Low-molecular-weight heparins
Low-molecular-weight heparins can be used as substitutes for unfractionated heparin (heparin sodium). Important differences exist between low-molecular-weight heparins and heparin sodium. Unlike heparin sodium, low-molecular-weight heparins cannot bind to antithrombin.¹⁹ Low-molecular-weight heparins have better activity against active factor X while minimally affecting clotting times.²⁰ Low-molecular-weight heparins also bind less to macrophages, proteins, and platelets.¹⁹ As a result, low-molecular-weight heparins are associated with a decreased incidence of bleeding and more predictive anticoagulant activity because of better bioavailability.²⁰

Because of the low-molecular-weight heparins' minimal effect on clotting times, APTT cannot be used to monitor efficacy. Instead, antifactor Xa activity should be used to monitor antithrombotic efficacy. In people, the targeted therapeutic range of antifactor Xa activity is 0.35 to 0.7 U/ml.¹⁹ During preliminary studies in cats, therapeutic concentrations of antifactor Xa activity were achieved at a low-molecular-weight heparin dose of 100 U/kg.¹⁹

Many low-molecular-heparin preparations are available with different pharmacokinetics. In our clinic, we use dalteparin at a dosage of 100 U/kg given subcutaneously twice a day for DIC in dogs and cats. Studies documenting dalteparin's efficacy have not been published. One disadvantage of low-molecular-weight heparin is cost. A 9.5-ml vial containing 10,000 U/ml costs about $450.

Maintain organ perfusion

Patients with DIC are predisposed to microvascular thrombosis and resultant decreased organ perfusion and risk of multiple organ dysfunction. Aggressive fluid therapy, in the form of crystalloids or colloids, is recommended to flush microthrombi from the circulation, dilute activated clotting factors, and maintain organ perfusion to ensure delivery of essential nutrients to tissues.¹ Crystalloids, such as lactated Ringer's solution, are administered at one-and-one-half to two times maintenance volumes (i.e. 60 to 90 ml/kg/day). Colloids, such as hetastarch (hydroxyethyl starch), are administered at a dosage of 10 to 20 ml/kg/day.

Replace coagulation components

The replacement of coagulation components is generally reserved for patients that have acute DIC with active evidence of hemorrhage or for patients with decreased antithrombin activity. Ideally, antithrombin activity would be measured. However, if this is not possible, it should be assumed to be low in most patients with DIC. Coagulation components can be replaced by administering whole blood or fresh frozen plasma, depending on the patient.

Administering blood or blood products is controversial because of potential, but unproven, adverse effects of fibrinogen, which can lead to severe microvascular thrombosis and multiple organ dysfunction syndrome. It is unfortunate that there is no source of antithrombin replacement that does not contain other coagulation factors. We limit blood and blood product administration to patients that are actively bleeding, patients in which the bleeding can be catastrophic and lead to death, or patients with markedly decreased (< 70%) antithrombin activity.

PROGNOSIS

Treating DIC is complicated and must be individualized for each patient. Recognizing DIC early should provide a better chance of a positive outcome. So patients that present with a disease process capable of initiating DIC should be carefully monitored and receive appropriate therapy to decrease morbidity and mortality. The prognosis for patients with acute DIC is grave. However, if the primary disease can be eliminated and DIC is appropriately treated, most other patients recover.¹ Severe organ failure or thrombosis is often life-threatening.

Justin D. Thomason, DVM
Clay A. Calvert, DVM, DACVIM
Craig E. Greene, DVM, MS, DACVIM
Department of Small Animal Medicine and Surgery
College of Veterinary Medicine
University of Georgia
Athens, GA 30602

REFERENCES

1. Couto CG. Disseminated intravascular coagulation in dogs and cats. Vet Med 1999;94:547-554.