acquired amegakaryocytic thrombocytopenia ( amt ) is a rare hematologic disorder characterized by thrombocytopenia and is association with a markedly diminished number of bone marrow megakaryocytes .
this condition has been observed in patients with lupus erythematosus , t - cell large granular lymphocyte leukemia and eosinophilic fasciitis .
amt is associated with a marked increase of t - activated suppressor cells ( cd8 + /dr+ ) and a high level of autoantibodies against the thrombopoietin receptor ( c - mpl ) .
no cytogenetic abnormality has been shown to be consistently present in amt . in most patients
we describe a rare case of amt syndrome which did not respond to any of the previous therapies except rituximab ( ant - cd20 antibody ) .
in september 2008 ; a 50-year - old man with petechial rash , large ecchymosed , gross hematuria and severe shoulder and periumbilical pain was admitted to our center . in the past medical history : he had symptoms of bleeding for 15 months ago and laboratory studies revealed a severe thrombocytopenia with platelet count of 12000/l , a leukocytosis with white blood cell ( wbc ) count of 25000/l and hemoglobin ( hb ) of 15 gr / dl .
there was an increased level of myeloid / erythroid series and a severe decrease of megakaryocytes series , in the bone marrow examinations .
patient was treated with intravenous immunoglobulin ( ivig ) and transient clinical response was taken .
after six months , he was referred to our center for the complaint of severe bleeding .
he had a wbc count of 12100/l , hgb of 13 gm / dl , hematocrit ( hct ) of 31.3% , a mean corpuscular volume ( mcv ) of 93fl , and a platelet count of 7000/l .
the patient undergone bone marrow examination again , cellularity was 75% , myeloid and erythroid series were mildly increased and megakaryocytes severely decreased to absented .
additional studies including antinuclear antibodies ( ana ) , rheumatoid factor ( rf ) , and igm / igg antiplatelet antibody tests were normal .
the patient with diagnosis of amegakaryocytic thrombocytopenia was treated with ivig again , but clinical and laboratory response were not taken .
there was not any improvement in patient 's signs and symptoms ( figure 1 ) .
platelet count was lower than 10000/l and he was experiencing diffuse petechial rash , easy bruising , gingival bleeding and hematuria .
bleeding symptoms were controlled by platelets transfusions , however it did not cause into a dramatic increase in the platelets count .
we explained the treatment options , including anti - thymocyte globulin ( atg ) and rituximab to the patient .
hence rituximab ( anti - cd20 antibody ) with dose of 375 mg / m , with three weeks interval , for three consequent doses was started .
the platelet count rose dramatically to 20000/l on the 6th day , to 30000/l on the 29th day and to 200 000/l on the 42th day . in 25 months
follow up ; the patient had normal blood counts without any medications , except that wbc was mildly increased ( figure 1 ) .
hemoglobin the patient had a hypercellular marrow with adequate to increased megakaryocyte in the 63th day after treatment .
we diagnosed myeloproliferative disease according to the morphological changes observed in the bone marrow examinations .
the search for bcr / abl , philadelphia chromosome , and janus kinase2 ( jak2 ) v617f by pcr test was also negative , and the diagnosis of myeloproliferative disease was not approved in our patient .
here we presented a case of refractory amt which responded to anti cd-20 antibody therapy .
the differential diagnosis of patients suspected to have amt are idiopatic ( immune ) thrombocytopenic purpura , with misinterpretation of morphologic findings , hereditary and acquired aplastic anemia , preleukemia and systemic lupus erythematosis .
the clinical course of the disease is variable , and suggested treatment have shown variable efficacy in the management of disease .
immunosuppressive therapies including administration of steroids , cyclophosphamide , cyclosporine , androgens , atg have been used with varying degrees of success . 
 
ivig , prednisone , cyclophosphamide , and vincristine have not been efficacious in amt , unlike the response to these agents in immune - mediated thrombocytopenia , although there are isolated reports of prednisone , ivig , and cyclophosphamide being transiently effective in occasional patients with amt .
myeloablative chemotherapy ( busulfan and cyclophosphamide ) followed by allogeneic bone marrow transplant from a fully hla - matched sibling has been reported to be effective .
atg was also reportedly effective in a case of amt associated with a marked increase of t - activated suppressor cells ( cd8+/dr+ ) .
cyclosporine alone or in combination with atg has been shown to be very effective in treatment of amt . in one of the reports of cyclosporine use ,
longitudinal follow - up revealed a relapsing and remitting disease course of amt , which correlated with the dosing of cyclosporine .
it has been shown to be effective in patients with bone marrow failure due to myelodysplastic syndromes ( mds ) , graft failure , chemotherapy , or aplastic anemia .
there are a limited number of studies reporting hematopoietic cell transplantation in patient with the acquired amt.17 in 2008 , fukushima et al . , firstly reported a case of amegakaryocytic thrombocytopenia due to systemic lupus erythematosis .
rituximab is a chimeric monoclonal antibody against the protein cd20 , which is primarily found on the surface of b cells .
cd20 is expressed on most stages of b cells , such as immature b cells , naive b cells , memory b cells , and germinal center b cells , but not early pro - b cells or plasma cells .
it has been described that rituximab may suppress pathogenic b - cell clones which produce anti - tpo(thrombopoietin ) receptor antibodies that are resistant to conventional immunosuppressive therapy , including cyclosporine and prednisone . 
 
anti - cd20 antibody acting against cd20 receptors over membrane of b - cell type lymphocytes , and suppressed the humoral immunity .
anti - cd20 antibody was taken and this refractory amt patient that was depended to platelet transfusions , responded to this drug , and after first dose , the dependency of patient to platelet transfusions does not continued , and at the beginning of 3th dose , the platelet count became normal .
rituximab was effective in this refractory case of amt , the platelet count is normal after 25 months of last dose without any medication , but mild leukocytosis ( wbc 11000 to 25200/l ) remained sustained .
moreover we did not have any documentation for diagnosis of chronic myeloproliferative disease except morphology of bone marrow examination .
 amegakaryocytic thrombocytopenia ( amt ) is a rare cause of acquired thrombocytopenia . 
 the pathogenesis and treatment of amt is not clearly known . here 
 we demonstrate a 50-year - old man presented with the clinical manifestations of severe thrombocytopenia ( 7000 platelets/l ) with a marked decrease to absent of megakaryocytes in the bone marrow . 
 the patient did not respond to intravenous immunoglobulin , cyclosporine or high dose prednisone . 
 after the treatment with anti - cd20 antibody ( rituximab ) , the patient 's clinical symptoms and platelet counts improved . 
BACKGROUND
PRESENTATION OF CASE
DISCUSSION
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