Should we stop aspirin prophylaxis in pregnant women diagnosed with COVID-19?

The current coronavirus disease 2019 (COVID‐19), caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), can progress to critical illness with acute respiratory distress and disseminated intravascular coagulation (DIC). Biomarkers of DIC (elevated D‐dimer and thrombocytopenia) are detectable early in the course of the disease and correlate with a poor prognosis1, 2. In the first SARS outbreak, thrombocytopenia was reported in 20–55% of patients2. Data for the current SARS‐CoV‐2 pandemic are less mature and the reported rate of thrombocytopenia varies between 5% and 41.7% of cases2. Multiple phenomena underpin SARS‐CoV‐2‐associated thrombocytopenia, namely decreased thrombocyte production in infected hematopoietic marrow as well as increased consumption by DIC and in damaged lung tissue and capillaries3. The natural course of COVID‐19 in non‐pregnant adults, in which patients show mild symptoms for days before clinical deterioration, including those who will subsequently present with a severe form or a fatal outcome, is not different from that in pregnant women4. Furthermore, as children with COVID‐19 have mild or asymptomatic disease, those within a household are highly contagious to future mothers.

Prophylactic administration of low‐dose aspirin to pregnant women is common. It is currently indicated in those at moderate to high risk of pre‐eclampsia5, a group which represents 10–15% of all pregnancies. In the Combined Multimarker Screening and Randomized Patient Treatment with Aspirin for Evidence‐Based Preeclampsia Prevention (ASPRE) trial, daily administration of 150 mg of aspirin, initiated between 11 and 14 weeks of gestation, resulted in a 62% reduction in the incidence of preterm pre‐eclampsia when compared with placebo in high‐risk women (incidence of 1.6% in the aspirin group vs 4.3% in the placebo group; odds ratio, 0.38 (95% CI, 0.20–0.74); P = 0.004) identified by means of a predictive algorithm that combines maternal characteristics, medical history and biomarkers5. Low‐dose aspirin is also indicated in pregnant women with antiphospholipid syndrome and those with a mechanical heart valve, or may be prescribed for prevention of early pregnancy loss, fetal growth restriction or stillbirth (Table 1)6.

Table 1

Indications for aspirin prophylaxis in pregnant women and recommendation in those who test positive for SARS‐CoV‐2

Indication	Proportion of pregnancies affected	Aspirin therapy	Benefit	Recommendation if positive SARS‐CoV‐2 test
Moderate‐to‐high risk for PE	10–15%, depending on screening method used	Low‐dose aspirin < 14 weeks until 36 weeks (or delivery)	ASPRE trial (high‐risk pregnancies): preterm PE occurred in 1.6% of those taking aspirin vs 4.3% in placebo group (odds ratio, 0.38; P = 0.004)5	Immediate cessation of aspirin, avoidance for duration of COVID‐19 and consider restarting medication after full recovery
Fetal growth restriction	Varies with local practice	Low‐dose aspirin	Not demonstrated in absence of risk factors for PE	Immediate cessation of aspirin and consider not restarting
History of preterm birth	Varies with local practice	Low‐dose aspirin	Not demonstrated in absence of risk factors for PE	Immediate cessation of aspirin and consider not restarting
History of stillbirth	Varies with local practice	Low‐dose aspirin	Not demonstrated in absence of risk factors for PE	Immediate cessation of aspirin and consider not restarting
History of recurrent pregnancy loss (without APS)	Varies with local practice	Low‐dose aspirin	Not demonstrated in absence of APS	Immediate cessation of aspirin and consider not restarting
All nulliparous singleton pregnancies (in low‐income countries)	Up to 100% in certain areas	Low‐dose aspirin	Significant reduction in preterm birth and reduced perinatal morbidity	Immediate cessation of aspirin, avoidance for duration of COVID‐19 and restart medication after full recovery
APS	Approximately 0.05%	Low‐dose aspirin +/− LMWH	Reduction in risk of thrombosis (> 10% if untreated vs < 1% if treated) Significantly increased rate of live birth	Continue aspirin therapy, with close monitoring of platelet count and coagulation parameters during course of COVID‐19
Mechanical heart valve	Approximately 0.02%	Low‐dose aspirin + anticoagulant	Significant reduction in valve thrombosis and thromboembolic events	Continue aspirin therapy, with close monitoring of platelet count and coagulation parameters during course of COVID‐19

APS, antiphospholipid syndrome; LMWH, low‐molecular‐weight heparin; PE, pre‐eclampsia.

During the current COVID‐19 pandemic, systematic testing of all suspected cases of SARS‐CoV‐2 infection in pregnancy is recommended4. Positive cases should have careful evaluation of the risk‐to‐benefit ratio of low‐dose aspirin therapy, taking into account the indication, gestational age and platelet count (Table 1). Aspirin belongs to the group of non‐steroidal anti‐inflammatory drugs, the use of which is controversial in COVID‐19 patients. As aspirin irreversibly inhibits platelet cyclooxygenase, its effect persists for the duration of the circulating life of platelets (7–10 days). Thus, the delay between SARS‐CoV‐2 test positivity and clinical deterioration is similar in length to the delay between the last aspirin intake and the end of its clinical effect. Furthermore, aspirin is not indicated for the treatment of DIC or other venous thromboembolic complications that might be associated with severe COVID‐19, and may increase the bleeding risk in severely thrombocytopenic patients.

While we support the continuous use of prophylactic aspirin in pregnant women during the COVID‐19 pandemic, which is consistent with the views expressed recently by Kwiatkowski et al.7 in this Journal, our view is more nuanced. We recommend immediate cessation of aspirin prophylaxis prescribed for pre‐eclampsia upon diagnosis of SARS‐CoV‐2 infection, avoidance of aspirin for the duration of the disease and restarting the medication after full recovery (Table 1), especially in women in the third trimester of pregnancy as the benefit of aspirin is minimal and could contribute to severe bleeding in thrombocytopenic COVID‐19 patients or if emergency Cesarean delivery is indicated by the maternal condition. The above‐listed propositions should help in tailoring individualized therapeutic decisions for pregnant women during the COVID‐19 pandemic.