Page 210 - Haematologica Atlas of Hematologic Cytology

Chapter 25 INHERITED HEMOGLOBIN DISORDERS
Inherited hemoglobin disorders
are the most common monogenic diseases worldwide Thalassemias and he- moglobinopathies are chronic hemolytic anemias that result from a a a a a a defect of of synthesis or structure of of the the -like and -like globin globin globin chains that form tetramers of hemoglobin hemoglobin ( 2 2 2) The most relevant hemoglobinopathy is si- ckle cell disease (SCD) characterized by the presence of hemoglobin S S S variant (HbS) (Rees et et al al 2010 Piel et et al al 2017) Several clinical forms of of -thalassemia -thalassemia -thalassemia and -thalassemia -thalassemia -thalassemia including the co-inheritance of of -thalassemia -thalassemia -thalassemia with hemoglobin hemoglobin hemoglobin variants (i e e e e e e e HbS HbE HbC HbD etc ) resulting in in in in in hemoglobin hemoglobin hemoglobin S/ -thalassemia hemoglobin hemoglobin hemoglobin E/ -thalassemia etc have been described (Weatherall 2001 Taher et et al al al al 2018) The molecular bases of thalas- semias are summarized in Table 1 Table 1 Thalassemias: molecular bases Locus
Muta on/Dele on on types
ommon Muta on/Dele on on on and rigin
globin gene cluster
0-dele on +-dele on T ( 2 gene)
T ( 1 gene)
--SEA (Southeast Asia) --MED (Mediterranean)
- - 3 7 - - 4 2 (Worldwide)
HbCS (Southeast Asia) I S1(-5nt) (Mediterranean)
PA(AATAAG) (Middle Eastern Asia) Hb -Thailand (Southeast Asia) globin gene cluster
++-muta on +-muta on 0-muta on dele on ( gene)
dele on ( / genes) dele on (HPFH/ ) -muta on -101(C>T) (Mediterranean)
I S1-110(G>A) (Mediterranean)
I S1-6(T>C) (Mediterranean)
-29(A>G) (Africa)
-87(C>A) -87(C>T) -87(C>G) (Mediterranean)
-88(C>A) -88(C>T) (Africa)
CD39 (C>T) (Mediterranean)
CD41-42 (-TTCT) (Southeast Asia) I I S1-1 S1-1 (G>A) (Mediterranean)
I I S1-1 S1-1 (G>C) (Southeast Asia) I S2-1 (G>A) (Middle East Asia) 619 bp dele on on (Asian subcon nent)
sic (Mediterranean)
SEA-HPFH Chinese Chinese G (A )0 dele on (Chinese) CD26 (G>A) (HbE) (Glu Lys) (Southeast Asia) CD27 (G>T) (Hb Knossos) (Middle East)
(A>T) 6 Glu> al (HbS) (Africa Southeast Asia) (G>A) 6 Glu>Lys (HbC) (Africa)
The physiopathology of of the thalassemias is characterized by an an imbalance of of /non- globin chain ratio based on on on ineffective erythropoiesis with with compensatory hemopoietic expansion chronic hemolytic anemia with with spleno- megaly hypercoagulability and increased intestinal iron absorption Thalassemia syndromes are clinically clas- sified into transfusion- transfusion- and non-transfusion-dependent thalassemia according to to the the severity of the the phenotype and the blood requirement The clinical expression of SCD is due to to hemoglobin S S polymerization that leads to to the erythrocyte rigidity responsible for chronic hemolytic anemia and vaso-occlusion with ischemia-reperfusion in in in ury resulting in in in multi-organ damage with functional asplenia Table Thalassemias and sic le le cell disease laboratory features Transfusion dependent thalassemia on on transfusion dependent thalassemia Sic le ell Disease (HbSS)
nemia Severe hypochromic microcy c c c Mild/moderate hypochromic microcy c c c c c Absent/mild hypochromic normo-microcy c c c lood lm Target cells anisopoiki- locytosis polychromasia erythroblasts (few) schi- stocytes (splenectomy) dacryocytes and basophilic s s ppling (splenomegaly)
Target cells anisopoikilocytosis polychromasia erythroblasts (numerous) schistocytes (sple- nectomy) dacryocytes and ba- sophilic s s s ppling (splenomegaly)
Sickle cell polychromasia anisopoikilocytosis schistocytes (func onal asplenia) dacryocytes and basophilic s s ppling (splenomegaly)
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