Consumption Coagulopathy Medication

Updated: Aug 24, 2017
  • Author: Alexander Gozman, MD; Chief Editor: Robert J Arceci, MD, PhD  more...
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Medication

Medication Summary

Every effort is made to remove the underlying cause, but further management of childhood disseminated intravascular coagulation (DIC) varies. No evidence suggests that replacement blood products exacerbate the problem, and these should be aggressively used to provide hemostasis. The role of heparin is controversial, but it may be beneficial in purpura fulminans.

Activated protein C and protein C products have shown promising results in sepsis-related DIC. Protein C replacement therapy has been shown to lead to increased activated protein C levels, resolution of coagulopathy, and correction of hemostasis. [22, 23, 24, 25] Similarly, recombinant factor VIIa has also been successfully used in a small sample of neonates with DIC, and larger studies are awaited. [26, 27] However, these products are expensive and difficult to obtain, and their benefit in childhood DIC remains unproven.

Despite promising initial pilot studies, a randomized, double-blind, placebo-controlled trial (RESOLVE [REsearching severe Sepsis and Organ dysfunction in children: a gLobal perspectiVE]) of activated drotrecogin alfa (Xigris) in 477 pediatric patients with severe sepsis showed no decrease in mortality. [28]

Drotrecogin alfa (Xigris) was withdrawn from the worldwide market October 25, 2011. In the Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis (PROWESS)-SHOCK clinical trial, drotrecogin alfa failed to demonstrate a statistically significant reduction in 28-day all-cause mortality in patients with severe sepsis and septic shock. Trial results observed a 28-day all-cause mortality rate of 26.4% in patients treated with activated drotrecogin alfa compared with 24.2% in the placebo group of the study.

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Blood products

Class Summary

Blood products are administered for supportive care in children with severe DIC. The goal is to replace platelets, depleted coagulation factors, and fibrinogen.

Platelets

In patients with DIC, platelet activity may be abnormal because of fibrin or fibrinogen degradation products. Therefore, consider platelet transfusions at a platelet count of 50 X 109/L, especially for patients who are intubated and have lines inserted. Most institutions use apheresis-derived platelets administered at 10ml/kg over 1 hour.

Fresh-frozen plasma (FFP)

Considered first-line blood product in patients with bleeding from unknown etiology. Although long-term benefit is uncertain in DIC, it is routine practice to administer FFP to correct the PTT once it exceeds 1.5-2 times normal.

Cryoprecipitate

Contains high concentrations of factor VIII, von Willebrand factor, fibrinogen, and fibronectin. In DIC, main use is to correct hypofibrinogenemia (

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Anticoagulants

Class Summary

In acute DIC, the value of intravenous heparin is uncertain, but it may be used in purpura fulminans. Low-molecular-weight heparin (LMWH) may be used in patients with chronic DIC. No randomized controlled trials have been performed to prove the value for heparin in DIC in adult settings, such as peripartum DIC. [29]

Heparin

Cofactor for antithrombin III; activating stops production of thrombin. Useful in chronic DIC but less effective in acute DIC. aPTT cannot be used to monitor levels of anticoagulation. Some monitor heparin levels. Target heparin levels 0.35-0.7 U/mL with antifactor-Xa method.

Enoxaparin (Lovenox)

Clinical benefit of LMWH primarily seen in chronic DIC.

Thrombomodulin alfa

While the recombinant product is available in Japan and Europe, it is not routinely used in the United States, and its benefit in pediatric DIC is uncertain

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Coagulation inhibitors

Class Summary

Antithrombin III and drotrecogin alfa (recombinant human-activated protein C) both have an antithrombotic effect, but their benefit in sepsis-related childhood DIC remains anecdotal. In the PROWESS-SHOCK trial, administration of recombinant human APC was not shown to improve mortality, and therefore, the drug was withdrawn from the worldwide market on October 25, 2011.

Antithrombin III (ATnativ, Thrombate III)

Concentrate has been used to treat adults with severe DIC resulting from sepsis. Infusion speeds resolution and reduces multiorgan dysfunction. Studies relatively small, and few have involved children. Some recommend use only with concurrent heparin therapy.

Drotrecogin alfa (Xigris)

October 25, 2011: Withdrawn from worldwide market. Recombinant human activated protein C. Was indicated to reduce mortality in patients with severe sepsis associated with acute organ dysfunction and at high risk of death. Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) trial showed a significant decrease in mortality in patients with sepsis and DIC treated with activated protein C. Exerts antithrombotic effect by inhibiting factors Va and VIIIa. Has indirect profibrinolytic activity by inhibiting PAI-1 and limiting formation of activated thrombin-activatable-fibrinolysis-inhibitor. May exert anti-inflammatory effect by inhibiting human TNF production by monocytes, blocking leukocyte adhesion to selectins, and limiting thrombin-induced inflammatory responses within microvascular endothelium.

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Coagulation factors

Class Summary

Recombinant factor VII may help reduce active bleeding, but its benefit in childhood DIC remains anecdotal.

Recombinant coagulation factor VIIa (NovoSeven)

Indicated for hemophilia with inhibitors refractory to routine therapy and for congenital factor VII deficiency. Used off label for uncontrolled bleeding secondary to trauma or DIC and refractory to usual measures. Recombinant activated factor VII complexes with TF to activate factors IX and X, which converts prothrombin to thrombin.

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