Approach to the Patient with Thrombocytopenia

Before assessing a patient with primary hemostatic bleeding, the clinician must remember than in some breeds platelet counts below the reference range for dogs are common. Platelet counts in Greyhounds typically range between 80,000 and 120,000/μL, whereas in Cavalier King Charles Spaniels with macrothrombocytopenia platelet counts <50,000/μL are common. In the latter the global platelet function is normal. Once thrombocytopenia has been confirmed by a platelet count or evaluation of a blood smear, its pathogenesis should be identified. The absolute platelet count may offer clues to its cause; for example, platelet counts of less than 25,000/μL are common in dogs with immune-mediated thrombocytopenia (IMT), whereas platelet counts of 50,000 to 75,000//μL are more common in dogs with ehrlichiosis, lymphoma affecting the spleen, or rodenticide toxicity.

The patient’s drug history should be obtained from the owner. If the animal is receiving any medication, the thrombocytopenia should be considered drug related until proven otherwise. The drug should be discontinued if possible and the platelet count reevaluated within 2 to 6 days. If the count returns to normal, a retrospective diagnosis of drug-associated thrombocytopenia is made. Drugs that have been associated with thrombocytopenia in cats and dogs can also cause anemia and neutropenia (see Boxes 83-2 and 85-1).

Because retroviral disorders commonly affect the bone marrow and may result in thrombocytopenia in cats, bone marrow aspiration is indicated in a thrombocytopenic cat with no history of previous medication. The risk of bleeding during or after bone marrow aspiration in a thrombocytopenic animal is minimal. Feline leukemia virus (FeLV) and feline immunodeficiency virus tests should also be performed. If determined by the laboratory, a mean platelet volume is high in most cats with FeLV infection (i.e., macrothrombocytosis); however, macrothrombocytes are also seen in cats and dogs with peripheral platelet destruction, consumption, or sequestration, in which they may be analogous to reticulocytes (young, immature, large platelets).

Bone marrow evaluation may also be indicated in dogs with thrombocytopenia. Given the high prevalence of IMT, at our clinic we usually elect to treat a dog with a presumed diagnosis of IMT. If the patient does not respond to immunosuppressive drugs within 2 to 3 days, a bone marrow aspiration may be performed.

Hyperplasia of megakaryocytes occurs in response to peripheral destruction, consumption, or sequestration of platelets. Occasionally dogs and cats with IMT have decreased numbers of megakaryocytes and abundant free megakaryocyte nuclei in the bone marrow. This is thought to be mediated by antibodies directed against platelets that also destroy the megakaryocytes. Infiltrative or dysplastic bone marrow disorders causing thrombocytopenia are easy to identify on a bone marrow smear.

Because IMT is a diagnosis of exclusion, tick-borne diseases (e.g., canine ehrlichiosis, Rocky Mountain spotted fever, cyclic thrombocytopenia, babesiosis, bartonellosis) should theoretically be ruled out by evaluating the appropriate serology or PCR and a blood smear. However, if the animal does not have clinical signs unrelated to the bleeding, the thrombocytopenia is not likely caused by sepsis or tick-borne diseases, although occasionally asymptomatic thrombocytopenic dogs have subclinical rickettsial diseases. If sepsis is suspected on the basis of clinical signs and clinicopathologic findings (e.g., fever, tachycardia, poor perfusion, degenerative left shift in the leukogram, hypoglycemia, hyperbilirubinemia), urine and blood should be obtained for bacterial cultures.

The presence of spherocytic hemolytic anemia or autoagglutination in a dog with thrombocytopenia is highly suggestive of Evans syndrome (combination of IMT and immune hemolytic anemia [IHA]). A direct Coombs test is usually positive in these cases. On rare occasions a direct Coombs test is positive in a dog with IMT and borderline anemia, further supporting a diagnosis of Evans syndrome.

A hemostasis screen should always be performed to rule out DIC in a thrombocytopenic animal found to have RBC fragments in a blood smear or evidence of secondary bleeding (e.g., hematomas, bleeding into body cavities). The remainder of the hemostasis screen is usually normal in dogs and cats with selective thrombocytopenia.

Several tests are available to evaluate antiplatelet antibodies, including direct immunofluorescence of bone marrow megakaryocytes and enzyme-linked immunosorbent assays for circulating or platelet-bound antibodies (see Chapter 92). However, most of these are not clinically reliable, and a diagnosis of IMT can be made only after other causes of thrombocytopenia have been excluded (i.e., regardless of the results of the antiplatelet antibody tests).

Abdominal radiographs and ultrasonograms may reveal an enlarged spleen not evident during physical examination. Diffuse splenomegaly (i.e., splenic sequestration of platelets) may be the cause of the thrombocytopenia, or it may reflect “work hypertrophy” (i.e., mononuclear phagocytic system hyperplasia) and extramedullary hematopoiesis in a dog with IMT. Splenic nodules are usually an incidental finding in dogs with thrombocytopenia, and they may represent extramedullary hematopoiesis or hyperplasia; fine-needle aspiration of the nodules should establish a cytologic diagnosis. Despite the low platelet counts, clinically relevant bleeding rarely occurs.

Often a specific diagnosis of IMT is obtained only after a therapeutic trial with corticosteroids (see later discussion) results in resolution of the thrombocytopenia. If the clinician is in doubt regarding whether the thrombocytopenia is caused by a rickettsial disease or IMT (in dogs), immunosuppressive doses of corticosteroids can be administered in conjunction with doxycycline (5 to 10mg/kg PO q12-24h) until serologic or PCR test results become available. This combination of agents has no deleterious effects on dogs with rickettsial diseases.

Blood or blood products should be transfused as needed (see Chapter 83). However, the transfusion of whole fresh blood, platelet-rich plasma, or platelets rarely, if ever, results in normalization of the platelet count or even in increases in the platelet count to “safe” levels.

Immune-Mediated Thrombocytopenia

IMT is the most common cause of spontaneous bleeding in dogs but is rare in cats. It affects primarily middle-aged, female dogs, and Cocker Spaniels and Old English Sheepdogs are overrepresented. The clinical signs are those of a primary hemostatic defect and include petechiae, ecchymoses, and mucosal bleeding. Acute collapse may occur if bleeding is pronounced; if the anemia is mild, most dogs are fairly asymptomatic. IMT is acute or peracute in onset in most dogs. During physical examination, signs of primary hemostatic bleeding (e.g., petechiae, ecchymoses, mucosal bleeding) with or without splenomegaly may be found.

The complete blood count in dogs with IMT is characterized by thrombocytopenia with or without anemia (depending on the degree of spontaneous bleeding and the presence or absence of concurrent IHA); leukocytosis with a left shift may also be present. As a general rule, hematologic changes are limited to the thrombocytopenia. If IHA is associated with IMT (i.e., Evans syndrome), a Coombs-positive, regenerative anemia with spherocytosis or autoagglutination is usually present. Bone marrow cytologic studies typically reveal megakaryocytic hyperplasia, although megakaryocytic hypoplasia with free megakaryocyte nuclei is occasionally present. In addition to the thrombocytopenia, the bleeding time is the only other abnormal test result (ACT, APTT, OSPT, FDP, and fibrinogen concentration are normal). An inverse linear correlation is usually present between the platelet count and the BMBT (i.e., a longer BMBT with lower platelet counts). Ideally, tick-borne diseases and drug-induced thrombocytopenia should be ruled out before establishing a definitive diagnosis of IMT.

If the index of suspicion for IMT is high (i.e., a fairly asymptomatic dog with spontaneous primary hemostatic bleeding and thrombocytopenia as the sole hematologic abnormality), a therapeutic trial with immunosuppressive doses of corticosteroids (equivalent to 2 to 8mg/kg/day of prednisone) should be instituted. Responses are usually seen within 24 to 96 hours. No clinical evidence exists that dexamethasone is more effective than prednisone in controlling IMT. Indeed, in my experience acute gastrointestinal tract ulceration is considerably more prevalent in dogs receiving dexamethasone than in those receiving prednisone. Because an acute upper gastrointestinal tract bleed is usually catastrophic in a dog with thrombocytopenia, prednisone is my drug of choice. H₂-antihistamines, such as famotidine (0.5mg/kg PO q24h), should be used in combination with the corticosteroids.

Fresh whole blood, stored blood, packed RBCs, or hemoglobin solutions should be administered as needed to maintain adequate oxygen-carrying capacity (see Transfusion Therapy in Chapter 83). In addition to immunosuppressive doses of corticosteroids, cyclophosphamide, given intravenously or orally in a single dose of 200 to 300mg/m², is effective for inducing remission. However, it should not be used as a maintenance agent because it usually causes sterile hemorrhagic cystitis when used on a long-term basis. Vincristine, at a dose of 0.5mg/m² given intravenously, traditionally has been recommended for dogs with IMT. This drug stimulates megakaryocyte endomitosis, resulting in early platelet release from the bone marrow. However, because vinca alkaloids bind to tubulin, the platelets released prematurely are not fully functional (tubulin is responsible for platelet aggregation), and the patients may have further bleeding before the platelet count increases. As discussed in Chapters 85 and 93, human intravenous immunoglobulin (0.5 to 1g/kg, single dose) can also be used successfully in dogs with refractory or life-threatening IMT.

Failure to induce remission (i.e., to normalize the platelet count) is usually the result of insufficient drug (low doses or the need for a second agent), insufficient duration of therapy (the drugs have not yet had time to become effective), or an incorrect diagnosis. In the event of one of these, the treatment protocol can easily be amended, with the thrombocytopenia usually resolving as a result. Azathioprine (50mg/m² PO q24-48h) is effective in maintaining remission but is not a good agent for inducing remission. In some dogs azathioprine is better tolerated than long-term corticosteroid therapy, although close hematologic monitoring is recommended given its myelosuppressive properties and potential for hepatotoxicity. The androgenic steroid danazol or cyclosporine A may also be beneficial in dogs with IMT. (See Chapter 93 for additional information and drug dosages.)

The prognosis is good in most dogs with IMT, although they may require lifelong treatment. Dogs with refractory IMT can be successfully treated with vinca-loaded platelets, pulse-dose cyclophosphamide, human immunoglobulin, or splenectomy.

IMT has become more prevalent in cats over the past few years. The typical clinical presentation is different from dogs in that most cats have chronic thrombocytopenia that does not lead to spontaneous bleeding. A platelet count of 10,000 to 30,000/μL is relatively common in an otherwise healthy cat without spontaneous bleeding. I have followed up several of these cats for months to years, and their platelet counts do not increase markedly with treatment. Interestingly, a high proportion of these cats also have regenerative or nonregenerative anemia, neutropenia, lymphocytosis, or combinations thereof. The cytopenias may resolve for no apparent reason, only to have a decrease in another cell line months later. Because most of these cats do not bleed, the clinician should be aware that increasing drug dosages or adding drugs may cause more problems than monitoring the platelet count. My treatment of choice for cats with IMT or immune-mediated cytopenias is a combination of dexamethasone (4mg q1-2wk) and chlorambucil (20-30mg/m² PO q2wk). I have also successfully used human intravenous immunoglobulin G in a limited number of cats with immune-mediated cytopenias.

von Willebrand Disease

vWD is the most common inherited bleeding disorder in human beings and dogs but is rare in cats. The term von Willebrand syndrome is reserved for an acquired vWF deficiency. vWD can be classified into three types (Table 87-4). Dogs with the disease typically have a decreased concentration or activity (type 1 vWD), absence of circulating vWF (type 3 vWD), or low to normal concentrations of an abnormal vWF (type 2 vWD), which result in mild (if any) spontaneous bleeding or, more likely, prolonged surgical bleeding. In dogs vWD can be inherited as an autosomal dominant trait with incomplete penetrance or, more rarely, an autosomal recessive trait (see later discussion). This disorder has been reported to occur in more than 50 breeds of dogs but is more common in Doberman Pinschers, German Shepherd dogs, Poodles, Golden Retrievers, and Shetland Sheepdogs. In these breeds the defect is inherited as an autosomal dominant trait with incomplete penetrance. In Scottish Terriers and Shetland Sheepdogs, it can be inherited as an autosomal recessive trait; homozygous dogs have no detectable vWF concentrations and are usually severely affected. Type 1 vWD may purportedly occur in association with clinical hypothyroidism in dogs; however, most scientifically controlled studies have failed to prove an association between vWD and hypothyroidism. Type 2 vWD was recently reported in dogs with aortic valvular disease; in those dogs, the high shear associated with turbulent flow across the valve resulted in selective depletion of high-molecular-weight VWF multimers (Tarnow et al., 2005).

TABLE 87-4 Classification of vWD in Dogs

vWD, von Willebrand disease; vWF, von Willebrand factor.

Modified from Brooks M: von Willebrand disease. In Feldman BF et al, editors: Schalm’s veterinary hematology, ed 5, Philadelphia, 2000, Lippincott Williams & Wilkins, p 509.

In human beings vWF is produced by megakaryocytes and endothelial cells, circulates in plasma complexed to factor VIII coagulant (factor VIII : C), and is one of the major adhesive proteins in the body. In the dog, platelets do not contribute as much vWF to plasma as in human beings. vWF is mainly responsible for causing platelets to adhere to the subendothelial structures (e.g., collagen) in areas of high shear once endothelial cell damage has occurred, thus initiating the formation of the primary hemostatic plug (Fig. 87-2). The vWF molecule circulates coiled; it uncoils at the site of endothelial damage, binds to the subendothelium and then to the platelet receptors, and the platelets are “reeled” in to the site of injury. As a consequence, vWD is usually characterized by primary hemostatic defects (e.g., petechiae, ecchymoses, mucosal bleeding). However, most dogs with vWD do not bleed spontaneously but rather bleed excessively during or after surgery; excessive bleeding during teething or estrus can also occur, but petechiae and ecchymoses are rarer. Most dogs with vWD and spontaneous bleeding seen at our clinic are brought in for evaluation of diffuse oropharyngeal or vaginal bleeding. People with vWD can also have low circulating concentrations of factor VIII leading to spontaneous secondary hemostatic bleeding (i.e., the clinical findings of hemophilia A); however, this is extremely rare in dogs. Perinatal death or abortions/stillbirths are common in litters with vWD.

FIG 87-2 The interaction between vWF, platelet, and subendothelial surfaces. GP, Glycoprotein; vWF, von Willebrand factor; FVIII : C, factor VIII coagulant.

The hemostasis screen results are normal in most dogs with vWD. The platelet counts in dogs with vWD are also normal. However, the results of a PFA-100 or BMBT usually inversely correlate with the degree of vWF deficiency (i.e., the PFA-100 closure time or the BMBT is prolonged if the vWF concentration or activity is low). Indeed, the BMBT may be the most cost-effective method for screening dogs for vWD, although its results are not foolproof. It can be done before surgery in breeds at risk or if the owner or breeder is interested in determining whether the dog is likely to have this disorder. However, a normal bleeding time does not necessarily rule out vWD. At our clinic we routinely use the PFA-100 before surgery in dogs at high risk for vWD so that appropriate therapy can be instituted before or during surgery. A diagnosis of vWD can be confirmed by quantifying vWF in specialized veterinary coagulation laboratories. Genetic testing for vWD in specific breeds is available through commercial diagnostic laboratories.

Most dogs with type 1 vWD can be successfully treated before surgery or during a bleeding episode with desmopressin acetate (DDAVP), which causes a massive release of vWF from the endothelial cells and results in shortening of the BMBT and the PFA-100 closure times within 30 minutes of administration. A single 1μg/kg dose of DDAVP (intranasal preparation) given subcutaneously consistently lessens bleeding in dogs with type 1 vWD despite modest increases in vWF concentration. DDAVP is not effective in dogs with types 2 or 3 vWD because these dogs either lack or have an abnormal (i.e., nonfunctional) vWF. Cryoprecipitate is the blood component of choice for dogs with vWD; a unit of cryoprecipitate is defined as the volume obtained from a unit of fresh frozen plasma. We dose it at 1U cryoprecipitate per 10kg of body weight; therefore, a Doberman Pinscher typically receives 3U. If cryoprecipitate is not available, fresh frozen plasma or whole fresh blood can be used. DDAVP can also be administered to the blood donor dog 1 hour before blood is collected to maximize the yield of vWF. The use of topical hemostatic agents such as fibrin, collagen, or methacrylate is also indicated to control the local bleeding. As is the case in dogs with other inheritable disorders, dogs with congenital vWD should not be bred.

Other Congenital Platelet Function Defects

Platelet function defects leading to spontaneous primary hemostatic bleeding have been reported in at least three breeds of dogs (Otterhounds, Foxhounds, and Basset Hounds). The clinical signs and clinicopathologic abnormalities are similar to those seen in dogs with vWD, but the vWF concentrations are normal or high. A syndrome of spontaneous and postoperative bleeding resembling Scott syndrome in human beings from a lack of platelet procoagulant activity was described in German Shepherd dogs (Brooks et al., 2002).

Pathogenesis

Several general mechanisms can lead to activation of intravascular coagulation and therefore to the development of DIC, including the following:

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) or sepsis. Tissue procoagulants (likely tissue factor) 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 pathophysiologic process 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 (see p. 1242). Because this is happening in thousands or tens of thousands of small vessels simultaneously, multiple thrombi form in the microcirculation. If this process is left unchecked, ischemia (resulting in MOF) eventually develops. During this excessive intravascular coagulation, platelets are consumed and destroyed 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 and possibly proteins C and S are consumed in an attempt to halt intravascular coagulation, leading to “exhaustion” of the natural anticoagulants. Fourth, the formation of fibrin within the microcirculation leads to the development of hemolytic anemia and further compounds the thrombocytopenia as the RBCs are sheared by these fibrin strands (i.e., fragmented RBCs or schistocytes).

When all these events are considered, it is easy to understand (1) why an animal with multiple organ thrombosis (caused by excessive intravascular coagulation and the depletion of natural anticoagulants) is bleeding spontaneously (as a result of thrombocytopenia, impaired platelet function, and inactivation of clotting factors) and (2) why one of the therapeutic approaches that appears to be beneficial in halting the bleeding in dogs and cats with DIC is to paradoxically administer heparin or other anticoagulants (i.e., if sufficient AT is available, heparin halts intravascular coagulation, which in turn decreases activation of the fibrinolytic system, thus releasing its inhibitory effect on the clotting factors and platelet function).

In addition to the events just described, impaired tissue perfusion results in the development of secondary “enhancers” of DIC, including hypoxia; acidosis; and hepatic, renal, and pulmonary dysfunction; and the release of myocardial depressant factor. The function of the mononuclearphagocytic system also is impaired so that FDPs and other byproducts, as well as bacteria absorbed from the intestine, cannot be cleared from the circulation. These factors also must be dealt with therapeutically (see p. 1256).

The prevalence of primary disorders associated with DIC in 50 dogs and 21 cats recently evaluated at The Ohio State University Veterinary Teaching Hospital (OSU-VTH) is depicted in Table 87-5. Neoplasia (primarily HSA), liver disease, and immune-mediated blood diseases were the most common disorders associated with DIC in dogs; liver disease (primarily hepatic lipidosis), neoplasia (mainly lymphoma), and FIP were the disorders most frequently associated with DIC in cats.

TABLE 87-5 Primary Disorders Associated with DIC in 50 Dogs and 21 Cats Evaluated at The OSU-VTH

Reprinted from Couto CG: Disseminated intravascular coagulation in dogs and cats, Vet Med 94:547, 1999. This table originally appeared in the June 1999 issue of Veterinary Medicine. It is reprinted here by permission of Thomson Veterinary Healthcare Communications, 8033 Flint, Lenexa, KS 66214; (913) 492-4300; fax: (913) 492-4157; www.vetmedpub.com. All rights reserved.

DIC, Disseminated intravascular coagulation; OSU-VTH, Ohio State University Veterinary Teaching Hospital; HSA, hemangiosarcoma; LSA, lymphoma; HA, hemangioma; PSS, portosystemic shunt; IHA, immune-mediated hemolytic anemia; IMT, immune-mediated thrombocytopenia; IMN, immune-mediated neutropenia; FIP, feline infectious peritonitis; GDV, gastric dilation-volvulus; HBC, hit by car.

* The results of hemostasis profiles in dogs with rodenticide toxicity mimic those seen in DIC.

At our clinic, symptomatic DIC in dogs (i.e., that associated with bleeding) is most commonly associated with HSA, followed by sepsis, pancreatitis, hemolytic anemia, gastric dilation-volvulus, and liver disease. Symptomatic DIC is extremely rare in cats but hemostatic evidence of DIC is common, accounting for approximately two thirds of the abnormal hemostatic profiles in this species in our clinic. As previously discussed, DIC is common in cats with liver disease, malignant neoplasms, or FIP. We have also observed symptomatic DIC in two cats receiving methimazole. The pathogenesis of DIC in dogs with HSA appears to be complex and multifactorial; the major mechanism triggering intravascular coagulation in dogs with this neoplasm was believed to be the abnormal irregular endothelium in the neoplasm (i.e., exposure to subendothelial collagen and the activation of coagulation). However, some canine HSAs appear to synthesize a cancer procoagulant because dogs with small HSAs can have severe DIC, whereas some dogs with widely disseminated HSA have normal hemostasis.

Clinical Features

Dogs with DIC can have several clinical presentations; the two common forms are chronic silent (subclinical) and acute (fulminant) DIC. In the chronic silent form, the patient does not have evidence of spontaneous bleeding, but clinicopathologic evaluation of the hemostatic system reveals abnormalities compatible with this syndrome (see the next page). This form of DIC appears to be common in dogs with malignancy and other chronic disorders. The acute form 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 and constitutional signs attributable to anemia or parenchymal organ thrombosis (i.e., MOF). The clinical signs of bleeding indicate both primary bleeding (e.g., petechiae, ecchymoses, mucosal bleeding) and secondary bleeding (blood in body cavities). Clinical and clinicopathologic evidence of organ dysfunction is also present. 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.

In a recent retrospective study of 50 dogs with DIC conducted in our clinic, only 26% had evidence of spontaneous bleeding, whereas only one of 21 cats with DIC had evidence of spontaneous bleeding. Most patients were presented for evaluation of their primary problem and were not bleeding spontaneously; DIC was diagnosed as part of the routine clinical evaluation.

Diagnosis

Because clinical DIC is uncommon in cats, the discussion on diagnosis and treatment focuses on dogs. 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 evident with evaluation of a spun hematocrit and a blood smear.

Serum biochemical abnormalities in dogs with DIC include hyperbilirubinemia from hemolysis or hepatic thrombosis, azotemia and hyperphosphatemia if severe renal microembolization has occurred, an increase in liver enzyme activities caused by hypoxia or hepatic microembolization, a decreased total carbon dioxide content caused by metabolic acidosis, and panhypoproteinemia if the bleeding is severe enough. Another manifestation of MOF is the development of multifocal ventricular premature contractions detected in an electrocardiogram.

Urinalysis usually reveals hemoglobinuria and bilirubinuria and occasionally proteinuria and cylindruria. Urine samples in dogs with acute DIC should not be obtained by cystocentesis because severe intravesical or intramural bleeding may result.

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 or d-dimer test, and a decreased AT concentration. Using a TEG, fibrinolysis can be enhanced in these animals. At our clinic, DIC is diagnosed if the patient has four or more of the hemostatic abnormalities just described, particularly if schistocytes are present.

The hemostatic abnormalities in 50 dogs and 21 cats with DIC evaluated in our clinic are listed in Table 87-6. In dogs thrombocytopenia, prolongation of the APTT, anemia, and schistocytosis were common; in contrast with previous descriptions of the syndrome in dogs, regenerative anemia, prolongation of the OSPT, and hypofibrinogenemia were not. In cats prolongation of the APTT and/or OSPT, schistocytosis, and thrombocytopenia were common, whereas the presence of FDPs and hypofibrinogenemia were rare.

TABLE 87-6 Hemostatic Abnormalities in 50 Dogs and 21 Cats with DIC Evaluated at The OSU-VTH

DIC, Disseminated intravascular coagulation; OSU-VTH, Ohio State University Veterinary Teaching Hospital; APTT, activated partial thromboplastin time; FDPs, fibrin degradation products; OSPT, one-stage prothrombin time.

From Couto CG: Disseminated intravascular coagulation in dogs and cats, Vet Med 94:547, 1999.

Treatment

Once a diagnosis of DIC has been established (or even if the degree of suspicion is high that DIC is present), treatment should be instituted without delay. Unfortunately, no controlled clinical trials have been performed in veterinary medicine evaluating the effects of different treatments in dogs with DIC. Therefore the following discussion reflects my beliefs in the management of dogs with this disorder (Box 87-6).

Unquestionably, removing or eliminating the precipitating cause constitutes the main therapeutic goal in patients with DIC. However, this is not always possible. Conditions in which the precipitating causes can be eliminated include a primary HSA (surgical excision), disseminated or metastatic HSA (chemotherapy), sepsis (appropriate antimicrobial treatment), and IHA (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 the following:

Of note, if blood and blood products were 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.