Thrombotic thrombocytopenic purpura (TTP)
Thrombotic thrombocytopenic purpura is a thrombotic microangiopathy caused by severe ADAMTS13 deficiency that lets ultralarge von Willebrand factor multimers drive platelet microthrombi; the key dyad of microangiopathic hemolytic anemia plus thrombocytopenia without another cause mandates the PLASMIC score, an ADAMTS13 activity and inhibitor level, and emergent plasma exchange started before results return.
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What this article covers
- Overview
Definition: thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy caused by severe deficiency of ADAMTS13, the metalloprotease that cleaves high-molecular-weight von Willebrand factor (vWF) multimers.
- Epidemiology
Rare disease: TTP is an uncommon cause of thrombocytopenia and MAHA, but it must be actively excluded whenever this dyad is found because delay is fatal.
- Risk factors
Autoantibody formation against ADAMTS13: the dominant mechanism in acquired TTP, producing severe (less than 10%) enzyme activity.
- Pathophysiology
ADAMTS13 normally cleaves vWF: this metalloprotease trims newly secreted, ultralarge vWF multimers down to smaller, less adhesive forms.
- Clinical features
Microangiopathic hemolytic anemia: present in 100% of patients, evidenced by schistocytes on peripheral smear, elevated lactate dehydrogenase, decreased haptoglobin, and a negative direct antiglobulin (Coombs) test.
- Differential diagnosis
Disseminated intravascular coagulation: MAHA and thrombocytopenia with an identifiable trigger (sepsis, trauma, malignancy) but, unlike TTP, prolonged PT and aPTT and low fibrinogen from consumption…
- Diagnosis
Confirm with an ADAMTS13 activity level below 10% plus inhibitor testing; use the PLASMIC score to guide empiric treatment while that result is pending.
- Management
Start therapeutic plasma exchange (PLEX) immediately on strong clinical suspicion, without waiting for ADAMTS13 results, because TTP is a medical emergency with high mortality if untreated; PLEX…
- Complications
Death from untreated or delayed-treatment disease: the mortality rate of TTP is high without prompt plasma exchange, which is why treatment starts on clinical suspicion rather than waiting for confirmatory testing.
- Prognosis
Treatment is successful in about 85% of patients who receive prompt plasma exchange and immunosuppression.
- Prevention
Monitor ADAMTS13 activity after remission: patients with persistently low ADAMTS13 activity (below 10%) despite platelet count recovery are at elevated relapse risk and are candidates for continued…
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- Hemolytic uremic syndrome
Hemolytic uremic syndrome is a thrombotic microangiopathy defined by the triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury, most often triggered in children by Shiga toxin-producing Escherichia coli O157:H7 after bloody diarrhea. Diagnosis rests on schistocytes with a negative Coombs test plus a normal ADAMTS13 level to exclude TTP, and typical STEC-HUS is managed supportively while antibiotics and antimotility agents are avoided, whereas complement-mediated atypical HUS requires eculizumab.
- Disseminated intravascular coagulation
Disseminated intravascular coagulation is a secondary, systemic activation of coagulation and fibrinolysis, most often from sepsis, that simultaneously consumes platelets and clotting factors, causing microvascular thrombosis and bleeding. Diagnosis rests on a laboratory constellation, thrombocytopenia, prolonged PT and aPTT, low fibrinogen, and elevated D-dimer, in a predisposing clinical setting, and management centers on treating the underlying trigger while replacing blood components only for active or high-risk bleeding.
- Thrombocytopenia: an overview
Thrombocytopenia, a platelet count below 150,000/microL, is a laboratory finding rather than a single disease, so evaluation starts with the smear to exclude pseudothrombocytopenia and identify the can't-miss consumptive emergencies TTP, HIT, and DIC before working through production, destructive, and sequestration causes. Management treats the underlying cause, reserves platelet transfusion for bleeding or procedural thresholds, and specifically avoids platelet transfusion in TTP and HIT except for life-threatening hemorrhage.
- HELLP syndrome
HELLP syndrome is a thrombotic microangiopathy of pregnancy, a severe-feature variant of preeclampsia defined by hemolysis, transaminases at least twice the upper limit of normal, and a platelet count under 100,000/uL. Delivery is the only curative treatment; management pairs blood pressure control and magnesium sulfate seizure prophylaxis with prompt, gestational-age-guided delivery.