A new Italian family with severe prekallikrein deficiency. Desmopressin-induced fibrinolysis and coagulation changes in homozygous and heterozygous members

Summary

In this paper we report the case of a new Italian family with severe cross-reacting material prekallikrein deficiency (CRM⁻). The proposita is a 22-year-old woman referred for evaluating an extremely prolonged activated partial thromboplastin time (APTT) detected during a routine screening. No clearcut bleeding history was reported. Prekallikrein antigen and activity were not measurable. The other contact-phase factors were within the normal range. Using an electromechanical coagulometer, six different commercial reagents yielded a markedly prolonged APTT (ratio>2). By prolonging the incubation time up to 10 min, APTT was normalized only with reagents employing ellagic acid as activator. On the contrary, APTT remained markedly prolonged using particulate activators (i.e. micronized silica and celite). No differences were observed using either rabbit or bovine brain cephalin. APTT was also performed on a laser automated ACL instrument; in this case reagents using ellagic acid yielded only moderately prolonged APTT values (ratio 1.3vs 1.4). The intrinsic fibrinolytic activity, as assessed by blood activator inventory test, was found to be moderately reduced (about 50% of normal) in the proposita, whereas normal values were measured in the heterozygous relatives. After infusion of 0.3 µg/kg 1-desamino-8-D-arginine vasopressin (DDAVP), kallikrein levels did not change in the proposita and her heterozygous relatives. A normal release of tissue-plasminogen activator, as assessed by fibrin-plate assay, was observed in all family members including the proposita.