Evaluating Treatment of Antiphospholipid Syndrome during Pregnancy with Knowledge Synthesis Methods

Background: Pregnancies complicated by antiphospholipid syndrome (APS) are at an increased risk of adverse pregnancy outcomes, including recurrent miscarriage, stillbirths, placental insufficiencies and maternal thrombosis. APS during pregnancy remains a challenge, since these complications persist, even when treated with standard regimens. Objective: To evaluate the published evidence on key information of medications to address their effectiveness and safety for pregnant women with APS. Methods: Given variability of the published information on pregnancy uses of APS medications, I approached this research in a systematic manner combining multiple methodologies. My first study was a systematic review and meta-analysis of the pregnancy safety of statins, which are being repurposed and have emerged as a new group of medications to manage APS. Next, I explored the use of vitamin k antagonists (VKAs) in pregnant women with APL using a scoping review approach, which are discontinued during the first trimester due to established teratogenicity. Finally, a systematic review was conducted to assess the pregnancy associated pharmacokinetic changes of three groups of medications used for APS (1. low-dose aspirin; 2. unfractionated heparin and low-molecular weight heparin; and 3. Chloroquine and hydroxychloroquine). Results and Conclusion: There was no significant increase in malformations in the statin exposed pregnancies. However, there was a small but significant increase in spontaneous abortions. It is not clear if this is due to the medication or underlying disease of the exposed group. There was an apparent geographical variation in the utilization of VKA and a lack of systematic investigation. The resultant information gap is wide relative to its exploration in pregnant women with mechanical heart valves. Although heterogeneity of PK analysis methods in the literature was striking, apparent clearance of these medications was consistently increased during pregnancy, likely based on the physiological changes in pregnancy. While doses of heparins are often increased during pregnancy, the other 2 medication groups are not fully investigated for the need of dose modification during pregnancy. Moreover, I confirmed PK evidence is largely lacking for women in general, let alone pregnant women with APS, creating a huge knowledge gap and therapeutic void in this population.

Department dc:contributor.department

Pharmaceutical Sciences

Year dc:date.issued

2024

Author dc:creator

• Zarek, Judith

Advisor dc:contributor.advisor

• Ito, Shinya

Statement dc:rights

• Attribution-NonCommercial 4.0 International

Licence dc:rights.uri

• http://creativecommons.org/licenses/by-nc/4.0/

Handle dc:identifier.uri

http://hdl.handle.net/1807/141298

OAI identifier oai:identifier

oai:utoronto.scholaris.ca:1807/141298