Bleeding and Thrombotic Risk in Low Dose Heparin Infusion As Compared to Standard Dose Heparin Infusion
Authors: Lutfi Forat , Boshnoi Rohit , Patel Vikas , Alfasi Aisha , Setteducato Michael , Zhang Shuyao , Shah Chintan , Kurian Saji , Kamath Chethana , Kim Dae Jun , Murphy Martina C. 
Published: October 2019

Introduction: At our institution, therapeutic use of unfractionated heparin (UFH) is administered by standard (target anti-Xa activity level 0.30 to 0.70 IU/mL) and low intensity (target anti-Xa activity level 0.25 to 0.35 IU/mL) protocols. In patients deemed high-risk for hemorrhage, the low intensity protocol is often employed. However, to date, there has been little study of differences in adverse events, namely hemorrhage, and efficacy between intensity protocols. Furthermore, identifying the effect of patient specific factors (e.g. age, indication for UFH, anticoagulant and antiplatelet use, medical, and surgical history) on outcomes has the potential to assist in determining the most optimal protocol.

Methods: A total of 377 adult patients receiving therapeutic UFH from July 2011 to July 2017 at a single institution were retrospectively studied. Patients receiving UFH by acute coronary syndrome protocol and those receiving thrombolytics were excluded. IRB approval was obtained prior to collection of data.

Results: Of the 377 patients, 42.0% (158/377) and 58.0% (219/377) were on low and standard intensity protocols, respectively. The majority of patients 76.1% (287/377) received an initial bolus. Patients were predominately Caucasian 74.0% (279/377), with median age of 63 years-old, and near equal gender distribution. The main indications for therapeutic UFH were venous thromboembolism VTE 46.9% (177/377) and atrial fibrillation 18.6% (70/377.) The indication for UFH was comparable between both groups with the exception of a higher percentage of those on full intensity protocol being treated for VTE (53.4% vs 38.0%.) Many patients were on home antiplatelet 35.0% (132/377) and anticoagulant 33.2% (125/377) therapy. The percentage of patients on aspirin, antiplatelet, and injectable anticoagulants was similar in both groups. A higher percentage of patients on low intensity protocol were on oral anticoagulants (36.1% vs 24.2%.) The median HAS-BLED score was two in both groups. Low intensity protocol patients were more likely to have had a history of previous bleeding (24.1% vs 12.8%) and had higher incidence of bleeding (10.8% vs 7.8%) than patients receiving standard intensity protocol. Transfusion requirement was greater in the low intensity protocol (29.7% vs 16.4%.) Both groups had similar risk of developing new thrombi (3.2% vs 3.7%) during the study period. All-cause mortality at three-months was higher in the low intensity group (19.6% vs 15.1%.) However, only 3.1% (2/64) of deaths within three-months were due to hemorrhage while on UFH and both were on the standard intensity protocol.

Conclusion: Low intensity UFH infusion is used in patients in whom there is clinical concern for increased risk of bleeding. Bleeding rates with both low and standard intensity protocols was comparable (10.8% vs 7.8%), although patients on the low intensity protocol had notably higher transfusion rates (29.7% vs 16.4%.) Rates of new or worsening thrombi were comparable (3.2% vs 3.7%.) Initial analysis of our data suggests that there is not a clinically significant difference in studied outcomes between standard and low intensity protocols. Furthermore, in patients where this is high clinical risk of bleeding, a low intensity protocol can be utilized with similar therapeutic efficacy as a standard intensity protocol.

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Disclosures

No relevant conflicts of interest to declare.