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Association of inherited dysfibrinogenaemia and protein C deficiency in two unrelated families
S Gandrille1, P Priollet, L Capron
1Laboratoire d'Hématologie, UER de Biologie Expérimentale et Humaine, Université Paris, France.
Insights
Inherited dysfibrinogenemia and protein C deficiency were found together, potentially increasing thrombotic risk. This dual defect may enhance atherosclerosis and venous thrombosis by affecting blood clot formation and degradation.
Area of Science:
- Hematology
- Molecular Biology
- Genetics
Background:
- Inherited thrombophilias, such as protein C deficiency, increase the risk of blood clots.
- Dysfibrinogenemia, a disorder of fibrinogen function, can also be associated with thrombotic events.
- The co-occurrence of these two conditions is rare and warrants further investigation.
Observation:
- Three family members presented with an inherited association of dysfibrinogenemia and protein C deficiency.
- The propositus exhibited severe atherosclerosis, suggesting a potential link between these defects and arterial thrombosis.
- Another patient with venous thrombosis also showed this combined inherited disorder.
Findings:
- The abnormal fibrinogen demonstrated reduced thrombin binding, a potentially thrombogenic characteristic.
- Fibrinogen and fibrin clots exhibited resistance to plasmin degradation, indicating impaired clot lysis.
- These findings suggest that the combined defects may significantly enhance the thrombotic process.
Implications:
- The study raises questions about whether the co-occurrence of protein C deficiency and dysfibrinogenemia is coincidental or due to a shared mechanism.
- It explores the potential link between this dual hemostatic defect and an increased tendency for thrombosis.
- Further research is needed to elucidate the precise contribution of each defect to thrombotic risk.
Abstract:
An inherited association of dysfibrinogenaemia and protein C deficiency was found in three members of the same family. The propositus was a 48-year-old man who suffered from severe and rapidly complicated atherosclerosis of the aorta and lower limbs arteries, which perhaps suggests that the association of these two molecular abnormalities may have enhanced the thrombotic process. The abnormal fibrinogen had a reduced ability to bind thrombin which may be thrombogenic. We found the same inherited association of dysfibrinogenaemia and protein C deficiency in a patient with venous thrombosis. The functional abnormality of the fibrinogen, which could have been responsible for thrombosis, was delayed proteolysis by plasmin. Not only fibrinogen, but also fibrin clots were resistant to plasmic degradation. These observations raise two questions: (1) Is the association of a protein C deficiency with a dysfibrinogenaemia fortuitous or the result of a common mechanism? (2) Is there a link between an increased thrombotic tendency and either both of the defects of haemostasis that we have found, or only one of them?