|Year : 2017 | Volume
| Issue : 9 | Page : 1145-1149
Prevalence of lupus anticoagulant in women with spontaneous abortion in Zaria
IN Ibrahim1, AI Mamman1, SE Adaji2, A Hassan1, AA Babadoko1
1 Departments of Haematology, Ahmadu Bello University Teaching Hospital, Zaria, Kaduna, Nigeria
2 Departments of Obstetrics and Gynaecology, Ahmadu Bello University Teaching Hospital, Zaria, Kaduna, Nigeria
|Date of Acceptance||08-Apr-2017|
|Date of Web Publication||26-Oct-2017|
I N Ibrahim
Department of Haematology, Ahmadu Bello University Teaching Hospital, P. M. B. 06 Shika, Zaria - 810 001, Kaduna
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Introduction: Spontaneous abortion (SA) is a common complication of pregnancy. Presence of lupus anticoagulant (LA), one of the antiphospholipid antibodies, has been associated with SA in many studies, especially in Caucasians. This study was carried out to determine the prevalence of LA in women with SA in ABUTH, Zaria. Materials and Methods: A cohort of 100 consecutive women presenting with SA with no history of thrombotic episodes were enrolled into the study. Prothrombin time (PT), kaolin clotting time (KCT), and activated partial thromboplastin time (APTT) were conducted on samples of all the participants. Eight patients had prolonged APTT, and after a 50:50 mixture of their plasma with pooled control plasma, four (50%) had uncorrected APTT. Staclot® (a hexagonal-phase phospholipid) test and calculated Rosner index for prolonged KCT were used for the confirmation of LA in samples with uncorrected APTT after mixing studies. Results: We analyzed 100 women with one or more SA with a mean age of 31.0 ± 3.8 years. Nearly 4% and 3% of the participants were LA positive with Staclot® and KCT tests, respectively. Patients with LA were more likely to have had a past history of preeclampsia/eclampsia, small for gestational age deliveries, and previous SA (prevalence odds ratio [95% confidence interval]) of 1.9 (0.2, 20.1), 3.2 (0.3, 34.3), and 1.4 (0.1–13.6), respectively. The PT, APTT, and KCT were significantly prolonged in patients with LA (P ≤ 0.001 for each, respectively). Conclusion: LA may be one of the causes of SA and other adverse pregnancy outcomes such as preeclampsia/eclampsia and small for date deliveries. It is recommended that patients with prolonged APTT, uncorrected with 50:50 mixing study with pooled control plasma, should be evaluated further for LA.
Keywords: Lupus anticoagulant, spontaneous abortion, uncorrected activated partial thromboplastin time
|How to cite this article:|
Ibrahim I N, Mamman A I, Adaji S E, Hassan A, Babadoko A A. Prevalence of lupus anticoagulant in women with spontaneous abortion in Zaria. Niger J Clin Pract 2017;20:1145-9
|How to cite this URL:|
Ibrahim I N, Mamman A I, Adaji S E, Hassan A, Babadoko A A. Prevalence of lupus anticoagulant in women with spontaneous abortion in Zaria. Niger J Clin Pract [serial online] 2017 [cited 2021 Jul 23];20:1145-9. Available from: https://www.njcponline.com/text.asp?2017/20/9/1145/217242
| Introduction|| |
Lupus anticoagulant (LA) is one of the antiphospholipid (APL) autoantibodies, which prolong phospholipid-dependent coagulation reactions that depend on protein-phospholipid complexes in vitro., APL antibodies are a mix of several immunoglobulins (Ig): IgG, IgM, and less commonly, IgA antibodies directed at phospholipid-associated proteins, particularly prothrombin and beta 2-glycoprotein 1 (β2-GP1). LA is a common cause of prolongation of phospholipid-dependent clotting assays such as activated partial thromboplastin time (APTT) and the dilute Russell's viper venom time. Paradoxically, LA has been related to thrombotic events, but could lead to bleeding in the presence of thrombocytopenia and other coagulopathy.,
Although LA was originally described in patients with systemic lupus erythematosus (SLE), it was detected subsequently in non-SLE disorders as well as in healthy individuals. Positivity for anti-mitochondrial type 5 antibodies (anti-M5) had been demonstrated in a patient with inflammatory hepatobiliary and kidney changes in a background of APL syndrome. Although anti-M5 has been regarded as a distinct serological marker for APL syndrome, the demonstration that β2-GPI can bind to anionic phospholipids and overall that it can react with mitochondrial particles supports the argument that it could be related to anti-β2-GPI activity.
Positive results in tests for APL antibodies are associated with adverse pregnancy outcomes such recurrent pregnancy losses, or one or more late-term (>10 weeks' gestation) spontaneous abortions (SAs). Other pregnancy complications include intra-uterine growth retardation, maternal thrombosis, thrombocytopenia, and pregnancy-induced hypertension. Despite this, some women with positive tests for APL antibodies have uncomplicated pregnancies without treatment., Although other autoantibodies such as anticardiolipin or anti-β2-GP1 antibodies are associated with recurrent abortions, LA has been reported to be more specific for predicting clinical outcomes. Most studies have been carried out in Caucasian populations; in this environment, literature is scarce on the association between APL antibodies and pregnancy loss. This study was to determine the prevalence of LA in women presenting with SA in Zaria, using Staclot® LA test for confirmation of LA.
| Materials and Methods|| |
It was a cross-sectional study carried out on a cohort of 100 consecutive patients with SA (defined as the termination of pregnancy before the gestational age of 28 weeks) at the Gynaecology Clinic of ABUTH Shika-Zaria. An informed written consent was obtained from all participants and those who met the inclusion criteria were selected. An interviewer-administered questionnaire was used to collect sociodemographic, gynaecological and obstetric data from the respondents. Women were questioned regarding the number and timing of their abortions, family history of recurrent abortions, history of still births or intrauterine deaths, and history of thrombotic episodes. Women on anticoagulants, cervical incompetence, uterine abnormalities, diabetes mellitus, HIV, and other medical conditions were excluded from the study. Seven milliliter (mL) of venous blood was obtained from each participant following standard aseptic procedure. Exactly 4.5 mL of blood was dispensed into a bottle containing 0.5 mL of 3.2% of trisodium citrate with blood: anticoagulant ratio of 9:1 for coagulation studies. The remaining 2.5 mL of blood was dispensed into an EDTA bottle for determination of full blood count (FBC) and direct Coombs' test (DAT).
The FBC and DAT were done manually using the procedure described by Dacie. Platelet poor plasma for coagulation tests was obtained by double centrifugation at 2500 g for 15 min. Prothrombin time (PT), APTT, and Kaolin clotting time (KCT) were performed using STA– NEOPLASTINE®, PTT-LA (Diagnostica STAGO), and LUPAKCT®,, respectively. Samples with prolonged APTT were screened for the presence of an inhibitor by 50:50 mixture of patient and pooled normal plasma while Rosner index was established for prolonged KCT. Failure of correction of prolonged APTT was confirmed using Staclot®-LA by diagnostic STAGO which is a phospholipid neutralization test. LA is confirmed when there was significant shortening of the APTT (difference of ≥8 s) or the Rosner index was >1.5. After 12 weeks, repeat LA tests for the four confirmed cases were positive; this ruled out transient LA.
Data were analyzed using Statistical Package for Social Sciences (SPSS) version 17.0 software (IBM). Quantitative variables were summarized using measure of central tendency, dispersion, and Student's t-test with P value set at 0.05. Chi-square test was used to demonstrate statistical significance.
| Results|| |
The mean age of the participants (±2 standard deviation) was 31.0 ± 3.8 years with a modal parity of 3 and a modal gestational age of 12 weeks. The past history of SA and confirmation of uncorrected prolonged APTT were shown in [Table 1].
LA-positive patients had a higher median age and a higher gestational age pregnancy than the LA-negative patients. Patients with LA, compared with those without LA, had significantly prolonged PT, APTT, and KCT (P ≤ 0.001, <0.001, and 0.01, respectively). However, there were no significant differences in their packed cell volume (PCV), white blood cell count (WBC), and platelet counts (P = 0.502, 0.271, and 0.121, respectively) [Table 2].
|Table 2: Characteristics of lupus anticoagulant-positive and lupus anticoagulant-negative participants|
Click here to view
The prevalence odds ratio and 95% confidence interval for preeclampsia/eclampsia, small for gestational age deliveries, and previous SA for LA-positive and LA-negative groups were shown in [Table 3].
|Table 3: Comparison of past obstetric history between lupus anticoagulant-positive and lupus anticoagulant-negative participants|
Click here to view
There is no difference in the detection rate of STACLOT and KCT as P = 1.000 (McNemar Chi–square test) [Table 4].
|Table 4: Comparison of the detection rate of Kaolin clotting time and Staclot®|
Click here to view
| Discussion|| |
This study found a prevalence of LA to be 3% using KCT and 4% using Staclot® in women with SA in Zaria, northern Nigeria. This is comparable to the finding of Awodu et al. working in southern Nigeria who reported a prevalence rate of 4.35% in women with recurrent SA s using KCT. However, this is lower than the prevalence of 13.5% reported by Al Samarrai in Iraq. The differences might be due to genetic variations in the two populations or due to sampling methods used. Furthermore, the low prevalence of LA in this study could be explained by the fact that the diagnosis of LA in pregnancy is often very difficult due to changes in coagulation proteins.
In this study, we found that the median gestational age for SA was 15 weeks. This is higher than for women without LA (12.8 weeks). This is different from the finding of Rai who reported that majority of SA in women with APL syndrome occur between 7th and 12th weeks of gestation. In another separate study, it was observed that women with APL antibodies have an unusually high proportion of pregnancy losses within the fetal period (10 or more weeks of gestation)., The reason for this could be because, women with LA, in this study, were older than women without LA (37 years vs. 29.2 years). It has been shown that prevalence of LA, like other autoantibodies, increases with age.
We also found that a woman with LA, although not statistically significant, was more likely to have previous bad obstetric histories such as preeclampsia/eclampsia, small for gestational age delivery, and previous SA than a woman without LA. These and other adverse pregnancy outcomes have been attributed to the presence of APL antibodies.
The detection rate of APTT/Staclot® was not significantly different from that of KCT, 4% versus 3% (P = 1.000). This is similar to the study by Kotila and Fasola who found a detection rate of 4.8% and 3.2% for APTT and KCT, respectively. However, Olayemi and Halim in Nigeria and Al Samarrai et al. in Iraq reported KCT to be most sensitive in screening for LA.
One of the four cases of LA had positive DAT although the mean platelet counts, PCV, and WBC were not different from those without LA (P = 0.716, 0.850, and 0.182, respectively). This is at variance with Al Samarrai who found reduction in platelet counts in patients with APA. Triplett reported varying degrees of immune-mediated thrombocytopenia, and to some extent, autoimmune hemolytic anemia in patients with APL antibody positivity.
Our study is not without limitations. First, the cross-sectional study design coupled with the small sample size could not establish causality and also makes generalization of findings difficult. Second, even though LA has been recognized to be the most specific predictor of SA, not investigating for other APS antibodies limits the scope of detection of LA. Third, other adverse pregnancy outcomes and pregnancies beyond 28 weeks of gestation were not explored in our study.
| Conclusion|| |
Patients with LA were more likely to have a previous history of SA, preeclampsia/eclampsia, and small for gestational age delivery. There is no significant difference between the detection rate of APPT/Staclot® and KCT. Therefore, every woman presenting with adverse pregnancy outcomes and having uncorrected APTT following 50:50 mixing study with pooled control plasma should be routinely investigated for LA.
My appreciation goes to doctors in the Departments of Haematology and Obstetrics and Gynaecology for their supports. I also wish to thank the nurses in Ante-natal and Reproductive Clinics for assisting in collecting patients' data. Finally, I also thank Drs. Sunday Audu and Ibrahim Mohammed of Community Medicine, and Mrs. Odengele of Iya Abubakar Centre, ABU, for data managements.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Olayemi EE, Bazuaye GN. Presence of lupus anticoagulant in an asymptomatic Nigerian. Afr Health Sci 2007;7:182-4.
Levine JS, Branch DW, Rauch J. The antiphospholipid syndrome. N
Engl J Med 2002;346:752-63.
Hillman RS, Ault KA, Rinder HM. Antiphospholipid antibodies. In: Haematology in Clinical Practice. 4th
ed. New York: McGraw-Hill; 2005. p. 404-5.
Barka N, Reagan K, Agopian M, Peter JP. Frequency of anticardiolipin and antiphosphatidylserine antibodies in patients with suspected antiphospholipid syndrome. Clin Chem 1995;41:5.
Olayemi E, Halim NK, Durosinmi MA, Awodu OA. Lupus anticoagulant in Nigerian children with homozygous sickle cell disease. Ann Afr Med 2005;4:122-6.
Rand JH, Senzel L. The antiphospholipid syndrome. In: Lichtman MA, Williams WJ, editors. Williams Hematology. 7th
ed. New York: McGraw-Hill; 2006. p. 2009-29.
Al-Mishari AA, Gader AG, Al-Jabbari AW, Al-Momen AK, El Rab MO, Babay ZH, et al.
The prevalence of lupus anticoagulant in normal pregnancy and in women with recurrent fetal loss – Recommendations for laboratory testing for lupus anticoagulant. Ann Saudi Med 2004;24:429-33.
Murdaca G, Colombo BM, Sprecacenere B, Caiti M, Massa G, Picciotto A, et al.
Autoimmune intrahepatic cholangiopathy associated with antiphospholipid antibody syndrome. Eur J Gastroenterol Hepatol 2007;19:910-2.
La Rosa L, Covini G, Galperin C, Catelli L, Del Papa N, Reina G, et al.
Anti-mitochondrial M5 type antibody represents one of the serological markers for anti-phospholipid syndrome distinct from anti-cardiolipin and anti-beta2-glycoprotein I antibodies. Clin Exp Immunol 1998;112:144-51.
Belilos E, Carsons S. Antiphospholipid Syndrome: eMedicine Rheumatology; 2007. Available from: https://www.googlesearch.com
. [Last accessed on 2011 Nov 04].
Topping J, Quenby S, Farquharson R, Malia R, Greaves M. Marked variation in antiphospholipid antibodies during pregnancy: Relationships to pregnancy outcome. Hum Reprod 1999;14:224-8.
Grudzinskas JG. Miscarriage, ectopic pregnancy and trophoblastic disease. In: Edmonds DK, editor. Dewhurst's Textbook of Obstetrics and Gynaecology for Postgraduates. 6th
ed. Malden, Massachusetts: Blackwell Science; 1999.
Yelnik CM, Laskin CA, Porter TF, Branch DW, Buyon JP, Guerra MM, et al.
Lupus anticoagulant is the main predictor of adverse pregnancy outcomes in aPL-positive patients: Validation of PROMISSE study results. Lupus Sci Med 2016;3:e000131.
Agboola A. Miscarriages. In: Textbook of Obstetrics and Gynaecology for Medical Students. 2nd
ed. Ibadan, Nigeria: Heinemann Educational Books (Nigeria) PLC; 2006. p. 95-100.
Lewis SM, Bain BJ, Bates I. Dacie and Lewis Practical Haematology. 10th
ed. Philadelphia: Churchill Livingstone Publishers; 2006. p. 1-463.
Diagnostica Stago, France (package insert). Determination of PT, APTT and detection of lupus anticoagulant. Available from: https://www.stago.com
. [Last accessed on 2011 Nov 12].
Tulip Diagnostics, India (package insert). LUPAKCT. Kaolin clotting time reagent for the detection of lupus anticoagulants. Available from: https://www.tulipgroup.com
. [Last accessed on 2011 Nov 12].
Awodu OA, Ejele OA, Shokunbi WA, Famodu AA. Lupus anticoagulant in African women with recurrent abortions. Niger J Clin Pract 2003;6:26-9.
Al Samarrai AA, Hilmi FA, Al-Allawi NA, Murad AF. Antiphospholipid antibodies in Iraqi women with recurrent mid-trimester abortions. J Lab Physicians 2012;4:78-82.
Triplett DA. Antiphospholipid-protein antibodies: Laboratory detection and clinical relevance. Thromb Res 1995;78:1-31.
Rai RS. Antiphospholipid syndrome and recurrent miscarriage. J Postgrad Med 2002;48:3-4.
] [Full text]
Lockshin MD, Druzin ML, Goei S, Qamar T, Magid MS, Jovanovic L, et al.
Antibody to cardiolipin as a predictor of fetal distress or death in pregnant patients with systemic lupus erythematosus. N
Engl J Med 1985;313:152-6.
Oshiro BT, Silver RM, Scott JR, Yu H, Branch DW. Antiphospholipid antibodies and fetal death. Obstet Gynecol 1996;87:489-93.
Olayemi E, Halim NK. Antiphospholipid antibodies in medical practice: A review. Niger J Med 2006;15:7-15.
Kotila TR, Fasola FA. Lupus anticoagulant in a population of healthy Nigerian adults. Ann Ib Postgrad Med 2005;3:45-8.
[Table 1], [Table 2], [Table 3], [Table 4]