Hemostasis is a process which causes bleeding to stop, meaning to keep blood within a damaged blood vessel. Fig.1 and its legend briefly describes this complex process.
Figure 1: The cell-based model of hemostasis shows the different components of the hemostatic system that are affected by snake venom proteins
(Reprinted from Toxicon, Sajevic et al., 2011, © 2011, with permission from Elsevier.)
Platelet aggregation: Following vessel wall injury, platelets bind to exposed sub-endothelium. Through receptors on their plasma membrane - glycoprotein complex GPIb-V-IX and GPVI and integrin α2β1 - platelets interact with vWF bound on the exposed collagen or directly to the collagen. Platelets are activated on binding. They change their shape from flat to spherical and numerous pseudopodia bursts. They release different mediators, e.g. ADP and thromboxane A2, and start to synthesise prostaglandins. Released molecules bind to receptors on neighbouring platelets and activate them. Activation of fibrinogen receptor GPIIb/IIIa on subsequent fibrinogen binding cross-links platelets and forms the plug.
Coagulation cascade: Following damage to the blood vessel wall, the cells bearing tissue factor (TF) (smooth muscle cells, macrophages and fibroblasts) come into the contact with coagulation factors in the blood. TF in complex with FVIIa activates minute amounts of FIX and FX. FXa activates prothrombin into thrombin which activates platelets, FV, FVIII and FXI. Additional FIXa is formed by FXIa, bound to platelets. On the surface of platelets, FIXa forms a complex with FVIIIa, which activates FX. FXa complexed with FVa then produces large amounts of thrombin. Thrombin converts fibrinogen to monomeric fibrin that polymerizes to fibrin fibres. These are cross-linked by thrombin activated FXIII.
Fibrinolysis: Tissue plasminogen activator (t-PA) and urokinase (u-PA) activate plasminogen to plasmin, which then degrades the fibrin clot. Regulation of coagulation. The coagulation is regulated by inhibitors of coagulation factors, such as anti-thrombin (AT), anti-plasmin (AP) and α2-macroglobulin (α2-MG). The most important inhibitory mechanism is the protein C (PROC) anticoagulant pathway that is activated at the same time as the activation of coagulation factors. On the surface of non-activated endothelial cells, thrombin binds to thrombomodulin and activates PROC (APROC) which then, in the complex protein S (PS), cleaves FVa and FVIIIa.
Snake venom contains numerous proteins that disturb hemostasis. They belong to a large variety of protein families and act at different levels of hemostasis. They cause hemorrhage (see hemorrhagic toxin) by damaging endothelial cells or disturbing their interactions with the basement membrane, disturb platelet aggregation (see platelet aggreg. activating toxin and Platelet aggreg. inhibiting toxin) which is crucial for forming blood clots, impair the blood coagulation cascade (blood coagulation cascade activating toxin and blood coagulation cascade inhibiting toxin), degrade fibrinogen (see fibrinogenolytic toxin) and even lyse already formed blood clot (fibrinolytic toxin). All these effects explain why disturbance of hemostasis is among the most severe effects following a snake bite.
In other venomous species, only a few toxins have been described to impair hemostasis.
See also UniProtKB-keyword.
Hemostasis impairing toxin
Venom protein entries in UniProtKB/Swiss-Prot
(all links/actions below point to uniprot.org website)915 entries grouped by species
2 entries
Acanthaster planci (Crown-of-thorns starfish)
2 entries
Acanthophis antarcticus (Common death adder)
4 entries
Agkistrodon bilineatus (Cantil) (Tropical moccasin)
6 entries
Agkistrodon contortrix contortrix (Southern copperhead)
4 entries
Agkistrodon contortrix laticinctus (Broad-banded copperhead) (Agkistrodon mokasen laticinctus)
5 entries
Agkistrodon piscivorus leucostoma (Western cottonmouth) (Acontias leucostoma)
3 entries
Agkistrodon piscivorus piscivorus (Eastern cottonmouth)
1 entry
Anuroctonus phaiodactylus (Mafia scorpion)
22 entries
Austrelaps superbus (Lowland copperhead snake) (Hoplocephalus superbus)
12 entries
Bitis arietans (African puff adder)
1 entry
Bitis caudalis (Horned adder) (Horned viper)
6 entries
Bitis gabonica (Gaboon adder) (Gaboon viper)
7 entries
Bitis rhinoceros (West African gaboon viper) (Vipera rhinoceros)
2 entries
Bombus ignitus (Bumblebee)
1 entry
Bombus terrestris (Buff-tailed bumblebee) (Apis terrestris)
1 entry
Borikenophis portoricensis (Puerto Rican racer) (Alsophis portoricensis)
1 entry
Bothriechis lateralis (Side-striped palm pitviper)
1 entry
Bothrocophias andianus (Andean lancehead) (Bothrops andianus)
7 entries
Bothrops alternatus (Urutu) (Rhinocerophis alternatus)
8 entries
Bothrops asper (Terciopelo)
9 entries
Bothrops atrox (Barba amarilla) (Fer-de-lance)
2 entries
Bothrops barnetti (Barnett's lancehead) (Trimeresurus barnetti)
4 entries
Bothrops brazili (Brazil's lancehead)
4 entries
Bothrops cotiara (Cotiara) (Rhinocerophis cotiara)
1 entry
Bothrops diporus (Chaco lancehead) (Bothrops neuwiedi diporus)
2 entries
Bothrops erythromelas (Caatinga lance head)
6 entries
Bothrops fonsecai (Fonseca's lancehead) (Rhinocerophis fonsecai)
7 entries
Bothrops insularis (Golden lancehead) (Lachesis insularis)
36 entries
Bothrops jararaca (Jararaca) (Bothrops jajaraca)
10 entries
Bothrops jararacussu (Jararacussu)
7 entries
Bothrops leucurus (Whitetail lancehead)
3 entries
Bothrops marajoensis (Marajo lancehead)
1 entry
Bothrops mattogrossensis (Pitviper) (Bothrops neuwiedi mattogrossensis)
4 entries
Bothrops moojeni (Lance-headed viper) (Caissaca)
9 entries
Bothrops pauloensis (Neuwied's lancehead) (Bothrops neuwiedi pauloensis)
2 entries
Bothrops pictus (Desert lancehead)
6 entries
Bothrops pirajai (Piraja's lancehead)
3 entries
Bungarus caeruleus (Indian krait)
3 entries
Bungarus fasciatus (Banded krait) (Pseudoboa fasciata)
6 entries
Bungarus multicinctus (Many-banded krait)
15 entries
Calloselasma rhodostoma (Malayan pit viper) (Agkistrodon rhodostoma)
11 entries
Cerastes cerastes (Horned desert viper)
3 entries
Cerastes vipera (Sahara sand viper)
5 entries
Cerberus rynchops (Dog-faced water snake)
1 entry
Cerrophidion sasai (Costa Rica montane pitviper)
1 entry
Condylactis gigantea (Giant Caribbean anemone) (Condylactis passiflora)
2 entries
Craspedocephalus borneensis (Borneo pit viper) (Trimeresurus borneensis)
9 entries
Craspedocephalus gramineus (Bamboo pit viper) (Trimeresurus gramineus)
5 entries
Craspedocephalus puniceus (Flat-nosed pitviper) (Trimeresurus puniceus)
26 entries
Crotalus adamanteus (Eastern diamondback rattlesnake)
25 entries
Crotalus atrox (Western diamondback rattlesnake)
1 entry
Crotalus basiliscus (Mexican west-coast rattlesnake)
1 entry
Crotalus cerastes cerastes (Mojave desert sidewinder)
1 entry
Crotalus cerberus (Arizona black rattlesnake) (Crotalus oreganus cerberus)
3 entries
Crotalus durissus cascavella (Northeastern Brazilian rattlesnake)
3 entries
Crotalus durissus collilineatus (Brazilian rattlesnake)
5 entries
Crotalus durissus cumanensis (South American rattlesnake)
3 entries
Crotalus durissus durissus (Central American rattlesnake)
15 entries
Crotalus durissus terrificus (South American rattlesnake)
6 entries
Crotalus horridus (Timber rattlesnake)
1 entry
Crotalus lutosus (Great basin rattlesnake) (Crotalus oreganus lutosus)
2 entries
Crotalus molossus molossus (Northern black-tailed rattlesnake)
1 entry
Crotalus molossus nigrescens (Black-tailed rattlesnake)
1 entry
Crotalus morulus (Tamaulipan rock rattlesnake) (Crotalus lepidus morulus)
1 entry
Crotalus oreganus abyssus (Grand Canyon rattlesnake) (Crotalus abyssus)
3 entries
Crotalus ruber ruber (Red diamond rattlesnake)
2 entries
Crotalus scutulatus scutulatus (Mojave rattlesnake)
1 entry
Crotalus simus (Central American rattlesnake) (Caudisona simus)
2 entries
Crotalus tzabcan (Yucatan neotropical rattlesnake) (Crotalus simus tzabcan)
2 entries
Crotalus vegrandis (Uracoan rattlesnake) (Crotalus durissus vegrandis)
13 entries
Crotalus viridis viridis (Prairie rattlesnake)
1 entry
Cryptophis nigrescens (Eastern small-eyed snake) (Rhinoplocephalus nigrescens)
1 entry
Daboia palaestinae (Palestine viper) (Vipera palaestinae)
14 entries
Daboia russelii (Russel's viper) (Vipera russelii)
14 entries
Daboia siamensis (Eastern Russel's viper) (Daboia russelii siamensis)
37 entries
Deinagkistrodon acutus (Hundred-pace snake) (Agkistrodon acutus)
3 entries
Demansia vestigiata (Lesser black whip snake) (Demansia atra)
1 entry
Dendroaspis angusticeps (Eastern green mamba) (Naja angusticeps)
2 entries
Dendroaspis jamesoni kaimosae (Eastern Jameson's mamba)
5 entries
Drysdalia coronoides (White-lipped snake) (Hoplocephalus coronoides)
12 entries
Echis carinatus (Saw-scaled viper)
7 entries
Echis carinatus sochureki (Saw-scaled viper)
2 entries
Echis leucogaster (Roman's saw-scaled viper) (Echis carinatus leucogaster)
6 entries
Echis multisquamatus (Central Asian sand viper)
17 entries
Echis ocellatus (Ocellated saw-scaled viper)
8 entries
Echis pyramidum leakeyi (Leakey's carpet viper) (Echis carinatus leakeyi)
5 entries
Eristicophis macmahoni (Leaf-nosed viper)
6 entries
Gloydius blomhoffii (Mamushi) (Agkistrodon halys blomhoffi)
18 entries
Gloydius brevicauda (Korean slamosa snake) (Agkistrodon halys brevicaudus)
22 entries
Gloydius halys (Chinese water mocassin) (Agkistrodon halys)
2 entries
Gloydius intermedius (Central Asian pit viper) (Agkistrodon intermedius)
2 entries
Gloydius shedaoensis (Shedao island pit viper) (Agkistrodon shedaoensis)
11 entries
Gloydius ussuriensis (Ussuri mamushi) (Gloydius blomhoffii ussuriensis)
4 entries
Hemachatus haemachatus (Rinkhals) (Sepedon haemachatus)
1 entry
Hippasa partita (Funnel-web spider) (Hippasa deserticola)
1 entry
Hoplocephalus stephensii (Stephens' banded snake)
1 entry
Hydrophis hardwickii (Hardwick's spine-bellied seasnake) (Lapemis hardwickii)
1 entry
Hydrophis schistosus (Beaked sea snake) (Enhydrina schistosa)
6 entries
Lachesis muta muta (Bushmaster)
8 entries
Lachesis muta rhombeata (Bushmaster)
1 entry
Lachesis stenophrys (Central American bushmaster)
1 entry
Loxosceles intermedia (Brown spider)
1 entry
Loxosceles laeta (South American recluse spider) (Scytodes laeta)
52 entries
Macrovipera lebetina (Levantine viper) (Vipera lebetina)
3 entries
Macrovipera lebetina obtusa (Levant blunt-nosed viper) (Vipera lebetina obtusa)
1 entry
Macrovipera lebetina transmediterranea (Blunt-nosed viper) (Vipera lebetina transmediterranea)
1 entry
Metlapilcoatlus mexicanus (Central American jumping pitviper) (Atropoides mexicanus)
1 entry
Micropechis ikaheca (New Guinean small-eyed snake)
1 entry
Micrurus corallinus (Brazilian coral snake)
1 entry
Micrurus mipartitus (Red-tailed coral snake)
8 entries
Naja atra (Chinese cobra)
1 entry
Naja haje haje (Egyptian cobra)
3 entries
Naja kaouthia (Monocled cobra) (Naja siamensis)
3 entries
Naja mossambica (Mozambique spitting cobra)
1 entry
Naja naja (Indian cobra)
3 entries
Naja nigricollis (Black-necked spitting cobra)
1 entry
Naja oxiana (Central Asian cobra) (Oxus cobra)
1 entry
Naja pallida (Red spitting cobra)
1 entry
Naja sagittifera (Andaman cobra)
1 entry
Notechis scutatus niger (Peninsula tiger snake) (Notechis ater niger)
3 entries
Notechis scutatus scutatus (Mainland tiger snake) (Common tiger snake)
7 entries
Ophiophagus hannah (King cobra) (Naja hannah)
1 entry
Ovophis monticola (Chinese mountain pitviper) (Trimeresurus monticola)
3 entries
Ovophis okinavensis (Ryukyu Island pit viper) (Trimeresurus okinavensis)
2 entries
Oxyuranus microlepidotus (Inland taipan) (Diemenia microlepidota)
2 entries
Oxyuranus scutellatus (Coastal taipan)
2 entries
Oxyuranus scutellatus scutellatus (Australian taipan) (Coastal taipan)
3 entries
Philodryas olfersii (Green snake)
1 entry
Philodryas patagoniensis (Ringless green snake)
1 entry
Porthidium nasutum (Hognosed pitviper) (Bothrops nasutus)
1 entry
Porthidium ophryomegas (Slender hognose viper)
1 entry
Proatheris superciliaris (Lowland swamp viper)
4 entries
Protobothrops elegans (Elegant pitviper) (Trimeresurus elegans)
18 entries
Protobothrops flavoviridis (Habu) (Trimeresurus flavoviridis)
16 entries
Protobothrops jerdonii (Jerdon's pitviper) (Trimeresurus jerdonii)
19 entries
Protobothrops mucrosquamatus (Taiwan habu) (Trimeresurus mucrosquamatus)
2 entries
Protobothrops tokarensis (Tokara habu) (Trimeresurus tokarensis)
1 entry
Pseudechis australis (Mulga snake) (King brown snake)
1 entry
Pseudechis papuanus (Papuan black snake)
1 entry
Pseudechis porphyriacus (Red-bellied black snake)
1 entry
Pseudocerastes fieldi (Field's horned viper) (Pseudocerastes persicus fieldi)
4 entries
Pseudonaja textilis (Eastern brown snake)
1 entry
Pseudonaja textilis textilis (Eastern brown snake)
3 entries
Scolopendra dehaani (Thai centipede) (Scolopendra subspinipes dehaani)
1 entry
Scorpaena plumieri (Spotted scorpionfish)
4 entries
Sistrurus catenatus edwardsii (Desert massasauga) (Crotalophorus edwardsii)
1 entry
Sistrurus miliarius barbouri (Dusky pigmy rattlesnake) (Sistrurus barbouri)
1 entry
Sistrurus tergeminus (Western massasauga) (Sistrurus catenatus tergeminus)
1 entry
Synanceia horrida (Estuarine stonefish) (Scorpaena horrida)
18 entries
Trimeresurus albolabris (White-lipped pit viper) (Cryptelytrops albolabris)
1 entry
Trimeresurus gracilis (Kikuchi habu)
3 entries
Trimeresurus purpureomaculatus (Mangrove pit viper) (Cryptelytrops purpureomaculatus)
54 entries
Trimeresurus stejnegeri (Chinese green tree viper) (Viridovipera stejnegeri)
1 entry
Tropidechis carinatus (Australian rough-scaled snake)
2 entries
Tropidolaemus wagleri (Wagler's pit viper) (Trimeresurus wagleri)
1 entry
Varanus komodoensis (Komodo dragon)
1 entry
Vespa bicolor (Black shield wasp)
1 entry
Vespa magnifica (Hornet)
18 entries
Vipera ammodytes ammodytes (Western sand viper)
1 entry
Vipera ammodytes meridionalis (Eastern sand viper)
1 entry
Vipera aspis aspis (Aspic viper)
4 entries
Vipera berus berus (Common viper)
4 entries
Vipera nikolskii (Nikolsky's adder) (Vipera berus nikolskii)
2 entries
Vipera renardi (Steppe viper) (Vipera ursinii renardi)
2 entries