Bailliere's clinical obstetrics and gynaecology最新文献

Heparin is the commonest mode of thromboprophylaxis used in pregnancy. It does not cross the placenta but has potential adverse effects on the mother, of which the most important is heparin-induced osteoporosis. The hazards of heparin, including bleeding, skin reactions, heparin-induced thrombocytopenia and osteoporosis are discussed and the relevant literature reviewed. Low-molecular-weight heparins have certain advantages over standard unfractionated heparins, especially in obstetrics. Their longer half-life and increased bioavailability enable once-daily injections, making them more convenient and acceptable. They are as effective as standard heparin but have a theoretically more favourable sideeffect profile, providing less anticoagulant relative to antithrombotic activity. Current evidence suggests a lower incidence of heparin-induced thrombocytopenia. A reduced risk of osteoporosis is suggested but not yet proven. Although thrombo-embolism is currently the leading cause of maternal mortality in the UK, antenatal heparin prophylaxis is not given to all women with previous thrombo-embolism because of continued fears concerning heparin-induced osteoporosis. A protocol is presented with guidelines for different levels of obstetric prophylaxis depending on the perceived level of risk.

It is important to continue or introduce prophylaxis of thrombo-embolism before elective delivery or during labour if the incidence of post partum thrombo-embolism is to be reduced. Women with previous thrombo-embolism, genetic or acquired thrombophilia should receive intrapartum and post partum prophylaxis for at least six weeks. Those having operative delivery may require prophylaxis for a shorter period if there are no other risk factors. Subcutaneous unfractionated or low molecular weight heparins are the anticoagulants of choice.

Available evidence shows that the use of prophylactic heparin during the course of epidural or spinal anaesthesia does not increase the risk of local haematoma although this remains an actively controversial area. To reduce the risk of osteopenia associated with long-term therapy and relieve the women of the onus of self-administered injections, heparin may be replaced by warfarin post-partum even if the mother is breastfeeding but warfarin dosage, unlike heparin, will require careful monitoring.

Accurate diagnosis of deep venous thrombosis (DVT) and pulmonary embolism (PE) is required because treatment can be life-saving, while inappropriate anticoagulation exposes the mother and fetus to haemorrhage and other hazards. Clinicians must be aware of which patients are at risk because DVT is frequently asymptomatic. Clinical diagnosis is unreliable for DVT and PE so objective tests are required. Venography is the gold standard test for DVT but is invasive and has been superseded by less invasive tests such as duplex ultrasound which is now the first-line investigation in pregnancy. However, where doubt remains, venography, CT and MRI have a role. Ventilation-perfusion scanning is the pivotal test for PE in pregnancy, and need not expose the fetus to excess radiation. If the result is unclear deep venous ultrasound can guide management of suspected PE, thus avoiding pulmonary angiography, the invasive gold standard test.

Clinically suspected deep vein thrombosis (DVT) or pulmonary thromboembolism (PE) should be initially treated with heparin, and an objective diagnosis obtained. In pregnancy, heparin is usually continued until delivery, following which warfarin is substituted. In the absence of pregnancy, warfarin is substituted and usually continued for 3 months after a first thrombo-embolic event. Low molecular weight heparins are increasingly preferred to unfractionated heparin in non-pregnant patients with acute DVT, because of efficacy when given by daily subcutaneous injection without routine monitoring of coagulation assays, greater efficacy, and lower risks of major bleeding and of mortality. Unfractionated heparin requires monitoring by the APTT (target ratio 1.5–2.5), and warfarin requires monitoring by the International Normalized Ratio (INR) of the prothrombin time (target ratio 2.0–3.0). Graduated elastic compression stockings reduce post-thrombotic leg symptoms after DVT. Secondary prevention is important in future high risk situations.

The oral contraceptive is one of the most widely taken medications in the healthy population. The clinically important side-effects are venous and arterial thrombosis. Accurate estimates of incidence of these side-effects have proven to be difficult. Diagnostic modalities for thrombosis are sub-optimal and the problems of study methodology, primarily a reliance on non-experimental studies, have limited the ability to define the attributable risk of thrombosis from oral contraception. Pharmacological attempts to further decrease venous thrombotic side-effects by the use of third-generation oral contraceptives have failed. This places a greater emphasis on the selection of patients to help avoid giving medication to those patients with underlying thrombotic risk factors. An example of this approach has been the clear confirmation of the adverse effects of cigarette smoking and arterial thrombosis in oral contraceptive users. At the biochemical level, hypercoagulability testing may be useful. Screening for high-frequency prothrombotic abnormalities, such as the Factor V Leiden genotype, represents an important addition to the process by which patients are selected, and may be prototypic of further advances.

Venous thrombo-embolism remains a major cause of mortality and morbidity following gynaecological surgery and in association with pregnancy and delivery. Specific risk factors can be identified pre-operatively and before or during pregnancy and delivery. Clinicians and units should develop guidelines for risk assessment and the implementation of specific thromboprophylactic measures in patients considered to have significant risk. The main prophylactic techniques are unfractionated and low-molecular-weight heparins and physical methods such as graduated elastic compression stockings. It should be noted that there are particular concerns with regard to the use of pharmacological thromboprophylaxis with both heparin and warfarin in pregnancy. Unfractionated heparin is associated with osteoporotic problems, allergy and heparin-induced thrombocytopenia which can cause significant thrombotic problems. Warfarin is associated with teratogenesis and the risk of bleeding in mother and fetus. Clearly, where antenatal thromboprophylaxis is to be used, the risk of the anticoagulants employed must be weighed against the potential benefits. Such assessment might be best done prior to pregnancy in order that the patient can enter pregnancy with a clear view of the potential hazards and benefits. Low-molecular-weight heparins are being increasingly used in pregnancy but it is unclear to what extent they are safer than unfractionated heparins. However, they do appear to have substantially less risk of heparin-induced thrombocytopenia and possibly less risk of heparin-induced osteoporosis. Increasingly, thrombophilia is recognized as underlying many thrombotic problems, particularly in young women, and when the events occur in association with pregnancy. In view of the complexity in the management of such patients, it is important that they be referred to a unit with specific expertise in the management of thrombophilia.

The clinical management of thrombo-embolic disease in obstetrics and gynaecology is hampered by the paucity of firm evidence on which to base clinical decisions. This is particularly so in obstetrics where there have been no randomized controlled trials of thromboprophylaxis in pregnancy or the puerperium of sufficient size to detect differences in the incidence of clinical thrombo-embolic events. The incidence of osteoporosis and bleeding complications associated with heparin have not been precisely defined in pregnancy and we are already using low-molecular-weight heparin in place of unfractionated heparin when we do not know whether either heparin is preferable to nothing. In gynaecology, the various thromboprophylactic modalities for use in relation to surgery need to be compared. The small randomized comparisons that have been performed suggest that relatively non-invasive procedures may be just as effective as heparin in preventing thrombo-embolism without the associated complications. Recent controversies concerning the effect of the OCP and HRT on the risk of thrombo-embolic disease indicate that the present methods we use to evaluate these interventions needs to be urgently addressed so that safety rather than efficacy becomes the principle outcome.

Anticoagulants are used during pregnancy to prevent venous thrombo-embolism in high-risk patients, to prevent systemic embolism in patients with prosthetic heart valves or native valvular heart disease, and to treat patients with acute venous thrombo-embolism. Neither unfractionated nor low-molecular-weight heparin cross the placenta and both appear to be safe for the fetus. Oral anticoagulants do cross the placenta and they have been associated with the development of warfarin embryopathy, central nervous system anomalies, and fetal haemorrhage. The true incidence of these events is not known. Both heparin and oral anticoagulants can be safely administered to nursing mothers.

The heritable defects which are at present accepted as proven to be associated with familial venous thrombosis are deficiency of antithrombin (AT), protein C (PC) or protein S (PS) and the FV Leiden mutation. In women from symptomatic kindred each of these defects is associated with increased risk of pregnancy-associated venous thrombosis and increased risk of fetal loss and other vascular complications of pregnancy. The risks appear to be greatest for some types of AT deficiency. These defects are very common but there is growing evidence that congenital thrombophilia is a multigene defect and abnormalities of AT or of the PC-PS system represent only part of the genetic thrombotic predisposition in symptomatic families. Currently it seems reasonable to focus resources on women with AT or PC-PS system abnormalities who are themselves already symptomatic or who come from symptomatic families rather than screen whole populations for these defects. In symptomatic families screening of females around the time of puberty allows time for education and counselling. Pregnancies should be planned, and each pregnancy in each patient managed individually. In general though, women with AT deficiency from symptomatic families require anticoagulant prophylaxis throughout pregnancy and for at least 3 months post-partum, whereas those with PC-PS system defects may require third-trimester plus post-partum prophylaxis or post-partum anticoagulant prophylaxis only.