Hematoma Growth and Outcome in Treated Neurocritical Care Patients With Intracerebral Hemorrhage Related to Oral Anticoagulant Therapy

Abstract

Background and Purpose-Intracerebral hemorrhage (ICH) is the most serious and potentially fatal complication of oral anticoagulant therapy (OAT). Still, there are no universally accepted treatment regimens for patients with OAT-ICH, and randomized controlled trials do not exist. The aim of the present study was to compare the acute treatment strategies of OAT-associated ICH using vitamin K (VAK), fresh frozen plasma (FFP), and prothrombin complex concentrates (PCCs) with regard to hematoma growth and outcome. Methods-In this retrospective study, a total of 55 treated patients were analyzed. Three groups were compared by reviewing the clinical, laboratory, and neuroradiological parameters: (1) patients who received PCCs alone or in combination with FFP or VAK (nϭ31), (2) patients treated with FFP alone or in combination with VAK (nϭ18), and (3) patients who received VAK as a monotherapy (nϭ6). The end points of early hematoma growth and outcome after 12 months were analyzed including multivariate analysis. Results-Hematoma growth within 24 hours occurred in 27% of patients. Incidence and extent of hematoma growth were significantly lower in patients receiving PCCs (19%/44%) compared with FFP (33%/54%) and VAK (50%/59%). However, this effect was no longer seen between PCC-and FFP-treated patients if international normalized ratio (INR) was completely reversed within 2 hours after admission. The overall outcome was poor (modified Rankin scale 4 to 6 in 77%). Predictors for hematoma growth were an increased INR after 2 hours, whereas administration of PCCs was significantly protective in multivariate analyses. Predictors for a poor outcome were age, baseline hematoma volume, and occurrence of hematoma growth. Conclusions-Overall, PCC was associated with a reduced incidence and extent of hematoma growth compared with FFP and VAK. This effect seems to be related to a more rapid INR reversal. Randomized controlled trials are needed to identify the most effective acute treatment regimen for lasting INR reversal because increased levels of INR were predisposing for hematoma enlargement.

Clinical review: Prothrombin complex concentrates - evaluation of safety and thrombogenicity

“…Several studies comparing the efficacy of PCCs with human plasma for emergency oral anticoagulant reversal have shown that PCCs provide more effective and more rapid correction of coagulopathy [44-47]. These findings, together with the improved safety profile of today's PCCs, suggest that PCCs should be considered preferable to FFP for emergency oral anticoagulant reversal.…”

Reversal strategies for vitamin K antagonists in acute intracerebral hemorrhage

“…A recent German observational study on VKA‐OAC (n = 1,176), published after the submission of our study, suggested that rapid reversal of INR is associated with less ICH expansion and lower in‐hospital mortality, but was not powered to compare reversal therapies due to a uniform national practice of using PCC 24. Previous observational studies comparing treatments have been small (17–181 patients), with variable results with regard to case fatality,14, 25, 26 functional outcome,27, 28 and hematoma expansion 29. These studies also combined patients receiving FFP with either PCC26, 29 or no reversal,14, 23, 27 precluding direct comparison of specific reversal strategies.…”

“…Previous observational studies comparing treatments have been small (17–181 patients), with variable results with regard to case fatality,14, 25, 26 functional outcome,27, 28 and hematoma expansion 29. These studies also combined patients receiving FFP with either PCC26, 29 or no reversal,14, 23, 27 precluding direct comparison of specific reversal strategies.…”

Reversal of vitamin K antagonists prior to urgent surgery

“…3,41,42 While the correction of the INR is a surrogate outcome, there is some, albeit limited, data to suggest that PCC may reverse the anticoagulation more rapidly and, therefore, the bleeding associated with VKA toxicity. In a retrospective single centre study, the use of PCC alone or in combination with vitamin K was associated with a reduced incidence and extent of ICH hematoma growth compared with FP alone or in combination with vitamin K. 43 While this study included a small population (n = 55), an association between early (i.e., within two hours) normalization of INR and the prevention of hematoma growth in both the FP-and PCC-treated groups supports the use of INR as an outcome to compare the efficacy of these treatment options.…”