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Enoxaparin in dogs with primary IMHA | VETgirl Veterinary Continuing Education Podcasts

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In today’s VETgirl online veterinary continuing education podcast, we review the use of enoxaparin, a low molecular weight heparin (LMWH) in dogs with primary immune-mediated hemolytic anemia (IMHA). Do you see a lot of dogs with primary IMHA in your practice? Do you have an anticoagulation protocol that you like to use in treating them? Does it involve aspirin? Clopidogrel? Unfractionated heparin? What about LMWH?

Patients with IMHA are hypercoagulable even before we begin to treat them, and the addition of steroids as a major part of their therapy may increase their risk for blood clots (Goggs). Since the patients we lose during the course of treatment frequently have thromboembolic complications such as pulmonary thromboembolism or splenic or portal vein thrombi, anticoagulation is very important! However, we don’t have a lot of information about what anticoagulants are most effective, or which ones are the safest.

In human medicine, LMWH has been used as a safe and effective means of anticoagulation, and because LMWH is smaller and more homogenous than unfractionated heparin, it may be more predictable in terms of its hemodynamic effects. Enoxaparin, a LMWH, has been studied in healthy dogs, but no studies exist examining its use in dogs with IMHA (Lunsford).

So, Panek et al wanted to retrospectively evaluate the use of enoxaparin in dogs with IMHA for safety. They searched the records of two private specialty hospitals (in California) for cases of newly diagnosed IMHA, which was diagnosed based on the presence of a regenerative anemia (reticulocyte count > 60×109/L), evidence of hemolysis, and at least one of the following: autoagglutination, spherocytes or a positive direct Coombs test. All of the dogs in the study were treated with sole anticoagulation using enoxaparin, starting within the first 24 hours following admission and at a dose of 0.8 mg/kg SQ q6.

In this retrospective study, 21 dogs were included and presented for complaints including pale mucous membranes, lethargy, and decreased appetite. Less common complaints included collapse, vomiting, and discolored urine. Breeds were variable, but the most common breeds were Cocker Spaniels (n=4) and mixed breed dogs (4). 62% (13/21) of dogs were spayed females; the rest were neutered (7) or intact (1) males.
Vector-borne disease testing was performed via PCR, and thoracic radiographs and abdominal ultrasound were normal in all dogs. All of the patients in the study were treated as you would expect with prednisone, at a median dose of 2.2 mg/kg/day, or with the dexamethasone sodium phosphate equivalent. 81% (17/21) of dogs also received additional immunosuppressives including azathioprine (6), cyclosporine (5), mycophenolate (4) and leflunomide (2). Steroid administration was continued and tapered over the course of 6-15 months in the patients who survived to discharge.

Enoxaparin was given to all dogs at a median dose of 0.81 mg/kg. 95% (20/21) dogs received it q6 hours, while 1 dog was administered it q8 hours. Most patients had the dose continued at home and then tapered over a course of 6-21 days. No drug reactions to the enoxaparin were noted in any of the patients, and none had major bleeding complications. Two dogs did have one incident each of injection site bleeding when the medication was being administered at home, which was considered a minor complication.

Overall, 86% (18/21) of the dogs survived to hospital discharge. Of the three that did not, two had necropsies performed which revealed pulmonary venous thrombi. Three patients who survived initially suffered a relapse of IMHA within 6 months and were euthanized; one of those three had a necropsy performed which revealed a mesenteric venous thrombus.

So, what can we take away from this VETgirl podcast? This small retrospective study demonstrates that enoxaparin is safe to use in dogs with IMHA, based on client monitoring and follow-up. Since there are so many different therapies for IMHA and severity of cases may vary, it’s really difficult to compare efficacy of different treatments. While the survival rates in this study are similar to previous studies looking at other anticoagulant medications, we need more information and a big, prospective study before recommendations can be made. Since no monitoring of enoxaparin therapy was performed in this study (it would involve measuring anti-Xa activity, but we don’t know the ideal target in dogs), we don’t know how effective the LMWH was in preventing clots.

Although this study is small, it is a good first attempt at characterizing enoxaparin use in dogs with IMHA. Ideally, we need a bigger, prospective study with better monitoring (ideally in-hospital), anti-Xa activity, and comparison to other anticoagulant medications. Another limitation of this study was that the authors state as an objective in their abstract that they would like to determine the frequency of thrombosis, but this was not assessed overall in the study. That said, this small retrospective study suggests that enoxaparin at a dose of 0.8 mg/kg SQ q6 hours is a safe medication in dogs with IMHA.

References:
1. Goggs R, Wiinberg B, Kjelgaard-Hansen M et al. Serial assessment of the coagulation status of dogs with immune-mediated hemolytic anemia using thromboelastography. Vet J 2012;191(3):347-353.
2. Lunsford KV, Mackin AJ, Langston VC et al. Pharmacokinetics of subcutaneous low molecular weight heparin (enoxaparin) in dogs. J Am Anim Hosp Assoc 2009;45:261-267.
3. Panek CM, Nakamura RK, Bianco D. Use of enoxaparin in dogs with primary immune-mediated hemolytic anemia: 21 cases. J Vet Emerg Crit Care 2015;25(2):273-277

Abbreviations:
IMHA: primary immune-mediated hemolytic anemia
LMWH: low molecular weight heparin

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