Hepatobiliary or Gastrointestinal Disease Causing Hemostatic Disorder

Because severe hepatic dysfunction is required to impair production of blood coagulation factors, acute massive hepatocellular necrosis and cirrhosis are more likely than other hepatopathies to cause clinically significant hemostatic disorders. Toxin ingestion appears to be the most common cause of massive hepatocellular necrosis and subsequent coagulopathy. Chapter 61 discusses hepatotoxins that cause hemostatic disorders.

Coagulation abnormalities in dogs and cats with hepatic disease are common. Sixty-six percent to 93% of dogs^6–8 and 82% of cats⁴ have at least one coagulation test abnormality, the most common being prolongation of the activated partial thromboplastin time (aPTT) in 75% of dogs and prothrombin time (PT) in 77% of cats evaluated. Histopathologic diagnoses reported in dogs with coagulation abnormalities include acute hepatitis with necrosis, chronic active hepatitis, cirrhosis, and diffuse hepatocellular carcinoma,⁸ whereas diagnoses reported in cats include hepatic lipidosis, cholangiohepatitis, and lymphoma.⁴ Approximately 45% of cats with severe hepatic lipidosis have abnormal coagulation profiles.⁹ Despite the high prevalence of coagulation test abnormalities in dogs and cats with hepatobiliary disease, few have clinically evident bleeding tendencies.^4,7–9

Vitamin K–dependent coagulopathies may develop in patients with EHBO, particularly if the obstruction is complete and of several days’ duration. The most common causes of EHBO in dogs include necrotizing cholecystitis secondary to cholelithiasis, pancreatitis, and neoplasia.^10–12 The most common causes of feline EHBO fall into two groups: neoplasia of either biliary or pancreatic origin, and inflammatory diseases including pancreatitis, cholangiohepatitis, cholecystitis, and cholelithiasis.¹³ The prevalence of coagulation test abnormalities in dogs and cats with extrahepatic biliary disease varies, potentially as a consequence of some patients having EHBOs that are partial or acute. In one retrospective study of cats with EHBO, eight of 18 (44%) cats had a prolonged PT whereas 10 of 18 (56%) had a prolonged aPTT; all cats with prolonged PT also had an aPTT prolongation.¹³ However, in a retrospective study of cats with obstructive cholelithiasis, a normal coagulation profile was noted in all eight cats tested.¹⁴ Similar differences have been noted in dogs with EHBO. Nine dogs undergoing choledochal tube stenting had normal PT and aPTT,¹¹ whereas prolongation of aPTT was associated with mortality among 57 dogs undergoing extrahepatic biliary surgery.¹⁰ In this latter study, the retrospective nature precluded determination of the cause of prolonged aPTT, but DIC and systemic inflammatory response syndrome (SIRS) secondary to septic bile peritonitis and vitamin K malabsorption may have contributed to the coagulopathy.¹⁰ Although coagulation profile results are variable amongst both dogs and cats with EHBO, bleeding is uncommonly observed in such patients with abnormal hemostatic profiles. However, there is a case report of excessive bleeding associated with vitamin K deficiency in a dog with an EHBO.¹⁵

Exocrine pancreatic insufficiency (EPI) may result in a vitamin K–dependent coagulopathy as a result of lipase deficiency preventing breakdown of dietary triglycerides into monoglycerides and fatty acids, a step in lipid digestion that is needed for adequate solubilization and absorption of fat soluble vitamins.¹⁶

Hemostatic Disorder Causing Gastrointestinal Bleeding

Primary hemostatic disorders are more likely than coagulopathies to cause gastrointestinal bleeding. Severe thrombocytopenia (platelet count <30,000/µL) is the most common primary hemostatic disorder causing mucosal surface bleeding. Differential diagnoses for severe thrombocytopenia include idiopathic thrombocytopenic purpura (ITP), secondary immune-mediated thrombocytopenia (associated with drugs, neoplasia, or infectious diseases), bone marrow suppression, or various infectious diseases (especially tick-borne diseases). ITP is the most common cause of severe thrombocytopenia in dogs but is rare in cats. vWD and thrombopathia are other primary hemostatic disorders that may cause gastrointestinal bleeding, either spontaneous or associated with underlying gastrointestinal disorders. Dogs and cats with hereditary thrombopathies may present with petechiae, ecchymoses, excessive bleeding following surgery or trauma, or bleeding from various mucosal surfaces including the gastrointestinal tract. Well-characterized canine hereditary thrombopathies include thrombasthenic thrombopathia (also referred to as Glanzmann thrombasthenia), an absence or deficiency of the platelet glycoprotein (GP) IIb/IIIa receptor for fibrinogen (documented in Otterhounds and Great Pyrenees¹⁷), Basset Hound thrombopathia (a platelet signal transduction defect resulting in abnormal cyclic adenosine monophosphate [cAMP] metabolism¹⁸), platelet δ-storage pool deficiency (caused by decreased dense granule ADP content, reported in the American Cocker Spaniel¹⁹), and platelet procoagulant deficiency (also referred to as Scott syndrome, which is a result of abnormal membrane PS exposure and described in the German Shepherd²⁰). A thrombopathia caused by a platelet δ-storage pool deficiency has also been documented in blue smoke Persian cats with Chediak-Higashi syndrome.²¹ Acquired platelet function defects may occur following ingestion of nonsteroidal antiinflammatory drugs (NSAIDs) or in association with uremia, cholestatic hepatic disease, and dysproteinemias. In gastrointestinal bleeding following NSAID administration, the cause is more likely gastrointestinal ulceration than an acquired thrombopathia, although concurrent platelet dysfunction could exacerbate bleeding.

Coagulopathies are more often associated with cavity bleeding than mucosal surface bleeding, but secondary hemostatic defects should be considered in patients with gastrointestinal bleeding. Mild to moderate thrombocytopenia has been documented in dogs with anticoagulant rodenticide poisoning, but marked thrombocytopenia (<30,000/µL) has also been reported.²² Melena, hematochezia, and other surface bleeding (e.g., epistaxis, hematuria, gingival bleeding) have been noted in dogs with anticoagulant rodenticide poisoning and normal platelet counts.²³ A hereditary vitamin K–dependent coagulopathy attributable to defective γ-glutamylcarboxylase has been reported in Devon Rex cats with spontaneous hemorrhage into the thoracic cavity, joint, and urinary bladder.^24,25 Hereditary FVII deficiency is typically considered an asymptomatic defect or a cause of minor bleeding, although severe bleeding has been reported, most often after surgery or trauma.²⁶ Hematochezia has been noted in FVII-deficient Beagles without other signs of colonic inflammation.²⁶ Of the intrinsic coagulopathies, hemophilia A (FVIII deficiency) or hemophilia B (FIX deficiency) may be more likely than others to cause bleeding within the gastrointestinal tract; severe gastrointestinal hemorrhage, potentially in association with coccidiosis, has been reported in hemophilic puppies.²⁷