Platelet Type Von Willebrand Disease - Diagnostic and Therapeutic Challenges.

Platelet-type von Willebrand disease (PT-VWD) is a rare thrombocytopathy caused by gain-of-function variants in , leading to increased binding of von Willebrand factor (VWF). Because its phenotype closely resembles VWD type 2B (VWD 2B), misdiagnosis is common, and distinction requires Ristocetin-induced platelet agglutination (RIPA) mixing studies and molecular genetic analysis. Although individual case reports, case series, and earlier summaries exist, an updated and comprehensive synthesis of all published cases has been lacking. We report a 4-year-old boy presenting with easy bruising, prolonged epistaxis, reduced VWF parameters (VWF collagen-binding activity 0.07 U/mL, VWF-antigen 0.33 U/mL), absence of high-molecular-weight multimers, and enhanced RIPA. Genetic testing identified the pathogenic variant p.Met255Val, causing PT-VWD. RIPA mixing studies confirmed the diagnosis. In the course of the disease, the patient developed recurrent mucosal bleeding and a hypersensitivity reaction to tranexamic acid. Therefore, desmopressin was used, and he showed partial clinical benefit from desmopressin without developing thrombocytopenia. To contextualize this case, we performed a literature review (PubMed, May 2025) and identified 67 documented patients with PT-VWD. Over 40% were initially misclassified as VWD 2B. p.Gly249Val and p.Met255Val were the most frequent variants. Baseline thrombocytopenia occurred in approximately one-third of cases, and pregnancy-associated thrombocytopenia was common. According to the literature, platelet transfusions were most effective (in case of major hemorrhage or surgical setting); VWF concentrates or desmopressin showed variable efficacy and occasional transient thrombocytopenia. These data demonstrate the diagnostic challenges of PT-VWD and emphasize the importance of clinical case collection to improve therapeutical management.

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PMID: 42665001