For grade 4 neutropenia persisting for >7 days, a dose delay >2 weeks, grade 4 thrombocytopenia or an episode of thrombocytopenic bleeding, the dose was reduced by 20 mg m or one dose level.
For treatment of a bleeding episode, the dose was based upon subject's PK profile, WFH guidelines and local standard of care, with a minimum dose of 25 IU kg−1 rIX-FP.
If clotting was noticed (by vision) in the system or if there was a bleeding tendency, the dose was changed in steps of 500 units, according to the manufacturer's recommendations.
If a patient experienced significant toxicities (grade 3 or worse non-haematological toxicities, grade 4 neutropenia lasting ⩾7 days, grade 3 thrombocytopenia with bleeding, or grade 4 thrombocytopenia), the dose was reduced to that of the previous cycle and re-escalation of irinotecan was not allowed.
There was no difference in the incidences of renal or electrolyte abnormalities, gastrointestinal bleeding, IVH, and PVL when high dose was compared with the conventional one.
After adjustment for baseline characteristics, an excess dose was significantly associated with major bleeding (odds ratio, 1.43; 95% confidence interval [CI], 1.18-1.75) andeathth (odds ratio, 1.35; 95% CI, 1.03-1.77) compared with a recommended dose.
The same dose was repeated in case of persistent bleeding.
Menstrual bleeding pattern after using 1.5 mg levonorgestrel in a single dose was also examined [ 36].
The heparin dose was adapted at least once daily, according the aPTT value and clinical tolerance; it was stopped when bleeding occurred and restarted after bleeding was controlled.
However, no bleeding events related to heparin dose were identified.
