Anaphylactic shock caused by haemocoagulase injection in China

Abstract

Haemocoagulase injection is a mixture of purified enzymes isolated from the venom of Bothrops atrox, which is used for the prevention and treatment of haemorrhage. It is a relatively safe pharmacological agent that does not require a skin test prior to administration. However, following a literature search, 14 reported cases of anaphylactic shock caused by haemocoagulase injection were identified, including one lethal case in China. Using SDS-PAGE and protein identification, four primary components in haemocoagulase injection were characterized, including one metalloproteinase, which may be a thromboplastin-like enzyme, and two serine proteinases, which may be thrombin-like enzymes. Administering concentrated haemocoagulase injections failed to provoke a positive skin reaction in allergic patients. Basophil activation tests revealed that haemocoagulase injections did not upregulate cluster of differentiation 63 or C-C chemokine receptor type 3 expression. These findings suggest that haemocoagulase injection may cause fetal anaphylaxis. Although it is difficult to determine a clear conclusion without being able to evaluate the patients that underwent haemocoagulase injection-induced shock, it is unlikely that the venomous components of haemocoagulase injection cross-react with common allergens in allergic patients. It is possible that haemocoagulase injection-induced anaphylaxis is caused by its additive components, such as mannitol and succinylated gelatin.

Keywords: allergen; anaphylactic shock; basophil; haemocoagulase.

Figure 1.

SDS-PAGE of haemocoagulase injection. Lane 1: protein markers including rabbit muscle phosphorylase b (97.2 kDa), bovine serum albumin (66.4 kDa), chicken egg ovalbumin (44.3 kDa), bovine carbonic anhydrase (29 kDa), soya bean trypsin inhibitor (20.1 kDa) and chicken egg lysozyme (14.2 kDa). Lane 2: Haemocoagulase in reducing conditions. Haemocoagulase exhibited four major bands via silver staining.

Figure 2.

Effect of haemocoagulase and its components on expression of CD63 and CCR3 on basophils. Sample 1, 2 and 3 represent the molecular weights of the protein components >10, between 3 and 10, and <3 kDa, respectively. Values are presented as the mean ± standard deviation for 10 different allergic patients. CCR3, C-C chemokine receptor type 3; CD63, cluster of differentiation 63; FITC, fluorescein isothiocyanate; PE, phycoerythrin; IgE, immunoglobulin E. *P<0.05 vs. control.