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Disseminated Intravascular Coagulation (DIC)

Sections Disseminated Intravascular Coagulation (DIC)
Overview
Presentation
DDx
Workup
Treatment
Medication
Questions & Answers
Media Gallery
Tables
References

Presentation

History

The symptoms of disseminated intravascular coagulation (DIC) are often those of the underlying inciting condition (see Etiology). Such conditions may include the following:

Sepsis or severe infection (with any microorganism)
Trauma (eg, polytrauma, neurotrauma, or fat embolism)
Organ destruction (eg, severe pancreatitis)
Malignancy – Solid tumors and myeloproliferative/ lymphoproliferative malignancies
Obstetric calamities (eg, amniotic fluid embolism; abruptio placentae)
Vascular abnormalities – Kasabach-Merritt syndrome and large vascular aneurysms
Severe hepatic failure
Severe toxic or immunologic reactions – Snake bites, recreational drugs, transfusion reactions, and transplant rejection

In addition to the symptoms related to the underlying disease process, there is typically a history of blood loss through bleeding in areas such the gingivae and the gastrointestinal (GI) system (see Table 3 below).^[50]Acutely presenting DIC often manifests as petechiae and ecchymosis, along with blood loss from intravenous (IV) lines and catheters. In postoperative DIC, bleeding can occur in the vicinity of surgical sites, drains, and tracheostomies, as well as within serous cavities.

Table 3. Main Features of Disseminated Intravascular Coagulation in Series of 118 Patients (Open Table in a new window)

Features	Affected Patients, %
Bleeding	64%
Renal dysfunction	25%
Hepatic dysfunction	19%
Respiratory dysfunction	16%
Shock	14%
Central nervous system dysfunction	2%

Look for symptoms and signs of thrombosis in large vessels (eg, deep vein thrombosis [DVT]) and microvascular thrombosis (as in renal failure). Bleeding from at least 3 unrelated sites is particularly suggestive of DIC. As many as 25% of patients present with renal failure. Patients with pulmonary involvement can present with dyspnea, hemoptysis, and cough. Comorbid liver disease as well as rapid hemolytic bilirubin production may lead to jaundice. Neurologic changes (eg, coma, obtunded mental status, and paresthesias) are also possible.

Physical Examination

With acute DIC, the physical findings are usually those of the underlying or inciting condition; however, patients with the acute disease (ie, the hemorrhagic variety associated with excess plasmin formation) have petechiae on the soft palate, trunk, and extremities from thrombocytopenia and ecchymosis at venipuncture sites. These patients also manifest ecchymosis in traumatized areas.

In patients with so-called chronic or subacute DIC, of which the primary manifestation is thrombosis from excess thrombin formation, the signs of venous thromboembolism may be present.

Circulatory signs include the following:

Signs of spontaneous and life-threatening hemorrhage
Signs of subacute bleeding
Signs of diffuse or localized thrombosis
Bleeding into serous cavities

Central nervous system signs include the following:

Nonspecific altered consciousness or stupor
Transient focal neurologic deficits

Cardiovascular signs include the following:

Hypotension
Tachycardia
Circulatory collapse

Respiratory signs include the following:

Pleural friction rub
Signs of acute respiratory distress syndrome (ARDS)

Gastrointestinal signs include the following:

Hematemesis
Hematochezia

Genitourinary signs include the following:

Signs of azotemia and renal failure
Acidosis
Hematuria
Oliguria
Metrorrhagia
Uterine hemorrhage

Dermatologic signs include the following:

Petechiae
Jaundice (liver dysfunction or hemolysis)
Purpura
Hemorrhagic bullae
Acral cyanosis
Skin necrosis of lower limbs (purpura fulminans)
Localized infarction and gangrene
Wound bleeding and deep subcutaneous hematomas
Thrombosis

Differential Diagnoses

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Diagnostic algorithm for the diagnosis of overt disseminated intravascular coagulation.
Coagulation pathway.

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Table 1. Causes of Acute (Hemorrhagic) Disseminated Intravascular Coagulation

Type	Cause
Infectious	Bacterial (eg, gram-negative sepsis, gram-positive infections, rickettsial) Viral (eg, HIV, cytomegalovirus [CMV], varicella-zoster virus [VZV], and hepatitis virus) Fungal (eg, Histoplasma) Parasitic (eg, malaria)
Malignancy	Hematologic (eg, acute myelocytic leukemia) Metastatic (eg, mucin-secreting adenocarcinoma)
Obstetric	Amniotic fluid embolism Abruptio placentae Acute peripartum hemorrhage Preeclampsia/eclampsia/hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome Retained stillbirth Septic abortion and intrauterine infection Acute fatty liver of pregnancy^[40]
Trauma	Burns Motor vehicle accidents Snake envenomation
Transfusion	Hemolytic reactions Transfusion
Other	Liver disease/acute hepatic failure* Prosthetic devices Shunts (Denver or LeVeen) Ventricular assist devices
*Some do not classify this as DIC; rather, it is liver disease with reduced blood coagulation factor synthesis and reduced clearance of activate products of coagulation.

Table 2. Causes of Chronic Disseminated Intravascular Coagulation

Type	Cause
Malignancies	Solid tumors Leukemia
Obstetric	Retained dead fetus syndrome Retained products of conception
Hematologic	Myeloproliferative syndromes
Vascular	Rheumatoid arthritis Raynaud disease
Cardiovascular	Myocardial infarction
Inflammatory	Ulcerative colitis Crohn disease Sarcoidosis
Localized DIC	Aortic aneurysms Giant hemangioma (Kasabach-Merritt syndrome) Acute renal allograft rejection

Table 3. Main Features of Disseminated Intravascular Coagulation in Series of 118 Patients

Features	Affected Patients, %
Bleeding	64%
Renal dysfunction	25%
Hepatic dysfunction	19%
Respiratory dysfunction	16%
Shock	14%
Central nervous system dysfunction	2%

Table 4. Japanese Association for Acute Medicine (JAAM) Scoring System for DIC

Clinical conditions that should be ruled out
Thrombocytopenia Dilution and abnormal distribution Massive blood loss, massive infusion ITP, TTP-HUS, HIT, HELLP syndrome Disorders of hematopoiesis Liver disease Hypothermia Spurious laboratory results
Diagnostic algorithm for SIRS
Temperature >38°C or < 36°C Heart rate >90 beats/min Respiratory rate >20 breaths/min or PaCO₂< 32 mm Hg (< 4.3 kPa) WBC count >12,000 cells/µL, < 4000 cells/ µL, or 10% immature (band) forms
Diagnostic algorithm SIRS criteria	Score
>3	1
0-2	0
Platelet count (× 10⁹/L)
< 80 or >50 % decrease within 24 hours	3
>80 and < 120 or >30% decrease within 24 hours	1
>120	0
Prothrombin time (value of patient/normal value)
>1.2	1
< 1.2	0
Fibrin/FDPs (mg/L)
>25	3
>10 and < 25	1
< 10	0
Diagnosis 4 points or more	DIC
DIC = disseminated intravascular coagulation; FDP = fibrin degradation product; HELLP = hemolysis, elevated liver enzymes, low platelet count; HIT = heparin-induced thrombocytopenia; HUS = hemolytic uremic syndrome; ITP = idiopathic thrombocytopenic purpura; PaCO₂ = partial pressure of carbon dioxide in arterial blood; SIRS = systemic inflammatory response syndrome; TTP = thrombotic thrombocytopenic purpura; WBC = white blood cell.

Table 5. Japanese Society on Thrombosis and Hemostasis (JSTH) Diagnostic Criteria for DIC

Test Results		Points
Platelet count (×10³/μl)*	80-120	1
	51-80	2
	≤50	3
Fibrin degradation products (FDP; μg/ml)**	10-19	1
	20-39	2
	≥40	3
Fibrinogen (mg/dl)	101-150	1
Fibrinogen (mg/dl)	≤100	2
Prothrombin time ratio	1.25-1.66	1
Prothrombin time ratio	≥1.67	2
Antithrombin (%)	≤70	1
TAT, SF, or F₁₊₂	≥2-fold upper limit of normal	1
Liver failure	Acute: Prothrombin time activity 40% or International Normalized Ratio ≥1.5) Chronic: Cirrhosis with Child-Pugh B or C (≥7 points)	-3
F₁₊₂= prothrombin fragment 1 + 2; SF=soluble fibrin; TAT=thrombin-antithrombin complex For a platelet count of >50 × 10³/μL, add 1 point if the count decreases ≥30% within 24 h. The maximum score for the platelet count is 3 points. *For institutions that do not measure FDP, a D-dimer increase of ≥2-fold the upper limit of normal scores 1 point.

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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, 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, University Hospitals Case Medical Center

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 and Translational Research, International Society on Thrombosis and Haemostasis

Disclosure: Nothing to disclose.

Chief Editor

Srikanth Nagalla, MD, MS, FACP Chief of Benign Hematology, Miami Cancer Institute, Baptist Health South Florida; Clinical Professor of Medicine, Florida International University, Herbert Wertheim College of Medicine

Srikanth Nagalla, MD, MS, FACP is a member of the following medical societies: American Society of Hematology, Association of Specialty Professors

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Alexion; Alnylam; Kedrion; Sanofi; Dova; Apellis; Pharmacosmos<br/>Serve(d) as a speaker or a member of a speakers bureau for: Sobi; Sanofi; Rigel.

Acknowledgements

Jeffrey L Arnold, MD, FACEP Chairman, Department of Emergency Medicine, Santa Clara Valley Medical Center

Jeffrey L Arnold, MD, FACEP is a member of the following medical societies: American Academy of Emergency Medicine and American College of Physicians

Disclosure: Nothing to disclose.

Joseph U Becker, MD Fellow, Global Health and International Emergency Medicine, Stanford University School of Medicine

Joseph U Becker, MD is a member of the following medical societies: American College of Emergency Physicians, Emergency Medicine Residents Association, Phi Beta Kappa, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Barry E Brenner, MD, PhD, FACEP Professor of Emergency Medicine, Professor of Internal Medicine, Program Director, Emergency Medicine, Case Medical Center, University Hospitals, Case Western Reserve University School of Medicine

Barry E Brenner, MD, PhD, FACEP is a member of the following medical societies: Alpha Omega Alpha, American Academy of Emergency Medicine, American College of Chest Physicians, American College of Emergency Physicians, American College of Physicians, American Heart Association, American Thoracic Society, Arkansas Medical Society, New York Academy of Medicine, New York Academy of Sciences, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Steven A Conrad, MD, PhD Chief, Department of Emergency Medicine; Chief, Multidisciplinary Critical Care Service, Professor, Department of Emergency and Internal Medicine, Louisiana State University Health Sciences Center

Steven A Conrad, MD, PhD is a member of the following medical societies: American College of Chest Physicians, American College of Critical Care Medicine, American College of Emergency Physicians, American College of Physicians, International Society for Heart and Lung Transplantation, Louisiana State Medical Society, Shock Society, Society for Academic Emergency Medicine, and Society of Critical Care Medicine

Disclosure: Nothing to disclose.

Brendan R Furlong, MD Clinical Chief, Department of Emergency Medicine, Georgetown University Hospital

Disclosure: Nothing to disclose.

Mary A Furlong, MD Associate Professor and Program/Residency Director, Department of Pathology, Georgetown University School of Medicine

Disclosure: Nothing to disclose.

Avishek Kumar, MD Resident Physician, Department of Internal Medicine, St Michael's Medical Center, Seton Hall University School of Health and Medical Sciences

Avishek Kumar, MD is a member of the following medical societies: American Medical Association

Disclosure: Nothing to disclose.

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

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

Hamid Salim Shaaban MD, Fellow in Hematology/ Oncology, Department of Internal Medicine, Seton Hall University School of Health and Medical Sciences

Hamid Salim Shaaban is a member of the following medical societies: American College of Physicians

Disclosure: Nothing to disclose.

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

Charles R Wira, MD Assistant Professor, Department of Surgery, Section of Emergency Medicine, Yale School of Medicine

Charles R Wira, MD is a member of the following medical societies: American College of Emergency Physicians, Society for Academic Emergency Medicine, and Society of Critical Care Medicine

Disclosure: Nothing to disclose.