Prekallikrein/Kallikrein
Biochemistry
Synonym | Fletcher Factor |
---|---|
Molecular mass | 100.000 Da |
Synthesis | Liver |
Plasma concentration | 35 - 50 mg/l |
Normal range | 50 - 150% or 0.5 - 1.5 E/ml |
Prekallikrein is the inactive precursor (zymogen, proenzyme) of kallikrein. After activation of the intrinsic coagulation system, prekallikrein - with participation of high molecular weight kininogen - is bound to negatively charged surfaces. Factor XIIa then activates it to kallikrein. In turn, kallikrein in a positive recoupling mechanism activates factor XII to factor XIIa.
Clinical significance
We differentiate between the hereditary deficiency, which occurs extremely seldom, and the acquired kallikrein deficiency. The acquired deficiency can be caused by interference of synthesis (serious liver disease) as well as by an increased consumption (e.g. DIC, septic shock, nephrotic syndrome).
Indication
- Impairment of the kallikrein system
- Suspected hereditary prekallikrein deficiency
- Prolongation of the aPTT of unknown reason
Literature
- Gallimore MJ. Plasma Präkallikrein. Hämostaseologie 7, 166-171, 1987.
- Schmaier A et al. Activation of the Plasma Kallikrein/Kinin System on cells: A revised Hypothesis. Thromb Haemost 82, 226-233, 1999.
- De La Cadena R, Scott CF & Colman RW. Evaluation of a microassay for human plasma prekallikrein, J Lab Clin Med 109, 601-607, 1987.
- Friberger P, Aurell L & Claeson G. Chromogenic substrates for kallikreins and related enzymes. Agents and Actions Suppl. 9, 83-90, 1982.
- Scott C et al. A new assay for high molecular weight kininogen in human plasma using a chromogenic substrate. Thromb Res 48, 685-700, 1987.
- Karlsrud T et al. Evaluation of a Microassay for Human Kininogens as Cysteine Protease Inhibitors. J Pharm Meth 26, 113-124, 1991.
- Prassas I, Eissa A, Poda G, Diamandis EP. Unleashing the therapeutic potential of human kallikrein-related serine proteas-es. Nat Rev Drug Discov. Mar 14(3), 183-202, 2015.
- Potier L, Waeckel L, Richer C, Roussel R, Bouby N, Alhenc-Gelas F. Tissue kallikrein, blood pressure regulation, and hyper-tension: insight from genetic kallikrein deficiency. Biol Chem. Mar 394(3), 329-33, 2013.