Thrombotic Thrombocytopenic Purpura

OVERVIEW

Thrombotic Thrombocytopenic Purpura (TTP) is a rare life-threatening condition that resembles HUS, the distinction is important because TTP can be treated with plasmapheresis

PATHOPHYSIOLOGY

  • vWF synthesized in endothelial cells and assembled in larger multimers than those seen in plasma (ultra large vWF)
  • rapidly degraded to normal sized multimers in plasma by the protease ADAMTS13
  • in TTP there are autoantibodies against ADAMTS13
    -> accumulation of ULvWF
    -> platelet aggregation and clumping
    -> extensive microthrombi formation with haemolysis (MAHA) and end organ effects
  • TTP may be triggered by an intercurrent event (e.g. surgery, pancreatitis, sepsis, pregnancy) resulting in endothelial activation

CLINICAL FEATURES

Classic pentad (FAT R/N)

  • fever
  • anaemia (microangiopathic haemolytic anaemia)
  • thrombocytopenia
  • renal problems (88% have renal problems, 15% haematuria) – more likely in HUS than TTP
  • neurological problems (headaches, confusion, seizures, intracranial hemorrhage, focal deficits) – more likely in TTP than HUS

Risk factors

  • infection (enterohemorrhagic E.coli 0157) (classically HUS)
  • drugs (calcineurin antagonists, clopidogrel, cyclosporin, ticlopidine)
  • pregnancy
  • SLE
  • graft versus host disease
  • HIV-1
  • connective tissue disorders
  • malignancy

INVESTIGATIONS

FBC

  • anaemia
  • thrombocytopenia
  • variable neutrophilia (should exclude toxic appearance)

Peripheral Blood Film

  • markers of microangiopathic anaemia
    -> polychromasia, schistocytes and spherocytes
    -> increased reticulocytes

Haemolysis Screen

  • reduced haptoglobins
  • increased LDH (this is the most sensitive marker of severity and disease activity)
  • unconjugated hyperbilirubinaemia
  • increased urinary urobilinogen
  • negative Coomb’s test (no antibodies bound to patient RBCs)

Urinalysis

  • near normal
  • exclude active sediment

Biochemistry

  • increased urea and creatinine levels (greater in HUS)

Coagulation

  • normal

CT Head

  • excludes intracranial pathology as a cause for the seizures

Other microbiological cultures

  • urine, blood, LP (often contra-indicated by thrombocytopenia)
  • all should exclude active infection

ADAMTS13 protease

  • low

Biopsy

  • skin, muscle, gingival, lymph nodes, bone marrow -> typical microaneurysms and fibrin

MANAGEMENT

  • plasmapheresis
    -> decreased mortality to < 10% (can perform plasma exchange up twice daily)
    -> initiate emergently
    -> FFP or cryoprecipitate replacement (not albumin)
    -> 1.5 plasma volumes daily until remission (plts >150)
  • corticosteroids 1mg/kg/day
  • seek and treat thrombotic complications
  • don’t transfuse unless clinically indicated (e.g. life-threatening haemorrhage)
  • daily platelets level until > 150 and LDH normal for 2-3 days
  • rituximab IV (chimeric monoclonal anti-CD20 antibody – CD20 is mostly found on B cells)

References and Links

  • Booth KK, Terrell DR, Vesely SK, George JN. Systemic infections mimicking thrombotic thrombocytopenic purpura. Am J Hematol. 2011 Sep;86(9):743-51. PMC3420338.
  • Sadler JE. Thrombotic thrombocytopenic purpura: a moving target. Hematology Am Soc Hematol Educ Program. 2006:415-20. PMID: 17124092.
  • Tsai HM. Pathophysiology of thrombotic thrombocytopenic purpura. Int J Hematol. 2010 Jan;91(1):1-19. PMC3159000.
  • Eponymictionary. Moschcowitz disease (1925)
  • Eponymictionary. Eli Moschcowitz (1879 – 1964)

CCC 700 6

Critical Care

Compendium

Chris is an Intensivist and ECMO specialist at the Alfred ICU in Melbourne. He is also the Innovation Lead for the Australian Centre for Health Innovation at Alfred Health and Clinical Adjunct Associate Professor at Monash University. He is a co-founder of the Australia and New Zealand Clinician Educator Network (ANZCEN) and is the Lead for the ANZCEN Clinician Educator Incubator programme. He is on the Board of Directors for the Intensive Care Foundation and is a First Part Examiner for the College of Intensive Care Medicine. He is an internationally recognised Clinician Educator with a passion for helping clinicians learn and for improving the clinical performance of individuals and collectives.

After finishing his medical degree at the University of Auckland, he continued post-graduate training in New Zealand as well as Australia’s Northern Territory, Perth and Melbourne. He has completed fellowship training in both intensive care medicine and emergency medicine, as well as post-graduate training in biochemistry, clinical toxicology, clinical epidemiology, and health professional education.

He is actively involved in in using translational simulation to improve patient care and the design of processes and systems at Alfred Health. He coordinates the Alfred ICU’s education and simulation programmes and runs the unit’s education website, INTENSIVE.  He created the ‘Critically Ill Airway’ course and teaches on numerous courses around the world. He is one of the founders of the FOAM movement (Free Open-Access Medical education) and is co-creator of litfl.com, the RAGE podcast, the Resuscitology course, and the SMACC conference.

His one great achievement is being the father of two amazing children.

On Twitter, he is @precordialthump.

| INTENSIVE | RAGE | Resuscitology | SMACC

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