Thromboprophylaxis with low molecular weight heparin (Fragmin) in high risk pregnancies.

Venous thromboembolic disease remains the commonest cause of maternal death. The management of thromboprophylaxis in high risk women during pregnancy is contentious. Low molecular weight heparins (LMW) have theoretical advantages compared with unfractionated heparin and warfarin but have been poorly studied in pregnancy. We report on the use of LMW heparin (Fragmin) as thromboprophylaxis in thirty four high risk pregnancies. All the women had a previous thrombosis or a thrombosis in their current pregnancy +/- a recognised thrombophilic state (eleven had the antiphospholipid syndrome). Fragmin was given subcutaneously to maintain trough anti-Xa activity of 0.15-0.2 U/ml and 2 h post injection levels of 0.4-0.6 U/ml. The levels were checked monthly during pregnancy. Most women required 5,000U Fragmin once daily during the first trimester unless they were greater than 100 kg at the start of pregnancy. The mean time for dosage increase was 20.5 week (S.D. 8.2). 26/34 pregnancies (76%) required 5,000 twice daily at the end of pregnancy. Epidural anaesthesia was managed by omitting Fragmin dose or inserting the needle 6 hours after the previous Fragmin injection. There were no thromboembolic events thrombocytopenias or excessive haemorrhage. One woman had osteoporotic vertebral collapse post partum, she had no other risk factors for osteoporosis. LWM heparin (Fragmin) appears to be efficacious in preventing recurrent thromboembolic disease in pregnant women at high risk, but it is notable that osteoporotic fractures occurred post partum in one woman. Further trials are required to determine optimal dosage and safety.

Obstetric outcome in systemic lupus erythematosus.

A prospective study was performed to investigate the fetal and maternal outcome of 108 pregnancies in 90 lupus patients. The protocol was based on shared care of the patients by a rheumatologist and an obstetrician, with input from a hematologist, if necessary. Lupus flares were treated with low-dose prednisolone, azathioprine and hydroxychloroquine. The live birth rate was increased from 31 % in the patients' previous obstetric history to 82%. A high incidence of prematurity was observed (43%). Lupus patients with secondary antiphospholipid syndrome presented a higher risk for fetal loss (P = .006). Flares occurred in 57% of the pregnancies, but most were mild (skin and joints). Flare during pregnancy did not increase the risk of fetal loss. We believe that careful monitoring and management of the lupus pregnancy has substantially improved the fetal outcome.

The effect of intra-articular capsaicin on nerve fibres within the synovium of the rat knee joint.

The aim of this study was to establish the effects of intra-articular capsaicin (pelargonic acid vallinylamide) on synovial innervation of the rat knee. Rats were sacrificed 1, 2, 4 and 7 days after intra-articular injection of capsaicin and joint tissues stained with either conventional haematoxylin and eosin (H and E) or with specific antibodies to the calcitonin gene-related peptide (CGRP), substance P (both of which are markers for primary afferent fibres), the C-flanking peptide of neuropeptide Y (CPON) (localised in postganglionic sympathetic fibres), or protein gene product 9.5 (a pan-neuronal marker). At lower concentrations (0.1% and 0.25%), capsaicin produced no change in peptide staining pattern or histological appearance. At 0.5% capsaicin, there was complete loss of nerve fibres showing positive staining for CGRP and substance P at all time points. Staining for CPON and protein gene product 9.5 was still present, but decreased, 1 and 2 days after treatment and virtually absent at 4 and 7 days. These findings provide evidence for partially selective denervation induced by 0.5% capsaicin, in contrast to 1% capsaicin which abolished staining for all peptide markers, indicating a total ablation of nerve fibres. A consistent but unexpected finding was the presence of a severe inflammatory response in joints treated with 0.5% and 1% capsaicin. An influx of polymorphonuclear leucocytes was found to occur within 4 h of injection, with progressive appearance of mononuclear cells after this time. We conclude that it is difficult to specifically deplete sensory nerve fibres from the synovium by means of local capsaicin injection. Although selective loss of staining for sensory nerve fibres could be achieved by injection of 0.5% capsaicin, there was progressive non-specific loss of post-ganglionic autonomic fibres which may be related to the severe inflammatory response provoked by the higher doses of capsaicin.

A study of sixty pregnancies in patients with the antiphospholipid syndrome.

OBJECTIVE: To study the maternal and fetal outcome in treated antiphospholipid syndrome (APS) pregnancies. METHODS: Sixty pregnancies in 47 APS patients (11 primary and 36 secondary) were followed in a multidisciplinary clinic. Patients testing antiphospholipid antibody positive and having a history of recurrent miscarriages were treated with low-dose aspirin (75 mg) daily. Patients with APS and a previous history of thrombotic events were treated with subcutaneous unfractionated or low molecular weight heparin and low-dose aspirin (75 mg) daily. RESULTS: The live birth rate increased from 19% of their previous non-treated pregnancies to 70% despite a high incidence of obstetric and fetal complications: pre-eclampsia (18%), prematurity (43%), fetal distress (50%) and intrauterine growth retardation (31%). Two predictors of fetal outcome were observed: the previous obstetric history and the presence of thrombocytopenia. Seven pregnancies (12%) were complicated by thrombotic events during pregnancy or during the puerperium. There were no thrombotic events in those receiving a low molecular weight heparin regimen. CONCLUSION: Close obstetric monitoring by a multidisciplinary team and the use of antithrombotic therapy was effective in reducing the fetal wastage in APS pregnancies despite a high incidence of obstetric and fetal complications.

Pregnancy in granulomatous vasculitis.

OBJECTIVE: To study the fetal and maternal outcome of pregnancy in patients with granulomatous vasculitis. METHODS: Four pregnancies in two patients with Wegener's granulomatosis (WG) and one patient with Churg-Strauss syndrome (CSS) were identified and followed in our specialised clinic for pregnancy and connective tissue diseases. RESULTS: Three pregnancies ended with live babies and one with intrauterine death at 25 weeks of gestation. One WG patient remained in remission throughout pregnancy and the other experienced severe activity at 12 weeks. The CSS patient was in remission during her first pregnancy, but the disease flared severely in the second. CONCLUSIONS: Pregnancy in patients with granulomatous vasculitis requires preconceptual planning, careful clinical management, and vigorous treatment of active disease.

Hydroxychloroquine and lupus pregnancy: review of a series of 36 cases.

OBJECTIVE: To study maternal and fetal outcome of pregnancy in patients with lupus who were exposed to hydroxychloroquine (HCQ). METHODS: The case records of women (n = 33) exposed to HCQ during their pregnancies (n = 36) and of 53 control patients from a single lupus pregnancy centre were reviewed to determine lupus activity, obstetric experience, and infant outcome. RESULTS: HCQ was not apparently teratogenic. Lupus activity and obstetric outcome in the two groups were similar. CONCLUSION: HCQ continuation is probably safe during pregnancy in patients with lupus, but there is no obvious advantage in commencing treatment.

A study of 100 high risk lupus pregnancies.

Certain subgroups of lupus patients and those with circulating antiphospholipid antibodies (aPL) in particular, suffer a high rate of fetal loss. Over the past 4 years, we have prospectively studied 100 pregnancies in patients with systemic lupus erythematosus (SLE) and primary antiphospholipid syndrome. In addition to conventional methods of monitoring SLE and fetal development, we have also used Doppler flow assessment of placental perfusion from the 14th wk of pregnancy onward. Patients with the antiphospholipid syndrome and previous history of thrombotic events were treated with daily heparin (10,000 IU) and low-dose aspirin (75 mg). Those without a history of thrombosis were treated with low-dose prednisolone, azathioprine, or hydroxychloroquine. Pregnancy loss was reduced from 81.3% in 101 previous pregnancies to 36.8% in 100 pregnancies managed by us. None of the patients who received hydroxychloroquine throughout the pregnancy presented fetal malformations. Careful management and close monitoring of the lupus pregnancy has substantially improved fetal outcome.

Early Doppler studies in lupus pregnancy.

The management of 56 pregnancies in 54 patients is presented, 52 with systemic lupus erythematosus and two patients with primary antiphospholipid syndrome. All underwent serial Doppler blood flow studies of the umbilical and uterine arteries from 14 weeks of gestation. Drug therapy was directed at disease activity and the fetus and mother monitored intensively to identify optimum time for delivery. End diastolic blood flow (EDF) studies were compared with anticardiolipin antibodies (aCL) and the lupus anticoagulant (LAC) to predict outcome of pregnancy in terms of mortality, Caesarian delivery, hypertension, and gestation. The absence of end-diastolic blood flow predicted Caesarian delivery more accurately. The presence of EDF and the absence of aCL was consistent with a normotensive pregnancy. The presence of LAC was the best of the three in predicting fetal demise.