On the pathogenesis of “disseminated intravascular coagulation.”

Alternative Hypothesis ◽

Animal Experiments ◽

Coagulation Factors ◽

Alternative Interpretation ◽

Clotting Factors ◽

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.

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

10.1055/s-0038-1649835 ◽

1995 ◽

Vol 74 (03) ◽

pp. 848-852 ◽

Cited By ~ 130

Author(s):

Hideo Wada ◽

Yoshihiro Wakita ◽

Tutomu Nakase ◽

Minori Shimura ◽

Katsuyo Hiyoyama ◽

...

Keyword(s):

Plasma Levels ◽

Early Stage ◽

Coagulation Factors ◽

Underlying Disease ◽

The Relationship ◽

Plasmin Inhibitor ◽

D Dimer

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.

Increased Activity of Vitamin K-Dependent Clotting Factors in Human Hyperlipoproteinaemia – Association with Cholesterol and Triglyceride Levels

10.1055/s-0038-1651852 ◽

1977 ◽

Vol 38 (02) ◽

pp. 0465-0474 ◽

Cited By ~ 46

Author(s):

M Constantino ◽

C Merskey ◽

D. J Kudzma ◽

M. B Zucker

Keyword(s):

Vitamin K ◽

Plasma Lipids ◽

Coagulation Factors ◽

Clotting Factor ◽

Factor X ◽

Clotting Factors ◽

Cholesterol Levels ◽

Type V ◽

Increased Activity

SummaryLevels of blood coagulation factors, cholesterol and triglyceride were measured in human plasma. Prothrombin was significantly elevated in type Ha hyperlipidaemia; prothrombin and factors VII, IX and X in type lib; and prothrombin and factors VII and IX in type V. Multiple regression analysis showed significant correlation between the levels of these plasma lipids and the vitamin K-dependent clotting factors (prothrombin, factors VII, IX and X). Higher cholesterol levels were associated with higher levels of prothrombin and factor X while higher triglyceride levels were associated with higher levels of these as well as factors VII and IX. Prothrombin showed a significant cholesterol-triglyceride interaction in that higher cholesterol levels were associated with higher prothrombin levels at all levels of triglyceride, with the most marked effects in subjects with higher triglyceride levels. Higher prothrombin levels were noted in subjects with high or moderately elevated (but not low) cholesterol levels. Ultracentrifugation of plasma in a density of 1.21 showed activity for prothrombin and factors VII and X only in the lipoprotein-free subnatant fraction. Thus, a true increase in clotting factor protein was probably present. The significance of the correlation between levels of vitamin K-dependent clotting factors and plasma lipids remains to be determined.

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):

Clinical Condition ◽

Underlying Disease ◽

Fibrinogen Concentration ◽

Fixed Amount ◽

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.

Simvastatin improves the prognosis of endotoxin-induced disseminated intravascular coagulation by regulating the intestinal microenvironment

10.21203/rs.3.rs-76982/v1 ◽

2020 ◽

Author(s):

Min Xu ◽

Lili Luo ◽

Mengyi Du ◽

Lu Tang ◽

Jie Zhou ◽

...

Keyword(s):

Bacterial Translocation ◽

Intestinal Barrier ◽

Plasminogen Activator Inhibitor ◽

Coagulation Factors ◽

Organ Damage ◽

Multiple Organ ◽

Plasminogen Activator Inhibitor 1 ◽

Coagulation Dysfunction

Abstract Background: Disseminated intravascular coagulation (DIC) is characterized by extensive endothelial injury and coagulation activation that is primarily caused by infection and can be aggravated by the gut due to increased permeability and bacterial translocation. Studies have shown that statins play an important role in reducing inflammation, protecting the endothelium and improving coagulation. In addition, statins regulate tight junction (TJ) proteins and gut microbes. Therefore, we aimed to investigate whether simvastatin improves DIC prognosis by regulating the intestinal microenvironment. Methods: Mice were administered 20 mg/kg simvastatin by gavage for 2 weeks and then intraperitoneally injected with 50 mg/kg endotoxin. Twelve hours later, cytokine release, coagulation dysfunction, multiple organ damage and survival were assessed. In addition, intestinal barrier and permeability and bacteria and bacteria translocation were evaluated. Results: We found that the severity of endotoxin-induced DIC was significantly improved in simvastatin-pretreated mice, who showed attenuated depletion of coagulation factors and platelets, decreased plasminogen activator inhibitor-1 (PAI-1) expression, reduced organ fibrin deposition and an improved survival rate. In addition, simvastatin reduced epithelial apoptosis, increased TJ gene expression, and upregulated antimicrobial peptides, lysozyme and mucins. Simvastatin-pretreated mice showed increased Lactobacillales counts, while the LPS group had increased numbers of Desulfovibrio and Mucispirillum, which produce harmful toxins and damage the intestinal epithelium and mucosa. Finally, with the decreased intestinal permeability in the simvastatin group, bacterial translocation in the organs and blood was significantly reduced, both in quantity and species. Conclusions: Simvastatin improves DIC prognosis, and the intestinal microenvironment participates in this process.

Disseminated Intravascular Coagulation (DIC) in Obstetric Practice

Journal of Dhaka Medical College ◽

10.3329/jdmc.v20i1.8585 ◽

1970 ◽

Vol 20 (1) ◽

pp. 68-74 ◽

Cited By ~ 1

Author(s):

S Sultana ◽

A Begum ◽

MA Khan

Keyword(s):

Early Recognition ◽

Cell Damage ◽

Heat Stroke ◽

Laboratory Diagnosis ◽

Placental Site ◽

Obstetrical Complication ◽

Abruptio Placenta ◽

Clinical Conditions

Disseminated intravascular coagulation (DIC) is an acquired and complex disorder that occurs in a wide variety of clinical conditions. This is basically a state of increased propensity for clot formation triggered by a variety of stimuli related to such diverse disorders as sepsis, endothelial cell damage (heat stroke, shock), obstetrical complication (abruptio placenta, amniotic fluid embolism, severe preeclampsia and retained intrauterine dead foetus) and neoplasm. DIC is a classic complication of obstetric conditions occurring in more than 50 percent of patients with obstetric causes. In DIC, an unregulated thrombin explosion cause release of free thrombin into the circulation that leads to the clinical features of DIC, with thrombin and plasmin responsible for the thrombotic and haemorrhagic manifestations, respectively. The diagnosis and treatment of this syndrome require an understanding of its pathophysiology, awareness of the disorders that can trigger it and its early recognition. Acute DIC is usually associated with infections, the commonest cause, about 10-20% of patients with gram negative sepsis have evidence of DIC. Chronic DIC is usually associated with retained dead fetus, carcinomatosis. The diagnosis of this syndrome is essentially clinical, with laboratory tests providing confirmatory evidence. Microvascular thrombosis is the primary mechanism in most cases, and end organ failure is a major cause of death. No single diagnostic test exists for DIC. DIC is initially suggested by the following combination; a clinical condition consistent with DIC, thrombocytopenia, prolonged PT, APTT, and presence of FDP/D-dimer. Medical treatment depends on the cause of the DIC. Basically it involves removing the cause for example, delivery of placenta if it is retained or abrupted, delivery of foetus if retained, quick delivery if severe eclampsia and so on, hysterectomy if bleeding can not be controlled from placental site. After then, and/or con-currently treat DIC with blood and plasma transfusions and appropriate supportive measures. As the sequel of DIC can be devastating, early clinical suspicion and laboratory diagnosis are essential. This review article provides essential guideline for the appropriate diagnosis and clinical management of DIC in obstetric patients. Key words: Disseminated intravascular coagulation (DIC); Obstetric; Thrombosis; Fibrin; Ddimer; FDP; Anticoagulant. DOI: http://dx.doi.org/10.3329/jdmc.v20i1.8585 J Dhaka Med Coll. 2011; 20(1) :68-74

Measuring tissue factor (factor III) activity in plasma.

Clinical Chemistry ◽

10.1093/clinchem/35.9.1897 ◽

1989 ◽

Vol 35 (9) ◽

pp. 1897-1900 ◽

Cited By ~ 27

Author(s):

C Fukuda ◽

K Iijima ◽

K Nakamura

Keyword(s):

Tissue Factor ◽

Coagulation Factors ◽

High Plasma ◽

Mean Value ◽

Chromogenic Substrate ◽

Endogenous Inhibitors ◽

Tissue Thromboplastin ◽

The Mean

Abstract This is a method for measuring tissue factor (TF, Factor III, tissue thromboplastin) activity in plasma by using a chromogenic substrate. As pretreatment, the euglobulin fraction of plasma was prepared by removing endogenous inhibitors and heated at 60 degrees C for 3 min to remove fibrinogen. This allowed us to measure the low TF activity in plasma that could not otherwise be measured. Neither phospholipids nor coagulation factors VII, IX, X, or Xa in the samples interfere. Within-run and day-to-day reproducibility were both good. The mean value obtained by this method for normal persons was 1.02 (SD 0.91) arbitrary units/L. A markedly high plasma TF activity of 20 arb. units/L or more was observed in patients with some types of disseminated intravascular coagulation.

Disseminated Intravascular Coagulation: An Update on Pathogenesis, Diagnosis, and Therapeutic Strategies

Clinical and Applied Thrombosis/Hemostasis ◽

10.1177/1076029618806424 ◽

2018 ◽

Vol 24 (9_suppl) ◽

pp. 8S-28S ◽

Cited By ~ 24

Author(s):

Chrysoula Papageorgiou ◽

Georges Jourdi ◽

Eusebe Adjambri ◽

Amanda Walborn ◽

Priya Patel ◽

...

Keyword(s):

Clinical Trials ◽

Severe Sepsis ◽

Bleeding Risk ◽

Therapeutic Strategies ◽

Phase Iii ◽

Clotting Factor ◽

Clotting Factors ◽

Positive Effects

Disseminated intravascular coagulation (DIC) is an acquired clinicobiological syndrome characterized by widespread activation of coagulation leading to fibrin deposition in the vasculature, organ dysfunction, consumption of clotting factors and platelets, and life-threatening hemorrhage. Disseminated intravascular coagulation is provoked by several underlying disorders (sepsis, cancer, trauma, and pregnancy complicated with eclampsia or other calamities). Treatment of the underlying disease and elimination of the trigger mechanism are the cornerstone therapeutic approaches. Therapeutic strategies specific for DIC aim to control activation of blood coagulation and bleeding risk. The clinical trials using DIC as entry criterion are limited. Large randomized, phase III clinical trials have investigated the efficacy of antithrombin (AT), activated protein C (APC), tissue factor pathway inhibitor (TFPI), and thrombomodulin (TM) in patients with sepsis, but the diagnosis of DIC was not part of the inclusion criteria. Treatment with APC reduced 28-day mortality of patients with severe sepsis, including patients retrospectively assigned to a subgroup with sepsis-associated DIC. Treatment with APC did not have any positive effects in other patient groups. The APC treatment increased the bleeding risk in patients with sepsis, which led to the withdrawal of this drug from the market. Treatment with AT failed to reduce 28-day mortality in patients with severe sepsis, but a retrospective subgroup analysis suggested possible efficacy in patients with DIC. Clinical studies with recombinant TFPI or TM have been carried out showing promising results. The efficacy and safety of other anticoagulants (ie, unfractionated heparin, low-molecular-weight heparin) or transfusion of platelet concentrates or clotting factor concentrates have not been objectively assessed.

Pathogenesis, diagnosis, prevention and treatment of disseminated intravascular coagulation syndrome in COVID-19 infection

Terapevticheskii arkhiv ◽

10.26442/00403660.2020.11.000887 ◽

2020 ◽

Vol 92 (11) ◽

pp. 51-56

Author(s):

P. A. Vorobyev ◽

A. P. Momot ◽

L. S. Krasnova ◽

A. P. Vorobiev ◽

A. K. Talipov

Keyword(s):

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Fresh Frozen Plasma ◽

Clotting Factors ◽

Prevention And Treatment ◽

Fresh Frozen ◽

Direct Anticoagulants ◽

Frozen Plasma

Aim. Clinical characteristics of disseminated intravascular coagulation (DIC) in COVID-19 infection and assessment of the effectiveness of complex therapy for this syndrome at the stages of prevention and treatment of various complications. Materials and methods. The study of publications was carried out through search engines on the Internet using keywords. To diagnose the infection, the COVID-19 program was used on the MeDiCase platform, which is publicly available on www.medicase.pro, which suggests a diagnosis with a sensitivity of 89.47%. The study included 85 patients with acute COVID-19 with mild to moderate disease, aged 11 to 81 years. The presence of the pathogen was confirmed immunologically in 12% of patients; in other cases, the diagnosis was based on the results of an automated survey in the MeDiCase system. All patients, according to the MGNOT recommendations, were prescribed one of the oral direct anticoagulants - Eliquis at a dose of 5 mg 2 times a day, Ksarelto at a dose of 10 mg 2 times a day or Pradax at a dose of 110 mg 2 times a day for at least 2 weeks. All other drugs with antiviral, immunomodulatory effects, antibiotics were canceled. Results. The presence of DIC is substantiated by the morphological picture of changes in organs and tissues, clinical (hematoma-petechial type of bleeding in combination with thromboembolic syndrome and the presence of thrombovasculitis) and laboratory changes: an increase in the level of soluble fibrin-monomer complexes, D-dimer, hyperfibrinogenaemia, less often - thrombocytopenia, violation of fibrinolytic activity. The phenomenon of consumption of clotting factors and profuse bleeding are rare. Direct anticoagulants, fresh frozen plasma transfusions and plasmapheresis are used in the treatment of disseminated intravascular coagulation. The paper presents its own positive results of early prescription at the outpatient stage of direct oral anticoagulants in prophylactic doses (no case of disease progression), individual cases of the use of fresh frozen plasma and plasapheresis. Conclusion. DIC syndrome with the development of thrombovasculitis is the most important pathogenetic mechanism for the development of microthrombotic and hemorrhagic disorders in organs during infection with COVID-19, leading to dysfunction of the lungs, brain and other nerve tissues, kidneys, thromboembolic complications, etc. Many symptoms of the disease may be associated with a violation of the nervous regulation of the functions of organs and systems. Prevention of thrombovasculitis is effective already at the stage of the first manifestation of the disease with the outpatient use of direct anticoagulants (oral, low molecular weight heparins). In case of more severe manifestations (complications) of the disease, additional use of freshly frozen plasma and plasmapheresis is effective.

Induction of Disseminated Intravascular Coagulation in the Factor XII-deficient Fowl

10.1055/s-0038-1649099 ◽

1973 ◽

Vol 30 (01) ◽

pp. 025-035 ◽

Cited By ~ 3

Author(s):

Fredrik Skjørten ◽

Stein A. Evensen

Keyword(s):

Plasma Proteins ◽

Coagulation Factors ◽

Factor Xii ◽

Contact Activation ◽

Fibrillar Material ◽

Ultrastructural Appearance ◽

Tissue Thromboplastin ◽

Homologous Tissue

SummaryBirds are naturally deficient in the coagulation factors responsible for the contact activation reactions in mammalian plasma. In the present study, fowl lungs were examined for evidence of disseminated intravascular coagulation (DIC) 5 min or 4 hours after injection of either Liquoid or bacterial endotoxin. These substances are potent initiators of DIC in mammals, and activation of factor XII is believed to be essential for their triggering effect.Liquoid injection produced intravascular deposits with the light microscopical staining properties of fibrin. However these deposits had a purely granular ultra-structure; their formation was not prevented by adequate anticoagulation, and there was no concomitant thrombocyte aggregation. It is suggested that the deposits represent precipitates of plasma proteins, including fibrinogen.Endotoxin failed to produce clinical reactions, intravascular deposits or thrombocyte aggregates. In contrast, animals injected with homologous tissue thromboplastin died, and fibrillar material with the ultrastructural appearance of fibrin, as well as thrombocyte aggregates were found in small pulmonary vessels. These effects were completely prevented by anticoagulation.We conclude that both Liquoid and endotoxin failed to trigger DIC in the factor XII-deficient fowl, suggesting that these substances depend on the contact activation reactions for the generation of thrombin.

Haemostatic Studies in Carbohydrate-deficient Glycoprotein Syndrome Type I

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 ◽

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.