A multicenter, placebo-controlled pilot study of intravenous immune globulin treatment of antiphospholipid syndrome during pregnancy

Management of the obstetric antiphospholipid syndrome

“…Unfortunately, several studies on aPL-related pregnancy included primigravidae (51)(52)(53)55) and women with Ͻ3 early pregnancy losses (29,44,48,49), and this may have influenced their results. Adhering to strict criteria for obstetric APS is important to minimize the role of causes other than aPL (particularly abnormal karyotypes), because even among losses in treated aPLpositive women with Ն3 previous early losses, abnormal fetal karyotypes may be expected in up to 24% of conception products (45).…”

“…The pregnancy outcomes in women in the third category (those with a high frequency of fetal loss, SLE, thrombosis, or a combination) were reported in 3 retrospective studies in which patients received treatment according to the patient's and physician's judgment (51-53), one retrospective study in which all women received monotherapy with heparin (54), and one placebo-controlled study that evaluated the effects of high-dose intravenous immunoglobulins (IVIG) added to treatment with heparin and aspirin (55).…”

“…Many patients in these studies had SLE (77% [53], 36% [54], 32% [52], 13% [55], not specified [51]), previous thrombotic events (56% [55], 41% [52], 30% [53], 29% [54], not specified [51]), or both. All patients had APS according to the 1987 criteria (7), but many did not fulfill the obstetric criteria (7,14), because several studies included primigravidae (accounting for 11% [52], 17% [53], 36% [51], and an unspecified percentage [55] of included women) or included women with 1 or 2 first trimester losses or only successful pregnancies (52)(53)(54). All patients fulfilled the serologic criteria for APS, because all studies apparently used adequate tests for LAC and aCL and included patients with at least medium levels of aCL.…”

“…In one study (51), an insensitive LAC test was used, and another study (52) excluded patients with IgM aCL only. In the studies in which pharmacologic treatment was administered according to the patient's and physician's judgment, therapy in individual patients included no treatment (51), monotherapy with low-dose aspirin (51,53), prednisone (51,52) or heparin (52), a combination of aspirin and prednisone (51-53), a combination of aspirin, prednisone, and heparin (52), a combination of heparin and prednisone (53), a combination of aspirin and heparin (52), and a combination of IVIG, aspirin, and heparin (55). The daily dose of aspirin was 75-80 mg (51)(52)(53) and that of prednisone was 10-30 mg (51), 40 mg (with adjustments upon evaluation of LAC) (52), or was not specified (53).…”

“…Treatment with heparin was either low molecular weight heparin in a dose aiming for target values of 0.15-0.2 IU/ml of anti-factor Xa activity preinjection (53) or unfractionated heparin in a daily dose of 10,000-20,000 IU divided into 2 or 3 injections, with dosage adjustments to 15,000-20,000 IU/day at the beginning of the second trimester (52) or an unadjusted dose of 10,000-15,000 IU divided into 2 doses (53). Branch et al (55) started with a dosage of 15,000 IU of unfractionated heparin per day and increased the dosage to 20,000 IU/day in the second trimester. Rosove et al (54) used unfractionated heparin with a daily dose divided into 2 subcutaneous injections, with dose adjustments to obtain a mid-interval APTT of 1.5-2 times the control value (daily dose 10,000-36,000 IU).…”