Page 704 - Hematology_ Basic Principles and Practice ( PDFDrive )

596 Part V Red Blood Cells

the intracellular Hb S concentration by preventing RBC dehydration useful guideline for transfusion in the context of an aplastic crisis is
(Gardos channel inhibitors). the reticulocyte count. A patient having an aplastic crisis with a
reticulocyte count that is recovering is less likely to require urgent
transfusion than one with a normal or low absolute reticulocyte
Exacerbations of Anemia count.

The rather constant level of hemolytic anemia may be exacerbated Sequestration Crisis (Spleen or Liver)
by additional events such as aplastic crises, acute splenic sequestra- Acute splenic sequestration of blood is characterized by acute exacer-
tion, acute hepatic sequestration, chronic renal disease, or renal bation of anemia; persistent reticulocytosis; a tender, enlarging spleen;
140
endocrine deficiency that may be present without overt renal failure, and sometimes hypovolemia. The LDH level may remain stable or
bone marrow necrosis, deficiency of folic acid or iron, delayed increase. Patients susceptible to this complication are those whose
hemolytic transfusion reactions, autoimmune hemolytic anemia, or spleens have not undergone fibrosis—young patients with sickle cell
+
hyperhemolysis (hemolytic exacerbations) of unknown etiology. anemia and adults with Hb SC disease or sickle cell–β -thalassemia.
Laboratory evaluations that are very useful in the evaluation of a Sequestration may occur as early as a few weeks of age and may cause
patient with anemia exacerbation are the reticulocyte count, LDH, death before SCD is diagnosed. In one study, 30% of children had
alloantibody screening, the direct antiglobulin (Coombs) test, and splenic sequestration over a 10-year period and 15% of the attacks
EPO level. were fatal. 141
The basis of therapy is to restore blood volume and RBC mass.
Aplastic Crises Because splenic sequestration recurs in 50% of cases, splenectomy is
Aplastic crises are transient arrests of erythropoiesis characterized by recommended after the event has abated. Alternatively, chronic
abrupt falls in Hb levels, reticulocyte number, and RBC precursors transfusion therapy is used in young children to delay splenectomy
in the bone marrow without necessarily an increase in the LDH. until it can be tolerated safely. Because recurrence is possible during
Although these episodes typically last only a few days, the level of transfusion therapy, parents should be trained to detect a rapidly
anemia may be severe because the hemolysis continues unabated in enlarging spleen and to seek immediate medical attention in this
the absence of RBC production. Although the mechanisms that event. Less common sites of acute sequestration include the liver and
impair erythropoiesis in inflammation are operative in infections of possibly the lung. 142,143
all types (see Chapter 37), human parvovirus B19 specifically invades
proliferating erythroid progenitors, which accounts for its importance Delayed Hemolytic Transfusion Reaction and
135
in SCD (see Chapters 30 and 32). Parvovirus B19 (Fig. 42.10) Autoimmune Hemolytic Anemia
136
accounts for 68% of aplastic crises in children with SCD, but the Approximately 30% of patients are predisposed to develop alloanti-
high incidence of protective antibodies in adults makes parvovirus a bodies, in part because of minor blood group incompatibilities in
less frequent cause of aplasia in this age group (see also Infections, racially mismatched blood. 77,78 The corollary is that the other patients
later in this chapter). Other reported causes of transient aplasia are can receive multiple transfusions without demonstrating alloantibod-
infections by S. pneumoniae, salmonella, streptococci, and Epstein- ies. After alloimmunization, there is a subsequent decrease in antibody
Barr virus. Bone marrow necrosis, which also may be the result of titer that can fall below serologically detectable levels. Therefore
parvovirus infection, characterized by fever, bone pain, reticulocyto- antigen-positive RBCs appear compatible in cross-matching and are
penia, and a leukoerythroblastic response, also causes aplastic transfused. This can result in a delayed hemolytic transfusion reaction
crisis. 137,138 produced by the amnestic response of the immune system (as opposed
Inhaled oxygen therapy also causes transient RBC hypoproduc- to the immediate hemolytic reaction that occurs with preformed
tion; supraphysiologic oxygen tensions curtail EPO production antibody). The delayed hemolytic transfusion reaction consists of an
promptly and suppress reticulocytosis within 2 days. 139 unexplained fall in Hb, elevated LDH level, elevated bilirubin above
The mainstay of treating aplastic crises is RBC transfusion. When baseline, and hemoglobinuria, all occurring between 4 and 10 days
transfusion is necessitated by the degree of anemia or cardiorespira- after the RBC transfusion. Delayed hemolytic reactions and hyper-
tory symptoms, a single transfusion usually will suffice because reticu- hemolysis have been shown to occur in 11% of pediatric patients
144
locytosis resumes spontaneously within a few days. Transfusion may with SCD and a history of alloantibodies. In SCD the delayed
be avoided by keeping severely anemic patients on bed rest to prevent hemolytic transfusion reaction can be particularly devastating because
symptoms and by avoiding supraphysiologic oxygen tensions. A it can be accompanied by reticulocytopenia, which together with a

D

A B C E

Fig. 42.10 PARVOVIRUS. Bone marrow aspirate in a patient with sickle cell disease and aplastic crisis (A).
Note the absence of red blood cell precursors except for the single, large degenerating pronormoblast (lower
center). Such pronormoblasts contain large nuclear inclusions (B) as a result of replication of parvovirus B19.
The same can be seen in the tissue sections of a bone core biopsy (C and D). The parvovirus can now be
recognized immunohistochemically with an immunostain (E).