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A case of bilateral cortical necrosis (BCN) was reported because of her abnormal platelet count and aggregability. She was 26 years old primipara.In her past history, at the age of 11, she was operated because of papillary adenocarcinoma of the thyroid gland, when no abnormal bleeding was reported.After cesarean section, atonic hemorrhage occurred and anuria developed. Because BCN was suspected heparin and urokinase therapy were started (later, patchy BCN was verified by renal biopsy). Uremia was controlled by hemodialysis (3/week). Platelet count (Plt.) increased gradually to normal level within a week. After heparin cessation, Plt. continued to increase and exceeded 60×104/mm3. In spite of thrombocytosis, bleeding time (BT) was prolonged to more than 15 min. On 31st hospital day when Plt. was 40×104/mm3and BT more than 15 min., platelet aggregability was investigated by screen filtration pressure (SFP) method (normal range: 264.9±14.3mmHg when induced by 3μM ADP). Her aggregability was no more than 20mmHg. On 34th hospital day, she was attacked by generalized convulsion and tracheotomy was done. Despite 17 units of blood transfusion bleeding was not discontinued. Therfore, 6 units of packed platelet were transfused and bleeding was dramatically stopped within 2 hours. After this episode, BT was normalized while thrombocytosis persisted. On 59th hospital day when Plt. showed 48.1×104/mm3 and BT was 3.5min., platelet aggregability was investigated by SEP method and optical density (O. D.) method. Using SFP method 3μM ADP induced aggregability was 400mmHg. By O. D. method, 10μM ADP induced maximum aggregability (ADP max) was 32.8% (normal 70.2±2.6), 1μg/ml adrenaline induced maximum aggregability (adrenaline max) 90.8% (normal 40.6±4.0), and 1mg/ml collagen induded maximum aggregability (collagen max) 69.6% (normal 74.8±5.6), respectively.She discharged on 14th hospital day, when her creatinine clearance was 17L/day, BUN 31mg/dl, and creatinine 3.3mg/dl, and conservative management was indicated. On 178 th day after BCN, when Plt. revealed 27.6×104/mm3 and was 3min., platelet aggregability was investigated again. Using SFP method, 3μM ADP induced aggregability was 390mmHg, while by O. D. method, ADP max was 63.2%, adrenalin max 98.5%, and collagen max 82.4%, respectively.Throughout her clinical course, fibrin degradation products were 40μg/ml or less, fibrinogen 370-900mg/dl, and euglobulin lysis time 24 hours or more. CB-PC and cephalothin, which were administered when platelet aggregability decreased, were investigated in vitro by O. D. method, with no effect to platelet aggregability being found.

It has been said that the incidence of postoperative deep vein thrombosis is significantly low in Japanese compared to Western peoples. The study was undertaken to investigate its incidence and risk factors in Japanese.One hundred and twenty patients undergoing major abdominal surgery were investigated for deep vein thrombosis. All patients underwent postoperative isotopic scanning of the legs using the 125I-fibrinogen technique. Systematic studies on blood coagulation and fibrinolysis were performed on the patients before and after operation.In 15 of 120 patients there was the isotopic evidence of deep vein thrombosis, which was confirmed by ascending phlebography in ten in whom this procedure was performed. Thrombosis was unilateral in five and bilateral in ten. There were no physical signs suggesting thrombosis nor further propagation of thrombi into the popliteal vein or more proximal veins in any case, although seven of them recieved urokinase treatment immediately after detection of thrombosis in calf veins.Deep vein thrombosis developed more frequently in patients older than 50 years and in female. Deep vein trombosis was mostly found in patients who had colorectal surgery. All except one had malignant disease. Ten of fifteen cases who developed deep vein thrombosis had complete study of blood coagulation and fibrinolysis showed definite hypercoagulability in thromboelastgram and increase of heparin tolerance compared to those who had no thrombosis. However, euglobulin lysis time was rather shortened, suggesting increased fibrinolysis.The incidence of deep vein thrombosis in our series is definitely low compared to many reports in Western literatures. The cause of the low incidence remain open. Whatever the cause, the differences that we have demonstrated provide the first objective evidence that deep vein thrombosis is truely less frequent in Japanese than in Western peoples.

It has been studied about the induction of experimental disease of thrombosis or disseminated intravascular coagulation (DIC) using small animals. The blood coagulation or fibrinolysis system in small animals are different from that of human.In present study, we investigated the coagulation and fibrinolysis systems of Japanese and Rhesus monkeys as compared with human.These monkey's coagulation system was very similar to that of human from the results of prothrombin time test, partial thromboplastin time test, thrombin time test and the level of fibrinogen, whereas the fibrinolysis system of these monkeys were different from that of human. That is, the plasma lysis time and euglobulin lysis time were extremely prolonged in comparison with that of human.The level of plasmin inhibitor (including antiactivator), however, was same as the human. And the concentration of plasminogen in plasma from monkeys was higher significantly (p

Studies from many laboratories have indicated that dextran sulphate (DS) enhanced the fibrinolytic system, as shown in shortening of euglobulin lysis time. For the activation mechanisms of DS on fibrinolytic activity, it has been proposed that DS enhanced the fibrinolytic activity induced by contact activation, or accelerated the action of plasminogen activators. In this paper, we investigated the activation mechanisms of DS on fibrinolytic activity in vitro and in vivo system.We discovered that DS, orally administrated into rabbits (ranged 50-300mg/kg), suppressed the plasmin inhibitory activity, as measured by the diameter of lysis area on plasminogen-free fibrin plates. The suppressive action of DS on plasmin inhibitory activity was related to the dosage of DS administrated, and occasionally the fibrinolytic activity of euglobulin was enhanced.Furthermore, 2 groups of 19 subjects, 14 patients with hyperlipemia and 5 healthy volunteers were administrated orally 1, 800mg of DS daily from 4 to 47 weeks. Abnormal high levels of plasmin inhibitory activity in patient peripheral blood were reduced to normal levels in a few weeks after the DS medication, but normal levels of that in healthy subjects were not significantly changed. In vitro system, we could not estimate that DS (ranged 10-500μg/ml) might enhance the action of urokinase, nor that DS might accelerate the fibrinolytic activity induced by contact activation.This result suggested that the activation mechanisms of DS on fibrinolytic activity could depend upon the reduction of plasmin inhibitors.

Changes of protein C, Factor V and antithrombin III (AT III) after DDAVP infusion in 10 normal subjects were examined serially, before and after 30min., 60min., 120min., 180min., 300min, and 24 hours. At 180min., 300min, and 24 hours protein C activity increased and at 120min., 180min., 300min. and 24 hours protein C antigen also increased. Factor V activity decreased at 60min, and 120min, and AT III activity also decreased at 30min., 60min, and 120min. These changes of Factor V and AT III would be due to the enhancement of fibrinolysis because shortening of euglobulin lysis time and decrease of α2-plasmin inhibitor were observed at the same time.Protein C (activity and antigen) increased after DDAVP infusion in normal subjects but raised protein C gave no influence on factor V and AT III.

A case of Hepatosplenomegaly associated with Pancytopenia, bleeding tendency and markedly shortened Euglobulin Clot Lysis Time (ELT) was presented. The patient was undergone Splenectomy aiming of recovery from Pancytopenia. Histologically spleen showed Splenitis-like changes. It is of interest ELT recovered to normal range after Splenectomy. Therefore, the results of fibrinolytic data obtained were as followed.1) In vitro, ELT of normal plasma was shortened in addition of patient's plasma to normal plasma.2) t-AMCHA and Trasylol prolonged ELT of patient's plasma in vitro and in vivo.3) Patient's plasma and euglobulin did not so strongly hydrolyze TAME, AGLME, S-2251, S-2238 and RM601-1 (Pentapharm).4) A supernatant of homogenized spleen digested Bovine Standard Fibrin Plate, but not Bovine Plasminogen free Fibrin Plate and also this supernatant did not inhibit Plasmin and Urokinase.From these results, fibrinolytic system of this case was specific, and it might be suggested that the spleen of this case with decreased liver function and inflammation of spleen released high amount of Plasminogen Activator. Furthermore, we discussed the spleen might play some rule in the fibrinolytic system.

The relationship between tissue plasminogen activator (tPA), its fast acting inhibitor (PAI-1) and euglobulin clot lysis assay (ELT) were investigated with healthy volunteers' plasma.New clot lysis assay method was utilized with a slight modification for ELT. Briefly, clot was made in a microtiter plate and turbidity of the clot was measured with 340nm by a microtiter plate reader periodically. The point of half lysis was determined as euglobulin lysis time 1/2 (Fig. 1). Duplicated samples were analyzed and the correlation coefficient (R) was 0.992 (p

We administered tissue-type plasminogen activator (t-PA) intravenously to 10 patients with acute myocardial infarction (AMI) within 6 hours after onset of symptoms, and then examined the state of reperfusion by coronary arteriography (CAG) and observed changes in blood coagulation and fibrinolytic activity to evaluate their effects. AK-124 (by Asahi Chemical Industry and Kowa Co., Ltd. in collaboration), a t-PA produced by tissue culture of normal human lung cells, was given in dosage of 48, 000-576, 000 A. K. units by intravenous infusion over 30-45 minutes. In 7 patients who received t-PA reflow or improved flow was detected on CAG. In t-PA treated patients, euglobulin lysis activity clearly increased, euglobulin lysis time clearly shortened, and D-dimer increased. Levels of circulating fibrinogen and α2-plasmin inhibitor decreased after treatment with t-PA by an average of 12%, 14% of baseline values respectively, but plasminogen showed no detectable change. A hematoma at the site of the catheter insertion was observed in one patient. These observations suggest that t-PA has a higher specificity for fibrin bound plasminogen than for plasminogen and prduces coronary thrombolysis without causing systemic fibrinolysis at least with the present dosage.

This report was undertaken to study the direct effects of endotoxin on the in vitro fibrinolytic system which has not been fully understood.Shartening of both euglobulin lysis time and partial thromboplastin time was observed by the activation of normal plasma with endotoxin proportionally to its dose above 0.1mg per ml. And it was suggested that contact system was activated and surface mediated fibrinolysis was induced with endotoxin. Endotoxin had no direct effect on the plasmin activity, but it has accelelating effect on the plasminogen activator activity of urokinase and streptokinase measured by the fibrin agar plate method.Endotoxin detected in various gram-negative bacterial infections is extremely little as compared with the in vitro effective dose in the present study. Thus it was suggested that the direct effect of endotoxin on the fibrinolytic system is not caused in vivo. Therefore the fibrinolytic system is mainly influenced by the secondary effects of platelet, leucocyte and vascular endothelium damage caused by endotoxin.

In addition to the coagulation and fibrinolytic activities, changes in plasma C3, C4 and C1INH levels were investigated in 52 patients with obstructive jaundice. Increase of fibrinogen levels and prolongation of euglobulin lysis time (ELT) were the common features in patients without cholangitis. Whereas, patients with cholangitis showed more prominent prolongation of activated partial thromboplastin time and ELT, and reduction of thrombotest values, hepaplastintest (HPT) values, antithrombin III levels and plasminogen levels than those without cholangitis. These abormalities improved favorably after the appropriate biliary drainage. A marked reduction of plasminogen levels associated with prolonged ELT was considered to be an unfavorable sign suggesting a significant risk of major complications especially acute gastrointestinal hemorrhage and shock after the biliary drainage. The postoperative rise of HPT values and plasminogen levels, which occurred generally in the control group, was not proved in the patients who had the postoperative complications especially gastrointestinal hemorrhage and liver failure.Among the complement system, levels of C3, C4 and C1INH showed a significant increase in obstructive jaundice. Increased levels of C3 and C1INH improvedd significantly after the biliary drainage. There was a significant correlation between the levels of C1INH and ELT. This result suggested that the increase of plasma C1INH levels should play a certain role in decrease of fibrinolytic activity in obstructive jaundice.

The effects of sardine diet on blood lipids and hemostasis were investigated. Five healthy male subjects took a daily 300g of canned sardine for 1 week. After taking sardine eicosapentaenoic acid (EPA) contents increased but arachidonic acid (AA) contents did not change in plasma. Therefore, plasma EPA/AA ratio was elevated after taking sardine (before; 0.35±0.22, after; 1.18±0.84). Platelet aggregation induced by ADP (final concentration; 0.6μM and 1.8μM), collagen (1.4μg/ml), adrenaline (1.3mg/ml), A23187 (2.5μM), PAF (1.0μg/ml) or ristocetin (1.2mg/ml), as well as platelet adhesiveness, was not inhibited by taking sardine. The venous occlusion test was done before and after taking sardine. In the pre-occlusion plasma, sardine diet had no effect on the euglobulin lysis time (ELT), von Willebrand Factor (vWF): Ag, plasminogen, plasminogen activator and protease inhibitor (α2PI, α1AT, α2M, C1-INA). In the post-occlusion plasma, a shortening of ELT and a increased concentration of vWF: Ag and plasminogen activator were significant after taking sardine. These results demonstrate that the release of vascular plasminogen activator and vWF: Ag from the endothelium was accelerated by taking sardine. This effect of sardine diet on the plasminogen activator release may prevent thrombosis.

Changes in euglobulin lysis time (ELT) and Bβ15-42 peptide were investigated on 14 patients with benign disease and 24 with malignant disease before and after operation. ELT prolonged significantly in patients with malignant disease compared to one with benign disease on the first and second postoperative day.A significant increase of Bβ15-42 peptide was found in patients with malignant disease compared to patients with benign disease, though a definite increase was found in the latter group compared to healthy control. No significant difference in Bβ15-42 peptide was found between both patient groups postoperatively, though it increased with linear pattern.The same investigation was performed on patient who had intermittent compression of the legs for 48 hours postoperatively. Shortning of ELT was found in them compared to control. No significant difference in Bβ15-42 peptide was found between both groups, though it increased with linear pattern in both postoperatively. It suggests that no influence on activity of plasmin was produced by leg compression.

Changes in platelet counts, prothrombin time, partial thromboplastin time, thrombo test, normo test (hepaplastin test), fibrinogen, euglobulin lysis time (ELT) and Bβ 15-42 peptide were investigated on 16 patients with benign disease and 27 with malignant disease before and after operation in general surgical patients. The same investigation was performed on 6 patients with benign disease and 29 with malignant disease who had intermittent sequential compression of the legs for 48 hours postoperatively.The 125I-fibrinogen uptake test was performed on 45 patients with malignant disease who had intermittent sequential compression of the legs for 48 hours postoperatively.Following results were obtained.1) It suggests that influence on activity of plasminogen activator was produced by leg compression but no influence on activity of plasmin and plasminogen was produced by leg compression.2) Incidence of deep vein thrombosis (DVT) in intermittent sequential leg compression group reduced to 8.9 per cent compared with 18.0 per cent in control group.