Barletta JF, Abdul-Rahman D, Hall ST, Mangram AJ, Dzandu JK, Frontera JA, Zach V. The role of desmopressin on hematoma expansion in patients with mild traumatic brain injury prescribed pre-injury antiplatelet medications. Neurocritical Care. 2020 Jan 2. doi: 10.1007/s12028-019-00899-x
Reviewed by Alexis Steinberg, MD
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Methods: An increased risk for traumatic intracerebral hemorrhage (ICH) and expansion of nontraumatic ICH has been associated with antiplatelet use. Guidelines exist for antiplatelet reversal for all types of intracerebral hemorrhage; however, the optimal treatment for reversal of platelet dysfunction is unknown.
This retrospective cohort study evaluated the effect of DDVAP on hematoma expansion in patients with TBI on antiplatelet medications. All adult patients (age >18) who were admitted to a single, level I, trauma center and were prescribed antiplatelet medications pre-injury were eligible for inclusion. Excluded patients were those who length of hospital stay were less than 24 hours, if they received DDVAP by any other route besides intravenous, if DDVAP dose was < 0.3 mcg/kg or no evidence of TBI on computed tomography (CT).
Baseline characteristics of patients included demographics, initial Glasgow Coma Scale (GSC), both pre-injury antiplatelet and anticoagulant prescriptions, hematoma expansion, thrombotic events, and discharge disposition. The use of pre-injury medications was determined by medication history and verification with dispensing pharmacy, but no platelet function assays were used as confirmation of medication adherence. Hematoma expansion was determined by two separate specialty-certified neurointensivists. The presence of hematoma expansion was considered if the expansion was > 20% from baseline or a new hematoma was found on follow up CT. The secondary analysis of thrombosis associated with DDVAP use was defined by a thrombotic event occurring within 48 hours of DDVAP administration or not.
Patients were retrospectively stratified into either DDVAP administration or not. To assess confounders, a univariate analysis was performed using hematoma expansion as dependent variable and associated collected factors were identified. Then, a multivariate model was built by identifying factors from the univariate analysis with a P-value <0.1 and clinical factors expected to influence hematoma expansion. Variables with P-value <0.05 were felt to be independent risk factors for hematoma expansion. A pair-wise comparison was used for continuous variables, implementing a Student’s t test (for normally distributed data) or Mann-Whitney for nonparametric (skewed) data. Either Pearson’s Chi-square test or Fischer’s exact test analyzed dichotomous data. Multivariate analysis used logistic regression to assess the confounders.
A total of 202 patients were included in the study. Majority of patients had a mild TBI based on GCS of 13-15 (91%) and the mechanism of injury was from a fall (76%). 158/202 (78%) of patients received DDVAP, with a median administration time of 3.1 (1.9-4.9) hours. Baseline characteristics, head injury classification, baseline GCS, severity illness, and antiplatelet or anticoagulation use did not differ between the two groups.
A total of 35 (17%) patients had hematoma expansion. The incidence of hematoma expansion was lower in the patients who received DDVAP (DDVAP, 14% vs no DDVAP, 30%, p=0.015). Thrombotic events were similar between the two groups (DDVAP, 2.5% vs no DDVAP 4.5%, p=0.613). After adjustment for age, DDVAP, high dose aspirin, pre-injury oral anticoagulation, multicompartmental head injury and platelet transfusion, DDVAP was still observed to be protective (OR = 0.259; 95% CI 0.103-0.646; p=0.004). A subgroup analysis demonstrated benefit of DDVAP in patients prescribed low dose aspirin (£81mg). Incidence of death or dependence was higher in the group who received platelet transfusion versus standard care (OR 2.05, 95%CI 1.18-3.56).
The authors conclude that in a retrospective cohort study, DDVAP was associated with a reduction in hematoma expansion in patients with mild TBI who were prescribed pre-injury antiplatelet medications. These results support further investigation on the use of DDVAP for antiplatelet reversal for patients with TBI, justifying future randomized control trials.
The authors appropriately address major limitations of the study in their discussion. Overall, the study has a small sample size and low power, especially for those not receiving DDVAP, indicating the need for future studies. The main limitation is that the study is done in single-center and is retrospective, limiting the generalizability of the results and the potential for selection bias with DDVAP administration. Decisions about DDVAP administration was based on clinician implementation and not protocol. Antiplatelet use was determined by medication history and verification of dispensing pharmacy; however, adherence cannot be confirmed given that platelet function tests were not performed. Additionally, this study only addresses the use of DDVAP in mild TBI and the effect on moderate to severe TBI cannot be concluded given that 91% of patients had a GCS 13-15 on arrival. The methodology for screening thrombotic events is not discussed, so it is currently unclear how they determined these adverse events. Finally, hematoma expansion is a radiographic outcome and it remains unclear if DDAVP use affects patient outcome. Further research is needed to understand the benefits of DDAVP in TBI populations.