Two studies have been done to establish recommendations for dosage and dose adjustment in the treatment of deep vein thrombosis (DVT) with low molecular weight heparin (LMWH). In the first, 56 patients were randomized in a double blind study to be treated either with unfractionated heparin (UFH) or LMWH s.c. every 12 h. Initial doses were given according to age and sex, disregarding bodyweight, and the dose was then adjusted when the peak plasma heparin concentration fell outside the desired range of 0.5-0.8 anti-FXa U/ml. There were fewer dose adjustments in the LMWH group. The correlation between injected dose (U/kg bodyweight) and the heparin concentration was higher in the LMWH group (r = 0.59) than in the UFH group (r = 0.38). The results suggest that, in order to obtain the desired heparin concentration, the initial dose of LMWH should be about 100 U/kg bodyweight every 12 h. In the second, open study, this dosage plan was followed in 15 patients. The peak heparin concentration on Day 2 ranged from 0.40 to 0.75 anti-FXa U/ml and adjustment was only required in 3 patients. Day to day variation in peak heparin activity in the individual patient varied little (CV 11-22%), and there was no accumulation. The results indicate that plasma heparin concentration is more predictable using LMWH than UFH, and they point to definite advantages in the use of LMWH in a bodyweight adjusted dosage.

In a double-blind study, patients with phlebographically proven deep venous thrombosis (DVT) were treated with subcutanous injections twice a day of either unfractionated heparin (UH; n = 27) or low molecular weight heparin (LH; n = 29) for 7 days, and the dose was adjusted until therapeutic range was reached, according to a chromogenic substrate anti-Xa assay. Forty-eight percent of the LH group did not need dose adjustment as compared to 24% of the UH group. During the course of heparin administration, deviation from initial heparin activity was frequent in both groups, but mean activity did not indicate a cumulative effect in either group. There was 1 incidence of pulmonary embolism (LH) and only 1 minor bleeding episode (UH). Half of the patients in both groups were phlebographically improved. We conclude that subcutaneous heparin treatment with UH or LH appears safe and convenient.

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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.

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