Thrombotic thrombocytopenic purpura: Difference between revisions

(Text replacement - "==Diagnosis==" to "==Evaluation==")
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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:
*Congenitally deficient ADAMTS-13 activity AND:
#Pregnancy
**[[Pregnancy]] '''OR'''
#Infection
**[[Infection]] '''OR'''
#Inflammation
**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>==
===Pentad (rarely all present)===
===Pentad (rarely all present)===
#'''[[Microangiopathic Hemolytic Anemia (MAHA)]]'''
#[[Microangiopathic Hemolytic Anemia (MAHA)]]
#'''Thrombocytopenia'''
#[[Thrombocytopenia]]
#'''Fever'''
#[[Fever]]
#'''Renal pathology'''
#[[AKI|Renal pathology]]
#'''CNS abnormalities (seizure, AMS, 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, '''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  
**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
#'''Platelet Transfusion is AVOIDED'''
*'''[[Glucocorticoids]]'''
#*Only used for life-threatening bleeding or intracranial hemorrhage under guidance from hematologist
**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
*'''[[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]]

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.