23例温冷双抗体型自身免疫性溶血性贫血的临床特征

目的 了解近十年温冷双抗体型自身免疫性溶血性贫血（AIHA）患者的临床特征，以加深对该病的认识。方法 对1994年1月至2004年4月诊断的23例温冷双抗体型AIHA的临床表现、实验室特征及治疗反应进行回顾性分析。结果 近十年温冷双抗体型AIHA在同期AIHA中占22．1％，较20世纪80年代的17．6％有所增加；原发性病例占73．9％；女性多见；自身抗体的类型以复合型为主，含IgM抗体者多见（56．5％），抗体温幅及补体水平与溶血程度相关；对肾上腺皮质激素合并其它免疫抑制剂反应较好；中位随访时间4个月，复发率为77．8％。结论 温冷双抗体型AIHA是一种女性多见、原发性为主、与抗体种类和温幅及补体激活相关、复发率较高的溶血性疾病，联合免疫抑制治疗效果较好。     

PEG adsorption of autoantibodies and detection of alloantibodies in warm autoimmune hemolytic anemia

BACKGROUND: The purpose of this study was to evaluate the effectiveness of PEG in the adsorption of autoantibodies and the detection of alloantibodies in patients with warm autoimmune hemolytic anemia (WAIHA). STUDY DESIGN AND METHODS: The study was divided into three parts. First, the effectiveness of antibody removal by a conventional adsorption procedure and that by the PEG adsorption method were compared by using commercial antisera adsorbed with antigen-positive RBCs. Second, patients' sera with known weak alloanti-E were used to test against screening cells after allogeneic adsorption to show nonspecific coating of antibodies and the dilution effect on the PEG adsorption procedure. Third, conventional and PEG one-cell sample allogeneic adsorptions of WAIHA patients' sera with and without alloantibodies were performed and compared. RESULTS: In the first part, seven of the eight polyclonal antisera gave a lower titer and score when tested against antigen-positive RBCs in the indirect antiglobulin test; this indicated that PEG is more efficient in removing antibodies. In the second part, similar reaction patterns were observed in antibody screening tests on unadsorbed sera and on sera after the first, second, and third adsorptions, which indicated that there was no alloantibody loss, nonspecific antibody coating, or dilution effect when PEG was added in the allogeneic adsorption procedures. In the third part, a 40-percent increase in efficiency in reducing the number of adsorptions and an 85-percent decrease in completion time of the adsorption procedures were obtained when PEG was used for adsorbing sera from 16 patients with WAIHA. Both conventional and PEG procedures were capable of removing autoantibodies to identify the specificities of alloantibodies. CONCLUSION: The PEG adsorption method is an effective, sensitive, and efficient method of enhancing auto- antibody adsorption and alloantibody detection. It can reduce the processing time and minimize the delay of urgent transfusions to patients with WAIHA and can indirectly enhance cost-effectiveness and decrease the labor-intensive testing required by these cases.     

Thyroid storm and warm autoimmune hemolytic anemia

Graves’ disease is often associated with other autoimmune disorders, including rare associations with autoimmune hemolytic anemia (AIHA). We describe a unique presentation of thyroid storm and warm AIHA diagnosed concurrently in a young female with hyperthyroidism. The patient presented with nausea, vomiting, diarrhea and altered mental status. Laboratory studies revealed hemoglobin 3.9 g/dL, platelets 171 × 10⁹ L^?1, haptoglobin <5 mg/dL, reticulocytosis, and positive direct antiglobulin test (IgG, C3d, warm). Additional workup revealed serum thyroid stimulating hormone (TSH) <0.01 μIU/mL and serum free-T4 (FT4) level 7.8 ng/dL. Our patient was diagnosed with concurrent thyroid storm and warm AIHA. She was started on glucocorticoids to treat both warm AIHA and thyroid storm, as well as antithyroid medications, propranolol and folic acid. Due to profound anemia and hemodynamic instability, the patient was transfused two units of uncrossmatched packed red blood cells slowly and tolerated this well. She was discharged on methimazole as well as a prolonged prednisone taper, and achieved complete resolution of the thyrotoxicosis and anemia at one month. Hyperthyroidism can affect all three blood cell lineages of the hematopoietic system. Anemia can be seen in 10–20% of patients with thyrotoxicosis. Several autoimmune processes can lead to anemia in Graves’ disease, including pernicious anemia, celiac disease, and warm AIHA. This case illustrates a rarely described presentation of a patient with Graves’ disease presenting with concurrent thyroid storm and warm AIHA.     

Hemolytic warm IgM autoagglutinins in autoimmune hemolytic anemia

The authors report a patient with fulminant autoimmune hemolytic anemia due to a rare warm IgM autoagglutinin more reactive at 37 degrees C than at lower temperatures and secondary to systemic lupus erythematosis. The patient's clinical course and the serologic and immunochemical characteristics of the antibody are described, including the possibility that transfusions of small amounts of incompatible red cells may have contributed to the hemolysis. The consequences of using the initial serologic test results as the basis for therapy are discussed.     

Autoimmune hemolytic anemia with concurrence of warm and cold red cell autoantibodies and a warm hemolysin

This report describes the laboratory findings and clinical course of a patient with thrombophlebitis, venous gangrene, and autoimmune hemolytic anemia. Three concomitant red cell autoantibody activities were detected: a low-titer, high-thermal-amplitude, IgM anti-I cold agglutinin; an IgG warm 'incomplete' panagglutinating autoantibody; and an IgM warm hemolysin.     

High pathogenic potential of low-affinity autoantibodies in experimental autoimmune hemolytic anemia

To assess the potency of low-affinity anti-red blood cell (RBC) autoantibodies in the induction of anemia, we generated an immunoglobulin (Ig)G2a class-switch variant of a 4C8 IgM anti-mouse RBC autoantibody, and compared its pathogenic potential with that of its IgM isotype and a high-affinity 34-3C IgG2a autoantibody. The RBC-binding activity of the 4C8 IgG2a variant was barely detectable, at least 1,000 times lower than that of its IgM isotype, having a high-binding avidity, and that of the 34-3C IgG2a monoclonal antibody (mAb). This low-affinity feature of the 4C8 mAb was consistent with the lack of detection of opsonized RBCs in the circulating blood from the 4C8 IgG2a-injected mice. However, the 4C8 IgG2a variant was highly pathogenic, as potent as its IgM isotype and the 34-3C IgG2a mAb, due to its capacity to interact with Fc receptors involved in erythrophagocytosis. In addition, our results indicated that the pentameric form of the low-affinity IgM isotype, by promoting the binding and agglutination of RBCs, is critical for its pathogenic activity. Demonstration of the remarkably high pathogenic potency of low-affinity autoantibodies, if combined with appropriate heavy chain effector functions, highlights the critical role of the Ig heavy chain constant regions, but the relatively minor role of autoantigen-binding affinities, in autoimmune hemolytic anemia.     

Levofloxacin-induced autoimmune hemolytic anemia

OBJECTIVE: To report a case of autoimmune hemolytic anemia (AIHA) secondary to levofloxacin. CASE SUMMARY: An 82-year-old white man was treated with levofloxacin 500 mg/d for cellulitis. Three days following completion of levofloxacin therapy, the patient presented to the emergency department with severe jaundice, dizziness, and loss of vision. He received packed red blood cells (PRBCs) and was discharged home. Two days later at the follow-up visit, he was diagnosed with AIHA secondary to levofloxacin. The patient was hospitalized and treated with a tapering dose of prednisone and additional PRBC infusion. He was discharged from the hospital in stable condition after 3 days. Repeated hematologic laboratory studies following discharge demonstrated that the hemolytic anemia had resolved. DISCUSSION: Hemolytic anemia due to levofloxacin is an extremely rare, but potentially fatal, adverse drug event. An objective causality assessment revealed that the adverse reaction was probable. To our knowledge, this is the first published case of levofloxacin-induced AIHA. However, there are published case reports of hemolytic anemia with other fluoroquinolones including ciprofloxacin (n = 12) and temafloxacin (n = 95). Temafloxacin was withdrawn from the market in 1992 due to this adverse effect. The mechanism by which levofloxacin triggers hemolytic anemia is unknown. We believe that an immune-mediated reaction is most likely. CONCLUSIONS: Levofloxacin-induced AIHA is a rare but serious complication of therapy. Immediate discontinuation of the offending medication and treatment of the hemolytic anemia are essential. Until more information is available, levofloxacin should not be prescribed for patients with previous reactions to any fluoroquinolone.     

Further studies on the relationship of anti-Ena and anti-Wrb in warm autoimmune hemolytic anemia

The red blood cell eluates of two patients with warm autoimmune hemolytic anemia (AIHA) were found to have anti-dl and anti-Wrb in a study of 150 individuals with positive AHG tests.7 In that series 39 per cent of AIHA cases had anti-Wrb as part of the autoantibody specificity. The eluates of these two patients were of further interest since they showed weaker reactions with En(a−) cells than with En(a+), Wr(a+b−) cells. Further absorption of the eluates confirmed a second component that reacted with the En(a+), Wr(b−) cells but not the En(a−) cell, interpreted as autoanti-Ena. In one of the cases anti-Ena was recovered from the En(a−) absorbing cell although these cells were not agglutinated by the autoantibody. This effect was not due to polyagglutinability, the Matuhasi-Ogata phenomenon or the decreased sialic acid content of the En(a−) red blood cell membranes and remains unexplained.     

急性肾损伤并自身免疫性溶血二例并文献复习

目的 探讨急性肾损伤合并自身免疫性溶血性贫血的临床特点.方法 分析2例急性肾损伤合并自身免疫性溶血性贫血患者的临床资料,结合文献复习此类疾病的临床特点及诊治思路.结果 2例患者均表现为严重的急性肾损伤、进行性加重的贫血,促红素、铁剂、叶酸补充等常规纠正贫血治疗无效,直接Coombs阳性,外周血网织红细胞升高,血清乳酸脱氢酶、血清胆红素正常,类固醇激素治疗有效.结论 急性肾损伤合并进行性贫血需考虑是否合并自身免疫性溶血,及时给予类固醇激素治疗临床效果显著.     

pH-dependent anti-U in autoimmune hemolytic anemia

Auto anti-U of unusual serologic characteristics is described in a Caucasian patient with autoimmune hemolytic anemia associated with chronic lymphocytic leukemia. The direct antiglobulin test was strongly positive (3+) with broad spectrum and anticomplement reagents. Auto anti-U was demonstrated only when the serum was acidified to pH 6.5 and anticomplement reagent was used in the antiglobulin test. Multiple transfusions of U positive red blood cells had clinically decreased survival manifested by jaundice and return of hemoglobin to pretransfusion levels within days. The autoantibody reacted weakly with U positive cord red blood cells interpreted as mosaicism of the U antigen possibly on a developmental basis.     

自身免疫性溶血性贫血患者血清可溶性人类白细胞抗原G水平测定及意义

目的探讨血清可溶性人类白细胞抗原G（soluble human leukocyte antigen G, sHLA-G）在温抗体型自身免疫性溶血性贫血中的临床意义。方法76例初治温抗体型自身免疫性溶血性贫血患者（WAIHA组）,体检健康者48例（对照组）,采用双抗体夹心ELISA法检测2组治疗前、后血清sHLA—G水平并进行比较。结果治疗前WAIHA组sHLAG水平（13．57±5．19）μg／L高于对照组（6．15±4．11）μg／L（P〈0．05）;WAIHA组经治疗缓解者血清sHLA—G水平（6．20±3．89）μg／L低于治疗前及未缓解者（13．54±4．30）μg／L（P〈0．05）;未缓解者sHLA—G水平与治疗前比较差异无统计学意义（P〉0．05）。结论sHLAG可能参与了温抗体型自身免疫性溶血性贫血的发病,检测sHLA—G水平对病情判断有重要价值。     

Fine structure of the spleen in autoimmune hemolytic anemia associated with systemic lupus erythematosus

The fine structures of the red pulp of the spleen and the liver of a patient with autoimmune hemolytic anemia, neutropenia and thrombocytopenia associated with systemic lupus erythematosus are described. The red blood cells were phagocytized in toto by the splenic macrophages. These also contained neutrophils and platelets in various stages of degradation. Sinus endothelial cells revealed occasional erythrophagocytosis. The Kupffer cells in the liver occasionally contained red cells and platelets. These morphological findings and marked improvement of hematological abnormalities following splenectomy suggested that the spleen was the major site of destruction of blood cells. Undulating tubules associated with the endoplasmic reticulum were present in the sinus endothelial cells of the spleen.