Plasma fibronectin level in patients with connective tissue diseases.

The level of plasma fibronectin (Fn) was studied in 40 patients with connective tissue diseases. Fn concentration was found increased in patients with rheumatoid arthritis (mean +/- SE, 560 +/- 30 micrograms/ml, p less than 0.01) decreased in patients with mixed connective tissue disease (337 +/- 12 micrograms/ml, p less than 0.05) and was not significantly different from controls in systemic lupus erythematosus, scleroderma, polymyositis. The value of plasma Fn level was found increased in active diseases and decreased in the cases, with presence of cryoprecipitates. The factors which might influence the level of plasma Fn and the possibility of using the changes of Fn concentration in the estimation of the evolution of connective tissue diseases are discussed.

A longitudinal study of serum beta 2-microglobulin levels in haemophilia.

Serum beta 2-microglobulin (beta 2-m) levels were measured in 75 adults with haemophilia A. Beta 2-microglobulin was found to be significantly elevated in haemophiliacs compared with the non-haemophiliac population. There was a greater rise in beta 2-m in HIV antibody-positive haemophiliacs. No further significant increase occurred in the subgroup with HIV-related disease but all these patients had beta 2-m levels greater than or equal to 3 mg/l. Over the study period of 18 months no significant increase in beta 2-m was documented in either HIV antibody-negative or -positive groups. Beta 2-microglobulin was elevated in HIV antibody-negative subjects with raised transaminase levels. No correlation was found between beta 2-m and the amount of factor VIII concentrate infused, T-cell subsets, thrombocytopenia or age. It is concluded that probable reasons for elevated beta 2-m levels in haemophiliacs include infection with HIV and other viruses, chronic liver disease, and repeated antigenic challenge from multiple infusions of factor VIII. The role of serial measurement of beta 2-m in haemophiliacs with a view to predicting the onset of HIV-related disease warrants further study.

Factor VIII: C (FVIII: C) recovery and half-life after infusion of steam-treated high purity factor VIII concentrate in severe hemophilia A--comparison of one-stage assay, two-stage assay and a chromogenic substrate assay.

Factor VIII:C recovery and half-life was measured in 16 hemophilia A patients under comprehensively standardized conditions. Each patient received the same lot of a steam-treated high purity FVIII concentrate at a dose of 19-33 U/kg body weight. A comparison was made between the one-stage assay, the two-stage assay and a chromogenic substrate test for FVIII:C determination using a FXa-sensitive chromogenic substrate. Factor VIII:C potency of the administered FVIII concentrate was measured using calibration curves derived from a concentrate standard and FVIII:C plasma levels were read from calibration curves derived from a plasma standard. The chromogenic assay showed a good reproducibility at FVIII:C levels between 0.015 and 0.50 U/ml. The FVIII:C recoveries calculated from the results of the one-stage assay, the two-stage assay and the chromogenic substrate test were 109 +/- 20, 92 +/- 14 and 81 +/- 11% (mean +/- SD), respectively. The elimination half-lives of FVIII:C were calculated by non-linear least square analysis using a modified computerized Gauss-Newton algorithm. The half-lives calculated from the FVIII:C plasma levels measured by the one-stage assay, the two-stage assay and the chromogenic test were 23.8 +/- 6.4, 22.2 +/- 5.7 and 17.1 +/- 4.8 h (mean +/- SD), respectively. No previous study has reported such long half-life values. Our findings indicate that measurements of recoveries and half-lives by the chromogenic FVIII:C assay and by computerized non-linear least square analysis allow the possibility of individualized FVIII replacement therapy.

Increased level of plasma factor VIII-related antigen in peripheral arterial disease.

When compared to age-matched control subjects factor VIII-related antigen was found to be significantly increased in patients with peripheral arterial diseases, while there were no significant differences concerning its plasma level between patients with thrombangitis obliterans and those with atherosclerosis of the lower limbs or between the various stages of the disease. Acute phase reactants such as plasma fibrinogen and alpha 1 antitrypsin were changed to a much lesser extent in the initial stages of peripheral arterial disease, and the afore mentioned antiprotease increased significantly only in stage IV. It is considered that the increased plasma level of factor VIII-related antigen occurring already in the initial stages of arterial disease, should be interpreted as an expression of widespread endothelial lesions and not as the mere result of an acute phase reaction. The relevance of changes affecting factor VIII-related antigen for the development of thrombotic complications could be assessed only in the context of other abnormalities of the hemostatic variables.

Factor VIII activity in chronic renal disease.

F VIII coagulant, F VIII-related antigen and F VIII ristocetin cofactor activity were significantly increased in 68 patients with various chronic renal diseases. All three F VIII functions correlated generally well with each other. A striking relationship between some F VIII activities and serum creatinine was detectable in patients with glomerulonephritis and kidney transplants, with mild or moderate renal insufficiency. This correlation was no longer present in terminal renal failure. The results suggest that in initial stages of renal disease elevated F VIII levels may be attributable to glomerular endothelial damage. In terminal renal failure, however, increased F VIII concentrations seem to result from nonspecific causes related to uremia such as acute phase reactions.

An immunoradiometric assay for procoagulant factor VIII antigen: results in haemophilia, von Willebrand's disease and fetal plasma and serum.

An immunoradiometric assay (IRMA) has been developed based on the inhibitor which arose in a polytransfused severe haemophiliac. The two-site IRMA measures antigens closely associated with the procoagulant parts of the factor VIII complex, which are termed FVIIC antigens or FVIIICAG. FVIIICAG was present in normal plasma and also, at a slightly lower concentration, in normal serum. In 37 patients with haemophilia A, 36 had FVIIICAG levels of less than 10% of the normal plasma pool. In patients with von Willebrand's disease the levels of FVIIIC and FVIIICAG were in good agreement, both before and after treatment with cryoprecipitate or DDAVP. FVIIICAG was relatively stable in plasma at 37 degrees C and could also be detected in cord and fetal serum. The assay is of potential value for detecting reduced levels of factor VIII, for carrier detection and for the prenatal diagnosis of haemophilia.

Haemostatic mechanism in the uterine circulation during placental separation.

The haemostatic mechanism in the uterus during parturition was investigated in 12 patients being delivered by caesarean section. Detailed sequential study of the blood coagulation and fibrinolytic systems in the uterine circulation showed that placental separation is accompanied by a striking local activation of the clotting mechanism. Uterine vein blood draining the placental site while the placenta was separating showed a pronounced shortening of the whole-blood clotting-time, a significant shortening of other clotting-tests, and a sharp increase in factor VIII activity, though these changes were transitory. After delivery the level of fibrinogen and circulating platelets steadily increased and factor VIII activity remained high.Activation of the clotting mechanism during placental separation appears to play an essential part in controlling uterine haemorrhage. The subsequent changes in the haemostatic mechanism in the puerperium are likely to predispose to thromboembolic complications.