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==Background==
==Background==
*Untreated mortality is >90%
*Untreated mortality is >90%
*Similar clinical symptoms but different pathophysiology than [[HUS]]
**[[HUS]] more common in pediatrics
*[[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


===Pathophysiology===
===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.
*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]]
**[[HUS]] More common in pediatrics
*'''[[Microangiopathic Hemolytic Anemia (MAHA)]] + [[thrombocytopenia|low Platelets]] is TTP until proven otherwise'''
*Can occur as a result of [[Plavix]] (clopidogrel) use, especially within the first 2 weeks


===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==
===Pentad (rarely all present)===
[[File:Echymosis.jpg|thumb|Spontaneous bruising in a woman with critically low platelets.]]
===Pentad (rarely all present)<ref>George J: Clinical practice. Thrombotic thrombocytopenic purpura. N Engl J Med 2006; 354:1927</ref>===
#[[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


;TTP pentad mnemonic = '''FAT RN'''
;TTP pentad mnemonic = FAT RN
*Fever, Anemia, Thrombocytopenia, Renal, Neuro Symptoms
*Fever, Anemia, Thrombocytopenia, Renal, Neuro Symptoms


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==Evaluation==
==Evaluation==
*CBC with peripheral smear (anemia, '''schistocytes''', thrombocytopenia are suggestive findings)
===Workup===
*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)


==Treatment<ref>George J. How I treat patients with thrombotic thrombocytopenic purpura: 2010. Blood 2010; 116:4060</ref>==
===Diagnosis===
;All treatments should be performed with a hematology consultation
*Plasma ADAMTS-13 Level:
**Ideally drawn prior to initiation of treatment, but results rarely available in the ER.
**Level Interpretation
***<10 IU/dL Confirms the diagnosis
***10-20 IU/dL Equivocal result
***>20 IU/dL within normal, consider other diagnoses
 
*PLASMIC Score: <5 features effectively rules out TTP (99% NPV)<ref>Paydary K, Banwell E, Tong J, Chen Y, Cuker A. Diagnostic accuracy of the PLASMIC score in patients with suspected thrombotic thrombocytopenic purpura: A systematic review and meta-analysis. Transfusion. 2020 Sep;60(9):2047-2057. doi: 10.1111/trf.15954. Epub 2020 Aug 5. PMID: 32757237.</ref>
**Platelets <30 x 10<sup>9</sup>/L
**Hemolysis with reticulocye count >2.5%, indirect bilirubin >2mg/dL, or low haptoglobin
**MCV <90fL
**INR <1.5
**Creatinine <2mg/dL
**No Current Cancer


#'''Plasma exchange (plasmapheresis)'''
==Management==
#*Replaces defective or insufficient ADAMTS-13 and clears vWF multimers  
''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>
#'''Transfusion of RBCs''' (only severe bleeding)
 
#*Generally only indicated if plasma exchange cannot be performed immediately
*[[Plasma exchange]] (plasmapheresis)
#'''FFP Transfusion'''
**Replaces defective or insufficient ADAMTS-13 and clears vWF multimers  
#*Contains ADAMTS-13
*[[FFP]] Transfusion
#*Should only be initiated if delay in plasmapheresis
**Contains ADAMTS-13
#'''Glucocorticoids'''
**Should only be initiated if delay in plasmapheresis
#*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>
*[[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>
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'''
*'''Biologic Therapies:''' ISTH guidelines now recommend adding both empiric rituximab and caplacizumab for patients with high pretest probability while awaiting ADAMTS-13 levels.<ref>Zheng XL, Vesely SK, Cataland SR, Coppo P, Geldziler B, Iorio A, Matsumoto M, Mustafa RA, Pai M, Rock G, Russell L, Tarawneh R, Valdes J, Peyvandi F. ISTH guidelines for treatment of thrombotic thrombocytopenic purpura. J Thromb Haemost. 2020 Oct;18(10):2496-2502. doi: 10.1111/jth.15010. Epub 2020 Sep 11. PMID: 32914526; PMCID: PMC8091490.</ref>
#*Only used for life-threatening bleeding or intracranial hemorrhage under guidance from hematologist
**Rituximab is a monoclonal antibody against CD20 and is used in many autoimmune disorders
#*Platelet infusion may lead to acutely worsened thrombosis, renal failure, and death
**Caplacizumab is a monoclonal antibody blocking platelet-vWF interactions and thus formation of microvascular thrombosis.
#'''Splenectomy''' - 2nd line therapy after stabilization
***Caplacizumab may be withheld in patients with whom no ADAMTS-13 can be obtained as there are concerns for increased bleeding risk with this therapy
**In patients with low pretest probability, consider empiric plasma exchange and steroids and withhold these biologics pending ADAMTS-13 results.
*Transfusion of [[pRBCs]] (only severe bleeding)
**Generally only indicated if plasma exchange cannot be performed immediately
*[[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==
*Admit for plasma exchange
*Admit for plasma exchange
==Medication Dosing==
*{{MedicationDose|drug=Methylprednisolone|dose=125 mg IV (or prednisone 1 mg/kg PO)|route=IV/PO|context=Glucocorticoid (adjunct to plasmapheresis)|indication=Thrombotic thrombocytopenic purpura|population=Adult}}


==See Also==
==See Also==
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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]]

Revisión actual - 09:34 22 mar 2026

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

Spontaneous bruising in a woman with critically low platelets.

Pentad (rarely all present)[1]

  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

Workup

  • 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)

Diagnosis

  • Plasma ADAMTS-13 Level:
    • Ideally drawn prior to initiation of treatment, but results rarely available in the ER.
    • Level Interpretation
      • <10 IU/dL Confirms the diagnosis
      • 10-20 IU/dL Equivocal result
      • >20 IU/dL within normal, consider other diagnoses
  • PLASMIC Score: <5 features effectively rules out TTP (99% NPV)[2]
    • Platelets <30 x 109/L
    • Hemolysis with reticulocye count >2.5%, indirect bilirubin >2mg/dL, or low haptoglobin
    • MCV <90fL
    • INR <1.5
    • Creatinine <2mg/dL
    • No Current Cancer

Management

Management ideally done in consultation with heme/onc[3]

  • Plasma exchange (plasmapheresis)
    • Replaces defective or insufficient ADAMTS-13 and clears vWF multimers
  • FFP Transfusion
    • Contains ADAMTS-13
    • Should only be initiated if delay in plasmapheresis
  • Glucocorticoids
  • Biologic Therapies: ISTH guidelines now recommend adding both empiric rituximab and caplacizumab for patients with high pretest probability while awaiting ADAMTS-13 levels.[6]
    • Rituximab is a monoclonal antibody against CD20 and is used in many autoimmune disorders
    • Caplacizumab is a monoclonal antibody blocking platelet-vWF interactions and thus formation of microvascular thrombosis.
      • Caplacizumab may be withheld in patients with whom no ADAMTS-13 can be obtained as there are concerns for increased bleeding risk with this therapy
    • In patients with low pretest probability, consider empiric plasma exchange and steroids and withhold these biologics pending ADAMTS-13 results.
  • Transfusion of pRBCs (only severe bleeding)
    • Generally only indicated if plasma exchange cannot be performed immediately
  • 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


Medication Dosing

See Also

References

  1. ↑ George J: Clinical practice. Thrombotic thrombocytopenic purpura. N Engl J Med 2006; 354:1927
  2. ↑ Paydary K, Banwell E, Tong J, Chen Y, Cuker A. Diagnostic accuracy of the PLASMIC score in patients with suspected thrombotic thrombocytopenic purpura: A systematic review and meta-analysis. Transfusion. 2020 Sep;60(9):2047-2057. doi: 10.1111/trf.15954. Epub 2020 Aug 5. PMID: 32757237.
  3. ↑ George J. How I treat patients with thrombotic thrombocytopenic purpura: 2010. Blood 2010; 116:4060
  4. ↑ 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.
  5. ↑ 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.
  6. ↑ Zheng XL, Vesely SK, Cataland SR, Coppo P, Geldziler B, Iorio A, Matsumoto M, Mustafa RA, Pai M, Rock G, Russell L, Tarawneh R, Valdes J, Peyvandi F. ISTH guidelines for treatment of thrombotic thrombocytopenic purpura. J Thromb Haemost. 2020 Oct;18(10):2496-2502. doi: 10.1111/jth.15010. Epub 2020 Sep 11. PMID: 32914526; PMCID: PMC8091490.
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