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.     

Acquired amegakaryocytic thrombocytopenic purpura treated with intravenous immunoglobulins

Acquired amegakaryocytic thrombocytopenic purpura is a rare disorder characterized by severe thrombocytopenia due to the absence of bone marrow megakaryocytes. The pathogenic mechanisms of this disorder have not well defined; consequently, several empirical therapies are used. We reported the case of a 38-year-old mean who was hospitalized for serious bleeding syndrome. The platelet count was 10 yen10(9)/L. The bone marrow aspirate and biopsy showed the absence of megakaryocytes but otherwise normal granulocyte and erythroid precursors. No definable etiology has been found. After the unsuccessful use of prednisone, intravenous immunoglobulin therapy was started and resulted in favorable reponse.     

Acquired amegakaryocytic thrombocytopenic purpura: a syndrome of diverse etiologies

The possible pathogenetic mechanisms responsible for the production of acquired amegakaryocytic thrombocytopenic purpura (AATP) were investigated in a group of patients with this disorder. Absence of megakaryocytes and small platelet glycoprotein-bearing mononuclear cells, as determined by immunochemical staining of patient marrows with an antisera to platelet glycoproteins, suggested that the defect in AATP occurs in an early progenitor cell of the megakaryocytic lineage. Using an in vitro clonal assay system for negakaryocytic progenitor cells or megakaryocyte colony-forming units (CFU-M), the proliferative capacity of AATP marrow cells was then assessed. Bone marrow cells from three of four patients formed virtually no megakaryocyte colonies, suggesting that in these individuals the AATP was due to an intrinsic defect in the CFU-M. Bone marrow cells from an additional patient, however, formed 12% of the normal numbers of colonies, providing evidence for at least partial integrity of the CFU-M compartment in this patient. Serum specimens from all six patients were screened for their capacity to alter in vitro megakaryocyte colony formation. Five of six sera enhanced colony formation in a stepwise fashion, demonstrating appropriately elevated levels of megakaryocyte colony- stimulating activity. The serum of the patient with partial integrity of the CFU-M compartment, however, stimulated colony formation only at low concentrations. At higher concentrations, this patient's serum actually inhibited the number of colonies cloned, suggesting the presence of a humoral inhibitor to CFU-M. Serum samples from all patients were further screened for such humoral inhibitors of megakaryocyte colony formation using a cytotoxicity assay. The patient whose serum was inhibitory to CFU-M at high concentrations was indeed found to have a complement-dependent serum IgG inhibitor that was cytotoxic to allogeneic and autologous marrow CFU-M but did not alter erythroid colony formation. These-studies suggest that AATP can be due to at least two mechanisms: either an intrinsic effect at the level of the CFU-M or a circulating cytotoxic autoantibody directed against the CFU-M.     

Non-Hodgkin's lymphoma presenting with amegakaryocytic thrombocytopenic purpura

 A 91-year-old patient was diagnosed with amegakaryocytic thrombocytopenic purpura (AATP) as a presenting symptom for CD5-positive B cell non-Hodgkin's lymphoma. Lymphoma is another condition that should be considered in the differential diagnosis of AATP. Received: 29 January 1996 / Accepted: 29 April 1996     

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

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.     

Treatment of acquired amegakaryocytic thrombocytopenic purpura with cyclophosphamide

A patient with severe amegakaryocytic thrombocytopenic purpura was treated with cyclophosphamide and had an excellent response after four weeks. His condition remained in complete remission for at least five months. Acquired amegakaryocytic thrombocytopenic purpura is a rare disorder with several possible causes. An intrinsic defect at the level of the megakaryocyte colony-forming units, or a circulating autoantibody directed against these colony-forming units has been suggested. This patient's response to cyclophosphamide supports the hypothesis of an immune mechanism in some of these cases, and it is recommended that immunosuppressive therapy be further evaluated.     

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.     

Acquired amegakaryocytic thrombocytopenia previously diagnosed as idiopathic thrombocytopenic purpura in a patient with hepatitis C virus infection

We report the first case of a patient with hepatitis C virus(HCV) infection and idiopathic thrombocytopenic purpura(ITP), who later developed acquired amegakaryocytic thrombocytopenia(AAMT), with autoantibodies to the thrombopoietin(TPO) receptor(c-Mpl). A 64-year-old woman, with chronic hepatitis C, developed severe thrombocytopenia and was diagnosed with ITP. She died of liver failure. Autopsy revealed cirrhosis and liver carcinoma. In the bone marrow, a marked reduction in the number of megakaryocytes was observed, while other cell lineages were preserved. Therefore, she was diagnosed with AAMT. Additionally, autoantibodies to c-Mpl were detected in her serum. Autoantibodies to c-Mpl are one of the causes of AAMT, acting through inhibition of TPO function, megakaryocytic maturation, and platelet formation. HCV infection induces several autoantibodies. HCV infection might also induce autoantibodies to c-Mpl, resulting in the development of AAMT. This mechanism may be one of the causes of thrombocytopenia in patients with HCV infection.     

Thrombotic thrombocytopenic purpura associated with the acquired immune deficiency syndrome

A bisexual male presented with acute thrombotic thrombocytopenic purpura (TTP) in association with established acquired immune deficiency syndrome. The patient had classic clinical and laboratory findings of TTP and responded well to plasmapheresis therapy. Previously reported cases of TTP in association with human immunodeficiency virus (HIV) infection are briefly reviewed. Basic concepts in the pathogenesis of TTP are examined in reference to HIV infection.     

Cell-mediated suppression of megakaryocytopoiesis in acquired amegakaryocytic thrombocytopenic purpura

Acquired amegakaryocytic thrombocytopenic purpura (AATP) is a disorder of hematopoiesis characterized by severe thrombocytopenia due to a selective reduction or total absence of megakaryocytes in an otherwise normal-appearing bone marrow. Although the development of autoantibodies directed against cells in the megakaryocyte progenitor cell pool has been implicated in the pathogenesis of this disorder, cell-mediated suppression of megakaryocytopoiesis has not been described. Accordingly, we report two cases of AATP in which in vitro suppression of megakaryocyte colony formation by autologous ancillary marrow cells was demonstrable. Light-density bone marrow mononuclear cells (MNCs) obtained from both patients were either plated directly into plasma clot cultures, or after first being depleted by adherent monocytes (M phi) or T lymphocytes using standard methodologies. In some experiments, the depleted ancillary marrow cells were recovered for autologous co-culture studies with the MNCs from which they had been depleted. Megakaryocyte colony formation was detected in the cultures using an indirect immunofluorescence assay with a rabbit anti- human platelet glycoprotein antiserum. Removal of M phi (n = 6), or T lymphocytes (n = 4) from normal marrow MNCs had no apparent effect on colony formation. In contrast, depleting T lymphocytes from the MNCs of patient 1 significantly augmented megakaryocyte colony formation; a similar effect was observed after depleting M phi from the MNCs of patient 2. This observed augmentation in colony formation could be abrogated by autologous co-culture with the putative suppressor cell at effector cell/target cell ratios of 1:10 in the case of T lymphocytes or 1:5 in the case of M phi. Neither suppression nor stimulation of megakaryocyte colony formation was observed after culturing normal MNCs with autologous T cells (n = 4) or M phi (n = 3) at similar or greater ratios. We also observed inhibition of megakaryocyte colony formation after culturing normal MNCs in the presence of tissue culture medium conditioned by the M phi of patient 2. This effect was shown to be specific for megakaryocytes since this same conditioned medium had no significant effect on BFU-E and CFU-E-derived colony formation by autologous marrow mononuclear cells. These results suggest that: both T cells and M phi are capable of exerting a regulatory effect on the proliferation of human megakaryocyte progenitor cells (CFU-Meg); in the case of M phi, a soluble factor elaborated by these cells may be responsible for suppressing CFU-Meg growth; and aberrant ancillary cell- megakaryocyte progenitor cell interactions may lead to clinically significant disease.     

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.     

Danazol in acquired amegakaryocytic thrombocytopenic purpura: A case report

Summary Acquired amegakaryocytic thrombocytopenic purpura is a rare disease. Most reported patients did not respond to any therapeutical approach. Recently we observed a striking improvement of this disorder in a female patient shortly after therapy with danazol had been initiated. This observation and its possible implication for the treatment of amegakaryocytic thrombocytopenia are reported herein.     

Thrombotic thrombocytopenic purpura associated with ticlopidine

Thrombotic thrombocytopenic purpura is a syndrome characterized by hemolytic anemia, thrombocytopenia, neurological symptoms, fever and renal dysfunction. Although the syndrome is usually associated with various infections, vasculitis and pregnancy, rarely can it be associated with certain neoplasms and drugs such as ticlopidine. A 63-year-old woman, who had undergone coronary angioplasty and had been started on ticlopidine, was admitted to our clinic with a history of vomiting, fatigue, hematuria and deterioration in her cognitive abilities. Thrombotic thrombocytopenic purpura was diagnosed on the basis of neurological changes, an increase in LDH, urea, creatinine, indirect bilirubin levels, anemia and peripheral smear findings. Treatment was initiated with daily plasmapheresis and complete clinical and laboratory recovery developed. The patient was discharged after 14 days.