Description
The approach to Thrombotic Thrombocytopenic Purpura (TTP) involves the prompt initiation of plasma exchange therapy to remove the circulating autoantibodies and replenish ADAMTS13 enzyme activity. Additionally, corticosteroids and immunosuppressive drugs are often administered to control the underlying autoimmune response and prevent relapse.
Résumé
- Thrombotic Thrombocytopenic Purpura (TTP) is a rare disorder characterized by thromboses in small blood vessels, leading to thrombocytopenia and microangiopathic hemolytic anemia. It was first described in 1995 and its etiology remained unknown with fatal outcomes until the identification of the role of von Willebrand factor (vWF) in 1982, followed by the identification of ADAMTS13 in 2001. TTP is classified into acquired (mainly adult-onset) and inherited forms (childhood-onset), with the acquired form being more prevalent.
- The diagnosis of TTP involves clinical criteria (ischemic symptoms) and biological criteria (thrombocytopenia and microangiopathic hemolytic anemia) in the absence of other causative factors. A key diagnostic feature is severe ADAMTS13 deficiency (activity <10%). Etiology involves known factors like ADAMTS13 deficiency (due to gene mutation or autoantibodies) and predisposing factors (female gender, obesity, black ethnicity). Precipitating factors include conditions increasing vWF levels, such as inflammation, infection, and fever.
- ADAMTS13 is an enzyme that cleaves vWF, a glycoprotein essential for normal hemostasis. Deficiency leads to uncleaved, large vWF multimers, promoting platelet aggregation and microthrombi formation. This process causes thrombocytopenia and hemolytic anemia, where red blood cells are fragmented (schistocytes) while passing through narrowed vessels. Tissue ischemia results, potentially damaging any affected organ.
- The classic pentad of TTP includes fever, thrombocytopenia, hemolytic anemia, neurological symptoms, and renal insufficiency. Symptoms vary widely, including bleeding manifestations, neurological deficits, cardiac ischemia, abdominal pain, and renal impairment. Differential diagnosis includes Hemolytic Uremic Syndrome (HUS), drug-induced TMA, and other secondary causes like infections, autoimmune diseases, pregnancy, HIV, cancers, and organ transplantation.
- Scoring systems like PLASMIC score, French score, and Bentley score aid in risk stratification and prompt treatment initiation. These scores incorporate variables such as platelet count, hemolysis markers, cancer history, MCV, INR, and creatinine levels. Laboratory diagnosis involves CBC with peripheral smear, coagulation parameters (usually normal in TTP), renal testing, and ADAMTS13 activity analysis.
- Pathological findings in kidneys include glassy appearance, subcapsular hemorrhages, and glomerular microthrombi. Light microscopy reveals microthrombi in glomeruli and fibrin deposition. Immunofluorescence demonstrates reactivity of thrombi to antifibrinogen antibodies, and electron microscopy shows platelet-rich glomerular thrombi. Specific TTP cases include obstetric TTP, autoimmune-associated TTP, HIV-associated TTP, and congenital TTP due to ADAMTS13 gene mutations.
- The approach to TTP diagnosis involves initial investigations to identify thrombocytopenia, microangiopathic hemolytic anemia, and normal coagulation profile. Urgent ADAMTS13 testing is performed, and treatment is initiated with plasma exchange (PEX). If ADAMTS13 activity is 10%.
- Poor prognostic factors include older age, high LDH levels, and organ damage, especially CNS and cardiac involvement. Treatment response is assessed by platelet count normalization, hemolysis resolution, and clinical recovery. Relapse is defined as recurrence within or after 30 days of achieving remission, while refractory disease is characterized by lack of response after 30 days.
- Plasma exchange (PEX) is the cornerstone of TTP treatment, performed daily until platelet counts normalize and hemolysis resolves. It removes autoantibodies and ultralarge vWF multimers while supplementing ADAMTS13. Adjunctive therapies include high-dose corticosteroids to reduce autoantibody production and rituximab, a B-cell depleting agent. Caplacizumab, a vWF inhibitor, can be used to prevent platelet aggregation.
- ISTH guidelines recommend PEX and steroids as essential treatments, with rituximab and caplacizumab as conditional recommendations in certain cases. Steroids are given in pulse doses followed by tapering, and rituximab is administered weekly for four weeks. Additional measures include transfusions for symptomatic anemia (avoiding unnecessary platelet transfusions) and thromboprophylaxis for platelet counts >50,000. Long-term monitoring involves regular platelet counts, LDH levels, and ADAMTS13 activity assessment. Congenital TTP is managed with prophylactic plasma infusions or recombinant ADAMTS13. Depression is a common long-term complication, requiring mental health support.
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À propos des intervenants
Dr. Sridatta Pawar
Consultant Nephrologist and Transplant Physician, GM hospitals, Bangalore
Divulgation financière
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