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668 Part V Red Blood Cells

Alteration of the Red Blood Cell Surface by Reduction of Dangerous Methemoglobin Levels
Bacterial Products Levels of methemoglobin in excess of 20% to 30% can be dangerous,
but they can be easily treated with methylene blue (1–2 mg/kg) infused
Infection can produce hemolysis by altering the RBC surface. An intravenously over 5 minutes as 0.1–0.2 mL/kg of a 1% solution. In the
example is the hemolysis caused by Haemophilus influenzae type b. presence of a functioning, intact reduced form of nicotinamide adenine
Severely affected patients, particularly those with meningitis, have dinucleotide phosphate (NADPH)–methemoglobin reductase system,
developed hemolytic anemias requiring RBC transfusions. The cap- methylene blue is reduced to leukomethylene blue, which reduces
sular polysaccharide of the bacterium, composed of polyribosyl ribitol methemoglobin to hemoglobin.
phosphate (PRP), is released during infection and binds to the RBC
surface. Infected patients develop antibodies to PRP. When the
balance between PRP-coated RBCs and anti-PRP antibodies is
correct, an immune-type hemolysis occurs and requires complement. The literature on RBC shape change in liver disease is consider-
RBC destruction is thought to be both intravascular and able. The target cell in cirrhosis has an increased SA:V that appears
extravascular. to be a consequence of increased cholesterol and phospholipid
content of the membrane bilayer. The cholesterol increase is usually
Bacterial Products Causing Hemolysis by Direct proportionately greater, resulting in an increased cholesterol-to-
phospholipid ratio. This increase in lipid probably accounts for the
Damage to Red Blood Cells increased RBC surface area, such that more membrane than usual is
present in relation to cellular contents. These RBCs probably circulate
The most dramatic example of hemolysis caused by bacterial action is as bell-shaped RBCs called codocytes. However, on dried blood films,
clostridial infection, during which the organism releases enzymes that they assume the appearance of target cells. Target cells do not have a
acutely degrade the phospholipids of the membrane bilayer and the shortened survival. The RBCs of patients with liver disease frequently
structural membrane proteins. The resulting spherocytes are extremely are echinocytes when wet preparations are examined, but these
sensitive to osmotic lysis. The setting can be any infection, but our echinocytes are not easily apparent on dried blood smears. The
experience is limited to acute cholecystitis, surgery of the biliary tree, echinocytes seem to be produced by a material in the patient’s plasma
and infections surrounding an obstetric event, including criminal or that causes normal RBCs to become echinocytic; this material is an
self-induced abortion, or other infection of the gravid uterus. Patients abnormal echinocytogenic high-density lipoprotein. Echinocytes do
may also have an underlying gastrointestinal, genitourinary, neuroen- not necessarily have a shortened survival. Some forms of echinocytic
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docrine, or hematologic malignancy. The signs of infections may be RBCs are normally deformable when studied in the ektacytometer or
obvious, but fever may be unimpressive. Signs of collapse appear rheoscope.
acutely, and the clue is profound intravascular hemolysis, with a A brisk, clinically important hemolysis can occur in some patients
spherocytic anemia developing with shocking suddenness. The blood with severe liver disease. The peripheral smear in these individuals
smear characteristically has numerous spherocytes with little evidence usually shows acanthocytes (i.e., distorted RBCs). Extreme forms are
of microangiopathy, may be tinged red because of marked hemoglo- called spur cells, which are probably acanthocytes additionally remod-
binemia, and may have ghost cells. A clue to the severity of the process eled by an enlarged spleen (see box on Reduction of Dangerous
may be the inability of the laboratory to perform chemical determina- Methemoglobin Levels) and are considerably enriched in cholesterol.
tions or to type and cross-match the blood because the sample is They are rapidly removed in the spleen, which is usually enlarged.
hemolyzed. With even the slightest suspicion of hemolysis caused by Increased RBC membrane proteolytic activity may be a partial
bacterial action, the physician immediately starts full doses of penicil- explanation for the differences between acanthocytosis and spur cells,
lin and clindamycin; evaluates the patient for DIC (see Chapter 139); and additional pathophysiologic mechanisms may be involved.
and prepares to support the patient for shock, DIC, acute renal failure, Although the adult RBC cannot synthesize phospholipids de novo,
and hemolytic anemia. Whether hysterectomy is lifesaving in the case it can identify and remove peroxidized fatty acid chains that interfere
of septic abortion is unclear. with normal membrane lipid fluidity. When the fatty acid is removed,
a lytic lysoderivative remains; therefore, the missing fatty acid chain
Hemolysis Caused by Less Well must be replaced. A store of acyl groups in the form of acylcarnitine
exists in RBC membranes. When needed, the fatty acid (i.e., acyl
Understood Infections group) is transferred to acyl-coenzyme A and then inserted into the
potentially lytic lysophospholipid by the enzyme lysophosphocholine
HIV infection can cause Coombs-positive autoimmune hemolytic acyltransferase. Lysophosphocholine acyltransferase is inhibited in
anemia, a TTP-like syndrome, and microangiopathic hemolysis. spur RBCs, and the same inhibition can be produced by heavily
CMV infection has been reported to cause severe Coombs-negative loading RBCs with cholesterol in vitro.
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hemolytic anemia in immunocompetent adults. Case reports of In a case of almost fatal oxidative hemolysis, hydrogen peroxide
autoimmune hemolytic anemia and HUS associated with CMV was injected directly into the Hickman catheter of a patient with
infection have emerged. The hemolytic anemia in visceral leishmani- AIDS because some persons infected with HIV had circulated a
asis may be caused in part by generation of oxidative metabolic pamphlet suggesting that hydrogen peroxide could be used therapeu-
products. Severe microangiopathic hemolytic anemia has been tically to control HIV infection. We now are seeing AIDS patients
described in cases of cutaneous anthrax. with dapsone-induced methemoglobinemia and hemolytic anemia
(see Chapter 42). Methemoglobinemia, if severe, is treated as
described in the preceding paragraph and in Chapter 24.
Hemolysis Associated With Liver Disease In spur cell anemia, the RBCs have an abnormal membrane SA:V
ratio, their membrane fluidity is impaired, and they are unable to
Hemolysis in liver disease by itself usually is not of overwhelming remove and repair peroxidatively damaged fatty acids. Occasionally,
clinical importance, but it may contribute to the severity of anemia spur cell hemolytic anemia is severe enough to necessitate consider-
when coupled with defects in RBC production and the type of ation of splenectomy. Operative morbidity in such cases is consider-
gastrointestinal blood loss that occurs in several forms of liver disease. able because the underlying liver disease usually produces problems
Hemolysis in patients with liver disease has several causes. The spleen with thrombocytopenia and leukopenia, as well as with procoagulants
may be enlarged as a consequence of portal hypertension and produce and intolerance to anesthesia. Spur cell anemia is typically associated
a hypersplenic picture, a phenomenon seen commonly in hepatic with alcoholic cirrhosis, but can also be seen in patients with nonal-
cirrhosis. coholic cirrhosis. The anemia tends to be severe and portends a poor