Disseminated Intravascular Coagulation Workup

  • Author: Marcel M Levi, MD; Chief Editor: Emmanuel C Besa, MD   more...
 
Updated: Oct 26, 2011
 

Laboratory Studies

  • No single routinely available laboratory test is sufficiently sensitive or specific to allow a diagnosis of disseminated intravascular coagulation (DIC).
  • Specialized tests
    • In a specialized setting, molecular markers for activation of coagulation or fibrin formation may be the most sensitive assays for disseminated intravascular coagulation (DIC).[12] A number of clinical studies show that the presence of soluble fibrin in plasma has a 90-100% sensitivity for the diagnosis of disseminated intravascular coagulation (DIC), but unfortunately the specificity is low. Another problem is that a reliable test for quantifying soluble fibrin in plasma is not available, and one study showed a wide discordance among various assays.
    • The dynamics of disseminated intravascular coagulation (DIC) can also be judged by measuring activation markers that are released upon the conversion of a coagulation factor zymogen to an active protease, such as prothrombin activation fragment F1+2 (F1+2). Indeed, these markers are markedly elevated in patients with disseminated intravascular coagulation (DIC), but, again, the specificity is a problem.
    • In addition to these shortcomings, most of the sensitive and sophisticated tests described above are not available to general hematology laboratories. Although these tests may be very helpful in clinical trials or other research, they often cannot be used in a routine setting.
  • Routine tests
    • In clinical practice, a diagnosis of disseminated intravascular coagulation (DIC) can often be made by a combination of platelet count, measurement of global clotting times (aPTT and PT), measurement of 1 or 2 clotting factors and inhibitors (eg, antithrombin), and a test for fibrin degradation products (FDPs).[13]
    • It should be emphasized that serial coagulation tests are usually more helpful than single laboratory results in establishing the diagnosis of disseminated intravascular coagulation (DIC). A reduction in the platelet count or a clear downward trend at subsequent measurements is a sensitive (although not specific) sign of disseminated intravascular coagulation (DIC).
    • The prolongation of global clotting times may reflect the consumption and depletion of various coagulation factors, which may be further substantiated by the measurement of selected coagulation factors, such as factor V and factor VII.
    • Measurement of coagulation factors may also may be helpful to detect additional hemostatic abnormalities (eg, those caused by vitamin K deficiency).
    • Measurement of fibrinogen has been widely advocated as a useful tool for the diagnosis of disseminated intravascular coagulation (DIC), but, in fact, it is not very helpful. Fibrinogen acts as an acute-phase reactant and is, for example, also increased in pregnancy, and, despite ongoing consumption, plasma levels can remain well within the normal range for a long time.
    • In a consecutive series of patients, the sensitivity of a low fibrinogen level for the diagnosis of disseminated intravascular coagulation (DIC) was only 28%, and hypofibrinogenemia was detected in a very small number of severe cases of disseminated intravascular coagulation (DIC) only. Sequential measurements of fibrinogen might be more useful and provide diagnostic clues.
    • Tests for FDPs (eg, D-dimer) may be helpful to differentiate disseminated intravascular coagulation (DIC) from other conditions that may be associated with a low platelet count and prolonged clotting times, such as chronic liver disease. Most laboratories will have an operational test for FDPs.
    • FDPs may be detected by specific enzyme-linked immunosorbent assays (ELISAs) or by latex agglutination assays, allowing rapid and bedside determination in emergency cases. However, some of the available assays for FDPs cross-react with FDPs, which may cause spuriously high results. The specificity of high levels of FDPs is therefore limited, and many other conditions, such as inflammation or recent surgery, are associated with elevated FDPs.
    • More recently developed tests are specifically aimed at the detection of neoantigens on degraded cross-linked fibrin, such as D-dimer. D-dimer levels are high in patients with disseminated intravascular coagulation (DIC), but they poorly distinguish patients with disseminated intravascular coagulation (DIC) from those with trauma or recent surgery.
  • Disseminated intravascular coagulation (DIC) scoring system
    • A scoring system that uses simple laboratory tests that are available in almost all hospital laboratories has been established by the Subcommittee on disseminated intravascular coagulation (DIC) of the International Society on Thrombosis and Haemostasis.[14] That system is shown in the algorithm below. Diagnostic algorithm for the diagnosis of overt diDiagnostic algorithm for the diagnosis of overt disseminated intravascular coagulation.
    • The presence of an underlying disorder known to be associated with disseminated intravascular coagulation (DIC), as listed previously, is a condition sine qua non for the use of the algorithm.
    • Based on a retrospective study, a score of 5 or more is considered to be compatible with disseminated intravascular coagulation (DIC). Prospective validation studies show a high accuracy of this scoring system for the diagnosis of disseminated intravascular coagulation (DIC). The sensitivity of the DIC score for a diagnosis of DIC is 91%, and the specificity is 97%.[12]
    • Other analyses show that the DIC scoring system is a strong independent predictor of a fatal outcome in intensive care unit patients. These studies show that patients with sepsis and disseminated intravascular coagulation (DIC), according to the scoring system, have a mortality of more than 40% compared with about 25% in patients without disseminated intravascular coagulation (DIC).
    • For each disseminated intravascular coagulation (DIC) point in the system, the odds ratio for mortality is 1.29, whereas, in comparison, for each Acute Physiology and Chronic Health Evaluation (APACHE) classification system point, the odds ratio for mortality is 1.07.
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Imaging Studies

  • Imaging studies are useful only to detect an underlying etiology; the diagnosis of disseminated intravascular coagulation (DIC) is made by combining the clinical impression and laboratory abnormalities.
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Procedures

  • No specific procedures help to diagnose disseminated intravascular coagulation (DIC). However, all procedures may help to diagnose the underlying etiology.
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Histologic Findings

  • Grossly, hemorrhage into all tissues (eg, brain, adrenal, lung, kidney) can develop in acute hemorrhagic disseminated intravascular coagulation (DIC). A review of pathologic specimens reveals evidence for fibrin deposition in vessels and thrombosis.
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Contributor Information and Disclosures
Author

Marcel M Levi, MD  Dean, Academic Medical Center, University of Amsterdam, the Netherlands

Marcel M Levi, MD is a member of the following medical societies: American Society of Hematology and International Society on Thrombosis and Haemostasis

Disclosure: Nothing to disclose.

Coauthor(s)

Alvin H Schmaier, MD  Robert W Kellermeyer Professor of Hematology/Oncology, Case Western Reserve University School of Medicine; Chief, Division of Hematology/Oncology, Case Western Reserve University

Alvin H Schmaier, MD is a member of the following medical societies: American Federation for Medical Research, American Heart Association, American Society for Clinical Investigation, American Society of Hematology, Association of American Physicians, Central Society for Clinical Research, and International Society on Thrombosis and Haemostasis

Disclosure: Nothing to disclose.

Specialty Editor Board

Pradyumna D Phatak, MBBS, MD  Chair, Division of Hematology and Medical Oncology, Rochester General Hospital; Clinical Professor of Oncology, Roswell Park Cancer Institute

Pradyumna D Phatak, MBBS, MD, is a member of the following medical societies: American Society of Hematology

Disclosure: Novartis Honoraria Speaking and teaching

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Ronald A Sacher, MB, BCh, MD, FRCPC  Professor, Internal Medicine and Pathology, Director, Hoxworth Blood Center, University of Cincinnati Academic Health Center

Ronald A Sacher, MB, BCh, MD, FRCPC is a member of the following medical societies: American Association for the Advancement of Science, American Association of Blood Banks, American Clinical and Climatological Association, American Society for Clinical Pathology, American Society of Hematology, College of American Pathologists, International Society of Blood Transfusion, International Society on Thrombosis and Haemostasis, and Royal College of Physicians and Surgeons of Canada

Disclosure: Glaxo Smith Kline Honoraria Speaking and teaching; Talecris Honoraria Board membership

Rajalaxmi McKenna, MD, FACP  Southwest Medical Consultants, SC, Department of Medicine, Good Samaritan Hospital, Advocate Health Systems

Rajalaxmi McKenna, MD, FACP is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology, and International Society on Thrombosis and Haemostasis

Disclosure: Nothing to disclose.

Chief Editor

Emmanuel C Besa, MD  Professor, Department of Medicine, Division of Hematologic Malignancies, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University

Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Clinical Oncology, American Society of Hematology, and New York Academy of Sciences

Disclosure: Nothing to disclose.

References

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  8. Sawamura A, Hayakawa M, Gando S, Kubota N, Sugano M, Wada T, et al. Application of the Japanese Association for Acute Medicine disseminated intravascular coagulation diagnostic criteria for patients at an early phase of trauma. Thromb Res. Aug 1 2009;[Medline].

  9. Zhu YJ, Huang XK. Relationship between disseminated intravascular coagulation and levels of plasma thrombinogen segment 1+2, D-dimer, and thrombomodulin in patients with multiple injuries. Chin J Traumatol. Aug 2009;12(4):203-9. [Medline].

  10. Duchesne JC, Islam TM, Stuke L, Timmer JR, Barbeau JM, Marr AB, et al. Hemostatic resuscitation during surgery improves survival in patients with traumatic-induced coagulopathy. J Trauma. Jul 2009;67(1):33-7; discussion 37-9. [Medline].

  11. Takashima A, Shirao K, Hirashima Y, Takahari D, Okita NT, Nakajima TE, et al. Sequential chemotherapy with methotrexate and 5-fluorouracil for chemotherapy-naive advanced gastric cancer with disseminated intravascular coagulation at initial diagnosis. J Cancer Res Clin Oncol. Sep 2 2009;[Medline].

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  14. Taylor FB Jr, Toh CH, Hoots WK, et al, for the Scientific Subcommittee on Disseminated Intravascular Coagulation (DIC) of the ISTH. Towards definition, clinical and laboratory criteria, and a scoring system for disseminated intravascular coagulation. Thromb Haemost. Nov 2001;86(5):1327-30. [Medline]. [Full Text].

  15. Levi M, Levy M, Williams MD, Douglas I, Artigas A, Antonelli M, et al. Prophylactic heparin in patients with severe sepsis treated with drotrecogin alfa (activated). Am J Respir Crit Care Med. Sep 1 2007;176(5):483-90. [Medline].

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  17. Yamakawa K, Fujimi S, Mohri T, Matsuda H, Nakamori Y, Hirose T, et al. Treatment effects of recombinant human soluble thrombomodulin in patients with severe sepsis: a historical control study. Crit Care. 2011;15(3):R123. [Medline].

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Diagnostic algorithm for the diagnosis of overt disseminated intravascular coagulation.
 
 
 
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