Patients with cryptogenic stroke and weakly positive antiphospholipid antibodies had a lower incidence of recurrent stroke (0.045 events/person-year) compared with those with strongly positive antibodies (0.169 events/person-year), despite receiving less intensive antithrombotic therapy.
Key Findings
Results
Warfarin was recommended less often and antiplatelet agents more often to patients with weakly positive aPLs compared with those with strongly positive aPLs.
Warfarin recommendation difference was statistically significant (P = .007)
Antiplatelet agent recommendation difference was statistically significant (P = .03)
Most patients with cryptogenic stroke and weakly positive aPLs received antiplatelet agents
Study population included 30 weakly positive and 17 strongly positive patients
Results
The incidence of recurrent ischemic stroke was substantially lower in the weakly positive aPL group compared with the strongly positive group.
Incidence in strongly positive group: 0.169 events/person-year
Incidence in weakly positive group: 0.045 events/person-year
Hazard ratio: 3.93 (95% CI, 1.14–13.55; P = .03), favoring lower risk in the weakly positive group
Median follow-up was 32 months (IQR, 24–48 months)
This difference occurred despite the weakly positive group receiving less intensive antithrombotic therapy
Results
Bleeding events were rare across both groups during follow-up.
Bleeding events described as 'rare' in both the weakly and strongly positive aPL groups
Survival analyses were used to evaluate major bleeding events
Median follow-up of 32 months (IQR, 24–48 months)
Methods
This retrospective cohort study identified 47 patients meeting eligibility criteria from the University of Pennsylvania Health System over approximately six years.
Study period: March 1, 2017 to December 31, 2023
Eligibility required index cryptogenic stroke or TIA, positive aPLs persisting for ≥12 weeks, and no antithrombotic therapy prior to the index event
30 patients had weakly positive aPLs and 17 had strongly positive aPLs
Univariate hypothesis testing was used for antithrombotic therapy comparisons; survival analyses were used for clinical outcomes
Background
The risk of recurrent stroke and optimal antithrombotic strategy for cryptogenic stroke patients with weakly positive aPLs were uncertain prior to this study.
Weakly positive aPLs represent a distinct category from strongly positive aPLs in antiphospholipid antibody testing
The study was designed to describe antithrombotic practice patterns and clinical outcomes to address this uncertainty
No antithrombotic therapy prior to the index event was required for eligibility, to focus on incident treatment decisions
What This Means
This research suggests that patients who have a stroke of unknown cause (called cryptogenic stroke) and test weakly positive for antiphospholipid antibodies—proteins that can increase clotting risk—face a meaningfully lower risk of having another stroke compared to patients who test strongly positive for these antibodies. In this study of 47 patients followed for a median of about 2.5 years, the strongly positive group had a stroke recurrence rate nearly four times higher than the weakly positive group. Despite this difference in underlying risk, doctors in real clinical practice were already tailoring treatment accordingly, recommending blood thinners like warfarin less often to weakly positive patients and instead using antiplatelet medications (like aspirin) more frequently.
The findings are notable because they suggest that the degree of antiphospholipid antibody positivity—weak versus strong—may be clinically meaningful when it comes to predicting future stroke risk. Bleeding complications were rare in both groups, suggesting that the treatments used were generally well tolerated over the follow-up period.
This research matters because cryptogenic stroke (stroke without a clearly identified cause) is common, and antiphospholipid antibodies are one potential contributing factor. Knowing whether a patient has weakly or strongly positive antibodies could help guide decisions about how aggressively to treat with blood thinners. However, because this was a small retrospective study at a single health system, larger studies will be needed to confirm these findings and establish clearer treatment guidelines.
Gatti M, Messé S, Cuker A. (2026). Management and outcomes in patients with cryptogenic stroke and weakly positive antiphospholipid antibodies.. Research and practice in thrombosis and haemostasis. https://doi.org/10.1016/j.rpth.2026.106895