Diagnosis Of DIC Research Articles

ＴＥＧを用いたＤＩＣの迅速診断法：ヘパリン緊急投与の指標として

The purpose of this study was to examine the usefulness of thromboelastography (TEG) for the rapid diagnosis of DIC. As previously reported, 10.0 or 12.5mg/kg of tissue thromboplastin (T. Tpl) was infused to mongrel dogs during 3hrs and severe DIC was brought about. DIC plasma revealed the marked prolongation of TEG reaction time (r) and coagulation time (k). When this DIC plasma was mixed with the same dose of normal plasma, TEG r shortened much more than that of normal plasma (p<0.02) because of the existence of numerous coagulant activities and the supply of normal coagulation factors in plasma. How-ever, TEG r of the mixed plasma did not show any shortening when fibrinopeptide A demonstrated high levels but DIC was not yet introduced. It shortened simultaneously when decompensated DIC was found to occur. Observation of TEG r was completed in a few minutes and so, in conclusion, TEG was a quite useful index for the rapid diagnosis of DIC and was a beneficial examining tool for the decision of the emergent administration of heparin.

Clinical application of platelet shape determination for diagnosis of DIC.

Clinical application of platelet shape determination for diagnosis of DIC.

Criteria for diagnosis of DIC based on the analysis of clinical and laboratory findings in 345 DIC patients collected by the Research Committee on DIC in Japan.

From analysis of the clinical and laboratory findings in the DIC patients collected by JRDC, diagnostic criteria for the diagnosis of DIC are proposed. The characteristics of the criteria are as follows: (1) a scoring system is adopted; (2) as the tests for scoring, PT, plasma Fbg level, serum FDP level, and platelet count are used; (3) different scores are given according to the grade of change in the results of the tests; (4) bleeding and clinical signs indicating organ dysfunction due to DIC are included in the scoring system; and (5) recognition of the well-known etiological factors of DIC is also scored.

The clinical relevance of factor VIII: C and factor VII R: Ag determination in newborns.

Higher levels of factor VIII: C and factor VIII R: Ag were found in healthy newborns (n = 60) as compared to adults. This could be explained as a stress reaction due to birth and the adaptation to extrauterine life. A further stress factor is disease. The highest values for factor VIII R: Ag were found in ill (n = 32) and in severely ill newborns (n = 21). The large ranges of factor VIII: C and of the ratio of factor VIII: C/VIII R: Ag in healthy newborns can be explained by an increased turnover of coagulation factors. Diseases in the newborn period lead to an increase of this process, resulting in even larger ranges of factor VIII: C and of the ratio of factor VIII: C/VIII R: Ag in ill and extremely ill newborns. Consumption of factor VIII: C with a low ratio of factor VIII: C/VIII R: Ag predominates in extremely ill newborns. The ratio of factor VIII: C/VIII R: Ag is more valuable than factor VIII: C for diagnosis of DIC in newborns. A diagnosis of hemophilia and von Willebrand's disease cannot be established with certainty in severely ill newborns. Stress and DIC may influence the characteristic changes of laboratory parameters.

Disseminated intravascular coagulation: a clinical/laboratory study of 48 patients.

In summary, this series of 48 patients with acute and chronic DIC demonstrates the reliability of laboratory tests in both aiding a diagnosis of DIC and in offering reasonable predictability of efficacy of therapy, as noted by the correction of abnormalities after delivery of antiprocoagulant therapy for this syndrome. It appears that the diagnostic tests most likely to aid in diagnosis and to reliably inform the clinician when the intravascular clotting process has been stopped are those that determine the antithrombin-III level, the presence of soluble fibrin monomer, and the finding of elevated fibrin(ogen) degradation products, thrombocytopenia and a prolonged thrombin time in the face of the appropriate type of bleeding in the appropriate clinical setting. In addition, it would appear that mini-dose heparin therapy is highly effective in controlling the intravascular clotting process in acute DIC, whereas antiplatelet therapy utilizing two agents is effective in chronic DIC. In addition, in this population, patients with acute disease demonstrated a 74 percent survival rate and those with chronic disease had a 100 percent survival rate from the disseminated intravascular clotting process.

Hemostasis in Massively Transfused Trauma Patients

COUNTS, R. B.; HAISCH, C.; SIMON, T. L.; MAXWELL, N. G.; HEIMBACH, D. M.; CARRICO, C. J. Author Information

Hemostasis in Massively Transfused Trauma Patients

Twenty-seven patients requiring massive transfusions were studied prospectively to determine whether administration of stored, modified whole blood induced a primary disorder of hemostasis evidenced by generalized microvascular oozing. Platelet counts fell in proportion to the number of units of blood transfused. In contrast, the levels of factors V and VIII correlated poorly with the units of blood transfused, 85% of the total variation in the levels being due to influences other than transfused blood. Levels of all other clotting factors were unrelated to the number of units of blood given. Eight patients developed abnormal bleeding. The cause appeared to be dilutional thrombocytopenia in five patients, and DIC in three. In six of the eight, bleeding was controlled with platelet concentrates alone. Two patients were given cryoprecipitate also. The most useful laboratory test for predicting abnormal bleeding was the platelet count. Fibrinogen levels should be followed as an aid in the diagnosis of DIC. The BT, PT, and PTT were not helpful in assessing the cause of bleeding, unless they were greater than 1.5 times the control value. We recommend that any patient receiving massive transfusions who develops diffuse microvascular bleeding be given platelet concentrates. Platelet counts as high as 100,000 may be required to control bleeding from surgical wounds. It is not necessary to supplement transfusions of stored, modified whole blood with fresh blood or fresh frozen plasma.

Studies on prognosis and effects of treatments on clinicopathological, hematological and autopsy findings in DIC

DIC related to APL (3 cases, No. 1-3), AML (No. 4), gastric cancer (No. 5), prostate cancer (No. 6), progressive systemic sclerosis (No. 7), and mitral stenosis & insufficiency (No. 8), were described.Most of them showed, more or less, remarkable hemorrhagic diathesis.In the terminal stage of Case No. 1, 2, 4 and 7, shock, oliguria and renal failure that might be due to DIC were observed in clinical and some laboratory findings. FDP and thrombocytopenia were demonstrable in all.Fibrinogen was reduced in most of them, however, in cases already complicated with some infections when the diagnosis of DIC was made, it revealed higher level than in the other.All cases were intravenously treated with heparin from 6, 000 to 20, 000U/day. In case No. 2, t-AMCHA was used because of negative paracoagulation test and few data suggesting DIC, and in case No. 1, 5, the same was done because of no improvement of hemorrhagic diathesis.It was impressed that in Case No. 1 t-AMCHA was effective and Case No. 6 recovered dramatically by heparin.However, it may be suggested that the effect of treatments on DIC might be affected by the improvement of each basic diseases, as they recovered simultaneously from each basic ones.Case No. 8 showed no change in clinical and hematological findings with or without therapy. In addition, from echocardiogram, thrombus, which was found in left atrium, might be a cause of DIC findings.Six cases (No. 1, 2, 3, 4, 5 and 7) ended lethally and autopsy was done in all.In three cases (No. 2, 3 and 7) of them, microthrombi were pathologically demonstrable in some tissues.As microthrombi are indispensable to pathological diagnosis of DIC, it was just identified in above three cases.From 1966 to 1975, microthrombi were observed in all of 23 DIC cases which were examined in our department of pathology.In comparison to it, less microthrombi were seen in this presentation. This discrepancy between two papers may depend on intensity of fibrinogenolysis and/or fibrinolysis, effects of treatments, degree of postmorten changes and tissue staining methods.As heparin was used in all cases, it may be suggested that it's use is related to one of the causes of decreased detection rate of microthrombi.It has been reported by some authors that DIC may not be always based on primary coagulation-secondary fibrinolysis, because sometimes antiplasmin therapy may be effective in DIC.As the mechanism of DIC has not been completely recognized at present, it may be suggested that “Defibrination Syndrome” may be prefered to DIC.

Disseminated intravascular coagulation after open heart surgery

Nine out of 319 patients who underwent open heart surgery from March 1977 to July 1978 at the University Hospital developed the laboratory evidence of DIC and were administrated heparin. Among the 9 patients, 6 cases were tetralogy or pentalogy of Fallot. (27 of 319 patients were Fallot's disease.) Other cases were endocardial cushion defect, annuloaortic ectasia and ventricular septal defect with pulmonary hypertension.Laboratory evidence of DIC was found within 3 days after surgery. They had many etiologic factors contributing to the production of DIC following cardiopulmonary bypass, i. e. a long term bypass, hemolysis, shock or low cardiac output, polycythemia and severe infection. Eight out of 9 patients were associated with shock or low cardiac output and 5 of them had a hematocrit greater than 50 per cent. We suggest that low cardiac output and polycythemia may be main factors to develop DIC.When diagnosis of DIC was established, all patients had a bleeding tendeney. One patient had acute renal failure. During heparin therapy, 2 patients had renal dysfunction and one of them developed acute renal failure. In this series of 9 patients, 2 who had renal failure ultimately died. In other cases, there were recovery from the bleeding tendency and improvement in coagulation findings.In coagulation studies, platelet count, prothrombin time, FDP and thrombelastograph were useful for diagnosis and judgement of recovery or progress of DIC.Early diagnosis is important because early administration of heparin may inhibit progress of DIC and dysfunction of organ, such as renal failure.

673 USE OF THE THROMBOELASTOGRAPH (TEG) IN DIAGNOSING DISSEMINATED INTRAVASCULAR COAGULATION (DIC) IN THE NEWBORN

The TEG is an automated and very sensitive technique for analyzing whole blood clotting time, requiring only 50 lambda whole blood. Its use in the newborn period has not been previously examined. We utilized thromboelastographic tracings in conjunction with standard coagulation studies to make the diagnosis of DIC in 6 of 13 critically ill newborns with severe birth asphyxia or respiratory failure from hyaline membrane disease. 7 healthy newborns served as a control population for normal values. Samples were drawn at 12 and 24 hrs of age in the control group and every 12 hrs for at least 72 hrs and up to 120 hrs in the study group. The control group showed a generally hypercoagulable state on samples drawn at 12 hrs of age as manifest by low R values and high MA and angle values. By 24 hrs of age the TEG conformed more to the normal adult curve. These patterns persisted after priming with Celite. The trend of the TEG in the study group was for the R values to increase, the MA and angle to decrease with time and the blood to become more hypocoagulable. The trend was accentuated in patients with DIC, progressing to a flat line in some patients. TEG patterns correlated well with elevations of fibrin split products and decreasing or low fibrinogen levels and platelet counts. This test is a technically simple, inexpensive and very rapid technique for diagnosing hyper- and hypo-coagulable states of blood clotting in the newborn.

Studies on abnormalities of blood coagulation, fibrinolysis and their inhibitors in neoplasmas of blood and blood forming organs

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.

Changes of anti-thrombin III, anti-thrombin and anti-thrombin in liver diseases

The hemorrhagic diathesis in liver diseases are very complicated because of the disorders of vessel-, platelet- and coagulofibrinolytic system. Severe bleeding is known to be caused in the patients with fulminant hepatitis with DIC. We have reported these facts several years. In this study, the hemorrhagic diathesis of liver diseases (especially with DIC) was studied with special references to the activities of anticoagulation and antifibrinolysis, and the diagnosis of hepatitis associated with DIC was also discussed.Quantative determination of antithrombin III, and α2-macroglobulin was carried out by single radial immunodiffusion. The mesurement of antiactivator and antiplasmin was carriedd out by means of the plasminogen free fibrin plate.The results obtained were as follows: (1) In liver cirrhosis (12 cases), the mean values of antithrombin III, α2 macroglobulin, antiplasmin and antiactivator were respectively 14.0±4.8, 344.4±135.0, 71.7±19.3(mg/dl). and 37.3±18.4(%).(2) In acute hepatitis (8 cases), the mean values of antithrombin III, α2 macroglobulin, antiplasmin and antiactivator were respectively 17.5±2.6, 220±24.9, 70.0±9.9(mg/dl) and 28.0±19.4(%).(3) The usual approach to detect the liver disease accompanied by DIC is to consider the low value of α2 macroglobulin and the markedly increased value of antiactivator. The dynamic change of antithrombin III, which plays an important role for the diagnosis of DIC, was not so helpful for the diagnosis of the liver diseases accompanied by DIC.(4) There noted the discrepancy between the value of Eug+SK and that of Eug+UK in the 2 patients with fulminant hepatitis accompanied by DIC.Therefore, this finding may be very useful for the diagnosis of DIC in liver diseases.

Incidence of disseminated intravascular coagulation in the course of septicemia in newborn infants.

Coagulation studies including platelet count, partial thromboplastin time, prothrombin index, and assays of fibrinogen, prothrombin, proaccelerin, antihemophilic globuline and fibrin (ogen)degradation products were carried out in 12 newborn infants afflicted with septicemia. All patients had a decrease of platelet counts. 8 patients showed characteristic signs of DIC. In 3 cases we found marked consumption and in 3 other cases mild forms of DIC. In 2 cases DIC had occurred a few days before we obtained samples. The remaining 4 patients exhibited as a result of endotoxinemia a low platelet count without affecting blood coagulation. The most reliable laboratory findings for the diagnosis of DIC seem to be reduced platelet counts and low levels of fibrinogen and factor V.