What laboratory tests are indicated for a patient suspected of having Thrombotic Thrombocytopenic Purpura (TTP)?

Laboratory Evaluation for Suspected Thrombotic Thrombocytopenic Purpura (TTP)

For suspected TTP, immediately obtain a complete blood count with peripheral blood smear examination looking specifically for schistocytes and thrombocytopenia, along with markers of hemolysis (LDH, indirect bilirubin, haptoglobin, reticulocyte count), and send ADAMTS13 activity level with inhibitor testing—but do not delay plasma exchange therapy while awaiting ADAMTS13 results if clinical suspicion is high. 1, 2

Essential Immediate Laboratory Tests

Core Diagnostic Panel

• Complete blood count demonstrating thrombocytopenia (typically severe, often <30,000/μL) 1, 2
• Peripheral blood smear is paramount—must show schistocytes (fragmented red blood cells) indicating microangiopathic hemolytic anemia, which distinguishes TTP from immune thrombocytopenic purpura 3, 1, 2
• Lactate dehydrogenase (LDH) will be markedly elevated, often >1000 IU/L, reflecting both hemolysis and tissue ischemia 4, 1, 2
• Indirect (unconjugated) bilirubin elevated due to hemolysis 1, 2
• Haptoglobin will be undetectable or severely decreased as it binds free hemoglobin from intravascular hemolysis 5, 1, 2
• Reticulocyte count elevated, demonstrating bone marrow response to hemolytic anemia 1, 2
• Hemoglobin decreased, typically with microangiopathic hemolytic anemia 1, 2

Definitive Diagnostic Test

• ADAMTS13 activity level <10% confirms TTP diagnosis, though treatment should begin before results return (typically takes 24-72 hours) 1, 2
• Anti-ADAMTS13 antibody testing distinguishes immune-mediated TTP (iTTP) from congenital TTP (cTTP)—positive antibodies indicate iTTP requiring immunosuppression 1, 2

Secondary Laboratory Tests to Exclude Mimics

Coagulation Studies

• PT, aPTT, fibrinogen, and D-dimer should be obtained to exclude disseminated intravascular coagulation (DIC)—these are typically normal in TTP, unlike DIC where fibrinogen is low and PT/aPTT are prolonged 6, 1

Renal Function

• Creatinine and BUN to assess renal involvement, though severe renal failure is more characteristic of atypical hemolytic uremic syndrome (aHUS) than TTP 1, 2

Cardiac Markers

• Troponin may be elevated due to cardiac microinfarcts, as myocardial involvement can occur 7

Critical Diagnostic Pitfalls to Avoid

The Schistocyte Timing Problem

• Schistocytes may be absent on initial peripheral smear and appear only after 24-72 hours, as demonstrated in the case where initial smear was normal but subsequent smear revealed schistocytes 7
• If clinical suspicion remains high despite negative initial smear, repeat the peripheral smear daily and do not rule out TTP based on a single negative smear 5, 7

The Classic Pentad Myth

• The historical "pentad" (fever, thrombocytopenia, microangiopathic hemolytic anemia, neurologic abnormalities, renal failure) is present in only a minority of patients 7
• Only thrombocytopenia and microangiopathic hemolytic anemia are required for diagnosis when ADAMTS13 is <10% 1, 2
• Waiting for all five features delays life-saving treatment and increases mortality 7

Do Not Delay Treatment for ADAMTS13 Results

• Plasma exchange must be initiated immediately based on clinical presentation (thrombocytopenia + schistocytes + elevated LDH + low haptoglobin) without waiting for ADAMTS13 confirmation 1, 2
• ADAMTS13 activity <10% confirms diagnosis retrospectively but should not delay therapy, as mortality approaches 90% without prompt plasma exchange 1, 2

Algorithmic Approach to Laboratory Diagnosis

Step 1: Patient presents with thrombocytopenia—obtain CBC, peripheral smear, LDH, haptoglobin, indirect bilirubin, reticulocyte count 1, 2

Step 2: If schistocytes present + thrombocytopenia + elevated LDH + low/absent haptoglobin → presumptive TTP diagnosis 1, 2

Step 3: Immediately send ADAMTS13 activity and inhibitor, but start plasma exchange without waiting for results 1, 2

Step 4: Obtain PT, aPTT, fibrinogen, D-dimer to exclude DIC (normal coagulation studies support TTP) 6, 1

Step 5: If schistocytes absent on initial smear but clinical suspicion high (unexplained thrombocytopenia + hemolytic anemia + neurologic symptoms), repeat smear in 24 hours and consider empiric plasma exchange 5, 7

Step 6: Once ADAMTS13 results return:

• ADAMTS13 <10% with positive inhibitor → immune-mediated TTP, continue plasma exchange + add corticosteroids and rituximab 1, 2
• ADAMTS13 <10% without inhibitor → consider congenital TTP, genetic testing indicated 1, 2
• ADAMTS13 >10% → alternative diagnosis (aHUS, DIC, other TMA), adjust management accordingly 2

Monitoring During Treatment

• Daily platelet counts to assess response—early responders achieve mean platelet count of 180 × 10⁹/L by Day 5, while late responders have only 122 × 10⁹/L by Day 5 4
• Daily LDH as a marker of ongoing hemolysis—early responders achieve mean LDH of 643 IU/L by Day 7 versus 885 IU/L in late responders 4
• Late responders require significantly more plasma exchanges (median 19 vs. 7) and have higher rates of exacerbation (77% vs. 7%) 4