C. Guillermo Couto, DVM, ACVIM
DIC, previously called consumptive coagulopathy or defibrination syndrome, is a complex syndrome in which excessive intravascular coagulation leads to multiple-organ microthrombosis (multiple organ failure-MOF) and paradoxical bleeding caused by the inactivation or excessive consumption of platelets and clotting factors secondary to enhanced fibrinolysis. DIC is not a specific disorder but rather a common pathway in a variety of disorders. Moreover, DIC constitutes a dynamic phenomenon in which the patient's status and results of coagulation tests change markedly, rapidly, and repeatedly during treatment. This syndrome is relatively common in dogs and cats.
Several general mechanisms can lead to activation of intravascular coagulation, and therefore to the development of DIC. These include:
Release of tissue "procoagulants"
Endothelial damage commonly results from electrocution or heat stroke, although it may also play a role in sepsis-associated DIC. Platelets can be activated by a variety of stimuli, but mainly they are activated by viral infections (e.g., FIP in cats). Tissue procoagulants are released in several common clinical conditions, including trauma, hemolysis, pancreatitis, bacterial infections, acute hepatitis, and possibly some neoplasms (e.g., HSA).
The best way to understand the pathophysiology of DIC is to think of the entire vascular system as a single, giant blood vessel and the pathogenesis of the disorder as an exaggeration of the normal hemostatic mechanisms. Once the coagulation cascade has been activated in this "giant vessel" (i.e., it is widespread within the microvasculature in the body), several events take place. Although they are described sequentially, most of them actually occur simultaneously and the intensity of each varies with time, thus making for an extremely dynamic process.
First, the primary and secondary hemostatic plugs are formed; if this process is left unchecked, eventually ischemia (resulting in MOF) develops. During this excessive intravascular coagulation, platelets are consumed in large quantities, leading to thrombocytopenia. Second, the fibrinolytic system is activated systemically, resulting in clot lysis and the inactivation (or lysis) of clotting factors and impaired platelet function. Third, AT III and possibly proteins C and S are consumed in an attempt to halt intravascular coagulation, thus leading to "exhaustion" of the normal anticoagulants. Fourth, the formation of fibrin within the microcirculation leads to the development of hemolytic anemia as the RBCs are sheared by these fibrin strands (i.e., fragmented RBCs or schistocytes).
A variety of disorders are commonly associated with DIC in dogs and cats. Neoplasia (primarily hemangiosarcoma-HSA), liver disease, and immune-mediated blood diseases are the most common disorders associated with DIC in dogs; liver disease (primarily hepatic lipidosis), neoplasia (mainly lymphoma), and feline infectious peritonitis are the disorders most frequently associated with DIC in cats.
There are several clinical presentations in dogs with DIC; the two common forms are chronic, silent (subclinical) and acute (fulminant) DIC. The former appears to be common in dogs with malignancy or possibly other chronic disorders. The latter may represent a true acute phenomenon (e.g., after heatstroke, electrocution, or acute pancreatitis), or more commonly, it represents acute decompensation of a chronic, silent process (e.g., HSA). Acute DIC is extremely rare in cats. Regardless of the pathogenesis, dogs with acute DIC often are brought in because of profuse spontaneous bleeding, plus constitutional signs secondary to anemia or to parenchymal organ thrombosis (i.e., end-organ failure). The clinical signs of bleeding indicate both primary (i.e., petechiae, ecchymoses, mucosal bleeding) and secondary (i.e., blood in body cavities) bleeding. There is also clinical and clinicopathologic evidence of organ dysfunction (see following paragraphs). Most cats with DIC seen at our clinic do not have evidence of spontaneous bleeding; clinical signs in these cats are those associated with the primary disease.
Several hematologic findings help support a presumptive clinical diagnosis of DIC and include a regenerative hemolytic anemia (although occasionally, because the animal has a chronic disorder such as cancer, the anemia is nonregenerative), hemoglobinemia (caused by intravascular hemolysis), RBC fragments or schistocytes, thrombocytopenia, neutrophilia with a left-shift, and rarely neutropenia. Most of these features are evidenced after evaluating a spun hematocrit and a blood smear.
Hemostatic abnormalities in dogs with DIC include thrombocytopenia, a prolongation of the OSPT or APTT (more than 25% of the concurrent control), normal or low fibrinogen concentration, a positive FDP test, and a decreased AT III concentration. If evaluated, fibrinolysis can also be documented to be enhanced in these animals (e.g., decreased plasminogen activity, enhanced clot lysis test). At our clinic, DIC is diagnosed if the patient has four or more of the hemostatic abnormalities just described, particularly if schistocytes are present.
Once a diagnosis of DIC has been established (or even if there is a high degree of suspicion that DIC is present), treatment should be instituted without delay. Unfortunately, there are no controlled clinical trials in veterinary medicine evaluating the effects of different treatments in dogs with DIC. Therefore the following discussion reflects my own beliefs in the management of dogs with DIC (Table 89-12).
It is unquestionable that removing or eliminating the precipitating cause constitutes the main therapeutic goal in patients with DIC. However, this is rarely possible. Those conditions in which the precipitating causes can be eliminated include a primary HSA (surgical excision), disseminated or metastatic HSA (chemotherapy), sepsis in dogs (appropriate antimicrobial treatment) and immune hemolytic anemia in dogs (immunosuppressive treatment). In most other situations (e.g., electrocution, heatstroke, pancreatitis), the cause can rarely be eliminated within a short time. Therefore the treatment of dogs with DIC is aimed at:
Halting intravascular coagulation
Maintaining good parenchymal organ perfusion
Preventing secondary complications
It should be remembered that, if blood and blood products were to be available in an unlimited supply (such as is the case in most human hospitals), dogs with DIC would not die of hypovolemic shock. Most dogs with DIC die of pulmonary or renal dysfunction. At our clinic, "DIC lungs" (i.e., intrapulmonary hemorrhages with alveolar septal microthrombi) appear to be a common cause of death in these patients.
Halting intravascular coagulation. At our clinic a dual approach is used to halt intravascular coagulation: the administration of heparin, and the administration of blood or blood products. As mentioned previously, heparin is a cofactor for AT III and therefore is not effective in preventing the activation of coagulation unless there is sufficient AT III activity in the plasma. Because AT III activity in animals with DIC is usually low (as a result of consumption and possibly inactivation), the patient should be provided with sufficient quantities of this anticoagulant. The most cost-efficient way of achieving this is to administer whole fresh blood or fresh-frozen plasma (or cryoprecipitate).
Heparin has been used historically to treat DIC in humans and dogs. However, there is still controversy as to whether it is beneficial. At our clinic the survival rate in dogs with DIC has increased markedly since we routinely started using heparin and blood products. Although this can also be attributed to improvement in patient care, I believe that heparin is beneficial in such patients and indeed may be responsible for their increased survival rate.
Sodium heparin is given in a wide range of doses. Traditionally there are four dose ranges:
Mini dose: 5 to 10 IU/kg SQ q8h
Low dose: 50 to 100 IU/kg SQ q8h
Intermediate dose: 300 to 500 IU/kg SQ or IV q8h
High dose: 750 to 1000 IU/kg SQ or IV q8h
Maintaining good parenchymal organ perfusion. Good parenchymal organ perfusion is best achieved with aggressive fluid therapy consisting of crystalloids or plasma expanders such as dextran. The purpose of this therapy is to dilute out the clotting and fibrinolytic factors in the circulation, to flush out microthrombi from the microcirculation, and to maintain the precapillary arterioles patent, so that blood is shunted to areas in which oxygen exchange is efficient.
Preventing secondary complications. As discussed in previous paragraphs, numerous complications occur in dogs with DIC. Attention should be directed toward maintaining oxygenation (i.e., by oxygen mask, cage, or nasopharyngeal catheter), correcting acidosis, eliminating cardiac arrhythmias, and preventing secondary bacterial infections (i.e., the ischemic gastrointestinal mucosa no longer functions as an effective barrier to microorganisms, bacteria are absorbed and cannot be cleared by the hepatic MPS, and sepsis occurs).