Amegakaryocytic Thrombocytopenic Purpura Research Articles

Acquired Amegakaryocytic Thrombocytopenic Purpura: A Review of Therapeutic Options.

Acquired amegakaryocytic thrombocytopenic purpura (AATP) is a rare bone marrow disorder characterized by either a marked decrease or a complete absence of megakaryocytes with the preservation of all other cell lines. To date, more than 60 cases of AATP have been reported in the literature. Due to the rarity of this disease, no standard treatment guidelines have been established, and therapy is based on a handful of case studies and expert opinions. Herein, we provide a comprehensive review of currently utilized therapeutic options for AATP.

Acquired Amegakaryocytic Thrombocytopenic Purpura that Presented as Cyclic Thrombocytopenia Associated with Anti-Phospholipid Antibody Syndrome

A 52-year-old female, who had been taking prednisolone (PSL) for anti-phospholipid antibody syndrome (APS), was admitted to our hospital because of repeated nasal bleeding, purpura and petechiae of the extremities, and a platelet count of 7,000/μL. The PSL dose was increased due to a tentative diagnosis of idiopathic thrombocytopenic purpura (ITP), but she presented with cyclic thrombocytopenia independent of the PSL dose and repeated nasal, oral, and gastrointestinal bleeding.

Acquired Amegakaryocytic Thrombocytopenic Purpura Associated with a Paroxysmal Nocturnal Hemoglobinuria Clone: A Case Report and Review of the Literature

Background: Acquired amegakaryocytic thrombocytopenic purpura (AATP) is a rare bone marrow disorder characterized by a marked reduction in megakaryocytes with otherwise normal hematopoiesis. Both humoral and cell-mediated suppression of megakaryocytopoeisis have been postulated as mechanisms causing AATP. Herein we report a case of a 67-year-old man diagnosed with AATP with a co-existent paroxysmal nocturnal hemoglobinuria (PNH) clone and review the literature on AATP, focusing on proposed etiologies for this rare condition. Case: A 67-year-old man presented to clinic with a 1-week history easy bruising, petechiae and a platelet count of 6 x 109/L. He had a history of left elbow bursitis caused by S. pyogenes, treated with antibiotics 6-months prior to his presentation. His CBC was normal at that time. On assessment, HIV, HBV, HCV, and H. pylori serologies were negative; CMV and EBV serologies were positive for IgG and negative for IgM. ANA and RF were negative, and vitamin B12 level was normal. There was no hepatosplenomegaly on ultrasound. Bone marrow aspirate and biopsy demonstrated a normocellular marrow with severe megakaryocytic hypoplasia. Cytogenetics demonstrated normal male karyotype with loss of Y chromosome in 9/20 metaphases. Flow cytometry revealed a population of 3.99% GPI-deficient neutrophils by FLAER assay. Molecular testing for myeloid mutations and T-cell gene rearrangement is pending. The patient was initially treated with corticosteroids and IVIG, and showed no response with persistent isolated thrombocytopenia. He was managed with platelet transfusions which resulted in a normal platelet increment of 35 x 109/L 1-hour post-transfusion. A diagnosis of AATP was established and he was admitted for immunosuppressive therapy (IST) with ATG and cyclosporine. Methods: We conducted a narrative review of the literature on AATP, searching MEDLINE and EMBASE for articles on AATP published in English between 1946 and 2020. Reference lists of selected articles were reviewed to identify additional cases. We extracted data on presentation, bone marrow findings (including cytogenetics, molecular genetics, and flow cytometry), treatment regimens and outcomes. Results: We identified 47 cases of adult patients with thrombocytopenia attributed to AATP reported in the literature (Table 1). Three main mechanisms were proposed: (i) cell-mediated autoimmunity, (ii) humoral autoimmunity, and (iii) intrinsic stem cell defect. All three mechanisms were supported by in vitro studies, which demonstrated suppression of colony forming unit-megakaryocytes (CFU-M) by patients' T-lymphocytes (Gerwitz et al. 1986; Colovic et al. 2004) and serum (Hoffman et al. 1982) found to contain IgG antibodies inhibiting CFU-M formation, as well as intrinsic defects in CFU-M progenitor proliferation. Few studies reported cytogenetic abnormalities and only one documented molecular genetic testing. Response to IST was reported in several cases, most commonly ATG and cyclosporine. Four recent cases demonstrated remission following treatment with TPO agonists eltrombopag and romiplostim. Six cases progressed to aplastic anemia and 4 to myelodysplastic syndrome (MDS). Flow cytometry results were not reported in the majority of cases, and only 1 case reported coexistence of a PNH clone, identified in a pregnant patient with AATP (Zimmerman et al. 2019). Discussion: AATP is defined as severe thrombocytopenia with bone marrow showing marked decrease or absence of megakaryocytes with preservation of other cell lineages. This broad definition encompasses a range of causes, and our review of the literature highlights the heterogenous nature of AATP which has several proposed mechanisms and a number of therapeutic options. The best evidence suggests that AATP is often secondary to T-cell-mediated suppression of megakaryocytopoeisis, which has been demonstrated by in vitro studies, and is supported in vivo by a case of AATP following PD-1 inhibition (Iyama et al. 2020), and frequent response of AATP to T-cell-directed IST. The co-existence of a PNH clone in our case lends further support to a T-cell-mediated autoimmune process, analogous to the mechanism described in aplastic anemia and hypoproliferative MDS. The application of molecular diagnostics may help to further elucidate the role of clonal hematopoiesis and intrinsic stem cell defects versus humoral and cell-mediated autoimmunity in AATP. Disclosures No relevant conflicts of interest to declare.

A rare case of acquired amegakaryocytic thrombocytopenic purpura and its clinical care

Introduction : Acquired amegakaryocytic thrombocytopenia is an unusual and rare hematologic disorder characterized by thrombocytopenia along with markedly reduced bone marrow megakaryocytes. Patients usually present with thrombocytopenia and severe bleeding that is unresponsive to steroids and intravenous immunoglobulin. Case : In our study, a 52-year-old female was diagnosed with acquired amegakaryocytic thrombo cytopenia and was treated with a combination of immunosuppressants namely antithymocyte globulin, methylprednisolone and cyclosporine. OUTCOME: Symptoms improved significantly following treatment and we confirm the successful management of this rare disease entity with combined immuno suppression therapy

Acquired amegakaryocytic thrombocytopenic purpura with literature review

Acquired amegakaryocytic thrombocytopenic purpura (AATP) is an uncommon disorder with thrombocytopenia and selectively suppressed megakaryopoiesis, often mistaken as immune thrombocytopenic purpura (ITP). It usually does not respond to steroids, and bone marrow examination shows complete absence of megakaryocytes. The treatment and prognosis of AATP vary greatly from ITP; therefore, it is important to diagnose and treat this condition early, as it can progress rapidly to complete bone marrow failure. In this case report, we report a patient with AATP responded well to cyclosporine therapy.

Acquired amegakaryocytic thrombocytopenic purpura induced by percutaneous ethanol injection during treatment of hepatocellular carcinoma: A case report.

Percutaneous ethanol injection is an important localized treatment method for patients presenting with hepatocellular carcinoma (HCC). Among the advantages of percutaneous ethanol injection are its minimal invasiveness, simplicity, low cost and low risk of complications. However, the increasing popularity of percutaneous ethanol injection has resulted in serious adverse effects attributed to individual variations. The present study describes the case of a patient who exhibited acquired amegakaryocytic thrombocytopenic purpura, caused by percutaneous ethanol injection treatment for HCC. This complication was promptly identified, and platelet transfusion and injection of recombinant human interleukin-11 resulted in a rapid recovery of the patient's platelet count. Attention should be given to this rare complication in patients administered percutaneous ethanol injection treatment for HCC.

Acquired Amegakaryocytic Thrombocytopenic Purpura - An Underdiagnosed Entity

Acquired Amegakaryocytic Thrombocytopenic Purpura (AATP) is a rare cause of thrombocytopenia presenting over a wide age group with symptoms of bleeding and bone marrow showing isolated absence of megakaryocytes in an otherwise normal marrow. Here, we report a case of AATP in a three year old female child who was then treated with anti thymocyte globulin successfully. We report this case because of it's under diagnosis or misdiagnosis as immune thrombocytopenia (ITP) in most of the cases. We also review the literature regarding the pathogenesis and treatment of this undiagnosed entity.

Successful rituximab treatment for acquired amegakaryocytic thrombocytopenic purpura complicated with Coombs-negative autoimmune hemolytic anemia

Successful rituximab treatment for acquired amegakaryocytic thrombocytopenic purpura complicated with Coombs-negative autoimmune hemolytic anemia

Successful treatment of acquired amegakaryocytic thrombocytopenic purpura refractory to corticosteroids and intravenous immunoglobulin with antithymocyte globulin and cyclosporin

Four patients with acquired amegakaryocytic thrombocytopenic purpura, who had failed corticosteroids, intravenous immunoglobulin and cyclophosphamide therapy, were treated with antithymocyte globulin, followed by cyclosporin. Three patients achieved complete remission in 28-178 days and the response duration was 16-60 months from the beginning of treatment. One patient achieved a partial response for 2 months followed by myelodysplastic syndrome 5 months later. He died in 9 months due to intracerebral bleeding. Marrow cytogenetics showed 47, XY, +21.

Clinical feature of acquired pure amegakaryocytic thrombocytopenic purpura

目的 探讨获得性纯巨核细胞再生障碍性血小板减少性紫癜(AATP)的临床特点.方法 对18例AATP患者的临床资料进行回顾性分析.以同一时期特发性血小板减少性紫癜(ITP)112例为对照组,对两组患者巨核细胞(MK)、血小板(PLT)计数、平均血小板容积(MPV)及血小板相关免疫球蛋白G(PAIgG)进行测定.结果 MK总数AATP组明显减少甚至缺如,ITP组明显增多,两组比较差异有统计学意义[(0.8±1.5)vs(195.0±47.3),P＜0.01].AATP组在MPV正常范围,ITP组大于正常[(7.1±2.4)vs(14.5±3.8),P＜0.05].初诊时PLT计数两组差异无统计学意义(P＞0.05).PAIgG阳性率AATP组55.6%,ITP组83.0%,差异有统计学意义(P＜0.01).结论 AATP是临床上少见的以巨核细胞再生障碍伴血小板减少为特征的出血性疾病,与ITP有本质区别.AATP在治疗上存在一定难度,在常规糖皮质激素治疗的基础上加用康力龙及环孢素A能获得一定疗效。

Megakaryocyte colony-forming unit growth is enhanced by alemtuzumab: in vitro experiments and a case report of acquired amegakaryocytic thrombocytopenic purpura

Megakaryocyte colony-forming unit growth is enhanced by alemtuzumab: in vitro experiments and a case report of acquired amegakaryocytic thrombocytopenic purpura

Acquired amegakaryocytic thrombocytopenic purpura

Acquired amegakaryocytic thrombocytopenia is an unusual hematologic disorder characterized by thrombocytopenia in association with markedly diminished bone marrow megakaryocytes. We report a case that responded to treatment with cyclosporine but not to IL-11. The bone marrow biopsy, repeated after resolution of thrombocytopenia, showed normal number of megakaryocytes.

Megakaryocyte Colony-Forming Units (CFU-Meg) Growth Is Enhanced by Alemtuzumab Mediated Lymphocyte Depletion: In Vitro Experiments and a Case Report of Acquired Amegakaryocytic Thrombocytopenic Purpura.

Background. Alemtuzumab (Ale) induces destruction of CD52 antigen-bearing cells by antibody-dependent cell-mediated lysis, complement-mediated lysis, and induction of apoptosis. As a potent T cell depleting agent, Ale is used also for GvHD prophylaxis, given either i.v. around the time of transplantation, or directly "in the bag" to the cell suspension containing hematopoietic stem cells and lymphocytes. Contrary to bone marrow-derived grafts, the experience with addition of Ale to the peripheral blood progenitor cells (PBPC) suspension is limited. Therefore, we decided to study the effect of short-time incubation of PBSC samples with Ale using flow-cytometry and cultivation assays.Methods. After an informed consent, a sample of PBSC product (15 mL) was obtained from the collection bag immediately after a leukapheresis (COBE Spectra) in 8 healthy donors mobilized by G-CSF. Cells were washed using 4% human albumin and then incubated at 37°C with 1) Ale at the dose of 5 μg/106 cells, and 2) water for injection as a control. Autologous plasma as a source of complement was added after 15 min of incubation and cells suspensions were further incubated for 15 minutes. Both cell suspensions were then washed, resuspended in 4% human albumin, and samples were collected for blood count, flow-cytometric analysis, and cultivation assays (CFU-GM, BFU-E, CFU-Meg).Results. As expected, Ale caused profound T-cell (by a median of 99.3% vs. 12.3% in control) as well as marked B-cell (by a median of 90.6% vs. 8.3% in control) depletion. CD4+ and CD8+ lymphocytes were eliminated equally by a median of 99.5%, and 99.1%, respectively. Ale also produced a moderate reduction of CFU-GM and BFU-E (by a median of 37.7% vs. 3.3%, and 49.7% vs. 10.8%, respectively). NK-cells were not significantly affected as well as granulocytes and monocytes. Surprisingly, incubation with Ale clearly enhanced the growth of CFU-Meg; in median 8-times more CFU-Meg were observed in samples after incubation with Ale comparing to control samples (from 3 to 21-times, p<0.01). Based on these findings we decided to use Ale for the treatment of 63-year-old woman suffering from severe and therapy resistant (steroids, cyclosporine A) acquired amegakaryocytic thrombocytopenic purpura (AATP). Patient's bone marrow samples were first tested as described above and a remarkable enhancement of CFU-Meg growth (106 CFU-Meg/1 ml of bone marrow) was observed in a sample incubated with Ale comparing to a control sample not incubated with Ale (2.4 CFU-Meg/1 ml of bone marrow). The patient subsequently received Ale at the dose of 10 mg 3 times weekly for 3 weeks. Ale administration had to be temporarily discontinued for CMV reactivation; however, platelets count significantly increased from 10x109/L to 50x109/L.Conclusion. Our results demonstrate that megakaryopoiesis is physiologically suppressed by lymphocytes. To the best of our knowledge, this is the first description that profound lymphocyte depletion by Ale enhances megakaryopoiesis in vitro and that Ale can also be used in vivo for the treatment of AATP.

Malignant thymoma complicated by amegakaryocytic thrombocytopenic purpura

We report the case of a 41-year-old man with malignant thymoma complicated by amegakaryocytic thrombocytopenia 10 years after diagnosis of myasthenia gravis. A bone marrow aspirate showed an absence of megakaryocytes with normal maturation and differentiation of myeloid precursors. Three months later, severe neutropenia occurred, and a bone marrow examination confirmed the diagnosis of severe aplastic anemia. Associations between thymoma and myasthenia gravis, between thymoma and pure red cell aplasia, and between thymoma and aplastic anemia are well documented. Amegakaryocytic thrombocytopenia is not a recognized paraneoplastic syndrome complicating thymoma. Amegakaryocytic thrombocytopenia complicating thymoma may be a very early presentation of impending aplastic anemia.

Relationship between megakaryocyte mass and serum thrombopoietin levels as revealed by a case of cyclic amegakaryocytic thrombocytopenic purpura

Relationship between megakaryocyte mass and serum thrombopoietin levels as revealed by a case of cyclic amegakaryocytic thrombocytopenic purpura

Relationship between megakaryocyte mass and serum thrombopoietin levels as revealed by a case of cyclic amegakaryocytic thrombocytopenic purpura

Cyclic amegakaryocytic thrombocytopenic purpura is a rare syndrome characterized by periodic failure of megakaryocytopoiesis. In this report we describe a patient with cyclic amegakaryocytic thrombocytopenic purpura associated with a megakaryocyte specific serum IgG antibody, who responded to cyclosporin A therapy. Serial serum thrombopoietin assays during an episode of platelet cycling demonstrated a reciprocal relationship between serum thrombopoietin level and megakaryocyte mass, suggesting that megakaryocytes have an important role in the regulation of thrombopoietin metabolism.

Acquired pure amegakaryocytic thrombocytopenic purpura in pregnancy

Acquired pure amegakaryocytic thrombocytopenic purpura in pregnancy

Activation of transfused platelets in a patient with amegakaryocytic thrombocytopenic purpura

Activation of transfused platelets in a patient with amegakaryocytic thrombocytopenic purpura

Acquired amegakaryocytic thrombocytopenic purpura with a Philadelphia chromosome

A 30-year-old Chinese man with acquired amegakaryocytic thrombocytopenic purpura (AATP) and a Ph chromosome is reported. At presentation, he had severe thrombocytopenia resulting in epistaxis, gingival bleeding, and ecchymoses, while other hematologic values were within the normal range. Bone marrow aspiration showed no megakaryocytes, with a normal appearance of erythroblastic and granulopoietic series. He failed to respond to prednisone treatment, and underwent a progress from isolated thrombocytopenia to full pancytopenia. At last he died of spontaneous intracranial hemorrhage. An in vitro culture for granulocyte-macrophage precursors showed very few colonies. Karyotypic analysis revealed a standard Ph chromosome translocation, t(9;22)(q34;q11), in the majority of bone marrow cells. Southern blot analysis using a 3′ bcr-HE probe didn't detect a rearrangement within the bcr DNA sequence. This patient, in fact, was a myelodysplastic disorder, initially presenting as AATP. The diagnosis of chronic myelogenous leukemia was excluded on the basis of clinical and hematologic findings. The heterogeneity of Ph chromosome in myelodysplastic syndrome is discussed.

Amegakaryocytic thrombocytopenia of 4 years duration: Successful treatment with antithymocyte globulin

Acquired amegakaryocytic thrombocytopenic purpura (AATP) is a rare cause of thrombocytopenia. Since it is a syndrome of diverse etiologies, the optimal treatment is often uncertain. In a patient with longstanding AATP, a complete remission was obtained with antithymocyte globulin.