AUTHOR AND EDITOR INFORMATION

Section 1 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

INTRODUCTION

Section 2 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Background

Disseminated intravascular coagulation (DIC) is not a specific diagnosis and its presence always indicates another underlying disease. There are many diseases that may lead to the occurrence of DIC (see Causes).

DIC is characterized by a systemic activation of the blood coagulation system, which results in the generation and deposition of fibrin, leading to microvascular thrombi in various organs and contributing to the development of multiorgan failure. Consumption and subsequent exhaustion of coagulation proteins and platelets, due to the ongoing activation of the coagulation system, may induce severe bleeding complications, although microclot formation may occur in the absence of severe clotting factor depletion and bleeding (Levi, 1999).

Derangement of the fibrinolytic system further contributes to intravascular clot formation, but in some cases, accelerated fibrinolysis (eg, due to consumption of alpha2-antiplasmin) may cause severe bleeding. Hence, a patient with DIC can present with a simultaneously occurring thrombotic and bleeding problem, which obviously complicates the proper treatment.

Pathophysiology

Several simultaneously occurring mechanisms play a role in the pathogenesis of DIC. Main pathways leading to fibrin deposition are (1) tissue factor-mediated thrombin generation and (2) dysfunctional physiologic anticoagulant mechanisms, such as the antithrombin system and the protein C system, which insufficiently balance this thrombin generation. A third pathway in addition to enhanced fibrin formation is impaired fibrin removal due to depression of the fibrinolytic system. This impairment of endogenous thrombolysis is mainly caused by high circulating levels of the fibrinolytic inhibitor PAI-1. As mentioned before, in exceptional forms of DIC, fibrinolytic activity may be increased and contribute to bleeding. These mechanisms are outlined in more detailed in the following:

Thrombin generation and tissue factor

Thrombin generation is detectable at 3-5 hours after the occurrence of bacteremia or endotoxemia. Ample evidence exists for a pivotal role of the tissue factor/factor VIIa system in the initiation of thrombin generation. Abrogation of the tissue factor/factor VII(a) pathway by monoclonal antibodies specifically directed against tissue factor or factor VIIa activity resulted in a complete inhibition of thrombin generation in endotoxin-challenged chimpanzees and prevented the occurrence of DIC and mortality in baboons that were infused with Escherichia coli. Indeed in most patients with DIC, tissue factor antigen is detectable in plasma. Hence, activation of coagulation in DIC is tissue factor–driven, whereas the intrinsic pathway of coagulation was shown not to play an important role.

An unresolved issue concerns the actual source of the tissue factor: Tissue factor may be expressed on mononuclear cells in vitro and tissue factor expression on circulating monocytes of patients with severe infection has indeed been demonstrated. In addition, tissue factor may be expressed on endothelial cells, although the importance of endothelial cell tissue factor expression in vivo and its role in the pathogenesis of DIC is disputed.

Another source of tissue factor may be its localization on polymorphonuclear cells and other cell types, although it is unlikely that these cells actually synthesize tissue factor in substantial quantities. Based on the observation of transfer of tissue factor from leucocytes to activated platelets on a collagen surface in an ex vivo perfusion system, it is hypothesized that this "blood borne" tissue factor is transferred between cells through microparticles derived from activated mononuclear cells.

Impaired coagulation inhibitor systems

An impaired function of various natural regulating pathways of coagulation activation may amplify the further thrombin generation and contribute to fibrin formation. Plasma levels of the most important inhibitor of thrombin, antithrombin III, are usually markedly reduced in patients with DIC. This reduction is caused by a combination of consumption, due to ongoing thrombin generation, degradation by elastase, that is released from activated neutrophils, and impaired synthesis. Low antithrombin III levels in DIC are associated with increased mortality. The fact that low levels of antithrombin precede the clinical manifestation of sepsis in prospective studies suggests that antithrombin is indeed involved in the pathogenesis of this disease and associated organ dysfunction (Mesters, 1996).

In addition to the decrease in antithrombin III, a significant depression of the protein C system may occur. This impaired function of the protein C pathway is mainly due to downregulation of thrombomodulin expression on endothelial cells by proinflammatory cytokines, like tumor necrosis factor-alpha (TNF-alpha) and interleukin 1b (IL-1b). The downregulation of thrombomodulin has been confirmed in studies in patients with meningococcal sepsis. This, in combination with low levels of zymogen protein C (due to similar mechanisms as described for antithrombin) results in diminished protein C activation, which will enhance the procoagulant state.

Animal experiments of severe inflammation-induced coagulation activation convincingly show that compromising the protein C system results in increased morbidity and mortality, whereas restoring an adequate function of activated protein C improves survival and organ failure. Interestingly, recent experiments in mice with a one-allele targeted deletion of the protein C gene (resulting in heterozygous protein C deficiency) have more severe DIC and organ dysfunction and a higher mortality than wild-type littermates. Besides being implicated in the physiological regulation of thrombin formation, activated protein C probably also has important inflammation-modulating effects, which may be of relevance in the pathogenesis of DIC.

The third significant inhibitor of coagulation is tissue factor pathway inhibitor (TFPI). The role of TFPI in the pathogenesis of DIC is not completely clear. Experiments showing that administration of recombinant TFPI (and thereby achieving higher than physiological plasma concentrations of TFPI) blocks inflammation-induced thrombin generation in humans and the observation that pharmacologic doses of TFPI are capable of preventing mortality during systemic infection and inflammation suggest that high concentrations of TFPI are capable of modulating tissue factor–mediated coagulation. However, the endogenous concentration of TFPI is presumably insufficiently capable of regulating coagulation activation and downstream consequences during systemic inflammation.

Defective fibrinolysis

Experimental models indicate that at the time of maximal activation of coagulation, the fibrinolytic system is largely shut off. Experimental bacteremia and endotoxemia result in a rapidly occurring increase in fibrinolytic activity, most probably due to the release of plasminogen activators from endothelial cells. However, this profibrinolytic response is almost immediately followed by a suppression of fibrinolytic activity due to a sustained increase in plasma levels of plasminogen activator inhibitor, type 1 (PAI-1). Of note, strategies that are able to completely block the endotoxin-induced thrombin generation, such as anti-tissue factor antibodies or recombinant hirudin, were without any effect on the activation and subsequent inhibition of fibrinolysis, suggesting an independent regulation of these two processes.

Rare cases of DIC are characterized by a severe hyperfibrinolytic state on top of an activated coagulation system. Examples of such situations are the DIC that occurs as a complication of acute promyelocytic leukemia (acute myeloid leukemia M-3, according to the FAB-classification) or the DIC that may occur secondary to some forms of adenocarcinoma (for example prostatic cancer). Although hyperfibrinolysis predominates in this situation, disseminated thrombosis is still found in a considerable number of patients at autopsy. Clinically, however, these patients suffer from severe bleeding.

Mortality/Morbidity

Obviously, the clinical importance of a severe depletion of platelets and coagulation factors in patients with diffuse, widespread bleeding or in patients who need to undergo an invasive procedure is clear. In addition, intravascular deposition of fibrin, as a result of the systemic activation of coagulation, contributes to organ failure and mortality.

Histologic studies in patients with DIC show the presence of ischemia and necrosis due to fibrin deposition in small- and mid-size vessels of various organs. The presence of these intravascular thrombi appears to be clearly and specifically related to the clinical dysfunction of the organ. Specific thrombotic complications that are sometimes seen in the framework of DIC are acral cyanosis, hemorrhagic skin infarcts, and limb ischemia.

Secondly, experimental animal studies of DIC show fibrin deposition in various organs. Amelioration of DIC by various interventions appears to improve organ failure and, in some but not all cases, mortality.

Lastly, DIC has shown to be an independent predictor of mortality in patients with sepsis and severe trauma. The presence of DIC may increase the risk of death by 1.5 to 2.0 in various studies. Increasing severity of DIC is directly related to increased mortality.

Race

DIC occurs in all races.

Sex

No particular gender predisposition exists.

Age

DIC affects all ages.

CLINICAL

Section 3 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

History

The symptoms of DIC often are those of the underlying inciting condition (see Causes). In addition, symptoms of thrombosis, embolism, organ dysfunction, or bleeding may be present.

• Sepsis/severe infection (any microorganism)
• Trauma (eg, polytrauma, neurotrauma, fat embolism)
• Organ destruction (eg, severe pancreatitis)
• Malignancy
• • Solid tumors
  • Myeloproliferative/lymphoproliferative malignancies
• Obstetric calamities
• • Amniotic fluid embolism
  • Abruptio placentae
• Vascular abnormalities
• • Kasabach-Merritt syndrome
  • Large vascular aneurysms
• Severe hepatic failure
• Severe toxic or immunologic reactions
• • Snake bites
  • Recreational drugs
  • Transfusion reactions
  • Transplant rejection

Physical

• Acute DIC: The physical findings associated with DIC usually are those of the underlying or inciting etiology; however, patients with acute DIC (ie, hemorrhagic variety associated with excess plasmin formation) have petechiae on the soft palate and legs from thrombocytopenia and ecchymosis at the venipuncture sites. These patients also manifest with ecchymosis in traumatized areas.
• Chronic or subacute DIC: In patients with so-called chronic or subacute DIC whose manifestation is thrombosis from excess thrombin formation, the symptoms and signs of venous thromboembolism may be present.

Causes

Several disease states may lead to the development of DIC. In general, two major pathways may cause DIC: (1) a systemic inflammatory response, leading to activation of the cytokine network and subsequent activation of coagulation (eg, in sepsis or major trauma), and/or (2) release or exposure of procoagulant material into the bloodstream (eg, in cancer or in obstetric cases). In some situations, both pathways may be present (for example, major trauma or severe necrotizing pancreatitis). Some of the most frequently occurring conditions are outlined below.

• Bacterial infection, in particular septicemia, is commonly associated with DIC. No difference exists in the incidence of DIC in patients with gram-negative sepsis or gram-positive sepsis. In addition, systemic infections with other microorganisms, such as viruses and parasites, may lead to DIC as well. Factors involved in the development of DIC in patients with infections may be specific cell membrane components of the microorganism (lipopolysaccharide or endotoxin) or bacterial exotoxins (eg, staphylococcal alpha toxin). These components cause a generalized inflammatory response, characterized by the systemic occurrence of proinflammatory cytokines.
• Severe trauma is another clinical condition frequently associated with DIC. A combination of mechanisms—including release of tissue material (fat, phospholipids) into the circulation, hemolysis, and endothelial damage—may contribute to the systemic activation of coagulation. In addition, solid evidence indicates that cytokines play a pivotal role in the occurrence of DIC in trauma patients as well. In fact, systemic cytokine patterns have been shown to be virtually identical in trauma patients and septic patients.
• Both solid tumors and hematologic malignancies may be complicated by DIC. The mechanism of the derangement of the coagulation system in this situation is poorly understood. Solid tumor cells can express different procoagulant molecules, including tissue factor and a cancer procoagulant, a cysteine protease with factor X–activating properties. Cancer procoagulant is found in extracts of neoplastic cells and in the plasma of patients with solid tumors. Some tumors are associated with a form of DIC that is characterized by severe hyperfibrinolysis on top of an activated coagulation system. For example, this is the case in acute promyelocytic leukemia and some forms of prostatic cancer. Although clinically bleeding predominates in this situation, disseminated thrombosis is found in a considerable number of patients at autopsy.
• Acute DIC occurs in obstetric calamities such as placental abruption and amniotic fluid emboli. Amniotic fluid has been shown to be able to activate coagulation in vitro, and the degree of placental separation correlates with the extent of DIC, suggesting that leakage of thromboplastinlike material from the placental system is responsible for the occurrence of DIC. Although the coagulation system may be activated in patients with preeclampsia, and HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome, clinically significant DIC only occurs in a small percentage of patients, usually with secondary complications.
• Vascular disorders, such as large aortic aneurysms or giant hemangiomas (Kasabach-Merritt syndrome), may result in local activation of coagulation. Activated coagulation factors can ultimately "overflow" to the systemic circulation and cause DIC but more common is the systemic depletion of coagulation factors and platelets as a result of local consumption.
• Other causes of DIC include severe toxic or immunologic reactions (eg, transfusion reactions) or severe inflammation (eg, acute pancreatitis).

DIFFERENTIALS

Section 4 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Other Problems to be Considered

Hemostatic disorders
Heparin-induced thrombocytopenia
Thrombotic microangiopathy (includes TTP, HUS, but also chemotherapy-induced or stem cell transplant–associated microangiopathy, HIV-induced TTP)

WORKUP

Section 5 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Lab Studies

• No single routinely available laboratory test is sufficiently sensitive or specific to allow a diagnosis of DIC.
• Specialized tests
• • In a specialized setting, molecular markers for activation of coagulation or fibrin formation may be the most sensitive assays. A number of clinical studies show that the presence of soluble fibrin in plasma has a 90-100% sensitivity for the diagnosis of DIC, but unfortunately the specificity is low. Another problem is that a reliable test for quantifying soluble fibrin in plasma is not available, and a recent study showed a wide discordance among various assays.
  • The dynamics of 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 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 can often not be used in a routine setting.
  • Routine tests
  • In clinical practice, a diagnosis of DIC often can 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 FDPs. It should be emphasized that serial coagulation tests are usually more helpful than single laboratory results in establishing the diagnosis of DIC. A reduction in the platelet count or a clear downward trend at subsequent measurements is a sensitive (though not specific) sign of 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 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 DIC but in fact 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 DIC was only 28%, and hypofibrinogenemia was detected in a very small number of severe cases of DIC only. Sequential measurements of fibrinogen might be more useful and provide diagnostic clues.
  • Tests for fibrin degradation products (eg, FDPs or D-dimer) may be helpful to differentiate 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 a test for fibrin degradation products operational. Fibrin degradation products (eg, 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 fibrinogen degradation products, 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 DIC, but poorly distinguish patients with DIC from patients with trauma or recent surgery.
• 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 DIC of the International Society on Thrombosis and Haemostasis (see Image 1). The presence of an underlying disorder known to be associated with DIC, as listed above, 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 DIC. Initial prospective validation studies show a high accuracy of this scoring system for the diagnosis of DIC. The sensitivity of the DIC score for a diagnosis of DIC is 91% and the specificity is 97%. Other analyses show that the DIC scoring system is a strong independent predictor of a fatal outcome in intensive care patients. These studies show that patients with sepsis and DIC, according to the scoring system, have a mortality of more than 40% compared with about 25% in patients without DIC.
  • For each DIC point in the system, the odds ratio for mortality is 1.29, whereas, in comparison, for each APACHE point, the odds ratio for mortality is 1.07.

Imaging Studies

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

Procedures

• No specific procedures help to diagnose DIC. All procedures may help to diagnose the underlying etiology.

Histologic Findings

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

TREATMENT

Section 6 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Medical Care

Treatment of DIC is controversial.

• Underlying disease
• • The first step is to treat the underlying disease.
  • For example, if infection is the underlying etiology, the appropriate administration of antibiotics and source control is the first line of therapy.
  • In case of an obstetric catastrophe, the primary approach is to deliver appropriate obstetric care, in which case the DIC will rapidly subside.
• Adjunctive treatment strategies
• • Platelet and plasma (component) transfusion
    • Low levels of platelets and coagulation factors may increase the risk of bleeding. However, plasma or platelet substitution therapy should not be instituted on the basis of laboratory results alone but is only indicated in patients with active bleeding and in those requiring an invasive procedure or who are otherwise at risk for bleeding complications. The suggestion that administration of blood components might add "fuel to the fire" has in fact never been proven in clinical or experimental studies. The presumed efficacy of treatment with plasma or platelets is not based on randomized controlled trials but appears to be rational therapy in bleeding patients or in patients at risk for bleeding with a significant depletion of these elements.
    • Coagulation factor concentrates, such as prothrombin complex concentrate, will overcome this obstacle, but these compounds lack essential factors, such as factor V. Moreover, in older literature caution is advocated with the use of prothrombin complex concentrates in DIC because it may worsen the coagulopathy due to small traces of activated factors in the concentrate. However, whether this is still relevant for the concentrates that are currently in use is not clear. Specific deficiencies in coagulation factors, such as fibrinogen, can be corrected by administration of purified coagulation factor concentrates.
    • Repeated measurement of global clotting tests, such as prothrombin time and activated partial thromboplastin time, might be useful to monitor the coagulation defect. In case of a (relative) vitamin K deficiency, administration of vitamin K is required.
    • Platelet transfusion may be considered in patients with DIC and severe thrombocytopenia, in particular in patients with bleeding or in patients at risk for bleeding, for example, in the early postoperative phase or if an invasive procedure is planned. The threshold for transfusing platelets depends on the clinical situation of the patient. In general, platelet transfusions are administered to patients who bleed and who have a platelet count of <50X10⁹/L. In nonbleeding patients, a much lower threshold for platelet transfusion is used (usually <10-20X10⁹/L), which is based on randomized controlled trials in patients with thrombocytopenia following chemotherapy.
  • Anticoagulant therapy
    • Experimental studies have shown that heparin can at least partly inhibit the activation of coagulation in sepsis and other causes of DIC. Uncontrolled case series in patients with DIC have claimed to be successful. However, a beneficial effect of heparin on clinically important outcome events in patients with DIC has never been demonstrated in controlled clinical trials. Also, the safety of heparin treatment is debatable in patients with DIC who are prone to bleeding. Therapeutic doses of heparin are indicated in patients with clinically overt thromboembolism or extensive fibrin deposition, such as purpura fulminans or acral ischemia.
    • Patients with DIC may benefit from prophylaxis to prevent venous thromboembolism, which will not be achieved with standard low-dose subcutaneous heparin. Theoretically, the most logical anticoagulant agent to use in DIC is directed against tissue factor activity. Potential agents, which are currently being evaluated in clinical trials, include recombinant tissue factor pathway inhibitor (TFPI), inactivated factor VIIa, and recombinant NAPc2, a potent and specific inhibitor of the ternary complex between tissue factor/factor VIIa and factor Xa.
  • Restoration of anticoagulant pathways
    • These strategies comprise administration of recombinant human activated protein C or antithrombin concentrate.
    • In experimental sepsis studies, activated protein C was shown to be effective in reducing mortality and organ failure. A beneficial effect of recombinant human activated protein C was demonstrated in two randomized controlled trials. Administration of recombinant human activated protein C in a large phase III randomized controlled clinical trial resulted in reduction of mortality to 24.7% compared with 30.8% in the placebo group (relative risk reduction 19.4%, 95% confidence interval, 6.6 to 30.5). In line with the beneficial effect on mortality, coagulation, and inflammation, organ function scores were significantly lower (ie, less organ failure) in the activated protein C group compared with the placebo group.
    • A recent study shows that patients with DIC in particular have the highest benefit of activated protein C treatment. Importantly, administration of activated protein C was effective in patients with a protein C deficiency at study entry as well as patients who had normal protein C levels. This finding may underline the importance of administering activated protein C rather the zymogen protein C in patients with DIC.
    • A recent nonrandomized comparison between heparin and activated protein C in patients with DIC showed a more rapid resolution of DIC, although the study was too small to demonstrate effects on organ failure and mortality.
    • Because antithrombin is one of the most important physiological inhibitors of coagulation and based on successful preclinical results, the use of antithrombin III concentrates in patients with DIC has been studied relatively intensively. Most of the randomized controlled trials concern patients with sepsis and/or septic shock. In the more recent clinical trials, very high doses of antithrombin concentrate to attain supraphysiological plasma levels were used. A series of relatively small trials showed a modest reduction in mortality in antithrombin-treated patients. However, in none of the trials, the effect reached statistical significance.

      A large-scale multicenter randomized controlled trial to directly address this issue showed no significant reduction in mortality of septic patients who were treated with antithrombin concentrate. In this trial, 2114 patients with severe sepsis and associated organ failure were included. Surprisingly, subgroup analyses indicated some benefit in patients who did not receive concomitant heparin, but this observation needs prospective validation.

Surgical Care

Surgical treatment is limited to primary treatment for certain underlying etiologies.

MEDICATION

Section 7 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

The goals of pharmacotherapy are to reduce morbidity and to prevent complications.

Drug Category: Anticoagulants

Heparin is the only currently available antithrombotic drug that has a role in the treatment of patients with DIC. Although most experience is with standard heparin, low molecular weight heparins are increasingly used. Although low molecular weight heparin usually does not require laboratory monitoring, it may be advisable to check anti-factor Xa levels in critically ill patients with serious renal failure.

Drug Name	Drotecogin alfa (Xigris)
Description	Indicated for reduction of mortality in patients with severe sepsis associated with acute organ dysfunction and at high risk of death. Recombinant form of human activated protein C that exerts antithrombotic effect by inhibiting factors Va and VIIIa. Has indirect profibrinolytic activity by inhibiting plasminogen activator inhibitor-1 (PAI-1) and limiting formation of activated thrombin-activatable-fibrinolysis-inhibitor. May exert anti-inflammatory effect by inhibiting human tumor necrosis factor (TNF) production by monocytes, blocking leukocyte adhesion to selectins, and limiting thrombin-induced inflammatory responses within microvascular endothelium.
Adult Dose	24 mcg/kg/h IV continuous infusion for 96 h; ideally, initiate within 48 h of sepsis onset
Pediatric Dose	Not established
Contraindications	Drotecogin alfa should not be used in case of severe thrombocytopenia (platelet count <30X109/L Documented hypersensitivity; increased risk of bleeding (eg, active internal bleeding, recent hemorrhagic stroke, recent intraspinal or intracranial surgery, recent or current trauma, presence of epidural catheter, intracranial neoplasm, cerebral herniation, severe head trauma)
Interactions	None reported; coadministration with drugs that affect hemostasis may increase risk of bleeding (eg, warfarin, heparin, thrombolytics, glycoprotein IIb/IIIa inhibitors)
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Bleeding is most common serious adverse effect; caution with conditions that increase risk of bleeding including INR >3, concurrent therapeutic heparin (>15 U/kg/h), within 6 wk of GI bleeding episode, within 3 d of thrombolytic therapy, within 7 d of platelet inhibitors administration, within 3 mo of ischemic stroke, intracranial arteriovenous malformation or aneurysm, known bleeding diathesis, chronic severe hepatic disease; stop infusion if clinically significant bleeding occurs

FOLLOW-UP

Section 8 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Further Inpatient Care

• If unclear, a diagnostic workup in search of the underlying condition causing DIC should be initiated.

Complications

• Death is the most serious complication.
• Organ dysfunction and limb ischemia may occur.
• Bleeding, which can be excessive, may seriously complicate the clinical course of a patient with DIC.

Prognosis

• The prognosis depends on the underlying disorder. If the underlying condition is self-limited or can be appropriately handled, the DIC will disappear and the coagulation status will normalize.

Patient Education

• For excellent patient education resources, visit eMedicine's Skin, Hair, and Nails Center. Also, see eMedicine's patient education article Bruises.

MISCELLANEOUS

Section 9 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Medical/Legal Pitfalls

• Failure to recognize the underlying etiology
• Failure to understand that a good patient outcome is more dependent on the nature of the underlying etiology than on the DIC itself, such as the following:
• • A patient with acute hemorrhagic DIC that is associated with metastatic gastric carcinoma likely has a lethal condition, one that does not alter patient demise, regardless of treatment.
  • Alternatively, a patient with acute DIC associated with abruptio placenta needs quick recognition and obstetric treatment; the DIC resolves when treating the obstetrical catastrophe.

MULTIMEDIA

Section 10 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Media file 1:  Diagnostic algorithm for the diagnosis of overt disseminated intravascular coagulation.
	View Full Size Image
Media type:  Image

REFERENCES

Section 11 of 11

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

• Dhainaut JF, Yan SB, Joyce DE. Treatment effects of drotrecogin alfa (activated) in patients with severe sepsis with or without overt disseminated intravascular coagulation. J Thromb Haemost. Nov 2004;2(11):1924-33.
• Levi M, Ten Cate H. Disseminated intravascular coagulation. N Engl J Med. Aug 19 1999;341(8):586-92. [Medline].
• Levi M. Current understanding of disseminated intravascular coagulation. Br J Haematol. Mar 2004;124(5):567-76.
• Levi M. Disseminated intravascular coagulation: What''s new?. Crit Care Clin. Jul 2005;21(3):449-67.
• Mesters RM, Mannucci PM, Coppola R. Factor VIIa and antithrombin III activity during severe sepsis and septic shock in neutropenic patients. Blood. Aug 1 1996;88(3):881-6. [Medline].
• Schmaier AH. Disseminated intravascular coagulation - pathogenesis and management. J Intensive Care Med. 1991;6:209-228.
• Taylor FB, Toh CH, Hoots WK. Towards definition, clinical and laboratory criteria, and a scoring system for disseminated intravascular coagulation. Thromb Haemost. Nov 2001;86(5):1327-30. [Medline].
• Vincent JL, De Backer D. Does disseminated intravascular coagulation lead to multiple organ failure?. Crit Care Clin. Jul 2005;21(3):469-77.

Article Last Updated: Jun 5, 2006