In spontaneous ICH patients, the in-hospital incidence of TECs is reported to range from 3–22% and the risk of VTE is up to four times higher than in patients with acute ischemic stroke.2, 8, 27, 28 Though chemical thromboprophylaxis has been recommended in ICH patients to prevent these complications, TECs continue to occur, necessitating improved risk stratification strategies for prevention and guidelines for timing of treatment initiation.8 While ABO blood type has been implicated as a risk factor for coagulopathy and thromboembolism, we did not identify a relationship between ABO blood type, specifically non-O blood types, with TECs in our racially diverse cohort of ICH patients.11–13 Although ABO blood type did not appear to impact clinical outcomes, we did identify that TEC were independently associated with worse clinical outcomes among ICH patients.
In healthy population studies, non-O blood phenotypes (i.e., A, B, AB) have been identified as a risk factor for both venous and arterial thromboembolism.11, 13, 29. This has been posited to occur due to elevated concentrations of factor VIII and von Willebrand factor in individuals with non-O blood, interactions between the immune-dominant blood group antigens in the endothelial lining of blood vessels and von Willebrand factor, and genetic differences in serum levels of soluble intracellular adhesion molecule 1, tumor necrosis factor, and soluble E- and P-selectin.14, 15, 30–32 Conversely, O blood type has also been established as a risk factor for bleeding.12, 33 In a meta-analysis of 22 studies, comprising 466,752 patients, Dentali et al. reported a significantly higher prevalence of O blood phenotype in patients with bleeding complications compared to those without bleeding complications.33
While these relationships have been observed in non-brain injured patients, the impact of ABO blood type on coagulation/coagulopathy after ICH is less clear.12, 34 Inconsistent relationships of different blood types on hematoma expansion after ICH have been reported, 16 17 but there have not been any reports to date assessing the impact of ABO blood type on TECs. Though our study was limited by its small sample size and single center, retrospective design requiring replication in a larger dataset, it provides initial data to suggest that ABO blood type may not confer the same risk of TECs in active bleeding disease states compared to healthy populations. Paradoxically, we observed an increased number of TECs in type O blood type patients, although this finding did not reach statistical significance. Though speculative, it is possible that the known acute inflammatory state following ICH alters systemic coagulation cascade activation which may overcome any relevant baseline coagulation differences that may be present between different ABO blood groups during non-disease states.35, 36 Thus, further study is necessary to understand the complex thromboinflammation that occurs following ICH and its impact on downstream bleeding and thrombotic complications.
In regards to the impact of blood type on ICH outcomes, our findings are consistent with prior studies which did not observe relationships between ABO blood type and functional outcome after ICH.16, 36, 37 We did, however, find independent associations between TECs and poor 90-day functional outcome after ICH. This is congruent with previously reported associations between VTE and worse functional outcome at discharge, 3 months and one year.2 28 The management of TECs presents a challenge in acute ICH, due to the competing interests of simultaneously preventing intracranial hematoma expansion and systemic thromboembolism. In a retrospective study of 42 ICH patients with TECs, therapeutic anticoagulation was initiated at the discretion of the treating physician, on average 13 days after the ictus, and resulted in hemorrhage expansion in one patient.38 IVC filter use, which has not been well studied in ICH patients, was not associated with differences in overall mortality in a randomized clinical trial of critical care patients with significant bleeding risk.39 Taken together, the findings from the present study emphasize the importance of TEC screening and prevention in ICH patients. Future prospective studies should seek to clarify appropriate timing of chemoprophylaxis initiation, determine safety of therapeutic anticoagulation, and identify novel methods for risk stratification and treatment.
While the relatively uniform VTE prophylactic practice and multidisciplinary adjudication of complications were a strength of this study, there are several limitations worth highlighting. As aforementioned, our primary limitation was our relatively small, single-center cohort size. It is possible that our exploratory analysis was underpowered and would have identified significant associations of blood type with TECs if a larger cohort had been evaluated. Similarly, though our ICH cohort was a racially diverse patient population, it is unclear whether our findings would be generalizable to other ICH patient cohorts as race/ethnicity and geographic locations also have known associations with blood type and coagulation. Additionally, given our small sample size, we were unable to evaluate individual effects of the A, B or AB blood types on our outcomes of interest. Furthermore, because the ICHOP study was not designed to investigate relationships between ABO blood type and TECs after spontaneous ICH, the present analysis is subject to confirmation bias in that variables were chosen based upon data availability. In this regard, our TEC outcomes were only identified based on clinically obtained diagnostic testing. While this reflects clinical practice, it is unclear what the true prevalence of VTE would be in this patient population if systemically screened. Finally, our study did not have comprehensive available coagulation parameters of interest including von Willebrand factor and factor VIII to be able to establish the absence (or presence) of relevant coagulation differences between non-O and O blood ICH patients. Thus, further work assessing coagulation factors and their impacts on ICH outcomes will be necessary to better understand specific drivers behind hemostasis and thrombotic complications in this vulnerable patient population.