Recurrent Thrombosis in Patients with Antiphospholipid Antibodies Following an Initial Venous or Arterial Thromboembolic Event

Tom Ortel¹, Sreelatha Meleth², Diane Catellier², Mark Crowther³, Doruk Erkan⁴, Paul R. Fortin⁵, David Garcia⁶, Nana Haywood², Steven R. Levine⁷, Michael J. Phillips² and Nedra Whitehead², ¹Duke University, Durham, NC, ²RTI International, Research, Triangle Park, NC, ³McMaster University, Hamilton, ON, Canada, ⁴Rheumatology, Hospital for Special Surgery- Weill Cornell Medicine, New York, NY, ⁵Medicine, CHU de Québec - University of Laval, Quebec, QC, Canada, ⁶Hematology, University of Washington Medical Center, Seattle, WA, ⁷Neurology, State University of New York Downstate Medical Center, Brooklyn, NY

Meeting: 2018 ACR/ARHP Annual Meeting

Keywords: Antiphospholipid antibodies, Antiphospholipid syndrome and thrombosis

Session Information

Date: Sunday, October 21, 2018

Title: Antiphospholipid Syndrome Poster

Session Type: ACR Poster Session A

Session Time: 9:00AM-11:00AM

Background/Purpose: After an initial thromboembolic event (TE), several studies reported that patients with antiphospholipid syndrome (APS) manifest a high-risk for recurrent TE. A systematic review found that antiphospholipid antibody (aPL) positivity in patients with a first venous TE (VTE) predicted an increased risk of recurrent VTE, but the strength of the association was uncertain because of low quality studies. Few studies report on recurrent TE after a first arterial TE (ATE). We performed a systematic review to determine if the risk for recurrence was comparable between VTE and ATE in patients with APS.

Methods: We used the systematic review methodology developed by Cochrane and the Evidence-based Practice Centers and EPPI-Reviewer 4 software. The population of interest was APS patients who had a single VTE or ATE. Outcomes included recurrent VTE, ATE, and death. Studies that did not distinguish patients based on an initial VTE or ATE were excluded. Risk of bias was formally assessed. Aggregate recurrence rates were estimated using meta-analysis. Statistical heterogeneity of pooled analysis was assessed using the chi-squared and the I² statistics. A weighted 24-month rate was estimated using OpenMeta software.

Results: Table1 demonstrates the number of articles. For patients with initial VTE, 10 studies described 257 patients on anticoagulation and 572 patients who had discontinued anticoagulation. For patients with initial ATE, 4 studies described 405 patients on anticoagulation and 370 patients who had discontinued anticoagulation. Patients with initial VTE who stopped anticoagulation were generally not treated with aspirin, whereas patients with an initial ATE who stopped anticoagulation took aspirin. Table 2 provides 2-year risk estimates of recurrent TE following an initial VTE or ATE. Limitations of studies included heterogeneous criteria for positive aPL definition and APS diagnosis, varying study designs (randomized trials vs. cohort studies), and small sample sizes. In addition, only 3 studies provided information about the same patients while taking anticoagulation as well as after stopping anticoagulation.

Conclusion: Compared to APS patients with an initial VTE, APS patients with an initial ATE have a higher risk for recurrent TE while taking anticoagulation, similar to the rate while not taking anticoagulation. Due to the limitations of literature, however, it is difficult to accurately estimate and compare recurrence rates for APS patients with different thrombotic phenotypes. Future studies need to clearly distinguish between different thrombotic manifestations of APS.

Table 1: The Number of Articles Identified at Each Stage of the Systematic Review
	VTE	ATE
# after the first search	3,137	1,694
# after the exclusion based on title and abstract screening	90	137
# after the exclusion based on full review	6	4
# after the inclusion of new studies based on manual review	13	5
# included in the final analysis	10	4
VTE: venous thromboembolism; ATE: arterial thromboembolism

Table 2: Overall Risk Estimates of Recurrent Thromboembolism (TE) in APS Patients Following an Initial Venous TE (VTE) and Arterial TE (ATE), Stratified by Long-term Anticoagulation (95% Confidence Interval)*
	VTE	ATE
On Anticoagulation	0.045 (0.020-0.070) 13 Events in 257 Patients	0.187 (0.101 – 0.274) 81 Events in 405 Patients
No Anticoagulation (c/s antiplatelet Rx)	0.167 (0.085-0.250) 105 Events in 572 Patients	0.168 (0.129 – 0.206) 62 Events in 370 Patients
* Results are provided as proportions and total number of events, and represent the rates over 24 months

Acknowledgement: Supported by U34HL123499

Disclosure: T. Ortel, None; S. Meleth, None; D. Catellier, None; M. Crowther, None; D. Erkan, None; P. R. Fortin, None; D. Garcia, None; N. Haywood, None; S. R. Levine, None; M. J. Phillips, None; N. Whitehead, None.

To cite this abstract in AMA style:

Ortel T, Meleth S, Catellier D, Crowther M, Erkan D, Fortin PR, Garcia D, Haywood N, Levine SR, Phillips MJ, Whitehead N. Recurrent Thrombosis in Patients with Antiphospholipid Antibodies Following an Initial Venous or Arterial Thromboembolic Event [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/recurrent-thrombosis-in-patients-with-antiphospholipid-antibodies-following-an-initial-venous-or-arterial-thromboembolic-event/. Accessed .

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