TY  - CHAP
M1  - Book, Section
TI  - Clinical Manifestations and Classification of Erythrocyte Disorders
A1  - Prchal, Josef T.
A2  - Prchal, Josef T.
A2  - Lichtman, Marshall A.
PY  - 2022
T2  - Williams Hematology The Red Cell and Its Diseases
AB  - SUMMARYAnemias  are  characterized  by  a  decrease  and  erythrocytoses  by  an  increase  of  the  red  cell  mass.  In  most  clinical  situations,  changes  in  red  cell  mass  are  inferred  from  the  hemoglobin  concentration  or  hematocrit.  Some  red  cell  disorders  are  associated  with  compensated  hemolysis  without  or  with  only  slight  anemia.  Their  clinical  manifestations  are  evident  not  by  the  effects  of  anemia  but  by  changes  associated  with  catabolism  of  hemoglobin  such  as  an  increase  in  serum  bilirubin  and,  if  sustained,  cholelithiasis,  decreased  haptoglobin,  and  usually  chronic  reticulocytosis.  Some  red  cell  disorders  are  only  showcased  by  morphologic  abnormalities  as  exemplified  by  hereditary  elliptocytosis  unaccompanied  by  hemolysis  or  anemia,  or  by  cyanosis  such  as  that  seen  with  methemoglobinemia  and  sulfhemoglobinemia.The  anemias  have  their  principal  effect  by  decreasing  the  oxygen-carrying  capacity  of  blood  and  their  severity  is  most  conveniently  considered  in  terms  of  blood  hemoglobin  concentration;  however,  oxygen-carrying  capacity  of  blood  is  also  influenced  by  red  cell  and  plasma  volumes.  Anemia  may  cause  symptoms  because  of  tissue  hypoxia  (eg,  fatigue,  dyspnea  on  exertion).  Some  manifestations  are  also  caused  by  compensatory  attempts  to  ameliorate  hypoxia  (eg,  hyperventilation,  tachycardia,  and  increased  cardiac  output).  These  manifestations  are  a  function  of  the  severity  and  rapidity  of  onset  of  the  anemia.  Tissue  hypoxia  sensing  is  ubiquitous  and  is  signaled  by  an  increased  level  of  hypoxia-inducible  transcription  factors  (HIFs),  HIF-1  and  HIF-2.  HIFs  upregulate  transcription  of  many  genes,  in  addition  to  the  principal  erythropoietic  factor  erythropoietin  (EPO),  that  are  involved  in  erythropoiesis,  but  also  in  angiogenesis,  energy  metabolism,  and  iron  balance.  The  classification  of  anemia  distinguishes  whether  the  anemia  is  inherited  or  acquired  and  considers  new  kinetic  and  molecular  findings.  Some  anemic  disorders  can  be  accompanied  by  nonerythroid  pathologic  indicators,  such  as  mutated  red  cell  enzyme  aldolase,  which  is  also  associated  with  glycogen  storage  disease  and  developmental  disability  in  addition  to  hemolytic  anemia.The  erythrocytoses  are  most  conveniently  expressed  in  terms  of  the  packed  red  cell  volume  (hematocrit),  because  their  clinical  manifestations  are  primarily  related  to  the  expanded  red  cell  mass  and  resulting  increased  viscosity  of  blood,  and  other  specific  features  related  to  the  pathophysiology  stemming  from  a  molecular  causative  defect  (eg,  thrombosis  in  polycythemia  vera  and  Chuvash  erythrocytosis  [also  Chuvash  polycythemia],  cyanosis  in  congenital  methemoglobinemia).  However,  normal  hematocrit  levels  associated  with  increased  plasma  volume  may  mask  an  increase  in  red  cell  mass  and,  in  turn,  elevated  hematocrit  levels  with  decreased  plasma  volume  may  falsely  lead  to  a  diagnosis  of  erythrocytosis  (spurious  erythrocytosis).  The  erythrocytoses  may  be  primary,  caused  by  acquired  somatic  or  inherited  germline  mutation(s)  dysregulating  expansion  of  erythroid  progenitors  and,  thus,  red  cell  production  (eg,  clonal  expansion  of  a  multipotential  hematopoietic  cell  [polycythemia  vera]);  or  it  may  be  caused  by  germline  gain-of-function  mutations  of  the  EPO  receptor  (EPOR),  resulting  in  polyclonal  hematopoiesis;  both  are  associated  with  low  EPO.  Secondary  erythrocytoses  may  be  acquired,  caused  by  increased  levels  of  circulating  erythropoiesis-stimulating  factors,  usually  EPO,  as  a  result  of  tissue  hypoxia  (eg,  chronic  pulmonary  disease,  exposure  to  high-altitude  hypoxia),  or  occurring  post  renal  transplant,  aberrant  EPO  expression,  and  EPO  doping,  induced  by  testosterone  and  other  ...
SN  - 
PB  - McGraw Hill
CY  - New York, NY
Y2  - 2024/04/18
UR  - hemonc.mhmedical.com/content.aspx?aid=1184009926
ER  -