IMHA: Diagnosing and treating a complex disease - Veterinary Medicine
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IMHA: Diagnosing and treating a complex disease
Differentiating IMHA from other causes of hemolytic anemia is challenging, but a careful diagnostic process will help you determine whether your veterinary patients will require long-term immunosuppressive therapy.


Thromboembolism and anticoagulants

DIC and thromboembolism are common causes of morbidity and mortality in patients with IMHA.1 The pathogenesis is largely unknown, but potential contributors include endogenous conditions such as blood flow stasis and hypercoaguability as well as exogenous factors such as repeated venipuncture, intravenous catheters, and glucocorticoid administration. Whether anticoagulant therapy is used at the time of diagnosis or added when thromboembolism is suspected is largely institution-dependent. Anticoagulants such as low-molecular-weight heparin, unfractionated heparin, warfarin, low-dose aspirin, and fresh-frozen plasma have all been used to prevent or treat this condition, although few studies have shown prolonged survival with their use.15

In one study, the use of fresh-frozen plasma (10 ml/kg) with unfractionated heparin (100 U/kg subcutaneously every six hours) failed to prevent thromboembolic complications in IMHA patients.38 Unfractionated heparin alone is generally not associated with an increased risk of bleeding, but neither is it associated with an improved outcome. Two studies failed to document increased survival with the use of unfractionated heparin.13,14 Another study demonstrated that relatively high doses of unfractionated heparin (300 to 375 U/kg subcutaneously every six hours) were needed to obtain target concentrations for anticoagulation, and even those concentrations may be inadequate in preventing thrombosis.39 If used, unfractionated heparin should be adjusted to prolong the activated partial thromboplastin time to 25% to 50% over baseline or to inhibit factor Xa to a target range of 0.35 to 0.7 U/ml.

Low-molecular-weight heparin (150 to 200 U/kg subcutaneously every six to eight hours) is an alternative to unfractionated heparin and is starting to be used to treat thromboembolic disease in veterinary medicine. Low-molecular-weight heparins have better subcutaneous bioavailability, are better able to inhibit factor Xa, and likely can be given at a decreased frequency compared with unfractionated heparin. No clinical studies have been done to determine whether this drug is effective in preventing thromboembolism in patients with IMHA. Measuring anti-Xa activity is necessary to monitor the anticoagulant effects of this drug.

The use of ultra low-dose aspirin (0.5 mg/kg orally once daily) in addition to immunosuppressive medications has shown clear promise in canine patients. The beneficial effects of aspirin are thought to be from vasodilation and modulation of platelet aggregation. One large study in dogs treated with glucocorticoids and azathioprine compared the use of ultra low-dose aspirin, unfractionated heparin, and a combination of these two medications.14 The results demonstrated that the patients treated with aspirin had significantly longer survival times than patients treated with unfractionated heparin alone. In this study, the use of aspirin was not associated with any adverse clinical effects, even when used with high-dose glucocorticoids.

Supportive care

Aggressive, detail-oriented supportive care is a critical factor for the successful treatment of IMHA. Timely recognition and treatment of an underlying disease can allow immunosuppressive drug therapy to be tapered more quickly. Antibiotic administration while awaiting confirmation of suspected infectious disease can improve the chances of recovery. Thorough diagnostic testing can help detect underlying infectious or neoplastic causes of immune-mediated hemolysis, which if missed would make treatment unlikely to succeed. Finally, the quick detection of complications and the speedy removal of nonessential drugs that can cause an immune reaction can also help improve the chances of survival.

Good nursing care that includes daily intravenous catheter care, proper nutrition, short walks, low-stress handling, and limited phlebotomy can also contribute to a better outcome. Peripheral intravenous catheter placement may be preferable to jugular placement in patients with the potential to develop a coagulopathy. Ancillary treatments and medications such as intravenous fluids, gastric protectants, promotility drugs, and antinausea medications can all support a patient through the initial days of treatment. Intravenous fluids, especially in patients with intravascular hemolysis, may help prevent hemogloblin nephrosis. Removing unnecessary indwelling catheters may reduce the risks of thromboembolism.15


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