Increased factor IX levels in puerperium during administration of diethylstilboestrol.

Abstract

Iron Absorption in Liver Disease-Brown et al. BRITIH 801The high absorption in lupoid hepatitis is interesting in that R. Williams (personal communication, 1965) has also found a high iron absorption in this condition; that this is not due to accompanying pancreatic damage is suggested by the finding that neither of these two patients showed a diminished iron absorption when the test was repeated with the addition of pancreatin. A third patient with infectious hepatitis also showed no change in absorption with the addition of pancreatin.The condition produced in rats by et-naphthyl isothiocyanate has been described as " experimental cirrhosis." It is a chemical damage characterized by massive proliferation of biliary epithelial cells, which occurs not only to areas recovering from coagulative necrosis of the parenchyma but also independently (Steiner and Carruthers, 1963 The administration of diethylstilboestrol for the suppression of lactation has been reported to increase the incidence of puerperal thromboembolism (Daniel et al., 1967). Though a relation between increased levels of coagulation factors in blood and thromboembolic disease has not been firmly established in vivo, there is evidence that the activity of factors IX, XI, and XII is essential for the development of thrombus in the ligated veins of experimental animals (Wessler and Reimer, 1960). The present paper describes the results of a study of factor IX levels in the plasma of puerperal women and reports the new observation that diethylstilboestrol administration causes a highly significant increase in factor IX level. MethodAll patients investigated had a normal labour and puerperium. There were no thromboembolic episodes. One group was lactating; in the second group lactation was suppressed without the use of oestrogens, diuretics, or changes in fluid intake-" natural suppression "; and in the third group lactation was suppressed by the administration of diethylstilboestrol (10 mg. t.i.d. for three days; 10 mg. b.d. for three days; and 10 mg. daily for three days)-" stilboestrol suppression." Treatment was begun on the first day of the puerperium, the first dose of diethylstilboestrol being given at 6 a.m. each day.At 8 a.m. 4.5 ml. of venous blood was obtained without stasis and added to 0.5 ml. of 3.8% sodium citrate. Factor IX was assayed "blind "-that is, without knowledge of the group to which the patient belonged. The technique used was a standard one-stage method similar to that described by Hardisty and Ingram (1964), utilizing a kaolin-activated system consisting of stored (-20' C.) plasma from a patient with severe factor IX deficiency, adsorbed fresh normal plasma to supply factors VIII and V, and phospholipid. The mean value in non-pregnant adults was 100%, with a normal range of 50 to 150%.

Plasma factor IX levels in patients given hexoestrol or stilboestrol to suppress lactation

“…The average factor IX level on the first puerperal day, before initiation of treatment, was a little higher in the stilboestrol group of patients, but the variation in this group was greater than in the other two groups and the group In lactating women we found a transient rise in mean plasma factor IX levels from the already raised levels of late pregnancy on the third puerperal day only. This agrees with the results of Daniel et al (1968). We have shown that after a single 45-mg. injection of hexoestrol factor IX levels are significantly increased over those in control patients until the fourth day.…”

“…We have shown that after a single 45-mg. injection of hexoestrol factor IX levels are significantly increased over those in control patients until the fourth day. Although the 90-mg. course of oral stilboestrol administered over a six-day period which we employed was only half the dose given by Daniel et al (1968), significantlv raised plasma factor It levels were still present until after the eighth day of the puerperium.…”

“…Daniel et al (1968) suggested that very high levels of plasma factor IX may be related to the development of puerperal venous thrombosis. It would appear reasonable to avoid the use of therapeutic agents which give rise to excessive or prolonged increases in factor IX levels during the puerperiuim.…”

“…Vernier, V. G. (1961) Plasma Factor IX Levels in Patients Given Hexoestrol or Stilboestrol to Suppress Lactation Introduction Oral administration of stilboestrol for the suppression of lactation has been reported to be associated with an increased incidence of thromboembolic episodes in the puerperium (Daniel et al, 1967). Stilboestrol administration is also known to cause an increase in the level of plasma factor IX in puerperal women (Daniel et al, 1968).…”

Progesterone oral contraception and blood coagulation.

“…There is also believed to be an increased thrombotic tendency in women whose lactation is suppressed by oestrogens (Daniel et al, 1968). Whether the action of oestrogens in haemostasis is due to an effect on blood-clotting factors, on blood platelets, or on the blood vessel wall is not certain (Ulutin, 1969).…”