Showing papers by "Wulf Dietrich published in 2001"

Anaphylactic reactions to aprotinin reexposure in cardiac surgery: Relation to antiaprotinin immunoglobulin G and E antibodies

Abstract: Background: Aprotinin, a serine proteinase inhibitor, reduces bleeding during cardiac surgery. As aprotinin is derived from bovine lung, it has antigenic properties. This investigation examined the incidence of anaphylactic reactions in patients reexposed to aprotinin and the relation to preformed antiaprotinin immunoglobulin (Ig)G and IgE antibodies. Methods: This prospective observational study conducted at five centers in Germany evaluated patients undergoing repeat cardiac surgery reexposed to aprotinin between 1995 and 1996. Antiaprotinin IgG and IgE antibody measurements, using a noncommercial enzyme-linked immunosorbent assay and an immunofluorescence assay, respectively, were performed preoperatively and postoperatively. An anaphylactic reaction was defined as major changes from baseline within 10 min of aprotinin administration of systolic pressure 20% or greater, heart rate 20% or greater, inspiratory pressure greater than 5 cm H2O, or a skin reaction. Results: In 121 cases (71 adults, 46 children), a mean aprotinin reexposure interval of 1,654 days (range, 16 ‐7,136 days) was observed. Preoperative antiaprotinin IgG (optical density ratio > 3) and IgE antibodies (radioallergosorbent test [RAST] score 10; IgE, RAST score > 3) were detected in five patients. Three patients (2.5%; 95% confidence interval, 0.51‐7.1%) experienced an anaphylactic reaction after aprotinin exposure, followed by full recovery; these patients had reexposure intervals less than 6 months (22, 25, and 25 days) and the highest preoperative IgG concentrations of all patients (P < 0.05). Assay sensitivity was 100%, as no anaphylactic reactions occurred in IgG-negative patients (95% confidence interval, 0.0 ‐3.1%); assay specificity was 98%. Preoperative IgE measurements were quantifiable in two of three reactive patients and in three nonreacting patients. Conclusions: Quantitative detection of antiaprotinin IgE and IgG lacks specificity for predictive purposes; however, quantitation of antiaprotinin IgG may identify patients at risk for developing an anaphylactic reaction to aprotinin reexposure. APROTININ (Trasylol, Bayer Vital, Leverkusen, Germany) reduces perioperative bleeding during cardiac surgery. 1,2 A polypeptide (58 amino acids; 6.5 kd) 3 serine proteinase inhibitor, aprotinin is thought to reduce bleeding through inhibiting the contact phase activation of hemostasis, preventing fibrinolysis, 4 and reducing thrombin generation. 5

Low preoperative antithrombin activity causes reduced response to heparin in adult but not in infant cardiac-surgical patients.

Abstract: We evaluated the interaction of preoperative antithrombin (AT) activity and intraoperative response to heparin in cardiac surgery. Heparin anticoagulation is essential during cardiopulmonary bypass (CPB). Heparin itself has no anticoagulant properties, however it causes a conformational change of the physiologic plasma inhibitor AT that converts this slow-acting serine protease inhibitor into a fast acting one. Thus, adequate AT activity is a prerequisite for sufficient heparin anticoagulation. AT activity is reduced by longterm heparin therapy. This prospective, observational study investigated 1516 consecutive cardiac-surgical patients (1304 patients >1 yr (Group A) and 212 patients ≤1 yr (Group I)). AT activity was measured the day before surgery by a chromogenic substrate assay. The celite-activated activated clotting time (ACT) was used to guide intraoperative heparin administration. Heparin sensitivity was calculated and the postoperative blood loss and perioperative blood requirement was recorded. Infant patients had significantly less pre-operative AT activity compared with older patients: 84 (33)% vs 97 (17)%, median (interquartile range) (P < 0.05). The subgroup of patients aged <1 mo (n = 64) demonstrated a preoperative AT activity of 56 (27)% as compared with 90 (23)% in infant patients between one month and one year (n = 148). In adult patients, preoperative AT activity depended predominantly on preoperative heparin treatment: 62% of the patients with an AT activity <80% were pretreated with heparin. Five minutes after heparin but before CPB the ACT was 587 (334) s in Group A patients with AT activity ≥80%, and 516 (232) in patients with AT activity ≤80% (P < 0.05). The target ACT of 480 s was achieved in 70% of patients with normal AT activity in Group A compared with only 54% of patients with AT activity <80% (P < 0.05). In Group A patients with decreased AT activity, 18% demonstrated an inadequate ACT response-defined as ACT <400 s-to the first bolus injection of heparin. In Group I, preoperative AT activity did not influence the ACT response (ACT 5 min after heparin: 846 [447] s in patients with AT activity ≥80% vs 1000 [364] s in patients with decreased AT activity). The heparin sensitivity was 2.4 (1.1) s/unit heparin/kg compared with 1.5 (0.8) s/unit heparin/KG in group A (P < 0.05). These results suggest that preoperative diminished AT activity causes reduced response to heparin in adult but not in infant patients. Infant patients demonstrate a higher heparin sensitivity despite lower preoperative AT activity. Measurement of preoperative AT activity identifies adult patients at risk of reduced sensitivity to heparin.