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Journal Club

Journal Club. February 2019 M. Thormann.  Gastroenterology 2018;155:705–718. Thrombocytopenia in CLD patients. Common finding Causes Splenic sequestration Increased destruction Decreased production of thrombopoietin Myeloid suppression Platelet transfusions to prevent bleeding ?.

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Journal Club

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  1. Journal Club February 2019 M. Thormann Gastroenterology 2018;155:705–718

  2. Thrombocytopenia in CLD patients • Common finding • Causes • Splenicsequestration • Increaseddestruction • Decreasedproductionofthrombopoietin • Myeloidsuppression • Platelettransfusionstopreventbleeding?

  3. Avatrombopag • TPO-R agonist (Mplbindingprotein) • Binding thetransmembranedomainof TPO receptor • First data 2004 • orallyadministered, for 5 days • Plateletadjusted dose • Similar: Eltrombopag, Romiplostim • Eltrombopagstudied in CLD patients • Lusutrombopag (7 days)

  4. ADAPT-1 & ADAPT-2

  5. ADAPT-1 & ADAPT-2 • Primary endpoint • Proportion ofpatients not requiring • Platelettransfusion • Rescueprocedureforbleeding • Secondaryefficacyendpoints • theproportionofpatientsachievingtargetplateletcountof > 50 on procedureday • thechange in plateletcountfrombaselinetoprocedureday Upto 7 days after procedure

  6. Selected procedures

  7. Results Proportion ofpatientswhoachievedplateletcounts > 50 on procedureday Proportion ofpatients not requiring a platelettransfusionoranyrescueprocedureforbleeding

  8. Results But: nodifference in bleedingevents Magnitude ofchange in plateletcountfrombaselinetoprocedureday.

  9. ADAPT-1 ADAPT-2

  10. Complications Overall safetyprofilesimilartoplacebo ADAPT-1 (high baseline): 2 deaths (not studyrelated) ADAPT-2 (high baseline): 1 partial portalveinthrombosis, day 13 (possiblyrelated) ADAPT-1 (lowbaseline): 1 portalveinthrombosis, day 31, receivedtransfusion (not related) (1 portalveinthrombosis in phase II)

  11. Conclusions Efficacy Safety Treatment window 10-13 days after first dose Shortfalls • Study design • onlyoneapplication • noprospectiveimagingincluded in protocol • Nodecrease in bleeding • qualityofthrombocytes • study design related?

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