Difference between revisions of "Thrombotic thrombocytopenic purpura"

(Management)
(Background)
 
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**[[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  
  
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===Risk Factors===
 
===Risk Factors===
 
*Congenitally deficient ADAMTS-13 activity AND:
 
*Congenitally deficient ADAMTS-13 activity AND:
**Pregnancy '''OR'''
+
**[[Pregnancy]] '''OR'''
**Infection '''OR'''
+
**[[Infection]] '''OR'''
 
**Inflammation '''OR'''
 
**Inflammation '''OR'''
**Medication use (quinolones, ticlopidine, clopidogrel)
+
**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>==
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#[[Microangiopathic Hemolytic Anemia (MAHA)]]
 
#[[Microangiopathic Hemolytic Anemia (MAHA)]]
 
#[[Thrombocytopenia]]
 
#[[Thrombocytopenia]]
#Fever
+
#[[Fever]]
#Renal pathology
+
#[[AKI|Renal pathology]]
#CNS abnormalities (headache, seizure, altered mental status, CVA, coma)
+
#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
  
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==Evaluation==
 
==Evaluation==
 
*CBC with peripheral smear (anemia, '''microspherocytes''', thrombocytopenia are suggestive findings)
 
*CBC with peripheral smear (anemia, '''microspherocytes''', thrombocytopenia are suggestive findings)
 +
**Microangiopathic hemolytic anemia produces '''schistocytes'''
 
*LDH (elevated)
 
*LDH (elevated)
 
*Haptoglobin (decreased)
 
*Haptoglobin (decreased)
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*[[Urinalysis]] (hemoglobinuria)  
 
*[[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 electropharesis
+
*Gel electrophoresis
  
 
==Management==
 
==Management==
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*'''[[Plasma exchange]] (plasmapheresis)'''
 
*'''[[Plasma exchange]] (plasmapheresis)'''
 
**Replaces defective or insufficient ADAMTS-13 and clears vWF multimers  
 
**Replaces defective or insufficient ADAMTS-13 and clears vWF multimers  
*'''Transfusion of RBCs''' (only severe bleeding)
+
*'''Transfusion of [[pRBCs]]''' (only severe bleeding)
 
**Generally only indicated if plasma exchange cannot be performed immediately  
 
**Generally only indicated if plasma exchange cannot be performed immediately  
*'''FFP Transfusion'''
+
*'''[[FFP]] Transfusion'''
 
**Contains ADAMTS-13
 
**Contains ADAMTS-13
 
**Should only be initiated if delay in plasmapheresis
 
**Should only be initiated if delay in plasmapheresis
*'''Glucocorticoids'''
+
*'''[[Glucocorticoids]]'''
**Consider 1 mg/kg [[prednisone]] PO or Solumedrol 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>
+
**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>
 
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>
*'''Platelet Transfusion is AVOIDED'''
+
*'''[[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
 
**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
 
**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==
 
==Disposition==

Latest revision as of 21:58, 25 February 2020

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

Clinical Features[1]

Pentad (rarely all present)

  1. Microangiopathic Hemolytic Anemia (MAHA)
  2. Thrombocytopenia
  3. Fever
  4. Renal pathology
  5. 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

Microangiopathic Hemolytic Anemia (MAHA)

Thrombocytopenia

Decreased production

Increased platelet destruction or use

Drug Induced

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
  • 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

  1. George J: Clinical practice. Thrombotic thrombocytopenic purpura. N Engl J Med 2006; 354:1927
  2. George J. How I treat patients with thrombotic thrombocytopenic purpura: 2010. Blood 2010; 116:4060
  3. 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.
  4. 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.