Probable Catastrophic Antiphospholipid Syndrome in a Patient with Immune Thrombocytopenia Treated with a Thrombopoietin Receptor Agonist

Introduction: Thrombopoietin receptor agonists (TPO-RAs) are approved and widely used as effective second-line treatment for patients with immune thrombocytopenia (ITP) refractory to corticosteroids or in relapse. However, TPO-RAs may slightly increase the risk of thromboembolism in patients with ITP [1]. The presence of antiphospholipid antibodies (APAs) in patients with ITP has been described and an increased risk of thrombotic event in patients with ITP and APAs is assumed [2]. Even cases with severe thrombotic complications have been described in several patients with ITP and APAs that were treated with TPO-RAs [3] [4] [5] [6].

Method: We here report a case of a 61-year-old female patient without prior history of thromboembolic events, who was treated with the TPO-RA avatrombopag for a steroid-refractory relapse of ITP. Nine days after initiating avatrombopag, she developed a probable catastrophic antiphospholipid syndrome (CAPS) affecting her brain, kidneys and heart.

Results: The patient was hospitalized nine days after initiating treatment with avatrombopag, presenting with nausea and vomiting. Diagnostic procedures revealed acute renal failure, confirmed by sonographic evidence of kidney injury. Cardiac enzyme levels (troponin T and NTproBNP) were highly elevated and a previously noted mild mitral regurgitation had exacerbated. The patient developed a speech disorder and left-sided weakness, with cerebral MRI revealing multiple small supratentorial ischaemic lesions. Apart from an increase of the platelet count into the normal range, high levels of APAs (triple-positive) were detected. These antibodies were reduced by plasmapheresis on five consecutive days. In addition, treatment with low molecular weight heparin and corticosteroid was initiated. The patient's condition improved further therapy with steroids, high-dose immunoglobulin and four weekly doses of Rituximab. The anticoagulation with low-molecular-weight heparin was switched to platelet aggregation inhibition with acetylsalicylic acid after ten weeks. Three months after the acute event the patient maintained a normal platelet count, while levels of antiphospholipid antibodies remained high. The cardiac enzyme levels showed initial rapid improvement and continued to decline slowly. Renal function slowly improved and then stabilized within the range of moderate renal insufficiency. Neurological deficits largely improved over time, supported by physiotherapy.

Conclusion: This case of a probable CAPS illustrates a possible rare severe side effect of the TPO-RA avatrombopag, in which the first manifestation of an antiphospholipid syndrome occurred shortly after the start of treatment with a TPO-RA. While causality remains to be elucidated and additional data are needed for more definitive recommendations, we suggest to consider testing for APAs before initiating treatment with a TPO-RA.

Publikationsverlauf

Artikel online veröffentlicht:
13. Februar 2025

• References

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