Cor Vasa 2006, 48(6):218-225 | DOI: 10.33678/cor.2006.067

Changes in coagulation after single i.v. bolus 0.75 mg per kg of the low molecular weight heparin enoxaparin during PCI-a pharmacokinetic study

Jan Kvasnička^1,*, Jan Horák², Tomáš Kvasnička³, Jana Bílková¹, Jiří Humhal², Stanislav Šimek², Tomáš Kovárník², Iva Malíková¹, Jan Bohuslávek⁴, Michael Aschermann²

¹ Trombotické centrum

² II. interní klinika

³ III. interní klinika, Všeobecná fakultní nemocnice a 1. lékařská fakulta Univerzity Karlovy

⁴ Anesteziologicko-resuscitační oddělení, Nemocnice Na Homolce, Praha, Česká republika

Goal and methods:
The clinical efficacy of unstable angina treatment with enoxaparin has been well established, but its indication for optimal anticoagulant treatment in percutaneous coronary intervention (PCI) remains uncertain. The objectives of our observational study were to investigate changes in coagulation tests (APTT, thrombin time [TT], inhibition of F Xa and F IIa and prothrombin fragments F 1 + 2 level) and bleeding complications (according to TIMI criteria) after single i.v. bolus administration of 0.75 mg/kg of enoxaparin to a group of 30 patients during urgent or elective PCI. Additional treatment consisted of only aspirin (100-300 mg) and clopidogrel (loading dose of 300 mg). Arterial blood samples were taken prior to enoxaparin administration (baseline) and 20 minutes, 1 hour, and 6 hours after enoxaparin administration.

Results:
The i.v. bolus of enoxaparin induced an increase in the inhibition of F Xa (1.07 - 0.31 IU/ml, baseline 0.05 - 0.06 IU/ml; p < 0.001) and in the inhibition of F IIa (0.60 - 0.45 IU/ml, baseline 0.28 - 0.14 IU/ml; p < 0.001) at 20 minutes, which continued for 1 hour (anti F Xa 0.91 - 0.34 IU/ml, anti F IIa 0.69 - 0.93 IU/ml; both p < 0,001). The tests were de-creased at baseline levels after 6 hours (anti F Xa 0.10 - 0.12 IU/ml, anti F IIa 0.27 - 0.06 IU/ml). After 20 minutes, we also observed > twofold prolongation of APTT (98.0 - 39.8 s, baseline 32.9 - 4.6 s; p < 0.001) and TT (99.7 - 64.2 s, baseline 15.4 - 2.9 s; p < 0.001), which continued for 1 hour (APTT 87.0 - 39.7 s, TT 75.3 - 61.8 s; both p < 0.001) and returned to baseline after 6 hours (APTT 34.8 - 6.6 s, TT 15.3 - 2.9 s). APTT correlated well with inhibition of F Xa in all periods after the i.v. bolus of enoxaparin, especially at 6 hours (r = 0.58; p < 0.001). Prior the enoxaparin treatment, the levels of F 1 + 2 were increased at baseline (1.21 - 0.36 nmol/l, healthy controls 0.70 - 0.36 nmol/l; p < 0.001). After the i.v. bolus of enoxaparin, the levels of F 1 + 2 were decreased at 20 minutes and at 1 hour (1.07 - 0.43 nmol/l and 1.15 - 0.40 nmol/l, respectively; both p < 0.001) and remained so even after 6 hours (1.04 - 0.33 nmol/l; p < 0.001). No significant bleeding was observed over a period of 6 hours.

Conclusion:
Target anti F Xa levels for PCI (> 0.6 IU/ml) were obtained in 93.3% of patients. No serious bleeding and no rebound phenomenon (increase in F 1 + 2) were observed during a period of 6 hours after a single i.v. dose of 0.75 mg/kg enoxaparin.

Keywords: Enoxaparin; Intravenous bolus; PCI; Coagulation; Pharmacokinetics

Published: June 1, 2006  Show citation