Characterization of Phenotypic Expression of Inherited Fibrinogen Coagulopathy in Pakistani Index Patients

Background: Congenital afibrinogenemia is inherited as an autosomal recessive trait and consanguinity is common among affected families. Phenotypic expression of this particular factor deficiency is still not unanimously established in research literature globally as the disease manifests with variability in symptoms which may ranges from minimal bleeding to catastrophic hemorrhage.

Aim: To characterize the clinical manifestations of patients to set a standard parameter of bleeding severity in our local population.

Materials and Methods: This descriptive and cross sectional study was conducted at NIBD Karachi in collaboration with Chugtai's Lab and CHL Lahore in conformance with the Helsinki declaration. Consent was signed from all participants. Inclusion criteria for index patients specifically encompass the diagnosed cases of congenital afibrinogenemia excluding all acquired causes of this condition. Initially all the samples were processed at collection centers and platelet poor plasma and serum was separated and collected in labeled aliquots. Samples were transported to NIBD Karachi by maintaining cold chain. First line investigations including prothrombin time (PT), activated partial thromboplastin time (APTT) and fibrinogen levels by clauss method were performed to reconfirm the results. Grading of every individual's signs and symptoms depends upon severity of the disease and define here as per bleeding score [Tossetto et al]

Results: Total 18 patients were evaluated with mean age group10±2 yrs and 11 were males. Two patients were sibling. PT was >120s, APTT >180s and fibrinogen levels were (<0.2g/l).The most common symptom is umbilical bleeding (95%) followed by circumcision hemorrhage (90%) in males, cutaneous manifestations (85%) and epistaxis (68%). Grading of bleeding was done by WHO bleeding scale criteria and very well correlated with bleeding score and haemorrhagic manifestations exhibiting by patients. Severe bleeding patients were shown to have high bleeding scores along with II and III grades of bleeding .

Conclusion:The clinical manifestations of congenital afibrinogenemia in our local population are more or less same as reported in global literature. Due to the low prevalence rate of RBDs and the variability of bleeding manifestations are not well characterized clinically so far. Few exceptions do exists as we didn't find most of the rare complications in our set of patients.