| Abstract: | BACKGROUND: Circadian variations have been described for a number of haemostaticand physiological factors, all of which might predispose towardsclotting in the late morning. The anticoagulation effect ofheparin has been shown to respond in a circadian manner, resultingin minimal prolongation of the activated partial thromboplastintime (aPTT) in the morning. METHODS: Recombinant hirudin (HBW 023) given as a bolus of 0.07, 0.1,0.2 or 0.4 mg.kg–1 followed by an infusion of 0.05, 0.06,0.1 or 0.15 mg. kg–1 over 48 h was used as conjunctivetherapy to thrombolysis with frontloaded recombinant tissue-typeplasminogen activator (100 mg . 90 min–1) in 40 patientswith acute myocardial infarction. APTT, activated clotting timeand free hirudin plasma levels were determined at baseline andat 8, 12, 16, 20, 24, 32, 40 and 48 h. RESULTS: The prolongation of aPTT and activated clotting time was dose-dependentand stable. In 82.5% of the patients, aPTT values were rangedbetween the highest and the lowest aPTT of <30 s. When theresults were divided into four time intervals (0000–0600,0600–1200, 1200–1800, 1800–2400) neither inthe individual patients nor in the mean values of the four differentdose groups was any significant circadian variation in aPTTor activated clotting time prolongation observed. The pharmacokineticstudies of free hirudin plasma levels revealed no circadianrhythm either. All but one patient (97.5%) had a patent vessel(TIMI grade 2/3) at the end of the hirudin infusion. CONCLUSIONS: Recombinant hirudin, in contrast to heparin, does not show anycircadian variation in its anticoagulation effect. This might,in part, explain the more stable and predictable anticoagulationachieved by hirudin, which is associated with a reduced rateof reocclusions after thrombolysis. |
