Snake venoms and coagulopathy
Introduction
Interference with aspects of the human haemostatic system is a common theme amongst snake venoms, encompassing all four families of venomous snakes, to a greater or lesser degree (Meier & Stocker 1995). This is reflected in the importance of coagulopathy clinically, following snakebite in all continents (except Antarctica, which has no snakes). However, while coagulopathy may be important in humans envenomed by snakes, it is not always the key venom effect responsible for morbidity or mortality, yet may act synergistically with other major venom effects, to the detriment of human health. Similarly it should be remembered that humans are not a natural prey species for any venomous snake and the effect of any venom component in the intended prey may be rather different to the effect in humans.
Section snippets
An overview of global snakebite
Globally venomous snakebite is estimated to affect greater than 2.5 million humans annually, of whom more than 100,000 will die (Chippaux, 1998). The burden of morbidity and mortality is greatest in the rural tropics (Lalloo et al., 1995, Laing et al., 1995, Warrell et al., 1999), but snakebite is not confined to poorer rural tropical areas. There is evidence that some of the most dangerous venomous snakes are invading urban areas, putting new groups of humans at significant risk (Melgarejo and
An overview of coagulopathy induced by snakebite
A brief summary of major snake groups causing coagulopathy and/or haemorrhage is presented in Table 1, Table 2. The diverse array of venom components affecting human haemostasis is mirrored only partially in a diversity of clinical effects. An outline of the broad effects is presented in Fig. 1. Indeed, in practical clinical terms, the range of clinical problems presented by this venom diversity is limited. The principal problems encountered are listed in Table 3. Essentially these can be
The procoagulants and coagulopathy
A wide variety of venom components can act as procoagulants, causing in-vivo activation of the coagulation system, but in most cases, this does not result in massive thrombosis and consequent embolic disease, but rather causes consumption of coagulation factors, resulting in clinical anticoagulation (White, 2004a, Markland, 1998). This may cause profound abnormalities of clinical laboratory tests, but unless there is some bleeding point, may not result in clinically significant bleeding (White,
The fibrinogen clotting toxins, fibrinolytics and coagulopathy
Fibrinogen clotting and fibrinolytic snake venom toxins exert a direct effect on the actual thrombus-forming protein, fibrinogen, but in varying ways (Markland, 1998). Fibrinogen may be split to fibrin and then degradation products, or it may be only partially split, leaving an ineffective form of fibrinogen circulating, the end result being an increased bleeding tendency through either mechanism. As with the procoagulants, this need not cause spontaneous bleeding, but certainly increases the
Platelet active venoms and coagulopathy
Platelets form a vital part of the haemostatic process, acting as the ‘front line’ in plugging any vascular defect, as well as providing activating surfaces for the coagulation cascade. They are metabolically active and subject to many forms of attack. There are two principal effects likely; (1) inhibition of platelet activity, thus reducing their effectiveness in haemostasis; (2) promotion of platelet activity, increasing their contribution to haemostasis, in this case pathologic. To these
Anticoagulant venoms and coagulopathy
Some snake venoms contain toxins that are direct or indirect anticoagulants, that inhibit the clotting process, thus increasing the risk of bleeding. Clinically this may be little different in effect than the consumptive route used by procoagulants, although, in general, anticoagulant venoms are associated with less severe pathologic bleeding than consumptive venoms (procoagulants etc). There will, however, be important differences in clinical laboratory results that can be useful
Thrombotic venoms and pathologic thrombosis
While a coagulant venom, by definition, induces some degree of clotting, in most cases this is accompanied by active fibrinolysis, resulting in a net loss of clotting capacity. As discussed earlier, there may be a brief window of thrombosis prior to activation of fibrinolysis. However, two snakes, the Martinique viper (Bothrops lanceolatus) and the Saint Lucia viper (Bothrops caribbaeus) cause clinical thrombosis and emboli routinely following envenoming (Thomas et al., 1995, Thomas et al., 1998
Venoms and vascular injury; the haemorrhagins
A number of viperid snakes have evolved toxins that act to increase vascular permeability or damage the vascular endothelium; the haemorrhagins. Many of these are zinc metalloproteinases (Markland, 1998). In their own right they can cause pathologic bleeding and cause more severe local effects in the bitten limb than might otherwise develop. However, when combined with toxins affecting haemostasis, reducing clotting ability, such as procoagulants, the effects can be severe indeed. The clinical
Diagnosing venom induced coagulopathy
Venom-induced coagulopathy is often easy to diagnose, either clinically, or by clinical laboratory testing. Clinically, clues include spontaneous bleeding from the bite site (Fig. 4), gums (Fig. 5) and any recent trauma, including venepuncture sites (Fig. 6, Fig. 7). Internal bleeding may be hidden, or manifest as haematemesis, haemoptysis, haematuria etc. Bleeds into crucial organs will result, generally, in signs, ranging from the very obvious (i.e. lapse into coma with dilating pupils as a
Treating venom induced coagulopathy
Coagulopathy is generally a direct effect of toxins in venom. It follows that removal of those toxins, using antivenom, should allow return to normal haemostasis. Of course, antivenom cannot repair injuries caused by the coagulopathy, such as critical organ damage, nor can it ‘switch off’ secondary phenomena activated during the coagulopathy, such as hyperfibrinolysis. It is therefore important to give the correct antivenom as early as possible, once coagulopathy is detected, in sufficient
Medical uses for haemostatically-active venoms
A detailed account of medical uses of snake venoms is beyond the scope of this paper. In particular, potential therapeutic uses will not be discussed. From the perspective of haemostatically active components, however, there is a long-standing role in diagnostic tests, both for coagulation abnormalities and related diseases. Amongst the most venerable are toxins from Russell's viper venom (Daboia russelii) (Marsh, 1998), long used as reagents for specific tests of clotting function. More
References (69)
- et al.
Neurotoxicity, haemostatic disturbances and haemolytic anaemia after a bite by a Tunisian saw-scaled or carpet viper (Echis pyramidum-complex); failure of antivenom treatment
Toxicon
(1994) - et al.
Experimental assessment of a new, low cost antivenom for treatment of carpet viper (Echis ocellatus) envenoming
Toxicon
(1995) - et al.
The epidemiology of snake bite in Central Province and National Capitol District, Papua New Guinea
Trans R Soc Trop Med Hyg
(1995) Snake venoms and the haemostatic system
Toxicon
(1998)- et al.
Risk indicators after envenomation in humans by Echis coloratus (Mid-east saw scaled viper)
Toxicon
(1992) - et al.
Clinical effects of bites by Malayan viper (Ancistrodon rhodostoma)
Lancet, March
(1963) - et al.
Prolonged coagulation defect (defibrination syndrome) in Malayan pit viper bite
Lancet, March
(1963) - et al.
BIASG Reliability of the simple 20 min whole blood clotting test (WBCT20) as an indicator of low plasma fibrinogen concentration in patients envenomed by Bothrops snakes
Toxicon
(1994) Control of antivenom treatment in Echis carinatus (carpet viper) poisoning
Trans. R Soc Trop Med Hyg
(1976)- et al.
Prognostic significance of clinical grading of patients envenomed by Bothrops lanceolatus in Martinique
Trans Roy Soc Trop Med Hyg
(1998)
Acute and chronic pituitary failure resembling Sheehan's syndrome following bites by Russell's viper in Burma
Lancet
Snake venoms in science and clinical medicine: Russell's viper; biology, venom and treatment of bites
Trans R Soc Trop Med Hyg
In vivo effect of Echis carinatus venom observed in a woman in Mali
Thromb Haemostasis
Middle cerebral occlusion following Russell's viper bite
J Trop Med Hyg
Complications of Echis colorata snake bites in the Asir region of Saudi Arabia
Ann Trop Paediat
Envenomation by ingram's brown snake (Pseudonaja ingrami)
Anaesth Intens Care
Coagulopathies in viper bites
J Postgrad Med
Snake bites: appraisal of the global situation
Bull. World Health. Organ
Haemolytic uraemic syndrome complicating snake bite
Nephron
The present position of snakebite and the snake bitten in Australia
Med J Aust
Clinical toxicology of snakebite in South America
Renal failure after snake bite
Med J Aust
The coagulation defect after envenomation by the bite of the dugite (Demansia nuchalis affinis) a Western Australian brown snake
Med J Aust
Clinical significance of venom antigen levels in patients envenomed by the Malayan pit viper (Calloselasma rhodostoma)
Am J Trop Med Hyg
Successful resuscitation after cardiac arrest following massive brown snake envenomation
Med J Aust
Consumptive coagulopathy caused by boomslang bite
S Afr Med J
Snake bites in adults from the Asir region of southern Saudi Arabia
Am J Trop Med Hyg
Use of snake venom fractions in the coagulation laboratory
Blood Coagulation and Fibrinolysis
Biology and distribution of venomous snakes of medical importance and the composition of snake venoms
Cerebral infarction after envenomation by viper
J Comput Assist Tomogr
Severe tiger snake envenomation in a wilderness environment
Med J Aust
Multiple cerebral infarctions following a snakebite by Bothrops caribbaeus
Am J Trop Med Hyg
Prolonged defibrination syndrome after bite by the carpet viper Echis carinatus
B M J
Cited by (286)
Systemic toxicity of snake venom metalloproteinases: Multi-omics analyses of kidney and blood plasma disturbances in a mouse model
2023, International Journal of Biological MacromoleculesComparative venom toxin analyses of Nigerian viperidae and elapidae snakes
2023, Scientific African