Viper envenomation and cerebral venous thrombosis
S Senthilkumaran1, N Balamurugan2, P Thirumalaikolandusubramanian3,
1 Department of Emergency and Critical Care Medicine, Sri Gokulam Hospitals and Research Institute, Salem, Tamil Nadu, India
2 Department of Neurosciences, Manipal Hospital, Salem, Tamil Nadu, India
3 Department of Internal Medicine, Chennai Medical College Hospital and Research Center, Irungalur, Trichy, Tamil Nadu, India
Department of Emergency and Critical Care Medicine, Sri Gokulam Hospitals and Research Institute, Salem, Tamil Nadu
|How to cite this article:|
Senthilkumaran S, Balamurugan N, Thirumalaikolandusubramanian P. Viper envenomation and cerebral venous thrombosis.J Postgrad Med 2013;59:171-172
|How to cite this URL:|
Senthilkumaran S, Balamurugan N, Thirumalaikolandusubramanian P. Viper envenomation and cerebral venous thrombosis. J Postgrad Med [serial online] 2013 [cited 2020 Oct 27 ];59:171-172
Available from: https://www.jpgmonline.com/text.asp?2013/59/3/171/118030
Snakebite is one of the most neglected environmental and occupational diseases of the modern world. The scourge of snake bite continues to cause considerable morbidity and mortality particularly in rural areas of the tropics.  In India, more than half of the snakebites are due to the snakes of the Viperidae family. The venom from this family are a complex mixture of bioactive substances and interact with almost all components of the hemostatic system, including the vascular wall, platelets, clotting factors, clot inhibitors, and fibrinolytic components. The venom also has pro and anticoagulant factors. This piqued the interest among research workers in exploring the many facets of hemostasis with the proteome of viper venom towards understanding mechanisms and therapeutic applications.
The syndrome of intracranial venous and sinus thrombosis was recognized in the early part of 18 th century. The thrombotic occlusion of cerebral veins and sinus are distinct forms of cerebro vascular disorders. They are often not considered as diagnostic possibilities and not well addressed unlike arterial stroke. This despite 70% of cerebral blood flowing through the venous system.  Formation of thrombi in venous systems which drain blood from the brain is a consequence of trauma to vessel wall, stasis and changes in the blood composition that is best described by Virchow triad. This begs the question of the venom action in the thrombosis formation.
The article on "Russell's viper envenomation presenting with cortical venous thrombosis" is both invigorating and interesting.  Though different kinds of thrombotic complications have been reported so far, most involving the arterial system,  involvement of the cerebral venous system seems to be an exception. Interestingly, even in the current paper on diagnosis and management of cerebral venous sinus thrombosis, envenomation was not listed as a predisposing factor.  Recently, Patil et al. have reported a case of bilateral thalamic and right sided pontine infarct secondary to cortical venous sinus thrombosis following a vasculotoxic envenomation by Russell viper. 
The direct action of venom causes vascular endothelial injury, with release of vascular endothelial growth factor and von Willebrand's factor, which in turn produces toxic vasculitis. The metalloproteinases in the venom act synergistically to degrade the extracellular matrix of the blood vessel thus affecting the integrity of the vessel wall and promoting thrombus formation.  The complete or partial occlusion of cerebral venous system by the thrombus results in stasis and rapid decline in intravascular oxygen tension, which accelerates the process of thrombosis.  Procoagulants such as hydrolase and arginine esterase activate the procoagulant pathway, which eventuates in vascular fibrin deposition and causes aggregation of platelets. Various C-type lectin-like proteins (snaclecs) influences the platelet aggregation. Under typical physiological conditions, these venom proteins bind either the adhesive protein itself or their receptors on the platelet surface, notably GPIb-V-IX and αIIbβ3 integrins.  Since these integrins are believed to serve as the final common pathway leading to formation of platelet-platelet bridges and platelet aggregation, which leads to intraluminal thrombus formation. A large number of snake venoms contain prothrombin activators, which convert prothrombin into meizothrombin or thrombin.  Like thrombin, thrombin-like enzymes specifically catalyze limited cleavage of fibrinogen and lead to clotting of fibrinogen. Also, prothrombin gene mutation and platelet receptor polymorphism might have contributed to thrombotic stroke. Considering the above, it is likely that the mechanisms of cerebral venous thrombosis (CVT) following viper bite are multiple.
Besides prevalence and risk factors, the clinical manifestations of CVT also differ from that of arterial stroke in different age groups and among men and women. Unlike arterial thrombosis, strict localization to one vascular territory may be often absent. A high index of suspicion is absolutely essential to diagnose cerebral venous thrombosis. Diagnosis is essentially clinical and usually confirmed by neuroimaging. These patients have an excellent outcome as compared to other cerebrovascular accidents, if promptly diagnosed and the contributory factors are identified and corrected as described in this report. The case reported in this issue will create wareness of this entity among health care professionals, help them to think of CVT as a potential diagnosis provide appropriate treatment and emphasize on accurate reporting in the future. A more detailed analysis of snake venom proteases should find their usefulness for the medical and pharmacological applications in the field of thrombosis and hemostasis.
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