Abstract

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.

Highlights

  • Vitamin K (VK) is an essential factor that is required for the post-translational modification of coagulation factors II, VII, IX and X, protein C and protein S

  • Reagents The following reagents were used in this study: vitamin K1 (VK1) injection (Cisen Pharmaceutical Co., Shandong, China,), VK1-fat emulsion (VK1-FE) (Anjian Pharmaceutical Co., Xi’an, China), Tween-80 (Sigma Co., UK), adrenaline hydrochloride injection (Shanghai Harvest Pharmaceutical Co., Ltd, Shanghai, China), diphenhydramine hydrochloride injection (Tianjin Jinyao Amino Acid Co., Ltd, Tianjin, China), p-nitrophenyl-N-acetyl-b-D- glucosaminide (Sigma Co., UK), IgE ELISA kits (KeyGENBioTECH, Nanjing, China), histamine ELISA kits (KeyGENBioTECH, Nanjing, China), and Annexin V-FITC apoptosis detection kits (KeyGENBioTECH, Nanjing, China)

  • The results indicated that both VK1 injection and Tween-80 significantly induced the apoptosis of RBL-2H3 cells compared with the control (Figure 4)

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Summary

Introduction

Vitamin K (VK) is an essential factor that is required for the post-translational modification of coagulation factors II, VII, IX and X, protein C and protein S (the natural inhibitors of coagulation). VK occurs naturally in two forms, VK1 and VK2. Reports of severe adverse reactions began to appear, and the number of adverse reactions to VK1 injection is always remarkable. The consistent symptoms include facial flushing, vague uneasy feelings of weakness, abdominal and low back pain, nausea, vomiting, dyspnea, and chest pain. In severe reactions, these symptoms are followed within minutes by cyanosis, loss of consciousness, and hypotension, with the potential for cardio-pulmonary arrest and death [2,3]

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