eMedicine Specialties > Pediatrics: General Medicine > Hematology
Consumption Coagulopathy: Treatment & Medication
Updated: Jan 6, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Treatment
Medical Care
The most important concept in disseminated intravascular coagulation (DIC) is that it is a secondary manifestation of an underlying disorder.
- The most important therapeutic maneuver is treating the initiating disorder. Without this, supportive measures ultimately fail.
- Shock is a frequent underlying factor, and important supportive measures include ventilatory support, volume support, and pressor support as well as close monitoring of neurologic and renal function. Dialysis may be needed.
Surgical Care
- Involve a pediatric surgeon, as the underlying disorder indicates.
- Surgical complications may include thrombotic occlusion of an artery with imminent loss of limb or organ function, bleeding, or compartment syndrome.
- DIC can result in bleeding at any surgical site.
Consultations
DIC is a complex pediatric disease that is best treated in tertiary care centers by using a multidisciplinary approach. Involving many services may be appropriate.
- Hematologist-oncologist
- Treatment involves complex decisions regarding differential diagnosis and treatment options.
- Involve a pediatric hematologist early.
- If DIC is thought to be secondary to malignancy, a pediatric oncologist can expedite diagnosis.
- Intensivist
- Most children with DIC are critically ill and require monitoring available in the pediatric ICU.
- Many children develop shock and respiratory failure and require ventilatory support.
- Blood bank specialist
- Treatment of patients may involve blood products.
- Blood bank specialists can provide resource advice on treatment decisions.
- Infectious disease specialist: Many children with DIC have underlying sepsis that requires aggressive management.
- Nephrologist: Renal derangement is not uncommon because thrombosis and shock interfere with renal perfusion.
- Neurologist: DIC may cause neurologic symptoms related to CNS thrombosis, infarction, or hemorrhage.
Medication
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.15,16,17,18 Similarly, recombinant factor VIIa has also been successfully used in a small sample of neonates with DIC, and larger studies are awaited.19,20 However, these products are expensive and difficult to obtain, and their benefit in childhood DIC remains unproven.
Blood products
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. Most institutions use apheresis-derived platelets.
Adult
Apheresis-derived units:
Most institutions use apheresis-derived platelets; 1 U IV infused over 1 h should raise the platelet count 30 X 109/L; additional units may be needed if there is a low posttransfusion platelet count, and/or active clinical bleeding
Random-donor units:
6 random-donor platelet units equals 1 unit of single-donor apheresis platelets; 6-8 U IV infused over 1 h should raise the platelet count 30 X 109/L
Pediatric
Apheresis-derived units: 10 mL/kg IV infused over 1 h should raise the platelet count 30 X 109/L
Random-donor units:
If using random donor units, the following should raise the platelet count 30 X 109/L:
Neonates: 0.1 U/kg IV infused over 1 h
Infants: 2 U IV infused over 1 h
Toddlers: 3 U IV infused over 1 h
Children: 4 U IV infused over 1 h
Adolescents: 6-8 U IV infused over 1 h
Avoid coadministration with antiplatelet agents or drugs that may cause thrombocytopenia; administer in IV line dedicated to blood products to avoid incompatibility with drugs
As with all products derived from whole blood, benefits of platelet transfusion must be balanced with risks of transfusion reactions and infection; perform transfusion with great caution in known immunoglobulin A (IgA) deficiency
Pregnancy
A - Fetal risk not revealed in controlled studies in humans
Precautions
Product should be CMV safe and leukoreduced; platelets should be irradiated for patients <6 wk and those with primary (ie, inherited) or secondary (ie, HIV, postchemotherapy, bone marrow transplantation) immunodeficiency; multiple transfusions may sensitize patients to platelet antigens.
Fresh-frozen plasma (FFP)
Considered first-line blood product in patients with bleeding from unknown etiology. In general, no data support use in DIC.
Adult
16 mL/kg IV when aPTT ratio >1.5
Pediatric
10-15 mL/kg IV increase levels of all coagulation factors by 10-20%; in ongoing consumption, repeat q8h
Administer in IV line dedicated to blood products to avoid incompatibility with drugs
As with all products derived from whole blood, benefits of transfusion must be balanced with risks of transfusion reactions and infection
Pregnancy
A - Fetal risk not revealed in controlled studies in humans
Precautions
Volume overload may be a concern in neonates or patients on fluid restrictions
Cryoprecipitate
Contains high concentrations of factor VIII, von Willebrand factor, fibrinogen, and fibronectin. In DIC, main use is to increase fibrinogen levels in patients with hypofibrinogenemia. Some suggest use only in patients with DIC that is self-limited, resolving, or controlled with heparin. Concern is that no HIV-inactivated products are available.
Adult
1 U raises fibrinogen by 6-8 mg/dL
Pediatric
One half pack/kg increases factor VIII by 80-100% and fibrinogen by 200-250 mg/dL; consider repeat infusion on basis of laboratory assessment and patient's condition
Administer in IV line dedicated to blood products to avoid incompatibility with drugs
Uncontrolled DIC
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Thrombosis in some adults
Anticoagulants
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.
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.
Adult
5-10 U/kg/h IV without bolus; adjust to response
Pediatric
Administer as in adults
Drugs that interfere with platelet function (eg, acetylsalicylic acid, NSAIDs, acetaminophen, penicillins, cephalosporins, nitrates, nitroprusside, psychotropic drugs) may increase risk of bleeding; digoxin, nicotine, tetracycline, and antihistamines may decrease effects
Documented hypersensitivity; bleeding; decide use of heparin in DIC on individual basis
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
May increase bleeding in DIC; in neonates, preservative-free heparin recommended to avoid possible toxicity (gasping syndrome) due to benzyl alcohol (preservative); caution in severe hypotension and shock; monitor for bleeding in peptic ulcer disease
Enoxaparin (Lovenox)
Clinical benefit of LMWH primarily seen in chronic DIC.
Adult
Not established
Pediatric
No studies in pediatric DIC; therefore, appropriate dosing difficult to determine
For anticoagulation in deep venous thrombosis (DVT) treatment, DVT prophylaxis, or treatment of thrombosis after resolution of DIC: 1-2 mg/kg/d SC divided bid; target antifactor-Xa activity (heparin level) for DVT treatment is 0.5-1 U/mL
Drugs that interfere with platelet function (eg, acetylsalicylic acid, NSAIDs, acetaminophen, penicillins, cephalosporins, nitrates, nitroprusside, psychotropic drugs)
Documented hypersensitivity; profuse bleeding
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
May increase bleeding in DIC
Coagulation inhibitors
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.
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.
Adult
3000-6000 U/d IV q12h or qd
Total U = (desired level - initial level) (0.6 X total body weight in kg)
IV q8h with desired level >125% loading dose of 100 U/kg IV over 3 h followed by continuous infusion of 100 U/kg/d
Pediatric
No standard achieved for dosing in DIC; dosages include 250 U IV q8h
Neonates: 40-60 U/kg/d along with heparin 200 U/kg/d)
120-250 U/kg/d IV continuous infusion; goal is to achieve antithrombin III levels of 100-120%
Enhances anticoagulant effect of heparin
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Despite measures to remove infectious agents from human product, may transmit disease or contain unknown infectious agents
Drotrecogin alfa (Xigris)
Recombinant human activated protein C. 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.
Adult
24 mcg/kg/h IV continuous infusion for 96 h; ideally start within 48 h of onset of sepsis
Pediatric
Not established
None reported; coadministration with drugs that affect hemostasis may increase risk of bleeding (eg, warfarin, heparin, thrombolytics, glycoprotein IIb/IIIa inhibitors)
Documented hypersensitivity; increased risk of bleeding (eg, active internal bleeding, recent hemorrhagic stroke, recent intraspinal or intracranial surgery, recent or current trauma, epidural catheter, intracranial neoplasm, cerebral herniation, severe head trauma)
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Bleeding most common serious adverse effect; caution in conditions that increase risk of bleeding: international normalized ratio (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 administration of platelet inhibitors; within 3 mo of ischemic stroke, intracranial arteriovenous malformation or aneurysm, known bleeding diathesis, or chronic severe hepatic disease; stop infusion if clinically significant bleeding occurs
Coagulation factors
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.
Adult
60-120 mcg/kg IV bolus; may repeat after 2-6 h
Pediatric
Not established
Coadministration with activated prothrombin complex concentrates (ie, FEIBA, Autoplex T) or
prothrombin complex concentrates (eg, AlphaNine, BeneFix) may increase risk of thrombosis
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Monitor for signs of thrombosis or activation of coagulation system; thrombotic events may increase in advanced atherosclerotic disease, crush injury, sepsis, or DIC
More on Consumption Coagulopathy |
| Overview: Consumption Coagulopathy |
| Differential Diagnoses & Workup: Consumption Coagulopathy |
 Treatment & Medication: Consumption Coagulopathy |
| Follow-up: Consumption Coagulopathy |
| Multimedia: Consumption Coagulopathy |
| References |
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References
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Further Reading
Keywords
consumption coagulopathy, disseminated intravascular coagulation, DIC, sepsis, sepsis-related DIC, trauma, massive head injuries, excess production of thrombin, brain trauma, acute promyelocytic leukemia, APL, hypotension, snake venom, snake bites, placental abruption, eclampsia, premature rupture of membranes, maternal fever, Kasabach-Merritt syndrome, Klippel-Trenaunay syndrome, vascular malformations, malignancy, thrombotic disorder, purpura fulminans, varicella, protein C deficiency, meningococcemia, Rocky Mountain spotted fever, herpes simplex, hepatitis, cytomegalovirus, CMV, Aspergillus infection, histoplasmosis, malaria, trypanosomiasis, neuroblastoma, systemic lupus erythematosus, juvenile rheumatoid arthritis
