Prekallikrein Deficiency

1
Prekallikrein Deficiency

• The surface-mediated pathway, or contact
  system, consists of four proteins Factor XII
  (FXII), High Molecular Weight Kininogen (HK),
  Prekallikrein (PK), C1-Inhibitor. PK bound to
  its cofactor, HK, in the presence of a surface
  (endothelial cell membrane or APTT reagent
  activator) is converted to the active serine
  protease, Kallikrein, which in turn activates
  FXII. Deficiencies of PK (also named Fletcher
  Factor after the index patient) will result in a
  prolonged APTT. The extent of APTT prolongation
  is dependent upon the type of activator present
  in the APTT reagent. Ellagic acid shows the
  least sensitivity to the deficiency.

2
Testing for Prekallikrein

• To identify a PK deficiency, APTT assays are
  performed as noted in Step 1 (Table at left).
• In Step 2 incubation times are extended from 5 to
  10 minutes in order to increase the time for
  surface activation. PK deficient plasmas will
  show a shortening of clotting times.
• Step 3 is a Mixing Study (11 mix) wherein
  patient plasma and a normal pooled plasma NPP,
  serving as a control, are challenged to correct
  the deficiency of a PK deficient substrate
  plasma. Mixing Study APTTs are tested using a 5
  minute incubation.
• If patient plasma is unable to correct a
  deficiency in PK deficient plasma in similar
  fashion to that of NPP, a PK deficiency is
  confirmed.

Triplett DA, Harms CS. Procedures for the
Coagulation Laboratory. ASCP Press 1981, pp
61-63.