Introduction
Thrombotic thrombocytopenic purpura
Congenital ADAMTS 13 deficiency (Upshaw–Schulman syndrome)
Acquired ADAMTS13 deficiency (autoimmune TTP)
Clinical symptoms
Initial diagnosis
Condition | Diagnostic tests |
---|---|
Hemolysis
| Hemoglobin, red blood cells, indices |
Reticulocyte and schistocyte counts | |
Lactate dehydrogenase, haptoglobin | |
Direct antiglobin test (DAT; Coombs test) | |
Thrombocytopenia
| Platelet counts; Immature platelet fraction |
Organ damage
| |
Brain | Imaging: CT scana, perfusion MRIa |
Electroencephalograma | |
S100 beta, neuron-specific enolase | |
Neurocognitive testinga | |
Kidneys | Serum creatinine, glomerular filtration rate |
Urine output | |
Heart | Electrocardiogram |
Troponin, NT-proBNP | |
Echocardiography | |
Lung | Oxygen saturation, gas exchange |
Imaging: chest x‑ray, high-resolution lung CT scana | |
Coagulation | Plasmatic coagulation assays |
Antiphospholipid antibodies | |
Pancreas | Blood glucose, serum lipase |
Specific diagnosis
| |
General | Biobanking, sampling for possible clinical trials |
Blood group typing | |
Pregnancy testa | |
Tests for viral infections (HIV, hepatitis B and C) | |
Urine analysis | |
Thyroid function tests | |
Thrombotic thrombocytopenic purpura (TTP) | ADAMTS13 activity, antigen |
Anti-ADAMTS13 antibodies and -inhibitor | |
VWF:Ag, VWF:activity, VWF:RCo, VWF:CBA, VWF multimeric pattern | |
ADAMTS13 gene analysis | |
Hemolytic uremic syndrome (HUS) | Tests for bacterial infection/toxins (E. coli, Shigella, etc) |
Complement C3 activation products, C4, CH50, APH50, C5a, terminal complement complex, CFH antibody | |
Complement factors gene analyses | |
Medical history
| Concomitant and previous diseases |
Underlying conditions (cancer, infections, systemic diseases, transplantation, pregnancy, surgery) | |
Drugs, medication | |
Family history |
Therapeutic option | Indication | Dose | Mechanism of action |
---|---|---|---|
Established options
| |||
Plasma exchange | Initial therapy in all types of TMA Treatment of choice in autoimmune TTP | 60–80 ml/kg/day | Elimination of autoantibodies, immune complexes, UL-VWF MM, sludge Replacement of ADAMTS13 and regularly composed VWF |
Plasma infusion | Congenital ADAMTS13 deficiency (Upshaw–Schulman syndrome) | 10–40 ml/kg every 2–3 weeks | Replacement of ADAMTS13 |
Corticosteroids | Autoantibody-induced TTP | 1–2 mg/kg/day | Immunosuppression |
Rituximab | Autoantibody-induced TTP | 4 doses of 100–375 mg/m2/week | Immunosuppression |
Immunomodulators (vincristine, MMF, cyclosporine, cyclophosphamide) | Autoantibody-induced TTP (3rd line immunotherapy) | As indicated | Immunosuppression |
Anti-platelet agents (ASS, clopidogrel, prasugrel, ticagrelor) | TTP with severe organ damage | Clopidogrel: 75–150 mg/day | Inhibition of platelet aggregation |
Splenectomy | Refractory TTP (after rituximab failure) | – | Unknown. Elimination of memory cells? |
Supportive therapy | Anemia: RBC transfusion organ failure: ICU | – | (Details: see text) |
Future options
| |||
Caplacizumaba | Acute autoimmune TTP | 10 mg/day sc | Blocking VWF A1 domains, competition with platelet GP Ib/IX |
Recombinant ADAMTS13b | Congenital deficiency of ADAMTS13 (Upshaw-Schulman syndrome) | 20–40 U/kg every 2–4 weeks | Replacement of ADAMTS13 |
Recombinant ADAMTS13b | Autoimmune TTP? | Unknown | Replacement of ADAMTS13 to overcome inhibitors |
N-acetylcysteineb | Acute and chronic TTP | 300 mg/kg/day | Cleavage of UL-VWF MM |