Page 723 - Hematology_ Basic Principles and Practice ( PDFDrive )

610 Part V Red Blood Cells

HbS
β 2 Shepherds Rahere β 1
Bush
Buenos Agenogi
Aires
Seattle Boras Crefeil Syracuse
Andrew-Minneapolis
Christchurch Olmsted Sabine Rainier
Wien North Shore Hiroshima
Olympia
M-Milwaukee
O-Arab
Riverdale-
Bronx Zurich Heathrow Brigham
Malmo
Köln
Freiburg
Peterborough Casper
Yoshizuka Kansas Kempsey
Torino
San Diego
Bucaresti

Philly G-Georgia M-Boston
Okaloosa Hirose Chesapeake
Tarrant
M-Iwate

Suresnes Bibba

α 2 α 1

Fig. 43.1 HEMOGLOBIN TETRAMER SHOWING THE POSITION OF THE MORE COMMON,
CLINICALLY SIGNIFICANT HEMOGLOBIN MUTANTS. Most of those that have been described occur
on the β-chain at invariant residue sites, near critical intermolecular contacts, or in proximity to the prosthetic
heme-binding site. (Modified from Dickerson RE, Geis I: Hemoglobin: Structure, function, evolution, and pathology,
Menlo Park, CA, 1983, Benjamin-Cummings. Copyright Irving Geis.)

anemia, reticulocytosis, hepatosplenomegaly, jaundice, leg ulcers, and Diagnosis
a propensity toward premature biliary tract disease.
For hemoglobin variants with a given degree of reduced solubil- The presence of an unstable hemoglobin should be suspected in
ity, the degree of anemia may fluctuate because some of these vari- patients with one or more stigmata of accelerated red blood cell
ants also exhibit altered oxygen affinity. Thus Hb Köln has increased destruction: chronic or intermittent hemolytic anemia or jaundice,
oxygen affinity, resulting in relatively higher levels of tissue hypoxia premature development of bilirubin gallstones or biliary tract disease
and erythropoietin stimulation at any given level of hematocrit (see (as a result of accelerated red blood cell turnover), unexplained reticu-
Diagnosis); therefore patients with Hb Köln tend to have higher locytosis, or bouts of intermittent symptoms that can be related to
hematocrit levels than expected on the basis of hemolytic severity exposure to oxidant drugs or infections. Other suggestive symptoms
because of increased erythropoietin stimulation. By contrast, Hb include dark urine, transient jaundice, and leg ulcers.
Hammersmith exhibits decreased oxygen affinity, improving oxygen Laboratory diagnosis depends on identification of a mutant
delivery and allowing patients to function at a lower hematocrit hemoglobin that precipitates more easily than normal hemoglobin.
level. Hb Zurich possesses, for complex molecular reasons, a higher- The peripheral blood smear may or may not show evidence of
than-normal affinity for carbon monoxide. A high hemoglobin hemolysis (i.e., poikilocytosis, polychromasia, or shift cells; Fig.
carbon monoxide level develops in patients with Hb Zurich who 43.3A). The morphologic evidence for precipitated hemoglobin is the
also smoke. Binding of carbon monoxide protects Hb Zurich from Heinz body, the intraerythrocytic inclusion body detected by staining
denaturation, thus reducing hemolysis, so these people tend to the peripheral blood smear with a supravital dye, such as brilliant
exhibit lesser degrees of hemolytic anemia than do nonsmoking cresyl blue or new methylene blue (see Fig. 43.3B–C). The spleen
relatives. removes Heinz bodies efficiently, especially if hemolysis is