Introduction

• A clinical syndrome arising secondary to a systemic disease resulting in a hypercoagulable state and exhaustion of the clotting cascade.
• Cause: viral (RHD), sepsis, heat stroke, neoplasia, immune-mediated disorders and severe injury.
• Signs: ongoing hemorrhage due to coagulopathy, hypovolemic shock.
• Diagnosis: hematology and biochemistry, diagnostic imaging, PCR.
• Treatment: removal or management of inciting cause, fluid therapy, plasma blood products, intensive supportive care.
• Prognosis: guarded to very poor. Some affected animals present deceased with no prior clinical signs.

Pathogenesis

Etiology

• Any condition with the potential to induce significant tissue inflammation may predispose to the development of DIC:
  • Bacterial sepsis, eg Bacillus anthracis, Pasteurella multocida Pasteurella multocida, Staphylococcus spp Staphylococcus spp. Exotoxins and enterotoxaemia associated with E. coli Escherichia coli has been identified as a cause.
  • Severe localized infection, eg dental abscessation Abscess.
  • Viral, eg calicivirus (Rabbit Hemorrhagic Disease strain 1 and 2) Viral hemorrhagic disease 1 Viral hemorrhagic disease 2.
  • Tissue ischemia, eg heat stroke Heat stroke, burns Electrical burn injury, trauma or significant gastrointestinal distention.
  • Immune-mediated hemolytic anemia.
  • Neoplasia, eg leukemia.

Predisposing factors

General

• Extensive tissue damage or trauma.

Specific

• Cellular apoptosis or necrosis and release of thromboplastin (phospholipid from cell membranes) into the blood.

Pathophysiology

• Exposure of collagen from damaged tissues and vasculature → stimulates thrombocyte aggregation (intrinsic pathway).
• Thromboplastin released by damaged cells into the bloodstream activates the clotting cascade → cleaves prothrombin into active thrombin → Fibrinogen is cleaved to form fibrin mesh → Part of clot with thrombocytes (extrinsic pathway).
• Intravascular clot formation is exacerbated, and thrombi form in many vessels and organs → impeded oxygen and nutrient supply, infarcts → Multiorgan failure.
• Depleted supply of coagulation factors and thrombocytes results in consumptive coagulopathy → bleeding disorders Thrombocytopenia.
• Excessive fibrin deposition activates fibrinolytic system → fibrinogen degradation products (FDPs) in blood → anticoagulant effect → fibrin dissolved and released into bloodstream.
• Ongoing tissue damage further stimulates the clotting cascade and fibrinolytic pathways leading to more extensive depletion of components → risk of bleeding increases.
• Bleeding is exacerbated by loss of anticoagulant factors, eg antithrombin III, via damaged renal tubules and decreased production by damaged liver tissue.
• Concurrent coagulopathy and thrombotic disease → kallikrein-kinin system → vasomotor abnormalities → Shock.

Timecourse

• Presents as an acute syndrome (1-5 days) in many cases even though the underlying cause may have been present for longer.
• DIC can be chronic and progress slowly over several days if the underlying cause is not addressed → it is not clear how common this may be in rabbits.
• In some cases, the disease may be self-limiting and resolve without progression to the overt hypocoagulable bleeding phase.

Epidemiology

• Outbreaks often occur in unvaccinated groups of rabbits where the underlying cause is RHD1/2 infection.

Diagnosis

Treatment

Prevention

Outcomes