FIBRINOGENEMIA TAMPERE - A DYSFIBRINOGENEMIA WITH DEFECTIVE GELATION AND THROMBOEMBOLIC DISEASE

Fibrinogen Tampere was found in a woman with a severe thromboembolic d isease. The thrombin induced clotting time of her plasma and purified fibrinogen was slightly prolonged. The activation of fibrinogen Tamper e appeared to be normal but subsequent gelation was defective. We stud ied fibrin gels formed at different ionic strengths and at different f ibrinogen and calcium concentrations by liquid permeation, turbidity, and 3D laser microscopy. Crosslinking was studied by SDS-gel electroph oresis. The gels formed from fibrinogen Tampere were at ionic strength above 0.2 much tighter and had lower fiber mass-length ratios than no rmal gels as judged by permeability and turbidity data. At ionic stren gth 0.15 and at different calcium concentrations analysis by permeabil ity showed the same results for fibrinogen Tampere as for normal gels. Analysis by turbidity at ionic strength 0.15 suggested swelling of th e fibers at low calcium concentrations. 3D microscopy revealed perturb ed clot architecture under all conditions. In fibrin gels from fibrino gen Tampere, the gamma-chain crosslinking was normal but the crosslink ing of alpha-chains was delayed at ionic strength 0.2 and also at lowe r ionic strengths on lowering the calcium concentration. The abnormal gelation may be due to a mutation in the fibrinogen molecule. Tendency to form tight fibrin gels and/or insufficient crosslinked fibrin matr ix may be pathogenetic in this thrombotic disease.