Background: Low molecular weight heparin (LMWH) overdose is a rare entity that may result in serious bleeding. There is no consensus on optimal management.

Aims: We explore management strategies for LMWH overdose.

Methods: We report four cases of intentional dalteparin overdose involving two patients and review the literature on LMWH overdose in adults.

Results: The first patient was a 42-year-old man who self-injected 225,000 units of dalteparin with intent to self-harm. Eighteen hours later, he developed left arm anterior compartment syndrome attributed to traumatic venipuncture and required urgent fasciotomy. Peak LMWH anti-Xa level was 8.94 U/mL with activated partial thromboplastin time (aPTT) >150 seconds. He was treated with five doses of protamine sulfate 50mg intravenously. Serial LMWH anti-Xa levels demonstrated a transient biochemical response to protamine sulfate. Anti-Xa levels remained elevated despite normalization of aPTT (Figure 1). After recovery, he was discharged on a direct oral anticoagulant with Thrombosis and Psychiatry follow-up.  
The second patient was a 39-year-old woman who on three separate occasions spanning 10 months, self-injected between 225,000-360,000 units of dalteparin with intent to self-harm. Peak LMWH anti-Xa levels were 7.33-10.0 U/mL with initial aPPTs >150 seconds. On two occasions, she was treated with empiric protamine sulfate with no bleeding complications and subsequent normalization of coagulation parameters (Figure 2, third episode).
We identified 10 case reports describing 16 cases of LMWH overdose. One patient died and five had major bleeding. Protamine sulfate, tranexamic acid and/or recombinant factor VIIa were used to treat most overdoses.

Figure 1:
Clinical and biochemical timeline for patient 1.

Figure 2:
Clinical and biochemical timeline for patient 2, third episode.

Conclusions: Pharmacokinetics and bleeding complications in LMWH overdose can be unpredictable. Our experience supports the use of empiric protamine sulfate to both prevent and treat bleeding. Serial LMWH anti-Xa activity measurements can help guide therapy. Patients often have complex medical and psychiatric comorbidities complicating the decision to resume anticoagulation following LMWH overdose.

« Back to ISTH 2021 Congress

ISTH Congress Abstracts - https://abstracts.isth.org/abstract/management-of-intentional-low-molecular-weight-heparin-overdose-the-mcmaster-university-experience/