Association of lupus anticoagulants with risk factors for obstetric complications and adverse gestational outcome

Abstract

BACKGROUND:

Lupus anticoagulant (LA) may be a cause of poor obstetric outcome.

OBJECTIVE:

To search the association of LA with risk factors for obstetric complications and adverse gestational outcome.

METHODS:

This retrospective cohort was consisted of 2 groups of pregnancies with poor obstetric history; 1) LA ( $+$ ) gestations (Study Group, $n=$ 20) and 2) LA ( $-$ ) gestations (Control Group, 78). All patients were admitted to a special antenatal care program and were examined in terms of risk factors for thrombotic events, placenta-related obstetric complications, and poor gestational outcomes. Patients were administered low-dose low-molecular-weight heparin (LMWH), low-dose salicylic acid and low-dose corticosteroid (if necessary) within the framework of a prophylaxis protocol in addition to their already existing medications.

RESULTS:

We have shown that adverse gestational outcome was 1.7-fold more frequent in LA ( $+$ ) pregnancies with poor obstetric history ( $p=$ 0.039, 70% vs. 41%). Higher rates of autoimmune diseases and hereditary thrombophilia were observed among LA ( $+$ ) patients compared to LA ( $-$ ) gestations (35% vs. 10.3%, $p<$ 0.012 and 55% vs. 19.2%, $p<$ 0.003, respectively). To identify the effectiveness of low-dose LMWH prophylaxis protocol, we compared gestational outcomes and demonstrated that the miscarriage rate was significantly decreased to half in current pregnancies compared to the previous gestations (73.6% vs. 35%, $p=$ 0.003).

CONCLUSIONS:

Autoimmune diseases and hereditary thrombophilia are more frequent in LA ( $+$ ) pregnancies, and these women are prone to obstetric problems. Low-dose LMWH and salicylic acid prophylaxis are critical in the management of LA ( $+$ ) pregnant women.

Keywords

Adverse gestational outcome autoimmune disorders hereditary thrombophilia lupus anticoagulants miscarriage preterm birth

1. Introduction

Lupus anticoagulants (LA) are a mixture of IgG and IgM that are produced by the immune system against the negatively charged phospholipid-binding proteins of the cell membrane [1, 2]. While the exact mechanisms by which LA leads to clotting problems are not fully understood, the main effect of LAs is binding to certain prothrombin-phospholipid complexes, preventing them from carrying out their normal clotting function [1, 3]. LA prolongs clotting process and is mostly associated with hypercoagulable states, thrombotic events, phospholipid syndromes, and autoimmune disorders such as systemic lupus erythematosus (SLE) [1, 2]. Besides, LA positivity is associated with stroke, transient ischemic stroke, acquired thrombophilia, pregnancy loss, gestational complications, infections, and it may also be present in asymptomatic patients [1, 4].

Hereditary thrombophilia, methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms, folate/B12 deficiencies, hyperhomocysteinemia, autoimmune disorders, and chronic inflammatory diseases are both risk factors for thrombotic events and placenta-related obstetric complications such as miscarriage, fetal growth restriction (FGR), preeclampsia, and preterm birth [5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15]. Thus, the predictive and/or prognostic values of LA are the concern of the physicians in the presence of these risk factors for thrombotic events and gestational disorders. The testing for LA requires a detailed history and examination of patients by the clinician to determine whether testing is necessary. The clinician should be able to answer two critical questions before conducting the test: the reason for testing and how the test result will change clinical management. Patient selection is crucial to minimize false positives and negatives, which can cause unnecessary anxiety for families and unnecessary treatments [16].

This study aims to demonstrate the whereness of LA in the management of pregnancies with poor obstetric history or/and risk factors for placenta-related obstetric complications and adverse gestational outcome.

2. Materials and methods

2.1 Patients

In this retrospective cohort, pregnancies with poor obstetric history and/or risk factors for placenta-related obstetric complications such as miscarriage and preterm birth were divided into two groups; 1) LA ( $+$ ) women (Study Group, $n=$ 20) and 2) LA ( $-$ ) women (Control Group, $n=$ 78). Power analysis was performed by G*Power 3.1.9.2. software program and 98 patients (total sample size) was enough to detect a significant difference between groups with 95% power at a level of $\alpha=$ 0.05 (effect size w:0.4, Df:2). All patients were admitted to a special antenatal care program between January 2016 to January 2020.

2.2 Data

All gestations were examined and evaluated in terms of the presence of immunological, inflammatory, metabolic, vascular and other risk factors for miscarriage, preterm birth and poor gestational outcomes. Risk factors for miscarriage, preterm birth, and poor gestational outcomes were defined as the presence of factor V Leiden mutation, G20210A mutation in the prothrombin gene, B12/folate deficiencies, hyperhomocysteinemia, C677T and A1298C homozygous mutations in MTHFR gene, autoimmune diseases (systemic lupus erythematosus, Sjögren’s disease and antiphospholipid syndrome, etc.), chronic inflammatory diseases (Celiac Disease, Crohn’s Disease, Ulcerative Colitis, Takayasu’s Arteritis, Behçet’s Disease, etc.) and autoimmune antibody positivities (anti-smooth muscle antibody $=$ ASMA, anti-parietal antibody $=$ APA, anti-tiroglobulin, anti-TPO). “Adverse gestational outcome” is defined as the presence of at least one of these medical conditions; miscarriage, preterm birth, FGR, stillbirth, 5 ${}^{\text{th}}$ minute APGAR score $<$ 7 and necessity of neonatal intensive care unit (NICU).

Table 1
Comparison of demographic features between groups

	LA ( $-$ ) $n=$ 78	LA ( $+$ ) $n=$ 20	Total $n=$ 98	$P$
Maternal age*	32.62 $\pm$ 5.2	34.80 $\pm$ 4.6	33.07 $\pm$ 5.11	0.090 ${}^{\text{a}}$
Gravidity	4.00 (2–10)	5.00 (2–12)	4.00 (2–12)	0.068 ${}^{\text{b}}$
Parity	2.00 (0–4)	2.00 (0–3)	2.00 (0–4)	0.785 ${}^{\text{b}}$
Miscarriage	2.00 (0–8)	2.00 (0–6)	2.00 (0–8)	0.177 ${}^{\text{b}}$
BOIp*	0.43 $\pm$ 0.36	0.34 $\pm$ 0.29	0.42 $\pm$ 0.35	0.267 ${}^{\text{b}}$

Data are presented as *Mean $\pm$ standard deviation or median (minimum-maximum). a: Independent $t$ test, b: Mann Whitney U, LA: Lupus anticoagulant, BOIp: Beksac Obstetric Index during pregnancy.

Laboratory tests were performed for protein S, protein C, antithrombin-III and B12/folate deficiencies together with C677T-A1298C homozygous polymorphisms in methylenetetrahydrofolate reductase (MTHFR) gene, factor V Leiden and prothrombin G20210A gene mutations. Complete blood count, hematological tests, autoimmune antibodies, biochemical tests, and other necessary laboratory tests were also performed at the beginning of the gestations. Antiphospholipid antibodies including LA, anticardiolipin antibodies, and anti- $\beta$ 2-glycoprotein I antibodies were also evaluated. We used dilute Russell viper venom test (dRVVT) for detection of Lupus Anticoagulants (Sysmex CS-2500, Siemens kit-Clotting Method) [17]. LA 1 Screening and LA 2 Confirmation Reagents were used. Russell’s viper venom present in LA 1 Screening Reagent initiate plasma clotting by directly activating factor X. Presence of LA antibodies prolong the LA 1 Screening Reagent clotting time. Although LA 2 Confirmation Reagent is similar to LA 1 Screening Reagent, it contains high phospholipid concentration which counteracts LA antibodies and largely corrects the clotting time [18, 19]. If the LA 1 Screening Reagent clotting time result is more than 2 SD longer than the mean of normal plasma (ideally $n\geqslant$ 20), the result should be considered abnormal. Then, mixing studies should be carried out on a 50:50 mixture of test plasma and normal plasma to exclude factor II, V and X deficiencies, If the mixing test is still prolonged, it indicates that a circulating inhibitor (such as LA) is present in the patient plasma. For our method; normal ranges for LA 1 Screening Reagent was 31–44 seconds and 30–38 seconds for LA 2 Confirmation Reagent. The ratio of LA 1 / LA 2 was 0.8–1.2. Coefficient of variation of our method was less than 3.5% on normal plasmas and less than 5% for abnormal samples.

All patients were administered low-dose low-molecular-weight heparin (LMWH) (enoxaparin 2000 anti-Xa IU/0.2 mL), low-dose salicylic acid (100 mg acetylsalicylic acid) and low-dose corticosteroid (if necessary, Methylprednisolone, 1 $\times$ 4 mg/day orally) within the framework of a prophylaxis protocol in addition to their already existing medications as soon as their pregnancies were confirmed [5]. Pregnancy follow-up consisted of serial ultrasonography to evaluate fetal growth, aneuploidy screening (combined or triple test), fetal anatomy scanning at the 20 ${}^{\text{th}}$ –24 ${}^{\text{th}}$ gestational week (gw), oral glucose challenge test, routine blood tests (CBC, biochemistry, immunological, etc.) and a non-stress test performed weekly after 28 ${}^{\text{th}}$ gw.

Table 2

The comparison of LA ( $-$ ) and LA ( $+$ ) groups in terms of maternal risk factors for miscarriage, preterm birth and adverse gestational outcome

Maternal risk factors	LA ( $-$ ) $n=$ 78 (%)	LA ( $+$ ) $n=$ 20 (%)	Total $n=$ 98 (%)	$P$
MTHFR polymorphisms ( $-$ )	41 (52.6)	10 (50)	51 (52)	0.838 ${}^{\text{a}}$
MTHFR polymorphisms ( $+$ )	37 (47.4)	10 (50)	47 (48)
Autoimmune disease ( $-$ )	70 (89.7)	13 (65)	83 (84.7)	0.012 ${}^{\text{b}}$ *
Autoimmune disease ( $+$ )	8 (10.3)	7 (35)	15 (15.3)
Autoantibody positivity ( $-$ )	37 (47.4)	10 (50)	47 (48)	0.838 ${}^{\text{a}}$
Autoantibody positivity ( $+$ )	41 (52.6)	10 (50)	51 (52)
Diabetes mellitus ( $-$ )	66 (84.6)	20 (100)	86 (87.8)	0.118 ${}^{\text{b}}$
Diabetes mellitus ( $+$ )	12 (15.4)	0 (0)	12 (12.2)
Hereditary thrombophilia ( $-$ )	63 (80.8)	9 (45)	72 (73.5)	0.003 ${}^{\text{c}}$
Hereditary thrombophilia ( $+$ )	15 (19.2)	11 (55)	26 (26.5)
Cardiovascular diseases ( $-$ )	63 (80.8)	17 (85)	80 (81.6)	0.472 ${}^{\text{b}}$
Cardiovascular diseases ( $+$ )	15 (19.2)	3 (15)	18 818.4)
Vitamin B12
Normal	57 (73.1)	18 (90)	75 (76.5)	0.312 ${}^{\text{b}}$
Low	14 (17.9)	1 (5)	15 (15.3)
High	7 (9)	1 (5)	8 (8.2)
Homocysteine levels
$<$ 10	32 (41)	6 (30)	38 (38.8)
10–15	33 (42.3)	9 (45)	42 (42.9)	0.545 ${}^{\text{b}}$
$>$ 15	13 (16.7)	5 (25)	18 (18.4)
Total	78 (100)	20 (100)	98 (100)

a: Pearson Chi-Square, b: Fisher’s Exact Test, c: Yates continuity test, *: $p<$ 0.05, LA: Lupus anticoagulant.

Table 3

The comparison of current pregnancies of the study groups in terms of gestational outcomes, obstetric complications and birth data

Current pregnancies	LA ( $-$ ) $n$ (%)	LA ( $+$ ) $n$ (%)	Total $n$ (%)	$P$
Adverse gestational outcome ( $-$ )	46 (59)	6 (30)	52 (53.1)
Adverse gestational outcome ( $+$ )	32 (41)	14 (70)	46 (46.9)	0.039 ${}^{\rm a*}$
Total	78 (100)	20 (100)	98 (100)
Preterm birth
( $-$ )	73 (93.6)	19 (95)	92 (93.9)	0.645 ${}^{\text{b}}$
( $+$ )	5 (6.4)	1 (5)	6 (6.1)	0.645 ${}^{\text{b}}$
Total	78 (100)	20 (100)	98 (100)
Miscarriage
( $-$ )	61(78.2)	13 (65)	74 (75.5)
( $+$ )	17 (21.8)	7 (35)	24 (24.5)	0.249 ${}^{\text{b}}$
Total	78 (100)	20 (100)	98 (100)
Stillbirth
( $-$ )	77 (98.7)	19 (95)	96 (98)
( $+$ )	1 (1.3)	1 (5)	2 (2)	0.368 ${}^{\text{b}}$
Total	78 (100)	20 (100)	98 (100)
APGAR score (5 ${}^{\text{th}}$ minute)
$<$ 7	4 (6.7)	1 (8.3)	5 (5.4)
$\geqslant$ 7	56 (93.3)	11 (91.7)	67 (94.6)	0.610 ${}^{\text{b}}$
Total	60 (100)	12 (100)	72 (100)
Necessity of NICU
( $-$ )	50 (83.3)	7 (58.3)	57 (79.2)
( $+$ )	10 (16.7)	5 (41.7)	15 (20.8)	0.111 ${}^{\text{b}}$
Total	60 (100)	12 (100)	72 (100)
Birthweight (Mean $\pm$ SD)	2927 $\pm$ 456.5	3045.83 $\pm$ 341.9	2946.8 $\pm$ 439.6	0.397 ${}^{\text{c}}$
Gestational age at birth (day, Mean $\pm$ SD)	259.11 $\pm$ 5.56	259.66 $\pm$ 7.92	259.20 $\pm$ 5.95	0.371 ${}^{\text{d}}$
Abnormal oral glucose challenge test
( $-$ )	63 (80.8)	16 (80)	79 (80.6)
( $+$ )	15 (19.2)	4 (20)	19 (19.4)	0.891 ${}^{\text{b}}$
Total	78 (100)	20 (100)	98 (100)

a: Yates Continuity Correction test, b: Fisher’s exact test, c: Independent $t$ -test, d: Mann Whitney U test, *: $p<$ 0.05, “Adverse gestational outcome” is defined as the presence of at least one of these outcomes: miscarriage, preterm births, stillbirth, APGAR score $<$ 7 and necessity of neonatal intensive care unit (NICU), LA: Lupus anticoagulant.

Control and study groups were compared in terms of the presence of defined maternal risk factors, maternal age, gravidity, parity, oral glucose challenge test result, presence of pregestational/ gestational diabetes mellitus, obstetric complications (miscarriage, preterm birth and stillbirth), gestational age (days) at birth, birth weight, APGAR scores, neonatal intensive care unit (NICU) admissions, adverse gestational outcome and Beksac Obstetric Index (BOI). BOI is defined as $[\text{number of living child}+(\pi/10)]/\text{gravida}$ [20]. BOIp is the BOI value calculated during pregnancy. All study subjects were delivered at Hacettepe University Hospital in between 2016–2020. Necessary data were extracted from the electronic database of the Division of Perinatology (Hacettepe University Hospital).

2.3 Statistics

The data analysis was performed using the Statistical Package for the Social Sciences (SPSS, version 23) (Armonk, NY, IBM Corp.). The results were reported as numbers, percentages, and means $\pm$ standard deviations. To compare the groups, the Pearson Chi-square test, Yates Continuity Correction test or Fischer’s exact test was used. Normality of numerical data such as age, gravidity, parity, BOI, and number of miscarriages were checked using the Shapiro-Wilks test. Normally distributed data were compared using the Independent $t$ -test, while non-normally distributed data were analyzed using the non-parametric Mann Whitney-U test. $P$ -values $<$ 0.05 were considered statistically significant. Informed consent was obtained from all individuals included in this study. The study was approved by the Hacettepe University Ethics Committee with reference number GO 19/1064.

3. Results

Maternal age, gravidity, parity, miscarriage, and BOIp were evaluated in the study (LA ( $+$ )) and control (LA ( $-$ )) groups. The mean age of the cohort was 33.07 $\pm$ 5.11 (range 28–44 years), and there was no significant difference between the LA ( $+$ ) (34.80 $\pm$ 4.6, range 28–44 years) and LA ( $-$ ) groups (32.62 $\pm$ 5.2, range 21–44 years). As seen in Table 1, study and control groups were similar in demographical characteristics ( $p>$ 0.05, for all).

To evaluate the adverse effect of LA positivity on pregnancies, we compared the study and control groups in terms of risk factors for adverse gestational outcome. Higher rates of autoimmune diseases were observed among LA ( $+$ ) patients compared LA ( $-$ ) gestations (35% vs. 10.3%, $p<$ 0.012) (Table 2). No statistically significant difference between groups was found for either MTHFR polymorphism ( $p=$ 0.838) or autoantibody positivity ( $p=$ 0.838). Both LA ( $+$ ) and LA ( $-$ ) groups showed similar rates of Diabetes mellitus, cardiovascular diseases, vitamin B12, and homocysteine levels ( $p>$ 0.05, for all), however, hereditary thrombophilia was more frequently found in LA ( $+$ ) women compared to LA ( $-$ ) women (55% vs. 19.2%, $p<$ 0.003) (Table 2).

We have also shown that adverse gestational outcome was 1.7-fold more frequent in LA ( $+$ ) women ( $p=$ 0.039, 70% vs. 41%). We did not observe preeclampsia and fetal growth restriction in this cohort, most probably due to pre-pregnancy care of the patients and “low-dose LMWH, salicylic acid and corticosteroid (in necessary cases)” prophylaxis which was started as soon as the pregnancy was confirmed [5]. Rates of preterm birth, miscarriage, stillbirth, and 5 ${}^{\text{th}}$ minute APGAR score $<$ 7 were found to be 5%, 35%, 5%, and 8.3%, respectively in the study group which were not significantly different than the control group ( $p>$ 0.05). Necessity of NICU rate was higher in LA ( $+$ ) group compared to LA ( $-$ ) group (41.7% vs. 16.7%), however, we could not demonstrate the statistically significant difference ( $p>$ 0.05) (Table 3). Furthermore, there was no statistically significant difference between groups according to birth weight, gestational age at birth, and abnormal oral glucose challenge test ( $p>$ 0.05, for all).

We evaluated 318 previous pregnancies of 98 patients (LA ( $+$ ) and LA ( $-$ ) groups). Ten pregnancies were excluded from the study cohort due to three of them being unintended pregnancies and resulting in termination of pregnancy, and seven pregnancies were medically terminated. Therefore, we considered 308 previous pregnancies in the final statistics. As seen in Table 4, there was no statistically significant difference between LA ( $+$ ) and LA ( $-$ ) women in terms of adverse gestational outcomes such as preterm birth, miscarriage, and stillbirth.

To identify the effectiveness of low-dose LMWH prophylaxis protocol, we compared gestational outcomes (miscarriage, preterm birth, and stillbirth) of previous and current pregnancies in the LA ( $+$ ) group. As seen in Table 5, the miscarriage rate was significantly decreased to half in current pregnancies compared to previous ones (73.6% vs. 35%, $p=$ 0.003).

4. Discussion

LA testing is important for evaluating patients with hypercoagulable states, thrombotic events, phospholipid syndromes, and pregnancy losses [1, 21, 22, 23]. Though the diagnostic value of LA is still challenging, it has been demonstrated that it correlates with pregnancy morbidity and thrombosis [1, 3, 22, 23]. LAs are identified by a systematic, laboratory-based approach that includes prolongation of a phospholipid-dependent screening assay, demonstration of an inhibitory activity by mixing studies with healthy pooled plasma, and documentation that the inhibitory activity is phospholipid dependent [17]. The activated partial thromboplastin time (aPTT) and dilute Russell viper venom time (dRVVT) constituted major testing methods [22]. In screening studies, LA-sensitive aPTT methods were more sensitive to weak LA than dRVVT-based methods but less specific [4, 22].

Table 4

The comparison of the previous pregnancies of the study groups in terms of miscarriage, preterm birth and stillbirth rates

Previous pregnancies	LA ( $-$ ) $n$ (%)	LA ( $+$ ) $n$ (%)	Total $n$ (%)	$P$
Preterm birth
( $-$ )	224 (94.9)	68 (94.4)	292 (94.8)
( $+$ )	12 (5.1)	4 (5.6)	16 (5.2)	0.538 ${}^{\text{b}}$
Total	236 (100)	72 (100)	308 (100)
Miscarriage
( $-$ )	76 (32.2)	19 (26.4)	95 (30.8)
( $+$ )	160 (67.8)	53 (73.6)	213 (69.2)	0.430 ${}^{\text{a}}$
Total	236 (100)	72 (100)	308 (100)
Stillbirth
( $-$ )	230 (97.5)	69 (95.8)	299 (97.1)
( $+$ )	6 (2.5)	3 (4.2)	9 (2.9)	0.441 ${}^{\text{b}}$
Total	236 (100)	72 (100)	308 (100)

a: Yates Continuity Correction test, b: Fisher’s exact test.

Table 5

The comparison of the gestational outcomes of previous and current pregnancies of LA ( $+$ ) women in order to see the effectiveness of low-dose LMWH prophylaxis protocol

Effectiveness of LMWH prophylaxis

protocol in LA (

+

) women

Previous pregnancies

n=

Current pregnancies

n=

Total

n=

P

Preterm birth

(

-

)

68 (94.4)

19 (95)

87 (94.6)

(

+

)

4 (5.6)

1 (5)

5 (5.4)

0.703

{}^{\text{a}}

Total

72 (100)

20 (100)

92 (100)

Miscarriage

(

-

)

19 (26.4)

13 (65)

32 (34.8)

(

+

)

53 (73.6)

7 (35)

60 (65.2)

0.003

{}^{\rm b*}

Total

72 (100)

20 (100)

92 (100)

Stillbirth

(

-

)

69 (95.8)

19 (95)

88 (95.7)

(

+

)

3 (4.2)

1 (5)

4 (4.3)

0.632

{}^{\text{a}}

Total

72 (100)

20 (100)

92 (100)

a: Fisher’s exact test, b: Yates Continuity correction, *: $p<$ 0.05, LA: Lupus anticoagulant.

The Scientific and Standardization Committee for LA/anti-phospholipid antibodies suggests that anticoagulation with any drug, including unfractionated heparin, LMWH, and direct oral anticoagulants, may potentially complicate LA detection, as anticoagulants often prolong test clotting times [24, 25]. Therefore, LA tests were performed on the patients in our cohort when they were not using anticoagulants. Our method bypass Factor VII of the extrinsic pathway in addition to contact and antihemophilic factors of the intrinsic pathway. Therefore, it is more specific for LA than APTTs as they are not affected by contact factor abnormalities or by factor VIII deficiencies or antibodies.

Autoimmune diseases, autoimmune antibody positivities, some metabolic disorders (B12/folate deficiencies, reduced MTHFR activity, and hyperhomocysteinemia) and chronic inflammatory diseases are all risk factors for thrombosis and placenta-related obstetric complications such as miscarriage, FGR, preeclampsia, preterm birth, and stillbirth [5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 26]. Immunological, metabolic, infectious, inflammatory and toxic factors create an environment that is conducive to the development of the injury of endothelial/cellular structures of intervillous space of placenta, thrombosis, and placental inflammation [5, 9, 12, 15]. Although the existence of a strong association between antiphospholipid antibodies and recurrent fetal losses in women with autoimmune disease has been demonstrated in many studies, the association is variable in women without autoimmune disease [27, 28]. Among the antiphospholipid antibodies, the association of LA with recurrent fetal loss, late fetal death, placenta-mediated complications, and intrauterine growth restriction has been most consistently reported [29, 30, 31]. In this study, we have demonstrated that LA positivity is associated with higher rates of autoimmune diseases and hereditary thrombophilia. We have also shown that adverse gestational outcome was 1.7-fold more frequent in pregnancies with LA positivity. The role of LA on poor pregnancy outcomes may be explained by different mechanisms, such as thrombosis of placental vessels, decidual vasculopathy, and placental infarction leading to uteroplacental insufficiency [28, 32].

Gebhart et al. reported that the rate of pregnancy complications in their prospective study in persistent LA-positive patients was 70% despite the initiation of anticoagulant treatment with LMWH and low-dose aspirin in the majority of pregnancies [33]. In contrast to the mentioned study, we compared the miscarriage and preterm birth rates of previous and current pregnancies in the LA ( $+$ ) group to identify the effectiveness of low-dose LMWH and salicylic acid prophylaxis and demonstrated that the miscarriage rate significantly decreased to half in current pregnancies compared to previous ones (73.6% vs. 35%, $p=$ 0.003). Low-dose LMWH having anti-inflammatory, anti-thrombotic, and immune-modulatory affects is recommended for pregnancies with risk factors for placenta associated obstetric complications and adverse gestational outcomes [5, 6, 9, 34, 35]. Our results demonstrated the significance of low-dose LMWH prophylaxis in LA ( $+$ ) pregnancies who are prone to hypercoagulable states, phospholipid syndrome and pregnancy losses. Thus, LAs can be used for the prediction of adverse gestational outcomes in pregnancies with poor obstetric history.

The limitations of this study were the retrospective design and the narrow numbers of the LA ( $+$ ) cases. Additionally, our data report results of a very selected group of high-risk LA-positive women. However, the evaluation of LA in the special cohort with high-risk factors for poor pregnancy outcomes is the strength of the study.

In conclusion, risk factors for obstetric complications, including LA testing, should be meticulously investigated in order to achieve a good pregnancy outcome. Autoimmune diseases and hereditary thrombophilia are more frequent in LA ( $+$ ) pregnancies, and these women are prone to pregnancy losses. Low-dose LMWH and salicylic acid prophylaxis are critical in the management of LA ( $+$ ) pregnant women.

Research funding:

None declared.

Author contributions

Conception: Murat Cagan, Zeliha Gunnur Dikmen, Mehmet Sinan Beksac.

Methodology: Murat Cagan, Zeliha Gunnur Dikmen, Mehmet Sinan Beksac.

Data collection: Murat Cagan, Hanife Guler Donmez, Zeliha Gunnur Dikmen.

Interpretation or analysis of data: Murat Cagan, Hanife Guler Donmez, Mehmet Sinan Beksac.

Preparation of the manuscript: Murat Cagan, Hanife Guler Donmez, Zeliha Gunnur Dikmen, Mehmet Sinan Beksac.

Revision for important intellectual content: Zeliha Gunnur Dikmen, Mehmet Sinan Beksac.

Supervision: Mehmet Sinan Beksac.

Footnotes

Acknowledgments

Special thanks to all the medical staff who work with devotion in order to provide optimal health care to the patients in our institution.

Conflict of interest

The authors declare that they have no conflict of interest.

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Association of lupus anticoagulants with risk factors for obstetric complications and adverse gestational outcome

Abstract

BACKGROUND:

OBJECTIVE:

METHODS:

RESULTS:

CONCLUSIONS:

Keywords

1. Introduction

2. Materials and methods

2.1 Patients

2.2 Data

Table 1 Comparison of demographic features between groups

3. Results

4. Discussion

Research funding:

Author contributions

Footnotes

Acknowledgments

Conflict of interest

References

Table 1
Comparison of demographic features between groups