Outcome of Disseminated Intravascular Coagulation in Relation to the Score when Treatment was Begun

SummaryWe examined 395 patients with disseminated intravascular coagulation (DIC) divided into two groups: non-leukemic and leukemic. In 58% of the patients as a whole, treatment of DIC resulted in complete or partial remission, while exacerbation and death occurred in 31%. The efficacy of DIC treatment in the non-leukemic group was less than that in the leukemic group, indicating that the outcome of DIC depended, in part, on the underlying disease. We examined hemostatic indicators in relation to DIC score: prothrombin time (PT) ratio, FDP, platelet count, and fibrinogen levels were found to be important indicators for the diagnosis of DIC, but not for Pre-DIC. Plasma levels of fibrin-D-dimer, thrombin-antithrombin complex (TAT), and plasmin- plasmin inhibitor complex (PPIC) were significantly increased in pre-DIC. The efficacy of treatment in relation to the DIC score when the treatment was begun showed that greater efficacy was achieved in pre-DIC than in DIC patients. The outcome was poorer with increasing DIC score, suggesting that early diagnosis and early treatment are important. On examining the relationship between outcome and hemostatic indicators, we found that the PT ratio and the levels of antithrombin, plasminogen, PPIC, the PPIC/TAT ratio, and thrombomodulin were related to outcome, suggesting that very high consumption of blood coagulation factors, liver dysfunction, hypofibrinolysis, or organ failure caused a poor outcome. Although the outcome in DIC patients may not depend substantially on plasma levels of TAT and fibrin-D- dimer, we can use these indicators to treat DIC patients at an early stage.

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Attempt to Develop Rat Disseminated Intravascular Coagulation Model Using Yamakagashi (Rhabdophis tigrinus) Venom Injection

Toxins ◽

10.3390/toxins13020160 ◽

2021 ◽

Vol 13 (2) ◽

pp. 160

Author(s):

Akihiko Yamamoto ◽

Takashi Ito ◽

Toru Hifumi

Keyword(s):

Disseminated Intravascular Coagulation ◽

Clinical Condition ◽

Underlying Disease ◽

Fibrinogen Concentration ◽

Blood Coagulation Factors ◽

Fixed Amount ◽

Intravascular Coagulation ◽

Measurement Limit ◽

Human Pathology ◽

Rhabdophis Tigrinus

Disseminated intravascular coagulation, a severe clinical condition caused by an underlying disease, involves a markedly continuous and widespread activation of coagulation in the circulating blood and the formation of numerous microvascular thrombi. A snakebite, including that of the Yamakagashi (Rhabdophis tigrinus), demonstrates this clinical condition. Thus, an animal model using Yamakagashi venom was constructed. Yamakagashi venom was administered to rats, and its lethality and the changes in blood coagulation factors were detected after venom injection. When 300 μg venom was intramuscularly administered to 12-week-old rats, (1) they exhibited hematuria with plasma hemolysis and died within 48 h; (2) Thrombocytopenia in the blood was observed in the rats; (3) irreversible prolongation of prothrombin time in the plasma to the measurement limit occurred; (4) fibrinogen concentration in the plasma irreversibly decreased below the measurement limit; and (5) A transient increase in the plasma concentration of D-dimer was observed. In this model, a fixed amount of Rhabdophis tigrinus venom injection resulted in the clinical symptom similar to the human pathology with snakebite. The use of the rat model is very effective in validating the therapeutic effect of human disseminated intravascular coagulation condition due to snakebite.

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Haemostatic Studies in Carbohydrate-deficient Glycoprotein Syndrome Type I

Thrombosis and Haemostasis ◽

10.1055/s-0038-1650611 ◽

1996 ◽

Vol 76 (04) ◽

pp. 502-504 ◽

Cited By ~ 18

Author(s):

A Fiumara ◽

R Barone ◽

P Buttitta ◽

R Musso ◽

L Pavone ◽

...

Keyword(s):

Plasma Levels ◽

Protein C ◽

Antithrombin Iii ◽

Plasma Concentrations ◽

Protein S ◽

Coagulation Factors ◽

Type I ◽

Clotting Factors ◽

Blood Coagulation Factors ◽

D Dimer

SummaryCDG syndrome (CDGS) type I is the most frequent form of a group of metabolic disorders characterised by a defect of the carbohydrate moiety of glycoproteins. A large number of plasma glycoproteins, including clotting factors and inhibitors, are decreased and stroke-like episodes have been described in about half of the reported patients. We studied blood coagulation factors, inhibitors and D-dimer plasma levels in four subjects, aged 12-23 years, with CDGS type I. Factors VIII, XI, antithrombin III activity, antigen plasma levels of antithrombin III, free protein S and protein C were decreased whereas protein C as activity was normal. In addition two patients had reduction of factors II, V, VII, IX, X reflecting the phenotypic heterogeneity associated with CDGS type I. D-dimer plasma concentrations were elevated in all subjects. The hypercoagulable state as consequence of the combined deficiencies of coagulation inhibitors could contribute to the stroke-like phenomena in CDGS type I.

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Laboratory Diagnostics in Septic Disseminated Intravascular Coagulation

European Oncology & Haematology ◽

10.17925/eoh.2009.03.1.19 ◽

2009 ◽

Vol 03 (01) ◽

pp. 19

Author(s):

Giuseppe Lippi ◽

Gian Cesare Guidi ◽

◽

Keyword(s):

Disseminated Intravascular Coagulation ◽

Clinical Signs ◽

Signs And Symptoms ◽

Coagulation Factors ◽

Underlying Disease ◽

Laboratory Diagnostics ◽

Diagnostic Efficiency ◽

Intravascular Coagulation ◽

Diagnostic Algorithms ◽

Clinical Signs And Symptoms

The diagnosis of septic disseminated intravascular coagulation (DIC) relies on clinical signs and symptoms, identification of the underlying disease and results of laboratory testing. Since no single test result alone can definitely establish or rule out the diagnosis, the laboratory diagnostics of septic DIC encompass a combination of tests for which simple diagnostic algorithms are now available. Global tests of haemostasis provide evidence of activation of blood coagulation and, ultimately, consumption of coagulation factors, but their diagnostic efficiency is as yet questionable. Fibrinolytic markers, namely D-dimer, reflect the extent of activation of both coagulation and fibrinolysis, so a normal value can be used in a ruling-out strategy. Decreased levels of the natural inhibitors are frequently observed in patients with septic DIC, but antithrombin and protein C measurements are not incorporated in any of the widely used diagnostic algorithms. Among the inflammatory biomarkers, procalcitonin is currently regarded as the gold standard to differentiate the type of infection and guide antibiotic therapy, but its clinical usefulness in identifying and predicting the outcome of patients with septic DIC is still circumstantial.

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Increased Soluble Fibrin in Plasma of Patients with Disseminated Intravascular Coagulation

Clinical and Applied Thrombosis/Hemostasis ◽

10.1177/107602960300900308 ◽

2003 ◽

Vol 9 (3) ◽

pp. 233-240 ◽

Cited By ~ 27

Author(s):

Hideo Wada ◽

Tomohiro Sase ◽

Takeshi Matsumoto ◽

Fumihiko Kushiya ◽

Miho Sakakura ◽

...

Keyword(s):

Disseminated Intravascular Coagulation ◽

Plasma Levels ◽

Operating Characteristic ◽

Degradation Products ◽

Characteristic Analysis ◽

Soluble Fibrin ◽

Intravascular Coagulation ◽

Hemostatic Markers ◽

Plasmin Inhibitor

Plasma levels of soluble fibrin (SF) were measured in 1184 patients with disseminated intravascular coagulation (DIC) according to Japanese Ministry of Health and Welfare (JMHW) criteria. The usefulness of SF for the diagnosis of DIC was compared with other hemostatic molecular markers. Most hemostatic markers were significantly increased in patients with DIC than in those without DIC. Plasma levels of fibrin and fibrinogen degradation products, thrombin-antihtrombin complex, plasmin-plasmin inhibitor complex, D-dimer, thrombomodulin, and SF levels were also significantly higher in those with pre-DIC than in those without DIC. In classification of overt DIC by International Society of Thrombosis and Haemostasis (ISTH) criteria, most hemostatic markers were significantly increased in patients with overt DIC than in those without overt DIC. Plasma levels of SF 'in patients with DIC were significantly higher than those in patients with pre-DIC, which were significantly higher than in those without DIC. Plasma levels of SF were also significantly higher in patients with overt DIC than in those with non-overt DIC. The correlation between plasma SF levels and DIC score according to JMHW criteria or ISTH criteria was good. Receiver operating characteristic analysis shows that SF was the best marker for the diagnosis of DIC or overt DIC. These findings suggest that plasma SF might be useful marker for the diagnosis of DIC or overt DIC.

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Soluble C-Type Lectin-Like Receptor 2 Is a Biomarker for Disseminated Intravascular Coagulation

Journal of Clinical Medicine ◽

10.3390/jcm10132860 ◽

2021 ◽

Vol 10 (13) ◽

pp. 2860

Author(s):

Akitaka Yamamoto ◽

Hideo Wada ◽

Yuhuko Ichkawa ◽

Motoko Tanaka ◽

Haruhiko Tashiro ◽

...

Keyword(s):

Critically Ill ◽

Disseminated Intravascular Coagulation ◽

Critically Ill Patients ◽

Plasma Levels ◽

Clinical Syndrome ◽

Intravascular Coagulation ◽

Activated Platelets ◽

Underlying Diseases ◽

Soluble C ◽

D Dimer

Disseminated intravascular coagulation (DIC) is induced by excess activation coagulation, and activated platelets are also involved in pathogenesis. Therefore, plasma levels of soluble C-type lectin-like receptor 2 (sCLEC-2), a new marker for platelet activation, can be expected as a marker of DIC in critically ill patients. Plasma levels of sCLEC-2 and D-dimer were measured using the STACIA system. Plasma sCLEC-2 and D-dimer levels were significantly higher in patients with underlying diseases of DIC than in those with unidentified clinical syndrome (UCS). Plasma sCLEC-2 levels were significantly higher in the patients with DIC and Pre-DIC than in those without DIC or Pre-DIC. Similarly, plasma D-dimer levels were also significantly higher in patients with DIC and Pre-DIC than in those without DIC or Pre-DIC. The plasma sCLEC-2 levels in all patients and those with a DIC score ≤ 4 were significantly higher in non-survivors than survivors. The plasma D-dimer levels in all patients, those with a DIC score ≥ 5 and those with a DIC score ≤ 4, were significantly higher in non-survivors than in survivors. The plasma sCLEC-2 is expected as a marker for DIC/Pre-DIC as well as the prognostic marker in critically ill patients.

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Evaluation of haemostatic molecular markers for diagnosis of disseminated intravascular coagulation in patients with infections

Thrombosis and Haemostasis ◽

10.1160/th05-04-0286 ◽

2006 ◽

Vol 95 (02) ◽

pp. 282-287 ◽

Cited By ~ 30

Author(s):

Hidesaku Asakura ◽

Kohji Okamoto ◽

Toshiaki Iba ◽

Toshimasa Uchiyama ◽

Yutaka Eguchi ◽

...

Keyword(s):

Molecular Markers ◽

Disseminated Intravascular Coagulation ◽

Plasma Levels ◽

High Sensitivity ◽

High Specificity ◽

Intravascular Coagulation ◽

Cutoff Values ◽

Coagulation Tests ◽

Low Sensitivity ◽

D Dimer

SummaryEarly treatment of disseminated intravascular coagulation (DIC) is recommended but global coagulation tests used in authorized DIC criteria are not sensitive for diagnosis of early-phase DIC. We examined the plasma levels of thrombin-antithrombin complex (TAT), plasmin-plasmin inhibitor complex (PPIC) and D-dimer in patients with suspected DIC to determine the cutoff values for diagnosis of DIC. Plasma levels of D-dimer, TAT and PPIC were significantly elevated in patients with DIC and correlated with DIC score. The cutoff values were determined using the receiver operative curve analysis. The cutoff value represented the point at which the sensitivity curve crossed the specificity curve. The cutoff values of D-dimer, TAT and PPIC for DIC were 12. 0 µg/ml, 11.0 ng/ml and 1.8 µg/ml, respectively. These values were moderately to highly sensitive for the diagnosis of DIC but not for poor outcome. The combination of D-dimer, TAT and PPIC showed high sensitivity and low specificity when one or more tests were positive, but showed low sensitivity and high specificity when all three tests were positive. We conclude that hemostatic molecular markers might be useful for the diagnosis of DIC and should be confirmed by several trials.

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Concentration of D-dimers in healthy cats and sick cats with and without disseminated intravascular coagulation (DIC)

Journal of Feline Medicine and Surgery ◽

10.1016/j.jfms.2009.04.008 ◽

2009 ◽

Vol 11 (10) ◽

pp. 842-846 ◽

Cited By ~ 16

Author(s):

Inger Tholen ◽

Christiane Weingart ◽

Barbara Kohn

Keyword(s):

Disseminated Intravascular Coagulation ◽

Underlying Disease ◽

Latex Agglutination ◽

Activated Partial Thromboplastin Time ◽

Thrombin Time ◽

Intravascular Coagulation ◽

Specificity And Sensitivity ◽

Healthy Control ◽

Comparison Of The Results ◽

D Dimer

The objective of this prospective study was to measure concentrations of D-dimers in 48 cats with various diseases and in 20 healthy cats to evaluate the sensitivity and specificity for D-dimers to diagnose disseminated intravascular coagulation (DIC). The cats were classified as having DIC if an underlying disease and at least three of the following criteria were present: thrombocytopenia, prolonged activated partial thromboplastin time, prothrombin time or thrombin time, schistocytes and/or a reduced antithrombin activity. D-dimer concentrations were measured using a semi-quantitative latex agglutination (LA) test (Accuclot D-Dimer, Sigma Diagnostics). The D-dimer test was positive for 8/12 cats with DIC and for 16/36 sick cats without DIC. D-dimers were negative for all healthy control cats. The comparison of the sick cats with DIC and those without DIC revealed a specificity and sensitivity of the D-dimer test of 56% and 67%; a comparison of the results for healthy cats and cats with DIC revealed a specificity and sensitivity of 100% and 67%, respectively. The D-dimer LA test is only of limited value for the diagnosis of DIC in cats.

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Fibrinolysis and Fibrinogenolysis in Disseminated Intravascular Coagulation

Thrombosis and Haemostasis ◽

10.1055/s-0038-1645043 ◽

1990 ◽

Vol 63 (03) ◽

pp. 340-344 ◽

Cited By ~ 16

Author(s):

Hoyu Takahashi ◽

Wataru Tatewaki ◽

Ken Wada ◽

Hiroe Niwano ◽

Akira Shibata

Keyword(s):

Monoclonal Antibodies ◽

Disseminated Intravascular Coagulation ◽

Plasma Levels ◽

Antithrombin Iii ◽

Relative Proportion ◽

Vascular Diseases ◽

Underlying Disease ◽

Promyelocytic Leukemia ◽

Intravascular Coagulation ◽

Thrombin Antithrombin Iii Complex

SummaryIn order to assess precisely the fibrinolytic state in disseminated intravascular coagulation (DIC), plasma levels of fibrinogenolysis products (FgDP), fibrinolysis products (FbDP) and fibrinogenolysis plus fibrinolysis products (TDP) were measured with newly developed enzyme-linked immunosorbent assays based on monoclonal antibodies in 72 patients with DIC at presentation. Not only FbDP and TDP but also FgDP were markedly elevated in patients with DIC. When analyzed according to the underlying disease categories, the relative proportion of FgDP to TDP was high in patients with acute promyelocytic leukemia and vascular diseases, and it was the lowest in patients with sepsis. Correlation analysis revealed that plasma levels of FgDP correlated negatively with alpha 2-antiplasmin and positively with plasmin-alpha 2-antiplasmin complex (PAP) and a ratio of PAP to thrombin-antithrombin III complex (TAT). These findings indicate that besides fibrinolysis, fibrinogenolysis is markedly accelerated in the majority of the patients with DIC.

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On the pathogenesis of “disseminated intravascular coagulation.”

10.1055/s-0039-1682777 ◽

1977 ◽

Author(s):

Theodore H. Spaet

Keyword(s):

Disseminated Intravascular Coagulation ◽

Alternative Hypothesis ◽

Animal Experiments ◽

Coagulation Factors ◽

Alternative Interpretation ◽

Clotting Factors ◽

Blood Coagulation Factors ◽

Intravascular Coagulation ◽

Increased Sensitivity ◽

Clinical Conditions

The following remarks introduce an alternative hypothesis to those conventionally held concerning the hemostatic changes of “disseminated intravascular coagulation (DIC).”The concept that coagulant materials may enter the blood with sufficient rapidity to produce clotting within the vessels and reduction of various blood coagulation factors, particularly fibrinogen, has long been with us. In early animal experiments intravenous tissue factor or thrombin was administered; when these were given at sublethal rates, typical coagulopathies were observedoThe next step was to identify experimental situations or clinical conditions in which blood changes resembled those produced in coagulant-injected animals. These were readily found, and many tests were developed to achieve increased sensitivity in diagnosis of the process. In general, the most widely used have been those which demonstrate loss of certain clotting factors, and those which identify fibrinogen or fibrin fragments.“DIC” is now a generally accepted syndrome»Some neglected observations suggest an alternative interpretation of the blood changes in “DIC.”These raise the possibility that in some, if not many or even most of these syndromes, the source of the blood changes is extravascular processing of the clotting factors. Products may return to the circulation via lymphatics. It is proposed that present methodology cannot resolve this alternative.Supported by UoS. Public Health Service, NIH Grant #HL 16387.

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