Thrombotic thrombocytopenic purpura: Difference between revisions

(edit)
No edit summary
(30 intermediate revisions by 10 users not shown)
Line 1: Line 1:
==Background==
==Background==
*Pathophysiology
*Untreated mortality is >90%
**Insufficient ADAMTS-13 activity allows vWF multimers to accumulate in microcirculation
*Similar clinical symptoms but different pathophysiology than [[HUS]]
***Leads to platelet aggregation/thrombocytopenia and hemolysis of RBCs
**[[HUS]] More common in pediatrics
*Similar to but different from [[HUS]] (which is more common in peds)
*'''[[Microangiopathic Hemolytic Anemia (MAHA)]] + [[thrombocytopenia|low Platelets]] is TTP until proven otherwise'''
*[[Microangiopathic hemolytic anemia]] + low plts is TTP until proven otherwise
*Can occur as a result of [[Plavix]] (clopidogrel) use, especially within the first 2 weeks
*Can occur as a result of [[Plavix]] (clopidogrel) use (usually within first 2 wk of starting)
 
===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>==
===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


==Clinical Features==
;TTP pentad mnemonic = '''FAT RN'''
*Pentad
*Fever, Anemia, Thrombocytopenia, Renal, Neuro Symptoms
#[[Microangiopathic hemolytic anemia (MAHA)]]
#Thrombocytopenia
#Fever
#Renal pathology
#CNS abnormalities (seizure, AMS, CVA, coma)


*TTP pentad mnemonic = FAT RN
*''All features DO NOT need to be present at the same time''
**Fever, Anemia, Thrombocytopenia, Renal, Neuro sx
*Consider diagnosis without the full pentad


==DDX==
==Differential Diagnosis==
*Other microangiopathic hemolytic anemias (eg, [[HUS]], [[DIC]], [[malignant hypertension]])
*Other MAHAs (eg, [[HUS]], [[DIC]], [[malignant hypertension]])
*[[ITP]]
*[[ITP]]
*[[Sepsis]]
*[[Sepsis]]
*[[SLE]]
*[[SLE]]
*[[HELLP]] syndrome
*[[HELLP]] syndrome
**Difficult to distinguish
*Anemia, platelet count, and LDH tend to be more severe in TTP; LFTs more severe in HELLP
**Anemia, plt count, and LDH tend to be more severe in TTP; LFTs more severe in HELLP
 
{{Hemolytic anemia DDX}}


== Work-Up ==
{{Thrombocytopenia}}


*CBC with peripheral smear (anemia, '''schistocytes''', thrombocytopenia)
==Evaluation==
*CBC with peripheral smear (anemia, '''microspherocytes''', thrombocytopenia are suggestive findings)
*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 ==
==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)  
*'''[[Plasma exchange]] (plasmapheresis)'''
**Replaces defective or insufficient ADAMTS-13 and clears vWF multimers  
**Replaces defective or insufficient ADAMTS-13 and clears vWF multimers  
*Transfusion  
*'''Transfusion of [[pRBCs]]''' (only severe bleeding)
**Indicated if plasma exchange cannot be performed immediately  
**Generally only indicated if plasma exchange cannot be performed immediately  
**FFP
*'''[[FFP]] Transfusion'''
**Platelet (only for life-threatening bleeding or intracranial hemorrhage)
**Contains ADAMTS-13
***Platelet infusion may lead to acutely worsened thrombosis, renal failure, and death
**Should only be initiated if delay in plasmapheresis
*Splenectomy - 2nd line therapy
*'''[[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 61: Line 78:


==See Also==
==See Also==
*[[Microangiopathic hemolytic anemia]], [[HUS]], [[DIC]]
*[[Microangiopathic Hemolytic Anemia (MAHA)]]
*[[HELLP]], [[SLE]], [[antiphospholipid syndrome]]
*[[HUS]]
*[[DIC]]
*[[HELLP]], [[SLE]], [[Antiphospholipid Syndrome (APS)]]
*[[ITP]]
*[[ITP]]


==Source ==
==References==
*Tintinalli
<references/>
*Harwood Nuss
 
[[Category:Heme/Onc]]
[[Category:Heme/Onc]]

Revision as of 18:52, 1 October 2019

Background

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)
  • 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.
Retrieved from "https://www.wikem.org/w/index.php?title=Thrombotic_thrombocytopenic_purpura&oldid=231372"