Page 769 - Hematology_ Basic Principles and Practice ( PDFDrive )

656 Part V Red Blood Cells

glucose-6-phosphate-dehydrogenase deficiency should be considered. Transfusion Therapy in Selected Patients With Severe Autoimmune
Babesiosis or other infections may cause nonimmune hemolytic Hemolytic Anemia
anemia. In severely ill patients with hemolytic anemia and thrombo-
cytopenia, idiopathic or cancer-related thrombotic thrombocytopenic Immediate blood transfusion should not be withheld from patients with
purpura, hemolytic uremic syndrome, or disseminated intravascular severe anemia. Small amounts of RBCs may be lifesaving in patients
coagulation should prompt a search for schistocytes in the blood with acute cardiac or cerebral dysfunction caused by anemia. However,
smear. precautions have to be taken to avoid transfusion reactions. This
Paroxysmal nocturnal hemoglobinuria is diagnosed by a deficiency requires close cooperation between clinicians and the blood bank. The
of glycosylphosphatidylinositol anchor proteins on the cell surface exclusion of alloantibodies is most important. Patients with a low risk for
caused by a mutation of the PIG-A gene. Type II mixed cryoglobu- severe reactions caused by an alloantibody are those without a history
linemia is a condition caused by a monoclonal IgM autoantibody of previous transfusions or pregnancy. In high-risk patients, extended
RBC phenotyping should be performed for selection of compatible RBC
with anti-IgG activity with rheumatoid factor properties frequently concentrates. In all instances, a biologic in vivo compatibility test has
associated with hepatitis C. The clinical picture is characterized by a to be performed at the beginning of the transfusion.
systemic vasculitis syndrome but not by anemia.

TREATMENT pregnancy the risk of alloantibodies is low, allowing for transfusion
of only ABO- and RhD-matched RBCs. In all other patients,
For many years, drugs and procedures routinely used in the treatment extended phenotyping with respect to Rh subgroups (C, c, E, e), Kell,
of AIHA were not subjected to studies that today are regarded as the Kidd, and S/s using monoclonal IgM antibodies should be performed
gold standard for approval and recommendation. Only a few ran- for selection of compatible RBC concentrates. Warm autoadsorption
domized studies have been performed, and were usually small, and or allogeneic adsorption procedures for detection of alloantibodies
often with a heterogeneous population of patients with a short may be used in exceptional cases. In patients with CAIHAs, trans-
observation time. Thus, the treatment recommendation in this fused blood must be prewarmed using commercial warming coils. In
chapter should be viewed critically. 8 all instances, an important precaution is a biologic in vivo compatibil-
ity test, which includes rapid infusion of 20 mL of blood; 20 minutes
observation; and, if there is no reaction, further transfusion at usual
Goals of Treatment speed.

As in all diseases, the goal of treatment of AIHA is the achievement Treatment of Primary Warm Antibody
of a complete clinical and laboratory sustained remission without any
residual signs of the disease. Such results can be obtained not only in Hemolytic Anemia
primary AIHA but also in a substantial number of secondary cases
when the underlying disease disappears spontaneously (infection), First-Line Treatment With Steroids
when the causative drug is withdrawn, or after (curative) treatment
(surgery or chemoimmunotherapy) of an underlying malignancy. In Newly diagnosed severe WAIHAs should be treated immediately with
most patients with primary WAIHAs, the expectations for success glucocorticoids (steroids) (Fig. 46.5 and Table 46.5; see also box on
must be tempered. Therefore, a practical goal is the achievement of Initial Steroid Therapy). Therapy starts with an initial dose of 1 mg/
a good clinical response with freedom from symptoms in the absence kg/day of prednisone orally or an equivalent dose of methylpredni-
of side effects of treatment. Remission of AIHA after treatment is sone intravenously. It is recommended to continue with this dose
often defined by laboratory values, but there is no consensus on the until a hematocrit of greater than 30% or a Hb level of greater than
definition of CR or partial remission (PR) regarding Hb concentra- 10 g/dL is achieved. CR or PR is obtained in approximately 80% of
tion. Formally, one could define CR as absence of transfusion require- patients. Failure to achieve this goal after 3 weeks should result in a
ment, a normal Hb value (according to the age and sex of the patient), switch to second-line therapy. In responding patients, prednisone
and absence of signs of hemolysis (normal reticulocyte counts, hap- dose is gradually reduced to 20–30 mg/day within a few weeks.
toglobin, and LDH; negative DAT result). Such CR is sometimes Subsequently, the dose is tapered slowly by 2.5 mg to 5 mg/day per
seen in secondary AIHA. In primary AIHA, CR is often defined as month guided by Hb and reticulocyte counts. If the patient is still
Hb above 11.0 g/dL without sign of hemolysis, but the DAT result in remission after 3–4 months at a dose of 5 mg/day, withdrawal of
may remain positive. A minimal requirement for PR is the absence steroids can be attempted. The exact rate of patients remaining in
of transfusion requirement and a satisfactory clinical condition CR after the end of steroid therapy is not known but is estimated to
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(usually Hb >9–10 g/dL). Thus, in AIHA, the treatment goals must be around 20% to 40%. Most responders require maintenance
be defined individually and tailored to the patient’s needs. steroids to keep the Hb above 9–10g/dL. About 40% to 50% of
patients need 15 mg/day or less prednisone (regarded as the highest
tolerable dose for long-term treatment). However, 15% to 20% need
Blood Transfusions higher maintenance prednisone doses.
For rituximab, two prospective studies have been reported. 33,34
Blood transfusions may be necessary for emergency treatment of The first was an open-prospective phase II study testing the efficacy
AIHA. The problem is to find well-matched RBC concentrates. In and safety of low-dose rituximab and the second was a randomized
critical cases, transfusions should not be avoided or delayed because phase III open trial that showed the benefit of rituximab in combina-
of uncertainty in matching (see box on Transfusion Therapy in tion with prednisolone over prednisolone alone with an overall
Selected Patients With Severe Autoimmune Hemolytic Anemia). The response rate (ORR) of 75% at 1 year in the rituximab arm. Com-
decision is made on an individual basis depending on the speed of bination of rituximab with steroids compared with steroid mono-
development and severity of anemia, the type and cause of hemolytic therapy produced an increased response rate (75% vs 36% at 1 year)
anemia (the highest acute death rates were observed in patients with and a longer relapse-free survival (70% vs 45% at 3 years). Despite
fludarabine-associated AIHA, IgM WAIHAs, and DL antibodies), these encouraging data, the real value of rituximab in first-line
and the age and clinical condition of the patient. Because the antibody remains to be established.
in WAIHAs is directed against blood group antigens, no truly Therapeutic management of steroid treatment should include
matched blood transfusions are possible, but RBCs can be safely given blood glucose monitoring, prophylaxis against osteoporosis (com-
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if alloantibodies are excluded. However, some precautions have to mence early), supplementation with folic acid, and heparin treatment
be taken. In patients without a history of previous transfusions or in selected cases.