Laboratory Evaluation of Antiphospholipid Syndrome.

OBJECTIVES: Anti-ß2 glycoprotein I domain I (anti-domain I) and anti-phosphatidylserine/prothrombin (aPS/PT) antibodies are present in patients with antiphospholipid syndrome (APS); however, their use in evaluation remains unclear. METHODS: Diagnostic attributes of lupus anticoagulant (LAC), anti-domain I IgG, anti-cardiolipin, anti-ß2 glycoprotein I (anti-ß2GPI), and aPS/PT IgG and IgM antibodies were assessed in 216 patients evaluated for APS. RESULTS: LAC had the best odds ratio (OR, 14.2) while that for anti-domain 1 IgG was comparable to anti-ß2GPI IgG (OR, 8.3 vs 9.4) but higher than all others. Significant correlations were observed for thrombosis (P = .03) and pregnancy-related morbidity (P = .001) with anti-domain IgG and for any thrombosis with aPS/PT IgG (P = .006). Use of noncriteria antiphospholipid with or without criteria markers did not significantly increase the probability to diagnose APS. CONCLUSIONS: Noncriteria tests can contribute to diagnosis and stratification of APS but do not improve diagnostic yield. Optimal strategies for implementation require prospective investigation.

Correlation of serum fructosamine and recurrent pregnancy loss: Case-control study.

AIM: Pre-gestational diabetes is associated with an elevated risk of pregnancy loss, but it is unclear whether subclinical glucose intolerance is associated with pregnancy loss, especially recurrent pregnancy loss (RPL). The aim of this study was therefore to compare maternal serum fructosamine (a marker of glycemic control) in patients with and without RPL. METHODS: A case-control study was carried out of 117 women with unexplained RPL, defined as two or more pregnancy losses with no more than one live birth, and 117 age-matched controls with at least one full-term uncomplicated pregnancy and no more than one pregnancy loss. No RPL patients or controls had a clinical diagnosis of pre-gestational or gestational diabetes. Maternal serum was analyzed for fructosamine on quantitative spectrophotometry. RESULTS: Mean body mass index (BMI) of RPL patients was 26.0 ± 6.4 kg/m(2) compared with 26.6 ± 5.8 kg/m(2) (P = 0.40). Fructosamine was higher in women with RPL (224.1 ± 28.79 µmol/mL) compared with controls (188.9 ± 19.3 µmol/mL, P < 0.001). This difference persisted when RPL patients and controls were stratified by BMI. The proportion of women with elevated fructosamine considered diagnostic of diabetes (>285 µmol/L) was similar in RPL patients and controls. CONCLUSION: The RPL patients and controls had a similar proportion of women with elevated fructosamine considered diagnostic of diabetes. Serum fructosamine was increased in women with RPL compared with controls. Thus, subclinical glucose intolerance may be associated with an increased risk of RPL. These data support further investigation into the mechanisms of RPL associated with glucose intolerance, but do not support testing for subclinical glucose intolerance in women with RPL.

Pre-eclampsia as a manifestation of antiphospholipid syndrome: assessing the current status.

The presence of antiphospholipid antibodies is considered a risk factor for pre-eclampsia. Two meta-analyses and a number of case-control and cohort studies have found associations between pre-eclampsia and lupus anticoagulant, anticardiolipin, and/or anti-ß2 glycoprotein I. However, existing literature is inconsistent, with varying severity of pre-eclampsia phenotype examined, differing aPL titer cutoffs used to define positive status, and an overwhelming lack of repeat confirmatory aPL testing. This calls into question the link between aPLs and pre-eclampsia, or at least makes it less well defined. There is evidence for a mechanistic pathway between aPLs and adverse pregnancy outcomes (APOs) including pre-eclampsia via the complement pathway. Complement appears to be overactive in pregnancies affected by APOs. A mouse model has show that the fetal wastage caused by treatment with human aPLs can be salvaged by either creating genetic knockouts along the complement, TNF-alpha, and tissue factor pathways or be treating mice with monoclonal antibodies blocking key complement factors. Thus, this is worth further investigation to clarify the likely association of aPLs and pre-eclampsia in humans, as well is to further evaluate the interaction with complement in human pregnancies.

Contemporary patterns of spontaneous labor with normal neonatal outcomes.

OBJECTIVE: To use contemporary labor data to examine the labor patterns in a large, modern obstetric population in the United States. METHODS: Data were from the Consortium on Safe Labor, a multicenter retrospective study that abstracted detailed labor and delivery information from electronic medical records in 19 hospitals across the United States. A total of 62,415 parturients were selected who had a singleton term gestation, spontaneous onset of labor, vertex presentation, vaginal delivery, and a normal perinatal outcome. A repeated-measures analysis was used to construct average labor curves by parity. An interval-censored regression was used to estimate duration of labor, stratified by cervical dilation at admission and centimeter by centimeter. RESULTS: Labor may take more than 6 hours to progress from 4 to 5 cm and more than 3 hours to progress from 5 to 6 cm of dilation. Nulliparous and multiparous women appeared to progress at a similar pace before 6 cm. However, after 6 cm, labor accelerated much faster in multiparous than in nulliparous women. The 95 percentiles of the second stage of labor in nulliparous women with and without epidural analgesia were 3.6 and 2.8 hours, respectively. A partogram for nulliparous women is proposed. CONCLUSION: In a large, contemporary population, the rate of cervical dilation accelerated after 6 cm, and progress from 4 cm to 6 cm was far slower than previously described. Allowing labor to continue for a longer period before 6 cm of cervical dilation may reduce the rate of intrapartum and subsequent repeat cesarean deliveries in the United States.

Antiphospholipid syndrome and thrombosis.

The antiphospholipid syndrome is an autoimmune condition in which venous or arterial thrombosis is a primary clinical feature. The other primary clinical feature is adverse pregnancy outcome, specifically recurrent miscarriage, fetal death, or preterm delivery due to severe preeclampsia or placental insufficiency. The diagnostic autoantibodies for antiphospholipid syndrome are lupus anticoagulant, anticardiolipin, or anti-beta2-glycoprotein I.

The inherited thrombophilias: genetics, epidemiology, and laboratory evaluation.

It is now possible to identify a predisposing thrombophilic condition for venous thrombosis in well over half of the cases. Certain thrombophilia diagnoses have a major impact on anticoagulant therapy, and hence it is incumbent upon physicians to understand how to diagnose and manage these conditions. This chapter covers the genetics and epidemiology of the inherited thrombophilias and provides a useful, common-sense approach to the laboratory evaluation of a patient with venous thrombosis.

Antiphospholipid antibodies and infertility: fact or fallacy.

Some clinicians are convinced that antiphospholipid antibodies, including antibodies to any one of five-to-seven phospholipid antigens, are associated with infertility. Additionally, some clinicians recommend that infertile women who have antiphospholipid antibodies and are undergoing in-vitro fertilization should be treated with heparin to improve the rate of pregnancy. However, experts disagree regarding the relationship between antiphospholipid antibodies and infertility. There is also substantial evidence that treatment with heparin does not alter the rate of pregnancy following in-vitro fertilization. Why the confusion? Probable culprits include variation in study design and the selection of infertile patients. Another important problem is that assays for antiphospholipid antibodies other than anticardiolipin are not standardized. Before the real relationship between antiphospholipid antibodies and infertility is discovered, assays for antiphospholipid antibodies other than anticardiolipin must be standardized and properly designed studies conducted. Randomized, controlled trials must be done to determine if heparin should be recommended as an adjunctive treatment for in-vitro fertilization in women with antiphospholipid antibodies.