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Background: Babesia infections in dogs can result in a wide range of clinical and laboratory presentations, including coagulopathy. Expression of intercellular adhesion molecule-1 (ICAM-1) and von Willebrand factor (vWF) in dogs with babesiosis is unknown.Objectives: Whether inflammation in babesiosis triggers activation of ICAM-1 and the coagulation system. Animals: Twelve and 10 dogs with naturally occurring babesiosis before and after antiparasitic treatment, respectively, were compared with 10 healthy dogs.Methods: In this prospective study, diagnosis was made by blood smear examination and confirmed by PCR. C-reactive protein (CRP), soluble intercellular adhesion molecule 1 (sICAM-1), and von Willebrand factor (vWF) levels were measured by a canine ELISA kit, fibrinogen (FIB) and factor VIII activity levels were measured by coagulometric methods, and blood cell counts (WBC, RBC, PLT) were determined with an automatic analyzer.Results: Compared to healthy dogs, the CRP, sICAM-1, and FIB concentrations were significantly increased before therapy and remained high for 3 days after therapy in dogs with babesiosis. vWF activity was significantly decreased in dogs with babesiosis before treatment. FVIII activity did not differ between dogs with babesiosis and healthy dogs. WBC; RBC and PLT were significantly lower before treatment and normalized by 3 days after treatment.Conclusion and Clinical Importance: A proinflammatory condition in babesiosis appears to influence endothelial dysfunction and hemostatic activity. Although clearly beneficial for the parasite, sequestered blood cells can obstruct blood flow in small vessels, promote an inflammatory state, and could increase the severity of babesiosis.

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A procoagulant snake venom serine protease was isolated from the venom of the nose-horned viper (Vipera ammodytes ammodytes). This 34 kDa glycoprotein, termed VaaSP-VX, possesses five kDa N-linked carbohydrates. Amino acid sequencing showed VaaSP-VX to be a chymotrypsin-like serine protease. Structurally, it is highly homologous to VaaSP-6 from the same venom and to nikobin from the venom of Vipera nikolskii, neither of which have known functions. VaaSP-VX does not affect platelets. The specific proteolysis of blood coagulation factors X and V by VaaSP-VX suggests that its blood-coagulation-inducing effect is due to its ability to activate these two blood coagulation factors, which following activation, combine to form the prothrombinase complex. VaaSP-VX may thus represent the first example of a serine protease with such a dual activity, which makes it a highly suitable candidate to replace diluted Russell’s viper venom in lupus anticoagulant testing, thus achieving greater reliability of the analysis. As a blood-coagulation-promoting substance that is resistant to serpin inhibition, VaaSP-VX is also interesting from the therapeutic point of view for treating patients suffering from hemophilia.

Components of the intrinsic blood coagulation pathway, among them factor VIIIa (FVIIIa), have been recognized as suitable therapeutic targets to treat venous thromboembolism, pathological process behind two very serious cardiovascular diseases, deep vein thrombosis and pulmonary embolism. Here, we describe a unique glycoprotein from the nose-horned viper (Vipera ammodytes ammodytes [Vaa]) venom, Vaa serine proteinase homolog 1 (VaaSPH-1), structurally a serine protease but without an enzymatic activity and expressing potent anticoagulant action in human blood. We demonstrated that one of its targets in the blood coagulation system is FVIIIa of the intrinsic tenase complex, where it antagonizes the binding of FIXa. Anticoagulants with such characteristics are intensively sought, as they would be much safer for medical application as the contemporary drugs, which frequently induce excessive bleeding and other complications. VaaSPH-1 is unlikely to be orally available for chronic usage as it has molecular mass of 35 kDa. However, it represents a very promising template to design low molecular mass FVIIIa-directed anticoagulant substances, based on structural features of the interaction surface between VaaSPH-1 and FVIIIa. To this end, we constructed a three-dimensional model of VaaSPH-1 bound to FVIIIa. The model exposes the 157–loop and the preceding α-helix as the most appropriate structural elements of VaaSPH-1 to be considered as a guideline to synthesize small FVIIIa-binding molecules, potential new generation of anticoagulants.