Peripheral Arterial Thrombosis following Russell's Viper Bites

Abstract

Envenomings by Russell's viper (Daboia russelii), a species of high medical importance in India and other Asian countries, commonly result in hemorrhage, coagulopathies, necrosis, and acute kidney injury. Although bleeding complications are frequently reported following viper envenomings, thrombotic events occur rarely (reported only in coronary and carotid arteries) with serious consequences. For the first time, we report three serious cases of peripheral arterial thrombosis following Russell's viper bites and their diagnostic, clinical management, and mechanistic insights. These patients developed occlusive thrombi in their peripheral arteries and symptoms despite antivenom treatment. In addition to clinical features, computed tomography angiography was used to diagnose arterial thrombosis and ascertain its precise locations. They were treated using thrombectomy or amputation in one case that presented with gangrenous digits. Mechanistic insights into the pathology through investigations revealed the procoagulant actions of Russell's viper venom in standard clotting tests as well as in rotational thromboelastometry analysis. Notably, Russell's viper venom inhibited agonist-induced platelet activation. The procoagulant effects of Russell's viper venom were inhibited by a matrix metalloprotease inhibitor, marimastat, although a phospholipase A2 inhibitor (varespladib) did not show any inhibitory effects. Russell's viper venom induced pulmonary thrombosis when injected intravenously in mice and thrombi in the microvasculature and affected skeletal muscle when administered locally. These data emphasize the significance of peripheral arterial thrombosis in snakebite victims and provide awareness, mechanisms, and robust strategies for clinicians to tackle this issue in patients.

A murine experimental model of the unique pulmonary thrombotic effect induced by the venom of the snakeBothrops lanceolatus

“…The lack of major alterations in rotational thromboelastometry parameters is in contrast with observations carried out with the venom of B. asper, which causes a consumption coagulopathy and drastically affects these parameters in a mouse model [45]. by other viperid snake species [46,47], thus opening the possibility of using this experimental model to explore the development of thrombosis with other snake venoms.…”

Pulmonary Thromboembolism following Russell’s Viper Bites

“…Venom-induced consumption coagulopathy is a well-known phenomenon in SBE where the venom can induce a rapid consumption of coagulation factors and platelets by inducing clotting, and later resulting in excessive bleeding [33]. Indeed, Russell's viper venom has been demonstrated to induce peripheral arterial thrombosis in victims, and this was underpinned by its acute effects on platelet activation and plasma/whole blood clotting [34]. This venom contains a series of proteolytic enzymes, particularly thrombin-like enzymes with fibrinolytic properties, and they can activate coagulation disturbances resulting in unwanted clotting or bleeding complications [35].…”

Intramuscular Bleeding and Formation of Microthrombi during Skeletal Muscle Damage Caused by a Snake Venom Metalloprotease and a Cardiotoxin

“…The life-threatening pathophysiology of SBE is driven by the individual and synergistic actions of biologically active venom toxins with different molecular targets, which can lead to various effects in the body including haemostatic disturbances and muscle damage [ 18 , 19 ]. At the clinical level, venom-induced consumption coagulopathy (VICC) with diverse manifestations triggered by different toxins is a serious issue, and the resulting haemostatic effects may vary depending on the consumed factor in the coagulation cascade [ 20 , 21 ]. This systemic and potentially lethal phenomenon following SBE in patients is recognised via the activation of the clotting cascade and/or elevated degradation of the fibrinogen [ 22 ].…”