The identification of effective pharmacotherapies for traumatic brain injury (TBI) remains a major challenge. Treatment with heparin and its derivatives is associated with neuroprotective effects after experimental TBI; however, the optimal dosage and method of administration, modes of action, and effects on hemorrhage remain unclear. Therefore, this review aimed to systematically evaluate, analyze, and summarize the available literature on the use of heparin and low molecular weight heparins (LMWHs) as treatment options for experimental TBI. We searched two online databases (PubMed and ISI Web of Science) to identify relevant studies. Data pertaining to TBI paradigm, animal subjects, drug administration, and all pathological and behavior outcomes were extracted. Eleven studies met our pre-specified inclusion criteria, and for outcomes with sufficient numbers, data from seven publications were analyzed in a weighted mean difference meta-analysis using a random-effects model. Study quality and risk of bias were also determined. Meta-analysis revealed that heparin and its derivatives decreased brain edema, leukocyte rolling, and vascular permeability, and improved neurological function. Further, treatment did not aggravate hemorrhage. These findings must be interpreted with caution, however, because they were determined from a limited number of studies with substantial heterogeneity. Also, overall study quality was low based on absences of data reporting, and potential publication bias was identified. Importantly, we found that there are insufficient data to evaluate the variables we had hoped to investigate. The beneficial effects of heparin and LMWHs, however, suggest that further pre-clinical studies are warranted.
Stillbirth is a devastating event to the parents, relatives, friends, and families. The role of anticoagulants in the prevention of unexplained stillbirths is uncertain. An open-label interventional prospective cohort study was conducted on 144 women with a history of unexplained stillbirths. The intervention group had a high umbilical artery resistance index (RI) and received bemiparin. The nonintervention group had a normal RI and did not receive any intervention. We measured the adjusted odds ratio (OR) and 95% confidence interval (CI) of the main outcome for these variables using logistic regression analysis. Fresh stillbirth and early neonatal death rates were lower (P = .005, OR = 11.949 and 95% CI = 2.099-68.014) and newborn weight was higher (P = .015, OR = 0.048, 95% CI = 0.004-0.549) in the group that received bemiparin. Bemiparin is effective in decreasing the rate of stillbirth in women with a history of previous unexplained stillbirths.