Page 747 - Hematology_ Basic Principles and Practice ( PDFDrive )

634 Part V Red Blood Cells

Genetic Counseling
Splenectomy for Hereditary Spherocytosis
Splenectomy is a permanently curative treatment in most cases of HS. After a patient is diagnosed with HS, family members should be
Thus for years, splenectomy was recommended for all HS patients examined for the presence of HS. A history, physical examination for
regardless of the severity of anemia, gallbladder disease, or other splenomegaly, complete blood count with indices, reticulocyte count,
symptoms. However, increasing concerns regarding overwhelming examination of the peripheral blood smear for spherocytes, and
postsplenectomy infection (OPSI), the emergence of penicillin-resistant biochemical evaluation including bilirubin and haptoglobin levels
pneumococci, and increased risk for cardiovascular diseases have should be obtained for available close relatives.
tempered these recommendations. When considering splenectomy,
health care providers, the patient, and the patient’s family should
review and consider the risks and benefits. Individual factors that Future Directions
may pose additional risk, such as distance from medical care in case
of febrile illness and residence in or travel to areas where parasitic
diseases such as malaria or babesiosis occur, should be considered. Advances in high throughput DNA sequencing methodology have
Expert opinions vary on indications for splenectomy. There are no greatly facilitated the precise genetic diagnosis in many cases of sus-
studies to guide practice. However, because the risk for OPSI is pected inherited membrane-associated disorders. Both targeted gene
highest in infancy and childhood, most agree it is best to avoid total capture and whole exome sequencing have rapidly developed into
splenectomy in early childhood. effective tools for the identification of disease-causing variants in
Benefits genetic disease, particularly monogenic disorders. Because they can
Anemia ameliorated be applied to disorders with recessive or dominant inheritance or de
Risk for hemolysis-associated gallbladder disease eliminated novo occurrence, like HS, they obviate the need for cumbersome
Risk for aplastic crisis eliminated biochemical assays and for linkage analysis in large numbers of
individuals. As more patients are studied, it is likely that new
Risks HS-associated loci will be discovered. Identification of novel muta-
OPSI—especially with encapsulated organisms (Streptococcus tions will provide insight into the structure and function of associated
pneumoniae, Neisseria meningitides, and Haemophilus membrane protein genes, and our understanding of genotype-
influenzae)
Increased risk for thrombotic complications phenotype relationships, particularly those with variable influence on
Increased risk for vascular complications (pulmonary hypertension, disease severity, will be extended.
cardiovascular disease)
Indications for Splenectomy
Expert opinions vary HEREDITARY ELLIPTOCYTOSIS AND
Severe, symptomatic spherocytosis RELATED DISORDERS
Growth failure, skeletal changes, leg ulcers, and extramedullary
hematopoietic tumors (signs of severe anemia)
Older patients with vascular compromise of vital organs Introduction and Epidemiology
Moderate HS with compensated, asymptomatic anemia:
controversial; decision should be individualized Hereditary elliptocytosis designates a group of inherited disorders
that have in common the presence of elliptical RBCs on peripheral
blood films. Elliptocytosis was first described by Dresbach in 1904,
and its heritability was firmly established by Hunter. Subsequent
reports have revealed a considerable heterogeneity of clinical expres-
splenic phagocytic function. In initial cohorts of patients treated sion and have defined several distinct syndromes, including HPP and
with partial splenectomy, stable increases in hemoglobin levels with SAO.
decreased reticulocyte counts have been observed. The volume of Hereditary elliptocytosis is common in people of African and
splenic tissue left behind ranges from 10 mL to 30 mL. Although Mediterranean ancestries. In the U.S. population, the prevalence of
initial data are promising, it is not clear whether the remaining splenic HE is approximately 3 to 5 per 10,000. The true incidence of HE is
tissue will effectively prevent postsplenectomy sepsis. In addition, unknown because its clinical severity is heterogeneous and most
regrowth of the splenic remnant has been reported in many patients, patients are asymptomatic without anemia. HE is considerably more
which can eventually lead to recurrence of HS and another operative frequent in areas of endemic malaria. In equatorial Africa, the preva-
procedure. lence of common HE has been estimated at between 0.6% and 1.6%.
There are no specific data to support the use of prophylactic anti- Worldwide, HE appears to be more common among people of
biotics postsplenectomy. Some practitioners avoid the prescription of African origin. In Southeast Asian populations, the prevalence of
prophylactic antibiotics, others recommend prophylactic antibiotics SAO, a variant of HE, is as high as 30%.
for at least 5 years postsplenectomy, and others recommend their The molecular basis of HE remained obscure until a defect of
use for life. membrane skeletal proteins was suggested. Subsequently defects in
the erythrocyte membrane proteins α-spectrin, β-spectrin, protein
Postsplenectomy Failures 4.1R, GPC, and band 3 were described.
Postsplenectomy failures are caused either by the presence of an On the basis of RBC morphologic characteristics, HE can be
accessory spleen missed during surgery (accessory spleens were divided into three major groups. Common HE, a dominantly
found in 17% to 39% of all patients) or by the presence of another inherited condition, is morphologically characterized by biconcave
superimposed RBC disorder such as pyruvate kinase deficiency. elliptocytes and, in some patients, rod-shaped cells. The clinical
The recurrence of hemolytic anemia several years after splenectomy severity of common HE is highly variable, ranging from an asymp-
should raise the suspicion of development of splenunculi, result- tomatic condition to a severe recessively inherited hemolytic anemia,
ing from autotransplantation of splenic tissue during surgery. including hemolytic HE and HPP, in which the blood film reveals
The presence of an accessory spleen or splenunculus is suggested numerous RBC fragments, microspherocytes, and poikilocytes. Sphe-
by the absence of both Howell-Jolly bodies and the “pitted” cells rocytic HE, also called hemolytic ovalocytosis, is a much less common
with crater-like surface indentations readily seen by interference condition in which both round “fat” ovalocytes and spherocytes are
contrast microscopy. A definitive confirmation of splenosis is made present on the blood film. SAO, a disorder highly prevalent in the
by a radiocolloid liver-spleen scan or by a scan using chromium malaria belt of Southeast Asia and the Pacific, is characterized by
(Cr)-labeled heated RBCs, which are taken up by the ectopic rigid, spoon-shaped cells that have either a longitudinal slit or a
splenic tissue. transverse ridge.