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Blood Jan 2023Immune aplastic anemia (AA) is a severe blood disease characterized by T-lymphocyte- mediated stem cell destruction. Hematopoietic stem cell transplantation and...
Immune aplastic anemia (AA) is a severe blood disease characterized by T-lymphocyte- mediated stem cell destruction. Hematopoietic stem cell transplantation and immunosuppression are effective, but they entail costs and risks, and are not always successful. The Janus kinase (JAK) 1/2 inhibitor ruxolitinib (RUX) suppresses cytotoxic T-cell activation and inhibits cytokine production in models of graft-versus-host disease. We tested RUX in murine immune AA for potential therapeutic benefit. After infusion of lymph node (LN) cells mismatched at the major histocompatibility complex [C67BL/6 (B6)⇒CByB6F1], RUX, administered as a food additive (Rux-chow), attenuated bone marrow hypoplasia, ameliorated peripheral blood pancytopenia, preserved hematopoietic progenitors, and prevented mortality, when used either prophylactically or therapeutically. RUX suppressed the infiltration, proliferation, and activation of effector T cells in the bone marrow and mitigated Fas-mediated apoptotic destruction of target hematopoietic cells. Similar effects were obtained when Rux-chow was fed to C.B10 mice in a minor histocompatibility antigen mismatched (B6⇒C.B10) AA model. RUX only modestly suppressed lymphoid and erythroid hematopoiesis in normal and irradiated CByB6F1 mice. Our data support clinical trials of JAK/STAT inhibitors in human AA and other immune bone marrow failure syndromes.
Topics: Mice; Humans; Animals; Pancytopenia; Anemia, Aplastic; Bone Marrow Failure Disorders; Bone Marrow; Bone Marrow Diseases; Janus Kinase 1
PubMed: 36130301
DOI: 10.1182/blood.2022015898 -
Indian Journal of Dermatology,... 2023
Topics: Humans; Pancytopenia; Paraproteinemias
PubMed: 35146977
DOI: 10.25259/IJDVL_425_2021 -
Blood Nov 2012
Topics: Adult; Blood Cell Count; Bone Marrow; Female; Humans; Immunosuppressive Agents; Kidney Transplantation; Lymphoma, Large B-Cell, Diffuse; Pancytopenia
PubMed: 23289110
DOI: 10.1182/blood-2012-06-433003 -
Blood Oct 2012
Topics: Amphotericin B; Anti-Bacterial Agents; Histoplasma; Histoplasmosis; Humans; Male; Middle Aged; Pancytopenia; Prognosis
PubMed: 23230591
DOI: 10.1182/blood-2012-03-417782 -
Blood Cells, Molecules & Diseases Mar 2022Progressive pancytopenia is a common feature observed in DNA crosslink repair deficiency disorder, Fanconi anemia (FA). However, this phenotype has not been...
Progressive pancytopenia is a common feature observed in DNA crosslink repair deficiency disorder, Fanconi anemia (FA). However, this phenotype has not been recapitulated in single FA gene knockout animal models. In this study, we analyzed hematological characteristics in zebrafish null mutants for two FA genes, fanca and fanco. In adult mutants, we demonstrate age-associated reduction in blood cell counts for all lineages, resembling progressive pancytopenia in FA patients. In larval mutants, we demonstrate vascular injury-induced thrombosis defects, particularly upon treatment with crosslinking agent diepoxybutane (DEB), indicating DNA damage induced inefficiency of thrombocytes.
Topics: Animals; DNA Damage; Fanconi Anemia; Humans; Pancytopenia; Thrombosis; Zebrafish
PubMed: 34991062
DOI: 10.1016/j.bcmd.2021.102640 -
BMJ Case Reports Jan 2023We present the case of a young female landscaper who presented to an Australian tertiary hospital with persistent fevers and new pancytopenia. Extensive initial workup...
We present the case of a young female landscaper who presented to an Australian tertiary hospital with persistent fevers and new pancytopenia. Extensive initial workup for her presenting illness did not identify a cause; however, a detailed history of her occupation revealed she worked heavily with soil on farms that had domestic livestock in addition to rodents. Hence, further serological testing for leptospirosis was performed, revealing a diagnosis of infection with Leptospira interrogans serovar Hardjo. Treatment covering leptospirosis was commenced, and she improved clinically, and her cell counts returned to normal. Pancytopenia is a rare manifestation of leptospirosis and has only been reported in a handful of case studies. We highlight that leptospirosis should be considered as a differential diagnosis in those with fever, and new pancytopaenia, particularly in patients with relevant risk factors for exposure.
Topics: Female; Humans; Pancytopenia; Australia; Leptospirosis; Leptospira interrogans; Risk Factors; Leptospira; Antibodies, Bacterial
PubMed: 36604107
DOI: 10.1136/bcr-2022-251506 -
Pediatrics in Review Mar 2016
Review
Topics: Adolescent; Child, Preschool; Chronic Disease; Disease Management; Female; Humans; Infant; Male; Pancytopenia
PubMed: 26933225
DOI: 10.1542/pir.2014-0087 -
Scandinavian Journal of Immunology Aug 2020Some patients with pancytopenia do not conform to any diagnostic criteria of known haematological or non-haematological diseases; however, they respond well to... (Review)
Review
Some patients with pancytopenia do not conform to any diagnostic criteria of known haematological or non-haematological diseases; however, they respond well to corticosteroid, high-dose intravenous immunoglobulin and rituximab treatment. This abnormality is termed immunorelated pancytopenia (IRP). Later studies indicated that IRP might be a kind of autoimmune disease in which T helper (Th) type 2 cell function is enhanced, resulting in the hyperfunction of B lymphocytes, which then produce excess autoantibodies that attack the bone marrow (BM) and cause cytopenia. Hypofunction of regulatory T (Treg) cells and enhanced Th17 cell function, an elevated percentage of plasmacytoid dendritic cells (pDCs) and a decreased percentage of natural killer (NK) cells help to promote the process. Moreover, increased expression of a synergistic stimulator of B lymphocytes, CD70 and the reactive overexpression of the BCR inhibitory coreceptor CD22 also support this claim. Candidate autoantigens targeted by autoantibodies on haematopoietic cell membranes have also been reported in IRP. This review is focused on studies that demonstrate the role of immune responses in the pathogenesis of IRP. Current diagnostic criteria and treatments for IRP are also referenced to provide a thorough understanding. Distinguishing IRP from idiopathic cytopenias of undetermined significance (ICUS) and other haematological disorders, for example myelodysplastic syndrome (MDS), aplastic anaemia (AA), paroxysmal nocturnal hemoglobinuria (PNH) and Evans syndrome, may help patients with pancytopenia benefit from proper treatment. Further studies are required to achieve new insight into the pathophysiology of IRP with regard to the immune system, which will be instrumental for the development of novel therapies for inhibiting disease initiation and/or progression.
Topics: Humans; Pancytopenia
PubMed: 32474938
DOI: 10.1111/sji.12911 -
Hormones and the bone marrow: panhypopituitarism and pancytopenia in a man with a pituitary adenoma.Journal of General Internal Medicine May 2015In rare cases, pancytopenia results from hormonal deficiencies that arise in the setting of panhypopituitarism. Here we describe the unusual case of a 60-year-old man... (Review)
Review
In rare cases, pancytopenia results from hormonal deficiencies that arise in the setting of panhypopituitarism. Here we describe the unusual case of a 60-year-old man who presented with progressive fatigue and polyuria, and whose laboratory workup revealed a deficiency of the five hormones associated with the action of the anterior pituitary (thyroid hormone, testosterone, cortisol, prolactin, and insulin-like growth factor-1). Imaging of the pituitary demonstrated a cystic mass consistent with a pituitary adenoma replacing much of the normal pituitary tissue. His symptoms and hematologic abnormalities rapidly resolved with prednisone and levothyroxine supplementation. While the majority of reported cases of panhypopituitarism with bone marrow suppression are the result of peripartum sepsis or hemorrhage leading to pituitary gland necrosis (Sheehan's syndrome), it is also important to consider the diagnosis of hypopituitarism in patients with hypothyroidism, low cortisol levels, and pancytopenia. The causal relationship between pancytopenia and panhypopituitarism is not well understood, though it does reinforce the important influence of these endocrine hormones on the health of the bone marrow.
Topics: Adenoma; Bone Marrow; Drug Therapy, Combination; Hematologic Tests; Humans; Hypopituitarism; Kidney Function Tests; Magnetic Resonance Imaging; Male; Middle Aged; Pancytopenia; Pituitary Neoplasms; Prednisone; Rare Diseases; Thyroxine; Treatment Outcome
PubMed: 25583570
DOI: 10.1007/s11606-014-3161-x -
BMJ Case Reports May 2022A female child hailing from South Asia, India presented with pallor, multiple petechiae and ecchymosis. Based on the clinical picture and demography, the differentials...
A female child hailing from South Asia, India presented with pallor, multiple petechiae and ecchymosis. Based on the clinical picture and demography, the differentials considered were pancytopenia of nutritional origin, acute leukaemia, autoimmune and infective aetiologies. After ruling these out by respective tests, a literature review was done which revealed the possibility of filariasis especially in a patient with eosinophilia which was present in our case. A repeat peripheral blood smear study with a nocturnally drawn sample revealed multiple microfilariae and a diagnosis of filariasis was made. The patient was treated with triple drug therapy of diethylcarbamazine (6 mg/kg), ivermectin (6 µg/kg) and albendazole (400 mg) administered as a single dose. Subsequent haemograms showed improved cell counts. This along with a previous handful of case reports emphasises filariasis as one of the differentials of pancytopenia and should be kept in mind while evaluating for the same, especially in the endemic areas.
Topics: Albendazole; Animals; Child; Diethylcarbamazine; Drug Therapy, Combination; Elephantiasis, Filarial; Female; Filaricides; Humans; Ivermectin; Pancytopenia; Wuchereria bancrofti
PubMed: 35606041
DOI: 10.1136/bcr-2022-248930