The effects of reformulated 2-rod Norplant implant on hemostasis after three years.

ABSTRACT

Prolonged use of reformulated and the original 2-rod Norplant implants showed similar changes in most hemostatic parameters studied. Raised hemoglobin concentration and hematocrit values with not enhanced platelet activation or significant changes in platelet numbers were seen. Factor VII showed an increase from 18 months compared to the first 12 months of original Norplant implant use, while with reformulated Norplant implant, the level at 36 months was significantly higher than the first 24 months of implant use. Fibrinogen levels were significantly elevated by 36 months of both implant use. No evidence of enhanced activation of coagulation, fibrinolysis/inhibitor were observed during prolonged implant use. Overall, no significant changes in tissue plasminogen activator (t-PA) levels were observed but urokinase-like plasminogen activator (u-PA) levels were significantly reduced, indicating no enhancement of tissue breakdown. Plasminogen activation inhibitor (PAI-1) antigen levels were significantly reduced from 12 to 36 months with original Norplant implant use compared to the pre-insertion levels, while a nonsignificant decreased trend was seen with prolonged reformulated Norplant implant use. The increased levels of fibrinogen and FVII at the end of 36 months of implant use require further observation as these factors are known markers of hypercoagulation and associated with increased arteriosclerotic and cardiovascular risks. This study is on-going to evaluate the effects of levonorgestrel-containing subdermal reformulated Norplant implants on hemostasis after five years of use.

ABSTRACT

PIP Researchers compared data on women using the 2-rod Norplant implant system formulated with the Silastic elastomer 4092 (original system) with those using the 2-rod Norplant made with a different elastomer (Q74910) (reformulated system) to examine their hemostatic effects during 36 months of use. All 33 women lived in Singapore. Both systems released the same amount of levonorgestrel at the same rate. In most hemostatic parameters, prolonged use of both 2-rod Norplant implant systems effected similar changes increased hemoglobin concentration and hematocrit values, increased fibrinogen levels, no increased platelet activation, no increased activation of coagulation or fibrinolysis/inhibitor, no significant changes in platelet numbers, no significant changes in tissue plasminogen activator, and decreased urokinase-like plasminogen activator. Factor VII was higher after 18 months than it was during the first 12 months in original Norplant users (p 0.001). The factor VII level at 36 months during reformulated Norplant use was significantly higher than it was during the first 24 months of use (p 0.001). None of the changes common to both systems suggested tissue breakdown. Plasminogen activator inhibitor antigen levels were significantly lower during 12-36 months than preinsertion levels in original Norplant users, while they fell insignificantly in reformulated Norplant users. The increased levels of fibrinogen and factor VII at 36 months are areas of concern since they are markers of hypercoagulation and are linked to increased arteriosclerotic and cardiovascular risks. Researchers of this on-going study will later publish the two systems' effects on hemostasis after 5 years of use.