Henk J. Out

Histopathological findings in placentae from patients with intra-uterine fetal death and anti-phospholipid antibodies

Anti-phospholipid antibodies are associated with first trimester abortions and late intra-uterine fetal death. The histopathology of 47 placentae from 45 women with intra-uterine fetal death, including 16 patients with anti-phospholipid antibodies, was studied in order to detect potential differences between placentae from women with and without these antibodies. Thirteen patients had systemic lupus erythematosus or lupus-like disease, including 6 women with anti-phospholipid antibodies. In placentae from patients with anti-phospholipid antibodies, a decrease in vasculo-syncytial membranes, fibrosis mainly in infarcted areas, hypovascular villi and thrombosis or infarction was seen significantly more often than in placentae from women without these antibodies. Of 17 placentae from 16 patients with anti-phospholipid antibodies, only 3 did not demonstrate signs of thrombosis or infarction. Thrombosis/infarction was significantly associated with a decrease in vasculo-syncytial membranes, fibrosis, hypovascular villi and an increase in syncytial knots. These findings are most likely to be the result of prolonged hypoxia due to thrombosis or infarction. It is concluded that thrombosis or infarctions are prominent features in placenta from patients with anti-phospholipid antibodies and intra-uterine fetal death. Consequently, antithrombotic treatment during pregnancy forms a rational approach in these patients.

A prospective, controlled multicenter study on the obstetric risks of pregnant women with antiphospholipid antibodies

OBJECTIVESnA prospective, controlled multicenter study was performed to estimate the obstetric risks of antiphospholipid antibodies (the lupus anticoagulant and anticardiolipin antibodies). In addition, the risks of prior thrombosis, obstetric history, systemic lupus erythematosus, and high-dose prednisone treatment were evaluated.nnnSTUDY DESIGNnAfter screening for antiphospholipid antibodies in patients with lupus erythematosus or women with prior fetal loss(es), 59 subsequent pregnancies with and 54 without these antibodies were followed.nnnRESULTSnThe presence of the lupus anticoagulant and a history of at least three spontaneous abortions could predict fetal loss (p = 0.032 and 0.001, respectively). In live born infants, a low birth weight could be predicted by the presence of anticardiolipin antibodies (p = 0.034), prior intrauterine fetal death (p = 0.025), and treatment with high-dose prednisone (p = 0.002). No relationships were seen between antiphospholipid antibodies and small-for-gestational-age newborns and pregnancy-induced hypertension or preeclampsia. The disappearance of antiphospholipid antibodies during pregnancy was not correlated with live birth.nnnCONCLUSIONnIt is concluded that the presence of antiphospholipid antibodies is a risk factor for adverse pregnancy outcome.

Prevalence of antiphospholipid antibodies in patients with fetal loss.

The prevalence of antiphospholipid and antinuclear antibodies in 102 patients with at least three unexplained miscarriages before a gestational age of 12 weeks, or at least one intrauterine fetal death after 12 weeks, was investigated and compared with the prevalence in 102 normal pregnant controls. Six patients had a history of thrombosis and six had lupus-like disease. Twenty one patients had anticardiolipin antibodies compared with 10 controls. Serum samples of nine patients and one control contained antinuclear antibodies. The lupus anticoagulant was present in the plasma of five patients with anticardiolipin antibodies. The influence of patient selection on the results was illustrated by the finding that antiphospholipid antibodies and antinuclear antibodies were mainly detected in patients with lupus-like disease or a history of thrombosis. When these patients were excluded there was no significant difference in the prevalence of anticardiolipin and antinuclear antibodies between patients and controls. Therefore, in the absence of lupus-like disease or a history of thrombosis, screening for antiphospholipid antibodies in patients with adverse pregnancy outcomes seems not to be indicated.

Fluctuations of anticardiolipin antibody levels in patients with systemic lupus erythematosus: a prospective study.

In 53 patients with systemic lupus erythematosus sequential blood samples obtained during a four year period (range 6-47 months) were screened for anticardiolipin antibodies (ACAs). Disease activity and treatment with prednisone were also assessed and related to ACA concentrations. During follow up only 21 patients for ACA IgG (40%) and 25 for ACA IgM (47%) remained in the ACA category (negative, low positive, high positive) found at the first sample taken at entrance. Marked increases from negative to high positive concentrations were sometimes seen and were not accompanied by typical events such as thrombosis or thrombocytopenia (the ACA syndrome). Shifts in ACA concentrations could not always be explained by changes in prednisone dose. Also, in patients with low dose prednisone treatment or none at all (n = 22) 10 patients (45%) changed ACA IgG category and 12 patients (55%) fluctuated in ACA IgM categories during follow up. As a consequence of the variability in ACA titres relations of ACAs with the ACA syndrome depended on the blood sample studied. In the second sample, randomly taken half way through follow up, no significant relations with the ACA syndrome could be found. Anticardiolipin antibody IgG was significantly associated with disease activity in 11/47 patients (23%) and in the group as a whole. During remission ACA IgG was significantly associated with the ACA syndrome, whereas during moderate/severe disease activity in the same patients that correlation was not significant. Anticardiolipin antibody IgM was much less influenced by disease activity, and in only 4/47 patients (9%) could a significant relation with disease activity be shown. Associations of ACA IgM with the ACA syndrome were significant during both lupus flares and remission.

Prospective study of fluctuations of lupus anticoagulant activity and anticardiolipin antibody titre in patients with systemic lupus erythematosus.

Fluctuations of lupus anticoagulant activity and anticardiolipin antibody titres were studied in 53 patients with systemic lupus erythematosus (SLE). The median study time was 26 months with a median number of 12 samples. Lupus anticoagulant was measured by the kaolin clotting time (KCT) and dilute Russell viper venom time (dRVVT) assays; anticardiolipin antibodies were assayed by an enzyme linked immunosorbent assay (ELISA). Normal and increased KCTs or dRVVTs were seen during follow up in 13 and 12 patients, respectively. IgG anticardiolipin antibodies changed from negative to positive or positive to negative in 26 patients and IgM anticardiolipin antibodies in 16 patients. Disease activity and treatment with prednisone could account for these fluctuations in the kaolin clotting time (KCT) in 7 of 13 patients and in the dRVVT in 2 of 12 patients. Whole group analysis showed that the KCT, dRVVT, and IgM anticardiolipin antibodies were not associated with disease activity, in contrast with IgG anticardiolipin antibodies. During treatment with prednisone normal KCT and dRVVT results were obtained more easily than normal anticardiolipin antibody levels. It is recommended that lupus patients should not be classified as antiphospholipid antibody positive or negative on the basis of only one sample.