Disseminated Intravascular Coagulation Treatment & Management

Treatment of disseminated intravascular coagulation (DIC) is controversial but treatment guidelines have been published.^[13]

• 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 disseminated intravascular coagulation (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; it 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 disseminated intravascular coagulation (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 aPTT and PT, 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 disseminated intravascular coagulation (DIC) and severe thrombocytopenia, in particular, in patients with bleeding or in patients at risk for bleeding (eg, 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 < 50 × 10⁹/L. In nonbleeding patients, a much lower threshold for platelet transfusion is used (usually < 10-20 × 10⁹/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 cases of sepsis and other causes of disseminated intravascular coagulation (DIC). Uncontrolled case series in patients with disseminated intravascular coagulation (DIC) have claimed to be successful. However, a beneficial effect of heparin on clinically important outcome events in patients with disseminated intravascular coagulation (DIC) has never been demonstrated in controlled clinical trials. Also, the safety of heparin treatment is debatable in patients with disseminated intravascular coagulation (DIC) who are prone to bleeding. One randomized clinical trial showed superiority of (low molecular weight) heparin in reducing 28-day mortality in patients with severe sepsis.^[15] 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 disseminated intravascular coagulation (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 disseminated intravascular coagulation (DIC) is directed against tissue factor activity. Potential agents, which are under evaluation in clinical trials, include recombinant TFPI, inactivated factor VIIa, and recombinant nematode anticoagulant peptide (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 2 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, 6.6-30.5). 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.
  • Another study showed that patients with disseminated intravascular coagulation (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 in 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 disseminated intravascular coagulation (DIC) .
  • A nonrandomized comparison between heparin and activated protein C in patients with disseminated intravascular coagulation (DIC) showed a more rapid resolution of disseminated intravascular coagulation (DIC), although the study was too small to demonstrate effects on organ failure and mortality.
  • Because antithrombin is one of the most important physiologic inhibitors of coagulation and based on successful preclinical results, the use of antithrombin III concentrates in patients with disseminated intravascular coagulation (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 supraphysiologic 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.
    • In another study that evaluated the effects of antithrombin III in 23 patients with disseminated intravascular coagulation (DIC) diagnosed by the based on the Japanese Association for Acute Medicine (JAAM) criteria (a newly developed diagnostic criteria for critical illness), patients were treated with either high-dose (60 IU/kg/d; 12 patients) or low-dose (30 IU/kg/d; 11 patients) antithrombin concentrates for 3 days.^[16]
    • On day 0, the patients' backgrounds and antithrombin activity were identical in both groups. However, on day 7, the JAAM DIC score and PT ratio were significantly improved when compared with those on day 0. However, mortality at 28 days and interaction within the administered antithrombin doses showed no difference.^[16]
    • There were also no differences in the time course of the platelet counts, coagulation and fibrinolytic markers, and DIC scores in the 2 groups. The authors concluded that the effects of antithrombin on prognosis and coagulation and fibrinolytic parameters are independent of the doses administered in patients with systemic inflammatory response syndrome (SIRS)/sepsis-associated disseminated intravascular coagulation (DIC).^[16]
  • Recombinant soluble thrombomodulin is a new intervention that is currently evaluated in clinical studies and showed beneficial effects on DIC parameters and clinical outcome in initial trials.^[17]

Surgical treatment is limited to primary treatment for certain underlying etiologies in cases of disseminated intravascular coagulation (DIC).