Page 746 - Hematology_ Basic Principles and Practice ( PDFDrive )

Chapter 45 Red Blood Cell Membrane Disorders 633

most likely to occur in older children and young adults. The coin- Spherocytosis is transiently improved, and both the osmotic fragil-
heritance of Gilbert syndrome increases the risk for gallstones in HS ity and hemolysis are normalized in patients with obstructive jaundice.
patients. Because of the high incidence of gallstones, HS patients This is because of an expansion of RBC surface area that follows an
should be periodically examined by ultrasonography for the presence increased uptake of phospholipids and cholesterol from the abnormal
of gallstones, beginning in childhood. plasma lipoproteins. In normal RBCs, this leads to target cell forma-
tion; in HS, spherocytes are transformed to discocytes. Spherocytosis
and the increased osmotic fragility of HS red cells are likewise
Crises improved by iron deficiency, but the RBC life span remains short-
ened. In addition, coexistence of β-thalassemia trait and HS partially
True hemolytic crises are relatively rare and only occasionally reported corrects the HS phenotype.
in association with infections. Aplastic crises during viral infections
are largely attributable to infection by parvovirus B19. This infection
(erythema infectiosum, fifth disease) manifests with fever, chills, THERAPY AND PROGNOSIS
lethargy, malaise, nausea, vomiting, abdominal pain with occasional
diarrhea, respiratory symptoms, muscle and joint pains, and a macu- Splenectomy
lopapular rash on the face (slapped cheek appearance), trunk, and
extremities. The virus selectively infects erythroid precursors and Splenectomy is curative in almost all patients with typical forms of
inhibits their growth. The ensuing anemia, often profound, can be HS, because RBC survival is normalized, and anemia and hyperbili-
the first manifestation of HS. Multiple family members with undi- rubinemia are corrected. Spherocytosis and the increase in osmotic
agnosed HS who are infected with parvovirus have developed aplastic fragility persist, but the tail of the osmotic fragility curve, indicating
crises at the same time. Infection with parvovirus is a particular the presence of a subpopulation of cells conditioned by the spleen,
danger to susceptible pregnant women because it can infect the fetus, disappears. In patients with severe, nondominantly inherited HS,
leading to fetal anemia, hydrops fetalis, and fetal demise. splenectomy produces a dramatic clinical improvement, but hemoly-
Rarely, at least in developed countries, patients present with sis is only partially corrected.
megaloblastic crises caused by folate deficiency. This typically occurs Several weeks to months before splenectomy, patients should be
in patients with increased folate demands, such as those recovering immunized with polyvalent vaccine against pneumococcus as well as
from an aplastic crisis, pregnant women, and older adults. Megalo- vaccines against Haemophilus influenzae type b and meningococcus.
blastic crisis in pregnancy has been reported as the first manifestation
of HS. Folate supplementation is recommended for patients with
moderate to severe HS. Indications for Splenectomy
Risks and benefits should be considered carefully in HS patients before
Other Complications splenectomy is performed (see box on Splenectomy for Hereditary
Spherocytosis). A multitude of factors influence the decision for
In patients with more severe forms of HS, other complications splenectomy in HS patients, including the risk for overwhelm-
include gout, leg ulcers, or chronic dermatitis of the legs that heal ing postsplenectomy sepsis, the emergence of penicillin-resistant
after splenectomy. Symptoms of expanded erythroid space, including pneumococci, and the potentially increased risk for cardiovascular
paravertebral or renal pelvic masses of extramedullary hematopoiesis, disease and pulmonary hypertension later in life. Indications for
which can mimic an underlying neoplasm, may occur. Several cases splenectomy include growth retardation, skeletal changes, symptom-
of hemochromatosis in HS patients have been reported. In some, iron atic hemolytic disease, anemia-induced compromise of vital organs,
overload resulted from repeated transfusions; in others, the patients the development of leg ulcers, or the appearance of extramedul-
had two genetic defects, one involving HS and the other involving a lary hematopoietic tumors. Whether to perform splenectomy in
hemochromatosis carrier state. Other rare complications include patients with moderate HS without any of these factors remains
thrombosis, pulmonary hypertension, spinocerebellar degenerative controversial.
syndromes, movement disorders, myopathy, and hypertrophic Because of an increased frequency of postsplenectomy infection
cardiomyopathy. in young children, most practitioners avoid splenectomy in infancy
More than a dozen cases of HS and hematologic malignancy, and early childhood.
including myeloproliferative disorders, multiple myeloma, and leu-
kemia, have been reported. It is unknown if long-standing hemato- Operative Considerations
poietic stress predisposes to the development of these secondary When splenectomy is warranted, laparoscopic splenectomy has
disorders or if they occurred randomly. become the procedure of choice in many centers. Laparoscopic
splenectomy has been associated with less postoperative discomfort,
a quicker return to preoperative diet and activities, a shorter hospital-
DIFFERENTIAL DIAGNOSIS ization time, decreased costs, and smaller scars. Early complications
of splenectomy include local infection, bleeding, and pancreatitis. In
Because of the relatively asymptomatic presentation of HS, this general, the morbidity rate of splenectomy is lower in patients with
diagnosis should be considered during an evaluation for unexplained HS than with other hematologic diseases. However, the benefits of
splenomegaly, unconjugated hyperbilirubinemia of unknown cause, surgery must be weighed against possible complications, such as
gallstones at a young age, severe anemia during pregnancy, or transient postsplenectomy infections. Although these complications are rare
anemia during acute infections. The diagnosis of HS can be missed and their frequency is likely to diminish further with appropriate
in mild forms of the disease, because spherocytosis might not be vaccinations, the indiscriminate performance of splenectomy in all
apparent on the peripheral blood film. Autoimmune hemolytic HS patients with splenomegaly is unwarranted.
anemia should be ruled out by negative results of a Coombs test.
More typical forms of HS, characterized by relatively uniform Subtotal (Partial) Splenectomy
spherocytosis with increased MCHC, are usually easily distinguished Partial splenectomy was developed for infants and young children
from other disorders manifesting with spherocytosis, such as immune with severe HS, anemia, and poor growth with the goals of palliating
hemolytic anemias and unstable hemoglobins. In some patients, the anemia and decreasing transfusion requirements while preserving
spherostomatocytes in the rare Rh-null syndrome and the intermedi- splenic function. More recently, some have advocated expanding
ate syndromes of hereditary stomatocytosis can be confused with HS the procedure to all patients being splenectomized for HS. The
RBCs. goal of the operation is to decrease hemolysis while maintaining