Disseminated Intravascular Coagulation in Cancer: An Update

AbstractCancer often leads to the activation of coagulation, manifesting as disseminated intravascular coagulation (DIC) in its most extreme form. DIC is characterized by systemic intravascular coagulation activation (leading to deposition of intravascular platelets and fibrin) and simultaneous consumption of coagulation proteins and thrombocytes (which may cause bleeding complications). The clinical course of DIC in patients with malignancies is typically less intense compared with DIC complicating alternative clinical settings, including systemic inflammatory responses following infection or traumatic injury. A more slowly proceeding, less fulminant, and widespread hemostatic derangement can remain asymptomatic. Eventually, the ongoing consumption may result in low levels of platelets and coagulation factors, and bleeding complications (frequently localized at the site of the tumor or distant metastases) may be the first clinical manifestation of DIC. An alternative clinical scenario is dominated by thrombotic complications, ranging from clinically manifest vascular thrombosis to microvascular platelet plugs. The main principle of DIC management is adequate treatment of the precipitating disorder; however, there are clinical presentations that may require additional supportive strategies specifically aimed at the amelioration of the coagulopathy.

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Kinetics Of Antithrombin III During Severe Consumption Coagulopathy In An Infant Measured Without Radioactive Tracer Proteins

10.1055/s-0038-1652892 ◽

1981 ◽

Cited By ~ 1

Author(s):

B Schmidt ◽

U Wais ◽

I Witt ◽

W Pringsheim ◽

W Künz

Keyword(s):

Disseminated Intravascular Coagulation ◽

Antithrombin Iii ◽

Radioactive Tracer ◽

Coagulation Factors ◽

Turnover Rates ◽

Intravascular Coagulation ◽

Elimination Half ◽

Coagulation Proteins ◽

Precise Diagnosis ◽

Severe Coagulopathy

The precise diagnosis of disseminated intravascular coagulation remains difficult to achieve: Decreased production of coagulation factors and/or thrombocytes can mimic the laboratory pattern of disseminated intravascular coagulation. The measurement of increased turnover rates for coagulation proteins would provide more convincing criteria.During the course of severe coagulopathy in an infant suffering from septicaemia and shock, antithrombin levels were determined repeatedly before and during treatment with Antithrombin concentrate: Activities and concentrations were measured, using chromogenic substrates and immunodiffusion plates, respectively. By mathematical analysis of these data, using a biexponential function, the plasma elimination half-life of the antithrombin III was estimated to be 7.5 to 10.5 hours. Compared with known plasma half-lives of radioactively labelled antithrombin III in adults, the increase was five- to ten-fold. This indicates an accelerated consumption of antithrombin III in this case of severe coagulopathy.

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Disseminated Intravascular Coagulation

Family Medicine ◽

10.30841/2307-5112.5.2016.248654 ◽

2016 ◽

pp. 45-51

Author(s):

Stanislav Vydyborets ◽

Artem Andriiaka

Keyword(s):

Disseminated Intravascular Coagulation ◽

Standard Treatment ◽

Coagulation Factors ◽

Therapeutic Strategies ◽

Current Standard ◽

Intravascular Coagulation ◽

Current Standard Treatment ◽

Thrombotic Complications ◽

Novel Therapeutic Strategies ◽

Common Manifestation

Disseminated intravascular coagulation (DIC) is characterized by an acute generalized, widespread activation of coagulation, which results in thrombotic complications, due to the intravascular formation of fibrin, as well as diffuse hemorrhages, due to the consumption of platelets and coagulation factors. In this lecture, we discuss regarding the controversies in diagnosis and management of DIC. Bleeding is a more common manifestation of DIC. We report the present knowledge about the treatment of DIC. Therapy of DIC aims at treating the primary cause. We focus on the current standard treatment of overt DIC in clinical practice. Moreover, particular attention is made to novel therapeutic strategies, who reflect the important progresses in the understanding of the pathogenesis of this syndrome in the last few years.

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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 ◽

Disseminated Intravascular Coagulation ◽

Intestinal Barrier ◽

Plasminogen Activator Inhibitor ◽

Coagulation Factors ◽

Organ Damage ◽

Multiple Organ ◽

Plasminogen Activator Inhibitor 1 ◽

Intravascular Coagulation ◽

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.

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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 ◽

Disseminated Intravascular Coagulation ◽

Coagulation Factors ◽

High Plasma ◽

Mean Value ◽

Chromogenic Substrate ◽

Intravascular Coagulation ◽

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.

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Case 17: Severe bleeding complications, lymphocytosis and leukoerythroblastosis – disseminated intravascular coagulation in a patient with metastasizing carcinoma of the prostate and chronic lymphocytic leukemia

Therapeutische Umschau ◽

10.1024/0040-5930.56.9.533 ◽

1999 ◽

Vol 56 (9) ◽

pp. 533-536 ◽

Cited By ~ 1

Author(s):

Solenthaler ◽

Lämmle

Keyword(s):

Chronic Lymphocytic Leukemia ◽

Disseminated Intravascular Coagulation ◽

Lymphocytic Leukemia ◽

Bleeding Complications ◽

Severe Bleeding ◽

Disseminierte Intravasale Gerinnung ◽

Intravascular Coagulation ◽

Carcinoma Of The Prostate

Blutungskomplikationen bei chronischer lymphatischer Leukämie (CLL) stehen meist in Zusammenhang mit einer Thrombozytopenie, bedingt entweder durch eine direkte Verdrängung der Megakaryopoese bei diffuser Knochenmarksinfiltration oder durch einen vermehrten peripheren Verbrauch im Rahmen einer (sekundären) Immunthrombozytopenie. Eine disseminierte intravasale Gerinnung (DIC) gehört nicht zum Spektrum hämatologischer Komplikationen einer CLL. Das hier geschilderte Fallbeispiel eines Patienten mit schweren Blutungskomplikationen, labormäßigen Zeichen einer DIC und neu entdeckter CLL ließ eine Ursache der DIC vermissen. Das leukoerythroblastäre Blutbild lieferte den Schlüssel zur Diagnose eines metastasierenden Prostatakarzinoms, welches durch die Knochenmarksbiopsie bestätigt wurde und als Trigger für die DIC verantwortlich war.

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Optimal Timing and Early Intervention With Anticoagulant Therapy for Sepsis-Induced Disseminated Intravascular Coagulation

Clinical and Applied Thrombosis/Hemostasis ◽

10.1177/1076029619835055 ◽

2019 ◽

Vol 25 ◽

pp. 107602961983505 ◽

Cited By ~ 3

Author(s):

Kazuma Yamakawa ◽

Yutaka Umemura ◽

Shuhei Murao ◽

Mineji Hayakawa ◽

Satoshi Fujimi

Keyword(s):

Early Intervention ◽

Anticoagulant Therapy ◽

Disseminated Intravascular Coagulation ◽

Survival Data ◽

Scoring Systems ◽

Bleeding Complications ◽

Optimal Timing ◽

Optimal Cutoff ◽

Intravascular Coagulation ◽

Cutoff Points

Optimizing diagnostic criteria to detect specific patients likely to benefit from anticoagulants is warranted. A cutoff of 5 points for the International Society on Thrombosis and Haemostasis overt disseminated intravascular coagulation (DIC) scoring system was determined in the original article, but its validity was not evaluated. This study aimed to explore the optimal cutoff points of DIC scoring systems and evaluate the effectiveness of early intervention with anticoagulants. We used a nationwide retrospective registry of consecutive adult patients with sepsis in Japan to develop simulated survival data, assuming anticoagulants were conducted strictly according to each cutoff point. Estimated treatment effects of anticoagulants for in-hospital mortality and risk of bleeding were calculated by logistic regression analysis with inverse probability of treatment weighting using propensity scoring. Of 2663 patients with sepsis, 1247 patients received anticoagulants and 1416 none. The simulation model showed no increase in estimated mortality between 0 and 3 cutoff points, whereas at ≥4 cutoff points, mortality increased linearly. The estimated bleeding tended to decrease in accordance with the increase in cutoff points. The optimal cutoff for determining anticoagulant therapy may be 3 points to minimize nonsurvival with acceptable bleeding complications. The findings of the present study suggested a beneficial association of early intervention with anticoagulant therapy and mortality in the patients with sepsis-induced DIC. Present cutoff points of DIC scoring systems may be suboptimal for determining the start of anticoagulant therapy and delay its initiation.

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Roles of protease-activated receptors in a mouse model of endotoxemia

Blood ◽

10.1182/blood-2005-08-3130 ◽

2006 ◽

Vol 107 (10) ◽

pp. 3912-3921 ◽

Cited By ~ 70

Author(s):

Eric Camerer ◽

Ivo Cornelissen ◽

Hiroshi Kataoka ◽

Daniel N. Duong ◽

Yao-Wu Zheng ◽

...

Keyword(s):

Platelet Activation ◽

Disseminated Intravascular Coagulation ◽

Inflammatory Responses ◽

Endothelial Activation ◽

Wild Type ◽

Protease Activated Receptors ◽

Endotoxin Challenge ◽

Intravascular Coagulation ◽

Endotoxemia Model ◽

Independent Process

Endotoxemia is often associated with extreme inflammatory responses and disseminated intravascular coagulation. Protease-activated receptors (PARs) mediate cellular responses to coagulation proteases, including platelet activation and endothelial cell reactions predicted to promote inflammation. These observations suggested that PAR activation by coagulation proteases generated in the setting of endotoxemia might promote platelet activation, leukocyte-mediated endothelial injury, tissue damage, and death. Toward testing these hypotheses, we examined the effect of PAR deficiencies that ablate platelet and endothelial activation by coagulation proteases in a mouse endotoxemia model. Although coagulation was activated as measured by thrombin-antithrombin (TAT) production and antithrombin III (ATIII) depletion, Par1–/–, Par2–/–, Par4–/–, Par2–/–:Par4–/–, and Par1–/–:Par2–/– mice all failed to show improved survival or decreased cytokine responses after endotoxin challenge compared with wild type. Thus, our results fail to support a necessary role for PARs in linking coagulation to inflammation or death in this model. Interestingly, endotoxin-induced thrombocytopenia was not diminished in Par4–/– mice. Thus, a mechanism independent of platelet activation by thrombin was sufficient to cause thrombocytopenia in our model. These results raise the possibility that decreases in platelet count in the setting of sepsis may not be caused by disseminated intravascular coagulation but instead report on a sometimes parallel but independent process.

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

Thrombosis and Haemostasis ◽

10.1055/s-0038-1649099 ◽

1973 ◽

Vol 30 (01) ◽

pp. 025-035 ◽

Cited By ~ 3

Author(s):

Fredrik Skjørten ◽

Stein A. Evensen

Keyword(s):

Disseminated Intravascular Coagulation ◽

Plasma Proteins ◽

Coagulation Factors ◽

Factor Xii ◽

Contact Activation ◽

Intravascular Coagulation ◽

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.

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Crotalocytin: recognition and purification of a timber rattlesnake platelet aggregating protein

Blood ◽

10.1182/blood.v56.6.1013.1013 ◽

1980 ◽

Vol 56 (6) ◽

pp. 1013-1019 ◽

Cited By ~ 46

Author(s):

AH Schmaier ◽

W Claypool ◽

RW Colman

Keyword(s):

Disseminated Intravascular Coagulation ◽

Clinical Presentation ◽

Sodium Dodecyl ◽

Gel Filtration ◽

Coagulation Factors ◽

Single Chain ◽

Intravascular Coagulation ◽

Timber Rattlesnake ◽

Activated Platelets ◽

Low Ionic Strength

Abstract After being envenomated by the timber rattlesnake, a patient was found to have a platelet count of 5000 per microliter, prothrombin time and activated partial thromboplastin time both greater than 150 sec, plasma fibrinogen 0 mg/dl, and fibrinogen split products 2560 microgram/ml. However, this patient did not appear to have acute disseminated intravascular coagulation since coagulation factors II-XII were normal. We postulated that this venom contained, in addition to a fibrinogen clotting enzyme, a platelet activating protein, Crotalocytin. Crotalocytin was purified from crude timber rattlesnake venom by Sephadex G-100 gel-filtration, low ionic strength precipitation, and DEAE-A50 Sephadex chromatography. By sodium dodecyl sulfate gel electrophoresis and gel-filtration Crotalocytin was a single chain polypeptide, molecular weight 55,000. Thrombocytopenia after timber rattlesnake bite appeared to be due to a protein that directly activated platelets. Timber rattlesnake bite mimicked the clinical presentation of disseminated intravascular coagulation.

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The Elimination of Labelled Fibrinogen in Galactosamine-Induced Experimental Hepatitis in Rabbits

10.1055/s-0039-1689512 ◽

1975 ◽

Author(s):

I. Mahn ◽

C. Reuter ◽

H. Merkel ◽

G. Müller-Berghaus

Keyword(s):

Liver Disease ◽

Intravenous Injection ◽

Disseminated Intravascular Coagulation ◽

Isotonic Saline ◽

Coagulation Factors ◽

Virus Hepatitis ◽

Intravascular Coagulation ◽

Coagulation Defect ◽

Deutsche Forschungsgemeinschaft ◽

Glomerular Capillaries

The intravenous injection of D-galactosamine-HCl into animals induces a liver disease resembling virus hepatitis in man in its histological and clinico-phatological features. In a previous study disseminated intravascular coagulation was demonstrated by tracing fibrin-rich microdots in the renal glomerular capillaries, especially if the fibrinolytic system was inhibited by EACA (Thromb. Res. 1, 473, 1972). In order to differentiate between disturbance of synthesis and disseminated intravascular coagulation, investigations with 125I-fibrinogen were performed in rabbits treated with D-galactosamine (1 g/kg) and EACA (0.5 g/kg xhr). In rabbits infused with galactosamine and EACA the elimination of 125I-fibrinogen was increased in comparison to the control animals treated with EACA or isotonic saline only. If heparin (750 u/kg × hr) was infused additionally to galactosamine and EACA, the accelerated decay of labelled fibrinogen was prevented. The occurrence of 125I-activity in organs was pronounced in animals exhibiting microdot formation. These experiments indicate that due to a diminished synthesis of coagulation factors in this model of hepatitis disseminated intravascular coagulation may contribute to the coagulation defect.(Supported by the Deutsche Forschungsgemeinschaft, Bad Godesberg, Germany.)

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