Tyrosine Kinase Inhibitor Treatment of a Patient with Chronic Myeloid Leukemia and Congenital Thrombophilia

<b>Background and Clinical Significance:</b> Chronic Myeloid Leukemia (CML) management has been revolutionized by tyrosine kinase inhibitors (TKIs), though cardiovascular and thrombotic complications remain a concern, especially in patients with underlying risk factors. Inherited thrombophilia, including protein S deficiency and Factor V Leiden mutation, poses a substantial risk for venous thromboembolism (VTE). Managing CML in patients with such prothrombotic predispositions presents complex therapeutic challenges, particularly in selecting an appropriate TKI and managing anticoagulation. <b>Case Presentation:</b> A 33-year-old woman with congenital thrombophilia (type I protein S deficiency and heterozygous Factor V Leiden mutation) and a history of VTE on long-term anticoagulation with acenocoumarol presented with CML. She exhibited primary resistance to first-line imatinib and poor tolerance with suboptimal response to second-line bosutinib. Third-line treatment with asciminib led to a rapid and sustained major molecular response (MR4.5) without bleeding or thrombotic complications. <b>Conclusions:</b> This case highlights the importance of individualized, multidisciplinary management in CML patients with coexisting thrombophilia. Asciminib, with its favorable cardiovascular safety profile, represents a promising therapeutic option in high-risk patients where other TKIs may be contraindicated due to resistance, intolerance, or thrombotic risk.