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Thrombotic Thrombocytopenic Purpura

Life-threatening thrombotic microangiopathy from severe ADAMTS13 deficiency requiring urgent plasma exchange and immunosuppression.

Written by: Saygı Hospital Health Guide Editorial Board
Last updated:

This content has been compiled by the Saygı Hospital Health Guide Editorial Board and is periodically reviewed by a specialist physician.

References (5)

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What is Thrombotic Thrombocytopenic Purpura?

Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy characterized by severe deficiency (<10%) of ADAMTS13, a metalloprotease that cleaves ultra-large von Willebrand factor multimers. The deficiency leads to platelet thrombi in the microcirculation with microangiopathic hemolytic anemia, severe thrombocytopenia, organ ischemia (brain, heart, kidney), and a classical pentad (often incomplete) of fever, neurologic abnormalities, renal involvement, hemolytic anemia, and thrombocytopenia.

Two forms are recognized: immune-mediated TTP (iTTP, acquired) due to inhibitory autoantibodies against ADAMTS13 in 95% of cases, and congenital TTP (Upshaw-Schulman syndrome) from biallelic ADAMTS13 mutations. iTTP affects adults predominantly with female predominance and African ancestry overrepresented; triggers include pregnancy, infection, autoimmune disease (SLE), drugs (clopidogrel, ticlopidine, quinine), and vaccination.

Diagnosis requires high clinical suspicion. PLASMIC score (≥6 high probability) facilitates rapid stratification. Microangiopathic hemolytic anemia with schistocytes, severe thrombocytopenia (often <30,000/µL), elevated LDH, indirect hyperbilirubinemia, normal or near-normal coagulation, and direct antiglobulin test negative support diagnosis. Confirmatory ADAMTS13 activity (<10%) and inhibitor assay should be sent before plasma exchange. Treatment is urgent therapeutic plasma exchange (TPE) with fresh-frozen plasma replacement, high-dose corticosteroids, and caplacizumab (anti-vWF nanobody) for iTTP. Rituximab targets the autoantibody-producing B cells in iTTP. Congenital TTP requires plasma infusion with future recombinant ADAMTS13 (rADAMTS13) replacement therapy. Multidisciplinary critical care, neurologic and cardiac monitoring, and long-term follow-up with ADAMTS13 monitoring for relapse prevention are essential.

Symptoms

Severe thrombocytopenia (<30,000/µL) — petechiae, purpura, bleeding
Microangiopathic hemolytic anemia — pallor, jaundice, dark urine
Schistocytes on peripheral blood smear
Neurologic: headache, confusion, focal deficits, seizures, stroke, coma (waxing-waning)
Renal involvement (mild typically): hematuria, proteinuria, mild acute kidney injury
Cardiac: chest pain, troponin elevation, arrhythmia, sudden cardiac death
Fever
Abdominal pain, GI bleeding
Visual disturbance
Cutaneous purpura, ecchymoses
Mucosal bleeding
Hemolysis: indirect hyperbilirubinemia, elevated LDH, low haptoglobin
Pregnancy-related: presenting in second/third trimester or postpartum
Recurrent miscarriage in unrecognized congenital TTP
Mortality without treatment >90%; with PEX 10-20%

Risk Factors

Female sex
African ancestry
Age 30-50 (iTTP peak)
Pregnancy and postpartum
Infection (HIV, viral)
Autoimmune disease (SLE, antiphospholipid syndrome, Sjögren)
Drugs: clopidogrel, ticlopidine, quinine, calcineurin inhibitors, gemcitabine, mitomycin C, opana, immune checkpoint inhibitors
Recent vaccination (rare)
Stem cell transplantation (transplant-associated TMA)
Pancreatitis, sepsis (precipitants)
Family history (rare congenital)
ADAMTS13 mutation (Upshaw-Schulman, autosomal recessive)
Obesity, metabolic syndrome (controversial)
Past TTP episode (relapse risk)
Plasma exchange access limitations

When to See a Doctor?

If you experience any of the following symptoms, seek medical attention promptly:

  • Severe thrombocytopenia with anemia and schistocytes
  • Sudden neurologic symptoms with thrombocytopenia
  • Pregnancy or postpartum with low platelets and hemolysis
  • Patient with prior TTP returning with similar symptoms
  • Drug-induced thrombocytopenia with hemolysis
  • Fever, neurologic, renal, hematologic abnormalities
  • Stroke or chest pain in young adult with cytopenias
  • Family history of recurrent TTP for genetic evaluation
  • Postoperative or post-transplant unexplained TMA

Treatment Methods

01
Hospitalization in ICU or specialized TTP center; immediate hematology consult
02
PLASMIC score for rapid risk stratification (≥6 high probability)
03
Send ADAMTS13 activity and inhibitor before treatment; do not delay therapy waiting for results
04
Rule out alternative TMAs: hemolytic uremic syndrome (especially Shiga toxin in children), atypical HUS, drug-induced TMA, severe DIC, HELLP, pregnancy-induced TMA, transplant-associated TMA
05
Initiate therapeutic plasma exchange (TPE) ASAP, ideally within 4-8 hours of suspected diagnosis; daily 1-1.5 plasma volumes with FFP replacement until platelet recovery and LDH normalization for at least 2 days
06
If TPE not immediately available, plasma infusion as bridge
07
High-dose corticosteroids: methylprednisolone 1 g/day × 3 days then prednisone 1 mg/kg/day, taper after remission
08
Caplacizumab (anti-von Willebrand nanobody) for iTTP: IV bolus before TPE, then daily SC for at least 30 days post-TPE termination
09
Rituximab 375 mg/m² weekly × 4 in iTTP for B-cell depletion; consider front-line in high-risk or severe; salvage in refractory or relapsed
10
Avoid platelet transfusion unless life-threatening bleeding (paradoxically may worsen thrombosis); RBC transfusion as needed
11
Anticoagulation with low-dose LMWH after platelets >50,000 (debated); aspirin sometimes used
12
Treat triggers: stop offending drug, treat infection, autoimmune disease
13
Pregnancy: TPE, corticosteroids, caplacizumab (limited data) under multidisciplinary care
14
Congenital TTP: regular plasma infusion every 2-3 weeks; future rADAMTS13 replacement
15
Monitor: daily CBC, LDH, schistocytes, ADAMTS13 activity, neurologic exam, troponin, ECG
16
ICU support for organ dysfunction
17
Folate replacement during hemolysis
18
Bone marrow biopsy if concern for myelodysplasia
19
Long-term follow-up with hematology: ADAMTS13 every 3 months for first 2 years, then less frequently; rituximab or other immunosuppression if persistent severe deficiency to prevent relapse
20
Vaccination updates, infection avoidance, prompt treatment of recurrent symptoms
21
Family screening if congenital TTP confirmed; genetic counseling
22
Pregnancy planning with hematology and obstetrics; risk of relapse in pregnancy
23
Patient education on relapse symptoms, medication adherence, lifestyle

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