Difference between revisions of "Thrombotic thrombocytopenic purpura"

(Clarified diagnosis and minor aditions to pathophys)
(Background)
 
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==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
****Platelet clots are transient, symptoms, especially neuro, can be in flux
+
*'''[[Microangiopathic Hemolytic Anemia (MAHA)]] + [[thrombocytopenia|low Platelets]] is TTP until proven otherwise'''
*Similar to but different from [[HUS]] (which is more common in peds)
+
**MAHA is non-immune hemolysis (Coomb's-negative hemolysis) causing RBC fragmentation producing schistocytes
*[[Microangiopathic Hemolytic Anemia (MAHA)]] + 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==
+
==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
  
*TTP pentad mnemonic = FAT RN
+
;TTP pentad mnemonic = '''FAT RN'''
**Fever, Anemia, Thrombocytopenia, Renal, Neuro sx
+
*Fever, Anemia, Thrombocytopenia, Renal, Neuro Symptoms
***All features do not need to be present at the same time
 
  
 +
*''All features DO NOT need to be present at the same time''
 
*Consider diagnosis without the full pentad
 
*Consider diagnosis without the full pentad
**MAHA + Thrombocytopenia + any other feature
 
  
==DDX==
+
==Differential Diagnosis==
 
*Other MAHAs (eg, [[HUS]], [[DIC]], [[malignant hypertension]])
 
*Other MAHAs (eg, [[HUS]], [[DIC]], [[malignant hypertension]])
 
*[[ITP]]
 
*[[ITP]]
Line 37: Line 38:
 
*[[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
 
  
== Work-Up ==
+
{{Hemolytic anemia DDX}}
  
*CBC with peripheral smear (anemia, '''schistocytes''', thrombocytopenia)
+
{{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)
*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'''
***Contains ADAMTS-13
+
**Contains ADAMTS-13
**Platelet (only for life-threatening bleeding or intracranial hemorrhage)
+
**Should only be initiated if delay in plasmapheresis
***Platelet infusion may lead to acutely worsened thrombosis, renal failure, and death
+
*'''[[Glucocorticoids]]'''
*Splenectomy - 2nd line therapy
+
**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==
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==See Also==
 
==See Also==
*[[Microangiopathic Hemolytic Anemia (MAHA)]], [[HUS]], [[DIC]]
+
*[[Microangiopathic Hemolytic Anemia (MAHA)]]
 +
*[[HUS]]
 +
*[[DIC]]
 
*[[HELLP]], [[SLE]], [[Antiphospholipid Syndrome (APS)]]
 
*[[HELLP]], [[SLE]], [[Antiphospholipid Syndrome (APS)]]
 
*[[ITP]]
 
*[[ITP]]
  
==Source ==
+
==References==
*Tintinalli
+
<references/>
*Harwood Nuss
+
 
*Rosens
 
 
[[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.