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Benign Disorders of Leukocytes
Published in Harold R. Schumacher, William A. Rock, Sanford A. Stass, Handbook of Hematologic Pathology, 2019
Gene L. Gulati, Zoran Gatalica, Bong H. Hyun
An absolute neutrophil count below the lower limit of normal, usually below 1.8 × 109/L for white adults and below 1.0 × 109/L for black adults, is defined as neutropenia. The term agranulocytosis is generally used to denote severe neutropenia often revealing no neutrophils in the peripheral blood and myeloid hypoplasia and/or maturation arrest at the myelocyte stage in the bone marrow. When the neutrophil count falls below 0.5 × 109/L, the patient is very likely to have recurrent infections, necessitating the inclusion of isolation precautionary measures in the management plan. Neutropenia may result from (a) decreased production in the bone marrow, (b) ineffective production, (c) increased removal from the blood, (d) shift of cells from the circulating pool to the marginal pool, or (e) any combination of these. Neutropenia may be selective or part of a general pancytopenia, which refers to a reduction in all three cell lines, leukocytes, erythrocytes, and thrombocytes in the peripheral blood. Frequently, neutropenia is associated with relative lymphocytosis. The conditions associated with neutropenia are listed in Table 7.
Leprosy: Therapy-related emergencies
Published in Biju Vasudevan, Rajesh Verma, Dermatological Emergencies, 2019
Leprosy patients who are deficient in glucose-6–phosphate dehydrogenase (G6PD) are at risk of severe and potentially fatal hemolysis due to dapsone. Hemolytic anemia is one of the causes, which often leads to stoppage of dapsone during treatment [7,33,34]. Agranulocytosis is a rare but very serious complication of DDS. It has been reported to occur in 0.2%–0.4% of patients treated with dapsone. Agranulocytosis is an acute condition characterized by a sudden drop in white cell production leaving the body susceptible to bacterial infection and septicemia. Though reversible, it can be fatal if timely management is not started. The mechanism is the same as for methemoglobinemia and hemolytic anemia, that is, formation of hydroxylamine, the toxic metabolite of dapsone that ultimately leads to depression of bone marrow. Agranulocytosis due to dapsone is not dose related, and when severe, can also involve platelets causing thrombocytopenia [35,36]. It is neutropenia, which is noticed earliest, usually at 3 weeks. Fever, pallor, and pharyngitis in a patient of leprosy on the first few months of dapsone should be taken as warning symptoms. Agranulocytosis should be excluded at the earliest in such cases [35,37]. Prompt treatment with antibiotics and G-CSF is essential for the survival of the patient.
Haematology
Published in Michael McGhee, A Guide to Laboratory Investigations, 2019
Agranulocytosis can be caused by: drugs that give rise to pancytopenia (e.g. antimitotic drugs and antirheumatic drugs such as gold, as well as carbimazole)some malignancies (e.g. leukaemia, non-Hodgkin’s lymphoma) may present with low WBC.
An evaluation of deferiprone as twice-a-day tablets or in combination therapy for the treatment of transfusional iron overload in thalassemia syndromes
Published in Expert Review of Hematology, 2023
Richa Shah, Aashaka Shah, Sherif M. Badawy
Deferiprone has been FDA approved for use in patients with transfusional iron overload since 2011 in the form of three times daily tablets or oral solution. More recently, it has gained FDA approval for use as twice-daily tablets. Compared to other iron chelators, such as DFO and DFX, DFP has shown similar efficacy in decreasing systemic iron overload. DFP decreases serum ferritin and liver and myocardial iron content, as well as increases urinary iron excretion. DFP has also been shown to have higher medication adherence and an increased ability to decrease cardiac iron stores compared to other iron chelators. Common side effects of DFP include neutropenia, gastrointestinal disturbances, joint pain, and an increase in liver enzymes. Although not as common, agranulocytosis is a serious potential side effect that patients should be monitored for while receiving DFP treatment. However, studies have shown that agranulocytosis is reversible with cessation of the medication. Overall, deferiprone is an effective treatment for transfusional iron overload. Dual chelation regimens involving DFP, as well DFP’s recent approval for twice-daily usage, are anticipated to increase the use and reach of DFP in the coming years.
Study of the acute and repeated dose 28-day oral toxicity in mice treated with PT-31, a molecule with a potential antipsychotic profile
Published in Toxicology Mechanisms and Methods, 2022
Thalia Emmanoella Sebulsqui Saraiva, Gabriela Zimmermann Prado Rodrigues, Juliana Machado Kayser, Eliane Dallegrave, Nathália Pulz Maus, Andriele Veiverberg, Gabriel da Costa Berna, Andriéli Carolina Schuster, Maria Gabriela de Freitas, Marina Galdino da Rocha Pitta, Ivan da Rocha Pitta, Günther Gehlen, Andresa Heemann Betti
In addition to biochemical changes, hematological alterations, such as agranulocytosis, decreased neutrophils, increased eosinophils, anemia, thrombocytosis, and thrombocytopenia, can occur with the use of antipsychotics (Flanagan and Dunk 2008). One of the greatest concerns is agranulocytosis, characterized by a deficiency in the bone marrow in producing enough white blood cells, preferably neutrophils. PT-31 did not cause neutrophilia or leukopenia, suggesting that the molecule does not alter bone marrow function, even at doses four times higher than the effective dose in the preclinical evaluation (Betti et al. 2019). Unlike, clozapine, which is highly effective in treating different symptoms of schizophrenia, has cautious use among prescribers due to this serious adverse effect, that can occur in up to 1% of patients (Legge and Walters 2019).
Safety of antithyroid drugs in pregnancy: update and therapy implications
Published in Expert Opinion on Drug Safety, 2020
Thanuya Francis, Niroshan Francis, John H. Lazarus, Onyebuchi E. Okosieme
Agranulocytosis, defined as a neutrophil count below 500/µl, occurs in 0.1–0.5% of patients on antithyroid drugs [28]. The pathogenesis of agranulocytosis is uncertain but may occur either by direct intoxication or via immune mediated neutrophil destruction. An immune process is supported by studies which show an association between agranulocytosis and human leukocyte antigen or other immune response genes [51]. A genome-wide association study in a Caucasian population showed an association with HLA B*27:05 and other single nucleotide polymorphisms on chromosome 6 [52]. Agranulocytosis is equally seen in patients taking CMZ/MMI and PTU and is more likely to occur within the first three months of therapy, in older patients, and in patients receiving high treatment doses [28,53]. It is a serious condition with a potential mortality risk and in a study from Japan, 24 fatalities were observed out of 754 patients with agranulocytosis, equivalent to a 3% mortality rate [28].