Anticoagulant Therapy for Immune-mediated Hemolytic Anemia

Thrombosis, a common complication of canine immune-mediated hemolytic anemia (IMHA), is responsible for up to 80% of IMHA-related fatalities. Although pathogenesis of thrombotic complications is not fully understood, anticoagulant therapy is a mainstay in dogs with IMHA. The efficacy of anti-platelet agents, including ultra-low dose aspirin and clopidogrel, is unknown. Unfractionated heparin (UFH) requires individualized dosing and close monitoring. For these reasons, low-molecular-weight heparin (LMWH) is frequently used in human medicine. 

This retrospective case series evaluated enoxaparin, a LMWH, as the sole anticoagulant in 21 dogs with primary IMHA. All were treated with corticosteroids, and 17 with additional immunosuppressive agents. Median dose of enoxaparin was 0.81 mg/kg SC (q6h in 20 dogs, q8h in 1 dog). Enoxaparin doses were gradually decreased in frequency over 6-21 days in most dogs. No immediate or delayed adverse reactions associated with enoxaparin, including major hemorrhages, were noted. Two dogs had mild injection-site bleeding. Three dogs did not survive to discharge; necropsy on 2 revealed pulmonary venous thrombi. Of 3 dogs that relapsed and were euthanized in the 6-month follow-up period, necropsy of 1 showed a mesenteric venous thrombus. These survival statistics are comparable with other long-term anticoagulant protocols, but further studies are needed to assess the efficacy and optimal dosing of enoxaparin. Despite the ease of administration reported by owners, the frequency of administration required may make it more feasible for in-hospital use.

Global Commentary

Treatment for primary IMHA should always include antithrombotic therapy. Heparin (UFH or LMWH) and/or anti-platelet drugs (ultra-low dose aspirin alone or in combination with clopidogrel) have been used over the past several years with few results. As this paper shows, limited data are available on LMWH dosing protocols and clinical efficacy as sole anticoagulant therapy; thus, use of UFH (initial bolus of 80-100 U/kg followed by CRI of 18 U/kg/h) should still be preferred over LMWH. UFH anticoagulant response should also be monitored using PTT, and guidelines are available to adjust the dose (see Kirk’s Current Veterinary Therapy XV). The current recommendation is that heparin therapy be tapered over several days and adjunctive antiplatelet therapy instituted to minimize rebound thrombin generation.—Alice Tamborini, DVM, MRCVS, DECVIM-CA (Internal Medicine)

This capsule is part of the WSAVA Global Edition of Clinician's Brief.