Overview

• Liver is the sole/primary site of synthesis of coagulation, anticoagulant, and fibrinolytic proteins with few exceptions (e.g. Factors V, VIII, vWF, tPA).
• Despite abnormal clotting time test results, few patients exhibit spontaneous bleeding.
• Causes of hemostatic imbalance: (1) reduced synthesis or activation of procoagulant proteins; vitamin K deficiency, (2) dysfibrinogenemia due to abnormal fibrin polymerization, (3) reduced clearance of FDP, (4) thrombocytopenia or thrombocytopathy, (5) enhanced fibrinolysis.
• Vitamin K deficiency-linked to severe intra- or extrahepatic cholestasis or steatorrhea or prolonged oral antibiotic administration.

Signalment

Dog and cat of any age, breed, or sex

Signs

• Often minor or no bleeding.
• Melena; hematemesis; hematochezia; hematuria.
• Prolonged bleeding if provoked: venipuncture, cystocentesis, biopsy, surgical wounds.
• Spontaneous bruising/hematomas-rare unless severe vitamin K deficiency or fulminant DIC.

Causes & Risk Factors

• Severe hepatic failure of any etiology
• Acute viral liver disease
• EHBDO
• Chronic liver disease-especially cirrhosis
• Concurrent small bowel disease (e.g., cats with cholangiohepatitis or hepatic lipidosis) predisposing to vitamin K deficiency
• High CVP and portal hypertension
• PSVA: asymptomatic factor deficiency and prolonged APTT common; overt bleeding uncommon.

Differential Diagnosis

• Toxicities-anticoagulant rodenticides, NSAIDs (GI lesions), causes of acute liver failure (e.g., ingestion of aflatoxin or cycad)
• Hereditary hemostatic defects
• Thrombocytopenia
• DIC-any cause GI infiltrative disorders
• Hepatic amyloidosis (factor deficiency, spontaneous liver lobe fractures)
• Abdominal trauma

CBC/Biochemistry/Urinalysis

• CBC-normal or regenerative anemia: severe bleeding (2–5 days); microcytosis: portosystemic shunting; thrombocytopenia
• Biochemistry-high liver enzymes; bilirubinemia; low albumin; hypoglobulinemia; low cholesterol
• Urinalysis-hematuria; bilirubinuria

Other Laboratory Tests

Hemostatic tests-thrombocytopenia; prolonged APTT (ACT), PT, TCT, and PIVKA; low fibrinogen and coagulation factors; low anticoagulant factors (AT, protein C); high FDP and D-dimer.

Imaging

Biopsy

• High risk for bleeding-PIVKA, PT, APTT, or ACT prolonged by >50%; thrombocytopenia <50,000/µL; prolonged mucosal bleeding time.
• Iatrogenic hemorrhage-grave prognosis if spontaneous bleeding with undetermined cause.
• Hemostasis support-post-procedure bleeding.
• Ultrasound-guided needle core-highest risk; observe biopsy site within 15 minutes, then sequentially over several hours post-procedure.
• Laparoscopy-affords visibility and allows hemostasis (cautery, Gelfoam pack biopsy site).
• Laparotomy-wedge biopsy; ill-advised in patients with overt bleeding.

Drug(s)

• Based on cause of hepatic abnormality.
• Vitamin K deficiency-parenteral vitamin K₁ (0.5–1.5 mg/kg q12h SC up to 3 doses in 24-hour interval one time); vitamin K₁ PO (Mephyton, 1 mg/kg q24h) if normal enteric bile acid uptake.
• DIC-correct primary disease; consider heparin for overt thrombosis (unfractionated heparin [UFH]: 200 U/kg q6–12h; or low molecular weight heparin [enoxaparin]: 1mg/kg q12–24h), dose titration based on clinical status and laboratory monitoring (ACT, aPTT [UFH], heparin anti-Xa activity [all heparins]).
• Blood products-fresh whole blood: 12–20 mL/kg q24h; fresh frozen plasma: 10–20 mL/kg q12h; plasma cryosupernatant (albumin, vitamin K–dependent factors): 10–20 mL/kg q12h; cryoprecipitate (fibrinogen, vWF, factor VIII): 1 U/10 kg or dose to effect.
• DDAVP-0.5–1 µg/kg IV in saline; may increase coagulation factors, shortens bleeding times, reduces bleeding tendencies; empirically used for biopsy-induced bleeding.
• Antifibrinolytics-EACA: 100 mg/kg loading, 30 mg/kg/h; tranexamic acid: 25 mg/kg q8h; if hyperfibrinolysis.

Contraindications

• Stored whole blood-may provoke HE.
• Vitamin K₁ (cats)-too much causes Heinz body hemolysis and oxidant liver injury.
• Aspirin or other NSAIDs-may predispose to renal failure, worsen ascites, provoke emesis and spontaneous bleeding,
• High-volume transfusion in citrate-based anticoagulants (especially in animals <5 kg) may induce symptomatic hypocalcemia.
• Avoid provocative procedures-e.g., jugular venipuncture or catheter placement, cystocentesis if recognized bleeding tendencies.

Patient Monitoring

• Optimized PT test, PIVKA, factor VII-most sensitive to vitamin K deficiency; if no improvement after 48 hours of vitamin K₁ injection, unlikely benefit from further dosing.
• Heart rate, blood pressure, mucous membrane color and refill, PCV, and total solids to monitor response if active bleeding.
• Biopsy site-observe immediately and sequentially (ultrasonography) for hemorrhage.
• Sample abdominal effusion to determine if hemorrhage or ascites.

Prevention/Avoidance

• Well-balanced diet replete with vitamins.
• Consider impaired vitamin K availability or synthesis from chronic oral antimicrobials.
• Invasive procedures-anticipate bleeding; pretreat with vitamin K₁; give DDAVP within 20 minutes of anticipated biopsy or if bleeding tendencies persist despite vitamin K₁ therapy (repeated DDAVP of no use); fresh frozen plasma for factor/fibrinogen replacement and active bleeding; avoid volume overload and increased CVP.
• Eliminate enteric parasitism.

Possible Complications

Hemorrhage, anemia, hypovolemia, HE

Expected Course and Prognosis

Spontaneous hemorrhage, refractory coagulopathy, and DIC-poor prognosis.

Abbreviations

• ACT = activated clotting time
• APTT = activated partial thromboplastin time
• AT = antithrombin
• CVP = central venous pressure
• DDAVP = desmopressin acetate
• EACA = epsilon aminocaproic acid
• EHBDO = extrahepatic bile duct obstruction
• FDP = fibrin/fibrinogen degradation product
• HE = hepatic encephalopathy
• NSAID = nonsteroidal anti-inflammatory drug
• PIVKA = proteins induced by vitamin K absence
• PSVA = portosystemic vascular anomaly
• PT = prothrombin time
• TCT = thrombin clotting time
• tPA = tissue plasminogen activator
• vWD = von Willebrand's disease
• vWF = von Willebrand factor

Author Marjory Brooks

Consulting Editor Sharon A. Center