M. Egfjord et al., DOSE TITRATION STUDY OF TINZAPARIN, A LOW-MOLECULAR-WEIGHT HEPARIN, IN PATIENTS ON CHRONIC-HEMODIALYSIS, Artificial organs, 22(8), 1998, pp. 633-637
The minimal necessary dose of Innohep (IH) (MNDI) (Innohep [tinzaparin
], Leo Pharmaceutical Corp., Ballerup, Denmark) was examined in 40 pat
ients switched from conventional heparin ([CH], Leo Pharmaceutical Cor
p.) to IH and in 13 patients already treated with IH. Clotting in the
venous chamber and in the dialyzer was evaluated on a 4 point scale by
visual inspection. IH was administrated as a bolus injection into the
arterial side of the dialyzer at the beginning of dialysis sessions.
The initial dose of IH was 50% of the total dose of CH used before the
study (in respective IU). According to clotting in the venous chamber
or dialyzer, the dose of IH was titrated by stepwise changes of 500 I
U to the lowest possible dose until 3 subsequent dialysis sessions wit
hout clotting were obtained. The total dose of CH (bolus and infusion)
before switching was 6,162 +/- 2,100 IU. The bleeding time from the c
annulation site after dialysis, in 24 patients with A-V fistulas, was
7.1 +/- 2.8 min(triplicates). Eight patients were excluded before achi
eving the MNDI, 3 due to bleeding not clearly related to heparinizatio
n (1 due to gingival bleeding, 1 to epistaxis, and 1 to sugillations),
1 due to alopecia, 2 due to a need of more than 10,000 IU of IH, and
2 patients due to cessation of treatment resulting from anxiety. After
switching over, the MNDI amounted to 66 +/- 26% in respective IU. The
conversion IH/CH ratio correlated significantly to the blood flow rat
e and the type of dialyzer. When compared on 3 subsequent sessions bef
ore and after switching to IH, no differences were found in the bleedi
ng time after decannulation and in clotting in the venous chamber whil
e dialyzer clotting fell on the visual scale from an average of 0.36 t
o 0.19 (p < 0.01). No total clot formation was observed during the stu
dy. The MNDI correlated positively to the body weight, blood now rate,
and time on dialysis (with the respective coefficients of correlation
of r being 0.58, 0.44, and 0.30, p < 0.05) and was also influenced by
the type of dialyzer. The average MNDIs for the Hemoflow-FS hollow-fi
ber (Fresenius, Bad Homburg, Germany), Lundia PRO plate (Gambro, Lund,
Sweden), and Polyflux hollow fiber (Gambro) were 2,571, 3,727, and 5,
020 IU (p < 0.01, ANOVA). In patients on chronic hemodialysis, IH give
n as a bolus of 4,250 IU effectively prevented extracorporeal clotting
during dialysis, similarly to CH. However, a considerable individual
variation in MNDIs not related to the need for CH was observed, and th
is necessitates individual dosage adjustments to obtain the optimal pr
evention of clotting with minimal bleeding risk.