Difference between revisions of "Thrombotic thrombocytopenic purpura"

(Text replacement - "==Source ==" to "==References==")
(Background)
 
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==Background==
 
==Background==
===Pathophysiology===
+
*Untreated mortality is >90%
*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.
 
 
 
 
*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:
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*Congenitally deficient ADAMTS-13 activity AND:
#Pregnancy
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**[[Pregnancy]] '''OR'''
#Infection
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**[[Infection]] '''OR'''
#Inflammation
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**Inflammation '''OR'''
#Medication use (quinolones, ticlopidine, clopidogrel)
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**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)]]'''
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#[[Microangiopathic Hemolytic Anemia (MAHA)]]
#'''Thrombocytopenia'''
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#[[Thrombocytopenia]]
#'''Fever'''
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#[[Fever]]
#'''Renal pathology'''
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#[[AKI|Renal pathology]]
#'''CNS abnormalities (seizure, AMS, CVA, coma)'''
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#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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{{Thrombocytopenia}}
 
{{Thrombocytopenia}}
  
== Diagnosis ==
+
==Evaluation==
*CBC with peripheral smear (anemia, '''schistocytes''', 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)
 
*Reticulocyte count (appropriate)
 
*Reticulocyte count (appropriate)
*UA (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 electrophoresis
  
== Treatment<ref>George J. How I treat patients with thrombotic thrombocytopenic purpura: 2010. Blood 2010; 116:4060</ref> ==
+
==Management==
;All treatments should be performed with a hematology consultation
+
''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)'''
+
*'''[[Plasma exchange]] (plasmapheresis)'''
#*Replaces defective or insufficient ADAMTS-13 and clears vWF multimers  
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**Replaces defective or insufficient ADAMTS-13 and clears vWF multimers  
#'''Transfusion of RBCs''' (only severe bleeding)
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*'''Transfusion of [[pRBCs]]''' (only severe bleeding)
#*Generally only indicated if plasma exchange cannot be performed immediately  
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**Generally only indicated if plasma exchange cannot be performed immediately  
#'''FFP Transfusion'''
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*'''[[FFP]] Transfusion'''
#*Contains ADAMTS-13
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**Contains ADAMTS-13
#*Should only be initiated if delay in plasmapheresis
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**Should only be initiated if delay in plasmapheresis
#'''Platelet Transfusion is AVOIDED'''
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*'''[[Glucocorticoids]]'''
#*Only used for life-threatening bleeding or intracranial hemorrhage under guidance from hematologist
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**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>
#*Platelet infusion may lead to acutely worsened thrombosis, renal failure, and death
+
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
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*'''[[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==
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==References==
 
==References==
 
<references/>
 
<references/>
*Hirsh J et al. [Antithrombotic and thrombolytic therapy: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008; 133(Suppl):110S-112S http://journal.publications.chestnet.org/pdfaccess.ashx?ResourceID=2124970&PDFSource=13]
+
 
 
[[Category:Heme/Onc]]
 
[[Category:Heme/Onc]]

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.