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Characterization of a variant prothrombin in a patient congenitally deficient in factors II, VII, IX and X
Insights
A child with clotting factor deficiencies likely has a partially carboxylated prothrombin, an abnormal variant of a key blood protein. This finding suggests a novel cause for coagulation disorders in young patients.
Area of Science:
- Biochemistry
- Hematology
- Pediatrics
Background:
- Coagulation factor deficiencies can lead to bleeding disorders.
- Vitamin K-dependent clotting factors (II, VII, IX, X) are crucial for hemostasis.
- Identifying the specific molecular cause of factor deficiencies is essential for diagnosis and management.
Observation:
- An 18-month-old child presented with plasma deficiencies in factors II, VII, IX, and X without apparent liver disease or coumarin exposure.
- Immunological assays indicated normal or elevated antigenic activity for factors II and X, suggesting abnormal protein variants.
- Two-dimensional immunoelectrophoresis revealed both normal and abnormal prothrombin populations in the patient's plasma.
Findings:
- The abnormal prothrombin variant exhibited distinct electrophoretic mobility compared to normal prothrombin and acarboxyprothrombin.
- This abnormal prothrombin variant adsorbed to aluminum hydroxide and barium citrate, differentiating it from acarboxyprothrombin.
- The characteristics of the abnormal prothrombin suggest it is a partially carboxylated form.
Implications:
- This case highlights a potential novel molecular basis for inherited coagulation factor deficiencies.
- The identification of partially carboxylated prothrombin provides insights into the post-translational modification of Vitamin K-dependent proteins.
- Understanding such variants can improve diagnostic approaches and therapeutic strategies for bleeding disorders in children.
Abstract:
An 18-month-old child, who had no evidence of liver disease, malabsorption, or chronic ingestion of coumarin compounds, was found to have plasma deficiencies of factors II, VII, IX and X. Assays for factor II and X by immunological techniques (antibody neutralization and immunoelectrophoresis) revealed normal or elevated antigenic activity of these factors, suggesting the presence of abnormal protein variants in the patient's plasma. On two-dimensional immunoelectrophoresis of the patient's plasma in calcium, a normal and an abnormal population of prothrombin were seen. The abnormal prothrombin had a mobility more anodal than that of normal prothrombin, but less anodal than that of acarboxyprothrombin. The abnormal prothrombin, in contrast to acarboxyprothrombin, adsorbed readily to both aluminum hydroxide and barium citrate, and could be identified by two-dimensional immunoelectrophoresis of a barium citrate eluate. We suspect that the abnormal variant represents a partially carboxylated prothrombin.