Difference between revisions of "Thrombotic thrombocytopenic purpura"

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*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 electropharesis
  
 
==Treatment<ref>George J. How I treat patients with thrombotic thrombocytopenic purpura: 2010. Blood 2010; 116:4060</ref>==
 
==Treatment<ref>George J. How I treat patients with thrombotic thrombocytopenic purpura: 2010. Blood 2010; 116:4060</ref>==

Revision as of 02:01, 6 December 2016

Background

  • Untreated mortality is >90%

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

Congenitally deficient ADAMTS-13 activity AND
  1. Pregnancy
  2. Infection
  3. Inflammation
  4. Medication use (quinolones, ticlopidine, clopidogrel)

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, schistocytes, 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 electropharesis

Treatment[2]

All treatments should be performed with a hematology consultation
  1. Plasma exchange (plasmapheresis)
    • Replaces defective or insufficient ADAMTS-13 and clears vWF multimers
  2. Transfusion of RBCs (only severe bleeding)
    • Generally only indicated if plasma exchange cannot be performed immediately
  3. FFP Transfusion
    • Contains ADAMTS-13
    • Should only be initiated if delay in plasmapheresis
  4. Glucocorticoids
  5. 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
  6. Splenectomy - 2nd line therapy after stabilization

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.