vitamin-k-1 and Anaphylaxis

Parenteral vitamin K1 (phytonadione) is used for anticoagulant reversal, and a boxed warning exists with intravenous and intramuscular administration due to the possibility of severe reactions, including fatalities. These reactions resemble hypersensitivity or anaphylaxis, including anaphylactoid reaction, and have led to shock and cardiac and/or respiratory arrest. The objective of this review is to summarize the available literature detailing the anaphylactic/anaphylactoid reactions with parenteral vitamin K1 in order to better characterize the reaction and provide a more in-depth understanding of its importance. A comprehensive literature search of MEDLINE (1946 to June 2016) and EMBASE (1947 to June 2016) was conducted using the terms vitamin K1, phytonadione, phytomenadione, vitamin K group, anaphylaxis, polyoxyethylated castor oil, and cremophor. A total of 2 retrospective surveillance studies, 2 retrospective cohort studies, and 17 case reports were identified for inclusion and assessment. Based on a review of the literature, use of parenteral vitamin K1 may result in severe hypotension, bradycardia or tachycardia, dyspnea, bronchospasm, cardiac arrest, and death. These reactions are most consistent with a nonimmune-mediated anaphylactoid mechanism. It appears that intravenous administration is more frequently associated with these reactions and occurs at an incidence of 3 per 10 000 doses of intravenous vitamin K1. The solubilizer may also increase the risk of adverse reactions, which occurred in patients with and without previous exposure to vitamin K1. Although there are known factors that increase the risk of an adverse drug event occurring, reactions have been reported despite all precautions being properly followed.

Topics: Anaphylaxis; Anticoagulants; Antidotes; Drug Hypersensitivity; Female; Humans; Male; Vitamin K 1

Phytonadione (vitamin K1) administered intravenously (i.v.) has been associated with anaphylaxis, although the incidence is not known. The anaphylaxis is thought to be attributable to the solubilizing vehicle, polyethoxylated castor oil (Cremophor EL, BASF AG, Ludwingshafen, Germany).. To estimate the incidence of anaphylaxis after i.v. administration of phytonadione.. A retrospective review of anaphylaxis after i.v. phytonadione over a 58-month period at a large academic center was performed. During the period of the study a protocol for the administration of i.v. phytonadione was in place. A review of computerized records and survey of staff identified cases of anaphylaxis meeting predefined inclusion criteria. In addition, a literature review was performed for articles concerning anaphylaxis after i.v. phytonadione.. Over the 58 months of the study, a total of 6,572 doses of i.v. phytonadione were administered. Two cases of anaphylaxis after i.v. phytonadione were identified. The incidence of anaphylaxis was 3 per 10,000 doses with 95% confidence intervals of 0.04 to 11 per 10,000 doses. The literature review identified 14 cases meeting inclusion criteria with no reviews of the literature or estimates of incidence.. The incidence of anaphylaxis after i.v. phytonadione is overall comparable or slightly less than other drugs known to cause anaphylaxis. We do not recommend routine pretreatment with antihistamines or corticosteroids before administration of phytonadione.

Topics: Adult; Aged; Aged, 80 and over; Anaphylaxis; Child; Female; Humans; Incidence; Injections, Intravenous; Male; Middle Aged; Retrospective Studies; Vitamin K 1

Vitamin K1 injection induces severe dose-related anaphylactoid reactions and overdose for the treatment of vitamin K deficiency. We aimed to find an optimal and small dose of vitamin K1 injection to treat vitamin K deficiency and avoid anaphylactoid reactions in animal. Rats were administered a vitamin K-deficient diet and gentamicin to establish vitamin K deficiency model. Behaviour tests were performed in beagle dogs to observe anaphylactoid reactions. The results showed an increased protein induced by vitamin K absence or antagonist II (PIVKA-II) levels, a prolonging of prothrombin time (PT) and activated partial thromboplastin time (APTT) and a decrease in vitamin K-dependent coagulation factor (F) II, VII, IX and X activities in the model group. In vitamin K1 0.01 mg/kg group, the liver vitamin K1 levels increased fivefold and the liver vitamin K2 levels increased to the normal amount. Coagulation markers PT, APTT, FVII and FIX activities returned to normal. Both in the 0.1 and 1.0 mg/kg vitamin K1 groups, coagulation functions completely returned to normal. Moreover, the amount of liver vitamin K1 was 40 (0.1 mg/kg) or 100 (1.0 mg/kg) times as in normal. Vitamin K2 was about 4 (0.1 mg/kg) or 5 (1.0 mg/kg) times as the normal amount. There was no obvious anaphylactoid symptom in dogs with the dose of 0.03 mg/kg, which is equivalent to the dose of 0.01 mg/kg in rats. These results demonstrated that a small dose of vitamin K1 is effective to improve vitamin K deficiency and to prevent anaphylactoid reactions, simultaneously.

Topics: Anaphylaxis; Animals; Blood Coagulation; Dose-Response Relationship, Drug; Female; Male; Rats; Rats, Sprague-Dawley; Vitamin K 1; Vitamin K Deficiency

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.

Topics: Anaphylaxis; Animals; Apoptosis; beta-N-Acetylhexosaminidases; Blood Pressure; Cell Degranulation; Cell Line, Tumor; Dogs; Emulsions; Fat Emulsions, Intravenous; Female; Flow Cytometry; Histamine; Immunoglobulin E; Injections, Intravenous; Male; Rats; Vitamin K 1

Topics: Adult; Anaphylaxis; Cyclosporine; Drug Hypersensitivity; Female; Humans; Immunosuppressive Agents; Injections, Intravenous; Injections, Subcutaneous; Vitamin K 1

Topics: Adult; Aged; Anaphylaxis; Blood Coagulation Disorders; Female; Humans; Injections, Intravenous; Male; Middle Aged; Vitamin K; Vitamin K 1

A 28-year-old woman in labor developed a severe anaphylactoid reaction, necessitating acute cesarean section, with subsequent neonatal death, after receiving 10 mg of phytomenadione (Konakion) by the intramuscular route. Allergologic investigations revealed no type I reaction against the drug, and the symptoms were considered to be caused by drug-induced intolerance. Prophylactic administration of phytomenadione to the infant rather than to the parturient is recommended.

Topics: Adult; Anaphylaxis; Female; Humans; Infant, Newborn; Infant, Newborn, Diseases; Injections, Intramuscular; Male; Pregnancy; Vitamin K 1

Topics: Adult; Anaphylaxis; Female; Humans; Infusions, Intravenous; Vitamin K 1

The efficacy and tolerability of a conventional vitamin K1 preparation containing polyoxyethylated castor oil as solubilizer were compared with those of a new compound containing mixed micelles as solubilizer in 30 patients. A statistically significant increase in the thrombotest was detected after treatment in both groups. No hematological or chemical toxicity was observed during the observation period. One patient had an anaphylactoid reaction after intravenous injection of the mixed micelles preparation. Intradermal testing yielded positive results. The authors conclude that intravenous administration of vitamin K preparations should be reserved for acute emergencies.

Topics: Adult; Aged; Aged, 80 and over; Anaphylaxis; Blood Coagulation Tests; Excipients; Female; Humans; Infusions, Intravenous; Male; Middle Aged; Vitamin K 1; Vitamin K Deficiency

Topics: Acetylcholine; Aerosols; Albumins; Anaphylaxis; Animals; Anti-Inflammatory Agents; Bradykinin; Bronchial Spasm; Edema; Erythema; Exudates and Transudates; Female; Gossypium; Granuloma; Guinea Pigs; Histamine; History of Medicine; In Vitro Techniques; Inflammation; Irritants; Kaolin; Lung; Male; Prednisolone; Rats; Serotonin; Ultraviolet Rays; Vitamin K; Vitamin K 1