We describe the case of an 11-year-old boy with hemophilia B who presented with swelling and pain in the left index finger. The patient was referred to our hospital after first presenting to another hospital. The patient experienced slight difficulty making a fist because of limited flexion of the proximal interphalangeal joint. Radiography of the left index finger revealed an expansile remodeling osteolytic lesion with a well-defined sclerotic border and cortical thinning. The patient had prolonged activated partial thromboplastin times and decreased factor IX levels. We performed curettage of the tumor in the left proximal phalanx and artificial bone filling. A hemophilic pseudotumor was diagnosed. At 1 year postoperatively, the patient was able to mobilize the index finger without range of motion limitations. Radiography of the left index finger revealed no signs of recurrence. Hemophilic pseudotumor usually occurs in patients with severe hemophilia A; however, this is the first reported case of a hemophilic pseudotumor arising from the finger of a child with mild hemophilia B. When progressive expansile remodeling of bone in the hand of a patient with hemophilia is observed, the possibility of a hemophilic pseudotumor, regardless of the severity or type of hemophilia, should be considered. Hemophilia B is characterized by deficiency in factor IX clotting activity that results in prolonged oozing after injuries, tooth extractions, or surgery, and delayed or recurrent bleeding prior to complete wound healing. The age of diagnosis and frequency of bleeding episodes are related to the level of factor IX clotting activity. In any individual with hemophilia B, bleeding episodes may be more frequent in childhood and adolescence than in adulthood. Severe hemophilia B: Usually diagnosed during the first two years of life. Without prophylactic treatment, individuals may average up to two to five spontaneous bleeding episodes each month, including spontaneous joint or muscle bleeds, and prolonged bleeding or excessive pain and swelling from minor injuries, surgery, and tooth extractions. Moderate hemophilia B: Less frequent spontaneous bleeding, although it varies between individuals; however, individuals with moderate hemophilia B do have prolonged or delayed oozing after relatively minor trauma and are usually diagnosed before age five to six years. The frequency of bleeding episodes varies from once a month to once a year. Mild hemophilia B: Individuals generally do not have spontaneous bleeding episodes; however, without pre- and postoperative treatment, abnormal bleeding occurs with surgery or tooth extractions. The frequency of bleeding may vary from once a year to once every ten years. Individuals with mild hemophilia B are often not diagnosed until later in life. Heterozygous females: Approximately 30% of heterozygous females have factor IX clotting activity lower than 40% and are at risk for bleeding (even if the affected family member has mild hemophilia B). As in males, bleeding severity generally correlates with factor IX levels. After major trauma or invasive procedures, prolonged or excessive bleeding usually occurs, regardless of severity. The diagnosis of hemophilia B is established in individuals with low factor IX clotting activity. Identification of a hemizygous F9 pathogenic variant by molecular genetic testing confirms the diagnosis in a male proband. Identification of a heterozygous F9 pathogenic variant by molecular genetic testing confirms the diagnosis in a female proband. Targeted therapy: For those with severe hemophilia B and those with moderate or mild hemophilia B and frequent bleeding, prophylactic treatment with factor IX concentrate infusions to maintain factor IX clotting activity higher than 1% or as needed to prevent bleeding and allow normal activity improves outcomes and prevents chronic joint disease. Other non-factor prophylactic therapies (marstacimab, concizumab, and fitusiran) are approved in those age 12 years and older. Intravenous infusion of plasma-derived or recombinant factor IX for acute bleeding episodes should be given as soon as possible after symptoms occur. One product for adeno-associated virus (AAV)-mediated gene therapy for hemophilia B is approved and available for use in adult males with factor IX levels ≤2%. Most individuals who receive gene therapy for hemophilia B will have mild hemophilia following treatment, although levels vary widely. Supportive care: Referral to a hemophilia treatment center (HTC) for assessment, education, genetic counseling, and treatment. Training to facilitate home infusions administered by parents or affected individuals should be provided for individuals affected by moderate and severe hemophilia. Physical therapy for evaluation and treatment of musculoskeletal disease; standard treatments for pain with help from a pain specialist as needed; standard treatments for transfusion-related infections contracted prior to virucidal treatment of plasma-derived concentrates. Surveillance: For young children with severe or moderate hemophilia B, assessments every six to 12 months at an HTC; older children and adults with severe or moderate hemophilia B benefit from at least annual assessment at an HTC; for individuals with mild hemophilia B, assessment at an HTC every one to two years. Individuals with comorbidities may require more frequent visits. The assessment should include a review of bleeding episodes, adjustment of treatment plans as needed, a joint and muscle evaluation, an inhibitor screen, viral testing if indicated, and a discussion of any other issues related to the individual's hemophilia B as well as family and community support. Screening for alloimmune inhibitors is performed after treatment with factor IX concentrates has been initiated and in any individual with a suboptimal clinical response to treatment. Agents/circumstances to avoid: Circumcision of at-risk males until hemophilia B is either excluded or treated with factor IX concentrate regardless of severity; activities with a high risk of trauma, particularly head injury. Cautious use of medications and herbal remedies that affect platelet function, including aspirin. Use precaution with intramuscular injections (apply pressure and ice); intramuscular injection may be scheduled after factor IX treatment or while on prophylaxis. Evaluation of relatives at risk: It is appropriate to evaluate asymptomatic male and female at-risk relatives of an affected individual in order to identify as early as possible those who would benefit from prompt initiation of targeted therapies, supportive care, and surveillance. It is recommended that the genetic status of at-risk females be established prior to pregnancy or as early in a pregnancy as possible. Pregnancy management: Maternal factor IX levels do not significantly increase during pregnancy and heterozygous females may need factor IX infusion support for delivery and/or to treat or prevent postpartum hemorrhage. Heterozygous mothers should be monitored for delayed bleeding post partum. Tranexamic acid can be used to prevent and treat postpartum hemorrhage. Other: Vitamin K does not prevent or control bleeding in hemophilia B. Hemophilia B is inherited in an X-linked manner. The risk to sibs of a male proband depends on the genetic status of the mother. The risk to sibs of a female proband depends on the genetic status of the mother and father. If the mother of the proband has an F9 pathogenic variant, the chance of the mother transmitting it in each pregnancy is 50%. If the father of the proband has an F9 pathogenic variant, he will transmit it to all his daughters and none of his sons. Males who inherit the pathogenic variant will be affected; females who inherit the pathogenic variant are heterozygotes and may be at risk for bleeding. Once the F9 pathogenic variant has been identified in an affected family member, genetic testing for at-risk family members and prenatal/preimplantation genetic testing are possible.

A 5-year-old boy presented with bleeding gums following a fall from the swing. Initial treatment at a private clinic involved clot removal and gauze application. Despite no prior history of abnormal bleeding, the child experienced delayed and continuous bleeding, prompting further evaluation. Blood tests revealed normal prothrombin time (PT) but abnormal activated partial thromboplastin time (APTT), indicating a coagulation disorder. Vitamin K was administered, but profuse bleeding recurred, leading to hospital admission. Further tests confirmed a diagnosis of mild hemophilia B with low factor IX levels. The patient received fresh frozen plasma (FFP) transfusion, which stopped the bleeding. Follow-up showed a clean injury site after intervention. This case underscores the need for high suspicion, thorough investigation, and prompt management in bleeding disorders, especially since patients may be unaware of their condition until a bleeding episode occurs. Gaviappa D, Shetty AK, Jeniffer N, et al. Incidental Diagnosis of Christmas Disease in a 5-year-old Child: A Case Report. Int J Clin Pediatr Dent 2025;18(2):235-238.

 Discrepancy in factor IX activity (FIX:C) between one-stage assay (OSA) and chromogenic substrate assay (CSA) in patients with hemophilia B (PwHB) introduces challenges for clinical management.  To study the differences in FIX:C using OSA and CSA in moderate and mild hemophilia B (HB), their impact on classification of severity, and correlation with genotype.  Single-center study including 21 genotyped and clinically characterized PwHB. FIX:C by OSA was measured using ActinFSL (Siemens) and CSA by Biophen (Hyphen). In addition, in vitro experiments with wild-type FIX were performed. Reproducibility of CSA was assessed between three European coagulation laboratories.  FIX:C by CSA was consistently lower than by OSA, with 10/17 PwHB having a more severe hemophilia type by CSA. OSA displayed a more accurate description of the clinical bleeding severity, compared with CSA. A twofold difference between OSA:CSA FIX:C was present in 12/17 PwHB; all patients had genetic missense variants in the FIX serine protease domain. Discrepancy was also observed with diluted normal plasma, most significant for values below 0.10 IU/mL. Assessment of samples with low FIX:C showed excellent reproducibility of the CSA results between the laboratories.  FIX:C was consistently higher by OSA compared with the CSA. Assessing FIX:C by CSA alone would have led to diagnosis of a more severe hemophilia type in a significant proportion of patients. Our study suggests using both OSA and CSA FIX:C together with genotyping to classify HB severity and provide essential information for clinical management.

Hemophilia A and B are caused by variants in the factor (F) VIII or FIX gene. Selective reporting may influence the distribution of variants reported in genetic databases. To compare the spectrum of F8 and F9 variants in an international population-based pediatric cohort (PedNet Registry) with the spectrum found in the European Association for Haemophilia and Allied Disorders (EAHAD) and the Centers for Disease Control and Prevention Hemophilia A or Hemophilia B Mutation Project (CHAMP/CHBMP) databases. All patients registered in the PedNet Registry on January 1, 2021 were included in this study. As comparators, data from patients with severe hemophilia included in the CHAMP/CHBMP registry (US center data) and EAHAD were used. Genetic information was available for 1941 patients. Intron 22 inversion was present in 52% of patients with severe hemophilia A; frameshift (36%), missense (28%), and nonsense (20%) were the most frequent variants in patients with severe hemophilia A who were inversion-negative. The most frequent variants in severe hemophilia B were missense (48%). In nonsevere disease, most variants were missense variants (moderate hemophilia A: 91%; mild hemophilia A: 95%, moderate and mild hemophilia B: 86% each). Comparison with the databases demonstrated a higher proportion of missense variants associated with severe hemophilia B in EAHAD (68%) than in PedNet (48%) and CHBMP (46%). The PedNet population-based cohort provides an alternative to the established databases, which collect data by selective reporting, as it is a well-maintained database covering the full spectrum of pathogenic F8 and F9 variants, and indicates the number of patients affected by each particular variant.