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. 2022 May 19:13:849692.
doi: 10.3389/fphar.2022.849692. eCollection 2022.

Treatment of Refractory/High-Risk Pregnancies With Antiphospholipid Syndrome: A Systematic Review of the Literature

Ariela Hoxha  1   2 , Daniela Tormene  2 , Elena Campello  2 , Paolo Simioni  2
Affiliations

Treatment of Refractory/High-Risk Pregnancies With Antiphospholipid Syndrome: A Systematic Review of the Literature

Ariela Hoxha et al. Front Pharmacol. .

Abstract

Different treatment protocols have been employed to manage heparin/low-dose aspirin refractory or high-risk pregnancies in antiphospholipid antibody syndrome (APS) pregnancies. A systematic review of the literature on additional treatments used in refractory and/or high-risk APS pregnancies was conducted. Records from February 2006 to October 2021 were retrieved from PubMed, Web of Science, Cochrane, and the www.clinicaltrials.gov platform. Twenty-one studies met our eligibility criteria. Live birth rate is this study's primary endpoint, while pregnancy complications and adverse events are secondary endpoints. A total of 434 pregnancies, 162 (37.3%) refractory and 272 (62.7%) high-risk/refractory pregnancies, were included. Both IVIG <2 gr/kg/monthly/HCQ/LDS and PEX/IA ± LDS led to 100% viable infants in refractory APS. Furthermore, HCQ 200-400 mg showed a higher live birth rate than HCQ + LDS (88.6% vs. 82.7%). Following treatment protocol with HCQ 200-400 mg and IVIG <2 gr/kg/monthly/HCQ/LDS, pregnancy complications rates of 16.7 and 83.3% were registered, respectively. Pravastatin 20 mg, IA weekly + IVIG 2 gr/monthly, and PEX weekly + IVIg 2 gr/kg/monthly showed higher live birth rates in high-risk APS pregnancies of 100, 100 and 92%, respectively, whereas the lower severe pregnancy complications were reported in pregnancies treated with PEX weekly + IVIg 2 gr/kg/monthly (11.1%). One (0.6%) case of dermatitis during treatment with HCQ was observed. The results of this study showed that HCQ 200-400 mg and PEX weekly + IVIG 2 gr/kg/monthly achieved a higher live birth rate in refractory APS and high-risk/refractory APS, respectively. The results presented provide clinicians with up-to-date knowledge in the management of APS pregnancies according to risk stratification.

Keywords: antiphospholipid antibodies; antiphospholipid syndrome; obstetric antiphospholipid syndrome; pregnancy; therapy.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Flow diagram of study selection.
See this image and copyright information in PMC

References

    1. Abel J. J., Rowntree L. G., Turner B. B. (1990). Plasma Removal with Return of Corpuscles (Plasmaphaeresis). The Journal of Pharmacology and Experimental Therapeutics Vol. V. No. 6, July, 1914. Transfus Sci. 11, 166–177. - PubMed
    1. Abisror N., Mekinian A., Brechignac S., Ruffatti A., Carbillon L., Fain O. (2015). Inefficacy of Plasma Exchanges Associated to Rituximab in Refractory Obstetrical Antiphospholipid Syndrome. Presse Med. 44, 100–102. 10.1016/j.lpm.2014.05.021 - DOI - PubMed
    1. Albert C. R., Schlesinger W. J., Viall C. A., Mulla M. J., Brosens J. J., Chamley L. W., et al. (2014). Effect of Hydroxychloroquine on Antiphospholipid Antibody-Induced Changes in First Trimester Trophoblast Function. Am. J. Reprod. Immunol. 71, 154–164. 10.1111/aji.12184 - DOI - PubMed
    1. Alijotas-Reig J., Esteve-Valverde E., Llurba E., Gris J. M. (2019). Treatment of Refractory Poor aPL-Related Obstetric Outcomes with TNF-Alpha Blockers: Maternal-Fetal Outcomes in a Series of 18 Cases. Semin. Arthritis Rheum. 49, 314–318. 10.1016/j.semarthrit.2019.02.006 - DOI - PubMed
    1. Belizna C., Pregnolato F., Abad S., Alijotas-Reig J., Amital H., Amoura Z., et al. (2018). HIBISCUS: Hydroxychloroquine for the Secondary Prevention of Thrombotic and Obstetrical Events in Primary Antiphospholipid Syndrome. Autoimmun. Rev. 17, 1153–1168. 10.1016/j.autrev.2018.05.012 - DOI - PubMed

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