Mortality in virulent canine babesiosis is associated with a consumptive coagulopathy

Abstract

The inflammatory response to infection can activate the coagulation system via complex interactions. If uncontrolled, this may lead to a consumptive coagulopathy, which has been identified as a major risk factor for poor outcome in both human and canine medicine. This study was undertaken to prospectively determine whether the presence of a consumptive coagulopathy in dogs with Babesia rossi infection is related to mortality. A prospective, cross-sectional, observational study was performed. Seventy-two client-owned dogs diagnosed with canine babesiosis were included. Diagnosis was confirmed by polymerase chain reaction and reverse line blot and dogs infected with Babesia vogeli or Ehrlichia canis were excluded. Blood samples were collected at admission. Coagulation factor-, antithrombin (AT)-, and protein C (PC) activity, prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen and Ddimer concentrations were measured. The mortality rate was 18% (13/72) and results between non-survivors and survivors were compared. The median activities of all the coagulation factors were significantly lower in the non-survivors compared to the survivors. The median PT and aPTT were significantly longer in the non-survivors compared to the survivors. The median AT activity was not significantly different; however, the median PC activity was significantly 2 decreased in the non-survivors. The median D-dimer concentration was significantly higher in the non-survivors compared to the survivors. This study showed that dogs that died from B.canis infection suffered from a more severe consumptive coagulopathy compared to survivors, characterized by procoagulant activation, inhibitor consumption, and increased fibrinolytic activity.

Disease severity and blood cytokine concentrations in dogs with natural Babesia rossi infection

“…The higher the concentrations of this group of cytokines, the poorer the outcome of the disease. Cytokines are by no means the only biologically active family of molecules involved in Babesia pathogenesis but that cytokines indeed play an active role in disease pathogenesis and are not just a consequence of other events is evidenced by what has been demonstrated in various cytokine gene knockout experiments in sepsis, murine malaria and murine Babesia . Host response is thus largely responsible for the disease caused by B rossi infection.…”

Blood markers of fibrinolysis and endothelial activation in canine babesiosis

“…Plasminogen interaction with the surface of various parasites or with their secreted molecules has been shown [25]. Decreased plasminogen might therefore be the result of its increased use by the parasite and/or consumption due to the hypercoagulability reported in babesiosis [7]. The latter is strengthened by the fact that lower concentrations of fibrinolysis inhibitors, PAI-1 and TAFI (only in complicated babesiosis), were found in dogs with babesiosis at admission, followed by their increase on the 6th day, so it can be proposed that inhibition of fibrinolysis may be impaired in dogs with babesiosis.…”

Prognostic Markers in Acute Babesia canis Infections

“…Presumably, several factors are involved in the origin of thrombocytopenia in canine babesiosis including increased platelet activation and consumption by a SIRS (hypercoagulable state), increased platelet sequestration and aggregation, and a decreased platelet production . Comparable in B. rossi infections, poor outcome was associated with a consumptive coagulopathy, although even severe thrombocytopenia was not accompanied by apparent bleeding diathesis and hemorrhage …”

“…19,45,46 Comparable in B. rossi infections, poor outcome was associated with a consumptive coagulopathy, although even severe thrombocytopenia was not accompanied by apparent bleeding diathesis and hemorrhage. 25,47,48 Increased phosphate concentrations often are associated with metabolic acidosis characterized by tissue hypoxia and high blood lactate concentrations, although the underlying mechanisms have not been completely explained. 49 Hemorrhage, hypovolemia, and shock as cause or consequence of tissue hypoperfusion could further explain changes in altered variables, also including azotemia and potential protein-losing nephropathy caused by hypoxic renal damage.…”

“…19,20 In canine B. rossi infections, poor prognosis and mortality are associated with hyperlactatemia, hypoglycemia, clinically compromised circulation, high parasite load, increased serum cortisol concentrations, and signs of consumptive coagulopathy. [21][22][23][24][25] Accordingly in B. canis infections, an excessive inflammatory response with increased concentrations of fibrinogen, Creactive protein (CRP) and secreted intracellular adhesion molecule-1 (sICAM-1) from erythrocytes, and thrombocytopenia have been associated with poor outcome. 19 Furthermore, an increase in lipid mediators has been shown to be associated with severe complications such as development of SIRS and multiple organ dysfunction.…”