Pregnancy complicated by preeclampsia-eclampsia with the syndrome of hemolysis, elevated liver enzymes, and low platelet count: how rapid is postpartum recovery?

The rapidity of postpartum disease recovery for severe preeclampsia associated with hemolysis, elevated liver enzymes, and low platelet count (HELLP syndrome) has not been well studied. Between January 1980 and March 1989, 158 pregnancies with preeclampsia-eclampsia complicated by HELLP syndrome were managed at the University of Mississippi Medical Center. The 70 patients with platelet nadir below 50,000/microL (class 1 HELLP syndrome) required as long as 11 days for all members to achieve a platelet recovery concentration of more than 100,000/microL, whereas all 88 gravidas with platelet nadir between 50,000-100,000/microL (class 2 HELLP syndrome) exceeded this platelet concentration by the sixth postpartum day, a statistically significant difference (P less than .0001). The interval between delivery and the onset of diuresis (mean +/- SD) was significantly longer in class 1 than in class 2 patients with milder disease (22.7 +/- 18.9 compared with 15.9 +/- 11.1 hours). Significantly more postpartum days were required in class 1 than in class 2 HELLP parturients for the lactic dehydrogenase (LDH) concentration to decrease below 500 IU/L (4.2 +/- 4.9 compared with 3.2 +/- 2.7 days). No women in the class 2 group required plasma exchange therapy to effect disease arrest and reversal, but 11 of 58 severely ill women in class 1 were treated with this modality. We conclude that the platelet count and LDH serum concentration, as indicators of HELLP severity and recovery, are clinically useful tools and that a more protracted postpartum recovery period should be expected for progressively severe expressions of HELLP syndrome.

A new long-acting injectable microcapsule system for the administration of progesterone.

A long-acting injectable microcapsule system for the controlled-release systemic administration of progesterone (P4) is described. The system consists of microcapsules made of the biodegradable polymer, d,l-polylactic acid, which contain crystalline P4. Following injection, P4 is released from the microcapsules by diffusion and biodegradation of the polymer matrix. The rate of P4 release from the prototype microcapsule system in vivo is 1.3 microgram of P4/day/mg of microcapsules, and the duration of release is 30 days. Vaginal estrous cycles in rats and cyclic ovarian function in baboons were inhibited for 1 month following a single injection of P4 microcapsules. The effects of continuous progesterone therapy on reproductive function in both rats and baboons are dose-dependent. The utility of the system as a once-a-month injectable contraceptive is established in the baboon model.

PIP: A longacting injectable microcapsule system for the controlled-release systemic administration of progesterone is described and photographed. The microcapsules are made of biodegradable polymer which contain crystalline progesterone. After injection, the progesterone is released over time from the microcapsules by diffusion and biodegradation of the polymer matrix. Rats and baboons were used to evaluate the in vivo rates of progesterone release from different capsule preparations. Results are graphed and tabulated. Tests showed that 50% of the progesterone is available for quick release while the other 50% remains to be released at a slower rate. Smaller microcapsules released the progesterone at a greater rate and a shorter duration. By using larger microcapules, it should be possible to extend the useful duration of the microcapsule system. Vaginal estrus cycles in rats and cyclic ovarian function in baboons were inhibited for 1 month following injection of the progesterone microcapsules. This method of delivery has the advantages that it obviates cyclic overdosing and underdosing and it can be delivered both locally and systemically.

In vivo evaluation of cholesterol as a matrix for the controlled-release of progesterone.

Twelve adult, female baboons were used to test the rate and duration of progesterone (P4) release from cholesterol (C) pellets implanted subcutaneously. Four different preparations were tested (3 baboons per group). Each group was treated with pellets containing a different sized distribution and P4-cholesterol ratio (P4:C). Group 1 = 0.25--0.5 mm, 59% P4:41% C; Group 2 = 0.25--0.5 mm, 65% P4:35% C; Group 3 = 0.5 -1.0 mm, 59% P4:41% C; and Group 4 = 0.5 -1.0 mm, 65% P4:35% C. All baboons received the identical quantity of P4 (500 mg). Following treatment, blood samples were obtained at selected intervals, and the levels of progesterone were determined by radioimmunoassay. Serum-progesterone clearance curves were parallel for each experimental group. The rate of release of progesterone calculated from the serum clearance curves for groups 1--4 were: 42; 55; 29; and 38 mg P4/week. The mean duration of release for experimental groups 1--4 were 12, 9, 17, and 13 weeks respectively. The continuous progesterone treatment inhibited normal baboon ovarian function during the period of progesterone release.