Patterns of Recurrent Thrombosis in Primary Antiphospholipid Syndrome-Multicenter, Real-Life Long-Term Follow-Up

Stanley Niznik; Micha J Rapoport; Orly Avnery; Aharon Lubetsky; Soad Haj Yahia; Martin H Ellis; Nancy Agmon-Levin

doi:10.3389/fimmu.2022.843718

Patterns of Recurrent Thrombosis in Primary Antiphospholipid Syndrome-Multicenter, Real-Life Long-Term Follow-Up

Front Immunol. 2022 Apr 19:13:843718. doi: 10.3389/fimmu.2022.843718. eCollection 2022.

Authors

Stanley Niznik¹, Micha J Rapoport^{2

3}, Orly Avnery⁴, Aharon Lubetsky^{3

5}, Soad Haj Yahia^{1

3}, Martin H Ellis^{3

4}, Nancy Agmon-Levin^{1

3}

Affiliations

¹ Clinical Immunology, Angioedema and Allergy Unit, The Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Ramat Gan, Israel.
² Department of Internal Medicine "C", Shamir Medical Center, Zerifin, Israel.
³ Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
⁴ Hematology Institute and Blood Bank, Meir Medical Center, Kfar Saba, Israel.
⁵ The National Hemophilia Center and Thrombosis Unit, Amalia Biron Research Institute of Thrombosis and Hemostasis, Sheba Medical Center, Ramat Gan, Israel.

Abstract

Background: Antiphospholipid syndrome (APS) is an acquired hypercoagulable condition associated with antiphospholipid antibody (aPL) presence. Data on re-thrombosis following APS-diagnosis are limited.

Methods: This is a retrospective analysis of new thrombotic events among primary APS (pAPS) patients followed for up to 15 years in three medical centers in Israel.

Results: Among 312 primary-APS patients, 143 (46%) had new thrombotic event classified to three patterns: (1) Arterial-associated with heart valve disease (OR 7.24, 95% C.I. 2.26-24.6), hypertension (OR 3, 95% C.I. 1.44-6.25), elevated anti-B2-GPI IgM (OR 1.04, 95% C.I. 0.996-1.08), arterial thrombosis at presentation (OR 1.74 95% C.I. 0.992-3.26), and older age (41 vs. 34 years, p < 0.001). (2) Venous-linked with venous thrombosis at presentation (OR 12.9, 95% C.I. 5.27-31.6, p < 0.001), heart valve disease (OR 9.81 95% C.I. 1.82-52.9, p = 0.018), aGAPSS (OR 1.15 95% C.I. 1.02-1.29), and younger age (31 vs. 36.5 years, p = 0.001); and (3) Combined pattern-associated with heart valve disease (OR 40.5 95% C.I. 7.7-212) and pulmonary embolism (OR 7.47 95% C.I. 1.96-28.5). A 4th variant "the Breakthrough pattern" defined by re-thrombosis despite prophylactic therapy was observed in 100/143 (70%) patients and linked with heart valve disease (OR 8. 95% C.I. 2.43-26.3), venous thrombosis at presentation (OR 2.61 95% C.I. 1.47-4.66), leg ulcers (OR 12.2, 95% C.I. 1.4-107), hypertension (OR 1.99, 95% C.I. 0.92-4.34), and higher aGAPSS (OR 1.08, 95% C.I. 0.99-1.18).

Conclusion: In this real-life observation, re-thrombosis was common among pAPS patients including in those recommended to receive prophylactic therapy. Different patterns of recurrence were identified and linked with presenting symptoms, specific serological markers, APS manifestations, and comorbidities. Studies that will address interventions to prevent recurrences of APS-related events are needed.

Keywords: AGAPSS; antiphospholipid syndrome; cardiovascular disease; recurrence; therapy; thrombosis - immunology.

Publication types

Multicenter Study
Research Support, Non-U.S. Gov't

MeSH terms

Antiphospholipid Syndrome* / complications
Antiphospholipid Syndrome* / diagnosis
Antiphospholipid Syndrome* / epidemiology
Follow-Up Studies
Heart Valve Diseases*
Humans
Hypertension* / complications
Retrospective Studies
Thrombosis* / complications
Thrombosis* / etiology
Venous Thrombosis*