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ON-LINE MONITORING OF ECARIN CLOTTING TIME DURING CPB WITH HIRUDIN DUE TO HIT II

Koster, A. MD; Kuppe, H. MD, PhD; Hetzer, R. MD, PhD; Sodian, R. MD; Mertzlufft, F. MD, PhD

doi: 10.1097/00000539-199802001-00075
Abstracts of Posters Presented at the International Anesthesia Research Society; 72nd Clinical and Scientific Congress; Orlando, FL; March 7-11, 1998: Cardiovascular Anesthesia
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Institut fur Anaesthesie (Koster, Kuppe), Abteilung fur Herz-, Thorax- und Gefaesschirurgie (Hetzer, Sodian), Deutsches Herzzentrum Berlin, D-13353 Berlin; Klinik fuer Anaesthesiologie und Intensivmedizin der Universitaetskliniken des Saarlandes (Mertzlufft), D-66421 Homburg, FRG.

Abstract S75

THE PROBLEM: HIT and CPB: Heparin-induced thrombocytopenia (HIT) is an uncommon cause of arterial thrombosis (1.7% after bovine heparin administration and 0.3% after porcine heparin [1]), including lower-limb ischemia, stroke, coronary occlusion, mesenteric or skin infarctions, and venous thromboembolism. The syndrome is thought to be immunogeneic in origin, involving formation of complement-mediated, heparin-dependent IgG antiplatelet antibody. In the absence of heparin, the antibody cannot interact with platelet membranes. Therefore, therapy requires that any heparin administration be stopped. However, performing cardiac surgery with cardiopulmonary bypass (CPB) requires anticoagulation, thus causing significant difficulties in the management of patients with HIT.

PAST ALTERNATIVES: Patients with HIT requiring CPB have been alternatively managed by use of antiplatelet agents, fibrinolytics, heparinoids, and low-molecular-weight heparins (LMW). Among these, the heparinoid ORGARAN (a mixture of dermatan, heparan, and chondroitin sulfate with LMWs) was considered standard. However, relevant drawbacks may preclude it for CPB: (1) Platelet aggregation is not always eliminated, (2) neither protamine nor fresh-frozen plasma (FFP) antagonize its anticoagulant properties, (3) elimination half-life is quite long, (4) a 10% risk of imuunogeneic cross reactions must be anticipated. In addition, its anti-Xa activity, though correlating linearly with ACT in non CPB ranges (120 - 220 sec), cannot be adequately monitored.

ACTUAL SITUATION: HIRUDIN (a small 65-unit amino acid peptide) is a highly specific inhibitor of thrombin and has little effect on other serine proteases. It is considered superior to Orgaran due to its lack of cross reactions, its elimination half-life (60 min), its volume of distribution (9 - 17 L), its clearance (170 - 2,230 mL/min), and its short anticoagulant effect (about 40 min) [2]. However, monitoring anticoagulation with HIRUDIN comprises relevant problems: (1) aPTT and ACT, in general, are less sensitive to hirudin than to heparin, (2) neither aPTT nor ACT are suitable for Hirudin concentrations required for CPB, (3) monitoring of the ecarin clotting time (ECT) - the appropriate measure during CPB - has not been adequately available, i.e. at the point of patient's care.

FUTURE PERSPECTIVES (CASE REPORT): With the availability of a new point-of-care device (TAS Analyzer, Cardiovascular Diagnostics Inc., Raleigh, NC, USA) providing on-line measurement of ECT, aPTT, PT, INR, and HMT [3], five patients suffering from HIT II and urgently requiring CPB (CABG: n = 3; AVG: n = 2) have been safely managed applying both r-HIRUDIN and the TAS ECT monitoring. Hirudin administration consisted of a 0.25 mg/kgBW bolus, 0.2 mg/kgBW within the priming volume, and continuous infusion via perfusor pump of 0.5 mg/kgBW (modified according to [4]); additionally, aprotinin was administered according to the Hammersmith regimen. Anticoagulation was monitored by the TAS point-of-care ECT allowing to maintain ECT in the range of 400 - 600 sec. The time required for exracorporeal circulation (ECC) ranged from 100 - 113 min (mean). Allogeneic transfusion requirements were not increased. However, FFP requirements presented to be augmented (4 units/ patient on average), presumably due to an increased consumption of procoagulants at the surfaces of the ECC-systems. All 5 patients did well, and there were no clots in the CPB systems as analyzed postoperatively.

CONCLUSIONS: CPB in patients with HIT requiring HIRUDIN appears to be safely manageable using the new TAS on-line ECT monitoring. However, though the measurement proved easy and safe, ECT values of >or=to 600 sec caused elapse phenomenons (cf. [3]) requiring further evaluation.

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REFERENCES

1. Warkentin TE, Kelton JG: Hemat Oncol Clin NA 1990; 4:243.
2. Bichler J et al.: Arzneimittelforschung 1988; 38:707.
3. Mertzlufft F, Risch A, Seyfert UT: Anaesthesist 1997; 46:233.
4. K. Madlener et al.: Thromb Haemost 1997; 77:920.
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