Comparative response to splenectomy in coombs-positive autoimmune hemolytic anemia with or without associated disease

Akpek, Görgün; McAneny, David; Weintraub, Lewis R.

doi:10.1002/(sici)1096-8652(199906)61:2<98::aid-ajh4>3.0.co;2-g

Cited by 73 publications

(50 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…34,35 Finally, splenectomy does not always alleviate AIHA, because hepatic macrophages may be responsible for a significant proportion of RBC consumption. 36,37 In fact, the substantial role of hepatic Kupffer cells in the development of AIHA has been repeatedly shown in mice. [6][7][8][9] The unpredictable efficacy of splenectomy is of particular concern in light of the short-term (surgical) and life-long (infectious) morbidities of this procedure.…”

Section: Discussionmentioning

confidence: 99%

Liposomal clodronate as a novel agent for treating autoimmune hemolytic anemia in a mouse model

Jordan

Rooijen

Izui

et al. 2003

Blood

View full text Add to dashboard Cite

IntroductionAutoimmune hemolytic anemia (AIHA) is an autoimmune disease in which antibodies directed against the patient's own red blood cells (RBCs) lead to their premature destruction. 1 Anemia can be sudden and life threatening, or more gradual in onset. Although most cases are idiopathic, association with other forms of autoimmunity, malignancy, or infection is common. [2][3][4][5] AIHA occurs in both children and adults, with a wide age distribution.AIHA can be mediated by immunoglobulin G (IgG), IgM, or, rarely, IgA antibodies. 1 Most clinically significant cases, however, are caused by IgG antibodies. 1,3 In these patients, autoantibodies bind to RBCs and promote their uptake by splenic and hepatic macrophages via Fc receptors. 6 Although IgG antibodies can fix complement, the principal means of destruction of RBCs in these cases is via phagocytosis. 1,7-9 Therefore, even though B cells (often with T-cell help) are producing the offending autoantibody, macrophages are the essential effector cells for the development of anemia. This fact is reflected in the therapy for AIHA. Splenectomy and corticosteroids, mainstays of treatment, both ultimately interfere with the phagocytosis of opsonized RBCs. 1 Experimental therapy in animal models has also used the specific blocking of Fc-mediated uptake of RBCs by either genetic means or the use of anti-Fc antibodies. [10][11][12][13][14] Clodronate (dichloromethylene diphosphonate) is a bisphosphonate used for treating osteolytic bone diseases and osteoporosis. Bisphosphonates alleviate these disorders by inhibiting the function of osteoclasts. There is evidence for both a direct blocking effect on these cells as well as an apoptosis-inducing effect. 15,16 Over a decade ago, it was found that incorporation of this drug into liposomes allowed it to become a potent antimacrophage agent both in vivo and in vitro. 17,18 The liposomal drug is taken up by macrophages and rapidly causes apoptosis. 19,20 Its effects in vivo are influenced principally by its route of administration. Injection into tissues leads to the depletion of macrophages from the tissue itself and from draining lymph nodes. Intravenous injection of liposomally encapsulated clodronate leads to nearly complete depletion of splenic and hepatic macrophages as well as marginal zone dendritic cells within 24 hours. 21 Unlike other methods of macrophage depletion, however, this treatment does not lead to the secretion of proinflamatory cytokines by the dying macrophages. 22 Moreover, liposomal clodronate appears to have a very selective effect on macrophages and phagocytic dendritic cells. Neutrophils and lymphocytes have not been found to be directly affected by the drug. 21,[23][24] Due to the well-established, critical role of macrophages in AIHA, we wondered whether the potent and specific antimacrophage effects of liposomal clodronate could be harnessed to treat this disease. To study this question, we generated a model of AIHA in mice. In this model, we treated mice with monoclonal anti-RBC antibodies de...

show abstract

Section: Discussionmentioning

confidence: 99%

Liposomal clodronate as a novel agent for treating autoimmune hemolytic anemia in a mouse model

Jordan

Rooijen

Izui

et al. 2003

Blood

View full text Add to dashboard Cite

show abstract

“…24,30,31 Patients without an underlying autoimmune disease or hematologic malignancy are twice as likely to respond as those with such conditions (82% vs 19% complete response). 32 Although rituximab has increasingly superseded splenectomy in recent retrospective studies and may be primary second line for some centers, 33 we still consider splenectomy as the primary second-line option in idiopathic AIHA. In one study of 52 patients with AIHA, 64% were in unmaintained remission after a mean follow-up of 33 months.…”

Section: What Is the Value Of Splenectomy?mentioning

confidence: 99%

How I treat autoimmune hemolytic anemia

Go¹,

Winters

Kay³

2017

Blood

157

113

View full text Add to dashboard Cite

Autoimmune hemolytic anemia (AIHA) is an uncommon entity that presents diagnostic, prognostic, and therapeutic dilemmas despite being a well-recognized entity for over 150 years. This is because of significant differences in the rates of hemolysis and associated diseases and because there is considerable clinical heterogeneity. In addition, there is a lack of clinical trials required to refine and update standardized and evidence-based therapeutic approaches. To aid the clinician in AIHA management, we present four vignettes that represent and highlight distinct clinical presentations with separate diagnostic and therapeutic pathways that we use in our clinical practice setting. We also review the parameters present in diagnostic testing that allow for prognostic insight and present algorithms for both diagnosis and treatment of the AIHA patient in diverse situations. This is done in the hope that this review may offer guidance in regard to personalized therapy recommendations. A section is included for the diagnosis of suspected AIHA with negative test results, a relatively infrequent but challenging situation, in order to assist in the overall evaluation spectrum for these patients. (Blood. 2017; 129(22):2971-2979

show abstract

“…2 However, its efficacy has never been compared to that of other second-line approaches, and no convincing data on remission duration after surgery are available. 1 Factors in favor of splenectomy as the best second-line therapy include its short-term efficacy and the good initial response rate: a partial or complete remission is obtained in approximately 2 in 3 patients (38-82% depending on the percentage of secondary cases which seem to be less responsive than idiopathic forms 21 ). Moreover, a substantial number of them remain in remission for years without medication, with a presumed cure rate of up to 20%.…”

Section: Splenectomymentioning

confidence: 99%

Treatment of autoimmune hemolytic anemias

2014

View full text Add to dashboard Cite

Autoimmune hemolytic anemia (AIHA) is a relatively uncommon disorder caused by autoantibodies directed against self red blood cells. It can be idiopathic or secondary, and classified as warm, cold (cold hemagglutinin disease (CAD) and paroxysmal cold hemoglobinuria) or mixed, according to the thermal range of the autoantibody. AIHA may develop gradually, or have a fulminant onset with life-threatening anemia. The treatment of AIHA is still not evidence-based. The first-line therapy for warm AIHA are corticosteroids, which are effective in 70-85% of patients and should be slowly tapered over a time period of 6-12 months. For refractory/relapsed cases, the current sequence of second-line therapy is splenectomy (effective approx. in 2 out of 3 cases but with a presumed cure rate of up to 20%), rituximab (effective in approx. 80-90% of cases), and thereafter any of the immunosuppressive drugs (azathioprine, cyclophosphamide, cyclosporin, mycophenolate mofetil). Additional therapies are intravenous immunoglobulins, danazol, plasma-exchange, and alemtuzumab and high-dose cyclophosphamide as last resort option. As the experience with rituximab evolves, it is likely that this drug will be located at an earlier point in therapy of warm AIHA, before more toxic immunosuppressants, and in place of splenectomy in some cases. In CAD, rituximab is now recommended as first-line treatment. ABSTRACT Treatment of warm AIHAThe traditional treatment of AIHA includes corticosteroids, splenectomy and conventional immunosuppressive drugs. Over recent years, some new therapies have become available and there has been some evidence of success. These therapies are primarily used in patients who are not candidates for or fail to respond to splenectomy, those who relapse after splenectomy, and those who cannot maintain stable hemoglobin levels without unacceptably high doses of corticosteroids. First-line therapy CorticosteroidsThere is general agreement that corticosteroids represent the first-line treatment for patients with warm antibody type AIHA, albeit their use is based on experience rather than hard evidence. In fact, there is little published information on their effectiveness, 1,16,17 and this is not supported by clinical trials. Corticosteroids, usually prednisone, are given at the initial dose of 1.0-1.5 mg/kg/day for 1-3 weeks until hemoglobin levels greater than 10 g/dL are reached. Response occurs mainly during the second week, and if none or minimal improvement is observed in the third week, this therapy is assumed to be ineffective. After stabilization of hemoglobin, prednisone should be gradually and slowly tapered off at 10-15 mg weekly to a daily dose of 20-30 mg, then by 5 mg every 1-2 weeks until a dose of 15 mg, and subsequently by 2.5 mg every two weeks with the aim of withdrawing the drug. Although one might be tempted to discontinue steroids more rapidly, AIHA patients should be treated for a minimum of three or four months with low doses of prednisone (≤10 mg/day).1 In fact, patients receiving low doses of cortico...

show abstract

Comparative response to splenectomy in coombs-positive autoimmune hemolytic anemia with or without associated disease

Cited by 73 publications

References 14 publications

Liposomal clodronate as a novel agent for treating autoimmune hemolytic anemia in a mouse model

Liposomal clodronate as a novel agent for treating autoimmune hemolytic anemia in a mouse model

How I treat autoimmune hemolytic anemia

Treatment of autoimmune hemolytic anemias

Contact Info

Product

Resources

About