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818 Part VI: The Erythrocyte Chapter 53: Hemolytic Anemia Resulting from Infections with Microorganisms 819

babesiosis is higher than generally appreciated and represents a threat to disease may leave a residual B. microti infection because antibiotic ther-
the blood supply in endemic areas. Presumably because of the distribu- apy for the former will not eradicate the latter. 108
tion of the vector in the United States, the disease is most common in the
northeastern coastal and Great Lakes regions where it became known CLOSTRIDIUM PERFRINGENS
as “Nantucket fever,” but has also been encountered in the Midwest.
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Infections with B. divergens usually occur in splenectomized patients, SEPTICEMIA
but this is not the case with B. microti infections. 3
EPIDEMIOLOGY
CLINICAL FINDINGS C. perfringens (formerly Clostridium welchii) sepsis is most likely to
The symptoms are prompted by reproduction of the organisms in occur in patients who have undergone septic abortion. It has also been
observed following acute cholecystitis, as a result of an intrahepatic
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the red cell and subsequent cell lysis. The clinical expression is broad, abscess, and, rarely, after amniocentesis (amnionitis). 113
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reflecting the degree of parasitemia. The incubation period ranges from
1 week to 3 months but usually is about 3 weeks. The disease gener-
ally has a gradual onset with malaise, anorexia, and fatigue, followed by PATHOGENESIS
fever (sometimes as high as 40°C), chills, sweats, and muscle and joint C. perfringens are Gram-positive, encapsulated, spore-forming, anaer-
pains. The onset, occasionally, may be fulminant. Hepatic and splenic obic bacilli. The organism causes gas gangrene in soft tissues. The
enlargement may be evident. 108 α toxin of C. perfringens is a lecithinase C that reacts with lipoprotein
A moderate degree of hemolytic anemia is usually present; on complexes at cell surfaces, liberating potent hemolytic substances, lys-
occasion it has been sufficiently severe to cause hypotension, and olecithins. This toxin is the agent that causes intravascular hemolysis
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transfusion has occasionally been required. The hemolysis may last a and its subsequent effects. It has also been suggested that erythrocyte
97
few days, but in asplenic, elderly, or otherwise immunocompromised membrane proteolysis plays an important role in hemolysis. 114
patients, it can go on for months. Elevation in serum transaminases,
lactic dehydrogenase, unconjugated bilirubin, and alkaline phosphatase CLINICAL FEATURES
correlates with the severity of the parasitemia. Thrombocytopenia and
leukopenia may occur, which may be the result of inflammatory cytok- Severe, often fatal hemolysis occurs in patients with C. perfringens septi-
ine release. 108 cemia. Striking hemoglobinemia and hemoglobinuria occur. The serum
may become a brilliant red, and the urine is a dark-brown mahogany
color. The lysis of red cells (decreasing packed red cell volume) and the
DIAGNOSIS high plasma hemoglobin can produce a marked dissociation between
The history may indicate exposure to a tick-infested area, recent blood trans- the blood hemoglobin and hematocrit level. For example, hematocrits
fusion, or asplenia. Parasites can be seen in the red cells in Giemsa-stained approaching zero with blood hemoglobins as high as 8 g/dL can occur.
thin blood films. They appear as darkly stained ring forms with light Dehemoglobinized red cells (“ghosts”) may be evident on the blood film
blue cytoplasm. Merozoites may also be visible. Infrequently, the clas- (see Fig. 53–1D). Microspherocytes are prominent (Chap. 46), and both
sical Maltese cross tetrad can be found. This intraerythrocytic struc- leukocytosis with a left shift and thrombocytopenia are often present.
ture consists of four daughter cells of Babesia connected by cytoplasmic Acute renal and hepatic failure usually develops, and the prognosis is
bridges, resembling a Maltese cross. The parasitemia can be very high, grave; more than half of the patients die, even with appropriate treat-
108
affecting more than 75 percent of red cells (see Fig. 53–1C). Immun- ment (Chap. 129). 8,115
ofluorescent tests for antibodies to Babesia are available and PCR-based
diagnostic tests are the test of choice for confirmation of an active infec- THERAPY AND COURSE
tion in an individual bearing antibodies to Babesia and for following the Therapy consists of antibiotic therapy, fluid support, red cell transfu-
response to therapy. 108 sion, and where appropriate surgical debridement. The infection is
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The onset of fever and hemolytic anemia after transfusion should often of abrupt onset and overwhelming, and the profundity of the
lead to the consideration of babesiosis. hemolysis and secondary organ damage (e.g., renal) results in a high
mortality rate.
TREATMENT AND COURSE
Most mild B. microti infections respond without treatment. The infec- OTHER INFECTIONS
tion has responded to drug therapy with clindamycin and quinine,
110
but failure to respond to antibiotics has also been encountered. The A variety of other infections occasionally have been associated with
102
two-drug combination can increase rate of clearance of parasites, but hemolytic anemia. The mechanisms involved vary. Some organisms,
they have consequential side effects. A combination of atovaquone and among them such common pathogens as Haemophilus influenzae, E.
azithromycin has also been proposed as treatment. 98,111 Whole-blood coli, and Salmonella species, can produce red cell agglutination in vitro,
or red cell exchange can result in marked improvement in recalcitrant but it is not known whether this phenomenon is important in initiating
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cases. 108,111 in vivo hemolysis. Bacteria may also produce destruction of red cells
indirectly when bacterial polysaccharides are adsorbed onto erythro-
cytes. Action of an antibody directed against the antigen-coated cells
COINFECTION results in their agglutination or in complement-mediated lysis. The
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In endemic areas two or more parasites may coinfect an individual by unmasking of T-type antigens by bacteria renders the cell polyaggluti-
a tick bite. B. microti and Borrelia burgdorferi (Lyme disease) may both nable. This may be a rare cause of hemolysis occurring in the course of
enter the human circulation as a result of the Ixodes tick bite, as can bacterial infections. 119,120
several other parasites (e.g., human granulocytic ehrlichiosis). Initial Many different types of microorganisms may play a role in pre-
signs and symptoms may be similar. Successful early treatment for Lyme cipitating autoimmune hemolytic disease (Chap. 54). In one study of

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