RT Book, Section
A1 Rao, A. Koneti
A1 Coller, Barry S.
A2 Kaushansky, Kenneth
A2 Lichtman, Marshall A.
A2 Prchal, Josef T.
A2 Levi, Marcel M.
A2 Press, Oliver W.
A2 Burns, Linda J.
A2 Caligiuri, Michael
SR Print(0)
ID 1121103473
T1 Hereditary Qualitative Platelet Disorders
T2 Williams Hematology, 9e
YR 2015
FD 2015
PB McGraw-Hill Education
PP New York, NY
SN 9780071833004
LK accessmedicine.mhmedical.com/content.aspx?aid=1121103473
RD 2024/04/19
AB SUMMARYAbnormalities  of  platelet  function  manifest  themselves  primarily  as  excessive  hemorrhage  at  mucocutaneous  sites,  with  ecchymoses,  petechiae,  epistaxis,  gingival  hemorrhage,  and  menorrhagia  most  common.  Both  quantitative  and  qualitative  platelet  abnormalities  can  produce  these  symptoms,  so  it  is  necessary  to  exclude  thrombocytopenia  (Chap.  117)  by  performing  a  platelet  count.  Chapter  121  discusses  acquired  qualitative  platelet  abnormalities  and  this  chapter  discusses  the  hereditary  qualitative  platelet  abnormalities.The  hereditary  qualitative  platelet  disorders  can  be  classified  according  to  the  major  locus  of  the  defect  (see  Table  120–1  and  Fig.  120–1).  Thus,  abnormalities  of  platelet  glycoproteins,  platelet  granules,  and  signal  transduction  and  secretion  can  all  result  in  hemorrhagic  diatheses  and  prolonged  bleeding  times.  Glanzmann  thrombasthenia  results  from  abnormalities  in  one  of  two  integrin  subunits,  either  αIIb  (glycoprotein  [GP]  IIb)  or  β3  (GPIIIa),  resulting  in  loss  or  dysfunction  of  the  αIIbβ3  (GPIIb/IIIa)  receptor.  This  results  in  a  profound  defect  in  platelet  aggregation  and  secondary  defects  in  platelet  adhesion,  secretion,  and  platelet  coagulant  activity.  Heterozygous  gain  of  function  mutations  in  αIIbβ3  can  result  in  a  syndrome  of  macrothrombocytopenia.  Loss  of  the  platelet  GPIb–IX–V  complex  because  of  abnormalities  in  GPIbα,  GPIbβ,  or  GPIX  results  in  the  Bernard-Soulier  syndrome,  which  is  characterized  by  giant  platelets  and  modest  thrombocytopenia.  The  major  defect  is  in  platelet  adhesion  because  of  a  decrease  in  platelet  interactions  with  von  Willebrand  factor,  but  abnormalities  in  αIIbβ3  activation  and  thrombin-induced  aggregation  are  also  present.  A  gain  of  function  defect  in  GPIbα  (platelet-type  [pseudo-]  von  Willebrand  disease)  can  produce  a  hemorrhagic  disorder  via  depletion  of  high-molecular-weight  von  Willebrand  multimers.  Inherited  defects  in  platelet  dense  or  α  granules,  agonist  receptors,  or  proteins  and  mechanisms  involved  in  signal  transduction  and  secretion  also  lead  to  platelet  dysfunction  and  produce  hemorrhagic  symptoms.Abnormalities  of  platelet  coagulant  activity,  that  is,  the  ability  of  platelets  to  facilitate  thrombin  generation  (Chap.  112),  can  lead  to  a  hemorrhagic  diathesis.  Impaired  platelet  function  may  occur  in  association  with  mutations  in  transcription  factors  RUNX1,  GATA-1,  FLI-1,  and  GFI1B,  and  these  patients  have  thrombocytopenia  as  well.