Disseminated Intravascular Coagulation (DIC)

Introduction

Disseminated Intravascular Coagulation (DIC) is a very serious and life-threatining coagulation cascade disorder that is sometimes seen in patients with severe physiologic stressors such as sepsis, obstetric complications (for example, placental abruption, retained products of conception, or amniotic fluid embolization) or major tissue injury from trauma, burns, shock, snake bites, or malignancy (for example, acute promyelocytic leukemia). Patients with DIC have abnormal intravascular microthrombus formation and degradation, which leads to (1) hemolysis, (2) thrombocytopenia, and to (3) depletion of coagulation factors (coagulopathy).

Clinically, patients with DIC will be very ill and will be coagulopathic (abnormal bleeding) and anemic.

Laboratory diagnosis

On laboratory evaluation, four features should be sought:

1. Proof of an otherwise-unexplained coagulopathy: In most cases, an elevated INR is sufficient proof of coagulopathy, and here is no need for a PTT. However, when there is an alternative explanation for the elevated INR (for example, when the patient is on warfarin), order a PTT as well to help nail down this component of the laboratory diagnosis.
2. Thrombocytopenia
3. Proof of clot formation and degradation: either (↑) d-dimer or (↑) fibrin/fibrinogen degradation products assay. There is no need to order both tests.
4. Proof of otherwise-unexplained microangiopathic hemolytic anemia: order a peripheral blood smear and look for schistocytes (or ask your pathologist or hematologist for help). The presence of schistocytes is very compelling evidence for DIC in the setting of a coagulopathy and known physiologic stressors. If you cannot get a reliable and timely peripheral blood smear interpretation, use a hemolysis workup as a surrogate. A basic hemolysis workup includes:
   • Hemoglobin and hematocrit (↓).
   • Reticulocyte count (↑).
   • Lactate dehydrogenase (LDH, ↑) – a normal LDH is compelling evidence against hemolysis.
   • Unconjugated bilirubin (↑) in liver chemistry studies.
   • Haptoglobin level (↓) also points strongly toward hemolysis, but the test is not very useful because in most facilities it takes too long to get the results back.
   • Urinalysis showing clear (few, if any, whole red blood cells!) pink or dark urine. On dipstick, the urine will be positive for “blood,” but there will be no red blood cells on microscopy.
   • Know that a positive Coombs test, especially in the absence of schistocytes on peripheral blood smear, is very compelling evidence against DIC because a positive Coombs test suggests that the hemolytic anemia is autoimmune in nature (rather than microangiopathic). Therefore, and conversely, if there is evidence of hemolysis but no schistocytes are seen on the peripheral blood smear, order a Coombs test to help clarify the diagnosis!

More laboratory tips and tricks

• A single normal or elevated fibrinogen level is useless in terms of ruling out DIC because fibrinogen is an acute phase reactant that is commonly elevated in the presence of physiologic stressors, even in the absence of DIC. Nonetheless, serial fibrinogen levels, when trending downward over a short period of time strongly support the diagnosis of DIC. This is an extremely useful test, especially when other studies are inconclusive or unrevealing (for example in patients with decompensated cirrhosis).
• Liver chemistry studies can help you determine whether hepatic insufficiency might be an alternative or concomitant explanation for the presence of coagulopathy, anemia and thrombocytopenia. Get them! If liver disease is present, there are two things that point rather specifically to DIC:
  • (1) schistocytes on a peripheral smear
  • (2) serial laboratory findings showing dramatic changes in platelets (↓), coagulation profile (↑) and fibrinogen levels (↓) over a period of four to six hours.
• Microangiopathic hemolytic anemia and thrombocytopenia without coagulopathy is not DIC. Rather, diagnostic considerations here include Thrombotic Thrombocytopenic Purpura-Hemolytic Uremic Syndrome (TTP-HUS) or the HELLP syndrome (hemolysis, elevated liver enzyme levels and a low platelet count, seen in pregnant patients). So if you see microangiopathic hemolytic anemia and thrombocytopenia without coagulopathy, order a serum BUN and creatinine level (because patients with TTP-HUS will have renal dysfunction) and a pregnancy test in the appropriate settings.

References

• Laposata, Michael, MD, PhD., Coagulation Disorders: Quality in Laboratory Diagnosis (2010)
• Desai, Samir P., MD, Clinician’s Guide to Laboratory Medicine: Pocket (2009, reviewed here)