Antiphospholipid Antibodies in Indian Women with Spontaneous, Recurrent Fetal Loss

Sir,

We read with interest the article by Al-Allawi et al. [1] in a recent issue of the journal. We also determined the frequency of antiphospholipid antibodies: lupus anticoagulant (LA) and anticardiolipin antibodies (ACA) in 100 Indian women with spontaneous first and second trimester fetal loss/recurrent fetal loss attending the OPD of our Institution and 50 age matched controls (pregnant women with no history of previous abortion/other obstetric complaints) [2]. The study received prior clearance from the Institutional Ethical Committee. Written informed consent was obtained from all women before their enrolment in the study. After a detailed clinical history and thorough clinical examination, complete blood counts (automated hematology analyser LH 500) and tests of hemostasis (PT, APTT, LA sensitive APTT and dRVVT screening test) were performed using commercially available kits within 7 days of the abortion. The presence of LA was diagnosed using standard criteria [3, 4].

We would like to draw comparisons between the two studies (Table 1).

Table 1.

Comparison of the two studies

Parameter	Al-Allawi et al.		Our study
	Patients	Controls	Patients	Controls
Number	103	100	100	50
LA detected (%)	5.8	–	15	–
ACA positivity
IgG	11	1	1	–
IgM	4	–	3	–
IgG and IgM	2	–	–	–
Positivity for APA:LA and/or ACA (%)	19.4	1	15	–
APC-r (%)	9.7	1	Not studied
Association with fetal loss	+		+
Treatment outcome	+		Not studied

The patients in our study presented with history of spontaneous first or second trimester or recurrent abortion. Majority (87 %) of women had more than two abortions. Most (60 %) abortions occurred in the first trimester. In the said study, most patients had at least one mid trimester abortion.

Al-Allawi et al. included women at least 3 months after the last miscarriage while in our study screening was done within 7 days of the abortion. As per the International consensus statement on the criteria for classification of Antiphospholipid syndrome, there is no limit on the time interval between the clinical event and the positive laboratory finding [5].

Screening for LA in our study was done by APTT, LA sensitive APTT and dRVVT screening test using commercially available kits. In patients with a prolonged LA sensitive APTT/dRVVT screening time, confirmation was done by dRVVT confirmatory test based on a platelet neutralization procedure. The authors have used APTT and KCT to screen for LA and confirmed it by Hexagonal phospholipid assay.

In both studies, all women who were initially positive for LA underwent repeat testing at 12 weeks and LA was reported to be present when both results were positive. Also, none of the controls were positive for LA in the studies.

Based on prolonged screening tests, failure to correct them with normal plasma and confirmation by dRVVT confirmatory test, LA was detected in 15 (15 %) women in our study. This is higher than that reported by the authors who confirmed the presence of LA in 5.8 % women.

The results highlight the variability in the prevalence of LA due to a difference in sensitivity and specificity of screening tests. APTT and KCT have conventionally been used as screening tests but their sensitivity to LA varies according to the composition of the reagents [6]. Commercial preparations of APTT particularly have varied sensitivity. Inspite of the fact that KCT is a sensitive screening test it has drawbacks. In contrast, dRVVT is reported to be specific for detecting LA and also more sensitive than KCT. As no test is 100 % sensitive to LA, two tests with different assay principles are recommended for screening of which dRVVT should be one [3]. If APTT is used, it is important that a sensitive reagent should be used to give better detection capability [5]. Both LA sensitive APTT and dRVVT were used for screening in our study. Integrated tests using dRVVT or other assays are more convenient, less time consuming and are becoming increasingly popular as was also used by us.

We measured anticardiolipin antibodies by ELISA in 78 patients and all controls. IgG ACA’s were detected in 1 (1.3 %) patient and IgM antibodies in 3 (3.8 %) patients. This prevalence is considerably lower than that reported by the authors who identified ACA in 17 (16.5 %) patients; IgG antibodies in 11, IgM in 4 and both in 2 patients. The authors reported positivity for ACA in one control while all controls in our study were negative.

Both LA and/or ACA were present in 20 (19.4 %) patients. In our study, all patients who were ACA positive were positive for LA. So LA and/or ACA were present in 15 % patients.

The authors observed an increased risk of fetal loss in patients with ACA positivity as was also observed by us. In our study, other obstetric complications including prematurity (14 %), eclampsia and pre-eclampsia (15 %), IUGR (12 %) and neonatal death (9 %) in previous pregnancy were observed in these women. On comparing the frequency of these complications in LA positive and negative women, all complications were more frequent in the former as compared to the latter. The difference in eclampsia and pre eclampsia was statistically significant (p < 0.047).

APC resistance and treatment outcome were not measured in our study. The results of our study highlight the higher prevalence of LA as compared to ACA in Indian women with recurrent, spontaneous fetal loss and relevance of screening for it using a combination of tests such as LA sensitive APTT and dRVVT. As observed by Al-Allawi et al., treatment of these women increases the chance of a successful subsequent pregnancy.

Compliance with Ethical Standards

Conflict of interest

All the authors declare that they have no conflict of interest.