For the following eight weeks, he showed no response, with platelet count remaining in the mid 30?k/mm3 range. Open in a separate window Figure 1 Bone marrow biopsy before treatment with romiplostim showing the absence of reticulin fibrosis (Metallic stain, initial magnification ?400). Open in a separate window Figure 3 Bone marrow aspirate with normal megakaryocytes (Wright-Giemsa, initial magnification ?100). Open in a separate window Figure 5 Bone marrow aspirate with normal erythropoiesis (Wright-Giemsa, initial magnification ?100). Open in a separate window Figure 7 Mildly hypercellular bone marrow for age (50C60% cellularity) (hematoxylin-eosin, original magnification ?100). Due to his cardiac condition, the patient was not a candidate for splenectomy and instead started treatment with low dose of romiplostim (100?mcg subcutaneous injections every seven days during 5 weeks). the JAK-STAT pathway that results in increased platelet production [1, 2, 7, 8]. Romiplostim does not interfere with antibody production or binding to platelets [8]. Romiplostim has been shown to improve platelet counts during both short- and long-term use in adult individuals with chronic ITP [1]. The most frequently reported adverse events have been arthralgias (26%), fatigue (13%), and nausea (7%). Improved thromboembolic risk has been associated to the use GW1929 of romiplostim [9]. Bone marrow fibrosis has been reported in medical tests with romiplostim [1]. 10 out of 271 individuals were reported to have reticulin deposition [1], but the fibrosis was reversible and dose dependent [1]. There have been no reported instances of irreversible myelofibrosis in which thrombopoietic agents have been clearly implicated in causation [10]. 2. Case History A 76-year-old male was diagnosed with defense thrombocytopenic purpura (ITP) following a six-month GW1929 history of fatigue, increasing bruising on his top and lower extremities and gum bleeding. His past medical history included type 2 diabetes mellitus, hypertension, atrial fibrillation, coronary artery disease, and ischemic cardiomyopathy. He refused fevers, night time sweats, or excess weight loss. His physical exam did not display splenomegaly. His medications included lisinopril, spironolactone, sotalol, Coreg, Lipitor, aspirin 81?mg per day, insulin, and warfarin. A complete blood count showed hemoglobin of 10.4?gm/dL, mean corpuscular volume of 96.2 femtoliters, red blood cell count of 3.40?m/mm3, and platelets of 37 k/mm3. The patient was adopted with periodic blood counts for five weeks without treatment, but proven progressive thrombocytopenia for which he was referred to a hematologist. A bone marrow exam was performed showing mildly hypercellular marrow for age (50C60% cellularity), without fibrosis (Numbers ?(Numbers1,1, ?,3,3, ?,55 and ?and7).7). Cytogenetic results demonstrated a normal karyotype. The patient was diagnosed with ITP and superimposed anemia. Coumadin was discontinued, and the patient started treatment with rituximab. For the following eight weeks, he showed no response, with platelet count remaining in the mid 30?k/mm3 range. Open in a separate window Number 1 Bone marrow biopsy before treatment with romiplostim showing the absence of reticulin fibrosis (Metallic stain, unique magnification ?400). Open in a separate window Number 3 Bone marrow aspirate with normal megakaryocytes (Wright-Giemsa, unique magnification ?100). Open in a separate window Number 5 Bone marrow aspirate with normal erythropoiesis (Wright-Giemsa, unique magnification ?100). Open in a separate Rabbit polyclonal to Smac window Number 7 Mildly hypercellular bone marrow for age (50C60% cellularity) (hematoxylin-eosin, unique magnification ?100). Due to his cardiac condition, the patient was not a candidate for splenectomy and instead started treatment with low dose of romiplostim (100?mcg subcutaneous injections every seven days during 5 weeks). Initially, the patient showed response to the treatment, with platelet counts increasing to between 60C100?k/mm3. However, over the course of the following yr, his platelet counts gradually decreased, despite increasing doses of romiplostim to 300 and 400?mcg/week. During this time, the patient also developed worsening anemia, to hemoglobin 8.5?gm/dL, requiring transfusion of red blood cells about two occasions in the last 3 months. Along with the worsening cytopenias, the patient developed increasing fatigue and shortness of breath but remained without splenomegaly. A repeat bone marrow biopsy was performed showing markedly improved cellularity (90% cellularity), minor dyserythropoiesis, occasional atypical megakaryocytes, and now having a designated diffuse reticulin fibrosis (Numbers ?(Numbers2,2, ?,4,4, ?,66 and ?and8).8). Repeat karyotype remained normal. Fluorescence in situ hybridization failed to demonstrate deletion of chromosome 5 or 7. Open in a separate window Number 2 Bone marrow biopsy after treatment with romiplostim demonstrating designated diffuse reticulin fibrosis (Notice coarse reticulin dietary fiber network) (Metallic stain, unique magnification ?400). Open in a separate window Number 4 Bone marrow aspirate after treatment with romiplostim with hypolobated GW1929 megakaryocytes (Wright-Giemsa, unique magnification ?100). Open in a separate window Number 6 Bone marrow aspirate after treatment with romiplostim.
