Warfarin anticoagulation and pregnancy.
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Biomedical subjects
Publications and source records attributed to J Bonnar.
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The coagulation and fibrinolytic mechanisms were investigated in a group of patients with severe pre-eclampsia and eclampsia and the findings were compared with those of healthy women in late pregnancy. In patients with pre-eclampsia the following significant differences were found: (1) greater depression of plasma fibrinolytic activity (euglobulin lysis time) than in normal pregnancy, (2) a higher level of inhibitor to urokinaseinduced lysis, (3) increased levels of serum fibrin degradation products, and (4) reduced platelet counts.In patients with eclampsia a progressive increase of the level of serum fibrin degradation products was found over the three days following eclamptic seizures. No such increase occurred after grand mal seizures in late pregnancy. The findings in this study support the view that intravascular clotting is taking place in pre-eclampsia and that this disturbance of the balance between coagulation and fibrinolysis may be localized to certain areas of the vascular compartment, particularly the placental and renal circulations. Fibrin deposition in the maternal vessels supplying the placenta would impair the placental blood flow, which may explain the placental insufficiency which occurs in pre-eclampsia. Likewise fibrin deposition in the renal vasculature will result in glomerular damage and proteinuria. Hypertension may be related to the renal ischaemic changes or a compensatory response to the presence of fibrin deposition in the vascular compartment. This evidence of intravascular fibrin deposition raises the question of the possible therapeutic value of antithrombotic agents to inhibit the clotting process. On a theoretical basis such treatment might be expected to improve blood flow to the placenta and thereby fetal growth.
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The haemostatic mechanism in the uterus during parturition was investigated in 12 patients being delivered by caesarean section. Detailed sequential study of the blood coagulation and fibrinolytic systems in the uterine circulation showed that placental separation is accompanied by a striking local activation of the clotting mechanism. Uterine vein blood draining the placental site while the placenta was separating showed a pronounced shortening of the whole-blood clotting-time, a significant shortening of other clotting-tests, and a sharp increase in factor VIII activity, though these changes were transitory. After delivery the level of fibrinogen and circulating platelets steadily increased and factor VIII activity remained high.Activation of the clotting mechanism during placental separation appears to play an essential part in controlling uterine haemorrhage. The subsequent changes in the haemostatic mechanism in the puerperium are likely to predispose to thromboembolic complications.
A detailed sequential study of the coagulation and fibrinolytic systems in 15 healthy women during normal childbirth showed that striking changes in keeping with activation of the clotting mechanism take place during and after placental separation. Shortening of the clotting-test results, a sharp increase of factors VIII and V, and a decrease of the plasma fibrinogen were found as the placenta separated. Within one hour of normal delivery the levels of fibrin/fibrinogen degradation products increased and fibrinolytic activity returned to normal non-pregnant levels. In the early puerperium a secondary increase took place in the plasma fibrinogen level, factor VIII remained raised, and the platelet count showed a pronounced rise; these changes may explain the increased predisposition to thromboembolic complications in the puerperium.
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The effect of pregnancy on the components of the fibrinolytic enzyme system was determined by serial observations on 10 healthy women during normal pregnancy, labour, and the puerperium. The plasminogen level was substantially increased in the third trimester; the increase occurred pari passu with a pronounced increase in fibrinogen concentration. After allowing for the expansion of plasma volume in pregnancy a twofold increase in the absolute amounts of circulating fibrinogen and plasminogen was found. In late pregnancy and during labour the level of plasminogen activator was greatly decreased, whereas a normal or increased level was present in the first week of the puerperium. No alteration in the levels of inhibitors of plasminogen activation by urokinase was found during normal pregnancy. The thrombin time and platelet count remained unchanged during pregnancy and labour but the platelet count rose significantly during the first week of the puerperium.The haemostatic mechanism in pregnancy appears to be altered towards an enhanced capacity to form fibrin and a diminished ability to lyse fibrin. These changes may be a physiological development to ensure the integrity of the foetal and maternal circulations and provide rapid and effective haemostasis in the uterus during and after placental separation. Nevertheless, the changes may also establish a vulnerable state for intravascular fibrin deposition.
The levels of fibrin, fibrinogen degradation products (F.D.P.) in the serum were investigated in normal pregnancy and parturition, after caesarean section, and in patients with abruptio placentae, eclampsia, intrauterine death, and post-partum haemorrhage. No significant change occurred during normal pregnancy, but a highly significant increase was found during labour and again during the first week after normal delivery. After caesarean section the levels of F.D.P. were increased two to four hours after operation, and substantially higher levels were found three to eight days after operation than after normal delivery. High levels of F.D.P. were associated with abruptio placentae and eclampsia, and increased levels after intrauterine death and post-partum haemorrhage.An excess of F.D.P. with diminished or normal systemic fibrinolytic activity suggests that local intravascular fibrin deposition and fibrinolysis occur in normal parturition and in these complications of pregnancy. The very high levels of F.D.P. found in abruptio placentae will be important in the pathogenesis of the defective haemostasis that may accompany this complication.
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An ultrastructural study has been made of villi adjacent to decidual spiral arteries exhibiting varying degrees of luminal occlusion in placentae from cases of intrauterine growth retardation. Partially occluded spiral arteries are associated with placental villous syncytiotrophoblast exhibiting extensive budding of surface microvilli, vacuolation of the cytoplasm, clumping of nuclear chromatin and a thickening of the underlying basement membrane. Marked degeneration of the syncytium is present in association with severely occluded spiral arteries. In contrast, the capillary endothelium of the villus retains a normal structure despite degenerative changes in villous Langhan's and stromal cells. The most extensive pathological changes in the placental villi are found distal to completely occluded spiral arteries and consist of complete necrosis of the syncytium and underlying fetal blood vessels, These findings suggest that the occlusive lesions in the maternal uterine vasculature may be the major cause of the infarction and impairment of placental function found in pregnancies complicated by fetal growth retardation.
A pilot study was conducted in Ireland to test the effectiveness of the calendar method of contraception. A conservative rule was used, requiring on average 16 days of abstinence per cycle. Among the 19 couples who entered into the study and were followed for up to seven cycles, there were no pregnancies. Since the length of abstinence was relatively long, we collected data to determine how couples expressed love and affection towards each other during those days when the woman was potentially fertile. We also collected data about barrier method use during the fertile time. We found that almost all couples gave each other hugs and kisses to show affection although couples were taught to abstain from vaginal intercourse during the fertile time. About one-third of the couples avoided genital contact, while about half reported using oral sex and/or frottage (body rubbing). Twice as many men reported using masturbation compared to women, although about half of the couples practiced mutual (partner) masturbation. In addition, about one-fifth of the couples used condoms during the fertile time in some cycles. These findings show that a variety of sexual expressions are used by couples when vaginal intercourse is to be avoided. Knowledge about these alternative sexual expressions may be important for couples who wish to engage in sexual activity and to avoid pregnancy.