Rituximab for managing acquired hemophilia A in a case of chronic neutrophilic leukemia with the JAK2 kinase V617F mutation.

BACKGROUND: Acquired hemophilia A is rarely found in association with myeloproliferative neoplasms, such as the JAK2 kinase V617F mutation-positive chronic neutrophilic leukemia (CNL). CASE REPORT: An 80-year-old Japanese male was diagnosed with acquired hemophilia A. He had compartment-like symptoms due to soft tissue hemorrhage in his left forearm and right lower extremity. A blood examination showed neutrophilia with a white blood cell count of 31,900/µL (91.9% neutrophils), an activated partial thromboplastin time of 69.0 seconds, coagulation factor VIII (FVIII) < 1.0%, and anti-FVIII inhibitor, 190 BU/mL. The bleeding episodes were controlled with intravenous activated prothrombin complex concentrate (FEIBA(®)) followed by recombinant factor VIIa (NovoSeven(®)). In addition, oral prednisolone (maximum dose, 30 mg/day) plus four doses of rituximab effectively suppressed anti-FVIII inhibitor levels while simultaneously reducing the neutrophil count. CNL with the JAK2 kinase V617F mutation was identified as the underlying disease. CONCLUSION: This report describes the effectiveness of a combination of prednisolone and rituximab in managing acquired hemophilia A in an elderly man with a rare case of JAK2 kinase V617F mutation-positive CNL.

Validation of the revised 2008 WHO diagnostic criteria in 75 suspected cases of myeloproliferative neoplasm.

The objective of this study was to validate the recently revised 2008 WHO diagnostic criteria of myeloproliferative neoplasms (MPN) together with the analysis of correlation of JAK2 (Janus kinase 2)-V617F mutant allele burden with clinical/laboratory findings on each patient. We made a diagnosis of 75 suspected MPN patients based on both diagnostic criteria of the 2001 WHO classification and the revised 2008 WHO classification, and found that both criteria show a quite similar diagnostic power except for two patients (idiopathic erythrocytosis (IE) and thrombocytosis) who were diagnosed as essential thrombocythemia by the 2008 WHO criteria. From JAK2-V617F analysis, hemoglobin and hematocrit values were significantly higher and platelet count was lower in JAK2-V617F high allele burden group than JAK2-V617F middle allele burden group. Mutant allele burden of polycythemia vera (PV) group was higher than that of essential thrombocythemia group. Therefore, the amount of mutant allele seemed to define the disease phenotypes. We further found a PV case presenting a rare type of JAK2-exon12 mutation. In contrast, IE presented a good prognosis unlike MPN. Hereafter, the 2008 WHO criteria with JAK2 gene analysis are useful for precise diagnosis of MPN and the patients with erythrocytosis.