Background: Platelet transfusion refractoriness (PTR) is a complication of multiple transfusions in patients with hematological malignancies. PTR may induce a series of adverse events, such as delaying the treatment of the primary disease and life-threatening bleeding. Early prediction of PTR holds promise in facilitating prompt adjustments to treatment strategies by clinicians. Methods: We collected the clinical data of 250 patients with acute myeloid leukemia (AML). Subsequently, the patients were randomly divided into a training cohort and a validation cohort at a ratio of 7:3. The least absolute shrinkage and selection operator (LASSO) and multivariate logistic-regression methods were used to select characteristic variables. Assessment of the model was conducted through the receiver operating characteristic (ROC), calibration curve and decision curve analysis (DCA). Results: Out of 250 patients with AML, 95 individuals (38.0%) experienced PTR. Among those with positive platelet associated antibodies (PAAs), the incidence of PTR was 66.7% (30/45), while among patients positive for human leukocyte antigen(HLA)-I antibodies, the PTR incidence was 56.5% (48/85). The final predictive model incorporated risk factors such as KIT mutations, splenomegaly, the number of HLA-I antibodies, and positive PAAs. A prediction nomogram model was constructed based on these four risk factors. The LASSO-logistic regression model demonstrated excellent discrimination, calibration, and clinical decision value. Conclusion: The LASSO-logistic regression model in the study can better predict the risk of PTR. The study includes both PAAs and HLA antibodies, expanding the field of work that has not been involved in the previous prediction model of PTR.