Coagulation
Hereditary bleeding disorders
High molecular weight kininogen deficiency / assay

Authors: Julie Gober-Wilcox, M.D., Kendall Crookston, M.D., Ph.D. and Jeremy Parsons, M.D. (see Authors page)

Revised: 28 April 2016, last major update July 2011

Copyright: (c) 2002-2016, PathologyOutlines.com, Inc.

PubMed Search: High molecular weight kininogen deficiency/assay

Definition / General
  • High molecular weight kininogen deficiency is a rare congenital disorder inherited as an autosomal recessive trait, not associated with a bleeding diathesis
  • Typically discovered in individuals with an isolated prolonged PTT
Terminology
  • High molecular weight kininogen is also known as Fitzgerald factor, Williams factor and Flaujeac factor
Pathophysiology
  • High molecular weight kininogen is a protein produced by the liver (with no inherent catalytic activity) that is involved in the early steps of the intrinsic coagulation pathway; it functions as a cofactor and binds with prekallikrein and factor XI to help facilitate their activation by factor XIIa
  • The kininogens (low and high molecular weight) are also involved in the kinin-kallikrein system and function to inhibit thrombin activation of platelets and stimulate liberation of nitric oxide, prostacyclin and tissue plasminogen activator
Clinical Features
  • Not associated with bleeding
Laboratory
  • Isolated prolonged PTT
  • Negative lupus anticoagulant
  • Specific assay to test for deficiency uses high molecular weight kininogen deficient plasma mixed with patient plasma; a PTT is performed and is compared to a standard curve of high molecular weight kininogen vs. PTT
  • Interference occurs in these assays if patient is on heparin, hirudin or argatroban, possibly danaparoid
  • Lower levels in newborns, increase to adult levels by age 6 months
Case Reports