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Disseminated Intravascular Coagulation (DIC) in Adults

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General Information

Description

  • acquired clinicopathological syndrome characterized by systemic activation of coagulation that may cause organ-damaging thrombosis and/or severe bleeding due to consumption of coagulation factors and platelets1,2
  • develops as a complication of a large range of illnesses including infection, solid and hematological malignancies, obstetric diseases, trauma, aneurysms, and liver disease1,2,3

Also called

  • consumptive coagulopathy
  • disseminated intravascular coagulopathy
  • defibrination syndrome
  • defibrinogenation syndrome
  • diffuse intravascular thrombosis
  • acquired afibrinogenemia

Definitions

  • DIC - The Scientific and Standardization Committee (SSC) on DIC of the International Society on Thrombosis and Haemostasis (ISTH) defines DIC as "an acquired syndrome characterized by the intravascular activation of coagulation with a loss of localization arising from different causes; can originate from and cause damage to the microvasculature, which if sufficiently severe, can produce organ dysfunction" (Thromb Haemost 2001 Nov;86(5):1327OpenInNew)

Types

  • DIC is a type of thrombotic microangiopathy (TMA); TMAs are classified as
  • DIC may be classified
    • according to underlying cause
    • according to acute or chronic presentation
      • acute DIC - consumption coagulopathy state typically triggered by large quantities of tissue factor released into the intravascular space leading to
        • excess thrombin generation and generalized deposition of fibrin thrombi in the microvasculature, contributing to multiorgan dysfunction
        • rapid consumption of platelets and coagulation factors
      • chronic DIC
        • characterized by smaller amounts of thrombin generation for prolonged periods
        • occurs with
          • malignancy
          • metastasis
          • intrauterine fetal death
          • vasculitis
          • aneurysms
          • hemangiomas
        • slower consumption of platelets and coagulation factors compared to acute DIC, and can be partially compensated by increased production of coagulation factors, platelets, antithrombin, and antiplasmin
        • thrombosis usually dominates bleeding, though there may be no symptoms
        • only slightly prolonged or normal prothrombin time (PT) and activated partial thromboplastin time (aPTT) may be observed, and platelet count is usually only mildly decreased
        • fibrin degradation products are still efficiently cleared by the liver
      • Reference - Am J Clin Pathol 2016 Dec;146(6):670OpenInNew
    • according to predominant clinical phenotype4,5
      • thrombotic phenotype
        • also called organ failure type, hypercoagulation type, suppressed-fibrinolytic-type, or hypofibrinolysis type DIC
        • most often observed in patients with infection, especially sepsis
        • characterized by strong coagulation activation and suppressed fibrinolysis with microvascular thrombosis and ischemic organ dysfunction/failure
        • thrombosis of larger vessels may also occur
        • bleeding symptoms relatively mild
      • fibrinolytic phenotype
        • also called bleeding type, enhanced-fibrinolytic-type or hyperfibrinolysis type DIC
        • usually observed in patients with trauma, acute promyelocytic leukemia, aortic aneurysm, obstetric diseases, and prostate cancer
        • excessive fibrinolysis, with severe bleeding complications
        • organ failure (rare)
      • subclinical DIC
        • also called balanced-fibrinolytic-type DIC, non-symptomatic type of DIC or pre-DIC
        • characterized by presence of only laboratory features of DIC, with no evident of bleeding or thrombosis (usually seen in cancer-related DIC)
      • References -
  • according to clinical phase
    • non-overt DIC
      • also called latent DIC or compensated DIC
      • characterized by subtle hemostatic dysfunction with
        • stressed, but compensated hemostatic system
        • potential increase in thrombotic risk without obvious clinical symptoms
      • may progress to overt DIC or become a chronic condition
    • overt DIC
      • also called non-compensated or decompensated DIC
      • characterized by stressed but decompensated hemostatic system
      • associated with both bleeding and thrombotic manifestations
    • References -

References

General references used

  1. Wada H, Matsumoto T, Yamashita Y. Diagnosis and treatment of disseminated intravascular coagulation (DIC) according to four DIC guidelines. J Intensive Care. 2014;2(1):15OpenInNewfull-textOpenInNew
  2. Levi M. Diagnosis and treatment of disseminated intravascular coagulation. Int J Lab Hematol. 2014 Jun;36(3):228-36OpenInNew
  3. Levi M, Toh CH, Thachil J, Watson HG. Guidelines for the diagnosis and management of disseminated intravascular coagulation. British Committee for Standards in Haematology. Br J Haematol. 2009 Apr;145(1):24OpenInNew amendment can be found in Br J Haematol 2012 May;157(4):493OpenInNew
  4. Levi M, Scully M. How I treat disseminated intravascular coagulation. Blood. 2018 Feb 22;131(8):845-854OpenInNewfull-textOpenInNew
  5. Asakura H, Takahashi H, Uchiyama T et al. DIC subcommittee of the Japanese Society on Thrombosis and Hemostasis. Proposal for new diagnostic criteria for DIC from the Japanese Society on Thrombosis and Hemostasis. Thromb J. 2016;14:42OpenInNewfull-textOpenInNew

Recommendation grading systems used

  • British Committee for Standards in Haematology (BCSH) guideline grading system
    • grades of recommendations
      • Grade A - ≥ 1 randomized controlled trial in body of literature of overall good quality and consistency addressing specific recommendation (evidence levels Ia and Ib)
      • Grade B - well-conducted clinical studies but no randomized clinical trials on topic of recommendation (evidence levels IIa, IIb, and III)
      • Grade C - expert committee reports or opinions and/or clinical experiences of respected authorities; absence of directly applicable clinical studies of good quality (evidence level IV)
    • levels of evidence
      • Level Ia - evidence from meta-analysis of randomized controlled trials
      • Level Ib - evidence from ≥ 1 randomized controlled trial
      • Level IIa - evidence from ≥ 1 well-designed controlled study without randomization
      • Level IIb - evidence from ≥ 1 other type of well-designed quasi-experimental study
      • Level III - evidence from well-designed nonexperimental descriptive studies, such as comparative studies, correlation studies, and case studies
      • Level IV - evidence from expert committee reports or opinions and/or clinical experiences of respected authorities
    • Reference - BCSH guideline on diagnosis and management of disseminated intravascular coagulation (19222477Br J Haematol 2009 Apr;145(1):24OpenInNew)
  • European LeukemiaNet classification of recommendations and evidence
    • grades of recommendations
      • Grade A - at least 1 randomized controlled trial in body of literature of overall good quality and consistency addressing specific recommendation (evidence levels Ia and Ib)
      • Grade B - well-conducted clinical studies but no randomized clinical trials on topic of recommendation (evidence levels IIa, IIb, and III)
      • Grade C - absence of directly applicable clinical studies of good quality (evidence level IV)
    • levels of evidence
      • Level Ia - evidence from meta-analysis of randomized controlled trials
      • Level Ib - evidence from ≥ 1 randomized controlled trial
      • Level IIa - evidence from ≥ 1 well-designed nonrandomized controlled study
      • Level IIb - evidence from ≥ 1 other type of well-designed quasi-experimental study
      • Level III - evidence from well-designed nonexperimental descriptive studies, such as comparative studies, correlation studies, and case studies
      • Level IV - evidence from expert committee reports or opinions and/or clinical experiences of respected authorities
    • Reference - European LeukemiaNet recommendations on management of acute promyelocytic leukemia (18812465Blood 2009 Feb 26;113(9):1875OpenInNewfull-textOpenInNew)
  • Japanese Society of Thrombosis and Hemostasis (JSTH) recommendation levels
    • Recommendation
      • Consensus - does not have high quality evidence, should be carried out as common sense
      • Grade A - high quality evidence, clinical usefulness is clear
      • Grade B1 - moderately-high quality or high quality evidence, clinical usefulness is not significant
      • Grade B2 - does not have high quality evidence, has few deleterious effects and it is carried out clinically
      • Grade C - does not have high quality evidence, clinical usefulness is not clear
      • Grade D - high quality evidence, has deleterious effects
    • Reference - Japanese expert consensus for the treatment of disseminated intravascular coagulation (19782389Thromb Res 2010 Jan;125(1):6OpenInNew)
  • Italian Society for Haemostasis and Thrombosis (SISET) uses Scottish Intercollegiate Guideline Network (SIGN) grading system
    • grades of recommendations
      • Grade A
        • at least 1 meta-analysis, systematic review, or randomized controlled trial (RCT) rated as 1++ and directly applicable to the target population, or
        • body of evidence consisting principally of studies rated as 1+, directly applicable to target population and demonstrating overall consistency of results
      • Grade B
        • body of evidence including studies rated as 2++, directly applicable to target population and demonstrating overall consistency of results, or
        • extrapolated evidence from studies rated as 1++ or 1+
      • Grade C
        • body of evidence including studies rated as 2+, directly applicable to target population and demonstrating overall consistency of results, or
        • extrapolated evidence from studies rated as 2++
      • Grade D
        • evidence level 3 or 4, or
        • extrapolated evidence from studies rated as 2+
      • Good Practice Point (GPP) - recommended best practice based on clinical experience of guideline development group
    • levels of evidence
      • 1++ - high-quality meta-analyses, systematic reviews of RCTs, or RCTs with very low risk of bias
      • 1+ - well-conducted meta-analyses, systematic reviews of RCTs, or RCTs with low risk of bias
      • 1- - meta-analyses, systematic reviews of RCTs, or RCTs with high risk of bias
      • 2++
        • high-quality systematic reviews of case-control or cohort studies
        • high-quality case-control or cohort studies with very low risk of confounding or bias and high probability that relationship is causal
      • 2+ - well-conducted case-control or cohort studies with low risk of confounding or bias and moderate probability that relationship is causal
      • 2- - case-control or cohort studies with high risk of confounding or bias and significant risk that relationship is not causal
      • 3 - nonanalytical studies (for example, case reports, case series)
      • 4 - expert opinion
    • Reference - SISET diagnosis and treatment of disseminated intravascular coagulation (21930293Thromb Res 2012 May;129(5):e177OpenInNew, SIGN grading system 1999-2012PictureAsPdf)
  • International Society on Thrombosis and Haemostasis, Scientific and Standardization Committee (ISTH/SSC) guidance statement
    • quality of evidence
      • High quality - further research unlikely to change confidence in the estimate of the effect
      • Moderate quality - further research likely to have important impact on confidence in the estimate of the effect and may change the estimate
      • Low quality - further research is very likely to have important impact on confidence in the estimate of the effect and likely to change the estimate
    • Reference - ISTH guidance for diagnosis and treatment of DIC from harmonization of the recommendations from three guidelines (mnh23379279paph86928033t pa9h86928033t pcxh86928033t pmdc23379279pJ Thromb Haemost 2013 Feb 4 early onlineOpenInNew)

Synthesized Recommendation Grading System for DynaMed

  • DynaMed systematically monitors clinical evidence to continuously provide a synthesis of the most valid relevant evidence to support clinical decision-making (see 7-Step Evidence-Based MethodologyOpenInNew).
  • Guideline recommendations summarized in the body of a DynaMed topic are provided with the recommendation grading system used in the original guideline(s), and allow DynaMed users to quickly see where guidelines agree and where guidelines differ from each other and from the current evidence.
  • In DynaMed (DM), we synthesize the current evidence, current guidelines from leading authorities, and clinical expertise to provide recommendations to support clinical decision-making in the Overview & Recommendations section.
  • We use the Grading of Recommendations Assessment, Development and Evaluation (GRADE)OpenInNew to classify synthesized recommendations as Strong or Weak.
    • Strong recommendations are used when, based on the available evidence, clinicians (without conflicts of interest) consistently have a high degree of confidence that the desirable consequences (health benefits, decreased costs and burdens) outweigh the undesirable consequences (harms, costs, burdens).
    • Weak recommendations are used when, based on the available evidence, clinicians believe that desirable and undesirable consequences are finely balanced, or appreciable uncertainty exists about the magnitude of expected consequences (benefits and harms). Weak recommendations are used when clinicians disagree in judgments of relative benefit and harm, or have limited confidence in their judgments. Weak recommendations are also used when the range of patient values and preferences suggests that informed patients are likely to make different choices.
  • DynaMed (DM) synthesized recommendations (in the Overview & Recommendations section) are determined with a systematic methodology:
    • Recommendations are initially drafted by clinical editors (including ≥ 1 with methodological expertise and ≥ 1 with content domain expertise) aware of the best current evidence for benefits and harms, and the recommendations from guidelines.
    • Recommendations are phrased to match the strength of recommendation. Strong recommendations use "should do" phrasing, or phrasing implying an expectation to perform the recommended action for most patients. Weak recommendations use "consider" or "suggested" phrasing.
    • Recommendations are explicitly labeled as Strong recommendations or Weak recommendations when a qualified group has explicitly deliberated on making such a recommendation. Group deliberation may occur during guideline development. When group deliberation occurs through DynaMed-initiated groups:
      • Clinical questions will be formulated using the PICO (Population, Intervention, Comparison, Outcome) framework for all outcomes of interest specific to the recommendation to be developed.
      • Systematic searches will be conducted for any clinical questions where systematic searches were not already completed through DynaMed content development.
      • Evidence will be summarized for recommendation panel review including for each outcome, the relative importance of the outcome, the estimated effects comparing intervention and comparison, the sample size, and the overall quality rating for the body of evidence.
      • Recommendation panel members will be selected to include at least 3 members that together have sufficient clinical expertise for the subject(s) pertinent to the recommendation, methodological expertise for the evidence being considered, and experience with guideline development.
      • All recommendation panel members must disclose any potential conflicts of interest (professional, intellectual, and financial), and will not be included for the specific panel if a significant conflict exists for the recommendation in question.
      • Panel members will make Strong recommendations if and only if there is consistent agreement in a high confidence in the likelihood that desirable consequences outweigh undesirable consequences across the majority of expected patient values and preferences. Panel members will make Weak recommendations if there is limited confidence (or inconsistent assessment or dissenting opinions) that desirable consequences outweigh undesirable consequences across the majority of expected patient values and preferences. No recommendation will be made if there is insufficient confidence to make a recommendation.
      • All steps in this process (including evidence summaries which were shared with the panel, and identification of panel members) will be transparent and accessible in support of the recommendation.
    • Recommendations are verified by ≥ 1 editor with methodological expertise, not involved in recommendation drafting or development, with explicit confirmation that Strong recommendations are adequately supported.
    • Recommendations are published only after consensus is established with agreement in phrasing and strength of recommendation by all editors.
    • If consensus cannot be reached then the recommendation can be published with a notation of "dissenting commentary" and the dissenting commentary is included in the topic details.
    • If recommendations are questioned during peer review or post publication by a qualified individual, or reevaluation is warranted based on new information detected through systematic literature surveillance, the recommendation is subject to additional internal review.

DynaMed Editorial Process

Special acknowledgements

On behalf of the American College of Physicians
  • Barbara Turner, MD, MSEd, MACP, ACP Deputy Editor, Clinical Decision Resource, as part of the ACP-EBSCO Health collaboration, managed the ACP peer review of the Overview and Recommendations section and related clinical content in this topic.
  • DynaMed topics are written and edited through the collaborative efforts of the above individuals. Deputy Editors, Section Editors, and Topic Editors are active in clinical or academic medical practice. Recommendations Editors are actively involved in development and/or evaluation of guidelines.
  • Editorial Team role definitions
    Topic Editors define the scope and focus of each topic by formulating a set of clinical questions and suggesting important guidelines, clinical trials, and other data to be addressed within each topic. Topic Editors also serve as consultants for the internal DynaMed Editorial Team during the writing and editing process, and review the final topic drafts prior to publication.
    Section Editors have similar responsibilities to Topic Editors but have a broader role that includes the review of multiple topics, oversight of Topic Editors, and systematic surveillance of the medical literature.
    Recommendations Editors provide explicit review of DynaMed Overview and Recommendations sections to ensure that all recommendations are sound, supported, and evidence-based. This process is described in "Synthesized Recommendation Grading."
    Deputy Editors are employees of DynaMed and oversee DynaMed internal publishing groups. Each is responsible for all content published within that group, including supervising topic development at all stages of the writing and editing process, final review of all topics prior to publication, and direction of an internal team.

How to cite

National Library of Medicine, or "Vancouver style" (International Committee of Medical Journal Editors):

  • DynaMed [Internet]. Ipswich (MA): EBSCO Information Services. 1995 - . Record No. T116682, Disseminated Intravascular Coagulation (DIC) in Adults; [updated 2018 Nov 30, cited place cited date here]. Available from https://www.dynamed.com/topics/dmp~AN~T116682. Registration and login required.

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