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[Coagulation and fibrinolysis associated with contact phase in plasma with high molecular weight kininogen
Abstract:
Congenital deficiency of high molecular weight kininogen (HMWK), first reported by Saito et al. in 1975, is a rare disorder with homozygous defect of HMWK and only 14 cases have been reported so far. Prolonged partial thromboplastin time and depressed intrinsic fibrinolytic activity in plasma interacted with negatively charged surface were characterized in these patients without any bleeding problem. On the other hand, patients associated with hemorrhagic disorder, such as haemophiliacs, showed a markedly prolonged partial thromboplastin time but normal intrinsic fibrinolytic activity. These results give us a important suggestion on our understanding of why haemophiliacs bleed and why HMWK deficient patients do not. In immunological studies with specific antisera directed against human plasma HMWK and prekallikrein, HMWK in present in normal plasma in free form and a complexed form with prekallikrein, and whole prekallikrein in present in a complexed form with HMWK. This result is associated with diminished level of prekallikrein in plasma of patients with congenital HMWK deficiency. According to above-mentioned our experimental results and some reports, it is speculated that the deficiency of HMWK with normal level of prekallikrein is acquired.
Insights
Congenital high molecular weight kininogen (HMWK) deficiency is rare and doesn't cause bleeding. Unlike hemophiliacs, HMWK-deficient patients have prolonged clotting times but no hemorrhage, suggesting HMWK's role in bleeding disorders.
Area of Science:
- Hematology
- Biochemistry
Context:
- Congenital deficiency of high molecular weight kininogen (HMWK) is a rare genetic disorder.
- Only 14 cases have been reported since its initial description in 1975.
- Patients exhibit prolonged partial thromboplastin time and reduced intrinsic fibrinolytic activity without bleeding complications.
Purpose:
- To investigate the hemostatic and fibrinolytic characteristics of HMWK deficiency.
- To elucidate the relationship between HMWK, prekallikrein, and bleeding disorders.
- To differentiate the hemostatic profiles of HMWK deficiency and hemophilia.
Summary:
- HMWK-deficient patients show prolonged partial thromboplastin time but no bleeding, contrasting with hemophiliacs who also have prolonged partial thromboplastin time but do bleed.
- Immunological studies reveal HMWK exists in free and prekallikrein-complexed forms in normal plasma.
- Congenital HMWK deficiency is associated with diminished prekallikrein levels, suggesting a complex interplay between these factors.
Impact:
- Provides insights into the hemostatic role of HMWK and the mechanisms underlying bleeding in hemophilia.
- Suggests that HMWK deficiency with normal prekallikrein levels may be acquired rather than congenital.
- Contributes to understanding the pathophysiology of coagulation and fibrinolysis.