Page 2561 - Hematology_ Basic Principles and Practice ( PDFDrive )

2284 Part XIII Consultative Hematology

suggesting that the inhibition and abnormal maturation of erythroid Treatment for HMS is lifelong antimalarial prophylaxis. Signs and
precursors may have somewhat differing etiologies in acute and symptoms usually subside over 1 to 2 years, but relapse may occur if
chronic infection. 39 antimalarial therapy ceases. Splenectomy is contraindicated because
The role of hematinic deficiency in children presenting with it is technically difficult, with considerable intra-operative mortality,
malaria and anemia may be difficult to assess. The relative importance and it may predispose to severe infection.
of absolute and functional iron deficiency have not been defined. Iron
will not be absorbed during acute infection, because hepcidin levels
are raised. 54,55 Nevertheless, many hospitals give a course of iron Anemia and P. vivax, P. ovale, and
supplementation after an episode of acute malaria, although no P. malariae Infection
general guidelines have been established. Chronic hemolysis may
increase folate requirements, but frank deficiency is uncommon in In P. vivax and P. ovale malaria, high parasitemias are rare because
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children presenting with acute malaria, at least in East Africa. Folate invasion of erythrocytes is limited to reticulocytes. However, there is
deficiency may be more common in West Africa, and protocols for an emerging consensus that P. vivax monoinfection may cause severe
folate supplementation after malaria must reflect local experience. disease with cerebral malaria and/or anemia (for review, see Price
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et al ). The vivax-infected RBC can adhere to host cells, but seques-
tration in the peripheral circulation and organ-specific syndromes of
Malarial Anemia in Pregnancy disease are much less common than in falciparum malaria.
P. vivax malaria has been associated with anemia during preg-
Pregnancy is accompanied by a series of physiologic changes that nancy and with low birth weight of children of affected mothers.
predispose not only to anemia but also to malaria. Hemodilution Here cytokines or other inflammatory mediators appear to cause
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causes a physiologic decrease in hemoglobin. Moreover, the demand placental dysfunction. P. malariae infection is also rarely fatal but
for both iron and folate increases as the fetus grows and often pre- is distinguished by the persistence of blood-stage parasites for up
cipitates frank folate or iron deficiency, particularly in multigravid to 40 years. It can, however, cause a progressive and fatal nephrotic
women. syndrome. 106
Occult malarial infection, often without fever, may cause anemia
and placental dysfunction. This effect is greatest in primigravidas and
has been attributed to the adhesion of parasitized erythrocytes to Malaria Diagnosis
chondroitin sulfate A and hyaluronic acid in the placenta 97,98 (for
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review, see Rogerson et al ). Fetal growth is impaired, and babies The diagnosis of malaria is based on the identification of circulating
born to women with placental malaria are, on average, 100 g lighter blood-stage parasites. The standard methods of preparing thick and
than those born to women without malaria. The subsequent contri- thin films are straightforward and allow a simple method to diagnose
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bution of malaria to infant mortality is substantial. Furthermore, infection (Table 158.1). 107–109 However, malaria diagnosis poses par-
the increase in hematopoiesis demanded by hemolysis during malarial ticular problems for inexperienced staff. The main biologic problem
infection may precipitate frank folate deficiency. Finally, women who is that the level of circulating parasites is only weakly associated with
are not immune to malaria are more likely to develop hypoglycemia the overall parasite burden because falciparum-infected erythrocytes
and pulmonary edema during pregnancy. The increase in maternal are sequestered in capillary venules; thus the parasitemia is not a
and fetal morbidity and mortality secondary to malaria may be pre- reliable guide to the severity of disease. Second, missing or delaying
vented by routine hematinic supplementation and by intermittent the diagnosis of falciparum malaria may result in serious morbidity
treatment with antimalarials during the second and third trimesters and mortality. Finally, the most sensitive methods for diagnosis of
with sulfadoxine-pyrimethamine (Fansidar). 101 infection, namely microscopy, require both skill and time.

Hyperreactive Malarial Splenomegaly
TABLE Malaria Diagnosis
Although splenomegaly secondary to malarial infection usually 158.1
regresses as immunity is acquired, some people living in endemic • Thick and thin films should be prepared for cases of suspected
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areas develop progressive, massive splenomegaly. The pathophysiol- malaria.
ogy of such hyperreactive malarial splenomegaly (HMS) is poorly • Immunochromographic tests lack sensitivity to detect low levels of
understood but certainly results in B-cell hyperplasia with high levels parasites that may be highly clinically significant.
of polyclonal IgM, reaching a level greater than two standard devia- • Routine Giemsa or May-Grünwald-Giemsa stains are unlikely to give
tions (SDs) above the local reference mean. The specific antimalarial satisfactory results, because the pH is too low.
antibody titer is high, although only a small proportion of the • Films can be stained with Giemsa or Leishman stain (thin films) or
polyclonal IgM response is directed at malarial antigens. B-cell Field stain (thick films). (For details, see Bailey JW, Williams J,
hyperplasia may provoke proliferation of both T cells and macro- Bain BJ, et al: Guideline: the laboratory diagnosis of malaria. Br J
phages, and IgM levels may cause cryoglobulinemia and stimulate Haematol 2013;163[5]:573. doi: 10.1111/bjh.12572.)
erythrophagocytosis. • Two hundred high-power fields (×100 objectives) should be
Patients may present typically between 20 and 40 years old, with examined in a thick film.
massive splenomegaly without lymphadenopathy, anemia that may • Asexual parasitemia should be reported after counting 1000 RBCs
be severe, neutropenia, and thrombocytopenia. The anemia may in a thin film. A graticule or grid may help counting.
cause life-threatening hemolytic crises and/or neutropenia associated • If parasitemia is less than 1 : 1000 RBCs, parasitemia may be
with severe bacterial infection. Thrombocytopenia is rarely symptom- counted in a thick film in relation to the number of WBCs.
atic. The bone marrow shows hypercellularity, with a lymphocytosis • During active infection, a daily parasite count should be obtained.
in marrow and peripheral blood. The high IgM levels distinguish • Counting and species determination of malaria parasites should be
HMS from chronic lymphocytic leukemia or other lymphoprolifer- verified by a second observer.
ative disorders. However, the polyclonal proliferation of B cells may • Reports on negative films despite a strong clinical suspicion of
transform to a true clonal lymphoproliferative disorder. This appears malaria should be qualified that negative films do not exclude a
to be derived from a naive B cell, although the exact classification of diagnosis of malaria. Repeat films should be requested if clinically
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such lymphoproliferative disorders is poorly defined ; however, appropriate. Thrombocytopenia may heighten suspicion of malaria.
there is a single report of a high incidence of B prolymphocytic RBC, Red blood cell; WBC, white blood cell.
leukemia in one population.