Unusual Comorbid Conditions in Three Children with Congenital Dysfibrinogenemia: Lymphedema, Leukemia, and Sternal Defect

According to the International Council for Standardization in Hematology, the Clauss method, which measures fibrinogen activity, is routinely used in traditional hemostasis laboratories as the first step test in identifying fibrinogen disorders.[1] If fibrinogen activity is low, a fibrinogen antigen assay should be performed to rule out dysfibrinogenemia. ELISA is the gold standard immunoassay for measuring fibrinogen antigen; however, it is not widely available in clinical practice and is costly and time-consuming for hemostasis laboratories to employ.[2] A recent study revealed a strong correlation between prothrombin time (PT)-derived fibrinogen and ELISA-based fibrinogen antigen levels, suggesting that PT-derived fibrinogen assessment can identify dysfibrinogenemia patients.[3] The PT-derived fibrinogen result may be overestimated if the patient's international normalized ratio value is ≥1.25 and/or the fibrinogen concentration in plasma is >400 mg/dL, which affects the optic density on the coagulation analyzer.[4]

Congenital dysfibrinogenemia affects 0.3% of the Finnish population and 1% of African Americans, with very few cases reported in Türkiye.[5] [6] According to a recent review, congenital dysfibrinogenemia is an autosomal dominant genetic disorder that is usually diagnosed in childhood and has a diverse clinical history, including bleeding and thrombosis.[7] Although many individuals with congenital dysfibrinogenemia are asymptomatic, 20 to 57% have bleeding symptoms, 13.9 to 44% have arterial or venous thrombosis, and only a few have both.[8] The cumulative frequency of major bleeding is 2.5 per 1,000 patient-years, while thrombosis is reported to be 18.7 per 1,000 patient-years.[2] Patients with hypo/dysfibrinogenemia have low to normal fibrinogen antigen levels and low fibrinogen activity. To date, over 1,000 cases of congenital dysfibrinogenemia and 450 different mutations have been documented in a comprehensive systematic review, providing insight into the link between fibrinogen variations, structure, and clinical outcomes.[8] None of these investigations has reported chronic myeloid leukemia or uncommon concurrent abnormalities in children with congenital dysfibrinogenemia. Thus, we would like to share our experience with genetically confirmed dysfibrinogenemia, PT-derived fibrinogen assays in addition to routine Clauss methods, and unusual concomitant conditions in three pediatric patients, one with chronic myeloid leukemia, one with lymphedema, and the last with pectus excavatum.

Informed Consent

Informed consent was obtained from parents.

Data Availability

Data are available on request from the authors.

Publikationsverlauf

Eingereicht: 09. Dezember 2024

Angenommen: 03. April 2025

Artikel online veröffentlicht:
25. April 2025

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