may be less in patients on DOACs. Nonetheless, randomized clinical trials are needed to evaluate the true risk-benefit profile of anticoagulation resumption after ICH.

Disclosures

No relevant conflicts of interest to declare.

Author notes

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Asterisk with author names denotes non-ASH members.