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激活X因子的穴蝰蛇毒以及非洲抗蛇毒血清对相关凝血毒性的中和效力

Factor X activating Atractaspis snake venoms and the relative coagulotoxicity neutralising efficacy of African antivenoms.

作者信息

Oulion Brice, Dobson James S, Zdenek Christina N, Arbuckle Kevin, Lister Callum, Coimbra Francisco C P, Op den Brouw Bianca, Debono Jordan, Rogalski Aymeric, Violette Aude, Fourmy Rudy, Frank Nathaniel, Fry Bryan G

机构信息

Venom Evolution Lab, School of Biological Sciences, University of Queensland, St Lucia, QLD 4072, Australia.

Department of Biosciences, College of Science, Swansea University, Swansea SA2 8PP, UK.

出版信息

Toxicol Lett. 2018 May 15;288:119-128. doi: 10.1016/j.toxlet.2018.02.020. Epub 2018 Feb 17.

DOI:10.1016/j.toxlet.2018.02.020
PMID:29462691
Abstract

Atractaspis snake species are enigmatic in their natural history, and venom effects are correspondingly poorly described. Clinical reports are scarce but bites have been described as causing severe hypertension, profound local tissue damage leading to amputation, and deaths are on record. Clinical descriptions have largely concentrated upon tissue effects, and research efforts have focused upon the blood-pressure affecting sarafotoxins. However, coagulation disturbances suggestive of procoagulant functions have been reported in some clinical cases, yet this aspect has been uninvestigated. We used a suite of assays to investigate the coagulotoxic effects of venoms from six different Atractaspis specimens from central Africa. The procoagulant function of factor X activation was revealed, as was the pseudo-procoagulant function of direct cleavage of fibrinogen into weak clots. The relative neutralization efficacy of South African Antivenom Producer's antivenoms on Atractaspis venoms was boomslang>>>polyvalent>saw-scaled viper. While the boomslang antivenom was the most effective on Atractaspis venoms, the ability to neutralize the most potent Atractaspis species in this study was up to 4-6 times less effective than boomslang antivenom neutralizes boomslang venom. Therefore, while these results suggest cross-reactivity of boomslang antivenom with the unexpectedly potent coagulotoxic effects of Atractaspis venoms, a considerable amount of this rare antivenom may be needed. This report thus reveals potent venom actions upon blood coagulation that may lead to severe clinical effects with limited management strategies.

摘要

穴蝰属蛇类在其自然史方面颇具神秘色彩,其毒液作用相应地也鲜有描述。临床报告稀少,但已报道的咬伤案例显示会引发严重高血压、导致截肢的严重局部组织损伤,且有致死记录。临床描述主要集中在组织效应上,研究工作则聚焦于影响血压的沙罗毒素。然而,在一些临床病例中已报告存在提示促凝功能的凝血紊乱情况,但这方面尚未得到研究。我们使用了一系列检测方法来研究来自中非的六种不同穴蝰标本毒液的凝血毒性作用。结果显示了因子X激活的促凝功能,以及将纤维蛋白原直接裂解为弱凝块的假促凝功能。南非抗蛇毒血清生产商的抗蛇毒血清对穴蝰毒液的相对中和效力为:非洲树蛇抗蛇毒血清>多价抗蛇毒血清>锯鳞蝰抗蛇毒血清。虽然非洲树蛇抗蛇毒血清对穴蝰毒液最为有效,但在本研究中,其中和最具毒性的穴蝰物种毒液的能力比非洲树蛇抗蛇毒血清中和非洲树蛇毒液的效力低4至6倍。因此,虽然这些结果表明非洲树蛇抗蛇毒血清与穴蝰毒液意外强大的凝血毒性作用存在交叉反应,但可能需要大量这种稀有的抗蛇毒血清。本报告因此揭示了毒液对血液凝固有强大作用,可能导致严重临床后果,而应对策略有限。

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