Blood & Vessel
Online ISSN : 1884-2372
Print ISSN : 0386-9717
Volume 9, Issue 2
Displaying 1-27 of 27 articles from this issue
  • Eiichi KIMURA
    1978 Volume 9 Issue 2 Pages 151-158
    Published: June 01, 1978
    Released on J-STAGE: August 05, 2010
    JOURNAL FREE ACCESS
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  • Izumi TAKEUCHI, Masatoshi KATO, Michio FUJIMAKI, Katsuhiro FUKUTAKE
    1978 Volume 9 Issue 2 Pages 159-163
    Published: June 01, 1978
    Released on J-STAGE: August 05, 2010
    JOURNAL FREE ACCESS
    The influences of several kinds of snake venoms, which indicate thrombin-like actions on the blood coagulation and fibrinolysis were investigated with special reference to factor XIII, and the results that were obtained are as follows;
    1) Venoms are able to form cross-linkage of fibrin more slowly than thrombin can act.
    2) Ca-ion is necessary in the formation of the cross-linkage of fibrin by the use of venoms.
    3) When cysteine solutions are not added into the reaction mixture, the fibrin clot formed by thrombin does not dissolve in 1% monochlor acetic acid solution, but the fibrin clot formed by venoms dissolves in the acidic solution.
    4) When the reaction mixture containes cysteine, the fibrin clot formed by venoms becomes insoluble in 1% monochlor acetic acid solution, after 30min. or 1hr. incubation.
    5) The action of Defibrase prepared from Bothrops atrox marajoensis venom on the activation of factor XIII resembles tha of Venacil from Agkistrodon rhodostoma venom, but Defibrase from Bothrops atrox moojeni venom demonstrates a slightly stronger activity for the activation of factor XIII in comparison with the activities of the other two venoms.
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  • Iwao OIKAWA, Sadami SEKIGUCHI, Yoshikazu ONDA, Isao SAITO, Norio KAWAH ...
    1978 Volume 9 Issue 2 Pages 164-168
    Published: June 01, 1978
    Released on J-STAGE: August 05, 2010
    JOURNAL FREE ACCESS
    The hemorrhagic tendency after major hepatic resection is recognized to be related to the disorders of coagulation factors and the fibrinolytic phenomen.
    The regeneration of the liver after hepatic resection may promote to increase capacity of residual liver function as well as to improve the coagulation disorders and fibrinolysis.
    In this paper, we reported the comparative results of the coagulation disorders fibrinolysis after primary massive hepatic resection and secondery resection in dogs.
    In primary 70% hepatectomized group, the prologation of PT but not PTT were seen. The fibrinogen concentration and platelet counts were not decreased and GOT and Al-p recovered to the normal level soon.
    In primary 85% hepatectomized group, PT and PTT prolongations were remarkable in the first week after operation, but in secondary 85% hepatectomized group (50% residual liver resection, on six weeks after primary 70% hepatectomy). PT and PTT prolongation did not continued for 2 weeks.
    The level of GOT and Al-p in secondary group were much more elevated than in primary group and did not recover to the normar level in both group.
    Through these data, secondary hepatectomy might be less changed and safer than primary resection in the coagulation factors and hemorrhagic tendency after massine hepatic resection.
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  • Akio YAMASHINA, Isamu KAITO, Syunichi SATO, Takashi ISHII, Susumu MOTO ...
    1978 Volume 9 Issue 2 Pages 169-173
    Published: June 01, 1978
    Released on J-STAGE: August 05, 2010
    JOURNAL FREE ACCESS
    Hepaplastintest, thrombotest, prothrombin time and blood coagulation factors II, V, VII, VIII, IX and X were measured in 9 cases with fulminant hepatitis, in 34 cases with acute hepatitis and in mice with MHV-2 hepatitis. Also carbon index as pagocytic activity was measured in mice with MHV-2 hepatitis. The following results were obtained.
    1) The activities of the blood coagulation except for factor VIII showed a decrease in fulminant hepatitis and in acute stage of acute hepatitis as compared to healthy subjects, especially in fulminant hepatitis.
    2) In acute hepatitis including fulminant hepatitis, there was a correlation between the decrease of the activities of blood coagulation except for factor VIII and severity of the disease.
    3) In mice with MHV-2 hepatitis, the activities of the blood coagulation except for factor VIII decreased with the progression of hepatic necrosis. But the activities of factor VIII increased in early stage, and decreased in terminal stage of MHV-2 hepatitis with parallel to the pagocytic activity.
    Therefore, it is believed that the determination of blood coagulation tests in hepatitis is useful to determine the diagnosis and prognosis of the diseases, and that the changes of factor VIII in MHV-2 hepatitis are closely related to the function of RES.
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  • Hiroyasu HIRAKAWA, Wataru OHTA, Yoshihiro SHIMADA
    1978 Volume 9 Issue 2 Pages 174-178
    Published: June 01, 1978
    Released on J-STAGE: August 05, 2010
    JOURNAL FREE ACCESS
    Hemorrhagic diathesis was investiqated in 147 cases consisting of 12 acute hepatitis, 22 chronic hepatitis, inactive form, 27 chronic hepatitis, active form, 43 liver cirrhosis, 7 cholecystopathy and 36 other miscellaeous hepato-biliary diseases.
    Eight labolatory tests detecting bleeding tendency were performed: bleeding time clotting time, clot retraction, Rumpel-Leede phenomenon, platelet count, thrombotest, normotest and plasma prothrombin time. Bleeding time longer than 5min. was observed in 46 out of 120 (33%) cases, clotting time longer than 15min.; in 1 out of 140 (1%), incomplete clot retraction; in 29 out of 132 (22%), over two positive Rumpel-Leede phenomenon; in 24 out of 136 (18%), platelet count less than 120, 000; in 34 out of 146 (23%), thrombotest less than 70%; in 85 out of 135 (63%), normotest less than 70%; in 35 out of 70 (50%) and plasma plothrombin time longer than 15sec.; in 27 out of 137 (20%).
    In liver cirrhosis, following tests showed abnormal values more often than in other diseases: Rumpel-Leede phenomenon (14 out of 41 (34%) cirrhosis, 10 out of 95 (11%) other diseases), platelet count (20 out of 43 (47%), 14 out of 103 (14%)), thrombotest (35 out of 41 (85%), 50 out of 94 (53%)), normotest (24 out of 28 (86%), 11 out of 42 (26%)), and plasma prothrombin time (19 out of 42 (45%), 8 out of 95 (8%)). Clot retraction is one of the most reliable test to avoid the bleeding after liver biopsy. There is no difference, however, in various liver diseases of the impaired retractions rates.
    Hemorrhagic diathesis was often observed in acute hepatitis and chronic hepatitis as well as in liver cirrhosis. Therefore, previous to peritoneoscopy and liver biopsy, it is necessary to check hemorrhagic diathesis. And if there is bleeding tendency, it should be treated beforehand.
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  • Hidemi GONMORI, Hiroshi TANAKA, Tatsuo UENO, Miyoko TAKAHASHI, Syozo T ...
    1978 Volume 9 Issue 2 Pages 179-183
    Published: June 01, 1978
    Released on J-STAGE: August 05, 2010
    JOURNAL FREE ACCESS
    Tissue thromboplastin (TP) have been detected in various types of leukocytes as well as many other organs and it is suggested to play important roles in blood coagulation. In this report, we studied on TP in the leukocytes from various types of leukemia in order to estimate its responsibility for the development of DIC, which accompained by these patients. We also compared it to brain (B) and placenta (P) TP by means of immunological techniques.
    Washed leukocyte suspensions were prepared by centrifugation and hypotonic lysis technique from 9 acute myelocytic leukemias (AML), 5 acute promyelocytic leukemias (APL), 4 chronic myelocytic leukemias and 20 healthy subjects. The TP activity was estimated by Nemerson's two stage method and effects on clotting times of various deficient plasmas were studied by Quick's one stage method. The distribution of the activity in the homogenate of APL leukocytes was studied by defferential centrifugation. Anti-P-TP was produced and used for immunological studies employing Ouchterlony method and clotting activity neutralization technique.
    Homogenates of APL leukocytes showed significant TP activity as much as 152 units per 10 million cells on the average, while homogenates of other blood cells, except a case of AML which had an activity of 3.8 units per 10 million cells, showed little activity. APL homogenates demonstrated striking shortening of the clotting times of Factor VIII and IX deficient plasmas but did not show this effect on Factor VII and X deficient plasmas. This activity was week, when cell suspensions were used without homogenization. It sedimented mainly at 700G in the centrifugation study and was neutralized time dependently by anti-P-TP in the same manner as when B- and P-TP were examined. By Ouchterlony method, desoxycholate extract of APL leukocytes showed single precipitin line against anti-P-TP, which fused into the lines formed by purified B- and P-TP.
    In conclusion, APL leukocytes have strong TP, which has similar antigenicity to B- and P-TP. It is conceivable that this TP causes or enhances DIC, especially when leukemic cells were destroyed by anti-leukemic therapy.
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  • Reference to F. VIII activity, F. VIII-related antigen and the ratio of F. VIII activity/F. VIII antigen
    Masaaki KONISHI, Hiroyuki UMEMOTO, Humito KATO, Makoto KUTO, Akihiko S ...
    1978 Volume 9 Issue 2 Pages 184-190
    Published: June 01, 1978
    Released on J-STAGE: August 05, 2010
    JOURNAL FREE ACCESS
    A hemorrhagic tendency is a common feature in patients with leukemia and may occur in other forms of hematological malignancy. Bleeding in these diseases is generally associated with thrombocytopenia, but cases in which the hemorrhagic tendency was ascribed to pathological fibrinolytic activity or DIC have been described.
    From this point of view, the investigation on hemostatic abnormalities was carried out in 32 patients with acute leukemia (11 AML, 16 APL, 2 AM0L and 3 ALL), 31 with malignant lymphoma (stage III and IV), 13 with multiple myeloma and 20 with myeloproliferative disorders (10CML, 4CLL, 1 myelofibrosis, 3 primary thrombocythemia and 2 polycythemia vera).
    The diagnosis of DIC in neoplasmas of blood and blood forming organs is to be attentive because the finding in basic diseases themselves accompanied with thrombocytopenia.
    We studied F. VIII activity (F. VIII act.), F. VIII-related antigen (F. VIII ant.) and the ratio of F. VIII act./F. VIII ant. with other 18 hemostatic parameters: platelet count, PTT, prothrombin time, thrombotest, hepaplastintest, F. I, F. V, and F. VII were measured for coagulation system, STT (30'), FDP (HIT), plasminogen (single radial immunodiffusion method) and paracoagulation test (protamine sulphate test, ethanol gelation test and cryofibrinogen) for fibrinolytic system. Antithrombin III, alpha 1 antitrypsin and alpha 2 macroglobulin were also measured for their inhibitors by single radial immunodiffusion method.
    We observed a poor correlation between F. VIII act, and F. VIII ant. levels in neoplasmas of blood and blood forming organs in which the elevation of the F. VIII ant. was significantly higher than that of the F. VIII act.
    In most cases of DIC, F. VIII act, was various, but F. VIII ant. increased significantly, and therefore, the ratio of F. VIII act./F. VIII ant. was markedly low. A discrepancy between F. VIII act. and F. VIII ant. may be explained by consumption of F. VIII act. and accumulation of F. VIII ant., destruction of F. VIII act. and degradation of F. VIII ant. caused by plasmin, differences in the degree of catabolism of two components and so on.
    A discrepancy between F. VIII act. and F. VIII ant. disappered with improvement of DIC. It is suggested that the ratio of F. VIII act./F. VII ant. may be one of the most valuable parameters, not only for diagnosis but also prognosis of DIC.
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  • Yasuo KAWASHIMA, Fumio KITADE, Naoshi OSAWA, Tadashi SEKIMOTO, Tsuguhi ...
    1978 Volume 9 Issue 2 Pages 191-196
    Published: June 01, 1978
    Released on J-STAGE: August 05, 2010
    JOURNAL FREE ACCESS
    We have studied the changes of blood coagulation and fibrinolysis in 47 patients with gastric cancer undergoing preoperative antineoplasmic chemotherapy. We also have studied the relation between the plasma fibrinogen level and histological stage of the cancer. The control group was 17 patients of gastric cancer without preoperative treatment.
    1. There was no remarkable changes in the platelet count and fibrinolysis.
    2. Prothrombin time was slightly prolonged in the patients treated with 5-Fluorouracil Dry Syrup (5-FUDS) therapy, but its level was still within normal limit, and there was no significant difference in loss of blood during operation between the patients with 5-FUDS therapy and control group.
    3. Plasma fibrinogen level decreased in the patients with 5-FUDS therapy and five times combined Mitomycin C and 5-Fluorouracil (MF) therapy. The decrease in fibrinogen level was more prominent in the patients with histologically advanced cancer. This fact was perhaps due to the antineoplasmic effect of these drugs to gastric cancer. On the other hand, there was no decrease in fibrinogen level in control group and in 3-4 times MF group.
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  • Nobuyoshi YOKOE, Haruki KATO, Shuhei TAKEMURA, Toshikazu YOSHIKAWA, Mi ...
    1978 Volume 9 Issue 2 Pages 197-201
    Published: June 01, 1978
    Released on J-STAGE: August 05, 2010
    JOURNAL FREE ACCESS
    Effect of increased intravascular coagulation on the digestive mucosa was investigated in an experimental model of DIC (disseminated intravascular coagulation) produced in dogs and rats.
    Intravenous administration of bacterial endotoxin caused marked hemorrhagic necrosis of the intestinal mucosa of dogs within 3 to 8 hours, and the lesion was coated with whitish pseudomembrane. Histologically, the villi showed marked deformity, fall of epithelial cells, cellular infiltrations, and sludging of red cells or thrombic formation in the microcirculations. There was no evidence of the increased tissue fibrinolytic activity in the affected mucosa. These data led us to conclude that the intravascular coagulation in the microcirculation of the intestinal mucosa affords to produce hemorrhagic necrosis of the mucosa, and to which fibrinolytic activity does not participate.
    Pretreatment of the intestinal mucosa of a dog by trans-AMCHA, a potent antiplasmin compound, or by Trasylol prior to the endotoxin shock, prevented the intestinal mucosa from hemorrhagic necrosis, and it was indicated that proteolytic enzymes present along the intestinal wall played a role in the production of mucosal damage when the microcirculation of the mucosa was disturbed by endotoxin.
    Further, it was found that rats treated with trans-AMCHA showed enhancement of the production of intestinal lesions following to the administration of endotoxin, indicating the antiplasmin agent inhibited secondary fibrinolysis and accelerated the clot formation in the rat.
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  • Hiroshi EGAWA, Koji SUZUKI, Osamu MATSUZAKI, Akinori ISHIHARA, Hiroshi ...
    1978 Volume 9 Issue 2 Pages 202-207
    Published: June 01, 1978
    Released on J-STAGE: August 05, 2010
    JOURNAL FREE ACCESS
    It was noted that the coagulative and the fibrinolytic faculties of the Japanese monkey were similar to those of the human in our previous report.
    In the present paper, we have measured the movement of the blood coagulative and fibrinolytic faculties after the intravenous injection of the tissue thromboplastin by using Japanese monkeys in an attempt to induce the experimental disease of disseminated intravascular coagulation (DIC).
    The results were as follows;
    1) In the coagulation system, platelet and fibrinogen level decreased extremely at first 10min after the injection, and tended to recover their level gradually from about 60min later in the case of the injection of the small (10mg/kg) and middle (20mg/kg) dose of tissue thromboplastin.
    But in the case of the high dose (40mg/kg), the level of platelet and fibrinogen did not recovered.
    The prolongation of the PT, PTT and TT were found from 10min after the injection, and the recovery of those clotting time was depended on the fibrinogen level.
    It seems that the degree of response and recovery of these results depend upon the dose of tissue thromboplastin.
    2) In the fibrinolysis system, the PLT and ELT were extremely reduced at 10min after the injection, and its reduction was induced by smaller dose of tissue thromboplastin as compared with that in the coagulation system.
    The appearence of FDP and the positive reaction in paracoagulation test were observed later from the reduction of PLT and ELT.
    3) Fibrillar thrombosis with ultrastructual appearance were found in small pulmonary vessels by the injection of even small dose of tissue thromboplastin.
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  • Tamotsu MATSUDA, Midori OGAWARA, Naoko HIRABAYASHI, Toshiko SEKI, Masa ...
    1978 Volume 9 Issue 2 Pages 208-212
    Published: June 01, 1978
    Released on J-STAGE: August 05, 2010
    JOURNAL FREE ACCESS
    Recently, growing interests had been devoted largely to disseminated intravascular coagulation (DIC), because of its frequency and clinical importance. It has been known that shock is a frequent complication of DIC, although it has not been elucidated whether shock is a cause of DIC rather than a result. This study was made to clarify relationship between DIC and shock in 699 consecutive autopsied cases, almost all of whom was over age sixty, in Tokyo Metropolitan Geriatric Hospital.
    The diagnosis of DIC was established when coagulation analysis revealed presence of consumption coagulopathy. Among these cases, 106 had evidences of DIC and 30 had clinical and pathological findings highly suggestive of DIC although the coagulation findings were not specific. Shock was complicated in 38 of the former and 10 of the latter.
    Eight of these 48 patients with DIC complicated with shock revealed consumption coagulopathy simultaneously with the development of shock. 24 cases had not clea r-cut evidences of DIC immediately after the development of shock in coagulation findings, although they showed marked coagulation abnormalities indicating DIC after the shock developed. 44% of conditions associated with the shock in these patients was gram-negative septicaemia. The other underlying pathologic conditons in these cases consisted of cancer, peptic ulcer, acute myocardial infarction and pneumonia.
    Onset of shock was observed in 16 cases in whom diagnosis of DIC had been already established by coagulation analysis. 11 cases of these had cancer with metastases, primary organs of which were stomach, colon or biliary tracts. 70% of these patients were febrile.
    Acute renal failure, purpura, petechiae, melena, coma, epileptic seizure, systemic peripheral gangrene and/or red cell fragmentation in peripheral blood smear were main symptoms in DIC with shock. Four cases, excluding two cases in whom DIC developed following development of acute myocardial infarction, showed ECG findings indicating development of acute myocardial infartion, although myocardial infarction was evident in only one cases by postmortem examination.
    Presence of fibrin thrombi was confirmed in 36 cases out of the 48 autopsied cases with DIC accompained with shock. Terminal hemorrhagic necrotizing enteropathy was observed in 15 of those cases. Hemorrhage from adrenal was observed in 4 cases.
    From these results, it is concluded that shock does frequently cause DIC and that shock in gram-negative septicaemia is especially important because of its high incidence to result DIC.
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  • Mutsuyoshi KAZAMA, Takeshi ABE, Kazumichi NAKAMURA, Juzo MATSUDA, Ikur ...
    1978 Volume 9 Issue 2 Pages 213-218
    Published: June 01, 1978
    Released on J-STAGE: August 05, 2010
    JOURNAL FREE ACCESS
    In search for the adequate assay method for the hypercoagulable state, the chromatographic method was introduced which revealed the development of macromolecular fibrinogen/fibrin complex in plasma of hypercoagulable state by the principle of gel exclusion chromatography. Plasma specimens of 16 normal subjects and 80 patients including thrombotic diseases were chromatographed on Biogel A-5m column (15×300mm) with 0.02M borate buffer containing 0.38% citrate (pH 7.5). The elution profiles of clottable fibrinogen, fibrinogen-related antigen (FR-ag) were obtained. The elution volumes of the beginning of FR-ag from the column were measured and these values were arbitrarily named as “initiation volumes (Vi's)”.
    The elution profiles of FR-ag were classified into three: normal, thrombotic and DIC. Vi's of normal plasma and non-thrombotic diseases were the average of 20.5ml, but those of thrombotic diseases and DIC were 18.0ml with the significant difference from the former. These results suggested the development of macromolecular fibrinogen complex in the hypercoagulable states.
    Reproduction of macromolecular complex was tried in vitro. The chromatography revealed the thrombotic profiles and the decrease of Vi's of plasma specimens such as normal plasma mixed with 0.04ml thrombin (f. c.), cryoprecipitate from the normal plasma mixed with 0.08u/ml thrombin (f. c.) and normal plasma mixed with soluble fibrin in urea. Only the FDP gave the DIC profile with the decreased Vi, which was prepared immediately after the complete dissolution of fibrin clot with plasmin. At the experiment in vivo, intravenous injection of 12μg/kg of Russel Viper venom into rabbits brought about the temporary shortening of PTT, but no significant change of PT, A-PTT, fibrinogen or platelet count. The elution volumes of fibrinogen of these plasmas remained unchanged, but Vi's after the injection were apparently decreased an the elution profiles of FR-ag formed DIC profiles. It was concluded that these experiments supported the results of the clinical specimens and the usefulness of this assay method for the hypercoagulable state including thrombosis and DIC.
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  • Mitsuhiko MATSUDA, Minoru AOSHIMA, Nobuyoshi DAITOH, Kinya YAMADA, Nor ...
    1978 Volume 9 Issue 2 Pages 219-223
    Published: June 01, 1978
    Released on J-STAGE: August 05, 2010
    JOURNAL FREE ACCESS
    Heparin is widely used as anticoagulant for prophylaxis of thromboembolism, in extracorporeal circulation, angiography etc. Since the measurement of heparin concentration in whole blood is difficult and it's effect depends on individuals, determination of appropriate heparin dose during cardiopulmonary bypass is not easy. For solution of these problems, we introduced activated coagulation time (ACT) which is reported by Hattersley in 1966. ACT is measured after mixing diatomite with whole blood. ACT is obtained more rapidly than Lee-White coagulation time. In this study, Hemochron 800, an automated instrument for detecting blood coagulation, was used. ACT obtained by Hemochron 800 is called Hemochron Time.
    The study group consists of 24 patients who underwent open-hert surgery or recieved heparin therapy. Hemochron Time of non-heparinized blood ranged from 107 to 134 seconds and those of the heparinized blood with 3mg per kg ranged from 257 to 321 seconds. Before cardiopulmonary bypass, 3mg per kilogram body weight of heparin was administered intravenously, and 10mg per 200ml of ACD stored blood or 500ml of plasma expander was added in bypass circuit. Heparin was administered so as to control Hemochron Time between 300 and 400 seconds. At the end of bypass, Hemochron Time was also ued as indicator for determining protamine dose.
    After introduction of this method, the amount of heparin and protamine used were decreaced. We found Hemochron time to be helpful for the management of heparinization, and protamin administration. This method has further use for clinical applications.
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  • Junji MURASHITA, Mitsuru NAKAGAKI, Kazumi TAGUCHI
    1978 Volume 9 Issue 2 Pages 224-228
    Published: June 01, 1978
    Released on J-STAGE: August 05, 2010
    JOURNAL FREE ACCESS
    We are now engaged in a chronic left heart bypass experiment using an artificial assist heart on calves, but as of this date there has not yet been developed a completely non-thrombogenic material for use in the artificial heart pump. It is for this reason that prevention of thrombogenesis has become an important problem especially when long survival following surgery is sought, and thus there is a need to conduct a proper anti-thrombogenic therapy through an appropriate method. We first attempted general heparinization by one-shot intravenous injection of heparin, but by this method it was invariably difficult to maintain the heparin level and generalized bleeding tendency was frequently observed.
    In order to prevent the risk of bleeding due to this generalized heparinization and to remove the thrombogenic tendency during the acute stage within the artificial heart pump, it would be ideal to develop a method by which a non-clottable condition could be maintained only within the blood pump.
    To achieve this purpose we considered that local heparinization in which heparinization could be localized within the blood pump and blood neutralized by protamine could be pumped throughout the body would be effective.
    We thus attempted a method of neutralizing the heparinized blood by continuously injecting heparin in the inlet side of the blood pump and by continuously injecting protamine in the outlet side of the pump.
    In Group A the heparin dose was 50U/kg/h and in Group B the dose was 25U/kg/h. The protamine dose was equivalent to the heparin dose in one half of Group A and Group B and in the remaining half of Group A and Group B, the protamine dose was one half of the heparin dose.
    Furthermore, to determine the heparin level in the blood prothrombin time was determined over time, using prothrombin time as an index of heparin level.
    In both Group A and Group B satisfactory anti-thrombogenic effect was observed, but in Group B hardly any bleeding tendency could be noted, whereas in Group A bleeding tendency was noted in some cases. On the basis of these results, we have administered on 16 cases to date heparin at a dose of 25U/kg/h and protamine at a dose range of 10-25U/kg/h as early as 12-24hours following surgery when oral administration becomes possible.
    Prothrombin time can be controlled within the range of 1.5-2.0times that of the normal value and good anti-thrombogenic effect could be obtained, this range being sufficient to prevent bleeding tendency.
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  • Masahiro TAKIGUCHI, Shizuo TSUKADA, Misako NAKAJIMA, Tsutomu OYAMA, Ma ...
    1978 Volume 9 Issue 2 Pages 229-232
    Published: June 01, 1978
    Released on J-STAGE: August 05, 2010
    JOURNAL FREE ACCESS
    Changes in coagulation-fibrinolysis system were observed during anethesia and gynecologic operations (67 cases) with different kinds of fluid therapy (each 500ml of low molecular weight dextran, hydroxyethyl strach, gelatin and Hartman's solution, plus additional Hartman's solution or blood, in cases).
    Hypercoagulability characterized by shortening of partial thromboplastin time, elevated fibrinolytic activity characterized by decrease in plasminogen and increase in FDP were observed. Decreases in platelet count and fibrinogen were also observed.
    These changes seemed to be non-specific reaction during anesthesia and operations, and were independent on the fluids infused under the condition.
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  • Koretake MAJIMA, Manabu YAMAMURA, Tsuyoshi TSUDA, Keitaro OHARA, Masak ...
    1978 Volume 9 Issue 2 Pages 233-237
    Published: June 01, 1978
    Released on J-STAGE: August 05, 2010
    JOURNAL FREE ACCESS
    Patients with malignant disease are often complicated by bleeding or thrombosis. In recent years, altered blood coagulation and fibrinolytic system in malignancy has been reported by many investigators. In this study, the changes of coagulation and fibrinolytic system in patient with malignant tumors were followed up during and after operation.
    Material and method: The series consisted of twenty-three patients in the following diagnostic categories: malignant lymphoma (1); carcinoma of the stomach (10), breast (5), large intestine (3) and pancreas (1); and cholelithiasis (3). Plasma fibrinogen, plasminogen, α1-antitrypsin, α2-macroglobulin and antithrombin III were determined by single radial immunodiffusion method. Fibrin and fibrinogen degradation product in serum was determined by hemaggultination inhibition titer. Platelets were counted by automatic counter.
    Result and Discussion: The patients were divided in three groups; the first group (15 cases) was malignant disease with laparotomy, the second group (5 cases) was malignant desease without laparotomy and the third group (3 cases) was non-malignant disease. In many cases with tumors, plasma fibrinogen levels were elevated pre-operatively. It was observed that the concentration of fibrinogen was decreased during the first post-operative day and greatly increased until one or two weeks after operation. In most cases, the number of platelets was decreased for a few days and thereafter it was increased over the pre-operative value in two weeks after operation. The elevated concentration of FDP in serum was found in three of the twenty patients with tumors pre-operatively. After operation, serum FDP was elevated for two or three weeks in most cases of malignancy and especially in the cases of inoperable tumors, the elevated concentrations of FDP and fibrinogen were found at third week after operation.
    The concentrations of plasminogen, α2-macroglobulin and antithrombin III were decreased during operation and returned to pre-operative value until to seven days after operation. Although individual variations were observed pre-operatively, α1-antitrypsin concentrations in patients with tumors were increased during and after operation and returned to pre-operative value in about third week post-operatively.
    From these data, it is suggested that cancer patients have a delicately balanced coagulofibrinolytic system and its disorder may be induced by surgical treatment.
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  • Masataka OJIRO, Mitsumasa NISHI
    1978 Volume 9 Issue 2 Pages 238-242
    Published: June 01, 1978
    Released on J-STAGE: August 05, 2010
    JOURNAL FREE ACCESS
    Coagulation and fibrinolysis system is important on the release and stickness of criculating cancer cells after the cancer operation. We showed that pulmonary metastasis was protected by decrease of platelets, inhibition of platelet function and inducement of fibrinolytic activity in rat.
    According to those experimental studies, Influence of coagulant and antifibrinolytic agents on coagulo-fibrinolytic system after operation were investigated in pulmonary cancer cases. Inspite of un-used coagulant agents, we observed that fibrinolytic activity was decreased, antiplasmin activity was increased and adhesitveness of platelets was enhanced.
    The difference of coagulant agents used groupes and un-used groupes was not recognized. It is suported that the anti-coagulant and Fibrinolytic agents is better than the coagulant and antifibrinolytic agents for cacer operation.
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  • Masayuki MATSUNAGA, Yukichi YONEMASU, Shigeaki TAKEDA, Keiichi OHSATO
    1978 Volume 9 Issue 2 Pages 243-247
    Published: June 01, 1978
    Released on J-STAGE: August 05, 2010
    JOURNAL FREE ACCESS
    Prevention of rebleeding is one of the most imperative factors in the management of the patients with ruptured intracranial aneurysm. On the basis of an increase in fibrinolytic activity in the cerebrospinal fluid after subarachnoid hemorrhage (SAH), antifibrinolytic therapy has been advocated by many authors, and the results were reported to be satisfactory. On the other hand, little has been known about the changes of the coagulation and fibrinolytic systems in the blood after SAH. The changes in the blood are essential parameters in the administration of antifibrinolytic drugs.
    The purpose of this study is to know the changes in the coagulation and fibrinolytic systems of the blood after SAH. Twenty-four patients with ruptured intracranial aneurysm were studied. Thirty-five samples were obtained from the antecubital vein as the sample of the systemic blood and thirteen samples from the internal jugular vein as the sample which was presumed to be under the influence of the intracranial pathology.
    Elevation of fibrinogen, factor V and VIII levels, and shortened r and r+k and increased ma values in thrombelastogram were demonstrated in most of the samples. A slight increase in FDP was also proved in most of the samples, but other parameters of fibrinolysis such as plasminogen, plasminogenactivator, alpha-1-antitrypsin and alpha-2-macroglobulin were not changed to any significant degree.
    The results apparently indicated a hypercoagulability in the circulating blood in the patients after SAH. The results were also analysed in regard to the length of period after SAH and no significant difference was obtained. There was no particular increase in the fibrinolytic activity in the patients 7 to 21 days after SAH when liability to rebleeding is said to be large. In one patient who bled 4 days after SAH, the coagulation and fibrinolytic activities immediately before the third SAH were all within normal limits in both antecubital and internal jugular blood samples.
    Changes of the coagulation and fibrinolytic systems in the internal jugular blood in the patients with SAH were studied in 13 samples from 10 patients. No significant difference was noted between the antecubital and internal jugular blood.
    In conclusion, the blood in the patients after SAH showed a hypercoagulability within the period of 2 to 3 weeks after SAH and increase in the fibrinolytic activity was minimal. Accordingly the occurrence of rebleeding was not predicted on the basis of changes of the coagulation and fibrinolytic systems, and no evidence was obtained from this study to support antifibrinolytic therapy in the prevention of rebleeding.
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  • Atsuo IIZUKA, Hisato KIGASAWA, Takeshi NAGAO, Kazuhiko KOMIYA, Hideo F ...
    1978 Volume 9 Issue 2 Pages 248-251
    Published: June 01, 1978
    Released on J-STAGE: August 05, 2010
    JOURNAL FREE ACCESS
    Intracranial hemorrhage has been the lethal complication in hemophilia and is also the most common cause of death in hemophiliacs in Japan. So, we studied retrospectively on intracranial hemorrhage for 127 patients with hemophilia (hemophilia B, 18) referred to Kanagawa Children's Medical Center. Reported are 6 month old boy with hemophilia A and 5 month old boy with hemophilia B, who had neurosurgical treatment for intracranial hemorrhage. The case with hemophilia B is the first reported case treated with neurosurgery in Japan.
    The results of retrospective studies are follows: Incidence; 23/127 (18.1%), Traumatic history; 8/23 (34.8%), Bleeding sites; unknown 16, subarachnoid hemorrhage 5, and subdural hematoma 2, Relapse of symptoms; 6/23 (26%) and Prognosis; antiepileptic drugs 9/23 (39%), mental deterioration 2 and cerebral palsy 1. Motality rate of surgical treatment for intracranial hemorrhage was high in hemophiliacs because of inadequate replacement therapy.
    But, long term adequate replacement therapy has now became possible. So, neurosurgical ireatment can be more safely performed in hemophiliacs when adequate replacement therapy is maintained. We think that neurosurg tcal treatment should be indicated for intracr anial hematoma in hemophiliacs as well as the cases without bleeding tendency.
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  • Kanji OGATA, Junzo ISHIGURO, Tadashi KAMIYA, Katsuo KOIE, Fumitaka AND ...
    1978 Volume 9 Issue 2 Pages 252-256
    Published: June 01, 1978
    Released on J-STAGE: August 05, 2010
    JOURNAL FREE ACCESS
    Blood coagulation studies were performed on 57 occasions in 20 patients with Behcet's disease who had ocular manifestations, consisting of 15 males and 5 females from 27 to 52 years of age.
    ADP-induced platelet aggregation was increased on 4 occasions out of 8 in patients with exacerbated ocular inflammatory manifestations (attack), while it was increased only on 5 occasions out of 32 in patients in the stage of remission (remission). Kaolin-activated partial thromboplastin time was shortened and the levels of fibrinogen, factors V and VIII (AHF) were elevated on many occasions both in attack and remission.
    AHF procoagulant activity was 158.4±56.4% (Mean±SD) of normal in attack and 135.4±40.6% in remission. The level of AHF-like antigen measured by immunoelectrophoresis using rabbit antibody against human AHF was 181.9±64.4% of normal in attack and 125.6±43.8% in remission. There was a statistically significant increase in the level of AHF-like antigen in patients with attack (p<0.05). The ratio of AHF procoagulant activity to AHF-like antigen (activity/antigen) was 0.83±0.13 in attack and 1.08±0.29 in remission, and there was a significant difference between both values (p<0.05).
    These results suggest that the patients with this disease may generally be in hypercoagulable state and in the stage of aggravation of ocular inflammation there may be formed some microthrombi locally in the ocular venules (localized intravascular coagulation), which results in the increased production of AHF and some other clotting factors and leads to “vicious circle”.
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  • Yuhji HIGUCHI, Takashi YAMASHITA, Eiro TSUBURA, Junichi ISOBE
    1978 Volume 9 Issue 2 Pages 257-263
    Published: June 01, 1978
    Released on J-STAGE: August 05, 2010
    JOURNAL FREE ACCESS
    Blood coagulation plays a very important role for the attachment of tumor cells to the capillary endothelium at an early stage of hematogenous metastasis. Attempts were made to find more reliable antimetastatic agents by studying the effect of five sulfated polysaccharides having different molecular weight and sulfur content on intravenously induced blood-borne pulmonaly metastasis in rats. Xylan sulfate and dextran sulfate strongly inhibited the development of metastatic nodules on the pulmonary surface. Chondroitin polysulfate was less inhibitory, whereas chondroitin sulfate and glucose polysulfate were not inhibitory. Their antimeta-static effect depended on the dose and time of administration, being greatest when they were injected intraperitoneally 1hr. before intravenous inoculation of AH-109A cells.
    The mechanism of inhibition of blood-borne metastasis by these sulfated polysaccharides was studied in relation to the blood coagulation system. We examined the coagulative activity of three sulfated polysaccharides, xylan sulfate, chondroitin polysulfate and chondroitin sulfate which have strong, weak and no inhibitory effect on metastasis, respectively.
    The coagulative activity of blood was measured by determining whole blood clotting time, partial thromboplastin time, prothrombin time and thrombin time. Xylan sulfate had the strongest anticoagulative activity, and showed the dose dependence of it. Anticoagulative activity of chondroitin polysulfate was less than that of xylan sulfate. Chondroitin sulfate had no anticoagulative activity. These results indicated that the antimetastatic activity of sulfated polysaccharides were correlated with their anticoagulative activity.
    Subsequently, we investigated the effect of three compounds on blood coagulation factors. The surface contact factors, factor XI and XII in the plasma of rats injected with xylan sulfate were markedly inactivated. Moderate inactivations of factor II, V, VII, VIII, IX and X were noted in these plasma. Marked inactivations of factor XI and XII, and moderate inactivation of factor VIII were noted in the plasma of rats injected with chondroitin polysulfate. Chondroitin sulfate did not cause any inactivation of blood coagulation factors. The results indicated that the inactivation of surface contact factor was also closely related with inhibitory effects on blood-borne metastasis.
    Intravascular coagulation concerning mainly with the attachment of transported tumor cells to the endothelium of capillaries might be thought to be induced by 1) obstruction of blood flow by tumor cell emboli, 2) release of the tissue thromboplastin from injured endothelium, 3) activation of contact factors by injured endothelium due to tumor cells, 4) activation of the extrinsic coagulation factors by tumor cells. Xylan sulfate interfered with intrinsic thromboplastin formation due to in-activation of contact factors in intrinsic blood coagulation mechanism, and showed the antithrombin activity.
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  • Naohito OHMI, Junichi OIKAWA, Yutaka KOGO, Yoshiro NIITSU, Ichiro URUS ...
    1978 Volume 9 Issue 2 Pages 264-270
    Published: June 01, 1978
    Released on J-STAGE: August 05, 2010
    JOURNAL FREE ACCESS
    Fibrinogen and fibrin degradation products, fragment D (Fg D) and fragment E (Fg E), were measured in human serum by radioimmunoassay (RIA) technique.
    Fibrinogen was digested for five hours by plasmin to obtain Fg D and Fg E as the major products.
    Technique for separating these fragments from each other and from larger fragments (Fg X, Fg Y) present in the crude digest, comprise gelfiltration with Sephadex G-200 and isoelectric fractionation which gave satisfactory purity and efficiency for preparative purpose.
    A sensitive 2-sites immunoradiometric assay for FDP was newly developed using paper discs as solid phase.
    Detection limit of this method was 1ng/ml.
    In six healthy subjects, the serum levels ranged from 108 to 260ng/ml for Fg D, and from 60 to 120ng/ml for Fg E.
    Both raised levels were found in the patients with disseminated intravascular coagulation of hepatoma, gastric cancer, AML, APL and CML.
    Advantages of RIA system over tanned red cell haemagglutination inhibition immunoassay was its sensitivity.
    There is, however, a possibility that RIA of FgDP is detecting residual fibrinogen in the serum, since anti-FgDP antiserum showed weak cross-reaction to fibrinogen by double immunodiffusion test.
    In order to eliminate interference by residual fibrinogen in the serum, antiserum against FgDP was further purified by affinity chromatography to remove antifibrinogen activity.
    Thus purified antibody exhibited no crossreaction to fibrinogen by RIA method, and showed nonprecipitable property in double immunodiffusion test using 1% Agar which contains 4% polyethylene glycol.
    By using this antibody, FDP in plasma was detectable, thus eliminating the possibility of coprecipitation of FDP with blood clot when serum was collected.
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  • Yasuo OHKI, Takefumi MATSUO, Shigeo SASAKI
    1978 Volume 9 Issue 2 Pages 271-276
    Published: June 01, 1978
    Released on J-STAGE: August 05, 2010
    JOURNAL FREE ACCESS
    Study was dealed with the shortness of euglobulin lysis time (ELT) induced by adding urokinase to euglobulin fraction. After adding each of urokinase with 0.1, 0.2 and 0.4 units to euglobulin fraction, ELT was measured by use of ordinary method. Original ELT shorten by adding UK in vitro was expressed as UK-ELT. The ratio of UK-ELT to original ELT was calculated for knowing the degree of UK induced ELT.
    1) In original ELT between 101 and 2, 000 minutes, the shortness of ELT was observed to parallel to the concentration of UK in vitro. But there was no effect on the shortness of ELT accelerated within 100 minutes. When original ELT showed with over 2, 001 minutes, a little shortness of ELT was observed in original ELT prolonged more than 2, 001 minutes.
    2) Positive correlation was found between UK-ELT and the amount of fibrinogen that was equivalent to 1mg of plasminogen. The maximum shortness of ELT was obtained by the state of plasminogen rich and considerable amount of fibrinogen in plasma.
    3) In acute phase of myocardial infarction, UK-ELT by urokinase of 0.4 units showed 34.8±16.7% in the survival in comparison with 87.3±31.6% in the death. Namely, euglobulin fraction obtained from poor prognostic myocardial infarction remained to be in low response, which was thought to be induced by a lack of plasminogen and a latge amount of fibrinogen. In cerebral haemorrage as well as myocardial infarction, UK-ELT in the death showed 38.3±17.0% of lower response than in 73.3±27.5% of the survival.
    4) It was suggested that the prognosis in acute attack of vascular disease could be decided according to UK-ELT might show the result of breakdown of equilibrium between the amount of fibrinogen and plasminogen in plasma.
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  • Isao SAKASHITA, Kenichi ASANO, Masahiko WASHIO
    1978 Volume 9 Issue 2 Pages 277-280
    Published: June 01, 1978
    Released on J-STAGE: August 05, 2010
    JOURNAL FREE ACCESS
    Since September 1965 mitral valve replacement has been performed in 145 patients at the University Hospital and affiliated hospital. Hospital and late deaths were noted in respectively 10 patients.
    One hundred and nine survivors out of the remaining 125 patients were replaced with various Starr-Edwards ball valve proshteses and have elapsed more than one year after surgery.
    In this report, these 109 patients were divided into 3 parts depending on the sort of the replaced ball valves and of anticoagulation immediately after operation.
    The first part was consisted of 40 patients with the noncloth-covered ball valve and anticoagulated using Warfarin. Follow-up period ranged from 6 to 11 years and during the time, transiet ischemic cerebral attack (Type I) and cerebral embolism (Type II) were experienced in 15 and 8 patients respectively indicating the rates of 37.5 and 20per cent.
    The second part included 40 patients who were implanted by the cloth-covered ball valve, and Warfarin was given to them as an anticoagulation after surgery. Episodes of Type I and II were noted in 5 and 4 patients rating 12.5 and 10.3per cent respectively. Peripheral arterial embolism was also recognized in another 2 patients. Follow-up period in this part ranged from 28 to 72 months.
    The third part contained 29 patients with the cloth-covered ball valve and a combined anticoagulation of Warfarin and Bucolome which was supplemented in case of being unsatisfied with Warfarin alone. During the time of 12 to 27 months, episode of Type I was noted in 2 patients (6.9%) and that of Type II in 1 patient (3.4%).
    The results showed that implantation of the cloth-covered ball valve instead of the noncloth-covered one decreased the incidence of thrombo-embolic complication in the follow-up period when the incidence was expressed as per patient montlhs, and also supplement of Bucolome to Warfagrin to obtain more long-term stabilization of anticoagulation was expected to be promising from the data disclosed between the second and third part with the same sort of the cloth-covered ball valve. Effect of Bucolome on Warfarin as an anticoagulation is attributed by 1) preventing the combination of Warfarin and albumin and 2) displacing previously combined Warfar in to albumin into the blood as free Warfarin.
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  • Tadaaki SHIBA, Setsuo TAKEUCHI, Takeru TERASHIMA, Kazuhiro KUBOTA, Jun ...
    1978 Volume 9 Issue 2 Pages 281-285
    Published: June 01, 1978
    Released on J-STAGE: August 05, 2010
    JOURNAL FREE ACCESS
    It is known that the plasminogen activator of a certain type is an esterase for methylester of lysine or arginine. And we reported the method of isolating urokinase and other plasminogen activators, also by choosing lysine-agarose and arginine-agarose as the affinity-chromatography. Recently, we contrived a method which isolate urokinase, thrombin, plasmin, and plasminogen using affinity-chromatography on cetraxate-agarose. Cetraxate, one of methyl-ester of lysine and activator inhibitor, was produced by Fujii, Yamaura and others in 1971. So we would like to report them here.
    The results were as following.
    1; Urokinase was adsorbed to cetraxate-agarose, and was eluted with 0.005M phosphate buffer containing 0.85% NaCl.
    2; Cetraxate-agarose seemed to have a possibility of the separation of plasmin from the mixture of plasmin and plasminogen.
    3; It was suggested that affinity-chromatography on the inhibior-agarose has a possibility of discrimination between reversible and irreversible inhibition mechanism.
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  • Report of a case
    Shinichiro MORIMOTO, Masahiko AOSAKI, Makoto RYONO, Koshichiro HIROSAW ...
    1978 Volume 9 Issue 2 Pages 286-290
    Published: June 01, 1978
    Released on J-STAGE: August 05, 2010
    JOURNAL FREE ACCESS
    Recently, we experienced a case of hepatic injury in a patient who had undergone mitral valve replacement and was taking warfarin to prevent the thromboembolism.
    After starting warfarin treatment, it took approximately two weeks for the hepatic injury to appear. And the increase in the ratio of the eosinophilic leucocytes was roughly parallel to the deterioration of the liver function and the lymphocytes' blastoid transformation was positive. These findings suggest hepatitis due to a delayed hypersensitivity to warfarin.
    On the other hand, the clinical course (Fig. 1) seems to show the hepatic injury having a dose dependent factor to warfarin.
    This discrepancy between the laboratory data and the clinical course is very interesting and fully suggestive, and the etiology of this hepatic injury must be further studied.
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  • Nobuo SAKURAGAWA, Kaoru TAKAHASHI, Takeshi ASHIZAWA, Matsuzo MATSUOKA
    1978 Volume 9 Issue 2 Pages 291-297
    Published: June 01, 1978
    Released on J-STAGE: August 05, 2010
    JOURNAL FREE ACCESS
    The inhibitory effects of heparin, hirudin and OM-189 (Okamoto's synthetic thrombin inhibitor) on serine proteases were investigated by the estimating method using synthetic chromogenic substrate, and the results were as follows:
    (1) When heparin was added to plasma, antithrombin activity was increased, but decreased with addition of protamin sulfate.
    (2) Hirudin showed remarkable inhibitory effects on the proteolytic activity of trypsin and thrombin, and when hirudin (0.2mg) was infused into a rabbit (2.5kg by weight) PTT and thrombin time were prolonged with no changes of plateletes and fibrinogen.
    (3) OM-189 showed the inhibitory effects on the ploteolytic activities of trypsin, thrombin, Factor Xa and plasmin remarkably. When OM-189 (4.8mg) was injected into a rabbit, inhibitory effects similer to the results found in the case of hirudin were observed. The inhibitory effect of OM-189 to the activity of Defibrase was observed in the concentration of 1mol of it, but was not observed by the estimating method using fibrinogen as the substrate.
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