Haemostatic abnormalities in canine spirocercosis

Abstract

Spirocerca lupi (S. lupi) is a nematode that infects the dog’s oesophagus resulting in an inflammatory fibroblastic nodule that progresses to a sarcoma in approximately 25% of cases. Inflammation, coagulation and cancer are exquisitely intertwined and inflammatory changes are known to lead to coagulation abnormalities. The nature and degree of haemostatic alterations in canine spirocercosis are unknown. Evidence of inflammation in dogs with clinical spirocercosis is provided by pyrexia, leucocytosis, increased serum interleukin 8 and C-reactive protein as well as severe inflammatory infiltrates on histopathology of nodules. This study aimed to determine if haemostatic abnormalities exist in canine spirocercosis, and hypothesised that the severity of abnormalities could be used to differentiate non-neoplastic from neoplastic spirocercosis. Thirty-nine client-owned S. lupi-infected dogs and 15 healthy age- and sex-matched control dogs were included in this study. Blood samples were collected at the time of diagnosis. A complete blood count, prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen concentration, antithrombin (AT) activity, D-dimer concentration and thromboelastography (TEG) analysis were performed. Hypercoagulability was based on the maximum amplitude (MA) value derived from TEG. Inflammatory parameters were also determined and included C-reactive protein (CRP) and fibrinogen concentrations. The S lupi-infected dogs were divided into a non-neoplastic group (n=24) and a neoplastic group (n=15). Data were compared using the Kruskal-Wallis Test and Dunn’s multiple comparisons applied post-hoc. Correlation was determined using Spearman’s correlation. Hypercoagulabilty was found in the neoplastic and non-neoplastic spirocercosis cases. In addition, the neoplastic group was significantly more hypercoagulable than the non-neoplastic group, and the non-neoplastic group was significantly more hypercoagulable than the control group. The median fibrinogen concentration was significantly higher in the neoplastic group compared to the non-neoplastic group, but there was no significant difference between the non-neoplastic and control group. The median CRP concentration was significantly higher in the neoplastic group compared to the non-neoplastic group, with no significant difference between the non-neoplastic and control group. Compared to the control group the median AT activity was significantly decreased in both the non-neoplastic and neoplastic groups. No significant difference was found between the infected groups. Across the non-neoplastic and neoplastic groups, MA showed positive linear correlation with CRP and fibrinogen. The study showed that spirocercosis is associated with a hypercoagulable state that becomes progressively more severe with neoplastic transformation. Overlap did exist between the median MA values of the non-neoplastic and neoplastic groups, but an MA of >76 mm provided a specificity of 96% and sensitivity of 73% for the differentiation of disease state. Thromboelastography might therefore be used as an adjunctive assay to support the suspicion of neoplastic transformation of the oesophageal nodule as well as to determine the overall haemostatic status of the patient. The MA correlated positively with the indicators of inflammation (CRP&fibrinogen) supporting the hypothesis that an inflammatory state induced by the S. lupi nodule is at least partly responsible for the hypercoagulability. The link between inflammation, coagulation and neoplastic transformation in spirocercosis warrants further investigation to elucidate the exact factors resulting in the hypercoagulable state, whether clinically relevant complications develop and whether or not specific therapy should be instituted to prevent thrombotic sequelae.