Disseminated Intravascular Coagulation in Emergency Medicine Treatment & Management

  • Author: Joseph U Becker, MD; Chief Editor: Barry E Brenner, MD, PhD, FACEP   more...
 
Updated: Oct 26, 2011
 

Prehospital Care

Monitor vital signs, assess and document extent of hemorrhage and thrombosis, correct hypovolemia, and administer basic hemostatic procedures when indicated.

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Emergency Department Care

The management of acute and chronic forms of disseminated intravascular coagulation (DIC) should primarily be directed at treatment of the underlying disorder. Often, the DIC component will resolve on its own with treatment.

Typically, DIC results in significant reductions in platelet count and increases in coagulation times (PT and aPTT). Despite these abnormalities, routine platelet and coagulation factor replacement is not indicated in acute DIC unless ongoing bleeding is present or invasive procedures are planned.

Most clinicians will provide platelet replacement in nonbleeding patients if platelet counts drop below 20 X 106/mL, though the exact levels at which platelets should be transfused is a clinical decision based on each individual patient. In some instances, platelet transfusion is necessary at higher platelet counts, particularly if indicated as per clinical and laboratory findings.[49] In actively bleeding patients, platelet levels from 20 X 106/mL to 50 X 106/mL are grounds for platelet transfusion (1 or 2 units per kg, daily).

Previously, concern has been raised regarding "fueling the fire" of consumption by providing coagulation factor replacement therapy; however, this has never been established in research studies.[50] Current literature suggests that the consumption-induced deficiency of coagulation factors can be partially rectified by the administration of large quantities of FFP, particularly in those patients with elevated INR (>2.0), a 2-times prolongation of aPTT, and/or fibrinogen levels below 100 mg/dL.[51] The suggested starting dose is 15 mg/kg of FFPs.[30]

Cryoprecipitates should not routinely be used as replacement therapy in DIC as they lack several specific factors (factor V). Additionally, worsening of the coagulopathy via the presence of small amounts of activated factors is a theoretical risk. Provision of vitamin K to correct relative deficiencies in the face of consumption may be required.[11, 7, 13]

Anticoagulation in DIC has recently received much attention. Some past experimental studies have suggested that heparin shows some effect in the inhibition of coagulation pathways in DIC.[52] However, the beneficial effect of high- or low-dose heparin therapy in patients with acute DIC has never been convincingly established. Moreover, antithrombin (AT), the primary target of heparin activity is markedly decreased in DIC, limiting the effectiveness of heparin therapy without concomitant replacement of AT.

Furthermore, well-founded concern exists in anticoagulating patients already at high risk for hemorrhagic complications. It is generally agreed that heparin is indicated in cases with obvious thromboembolic disease or where fibrin deposition predominates.[53, 54, 55] The use of heparin in chronic DIC where there is preponderance of coagulation without consumption coagulopathy is well established.[56] Lovenox (Enoxaparin) has also seen use in the treatment and prophylaxis of chronic DIC in specific clinical situations. In a multicenter, cooperative, double-blinded trial in Japan that compared the low molecular weight Fragmin (Dalteparin) with unfractionated heparin, there was a decreased bleeding tendency and reduced organ failure (P < .05).[57]

As stated above, the AT pathway is an important inhibitor of coagulation in normal patients. This system is largely depleted and incapacitated in acute DIC. As a result, several studies have evaluated the utility of AT replacement in DIC. Most have demonstrated benefit in terms of improving laboratory values and even organ function.[38, 58, 59, 60] However, large-scale randomized trials have failed to demonstrate any mortality benefit in patients treated with AT concentrate.

The tissue factor pathway inhibitor (TFPI) mechanism of coagulation inhibition has likewise received attention as a potential therapy in sepsis-associated DIC. Indeed, initial results from animal studies have been very promising in demonstrating the ability of TFPI to arrest DIC and to prevent the mortality and end-organ damage witnessed in untreated animals.[61] However, a large, phase III human trial of TFPI in DIC did not show any mortality benefit.[62]

As with TFPI and AT, activated protein C (APC) is an important regulator of coagulation. It deactivates factor VIIIa and factor Va and additionally has a role in activating protease-activated receptor 1 (PAR-1), which has an inhibitory effect on inflammation and apoptosis.[51] In studies of patients with sepsis who had associated organ failure, APC has been shown to reduce mortality and improve organ function. The PROWESS study (Human Recombinant Activated Protein C Worldwide Evaluation in Sepsis) documented reductions in 28-day mortality and improved organ function in APC-treated patients, despite an increase in the overall number of bleeding complications.[63, 64] These results were confirmed by the ENHANCE trial, which also suggested that APC might be more effective when administered earlier.[65]

A retrospective, subgroup analysis of the PROWESS study demonstrated a lower mortality rate among patients treated with APC who met criteria for DIC with a modified DIC scoring system.[66] Other studies of APC in patients with a low risk of death from sepsis have failed to show an effect, suggesting that APC may be most useful in severely ill patients.[67]

Recombinant thrombomodulin (rTM) can be used for treatment of DIC in cases of severe sepsis and hematopoietic malignancy. Thrombomodulin binds with thrombin, and the resulting complex allows the conversion of protein C to activated protein C. Additionally, thrombomodulin can also bind high-mobility group B (HBGM-1), which inhibits the inflammatory process.[51] The effect of recombinant thrombomodulin was examined in a randomized controlled study with 234 subjects. A significant improvement in controlling DIC was noted versus unfractionated heparin, particularly in regard to the control of persistent bleeding diathesis.[68]

Future directions

As understanding of the inflammatory and coagulation derangements in DIC has improved in recent years, the range of therapeutic considerations has broadened. Treatment modalities focused on the TF-VIIa complex include inactivated factor VII and NAPc2, a member of the nematode family of anticoagulant proteins (NAPs) and an inhibitor of the complex between TF, factor VIIa, and factor Xa. NAPc2 has been observed to inhibit coagulation activation in a primate model of sepsis.[7, 13] Other research has used antibodies against tissue factor/factor VIIa in animal trials, with promising results.[13] Hirudin, a direct inhibitor of thrombin has also been shown to be effective in treating DIC in animal studies.[13]

A small pilot study (5 patients) analyzed the effects of recombinant hirudin (r-hirudin) in relation to thrombin-antithrombin III complex and thrombin-hirudin complex (THC) in patients with DIC. The subsequent results and statistical analysis indicated that r-hirudin was more efficacious in the inhibition of thrombin rather than ATIII without heparin; this suggests that r-hirudin potentially may have a clinical use as a DIC treatment modality.[69]

Recombinant factor VIIa has also been demonstrated to be useful in cases of severe bleeding as can be seen in DIC.[13] However, given the procoagulant effect of rVIIa, a careful consideration of the risks and benefits in patients with DIC should be undertaken before administration. Further, antifibrinolytic agents, such as epsilon-aminocaproic acid or tranexamic acid, can also be considered in patients with DIC in which bleeding predominates. These agents should always be administered with heparin to arrest their prothrombotic effects.[13, 70]

Recognition of the importance of inflammation in both sepsis and DIC has led to further investigation of inhibitors of inflammation. In a murine model, researchers have shown antiselectin antibodies and heparin to block leukocyte and platelet adhesion.[71] Similarly, focus has been placed on interleukin 10 (IL-10), an anti-inflammatory cytokine that may have effects on coagulation activation. Initial studies of IL-10 have shown promise in preventing coagulation activation associated with endotoxemia.[72]

Other researchers have targeted p38 mitogen activated protein kinase (MAPK), an important element in intracellular signaling responsible for inflammatory responses. Inhibition of MAPK has been shown to reduce coagulation activation, fibrinolysis, and endothelial activation in endotoxemia.[73]

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Consultations

  • Consult a hematologist for assistance with diagnosis and management if DIC is suspected based on the clinical picture.
  • Consult a transfusion specialist or a blood bank; determine the availability of general and specialized blood products that may be necessary for the acute management of fulminant DIC.
  • Consult a critical care specialist if multiple organ failure is present.
  • Early consultation is indicated for this complicated, life-threatening condition. Obtain other subspecialty consultations as indicated by the patient's primary diagnosis.
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Proceed to Medication
 
 
Contributor Information and Disclosures
Author

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.

Coauthor(s)

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.

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.

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.

Specialty Editor Board

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.

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

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.

John D Halamka, MD, MS  Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center

John D Halamka, MD, MS is a member of the following medical societies: American College of Emergency Physicians, American Medical Informatics Association, Phi Beta Kappa, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Chief Editor

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.

Additional Contributors

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous authors, Mary A Furlong, MD, and Brendan R Furlong, MD, to the development and writing of this article.

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Table 1. Main Features of DIC in a Series of 118 Patients[31]
Features Affected Patients, %
Bleeding64%
Renal dysfunction25%
Hepatic dysfunction19%
Respiratory dysfunction16%
Shock14%
Central nervous system dysfunction2%
Table 2. DIC Score[1]
Risk assessmentDoes the patient have an underlying disorder (eg, sepsis, trauma, obstetric emergency) compatible with DIC?
Laboratory coagulation testsPlatelet count



D-dimer and FDPs



Fibrinogen



PT and aPTT



ScoringPlatelet count: >100 = 0 points, < 100 = 1 point, < 50 = 2 points



Elevated fibrin marker: No elevation = 0 points, moderate increase = 2 points, strong increase = 3 points



Prolonged PT: < 3 sec = 0 points, >3 < 6 = 1 point, >6 = 2 points



Fibrinogen level: >1 g/L = 0 points, < 1 = 1 point



Calculate scoreGreater than or equal to 5 = compatible with overt DIC, repeat scoring daily



Less than 5 suggestive of non-overt DIC



Table 3: Scoring System for DIC (Japanese Association for Acute Medicine)[47]
Clinical conditions that should be ruled out
Thrombocytopenia



Dilution and abnormal distribution



Massive blood loss, massive infusion



Idiopathic thrombocytopenic purpura (ITP), TTP/HUS, HIT, HELLP



Disorders of hematopoiesis



Liver disease



Hypothermia



Spurious laboratory results



Diagnostic algorithm for systemic inflammatory response syndrome
Temperature >38ºC or < 36ºC



Heart rate >90 beats per minute



Respiratory rate >20 breaths/min or PaCO2 < 32 torr (< 4.3 kPa)



White blood cell >12,000 cells/mm3, < 4000 cells/mm3, or 10% immature (band) forms



Diagnostic algorithm



Systemic inflammatory response system criteria



Score
>31
0-20
Platelet count (109/L)
< 80 or >50 % decrease within 24 hours3
>80 and < 120 or >30% decrease within 24 hours1
>1200
Prothrombin time (value of patient/normal value)
>1.21
< 1.20
Fibrin/fibrinogen degradation products (mg/L)
>253
>10 and < 251
< 100
Diagnosis



4 points or more



DIC
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