Methods for the Evaluation of Human Fibrinolysis: Studies with Two Combined Technics

205

A B S T R A C T a2-Plasmin inhibitor (a2PI) is a recently characterized, fast-reacting plasmin inhibitor in human plasma that appears to play an important role in regulation of in vivo fibrinolysis. We report here a case of complete deficiency of a2PI in man. The patient, a 25-yr-old Japanese man, had a life-long severe bleeding tendency (hemarthrosis and excessive bleeding after trauma). The following tests were within normal limits: platelet count, bleeding time, thrombin time, prothrombin time, partial thromboplastin time, titers of known clotting factors, platelet glass bead retention, Factor VIII-related antigen, platelet aggregation by ADP, collagen and ristocetin, and clot retraction. Routine liver function tests were also normal. The only abnormal finding was that whole blood clot lysis was extemely rapid and was complete in 4-8 h. The concentration of plasma protease inhibitors, including a2-macroglobulin, antithrombin III, a,-antitrypsin, and C1INH, were all normal. The concentration of a2-PI in the patient's plasma, assayed by immunological methods, was <0.1 mg/100 ml (normal concentration, 6.1+0.88 mg/100 ml [mean±SE]) and functional assays showed a complete deficiency of a2PI. Addition of purified a2PI to the patient's whole blood completely corrected the accelerated fibrinolysis. The patient's parents, four siblings, and four other members of this family were asymptomatic, but the titers of a2PI in their plasmas were-50% of normal pooled plasma. There were three

Section: Methodsmentioning

confidence: 99%

Congenital Deficiency of α2-Plasmin Inhibitor Associated with Severe Hemorrhagic Tendency *

Aoki¹,

Saito²,

Kamiya³

et al. 1979

205

“…However, other reports claim that c-aminocaproic acid is not effective in reducing the incidence or severity of hemorrhage (4). Therefore, it seemed--*Received for publication 5 May 1967 and in revised form 8 July 1967.…”

Section: Introductionmentioning

confidence: 99%

“…The microhematocrit and the erythrocyte sedimenattion rate [Wintrobe's method (7)] were measured on all blood samples. Some plasma samples were analyzed for radioactivity unbound to fibrinogen (5) and euglobulin fibrinolysis time (8). In all subjects studied the euglobulin fibrinolysis time was within the normal limit, 2-6 hr.…”

Section: Introductionmentioning

confidence: 99%

Studies of the Metabolism and Distribution of Fibrinogen in Patients with Hemophilia A*

Takeda¹,

Chen²

1967

Abstract. Using autologous ""1I-fibrinogen, we made studies of the metabolism and distribution of fibrinogen in 10 patients with hemophilia A. In two patients simultaneous studies of autologous 13I-fibrinogen and homologous 125I-fibrinogen prepared from healthy donors' plasma were carried out. The average value for the plasma volume was 42.1 ± 8.8 ml/kg; for the plasma fibrinogen concentration, 349 + 90 mg/100 ml; for the intravascular fibrinogen, 144 ± 32 mg/kg; for the interstitial fibrinogen, 30 ± 11 mg/kg; for the slower half-life of 11I-fibrinogen, 2.34 + 0.17 days; for the transcapillary transfer rate of fibrinogen, 109 + 37 mg/kg per day; and for the catabolic and synthetic rates of fibrinogen, 51.7 + 13.1 mg/kg per day. Comparison of these results with those of the previous study in healthy male subjects showed that in patients with hemophilia A the catabolic and synthetic rates of fibrinogen are markedly increased, whereas the plasma fibrinogen concentration, intravascular and interstitial fibrinogen, and the transcapillary transfer rate of fibrinogen are not significantly different. The simultaneous studies of autologous 131I-fibrinogen and normal homologous 125I-fibrinogen in two subjects revealed that the two preparations behaved very similarly. Based on these findings, we concluded that our present findings are not due to the qualitative difference between the hemophilia A and normal fibrinogens, but that they are due to the difference in the host condition with respect to the fibrinogen metabolism, which is either an increased rate of direct breakdown of fibrinogen or an increased rate of fibrinogen breakdown after fibrin formation, or both.

“…Concentrations of fibrinogen/fibrin degradation products were estimated by hemagglutination inhibition test of Merskey et al (30). Euglobulin clot lysis time was performed by the method of von Kaulla and Schultz (31).…”

Section: Hereditary Molecular Abnormality Of Plasminogenmentioning

confidence: 99%

Abnormal Plasminogen

Aoki¹,

Moroi²,

Sakata³

et al. 1978

237

A B S T R A C T A patient who suffered a recurring thrombosis over the last 15 yr has been investigated. The only abnormality found in this patient was a significantly depressed level of plasminogen activity in plasma. In spite of the depressed plasminogen activity, the patient was found to have a normal level of plasminogen antigen concentration. It was calculated that the activity per milligram of plasminogen of the patient was approximately one-half the values of normal subjects. The same discrepancy between biological activity and antigen concentration was found in the other members of the kindred. A niece was found to have practically no plasminogen activity but possessed a normal concentration of plasminogen antigen. Both her parents were found to have approximately half the normal plasminogen activity and normal antigen levels. These studies suggested that the molecular abnormality was inherited as an autosomal characteristic, and the family members who had half the normal levels of activity with normal plasminogen antigen were heterozygotes whereas the one with practically no plasminogen activity was homozygote. Subsequent studies showed that the pattern of gel electrofocusing of purified plasminogen of the heterozygotes consisted of 10 normal bands and 10 additional abnormal bands, each of which had a slightly higher isoelectric point than each corresponding normal component. This indicates that plasminogen of the heterozygote is a mixture of' normal and abnormal molecules in an approximately equal amount, which was substantiated by active site titration of purified plasminogen preparations obtained from the propositus and a normal individual. The gel electrofocusing Portions of this work were presented at the annual meeting of the Japanese Society of Hematology, Kanazawa, Japan.