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This is a clinician-written, evidence-based summary aligned to the USMLE Step 2 CK Content Outline. It is intended for medical students preparing for USMLE Step 2 CK. Management reflects current ACC/AHA, USPSTF, and APA guidelines. Always cross-reference with UpToDate, institutional protocols, and clinical judgment.
The Bottom Line
- TTP is a hematologic emergency; mortality is high without urgent plasma exchange
- Classic pentad: MAHA, thrombocytopenia, neurologic symptoms, renal injury, fever — but most patients do not have all five
- Severe ADAMTS13 deficiency causes ultra-large vWF multimers and platelet-rich microthrombi
- Labs: schistocytes, low platelets, normal PT/aPTT, elevated LDH, low haptoglobin
- Do not wait for ADAMTS13 results before starting plasma exchange when suspicion is high
Overview
TTP is a thrombotic microangiopathy caused by severe deficiency of ADAMTS13, the protease that cleaves ultra-large von Willebrand factor multimers. The result is widespread platelet aggregation in small vessels, microangiopathic hemolytic anemia, severe thrombocytopenia, and ischemic organ injury. TTP may be immune-mediated from autoantibodies or rarely inherited.
Epidemiology
Acquired immune TTP is rare but often affects adults, with higher incidence in women and people of African ancestry. Triggers include pregnancy, autoimmune disease, HIV, malignancy, transplantation, and medications. Relapse can occur.
Clinical Features
Symptoms
Confusion, headache, seizure, focal neurologic deficits, or fluctuating mental status
Fatigue, dyspnea, jaundice, dark urine from hemolysis
Petechiae, bruising, mucosal bleeding from thrombocytopenia
Fever may be present but is not required
Abdominal pain, chest pain, or renal symptoms from microvascular ischemia
Signs
Petechiae or purpura
Jaundice, pallor, tachycardia
Neurologic deficits or encephalopathy
Hypertension or mild renal impairment; severe renal failure suggests HUS more strongly
Investigations
First-line
CBC and smearThrombocytopenia plus schistocytes; hemoglobin low; reticulocytes elevated
Hemolysis labsLDH high, indirect bilirubin high, haptoglobin low
Coagulation studiesPT and aPTT usually normal; helps distinguish from DIC
Second-line
Creatinine and urinalysisAssess renal involvement
Troponin and ECGCardiac ischemia can occur from microthrombi and worsens prognosis
PLASMIC scoreRisk stratifies severe ADAMTS13 deficiency; high score supports urgent treatment
Specialist
ADAMTS13 activity and inhibitorSevere activity <10% supports TTP; send before plasma exchange if possible, but do not delay treatment
1
Immediate treatment
- Urgent plasma exchange is the cornerstone and should start immediately when TTP is suspected
- High-dose corticosteroids for immune-mediated TTP
- Send ADAMTS13 before plasma exchange if feasible but do not delay therapy
- Avoid prophylactic platelet transfusion unless life-threatening bleeding or urgent invasive procedure
2
Adjunctive therapy
- Caplacizumab may be added to inhibit vWF-platelet interaction
- Rituximab is used for immune TTP, refractory disease, or relapse prevention
- Monitor platelets, LDH, neurologic status, renal function, and cardiac injury daily
3
Long-term follow-up
- Monitor for relapse with ADAMTS13 activity in specialist follow-up
- Educate about recurrence symptoms
- Manage cardiovascular risk and neurocognitive sequelae after recovery
Complications
- Stroke and seizures: Microvascular CNS ischemia
- Myocardial ischemia: Troponin elevation and arrhythmias can occur
- Renal injury: Usually less severe than typical HUS but clinically important
- Death: Untreated TTP has very high mortality
USMLE Step 2 CK Exam Tips
- 1Schistocytes + thrombocytopenia + neurologic symptoms + normal PT/aPTT = TTP
- 2Next best step in suspected TTP: plasma exchange, not platelet transfusion
- 3ADAMTS13 result confirms but treatment must not wait
- 4TTP is platelet microthrombi; DIC is coagulation factor consumption
- 5Platelet transfusion can worsen thrombosis in TTP unless severe bleeding
- 6Renal failure after bloody diarrhea points more toward HUS
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