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CHAPTER 25  ■  Principles of Hemostasis and Thrombosis: Vasculature and Platelets                                           493













                                                                             Megakaryoblast


























                                                                             Promegakaryocyte                                  FIGURE  25.3  Gr  nul  r   eg  k  ryocyte  ro     n MGG-st  ine

                                                                                                                               nor    l bone     rrow s  e  r. (Reprinte    ro   Mills SE. Histology

                                                                                                                                or Pathologists, 3r   e  , Phil    elphi  , PA: Lippincott Willi    s &
                                                                                                                               Wilkins, 2007, with per  ission.)




                                                                                                                               size  o     eg  k  ryocytes,  but  the  sensing    ech  nis  s  th  t

                                                                                                                               regul  te  pl  telet  pro  uction  h  ve  not  yet  been  i  entif e  .

                                                                                                                               Recently, the gene  or the hu    n   pl protein w  s clone

                                                                                                                                 n     oun    to  be  expresse    selectively  in    eg  k  ryocytic


                                                                             Megakaryocyte                                     cells. It w  s then  oun   th  t   ntisense oligonucleoti  es th  t
                                                                                                                               block the synthesis o  hu    n   pl protein inhibit the  or-

                                                                                                                                   tion o    eg  k  ryocyte colonies but not o  erythroi   or

                                                                                                                               gr  nulocyte-    croph  ge  colonies  in  vitro.  T is  orph  n

                                                                                                                               receptor  o   unknown   unction    ight  be  the  receptor   or

                                                                                                                               thro  bopoietin.  T e  protein      y    ct  synergistic  lly  with

                                                                                                                               other growth    ctors   uring the proli er  tion st  te. It is not

                                                                                                                               known whether  urther hor  on  l sti  ul  tion is nee  e    or

                                                                                                                               cytopl  s  ic     tur  tion or pl  telet rele  se.
                                                                             Platelets
                                                                                                                                    Meg  k  ryocytopoiesis procee  s initi  lly through    ph  se

                                                                                                                               ch  r  cterize   by   itotic   ivision o     progenitor cell,  ollowe

                                                                                                                               by      w  ve  o   nucle  r  en  ore  uplic  tion.  Endoreduplication

                                                                                                                               is the process in which chro  oso    l     teri  l (DNA)   n

                   FIGURE  25.2  Nor    l   eg  k  ryocytic series. (Reprinte    ro                                            the other events o    itosis occur without subsequent   ivi-

                   An  erson SC. Anderson’s Atlas o  Hematology, Phil    elphi  , PA:                                          sion o  the cytopl  s  ic   e  br  ne into i  entic  l     ughter

                   Wolters Kluwer He  lth/Lippincott Willi    s & Wilkins, Copyright                                           cells. Recogniz  ble   eg  k  ryocytes h  ve ploi  y v  lues o  4n,

                   2003, with per  ission.)                                                                                    8n, 16n,   n   32n. T e     tur  tion o    eg  k  ryocytes  ro

                                                                                                                               i      ture, l  rgely non–DNA-synthesizing cells to   orpho-


                   General Characteristics of Megakaryocytic                                                                   logic  lly  i  entif   ble    eg  k  ryocytes  involves  processes

                   Development                                                                                                 such   s the   ppe  r  nce o  cytopl  s  ic org  nelles, the   cqui-
                                                                                                                               sition o    e  br  ne   ntigens   n   glycoproteins (GPs),   n

                   Bone     rrow   eg  k  ryocytes (Fig. 25.3)   re   erive    ro                                              the rele  se o  pl  telets.

                   pluripotenti  l ste   cells. T e sequence o    evelop  ent  ro                                                   T ro  bopoietin, the hor  one thought to sti  ul  te the

                     eg  k  ryocytes  to  pl  telets  is  thought  to  progress   ro                                           pro  uction    n        tur  tion  o     eg  k  ryocytes,  which  in

                   the proli er  tion o  progenitors to polyploi  iz  tion, th  t is,                                          turn pro  uce pl  telets, h  s recently been purif e     n   clone  .

                   nucle  r en  ore  uplic  tion,   n   f n  lly to cytopl  s  ic     tu-                                      T ro  bopoietin   ctivity results  ro   sever  l   i  erent cyto-

                   r  tion   n   the  or    tion o  pl  telets. An   ver  ge o  1 to 3                                         kines:  erythropoietin,  IL-3,    n    gr  nulocyte-    croph  ge

                     eg  k  ryocytes shoul   be observe   when ex    ining bone                                                colony-sti  ul  ting    ctor (GM-CSF). T ese subst  nces h  ve

                       rrow   spir  te   t 10×     gnif c  tion. T e     jority o   or  s                                      been shown to be   ble to incre  se   eg  k  ryocyte size,     tu-

                    re the MK  st  ge. Qu  ntit  tive esti    tion is   one with 100×                                          r  tion  l st  ge,   n   ploi  y.
                                      1
                   oil i    ersion.

                        When   eg  k  ryocytes   re being stu  ie   in    bone     r-                                          The Developm ental Sequence of Platelets Early

                   row   spir  te, their   orphology   ust be   eter  ine    ro   the                                          Developm ent

                   biopsy section.                                                                                              wo cl  sses o  progenitors h  ve been i  entif e  : the burst-

                        T ere    ppe  rs  to  be      co  plex  rel  tionship  between                                          or  ing  unit-  eg  k  ryocyte  (BFU-M)    n    the  colony-

                   the  circul  ting pl  telet      ss   n   the nu  ber, ploi  y,   n                                          or  ing unit-  eg  k  ryocyte (CFU-M). T e BFU-M is the
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