During clinical trials of a human antihaemophilic globulin concentrate (HAHG) prepared from very fresh plasma by the method of Kekwick and Wolf (1957), it was observed (Maycock, Evans, Vallet, Combridge, Wolf, MacGibbon, French, Wallett, Dacie, Biggs, Handley and Macfarlane, 1963) that the transfusion of this material into haemophiliacs was sometimes followed by reactions similar to those observed by Fox, Goldsmith, Kidd and Lewis (1961) after the intravenous injection of purified bradykinin. A chemically similar fraction (ETF), prepared from aged plasma, has been used for many years for the treatment of hypofibrino-genaemia without any reported reactions.

The reactions described by Maycock et al. (1963) were sufficiently frequent and severe to warrant an investigation of the kininogenic properties of HAHG and, for comparative purposes, of ETF. For reasons not understood, but clearly associated with the adoption of a modification of the original technique (Kekwick and Walton, 1965), reactions occurring during the transfusion of recently prepared batches of HAHG into haemophiliacs are now no greater in number and severity than those occurring during the transfusion of fresh plasma. Human plasma contains prokininogenases, the precursors of enzymes which hydrolyse protein substrates (kininogens, kallidinogens) to produce kinins, polypeptides which cause vasodilation and plain muscle constriction (Lewis, 1960). Activation of two of these proenzymes, kallikrein and plasminogen (profibrinolysin), could lead to the production of kinin in HAHG either during preparation, or during transfusion, and might cause the observed reactions.