Prekallikrein deficiency: the characteristic normalization of the severely prolonged aPTT following increased preincubation time is due to autoactivation of factor XII.
Hereditary plasma prekallikrein (PK) deficiency was diagnosed in a 71-year-old man with an 8-year history of osteomyelofibrosis. PK deficiency was suspected in view of a severely prolonged activated partial thromboplastin time (aPTT) that nearly normalized following prolonged preincubation (10 min) of patient plasma with kaolin-inosithin reagent. Hereditary PK deficiency was demonstrated by very low PK values in the propositus (PK clotting activity 5%, PK amidolytic activity 5%, PK antigen 2% of normal plasma, respectively) and half normal PK values in his children. Normalization of a severely increased aPTT (>120 s) after prolonged preincubation with aPTT reagent occurred in plasma deficient in PK but not in plasma deficient in factor XII (FXII), high-molecular-weight kininogen (HK), factor XI (FXI), factor IX, factor VIII, Passovoy trait plasma or plasma containing lupus anticoagulant. Autoactivation of FXII in PK-deficient plasma in the presence of kaolin paralleled the normalization of aPTT. Addition of OT-2, a monoclonal antibody inhibiting activated FXII, prevented the normalization of aPTT. We conclude that the normalization of a severely prolonged aPTT upon increased preincubation time (PIT), characteristic of PK deficiency, is due to FXII autoactivation.
Asmis
Lars M
LM
Central Hematology Laboratory, University of Bern, Inselspital, Bern CH 3010, Switzerland. lars.asmis@hcuge.ch
Sulzer
Irmela
I
Furlan
Miha
M
Lämmle
Bernhard
B
D000368:Aged; D001778:Blood Coagulation Disorders / Q000097:blood / Q000151:congenital / Q000175:diagnosis*; D001779:Blood Coagulation Factors / Q000378:metabolism; D005174:Factor XII / Q000378:metabolism; D005192:Family Health; D006801:Humans; D015151:Immunoblotting; D008297:Male; D010314:Partial Thromboplastin Time; D011288:Prekallikrein / Q000172:deficiency*
D001779:Blood Coagulation Factors; D005174:Factor XII; D011288:Prekallikrein