Prekallikrein Activation and High-Molecular-Weight Kininogen Consumption in Hereditary Angioedema

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Abstract
Patients with hereditary angioedema lack C1̄ inhibitor, a plasma α2-glycoprotein that inhibits both the proteolytic action of C1̄, the activated first component of the complement system, and the activity of components of the contact phase of coagulation: kallikrein, factor XIa, and factor XIIa. Such patients have been shown to have low levels of C4 and C2, the natural substrates for C1̄, but the levels were not correlated with the presence of symptoms. We studied three patients with angioedema for evidence of activation of the contact system and found that during a symptomatic period they had decreased levels of prekallikrein, a substrate for the activated forms of factor XII, and reductions in high-molecular-weight kininogen, a substrate for plasma kalli-krein. These observations suggest that zymogens of the contact system are activated during attacks of hereditary angioedema and that some of the clinical manifestations may be mediated through products of this pathway, such as kinins. (N Engl J Med 1983; 308:1050–4.)