Page 864 - Williams Hematology ( PDFDrive )

838 Part VI: The Erythrocyte Chapter 54: Hemolytic Anemia Resulting from Immune Injury 839

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Other Immunosuppressive Drugs respond to colectomy. In patients with AHA associated with an ovar-
Cytotoxic drugs such as cyclophosphamide, 6-mercaptopurine, aza- ian dermoid cyst, cyst removal produces remission of the hemolysis. 345
thioprine, and 6-thioguanine have been given to patients with AHA to
suppress synthesis of autoantibody. Direct evidence of such an effect is THERAPY OF COLD-ANTIBODY HEMOLYTIC
lacking. Although immunosuppressive therapy is not universally accepted,
beneficial responses to immunosuppressive drugs have been observed in ANEMIA
some patients who did not respond to glucocorticoids. 11,326 Importantly, Keeping the patient warm, particularly the patient’s extremities, is
the majority of patients with warm-antibody AHA respond to glucocor- moderately effective in providing symptomatic relief. This action may
ticoids and/or splenectomy and usually are not candidates for immuno- be the only measure required in patients with mild chronic hemoly-
suppressive therapy. At present, immunosuppressive therapy should be sis. In symptomatic patients, rituximab is effective and well tolerated.
reserved primarily for patients who do not respond to glucocorticoids, In two prospective trials, approximately half the patients responded to
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rituximab, or splenectomy, or for patients who are poor surgical risks. 326 rituximab 375 mg/m weekly for 4 weeks. 346,347 Patients who relapsed
The most successful approach used high-dose cyclophosphamide responded to a second course of rituximab at about the same rate. In
50 mg/kg ideal body weight per day for 4 consecutive days, intrave- a prospective trial of rituximab and fludarabine, the response rate was
nously, with granulocyte colony-stimulating factor support. Of nine 76 percent, including complete responses in 21 percent with a median
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patients, eight of whom had warm autoantibodies, all became trans- response duration of 66 months. In another small study, 60 percent
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fusion independent. All patients had prolonged severe cytopenias and of patients responded to low dose rituximab, 100 mg/m , a rate compa-
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required hospitalization for a median of 21 days. Cyclophosphamide rable to that seen with rituximab 375 mg/m . Chlorambucil or cyclo-
may cause severe hemorrhagic cystitis and sodium 2-mercaptoethane- phosphamide may be helpful for patients with symptomatic chronic
sulfonate (mesna) 10 mg/kg was given at 3, 6, and 8 hours following cold agglutinin disease. 9–11,349,350 In patients with lymphoma, treatment
each cyclophosphamide dose, to minimize the effect of cyclophos- of the underlying disorder usually results in control of the cold agglu-
phamide on the bladder. tinin disease. Single patients with refractory cold agglutinin disease
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For patients who may not tolerate prolonged cytopenias, the drugs have exhibited responses to eculizumab 351,352 and bortezomib. Results
of choice are cyclophosphamide 60 mg/m or azathioprine 80 mg/m of splenectomy 10,11,354 or use of glucocorticoids 10,11 generally have been
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given daily. If the patient tolerates the drug, continue treatment for up disappointing, although exceptions have been reported, 10,196,277,278 par-
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to 6 months while waiting for a response. When response occurs, the ticularly in atypical cases. Experimental and clinical bases exist for
patient can be weaned slowly from the drug. If no response is observed, considering very high doses of glucocorticoids in seriously ill patients.
the alternative drug can be tried. Because cyclophosphamide and aza- RBC transfusions generally are reserved for patients with severe anemia
thioprine suppress hematopoiesis, blood counts, including reticulocyte of rapid onset who are in danger of cardiorespiratory complications.
count, must be monitored with extra care during therapy. Treatment Washed RBCs often are used to avoid replenishing depleted comple-
with either agent increases the risk of subsequent neoplasia. ment components and reactivating the hemolytic process. In critically
Patients with refractory AHA have been treated effectively with ill patients, plasma exchange (with replacement by albumin-containing
the purine analogue 2-chlorodeoxyadenosine (cladribine) and with saline solution) may provide transient amelioration of hemolysis. 355–357
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mycophenolate mofetil. 329,330 Alemtuzumab was successfully used to In patients with cold agglutinin disease secondary to infection,
treat 5 patients with refractory AHA associated with CLL. 331 spontaneous resolution of the hemolysis is expected in all patients after
resolution of the infection. RBC transfusion may be required as a tem-
Other Therapies porizing measure and in severe cases, plasma exchange may be bene-
For patients with chronic compensated hemolysis, treatment with folate ficial. There is little evidence to support the use of glucocorticoids or
at 1 mg/day, orally, is recommended to satisfy the increased demands for antiviral therapy.
the vitamin because of increased red cell production. Plasma exchange Most contemporary cases of paroxysmal cold hemoglobinuria are
or plasmapheresis has been used in patients with warm-antibody AHA. self-limited. Acute attacks in both chronic and transient forms of parox-
Improvement has been reported in a few cases, but use of the method is ysmal cold hemoglobinuria may be prevented by avoiding cold exposure.
controversial. 332,333 A patient with life-threatening warm IgG-mediated Glucocorticoid therapy and splenectomy have not been useful. When
AHA refractory to glucocorticoids and splenectomy exhibited rapid paroxysmal cold hemoglobinuria is associated with syphilis, effective
clinical improvement following manual whole blood exchange. A treatment of the infection may result in complete remission. Antihis-
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patient with severe warm IgM-mediated AHA was successfully treated taminic and adrenergic agents may relieve symptoms of cold urticaria.
with C1-esterase inhibitor (C1-inh) resulting in attenuation of comple-
ment deposition on RBCs and hemolysis, along with improved recovery THERAPY OF DRUG-INDUCED IMMUNE
of transfused RBCs. Another patient with refractory warm IgM-
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mediated AHA responded to rituximab and eculizumab. Thymec- HEMOLYTIC ANEMIA
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tomy has been reported useful in a few children who were refractory to Discontinuation of the offending drug often is the only treatment
glucocorticoids and splenectomy. Selective injury to splenic macro- needed. This measure is essential and may be lifesaving in patients with
326
phages by administration of vinblastine-loaded, IgG-sensitized platelets severe hemolysis mediated by the ternary complex mechanism.
reportedly was successful in a few patients. Several anecdotal reports In the past, high-dose penicillin was not necessarily discontinued
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and a case series indicate short-term successful treatment of patients because of a positive DAT alone. A change in therapy was considered
with AHA using high-dose intravenous γ-globulin. 338–341 Uncontrolled mainly in the presence of overt hemolytic anemia. For example, lower-
studies indicate danazol, a nonvirilizing androgen, may be useful in ing the penicillin dose and coadministering other antibiotics sometimes
patients with AHA. 342,343 Danazol may eliminate the need for splenec- allowed continuation of the drug, particularly if hemolysis was not
tomy when combined with prednisone and may allow for a shorter severe. For other drugs causing only mild hemolysis by the hapten-drug
duration of prednisone therapy. Some patients with ulcerative coli- adsorption mechanism, in the unlikely event that no alternatives are
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tis and AHA unresponsive to glucocorticoids and splenectomy may available, a similar approach may be effective.

Kaushansky_chapter 54_p0823-0846.indd 839 9/19/15 12:28 AM