Bleeding and severe hypodysfibrinogenemia: compound heterozygosity

BASTOS L; GROSSO SH; VERA MP; SÁNCHEZ LUCEROS A; MESCHENGIESER SS; MARTINEZ M; BLANCO AN; LAZZARI MA

Milan

Congreso; 21ST International Congress on Thrombosis; 2010

Mediterranean League on Thrombotic Diseases

Fibrinogen’s alterations may result in either hemorrhagic or thrombotic phenotypes. Qualitative deficiencies include dysfibrinogenemia and hypodysfibrinogenemia with low clotting activity and either normal or moderately reduced antigen levels. Dysfibrinogenemia (autosomal dominant) can affect polymerization, cross-linking or fibrinolysis of the fibrin clot. We present a 2 year-old girl, who had rupture of lingual frenulum with prolonged bleeding, requiring transfusion of red cells.Materials and methods: Citrate anticoagulated blood was used to perform coagulation assays (PT, APTT, TT). Fibrinogen was determined by Clauss’s (functional:F) and Laurell’s (immunological:I) methods. Polymerization of plasma was measured by turbidity studies at 350nm, upon addition of thrombin and CaCl2(0.025U/ml and 9.6mM final concentration). Results: The proposita showed unclottable PT, APTT, TT and reptilase times (RT);TT (N/2:20sec.; P+N:30sec.) and RT (N/2:19sec.; P+N:28sec.) were partiallycorrected by the addition of normal plasma. Low fibrinogen values were observed (F:8.9mg/dl; I:56mg/dl), functional activity was partially corrected by normal plasma (N:300mg/dl, P+N:125mg/dl). Parents’ tests: the father showed abnormal TT (51sec.; P+N:33sec.) and RT (45sec.;P+N:26sec.) not corrected by normal plasma and low fibrinogen values (F:31.5mg/dl; I:145mg/dl) with functional activity partially corrected by normal plasma (P+N:120mg/dl). The mother displayed fibrinogen, functional (170mg/dl) and immunological (185mg/dl), slightly below the reference value; functional activity was corrected by normal plasma. Proposita’s polymerization curves showed: prolonged lag phase, and markedly reduced slope and maximum absorbance level. Father’s plasma showed increased lag phase with reduced slope and maximal absorbance compared to normal plasma. Mother’s plasma displayed increased lag phase and reduced maximal absorbance. Conclusions: Discrepancy between functional and immunological fibrinogen levels, as well as the polymerization pattern in the proposita suggested a severe hypodysfibrinogenemia. A compound heterozygosity can be suspected considering her father had showed a less severe hypodysfibrinogenemia pattern and her mother, asymptomatic, showed slight decrease of fibrinogen. DNA sequencing is pending.