Difference between revisions of "Thrombotic thrombocytopenic purpura"
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==Background== | ==Background== | ||
| − | + | *Untreated mortality is >90% | |
| − | * | ||
| − | |||
*Similar clinical symptoms but different pathophysiology than [[HUS]] | *Similar clinical symptoms but different pathophysiology than [[HUS]] | ||
**[[HUS]] More common in pediatrics | **[[HUS]] More common in pediatrics | ||
*'''[[Microangiopathic Hemolytic Anemia (MAHA)]] + [[thrombocytopenia|low Platelets]] is TTP until proven otherwise''' | *'''[[Microangiopathic Hemolytic Anemia (MAHA)]] + [[thrombocytopenia|low Platelets]] is TTP until proven otherwise''' | ||
| + | **MAHA is non-immune hemolysis (Coomb's-negative hemolysis) causing RBC fragmentation producing schistocytes | ||
*Can occur as a result of [[Plavix]] (clopidogrel) use, especially within the first 2 weeks | *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=== | ===Risk Factors=== | ||
| − | + | *Congenitally deficient ADAMTS-13 activity AND: | |
| − | + | **[[Pregnancy]] '''OR''' | |
| − | + | **[[Infection]] '''OR''' | |
| − | + | **Inflammation '''OR''' | |
| − | + | **Medication use ([[quinolones]], [[ticlopidine]], [[clopidogrel]]) | |
==Clinical Features<ref>George J: Clinical practice. Thrombotic thrombocytopenic purpura. N Engl J Med 2006; 354:1927</ref>== | ==Clinical Features<ref>George J: Clinical practice. Thrombotic thrombocytopenic purpura. N Engl J Med 2006; 354:1927</ref>== | ||
===Pentad (rarely all present)=== | ===Pentad (rarely all present)=== | ||
| − | # | + | #[[Microangiopathic Hemolytic Anemia (MAHA)]] |
| − | # | + | #[[Thrombocytopenia]] |
| − | # | + | #[[Fever]] |
| − | # | + | #[[AKI|Renal pathology]] |
| − | # | + | #CNS abnormalities ([[headache]], [[seizure]], [[altered mental status]], [[CVA]], [[coma]]) |
#*Neuro symptoms are often transient, may not be present in ED | #*Neuro symptoms are often transient, may not be present in ED | ||
| Line 38: | Line 40: | ||
*Anemia, platelet count, and LDH tend to be more severe in TTP; LFTs more severe in HELLP | *Anemia, platelet count, and LDH tend to be more severe in TTP; LFTs more severe in HELLP | ||
| − | == | + | {{Hemolytic anemia DDX}} |
| − | *CBC with peripheral smear (anemia, ''' | + | |
| + | {{Thrombocytopenia}} | ||
| + | |||
| + | ==Evaluation== | ||
| + | *CBC with peripheral smear (anemia, '''microspherocytes''', thrombocytopenia are suggestive findings) | ||
| + | **Microangiopathic hemolytic anemia produces '''schistocytes''' | ||
*LDH (elevated) | *LDH (elevated) | ||
*Haptoglobin (decreased) | *Haptoglobin (decreased) | ||
*Reticulocyte count (appropriate) | *Reticulocyte count (appropriate) | ||
| − | * | + | *[[Urinalysis]] (hemoglobinuria) |
*Creatinine (possibly elevated) | *Creatinine (possibly elevated) | ||
| − | *LFTs (increased bilirubin) | + | *[[LFTs]] (increased bilirubin) |
*PT/PTT/INR (normal; differentiates from [[DIC]]) | *PT/PTT/INR (normal; differentiates from [[DIC]]) | ||
*Urine pregnancy (significant association between pregnancy and TTP) | *Urine pregnancy (significant association between pregnancy and TTP) | ||
| + | *Gel electrophoresis | ||
| − | == | + | ==Management== |
| − | + | ''Management ideally done in consultation with heme/onc''<ref>George J. How I treat patients with thrombotic thrombocytopenic purpura: 2010. Blood 2010; 116:4060</ref> | |
| − | + | *'''[[Plasma exchange]] (plasmapheresis)''' | |
| − | + | **Replaces defective or insufficient ADAMTS-13 and clears vWF multimers | |
| − | + | *'''Transfusion of [[pRBCs]]''' (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 [[methylprednisolone]] 125 mg IV<ref>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.</ref><ref> | |
| − | + | 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.</ref> | |
| − | + | *'''[[Splenectomy]]''' - 2nd line therapy after stabilization | |
| + | **Inhibitor antibody is made in the spleen | ||
| + | *[[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 | ||
==Disposition== | ==Disposition== | ||
| Line 74: | Line 86: | ||
*[[ITP]] | *[[ITP]] | ||
| − | == | + | ==References== |
<references/> | <references/> | ||
| − | + | ||
[[Category:Heme/Onc]] | [[Category:Heme/Onc]] | ||
Latest revision as of 21:58, 25 February 2020
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
- MAHA is non-immune hemolysis (Coomb's-negative hemolysis) causing RBC fragmentation producing schistocytes
- 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 (PNH)
- Malignant hypertension
- Scleroderma
- Antiphospholipid Syndrome (APS)
- 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)
- Congenital 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, thiazide diuretics/furosemide
Comparison by Etiology
| ITP | TTP | HUS | HIT | DIC | |
|---|---|---|---|---|---|
| ↓ PLT | Yes | Yes | Yes | Yes | Yes |
| ↑PT/INR | No | No | No | +/- | Yes |
| MAHA | No | Yes | Yes | No | Yes |
| ↓ 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)
- Microangiopathic hemolytic anemia produces schistocytes
- 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 electrophoresis
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 pRBCs (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 methylprednisolone 125 mg IV[3][4]
- Splenectomy - 2nd line therapy after stabilization
- Inhibitor antibody is made in the spleen
- 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
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.