What is the difference between chronic compensated Disseminated Intravascular Coagulation (DIC) and Thrombotic Thrombocytopenic Purpura/Hemolytic Uremic Syndrome (TTP/HUS)?

Distinguishing Chronic Compensated DIC from TTP/HUS

Chronic compensated DIC and TTP/HUS can be reliably differentiated using readily available laboratory tests: a platelet count <20 × 10³/μL combined with a prothrombin time (PT) within 5 seconds of the upper limit of normal has 92% specificity for TTP/HUS, while chronic DIC typically shows elevated PT/INR with less severe thrombocytopenia and markedly elevated D-dimer. 1

Key Laboratory Distinctions

Coagulation Parameters

• PT/INR: Normal or minimally prolonged in TTP/HUS (within 5 seconds of upper limit), whereas chronic DIC shows elevated PT/INR due to consumption of clotting factors 1
• APTT: Generally normal in TTP/HUS, may be slightly elevated in chronic DIC 2, 1
• Fibrinogen: Normal in TTP/HUS; normal or slightly decreased in chronic compensated DIC (unlike acute DIC where it drops significantly) 2, 3
• D-dimer: Markedly elevated in chronic DIC (often >5 μg/mL), less dramatically elevated in TTP/HUS 2

Platelet Count Patterns

• TTP/HUS: Profound thrombocytopenia, typically <20 × 10³/μL, is highly characteristic 1
• Chronic compensated DIC: Moderate thrombocytopenia (often 50-150 × 10³/μL) as platelets can be replenished over time 4, 2

Hemolysis Markers

• Both conditions show microangiopathic hemolytic anemia (MAHA) with schistocytes, elevated LDH, decreased haptoglobin, and indirect hyperbilirubinemia 5, 6, 2
• Reticulocyte count: Elevated in both due to hemolysis, but normal reticulocyte count with thrombocytopenia suggests chronic DIC rather than TTP/HUS 2

Clinical Context Differences

Underlying Conditions

• Chronic compensated DIC: Associated with metastatic malignancy (especially prostate, pancreatic, gastric cancers), chronic liver disease, or ongoing low-grade tissue factor exposure 4, 2, 3
• TTP/HUS: ADAMTS13 deficiency (TTP), complement dysregulation (atypical HUS), or Shiga toxin exposure (typical HUS) 7

Clinical Presentation

• Chronic DIC: Stable laboratory abnormalities over time, thrombosis more common than bleeding (occurs in >10% of chronic cases vs <10% in acute DIC), may have underlying cancer symptoms 4, 3
• TTP/HUS: Acute presentation with neurological symptoms (TTP), renal failure (HUS), and severe thrombocytopenia; bleeding less prominent than thrombotic complications 6, 7

Diagnostic Algorithm

Step 1: Assess Platelet Count and PT

• If platelet count <20 × 10³/μL AND PT normal/near-normal → strongly suggests TTP/HUS 1
• If platelet count 50-150 × 10³/μL AND PT elevated → suggests chronic DIC 2, 1

Step 2: Evaluate D-dimer and Fibrinogen

• Markedly elevated D-dimer (>5 μg/mL) with normal fibrinogen → chronic DIC 2
• Moderately elevated D-dimer with normal fibrinogen → consider TTP/HUS 2

Step 3: Check for MAHA

• Peripheral smear showing schistocytes/helmet cells confirms microangiopathic process in both conditions 5, 2

Step 4: Assess ADAMTS13 Activity (if TTP/HUS suspected)

• ADAMTS13 activity <10% with inhibitor → TTP 7
• Normal ADAMTS13 → consider HUS or chronic DIC 7

Step 5: Serial Monitoring

• Dynamic changes in coagulation parameters over hours to days suggest acute decompensation of DIC 8
• Stable abnormalities over weeks to months suggest chronic compensated DIC 8, 4

Critical Pitfalls to Avoid

Misdiagnosis Risk

• Do not delay plasma exchange if TTP/HUS is suspected based on profound thrombocytopenia and normal PT, as TTP/HUS is 90% fatal without treatment 1, 7
• Do not assume DIC in all patients with thrombocytopenia and elevated D-dimer; check PT and degree of thrombocytopenia first 1

Treatment Implications

• TTP/HUS requires urgent plasma exchange as first-line therapy 7
• Chronic DIC requires therapeutic-dose anticoagulation (LMWH or heparin) to prevent thrombosis, not plasma exchange 2, 3
• Treating TTP/HUS with heparin alone (as for DIC) will result in death 7
• Treating chronic DIC with plasma exchange alone (as for TTP/HUS) will not address ongoing thrombin generation 3

Underlying Cause Identification

• In chronic DIC, always search for occult malignancy (check PSA, CT imaging, tumor markers) as this drives prognosis and treatment 2
• In TTP/HUS presenting with renal failure and polyuria, check complement studies to identify atypical HUS requiring eculizumab 6