Hathaway et al. (1965) described a Kentucky kindred in which 4 sibs of the name Fletcher showed a previously undescribed coagulation defect. Although they had no abnormal bleeding tendency, their blood showed much prolonged activated partial thromboplastin time ... Hathaway et al. (1965) described a Kentucky kindred in which 4 sibs of the name Fletcher showed a previously undescribed coagulation defect. Although they had no abnormal bleeding tendency, their blood showed much prolonged activated partial thromboplastin time (aPTT) and delayed thromboplastin generation but normal prothrombin time. Plasmas deficient in factors VIII (300841), IX (300746), XI (264900), and XII (610619) corrected the abnormality. Further studies by Hathaway et al. (1976) suggested that severe prekallikrein deficiency has no clinically significant effect on hemostasis, fibrinolysis, inflammatory responses, or leukocyte function. Hattersley and Hayse (1970) reported 3 unrelated cases. Research by Saito et al. (1972) suggests that Fletcher factor deficiency is associated with an inhibitor to the clot-promoting activities of glass-like surfaces. Aznar et al. (1978) observed the abnormality in 3 sisters of a Mediterranean family. The parents were related. Two of the 3 sisters plus a brother without clotting abnormality had arthrogryposis multiplex congenita. A preponderant occurrence in black families had been suggested previously on the basis of 6 families. Kyrle et al. (1984) studied a case of severe PKK deficiency and identified the heterozygous state in 8 relatives. The possibility of relationship to the Graves disease in the proband was raised. Bouma et al. (1986) reported 3 sibs with the genetic compound state. The father had deficient clotting activity and normal ratio of antigen to activity. The mother had a variant prekallikrein, dubbed Long Beach, with elevated ratio of antigen to activity, i.e., a CRM+ variant. DeLa Cadena (1995) reported studies of a 9-year-old patient with markedly prolonged aPTT but normal prothrombin time and bleeding time. The prolonged aPTT was due to a PKK deficiency. DeLa Cadena (1995) also reviewed the role of prekallikrein in thrombosis.
In a 79-year-old Caucasian male with prekallikrein deficiency, Wynne Jones et al. (2004) identified a homozygous arg94-to-ter substitution in the KLKB1 gene (R94X; 229000.0001).