{"doi":"10.1002/ajh.26347","title":"Primary myelofibrosis in a patient with sickle cell disease","abstract":"A 76-year-old woman had been diagnosed with sickle cell disease at age 60 years after presenting with a splenic infarct. She did well until age 73 years, when she developed progressive transfusion-dependent anemia, leukocytosis and thrombocytosis. Hemoglobin electrophoresis in the absence of hydroxyurea treatment showed 70% hemoglobin S, 27% hemoglobin F and 3% hemoglobin A2, consistent with sickle cell-beta zero thalassemia with hereditary persistence of fetal hemoglobin. She was treated with hydroxyurea for anemia thought to be due to sickle cell disease, but it was discontinued due to gastrointestinal toxicity. She was subsequently referred to the University of Maryland for Hematology consultation. Comorbidities included hypertension, atrial fibrillation and congestive heart failure with preserved ejection fraction and moderate pulmonary hypertension. Liver and spleen were not palpable. Hemoglobin was 9.7 g/dL (recently transfused), white blood cell count (WBC) 12.2 × 109/L with 59% neutrophils, 9% bands, 1% metamyelocyte, 4% myelocytes, 3% basophils, 4% eosinophils, 10% monocytes and 9% lymphocytes, platelet count 1237 × 109/L, 97 nucleated red blood cells (NRBCs) per 100 WBC, absolute reticulocyte count 18 × 109/L (5.25%), lactate dehydrogenase (LDH) 2631 units/L, total bilirubin 2.0 mg/dL with direct bilirubin 0.5 mg/dL and creatinine 0.72 mg/dL. Peripheral smear showed anisopoikilocytosis, with target, sickle and teardrop cells, and scattered schistocytes, polychromatophilia, NRBCs and Howell-Jolly and Pappenheimer bodies, as well as occasional myeloblasts, giant platelets and rare megakaryocyte nuclear fragments (Image 1 A–C). Bone marrow biopsy was 60% to 70% cellular with grade 3 myelofibrosis (Image 1 D), without increased blasts. Karyotype was normal. A type 1 frameshift mutation in calreticulin (CALR), c.1099_1150del52 (p.Leu367Thrfs*46), was found, with an allele frequency of 51%, as well as a DNMT3A mutation, c.2196dup (pGlu733*), with an allele frequency of 4%. A diagnosis of primary myelofibrosis1 was made based on presence of grade 3 myelofibosis and a CALR mutation and not meeting criteria for other myeloid malignancies (major criteria), as well as elevated LDH and leukoerythroblastosis (minor criteria); anemia and leukocytosis were also present as minor criteria, but could also be attributed to sickle cell disease. Though presentation was confounded by coexisting sickle cell disease, myelofibrosis was best categorized as intermediate-risk (older age, severe anemia and dense fibrosis, but presence of CALR mutation and lack of unfavorable cytogenetic changes or mutations), and symptom-directed therapy was indicated.2 In the setting of transfusion-dependent anemia with an inappropriately low endogenous erythropoietin level (80 mIU/mL), epoietin 60 000 units subcutaneously weekly was initiated. The risk of stimulating production of sickle cells was thought to be low, given the high percentage of hemoglobin F. Cytoreductive therapy to control thrombocytosis was thought to be indicated in the setting of older age and cardiovascular disease. Given previous intolerance of hydroxyurea, pegylated interferon alfa-2a was initiated to control thrombocytosis, resulting in a gradual decrease in her platelet count. Outside blood counts 8 months after starting epoietin and pegylated interferon alfa-2a were hemoglobin 9.2 g/dL, WBC 41.5 × 109/L (including NRBCs) and platelet count 270 × 109/L. She subsequently relocated and no further follow-up information is available. This patient's course illustrates lack of symptoms and late diagnosis of sickle cell disease in association with hereditary persistence of fetal hemoglobin, development of a myeloid neoplasm in an older patient with sickle cell disease in the absence of hydroxyurea therapy, and management of anemia and thrombocytosis associated with myelofibrosis in the setting of sickle cell disease. Higher hemoglobin F levels are associated with a lower rate of acute painfu","journal":"American Journal of Hematology","year":2021,"id":212166,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9511,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":802117,"name":"Zeba N. Singh","orcid":"0000-0002-6269-4541","position":1,"is_corresponding":false},{"id":474925,"name":"Maria R. Baer","orcid":"0000-0002-9499-1348","position":2,"is_corresponding":false},{"id":802499,"name":"Sarah E. Green","orcid":null,"position":0,"is_corresponding":true}],"reference_count":10,"raw_metadata":null,"created_at":"2026-07-18T23:52:23.670339Z","pmid":"34498303","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}