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The Journal of Heart and Lung Transplantation
International Society for Heart and Lung Transplantation.

Chronic thromboembolic pulmonary hypertension in patients with antiphospholipid syndrome: Risk factors and management

  • Keren Rosen
    Affiliations
    Clinical Immunology, Angioedema and Allergy Unit, The Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel Hashomer, Israel

    Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv-Yafo, Israel
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  • Ehud Raanani
    Affiliations
    Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv-Yafo, Israel

    Department of Cardiac Surgery, Leviev Cardiothoracic and Vascular Center, Sheba Medical Center, Tel Hashomer, Israel
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  • Alexander Kogan
    Affiliations
    Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv-Yafo, Israel

    Department of Cardiac Surgery, Leviev Cardiothoracic and Vascular Center, Sheba Medical Center, Tel Hashomer, Israel
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  • Gili Kenet
    Affiliations
    Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv-Yafo, Israel

    The Israeli National Hemophilia Center, Sheba Medical Center, Tel Hashomer, Israel
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  • Mudi Misgav
    Affiliations
    Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv-Yafo, Israel

    The Israeli National Hemophilia Center, Sheba Medical Center, Tel Hashomer, Israel
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  • Aharon Lubetsky
    Affiliations
    Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv-Yafo, Israel

    The Israeli National Hemophilia Center, Sheba Medical Center, Tel Hashomer, Israel
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  • Stanely Niznik
    Affiliations
    Clinical Immunology, Angioedema and Allergy Unit, The Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel Hashomer, Israel
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  • Hans-Joachim Schäfers
    Affiliations
    Department of Thoracic and Cardiovascular Surgery, Saarland University Medical Center, Homburg, Germany
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  • Author Footnotes
    # Co-senior authors.
    Michael J. Segel
    Footnotes
    # Co-senior authors.
    Affiliations
    Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv-Yafo, Israel

    Pulmonary Institute, Sheba Medical Center, Tel Hashomer, Israel
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  • Author Footnotes
    # Co-senior authors.
    Nancy Agmon-Levin
    Correspondence
    Reprint requests: Nancy Agmon-Levin, MD, Clinical Immunology, Angioedema and Allergy Unit, The Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel Hashomer, 52621, Israel. Telephone: +972-3-5308087.
    Footnotes
    # Co-senior authors.
    Affiliations
    Clinical Immunology, Angioedema and Allergy Unit, The Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel Hashomer, Israel

    Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv-Yafo, Israel
    Search for articles by this author
  • Author Footnotes
    # Co-senior authors.
Published:October 27, 2021DOI:https://doi.org/10.1016/j.healun.2021.10.016

      Background

      Antiphospholipid syndrome (APS) may cause chronic thromboembolic pulmonary hypertension (CTEPH). Current knowledge regarding prevalence and risk factors for CTEPH among APS patients is limited. We sought to determine clinical features and biomarkers that could identify APS subjects suffering from CTEPH, and describe the prevalence, course and treatment outcomes of patients with APS-CTEPH.

      Methods

      504 APS patients were treated in our center during 2008 to 2019. We studied clinical and laboratory features of 69 APS patients, comparing 19 patients diagnosed with CTEPH (APS-CTEPH) and treated accordingly, with 50 consecutive age and gender matched patients with no evidence of pulmonary hypertension (APS-No-CTEPH).

      Results

      CTEPH prevalence was 3.8% in our APS cohort and was linked with the following parameters: primary APS (p < 0.05); prior pulmonary embolism (p < 0.001); recurrent venous thromboembolism (VTE) (p < 0.001); lower platelet counts (p < 0.001); triple anti-phospholipid antibodies positivity (p < 0.001), higher titers of anti-cardiolipin IgG (p < 0.001), anti-B2GPI IgG (p < 0.001), and high Russell viper venom time ratio (RVVT-ratio) (p < 0.05). Additionally, history of catastrophic APS was more prevalent in APS-CTEPH vs APS-No-CTEPH (p < 0.05). Of APS-CTEPH patients, 15/19 underwent pulmonary endarterectomy (PEA): In 12/15 the procedure was elective and resulted in good perioperative and long-term outcomes, while only 1 of 3 patients that underwent urgent PEA survived.

      Conclusions

      CTEPH is relatively common in APS. Primary APS, prior PE, recurrent VTE, thrombocytopenia and specific anti-phospholipid antibodies predict CTEPH in APS. Active assessment for CTEPH in APS patients should be considered, as PEA was found to be effective and relatively safe, especially if electively performed.

      KEYWORDS

      Abbreviations:

      APS (antiphospholipid syndrome), aPL (antiphospholipid antibodies), ARDS (acute respiratory distress syndrome), CAPS (catastrophic antiphospholipid syndrome), CTEPH (chronic thromboembolic pulmonary hypertension), DVT (deep vein thrombosis), HIT (heparin induced thrombocytopenia), INR (international normalized ratio), mPAP (mean pulmonary arterial pressure), PE (pulmonary embolism), PEA (pulmonary endarterectomy), PH (pulmonary hypertension), PTT (partial thromboplastin time), RVVT (Russell viper venom time), SPAP (systolic pulmonary artery pressure), VTE (venous thromboembolism)
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