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Biomedical subjects

P W Howie

Publications and source records attributed to P W Howie.

At least 19 recordsLinked to original sources

The effect of an injectable progestogen contraceptive on blood coagulation and fibrinolysis.

In 26 women receiving either medroxyprogesterone acetate (Depo-Provera) injections or combined oestrogen-progestogen pills for contraception, tests of coagulation and fibrinolysis were performed before treatment, and after 8, 16 and 24 weeks of therapy. In the medroxyprogesterone group no significant changes were induced in fibrinogen, the vitamin K-dependent factors, or antithrombin III. Plasminogen levels fell during therapy, and were significantly lower than pre-treatment values after 16 and 24 weeks. By contrast, the 13 women receiving oral contraceptives showed raised levels of fibrinogen and plasminogen after 8 weeks of treatment, and of factors VII and X after 24 weeks. These data suggest that medroxyprogesterone acetate injections induce fewer changes in the blood coagulation system than oral contraceptives.

Adult

Blood clotting and fibrinolysis in pregnancy.

During normal pregnancy, the concentrations of many of the clotting factors rise, thereby increasing the potential to generate fibrin. There is also evidence of increased thrombin activity during normal pregnancy which sharply increases during placental separation. Antithrombin III, the main inhibitor of thrombin and activated factor X, shows no compensatory rise during pregnancy but increases during the puerperium. Plasminogen and antiplasmin concentrations rise during pregnancy but systemic fibrinolytic activity, as measured by the euglobulin lysis time, is markedly depressed during pregnancy; the reduced fibrinolytic activity returns to non-pregnant values very soon after delivery. The loss of fibrinolytic activity is presumed to be loss of plasminogen activator, because when this is added in excess in the urokinase sensitivity test, the fibrinolytic response is normal. The capacity for localized fibrinolytic activity is not lost, however, because fibrinolytic degradation products are slightly raised during pregnancy. The overall pattern is one of increased coagulant and reduced fibrinolytic capacity during pregnancy which may protect the pregnant woman against the haemostatic challenge of placental separation.

Antigens

Soluble fibrinogen--fibrin complexes in intrauterine growth retardation.

Soluble fibrinogen--fibrin complex levels were found to be significantly higher in plasma samples from pregnant women with babies suffering from intrauterine growth retardation, when compared with levels found in normal pregnancy. As soluble fibrinogen--fibrin complexes are formed following activation of the coagulation pathway in vitro and in vivo these findings may reflect the increased local intravascular coagulation within the placenta demonstrated histologically in pregnancies complicated by growth retardation. The use of more sensitive methods for detecting alterations in coagulation, fibrinolysis and platelet function may prove useful in the diagnosis of intrauterine growth retardation antenatally.

Blood Coagulation Disorders

Single shot prostaglandin gel for labor induction.

A viscous suspension of prostaglandin E2 was introduced endocervically to induce labor in patients with favourable induction features. The method was found to be effective and compared favourably with the conventional practices of amniotomy and intravenous oxytocin infusion or oral prostaglandin therapy. Several advantages were found including a high degree of patient acceptability.

Clinical Trials as Topic

The effects of quinestrol and bromocriptine on blood coagulation, serum prolactin and serum FSH levels in puerperal women.

The effects of bromocriptine and quinestrol upon coagulation and fibrinolysis during the puerperium were studied. Quinestrol therapy was associated with increased levels of factors VII and IX and decreased antithrombin activity on the sixth postpartum day, and increased factor IX and plasminogen levels on the fourteenth postpartum day. Six weeks after delivery elevated levels of factors II and VII and of plasminogen were recorded in women given quinestrol. Bromocriptine therapy only caused an increase in the level of factor IX at six weeks after delivery. Compared to controls, patients given bromocriptine had lower prolactin and higher FSH levels during the puerperium whereas the patients given quinestrol had increased prolactin levels and a late fall in FSH levels.

Blood Coagulation

Abnormal platelet function in pre-eclampsia.

Platelet behaviour was studied in groups of women suffering from mild and severe pre-eclampsia, and compared with normal pregnant and non-pregnant controls. Platelets from women with severe pre-eclampsia were less responsive than normal to a variety of aggregating agents, and this impairment was significant in response to collagen and vasopressin. Women with severe pre-eclampsia had raised plasma adenine nucleotide levels and lowered platelet 5-hydroxytryptamine levels compared with the controls. Platelets from women with mild pre-eclampsia showed only a slight difference from normal. These findings may be the result of platelets having undergone aggregation and disaggregation within the circulation, and suggest that platelets may be involved in the pathogenesis of pre-eclampsia.

Adenine Nucleotides

Perinatal deaths: analysis by clinical cause to assess value of induction of labour.

Over the 10 years 1966-75 the rate of induction of labour in the Glasgow Royal Maternity Hospital has increased from 16-3% of all births. During the same period perinatal mortality fell from 33 to 22 per 1000, mainly because of significantly fewer deaths due to antepartum haemorrhage; trauma; maternal diseases; and unknown causes in mature babies. The reduction in the number of deaths of unknown causes in mature fetuses was achieved by preventing deaths occurring after 40 weeks and was recorded in all age and parity groups. The results suggested that increased use of induction of labour has contributed to the improved perinatal mortality rate.

Age Factors

Sequential studies in pre-eclampsia using plasma fibrinogen chromatography.

The technique of plasma fibrinogen chromatography was used to study sequential changes in coagulant and fibrinolytic activity in six patients with severe pre-eclampsia. Plasma soluble fibrinogen-fibrin complex and plasma fibrinogen-fibrin degradation product levels were measured as indices of coagulant and fibrinolytic activity respectively. Clinical deterioration antenatally was accompanied by increasing coagulant and decreasing fibrinolytic activity, while a more stable clinical picture was associated with steady coagulant and increasing fibrinolytic activity. Following delivery, a surge in fibrinolytic activity accompanied or preceded clinical recovery. The pattern of increased coagulant and diminished fibrinolytic activity would seem to favour the development of disseminated intravascular coagulation in these patients and it is possible that the balance between coagulant and fibrinolytic activity may influence the clinical course and outcome of the pregnancy.

Adolescent

Thromboembolism.

Fatal thromboembolism in pregnancy and the puerperium is becoming less frequent but remains the second commonest cause of maternal death. The mechanism responsible for the pathogenesis is complex and the predisposition to thrombus formation in pregnancy is probably the interaction of several different factors. Because of the risks of anticoagulant therapy, it is important to establish the diagnosis of thromboembolism before commencing treatment using venography and pulmonary angiography when necessary. When anticoagulants are used in pregnancy, coumarin derivatives can be used until 36 weeks and then substituted by heparin; alternatively heparin alone can be given throughout pregnancy. Subcutaneous heparin has no fetal effects and can be used successfully on an outpatient basis. Prevention is always better than cure, and it is essential that well-established preventive measures should be carried out diligently so that the incidence of this rare, but dreaded, complication can be reduced to an absolute minimum.

Anticoagulants

Use of coagulation tests to predict the clinical progress of pre-eclampsia.

The clinical manifestations of severe pre-eclampsia are normally separated from those of mild pre-eclampsia and normal pregnancy on arbitrary grounds. A clinical index, based on the increase in diastolic blood-pressure and the presence of proteinuria, was developed to reflect the spectrum of disease from mild to severe pre-eclampsia. This was related to a coagulation index based on the platelet-count, plasma-factor-VIII, and serum-fibrinolytic-degradation-products. The two indices were shown to be strongly correlated. All cases of perinatal death associated with pre-eclampsia had coagulation indices in the most severely abnormal range. These results suggest that intravascular coagulation is a highly characteristic feature of pre-eclampsia and that the coagulation index may be of value in monitoring the progress of the disease.

Blood Cell Count