Smith R E, Townsend G E, Berry B R, Bowen T
Royal Jubilee Hospital, Victoria, British Columbia, Canada.
Ann Pharmacother. 1996 May;30(5):476-80. doi: 10.1177/106002809603000508.
To describe a patient who presented with heparin allergy and required alternate anticoagulation for unstable angina and coronary artery bypass surgery. To review therapeutic alternatives to porcine heparin for patients with hypersensitivity or intolerance to standard heparin anticoagulation.
A 74-year-old man with a 15-year-old coronary artery bypass graft presented to the emergency room with unstable angina and was scheduled for urgent coronary artery revascularization. A bolus dose of porcine heparin was administered followed by a continuous infusion. Shortly afterward the patient developed a type I allergic reaction to the porcine heparin that was confirmed by rechallenge. Three alternatives to porcine heparin were tried, including bovine lung heparin, low-molecular-weight heparin (enoxaparin), and ancrod. The patient was found to be cross-sensitive to bovine lung heparin, but tolerated enoxaparin for unstable angina without cross-sensitivity. Anticoagulation for cardiopulmonary bypass was achieved with an infusion of ancrod that was later reversed with cryoprecipitate. The patient was discharged postoperatively on day 5 without the complication of excessive bleeding.
Type I allergic reaction to unfractionated heparin is a rare occurrence and could be the result of a variety of factors. Possible causes for the reaction include a porcine protein, a preservative contained in the heparin solution, or a hapten formed between heparin and a plasma protein. We considered four alternatives to heparin anticoagulation: rush desensitization, bovine lung heparin, low-molecular-weight heparin, and ancrod. The patient was cross-sensitive to bovine lung heparin, but was able to tolerate low-molecular-weight heparin (enoxaparin). This was unexpected because enoxaparin is derived from unfractionated porcine heparin. Testing for cross-sensitivity had no value in this case, as two negative subcutaneous test doses were followed by dramatic reactions when the drugs were given intravenously. Although enoxaparin has been used for anticoagulation during bypass surgery, there is more experience with ancrod as an alternative to heparin. Repeat bypass surgery, which normally results in above-average blood loss, was successfully performed with a very low fibrinogen concentration (< 0.15 g/L) during ancrod anticoagulation.
We conclude that ancrod was a safe and effective alternative to heparin for coronary artery bypass surgery in this patient in whom a heparin product had caused a hypersensitivity reaction. We discovered on two occasions that a negative subcutaneous test dose for heparin allergy did not predict a severe type I allergic reaction when the heparin was later administered intravenously. Furthermore, we found that a low-molecular-weight heparin administered subcutaneously for a short period of time did not cause cross-sensitivity in a patient with a type I allergy to unfractionated heparin.
描述一名出现肝素过敏且因不稳定型心绞痛和冠状动脉搭桥手术需要替代抗凝治疗的患者。回顾对于对标准肝素抗凝治疗过敏或不耐受的患者,猪源性肝素的治疗替代方案。
一名有15年冠状动脉搭桥史的74岁男性因不稳定型心绞痛就诊于急诊室,并计划接受紧急冠状动脉血运重建术。给予一剂猪源性肝素推注,随后持续输注。不久后,患者对猪源性肝素发生I型过敏反应,再次用药证实了这一点。尝试了三种猪源性肝素的替代药物,包括牛肺肝素、低分子量肝素(依诺肝素)和抗栓酶。发现该患者对牛肺肝素交叉敏感,但对不稳定型心绞痛能耐受依诺肝素且无交叉敏感反应。体外循环时通过输注抗栓酶进行抗凝,随后用冷沉淀物逆转。患者术后第5天出院,无出血过多的并发症。
对普通肝素的I型过敏反应罕见,可能由多种因素导致。反应的可能原因包括猪蛋白、肝素溶液中的防腐剂或肝素与血浆蛋白形成的半抗原。我们考虑了肝素抗凝的四种替代方案:快速脱敏、牛肺肝素、低分子量肝素和抗栓酶。该患者对牛肺肝素交叉敏感,但能耐受低分子量肝素(依诺肝素)。这出乎意料,因为依诺肝素是从普通猪源性肝素衍生而来。在这种情况下,交叉敏感性检测没有价值,因为两次皮下试验剂量为阴性后,静脉给药时出现了剧烈反应。虽然依诺肝素已用于搭桥手术期间的抗凝,但抗栓酶作为肝素的替代药物有更多经验。在抗栓酶抗凝期间,纤维蛋白原浓度非常低(<0.15g/L)的情况下,成功进行了通常导致失血高于平均水平的再次搭桥手术。
我们得出结论,对于该因肝素产品引起过敏反应的患者,抗栓酶是冠状动脉搭桥手术中肝素的安全有效替代药物。我们两次发现,肝素过敏皮下试验剂量为阴性并不能预测随后静脉注射肝素时会发生严重的I型过敏反应。此外,我们发现,对于对普通肝素I型过敏的患者,短期皮下注射低分子量肝素不会引起交叉敏感反应。