para>Neonatal purpura fulminans is associated with DIC and protein C or protein S deficiency (homozygous).
DIAGNOSIS
Symptoms and signs are related to the underlying disease process and DIC.
HISTORY
Symptoms of microvascular thrombosis (e.g., renal failure, hepatic and neurologic dysfunctions) as well as diffuse bleeding
PHYSICAL EXAM
- Bleeding manifestations are as follows:
- Skin (petechiae, purpura, ecchymosis, generalized oozing from venipuncture sites and wounds)
- Renal (hematuria)
- GI (mucous membranes and intestinal bleeding)
- Neurologic (hemorrhagic infarction, massive intracerebral bleeding)
- Respiratory (epistaxis, pulmonary hemorrhage)
- Adrenal (Waterhouse-Friderichsen syndrome from hemorrhage)
- Microvascular thrombosis
- Skin (skin infarction, digital gangrene)
- GI (mucosal ulcerations, bowel infarction)
- Renal (oliguria, anuria, uremia)
- Pulmonary (hypoxemia, acute respiratory distress syndrome)
- Neurologic (convulsions, delirium, coma, multifocal cortical infarction)
DIFFERENTIAL DIAGNOSIS
- Fulminant liver failure or massive hepatic necrosis
- Vitamin K deficiency
- Thrombotic thrombocytopenic purpura
- Hemolytic-uremic syndrome
- Heparin-induced thrombocytopenia
- Primary fibrinolysis
- HELLP syndrome in pregnancy
DIAGNOSTIC TESTS & INTERPRETATION
No single laboratory test is sensitive and specific enough to allow a definitive diagnosis of DIC.
Initial Tests (lab, imaging)
- CBC with differential, prothrombin time (PT)/INR, partial thromboplastin time (PTT), fibrinogen, fibrin degradation product (FDP), D-dimer, antithrombin III
- Thrombocytopenia (3)
- Increased PTT
- Increased PT
- Decreased fibrinogen (serial levels)
- Increased FDP
- Positive D-dimer
- Decreased antithrombin III, decreased protein C
- Other labs that may have prognostic significance
- Decreased ADAMTS13
- Increase soluble TM, plasminogen activator inhibitor-1 (PAI-1), von Willebrand factor peptide
- Decrease des-R-prothrombin activation peptide fragment 2 (4)
- Microangiopathic hemolytic anemia (schistocytes, increased lactate dehydrogenase levels, low hemoglobin)
ALERT
Diagnostic algorithm for overt DIC (International Society on Thrombosis and Haemostasis) (5)
- Assess if underlying disease is known to be associated with DIC.
- YES: Proceed with this algorithm.
- NO: Do not use this algorithm.
- Order global coagulation tests (PT, PTT, fibrinogen, soluble fibrin monomers, or FDPs).
- Score global coagulation test results
- Platelet count (>100 = 0, <100 = 1, <50 = 2)
- Elevated fibrin-related markers (no increase = 0, moderate increase = 2, strong increase = 3)
- Prolonged PT (<3 seconds = 0, >3 but <6 seconds = 1, >6 seconds = 2)
- Fibrinogen level (>1 g/L = 0, <1 g/L = 1)
- Calculate score
- If ≥5: compatible with DIC, repeat scoring daily. If <5: suggestive of nonovert DIC, repeat in 1 to 2 days
Follow-Up Tests & Special Considerations
Frequent follow-up of initially abnormal laboratory tests to see effect of therapeutic interventions
TREATMENT
Heterogeneity of the underlying disorders and the clinical presentations makes the therapeutic approach to DIC difficult:
- Appropriate health care: inpatient and intensive care unit (ICU) (depending on underlying condition)
- Treat underlying condition (e.g., evacuation of uterus in abruptio placentae; broad-spectrum antibiotics for gram-negative sepsis).
- Do not treat abnormal lab parameters. Supportive care with transfusions in patients who are bleeding, going for surgery, or at high risk of bleeding (6):
- Fresh frozen plasma if bleeding with prolonged PT/PTT
- Platelet concentrates if bleeding or count <10 to 20,000/μL
- Cryoprecipitate if fibrinogen level <1.5 g/L
- Anticoagulants remain very controversial. Therapeutic heparin may be considered in cases where thrombosis dominates. LMWH preferred to unfractionated heparin due to less bleeding risks.
- Deep venous thrombosis prophylaxis is recommended in patients who are not bleeding.
- Restoration of anticoagulant pathways
- Recombinant human-activated protein C once had a level of evidence for use only in selected high-risk patients in ICU setting. The drug was, however, removed from the market in 2012 (7).
- Activated factor VII and antithrombin use remains controversial. Investigation is ongoing.
- Recombinant TM in sepsis induced DIC seems to be promising (8).
- Antifibrinolytic treatment is generally not recommended but may be considered in those with severe bleeding and marked hyperfibrinolytic state (i.e., trauma, acute promyelocytic leukemia, cavernous hemangioma).
MEDICATION
Broad-spectrum antibiotics for sepsis
SURGERY/OTHER PROCEDURES
Surgical treatment or procedures should be considered, especially if they are treating the underlying condition (e.g., evacuation of uterus in abruptio placentae; some trauma or bleeding situations).
INPATIENT CONSIDERATIONS
Admission Criteria/Initial Stabilization
Usually dictated by severity of underlying condition. Some cases can be managed in a standard ward, but ICU care is typical.
- Treat underlying disorder.
- Frequent monitoring of clinical and laboratory response
Discharge Criteria
Once clinical and laboratory criteria are significantly improved and underlying reason for DIC is under control.
ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
Patient Monitoring
- Monitor closely until much improved.
- Serial platelet count, coagulation tests, and fibrinogen levels to see effect of therapeutic interventions
PROGNOSIS
- Related to the severity of cause
- Decreased antithrombin level is a poor prognostic factor in DIC.
COMPLICATIONS
- Acute renal failure
- Shock
- Cardiac tamponade
- Hemothorax
- Intracerebral hematoma
- Various thrombotic complications, including myocardial infarction, stroke, gangrene, and loss of digits
REFERENCES
11 Singh B, Hanson AC, Alhurani R, et al. Trends in the incidence and outcomes of disseminated intravascular coagulation in critically ill patients (2004-2010): a population-based study. Chest. 2013;143(5):1235-1242.22 Levi M. Disseminated intravascular coagulation. Crit Care Med. 2007;35(9):2191-2195.33 Levi M. Diagnosis and treatment of disseminated intravascular coagulation. Int J Lab Hematol. 2014;36(3):228-236.44 Chung S, Kim JE, Kim HK, et al. Serum des-R prothrombin activation peptide fragment 2: a novel prognostic marker for disseminated intravascular coagulation. Thromb Res. 2013;131(6):547-553.55 Voves C, Wuillemin WA, Zeerleder S. International Society on Thrombosis and Haemostasis score for overt disseminated intravascular coagulation predicts organ dysfunction and fatality in sepsis patients. Blood Coagul Fibrinolysis. 2006;17(6):445-451.66 Venugopal A. Disseminated intravascular coagulation. Indian J Anaesth. 2014;58(5):603-608.77 Vincent JL, Bernard GR, Beale R, et al. Drotrecogin alfa (activated) treatment in severe sepsis from the global open-label trial ENHANCE: further evidence for survival and safety and implications for early treatment. Crit Care Med. 2005;33(10):2266-2277.88 Yoshimura J, Yamakawa K, Ogura H, et al. Benefit profile of recombinant human soluble thrombomodulin in sepsis-induced disseminated intravascular coagulation: a multicenter propensity score analysis. Crit Care. 2015;19:78.
CODES
ICD10
- D65 Disseminated intravascular coagulation
- P60 Disseminated intravascular coagulation of newborn
ICD9
- 286.6 Defibrination syndrome
- 776.2 Disseminated intravascular coagulation in newborn
SNOMED
- Disseminated intravascular coagulation (disorder)
- Disseminated intravascular coagulation in newborn (disorder)
CLINICAL PEARLS
- Treat underlying condition(s); transfusions represent supportive measures.
- Transfusions are not indicated in patients with abnormal laboratory parameters without clinical bleeding.