WHAT IS THE OPTIMAL DOSAGE OF LMW HEPARIN IN THE SC TREATMENT OF DEEP VENOUS THROMBOSIS

LMW heparin (LMWH) is better suited for subcutaneous (sc) administration than is UF heparin due to higher bioavailability and slower elimination. Optimal dosage for sc treatment of DVT has not been defined. Our previous study suggested that LMWH should be given in doses according to bodyweight (bw), and that sc injection of 100 anti-Xa U/kg bw/12 hrs might result in therapeutic plasma levels (Holm et al. Haemostasis 16, supl 2,30-37, 1986). This dosage is now being evaluated in an open study including patients with venographically proven DVT. Excluded were patients with pulmonary embolism, thrombosis in the IIiacal vein and females beyond 70 yrs of age. LMWH (Fragmin) is administered sc for at least 5 days. Venography is repeated the last day of treatment and evaluated blindly (Marder score). Compared to the previous study in which doses were given according to age and sex, the present protocol results in more uniform and predictable heparin plasma concentrations : Peak concentration day 2 now ranged 0.40-0.75 U/ml (mean 0.58) (n = ll) as compared to the three-fold wider range (0.261.20 U/ml)(mean 0.57)(n = 29) in the previous study. The 12 hrs plasma heparin profile was determined on day 3. Peak concentrations in the 0.44-0.72 U/ml range were found 2.5-4 hrs after injection. The plasma heparin activity was subtherapeutic (< 0.2 U/ml) the last 3-6 hrs of the 12 hrs period. The heparin activity at the next injection averaged 0.05 U/ml (range 0-0.ll). Day to day variation of peak heparin activity in the individual patient, expressed as CV, ranged 11-22% and there was no heparin accumulation.

Conclusions: SC treatment of DVT with LMWH 100 anti-Xa U/kg bw/12 hrs results in peak plasma heparin activity in the 0.40-0.75 U/ml range. The plasma heparin activity was below therapeutic level 3-6 hrs of the 12 hrs period indicating that a larger dose (250 U/kg bw/ 24 hrs divided into 2 or perhaps 3 injections) is preferable.