Congenital Amegakaryocytic Thrombocytopenia



Congenital Amegakaryocytic Thrombocytopenia


David Czuchlewski, MD









Patients with congenital amegakaryocytic thrombocytopenia present at birth or soon after with platelet counts of around 20,000/µL. Platelets that are present image are morphologically normal.






Congenital amegakaryocytic thrombocytopenia is characterized by absent or markedly reduced megakaryocytes. Other lineages are unaffected, and early in the disease course, cellularity is normal.


TERMINOLOGY


Abbreviations



  • Congenital amegakaryocytic thrombocytopenia (CAMT)


Definitions



  • Autosomal recessive disease characterized by



    • Thrombocytopenia, usually presenting at birth


    • Absence of syndromic malformations or dysmorphism


    • Frequent evolution to multilineage bone marrow failure and pancytopenia


ETIOLOGY/PATHOGENESIS


Overview of Thrombopoietin (TPO) Signaling



  • TPO is produced at fairly constant rate


  • TPO is removed from circulation by binding to TPO receptors on platelets and megakaryocytes



    • TPO receptor is known as MPL (c-Mpl, CD110) and is encoded by gene MPL


    • As platelet count increases, more TPO is consumed by platelets bearing MPL and thus less is available to stimulate bone marrow production


  • Intact THPO and MPL expression is necessary for both megakaryopoiesis and proper maintenance of other bone marrow progenitor cells



    • In knockout mouse models, absence of functional MPL results in reduction of both platelets and stem cells to ˜ 10% of normal


  • MPL activation occurs via TPO binding and receptor dimerization


  • Further intracellular signaling relies upon JAK-STAT mechanism


MPL Mutations and CAMT

Jun 13, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Congenital Amegakaryocytic Thrombocytopenia
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