Review article
Acquired amegakaryocytic thrombocytopenic purpura: Review of a not very well-defined disorder

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Abstract

Acquired amegakaryocytic thrombocytopenic purpura (AATP) is a hematological disorder characterized by severe thrombocytopenia, probably due to an immunologically induced absence of megakaryocytes with a marked decrease or total absence of megakaryocytes in the bone marrow. AATP may be differentiated from other causes of peripheral destruction of platelets, such as immune thrombocytopenia (ITP). Currently, there are no standard treatments for AATP. However, immunosuppressive therapy including steroids, androgens, anti-thymocyte globulin (ATG), cyclophosphamide, cyclosporine A, immunoglobulins, splenectomy, and allogenic bone marrow transplantation (BMT) have all been utilized with varying degrees of success. However, a positive response in patients with AATP using steroids alone has rarely been reported in the literature.

Introduction

Acquired amegakaryocytic thrombocytopenic purpura (AATP), first reported by Korn [1], is a rare disorder that is characterized by severe thrombocytopenia (usually < 20,000/μl) with the other cell lines preserved and a marked decrease or total absence of megakaryocytes in the bone marrow [2]. This disorder was originally postulated to be analogous to acquired pure red cell aplasia in which antibodies against the megakaryocyte (MK) precursor were thought to inhibit MK maturation [3], [4], [5]. The clinical course of the disease is variable and some cases have been reported to progress to aplastic anemia, myelodysplasia, or leukemia [3], [4], [6], [7], [8], [9]. The usual clinical presentation of AATP is with bruising, bleeding, and the absence of splenomegaly with platelet survival studies being usually normal [9]. Due in part to the heterogeneous nature of the syndrome and the variety of pathogenic mechanisms, no standard treatment has yet been established. However, therapy for AATP has included the administration of steroids, androgens, anti-thymocyte globulin (ATG), cyclophosphamide, cyclosporine A, immunoglobulins, splenectomy, and allogenic BMT, all with varying degrees of success. This article will review the literature on AATP and discuss therapeutic options.

Section snippets

Pathogenic mechanisms

AATP may be a primary disorder in itself or it may be seen in other diseases, such as aplastic anemia, preleukemia, leukemia, systemic lupus erythematosus (SLE), systemic sclerosis (SSc), Graves disease treated previously with radioiodine, congenital rubella, dengue fever, HIV-1 infection, drug-induced nutritional B-12 deficiency, and ethanol abuse [3], [9], [10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20], [21].

A variety of pathogenetic mechanisms has been suggested. Previous

Therapy

Several empirical therapies are used in patients with AATP and include the administration of steroids, androgens, anti-thymocyte globulin (ATG), cyclophosphamide, cyclosporine A, vincristine, immunoglobulins (IVIG), splenectomy, and allogenic BMT, all with different results (Table 1). Manoharan et al. [35], in a literature review, reported 30 patients who were treated with numerous regimens. They found that the patients with the best response were those who received active immunosuppressive

Conclusion

Based on our review of the literature, it appears that AATP can be caused by a great variety of etiological mechanisms and that it is reasonable to try empiric therapy with steroids, IVIG, cyclophosphamide, cyclosporine A, vincristine, danazol, and ATG, either alone or in combination. However, therapy with either ATG or cyclosporine A in combination with steroids would seem to be more effective than other drug combinations. In the case of an asymptomatic patient, a trial of ATG or cyclosporine

Acknowledgment

The author would like to thank Kathy Fuller (Pharm. D., BCNSP, College of Pharmacy, NOVA Southeastern University) for her assistance in the preparation of the manuscript.

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