The severe adverse reaction to vitamin K1 injection is always remarkable and is thought to result from anaphylaxis. Paradoxically, however, some patients administered vitamin K1 injection for the first time have adverse reactions. Using beagle dogs, the present study tested the hypothesis that the response to vitamin K1 is an anaphylactoid reaction. The results showed that serious anaphylaxis-like symptoms appeared in beagle dogs after the administration of vitamin K1 injection for the first time. The plasma histamine concentration increased, and blood pressure decreased sharply. After sensitization, dogs were challenged with vitamin K1 injection and displayed the same degree of symptoms as prior to sensitization. However, when the vitamin K1 injection-sensitized dogs were challenged with a vitamin K1-fat emulsion without solubilizers such asTween-80, the abnormal reactions did not occur. Furthermore, there was no significant change in the plasma immunoglobulin E concentration after vitamin K1 challenge. Following treatment with vitamin K1 injection, the release of histamine and β-hexosaminidase by rat basophilic leukemia-2H3 cells as well as the rate of apoptosis increased. The Tween-80 group displayed results similar to those observed following vitamin K1 injection in vivo. However, the dogs in the vitamin K1-fat emulsion group did not display any abnormal behavior or significant change in plasma histamine. Additionally, degranulation and apoptosis did not occur in rat basophilic leukemia-2H3 cells. Our results indicate that the adverse reaction induced by vitamin K1 injection is an anaphylactoid reaction, not anaphylaxis. Vitamin K1 injection induces the release of inflammatory factors via a non-IgE-mediated immune pathway, for which the trigger may be the solubilizer.
References
[1]
Vandermeir J (1968) Vitamin K. Thromb Diath Haemorrh 29: 1–95.
[2]
Fiore LD, Scola MA, Cantillon CE, Brophy MT (2001) Anaphylactoid reactions to vitamin K. J Thromb Thrombolysis 11: 175–183. doi: 10.1023/a:1011237019082
[3]
Pereira SP, Williams R (1998) Adverse events associated with vitamin K1: results of a worldwide postmarketing surveillance programme. Pharmacoepidemiol Drug Saf 7: 173–182. doi: 10.1002/(sici)1099-1557(199805/06)7:3<173::aid-pds343>3.0.co;2-8
[4]
SFDA PRC (2011) Alert regarding serious allergic reactions to vitamin K1 injection. National Center for ADR Monitoring
[5]
Sousa T, Hunter L, Petitt M, Wilkerson MG (2010) Letter: Localized cutaneous reaction to intramuscular vitamin K in a patient with acute fatty liver of pregnancy. Dermatol Online J 16: 16.
[6]
Sommer S, Wilkinson SM, Peckham D, Wilson C (2002) Type IV hypersensitivity to vitamin K. Contact Dermatitis 46: 94–96. doi: 10.1034/j.1600-0536.2002.460206.x
[7]
Riegert-Johnson DL, Volcheck GW (2002) The incidence of anaphylaxis following intravenous phytonadione (vitamin K1): a 5-year retrospective review. Ann Allergy Asthma Immunol 89: 400–406. doi: 10.1016/s1081-1206(10)62042-x
[8]
Wilkins K, DeKoven J, Assaad D (2000) Cutaneous reactions associated with vitamin K1. J Cutan Med Surg 4: 164–168.
[9]
Yang G-H, Lei Z-B (2009) The analysis of 45 cases of the anaphylactic shock indused by vitamin K1 injection. Chin J of Clinical Rational Drug Use 2.
[10]
Martin JC (1991) Anaphylactoid reactions and vitamin K. Med J Aust 155: 851.
[11]
Riegert-Johnson DL, Kumar S, Volcheck GW (2001) A patient with anaphylactoid hypersensitivity to intravenous cyclosporine and subcutaneous phytonadione (vitamin K1). Bone Marrow Transplant 28: 1176–1177. doi: 10.1038/sj.bmt.1703305
[12]
Coors EA, Seybold H, Merk HF, Mahler V (2005) Polysorbate 80 in medical products and nonimmunologic anaphylactoid reactions. Ann Allergy Asthma Immunol 95: 593–599. doi: 10.1016/s1081-1206(10)61024-1
[13]
Qiu S, Liu Z, Hou L, Li Y, Wang J, et al. (2013) Complement activation associated with polysorbate 80 in beagle dogs. Int Immunopharmacol 15: 144–149. doi: 10.1016/j.intimp.2012.10.021
[14]
Sun WW, Li YK, Zhang JY (2011) [Anaphylactoid reactions inducing effect of polysorbate 80 and polysorbate 80 contained Houttuynia cordata injection on beagle]. Zhongguo Zhong Xi Yi Jie He Za Zhi 31: 90–93.
[15]
Wang Z, Wang D, Sui Y, Cui H, Yu Y (2012) Experimental study on anaphylaxis of qingkailing injection and its components on Beagle dogs. J Tradit Chin Med 32: 641–645. doi: 10.1016/s0254-6272(13)60085-0
[16]
Wang Z, Wang D, Yu Y, Li Y, Sui Y, et al. (2011) Experimental model of histamine-induced anaphylactoid reaction on beagle dogs. Zhongguo Zhong Yao Za Zhi 36: 1842–1844.
[17]
Liang A, Li C, Hao R, Cao C, Yi Y, et al. (2010) [Pseudoanaphylactoid reaction analysis of Chinese herbal injections in Beagle dogs]. Zhongguo Zhong Yao Za Zhi 35: 2328–2333. doi: 10.4268/cjcmm20101725
[18]
He P, Li F, Tang R, Li Y, Hao W, et al. (2012) [Experimental study on anaphylactoid reactions induced by different components of shengmai injection (new production process) on Beagle dogs]. Zhongguo Zhong Yao Za Zhi 37: 1880–1884.
[19]
Vo T, Kong C, Kim S (2011) Inhibitory effects of chitooligosaccharides on degranulation and cytokine generation in rat basophilic leukemia RBL-2H3 cells. CARBOHYDRATE POLYMERS 84: 649–655. doi: 10.1016/j.carbpol.2010.12.046
[20]
Na HJ, Moon PD, Lee HJ, Kim HR, Chae HJ, et al. (2005) Regulatory effect of atopic allergic reaction by Carpopeltis affinis. J Ethnopharmacol 101: 43–48. doi: 10.1016/j.jep.2005.03.026
[21]
Nishikawa H, Kitani S (2011) Gangliosides inhibit bee venom melittin cytotoxicity but not phospholipase A(2)-induced degranulation in mast cells. Toxicol Appl Pharmacol 252: 228–236. doi: 10.1016/j.taap.2011.02.011
[22]
Ng W, Lobach AR, Zhu X, Chen X, Liu F, et al. (2012) Animal models of idiosyncratic drug reactions. Adv Pharmacol 63: 81–135. doi: 10.1016/b978-0-12-398339-8.00003-3
[23]
Shenton JM, Chen J, Uetrecht JP (2004) Animal models of idiosyncratic drug reactions. Chem Biol Interact 150: 53–70. doi: 10.1016/j.cbi.2004.09.001
[24]
Huang FH, Zhang XY, Zhang LY, Li Q, Ni B, et al. (2010) Mast cell degranulation induced by chlorogenic acid. Acta Pharmacol Sin 31: 849–854. doi: 10.1038/aps.2010.63
[25]
Funaba M, Ikeda T, Abe M (2003) Degranulation in RBL-2H3 cells: regulation by calmodulin pathway. Cell Biol Int 27: 879–885. doi: 10.1016/s1065-6995(03)00177-x
[26]
Sun W, Li Y, Wang N, Du F, Hao W, et al. (2011) [Anaphylactoid reactions induced by polysorbate 80 on Beagle dogs]. Zhongguo Zhong Yao Za Zhi 36: 1874–1878.
[27]
Wang Z, Wang D, Yu Y, Sui Y, Cui H, et al. (2011) [Study on allergenicity of chlorogenic acid in Qingkailing injection]. Zhongguo Zhong Yao Za Zhi 36: 1870–1873.
