We need you! Join our contributor community and become a WikEM editor through our open and transparent promotion process.
Thrombotic thrombocytopenic purpura
From WikEM
Contents
Background
- Untreated mortality is >90%
- Similar clinical symptoms but different pathophysiology than HUS
- HUS More common in pediatrics
- Microangiopathic Hemolytic Anemia (MAHA) + low Platelets is TTP until proven otherwise
- Can occur as a result of Plavix (clopidogrel) use, especially within the first 2 weeks
Pathophysiology
- Insufficient ADAMTS-13 activity allows vWF multimers to accumulate in microcirculation which leads to platelet aggregation/thrombocytopenia and hemolysis of RBCs. Platelet clots are transient, but the symptoms especially neuro, can be in flux.
Risk Factors
- Congenitally deficient ADAMTS-13 activity AND:
- Pregnancy OR
- Infection OR
- Inflammation OR
- Medication use (quinolones, ticlopidine, clopidogrel)
Clinical Features[1]
Pentad (rarely all present)
- Microangiopathic Hemolytic Anemia (MAHA)
- Thrombocytopenia
- Fever
- Renal pathology
- CNS abnormalities (headache, seizure, altered mental status, CVA, coma)
- Neuro symptoms are often transient, may not be present in ED
- TTP pentad mnemonic = FAT RN
- Fever, Anemia, Thrombocytopenia, Renal, Neuro Symptoms
- All features DO NOT need to be present at the same time
- Consider diagnosis without the full pentad
Differential Diagnosis
- Other MAHAs (eg, HUS, DIC, malignant hypertension)
- ITP
- Sepsis
- SLE
- HELLP syndrome
- Anemia, platelet count, and LDH tend to be more severe in TTP; LFTs more severe in HELLP
Microangiopathic Hemolytic Anemia (MAHA)
- Disseminated Intravascular Coagulation (DIC)
- Thrombotic Thrombocytopenic Purpura (TTP)
- Hemolytic Uremic Syndrome (HUS)
- HELLP syndrome
- Heparin-Induced Thrombocytopenia (HIT)
- Hereditary spherocytosis
- Paroxysmal nocturnal hemoglobinuria
- Malignant hypertension
- Antiphospholipid syndrome
- Scleroderma
- Antiphospholipid Syndrome (APS)
- Paroxysmal Nocturnal Hemoglobinuria (PNH)
- Other medical causes: malignancy, renal allograft rejection, vasculitides like polyarteritis nodosa and Wegener's granulomatosis
- Drugs: chemotherapy; Clopidogrel (Plavix) associated with TTP
- Nonvascular causes: prosthetic valve (more common with mechanical, more common at aortic valve), LVAD, TIPS, coil embolization, patched AV shunt, AVM
Thrombocytopenia
Decreased production
- Marrow infiltration (tumor or infection)
- Viral infections (rubella, HIV)
- Marrow Suppression (commonly chemotherapy or radiation)
- Congentital thrombocytopenia
- Fanconi anemia
- Alport syndrome
- Bernand Soulier
- Vitamin B12 and/or folate deficiency
Increased platelet destruction or use
- Idiopathic thrombocytopenic purpura
- Thrombotic Thrombocytopenic Purpura (TTP)
- Hemolytic Uremic Syndrome (HUS)
- Disseminated Intravascular Coagulation (DIC)
- Viral infections (HIV, mumps, varicella, EBV)
- Drugs (heparin, protamine)
- Postransfusion or Posttransplantation
- Autoimmune destruction (SLE or Sarcoidosis)
- Mechanical destruction
- Artificial valves
- ECMO
- HELLP syndrome
- Excessive hemorrhage
- Hemodialysis, extracorporeal circulation
- Splenic Sequestration
- Occurs in Sickle cell disease and Cirrhosis
Drug Induced
- sulfa antibiotics, ETOH, ASA, thiazides/furosemide
Comparision by Etiology
| ITP | TTP | HUS | HIT | DIC | |
|---|---|---|---|---|---|
| ↓ PLT | Yes | Yes | Yes | Yes | Yes |
| ↑PT/INR | No | No | No | +/- | Yes |
| MAHA | No | Yes | Yes | No | No |
| ↓ Fibrinogen | No | No | No | No | Yes |
| Ok to give PLT | Yes | No | No | No | Yes |
Evaluation
- CBC with peripheral smear (anemia, microspherocytes, thrombocytopenia are suggestive findings)
- LDH (elevated)
- Haptoglobin (decreased)
- Reticulocyte count (appropriate)
- Urinalysis (hemoglobinuria)
- Creatinine (possibly elevated)
- LFTs (increased bilirubin)
- PT/PTT/INR (normal; differentiates from DIC)
- Urine pregnancy (significant association between pregnancy and TTP)
- Gel electropharesis
Management
Management ideally done in consultation with heme/onc[2]
- Plasma exchange (plasmapheresis)
- Replaces defective or insufficient ADAMTS-13 and clears vWF multimers
- Transfusion of RBCs (only severe bleeding)
- Generally only indicated if plasma exchange cannot be performed immediately
- FFP Transfusion
- Contains ADAMTS-13
- Should only be initiated if delay in plasmapheresis
- Glucocorticoids
- Consider 1 mg/kg prednisone PO or Solumedrol 125 mg IV[3][4]
- Platelet Transfusion is AVOIDED
- Only used for life-threatening bleeding or intracranial hemorrhage under guidance from hematologist
- Platelet infusion may lead to acutely worsened thrombosis, renal failure, and death
- Splenectomy - 2nd line therapy after stabilization
- Inhibitor antibody is made in the spleen
Disposition
- Admit for plasma exchange
See Also
References
- ↑ George J: Clinical practice. Thrombotic thrombocytopenic purpura. N Engl J Med 2006; 354:1927
- ↑ George J. How I treat patients with thrombotic thrombocytopenic purpura: 2010. Blood 2010; 116:4060
- ↑ Bell WR, Braine HG, Ness PM, Kickler TS. Improved survival in thrombotic thrombocytopenic purpura-hemolytic uremic syndrome. Clinical experience in 108 patients. N Engl J Med 1991; 325:398.
- ↑ Balduini CL, Gugliotta L, Luppi M, et al. High versus standard dose methylprednisolone in the acute phase of idiopathic thrombotic thrombocytopenic purpura: a randomized study. Ann Hematol 2010; 89:591.
