Guidance for the practical management of the heparin anticoagulants in the treatment of venous thromboembolism

Abstract

Venous thromboembolism (VTE) is a serious and often fatal medical condition with an increasing incidence. Despite the changing landscape of VTE treatment with the introduction of the new direct oral anticoagulants many uncertainties remain regarding the optimal use of traditional parenteral agents. This manuscript, initiated by the Anticoagulation Forum, provides clinical guidance based on existing guidelines and consensus expert opinion where guidelines are lacking. This specific chapter addresses the practical management of heparins including low molecular weight heparins and fondaparinux. For each anticoagulant a list of the most common practice related questions were created. Each question was addressed using a brief focused literature review followed by a multidisciplinary consensus guidance recommendation. Issues addressed included initial anticoagulant dosing recommendations, recommended baseline laboratory monitoring, managing dose adjustments, evidence to support a relationship between laboratory tests and meaningful clinical outcomes, special patient populations including extremes of weight and renal impairment, duration of necessary parenteral therapy during the transition to oral therapy, candidates for outpatient treatment where appropriate and management of over-anticoagulation and adverse effects including bleeding and heparin induced thrombocytopenia. This article concludes with a concise table of clinical management questions and guidance recommendations to provide a quick reference for the practical management of heparin, low molecular weight heparin and fondaparinux.

Synthetic oligosaccharides can replace animal-sourced low–molecular weight heparins

“…The overall risk of major bleeding associated with LMWH is 1 to 4% (39). The reversibility of 12-mer-1 anticoagulant activity using protamine should improve the safety of anticoagulant therapy.…”

Analysis of Partial Thromboplastin Times in Patients With Pulmonary Embolism During the First 48 Hours of Anticoagulation With Unfractionated Heparin

“…The dosing of UFH is weight‐based: the standard dose is an intravenous 80 unit/kg bolus followed by an infusion started at 18 units/kg/hour, titrated to a target activated partial thromboplastin time (aPTT) of 1.5 to 2.5 times the control range or an anti‐Xa level of 0.3 to 0.7 μ/mL . Although this “standard dose” has been developed, UFH has long been known to have unpredictable pharmacokinetics and thus far only one small study ( n = 45) has explored the efficacy of this standard dose in patients with acute PE, finding only 22% of aPTT values within the reference range …”

Clinical outcomes during anticoagulant therapy in fragile patients with venous thromboembolism

“…Thus, the increased risks of major bleeding during anticoagulation in fragile patients could be explained, at least in part, by these other drugs that might have potentiated the effect of the anticoagulant therapy. The similar risk for bleeding than for VTE recurrences in VTE patients weighing ≤50 kg has not been consistently reported 26, 27, 28. These findings suggest the potential benefit of tailored therapy for VTE according to clinical characteristics of the patients and warrant external validation.…”