Factor XII but not protein C, protein S, antithrombin III, or factor XIII is a predictor of recurrent miscarriage.

OBJECTIVE: To investigate whether a decrease in the values of protein C (PC), protein S (PS), antithrombin III (ATIII), factor XII (FXII), or factor XIII (FXIII) has predictive value for subsequent miscarriages. DESIGN: Prospective study. SETTING: Nagoya City University Medical School. PATIENT(S): A total of 536 patients with a history of two or more first-trimester miscarriages. INTERVENTION(S): One hundred and twelve patients treated with low-dose aspirin were excluded from the analysis. MAIN OUTCOME MEASURE(S): The subsequent pregnancy outcome of 424 patients was compared for abnormal and normal levels of each parameter. RESULT(S): There were no differences in the subsequent miscarriage rates between abnormal and normal values of PC, PS, ATIII, and FXIII. However, the rate with abnormal FXII is significantly higher than that with normal FXII. CONCLUSION(S): A decrease in FXII (but not in PC, PS, ATIII, or FXIII) predicts subsequent miscarriage in patients with a history of first-trimester recurrent miscarriages.

Hageman factor and kallikrein in pathogenesis of senile cataracts and the pseudoexfoliation syndrome.

It is thought that dystrophic changes in the human aging anterior eye are due to lipid peroxidation in both the cortical and nuclear structures of the lens under the conditions of ischemia. These changes are often accompanied by only lens opacification (senile cataract-SC) or by formation of amorphous or fibrillar deposits in anterior eye, disturbances of eye hydrodynamics and lens opacification (pseudoexfoliation syndrome-PES). Our results suggest that the main reason of dystrophic changes in the tissues of the aging anterior eye is the disturbance of the haemato-ophthalmic barrier and that the plasma kallikrein-kinin system takes part in this disturbance. Penetration of plasma proteins, such as C-reactive protein, complement components, immunoglobulins and coagulation factors, from plasma into the aqueous humor is responsible for damaging epithelial structures of anterior eye and formation of pseudoexfoliative material. Using ELISA, the C-reactive protein, IgG and IgM antigens have been shown to localize on the surface of the opaque lenses. Presence of these complement binding proteins in the superficial lens structures as well as the high C3a concentration in the aqueous humor substantiates the pathogenic role of complement activation in the lenticular epithelium upon cataract and PES formation.

Bradykinin-mediated hypotension after infusion of plasma-protein fraction.

In patients who required volume expansion during extracorporeal circulation, the plasma bradykinin concentration was monitored simultaneously with the mean arterial pressure during infusion of either albumin solution or PPF. The PKA content of the PPF and the albumin solution was 29 and 3 U/L, respectively, measured spectrophotometrically. In six patients receiving 250 ml of PPF, the mean arterial pressure decreased 22% to 54% within 1.5 min after infusion, whereas the plasma bradykinin concentration, measured by radioimmunoassay, increased significantly (p less than 0.0005) during the first minute. In six patients receiving 250 ml of 4% albumin solution, no blood pressure changes were found, and the plasma bradykinin concentration rose only slightly. In vitro, linear correlation (r = 0.94, p less than 0.0005) was observed between the level of PKA of 26 different lots of PPF and the concentrations of bradykinin that were generated in Hageman factor-deficient plasma after incubation with PPF. It is concluded that the hypotensive reactions observed after PPF infusion during extracorporeal circulation are caused by the PKA-induced bradykinin generation.

Hypotension associated with prekallikrein activator (Hageman-factor fragments) in plasma protein fraction.

Thirteen lots of plasma protein fraction made by one manufacturer were implicated in 23 recent reports of hypotension in surgical patients. Four of these patients required resuscitation after rapid administration of the product in the postoperative period. All implicated lots had prekallikrein-activator activity but low levels of bradykinin and kallikrein. The prekallikrein activator was identified as Hageman-factor fragments by molecular weight (35,000 as estimated by gel chromatography), isoelectric point (4.2 to 4.4), and inhibition by antibody to Hageman factor. These data suggest that Hageman-factor fragments are potent hypotensive agents, presumably because they trigger the generation of bradykinin in recipients. Prekallikrein-activator activity, usually at levels lower than those in the initial 13 implicated lots, was frequently detected in plasma protein fraction made by other manufactures. Several of these lots were associated with additional reports of hypotension. Prekallikrein-activator activity rarely occurred in albumin.