Pregnancy Outcome in Women with Obstetric and

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OAPS obstetric antiphospholipid syndrome, TAPS thrombotic antiphospholipid syndrome, .... values are greater than 1.0 and at least 20 % of the expected.
Pregnancy Outcome in Women with Obstetric and Thrombotic Antiphospholipid Syndrome—A Retrospective Analysis and a Review of Additional Treatment in Pregnancy Karoline Mayer-Pickel, Katharina Eberhard, Uwe Lang & Mila CervarZivkovic Clinical Reviews in Allergy & Immunology ISSN 1080-0549 Clinic Rev Allerg Immunol DOI 10.1007/s12016-016-8569-0

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Author's personal copy Clinic Rev Allerg Immunol DOI 10.1007/s12016-016-8569-0

Pregnancy Outcome in Women with Obstetric and Thrombotic Antiphospholipid Syndrome—A Retrospective Analysis and a Review of Additional Treatment in Pregnancy Karoline Mayer-Pickel 1

&

Katharina Eberhard 2 & Uwe Lang 1 & Mila Cervar-Zivkovic 1

# Springer Science+Business Media New York 2016

Abstract Antiphospholipid syndrome (APS) is associated with pregnancy complications such as recurrent early fetal loss (RFL), fetal death, preeclampsia (PE), and intrauterine growth restriction (obstetric APS/OAPS). Other clinical manifestations are venous and/or arterial thromboses (thrombotic APS/TAPS). The data of 37 pregnancies with OAPS and 37 pregnancies with TAPS were analyzed and compared. Overall, the most frequent APS antibodies (aPl) were LA as well as Btriple-positivity^; LA antibodies were significantly more frequent in women with TAPS (67.6 % TAPS vs. 29.7 % OAPS, p < 0.010), whereas Btriple-positivity^ was significantly more seen in women with OAPS (40.5 % OAPS vs. 13.5 % TAPS, p < 0.010). Adequate therapy has been administered in nearly all pregnancies with TAPS, whereas in 18.9 % of pregnancies with OPS, no therapy has been given at all. One woman in OAPS and four women in TAPS were treated with plasmapheresis and immunoadsorption. There was no significant association between adverse obstetric outcome and therapy. The most frequent pregnancy complications were RFL in the OAPS group (32.4 vs. 13.5 % in TAPS) and PE in the TAPS group (18.9 % in OAPS and TAPS, respectively). The data of our study showed that pregnancies with OAPS and TAPS have a similar rate of pregnancy complications. However, pregnancies with OAPS tend to have rather RFL. Although we were not able to reveal a

* Karoline Mayer-Pickel [email protected]

1

Department of Obstetrics and Gynecology, Medical University of Graz, Auenbruggerplatz 14, A-8036 Graz, Austria

2

Research Facility for Biostatistics, Medical University of Graz, Graz, Austria

significant association with adverse obstetric outcome, it seems that the current adequate therapy for APS in pregnancy, consisting of LDA and LMWH, might rather prevent the development of RFL. Additionally, it might be considered to divide the obstetric APS into obstetric APS with early pregnancy complications and obstetric APS with late pregnancy complications. The division into two groups of obstetric APS might facilitate the choice of additional therapy in these women. Keywords Antiphospholipid syndrome . Pregnancy . Preeclampsia . Thrombosis

Introduction Antiphospholipid syndrome (APS) is an autoimmune disease and is characterized by the presence of antiphospholipid antibodies (anticardiolipin antibodies/ACLA, lupus anticoagulants/LA, and anti-β2-glycoprotein) in the maternal circulation. These antibodies are associated with arterial and/or venous thromboses and with adverse obstetric outcome such as early and recurrent fetal loss, preeclampsia (PE), intrauterine growth restriction (IUGR), and intrauterine fetal death (IUFD). APS occurs isolated as primary APS or combined with other autoimmune diseases, such as systemic lupus erythematosus (SLE) or Raynaud disease [1–4]. APS is characterized by a broad clinical spectrum, ranging from non-criteria manifestations such as livedo reticularis, thrombocytopenia, or skin ulcers to the classical pregnancy morbidities and vascular events [5, 6]. Antiphospholipid antibodies (aPL) activate platelets and endothelial cells, inhibit fibrinolysis, and interfere with the protein C pathway in patients with APS. Platelet activation leads to the clinical manifestations of thrombocytopenia and

Author's personal copy Clinic Rev Allerg Immunol

thrombosis [7]. In obstetric APS, aPL impair placentation and decrease trophoblast proliferation and invasion. Generally, involvement of inflammatory mediators is part of both the etiology and pathophysiology in thrombotic (TAPS) and obstetric APS (OAPS). Activation of the complement system and leukocyte activation are i.a. considered important in the pathophysiology of TAPS and OAPS [8–11]. Nevertheless, there is increasing knowledge that the pathophysiological mechanisms behind OAPS and TAPS are different despite the serological similarities [8]. Additionally, it seems that due to the broad spectrum of clinical manifestations, APS might not be a unique disease, but rather a syndrome with the occurrence of aPl [12]. It has been suggested that i.a. treatment response, maternal complications and long-term follow-up in OAPS differ from TAPS [13–17]. However, obstetric complications are heterogeneous, complex, and not totally understood. It seems that the negative effect on placentation is not necessarily associated with prothrombotic or inflammatory events [18]. The aim of this study was to analyze the pregnancy outcome in pregnancies with antiphospholipid syndrome. For study purposes, pregnancies with obstetric and thrombotic antiphospholipid syndrome were compared.

were performed in order to exclude an atrioventricular heart block. Decisions regarding the therapy in all women were made collectively according to our management protocol, which was developed corresponding to international guidelines [19]. Low molecular weight heparin (LMWH/enoxiparin) was started early in pregnancy and continued until onset of labor or the day before planned cesarean section and restarted immediately after delivery and continued for 6 weeks postpartum. Low-dose aspirin (LDA; 100 mg) prophylaxis was started after confirmation of fetal heart rate and continued until 34 weeks of gestation. Preeclampsia and hemolysis (H), elevated liver Enzymes (EL) and low platelets (LP) syndrome were defined according to international criteria [20, 21] and managed according to the obstetric unit protocol based on international guidelines [20, 21]. Recurrent early fetal loss was defined as three or more consecutive miscarriages before 10 weeks of gestation; late fetal loss/intrauterine fetal death (IUFD) was defined as fetal death after 10 weeks of gestation; intrauterine growth restriction (IUGR) was defined as 0.05 normally distributed data assumed) and Q-Q plots. If assumptions were met, independent t test was used for group comparisons according to clinical characteristics; otherwise, the non-parametric Mann-Whitney U test was applied. Chi-square test was used to compare categorical variables and Fisher exact test for 2 x 2 contingency tables if expected count was less than 5. Data are presented as total number (%), as mean ± standard deviation, or, in case of a skewed distribution, as median and interquartile range (25th percentile and 75th percentile). All statistical tests were performed using SPSS version 23.0 (SPSS Inc., Chicago, IL), and GraphPad Prism version 6.05 was used for visualizations. A two tailed p value of less than 0.05 was considered as statistically significant.

Results During the study period, 38 women with definite APS had 72 pregnancies. Nineteen women with obstetric antiphospholipid syndrome (OAPS) had 37 pregnancies and 21 women with thrombotic antiphospholipid syndrome (TAPS) had 37 pregnancies. Demographic characteristics of all women and pregnancies with OAPS and TAPS are shown and compared in Table 1.

Author's personal copy Clinic Rev Allerg Immunol Table 1 Demographic characteristics of patients included in the study compared OAPS with TAPS

OAPS (n = 37)

TAPS (n = 37)

p value

Age of patients (years)

28.65 ± 5.22

28.49 ± 6.84

0.909

Pregnancy BMI

22.30 (19.50–25.10)

22.90 (20.15–28.15)

0.754

Average systolic blood pressure (mmHg) Average diastolic blood pressure (mmHg)

130.95 ± 11.66 85.27 ± 10.05

127.27 ± 12.10 79.35 ± 9.50

0.187 0.011

Caucasian Arabian

31 (83.8 %) 2 (5.4 %)

34 (91.9 %) 3 (8.1 %)

0.114

African Nicotine abuse

4 (10.8 %)

0 (0 %)

Yes No Gestational diabetes

0 (0 %) 37 (100.0 %)

11 (29.7 %) 26 (70.3 %)

Ethnicity

Yes