High-Molecular-Weight-Kininogen-deficiency D68.2-

High molecular weight kininogen (HMWK) deficiency is an autosomal recessive coagulation defect. It is known by several names, including Fitzgerald trait, Flaujeac trait, and Williams trait. Patients with HWMK deficiency are not prone to hemorrhage but exhibit abnormal surface-mediated activation of fibrinolysis. The Fitzgerald trait represents a "true" deficiency of HMWK, whereas the Flaujeac and Williams traits represent a total kininogen deficiency in which both HMWK and low molecular weight kininogen (LMWK) are deficient. HMWK and LMWK are both encoded by the KNG1 gene (612358) (Bick, 2002).

Abnormality of surface-activated intrinsic coagulation: Colman et al (1975) studied an asymptomatic 64-year-old black woman who had a severe abnormality of surface-activated intrinsic coagulation and of the fibrinolytic and kininogen-forming pathways. Fractionation of normal plasma showed that the factor that corrected the defect was kininogen. The proband was identified when a prolonged partial thromboplastin time was noted during a routine preoperative evaluation of its hemostatic mechanism.

Lefrere et al (1986) discovered HMWK deficiency during a preoperative hemostasis study in a 23-year-old Portuguese woman with no personal or family history of bleeding or thrombosis. A family history revealed heterozygous HMWK deficiency in the proband, her father, and 3 of her siblings.

Hayashi et al (1990) studied 4 Japanese families with complete kininogen deficiency and 1 family with exclusive HMWK deficiency.

Cerebral artery thrombosis: Krijanovski et al (2003) reported on a 6-year-old child of first cousins who had cerebral artery thrombosis and HMWK deficiency. The previously healthy child had headache and vomiting 10 days after moderate traumatic brain injury, followed by loss of consciousness and subsequent visual impairment. CT scan and angiography showed extensive thrombosis of the left vertebral basilar artery and dissection of the left vertebral artery. The patient had prolonged activated partial thromboplastin time (APTT) and received fresh frozen plasma before arteriography and then daily for 8 days, which resulted in normalization of APTT and improvement of neurologic symptoms. Complete neurological recovery occurred during anticoagulant therapy with warfarin, and no recurrence had occurred after 2 years of follow-up.

1. Bick RL (2002) Disorders of thrombosis and hemostasis: clinical and laboratory practice. (3rd ed.) Philadelphia: Lippincott, Williams and Wilkins S 127.
2. Hayashi H et al (1990) Molecular genetic survey of five Japanese families with high molecular weight kininogen deficiency. Blood 75: 1296-1304.
3. Jeong D et al (2020) The First Korean Case of High-Molecular-Weight Kininogen Deficiency, With a Novel Variant, c.488delG, in the KNG1 Gene. Ann Lab Med 40: 264-266.
4. Krijanovski Y et al (2003) Characterization of molecular defects of Fitzgerald trait and another novel high-molecular-weight kininogen-deficient patient: insights into structural requirements for kininogen expression. Blood 101: 4430-4436.
5. Lefrere JJ et al (1986) A new case of high molecular weight kininogen inherited deficiency. Am J Hemat 22: 415-419.