Prognostic value of immunogenetic, coagulation and inflammatory markers for stratification of the risk of thrombohemorrhagic complications and optimization of transfusion support in chronic myeloid leukemia

Aim. To synthesize and critically appraise evidence on the prognostic value of immunogenetic, coagulation, and inflammatory biomarkers for stratifying the risk of thrombohemorrhagic complications in chronic myeloid leukemia (CML), and to outline implications for optimizing transfusion support during tyrosine-kinase inhibitor (TKI) therapy. Materials and methods. Narrative, focused review of experimental and clinical studies on CML pathophysiology and vascular toxicity under TKI exposure, with emphasis on inflammatory mediators and their ratios (notably interleukin-6/interleukin-10), cellular and plasma hemostatic activation markers (soluble P-selectin and prothrombin fragment F1+2), and immunogenetic determinants of platelet reactivity (ITGB3 HPA-1 polymorphism). Contemporary guidelines and multicenter prospective data were examined to contextualize biomarker performance for risk prediction and to derive practice-oriented proposals for transfusion management in TKI-induced thrombocytopenia. Results. CML constitutes a prototypical “thrombo-inflammatory” neoplasm in which leukemic-driven cytokine signaling, endothelial dysfunction, and platelet hyperreactivity create a prothrombotic baseline that is variably amplified by off-target vascular effects of second- and third-generation TKIs. Across cohorts, elevated soluble P-selectin indicates platelet and endothelial activation and predicts enhanced leukocyte–platelet aggregate formation; increased F1+2 reflects in-vivo thrombin generation and plasma-cascade activation; and a persistently high IL-6/IL-10 ratio–especially reported during nilotinib therapy–captures a maladaptive anti-inflammatory response, aligning with pro-oxidative and pro-atherogenic profiles. Although definitive CML-specific data are lacking, strong biological plausibility supports ITGB3 HPA-1 (PlA2) carriage as an independent amplifier of arterial occlusive risk under prothrombotic TKIs. Existing CML (Sokal/ELTS) and general CV risk scores insufficiently model vascular events because they omit these biomarker and genetic axes. Transfusion support in TKI-related thrombocytopenia presents a bidirectional hazard: while low platelet counts necessitate hemostatic safety, prophylactic platelet transfusion may fuel thrombosis in patients with concurrent biomarker-defined hypercoagulability. Evidence from hypoproliferative settings is not directly generalizable to this scenario. Conclusions. Integrating inflammatory (IL-6/IL-10 ratio), cellular/plasma hemostatic (soluble P-selectin, F1+2), and immunogenetic (ITGB3 HPA-1) markers into a CML-specific thrombotic risk model is conceptually and clinically justified. We propose a staged program: prospective validation of the above predictors stratified by TKI class; development of a multivariable, CML-tailored vascular risk score; randomized comparisons of liberal versus restrictive platelet-transfusion thresholds in high-risk patients; and targeted evaluation of cardio-/vasculoprotective interventions (e.g., statins, PCSK9 inhibitors, low-grade anti-inflammatories). Such a framework would enable genuinely personalized prevention and safer transfusion strategies without compromising antileukemic efficacy.