Elizabeth M. Aradine, DO

Cooray C, Mazya M, Mikulik R, Jurak L, Brozman M, Ringleb P, et al. Safety and Outcome of Intravenous Thrombolysis in Stroke Patients on Prophylactic Doses of Low Molecular Weight Heparins at Stroke Onset. Stroke. 2019;50:1149-1155.

In 2018, the American Heart Association updated its stroke guidelines and allowed patients on prophylactic low molecular weight heparin (LMWH) to be considered for thrombolytic therapy. This has led to an increased number of patients receiving thrombolysis; however, less is known about the safety of doing so. Prior observational studies demonstrated increased risk of symptomatic hemorrhage and death with administration of thrombolytic therapy and concomitant use of LMWH; however, this was in studies with a limited sample size. The article, “Safety and Outcome of Intravenous Thrombolysis in Stroke Patients on Prophylactic Doses of Low Molecular Weight Heparins at Stroke Onset,” published in Stroke sought to elucidate the safety of thrombolysis in a large sample size.

In this observational study, 109,291 patients with acute ischemic stroke not on anticoagulation or heparin were treated with intravenous thrombolysis. 1,411 (1.3%) were on prophylactic LMWH at stroke onset. The primary outcome of symptomatic intracranial hemorrhage (ICH) using the SICH SITS-MOST definition did not show a difference in rates of hemorrhage between the prophylactic LMWH and non LMWH groups. Using the SICH-NINDS definition, there was an increased rate of hemorrhage in the prophylactic LMWH group. However, after baseline variables were matched, the rates of hemorrhage were similar. Three-month mortality was higher in the prophylactic LMWH group both before and after matching of baseline variables. Seven-day mortality and three-month functional disability using the modified Rankin Scale score were higher in the LMWH group. When variables were matched, mortality and disability were equal in both groups.

This study sheds light on the safety profile of thrombolytic therapy in those on prophylactic doses of LMWH. However, there are limitations of this study that merit discussion. First, both the name and dose of LMWH used were not mentioned. While there are two approved prophylactic LMWHs available in the United States, there are at least four LMWHs available in Europe. The prophylactic dose of enoxaparin, for example, is lower in Europe than the United States. Secondly, body mass index (BMI) and renal function were not accounted for, but bleeding risk can increase based on these variables. Also, it would be important to know why each patient was on prophylactic LMWH. Clinical situations such as post-operative DVT prophylaxis, severe immobility, and acute illness requiring hospitalization are all factors that can independently influence risk of ICH, mortality, or functional outcome. Lastly, the number of doses of LMWH given prior to thrombolytic therapy was not included.

Since higher doses of prophylactic LMWH are used in the United States, it is plausible that the rate of ICH could be higher than reported in this European study. Thrombolytic candidates should be informed of a potentially increased risk of ICH and death with concomitant LMWH use at time of consent. While it is possibly safe, a similar study in the United States should be conducted but also include factors such as LMWH dose, indication, duration of treatment, renal function, and BMI.