Blood and hemostasis
Laurie K. McCorry, Martin M. Zdanowicz, Cynthia Y. Gonnella in Essentials of Human Physiology and Pathophysiology for Pharmacy and Allied Health, 2019
Aplastic anemia is caused by a lack of red blood cell production by the bone marrow. If erythrocyte stem cells precursors are lacking or destroyed, the process of erythropoiesis will be severely impaired. Aplastic anemia may result from a congenital defect in stem cell production or can be caused by exposure to agents that damage the bone marrow, such as solvents, radiation, infection, chemotherapeutic drugs, and certain antibiotics (see Table 5.4). Drug-induced aplastic anemia is usually a dose-dependent phenomenon. The clinical manifestations of aplastic anemia will depend upon the extent to which hematopoiesis is impaired. General symptoms of anemia such as pallor, fatigue, lethargy can occur initially. Bleeding in the skin and from the nose, mouth and body orifices may also occur from a lack of platelet production by the abnormal bone marrow. Increased susceptibility to infection is also seen as a result of diminished white blood cell production. The underlying cause of the aplastic anemia needs to be identified and further exposure prevented. Treatment should also include avoidance of physiologic stresses and infection. Transfusions are effective for temporarily improving oxygen carrying capacity. In severe cases, bone marrow transplant may offer a cure.
Chemoprotective and Immunomodulating Effects of Ferulic Acid on Cisplatin Chemotherapy in Dalton’s Lymphoma Xenografted Mice
Parimelazhagan Thangaraj in Phytomedicine, 2020
Most commonly, chemotherapy acts by killing cells that divide rapidly which is an important property of the cancer cells. These drugs are also harmful to cells that divide rapidly under normal circumstances, such as cells in the bone marrow, digestive tract, and hair follicles, resulting in side effects such as myelosuppression (decreased production of blood cells) and immunosuppression (Rüther et al. 2000). It is known that tumor development causes immunosuppression in the host. Most anti-cancer drugs are anti-proliferative and will also affect actively dividing normal cells. Furthermore, the side effects of chemotherapeutics include toxicity to bone marrow. Bone marrow depression occurs after cisplatin administration, which is indicated by a fall in circulating leukocytes and platelets. This may lead to bleeding disorders, increased susceptibility to infection, and bone marrow aplasia. FA restores back the bone marrow cells, which were decreased by cisplatin treatment.
Nucleic Acids as Therapeutic Targets and Agents
David E. Thurston, Ilona Pysz in Chemistry and Pharmacology of Anticancer Drugs, 2021
When administered orally, busulfan causes significantly less nausea and vomiting than other DNA cross-linking agents and is therefore more acceptable to patients. Thus, when used to treat CML, it can keep patients almost symptom-free for long periods of time with relatively few side effects. However, frequent blood tests are necessary because myelosuppression may result in irreversible bone-marrow aplasia. Skin hyperpigmentation is also a common side effect during oral therapy, and progressive interstitial pulmonary fibrosis may occur more rarely. Other less frequent side effects include seizures, hepatic toxicity (i.e., veno-occlusive disease), and wasting syndrome. Levetiracetam has proved effective as prophylaxis for busulfan-induced seizures, and the anticonvulsant phenytoin is sometimes administered concurrently to prevent seizures, and benzodiazepines can be used to ameliorate busulfan-induced seizures when they are in progress. Finally, busulfan is a Group 1 carcinogen, and so should be avoided during conception, pregnancy and breast feeding.
Eltrombopag, oral immunosuppressant and androgen combination therapy in twelve patients with refractory severe aplastic anemia
Published in Hematology, 2020
Qingyan Gao, Li Zhang, Xin Zhao, Yangmin Zhu, Guangxin Peng, Yang Li, Yuan Li, Jianping Li, Lin Song, Lei Ye, Huihui Fan, Kang Zhou, Wenrui Yang, Yang Yang, Liping Jing, Fengkui Zhang
Acquired aplastic anemia is an immune-mediated bone marrow failure syndrome [1] that is mainly characterized by hypocellular marrow and a reduction of whole blood cells. The abnormal activation and hyperfunction of T lymphocytes is believed to cause hematopoietic stem and progenitor cell destruction, which was inferred mainly from effective immunosuppressive therapies for the disease [1,2]. Successful management of severe aplastic anemia (SAA) relies on adequate hematopoietic stem cells and effective interruption of abnormal immunity. Immunosuppressive therapy (IST) with antithymocyte globulin (ATG) and cyclosporine A (CsA) is the first-line choice for patients without a matched sibling donor, elderly patients, and patients who are ineligible for hematopoietic stem cell transplantation (HSCT) [2–5] and has a response rate between 50–70% [3,6]. However, 60% patients are still in need of further treatment after frontline standard IST [7].
Phenotypic variation in sickle cell disease: the role of beta globin haplotype, alpha thalassemia, and fetal hemoglobin in HbSS
Published in Expert Review of Hematology, 2022
Traditionally measured in peripheral blood as the percentage of HbF quantitated by alkali denaturation or HPLC is less informative than more direct measurements of the ‘F cells’ or ‘F reticulocytes’ [54] but these indices, although valuable research tools, are not usually available in the clinical setting. The uneven distribution among the red cell population also implies that red cells with low HbF levels are more likely to be destroyed, there being a direct relationship between HbF levels and irreversibly sickled cells [59]. This implies that blood, as sampled from peripheral veins, does not necessarily reflect the output from the bone marrow. In the aplastic crisis, where bone marrow aplasia occurs for 6–8 days, selective destruction of low HbF containing cells leads to a steep rise in overall HbF levels [60], and although this may be an extreme example, a similar effect could occur in other clinical complications. Analysis of the relevance of HbF levels to clinical complications should therefore be confined to HbF estimates during the steady state. Non-steady state conditions linked to increases in HbF include pregnancy [61], medroxy-progesterone acetate [62], and the use of hydroxyurea [63,64].
A New Zealand White rabbit model of thrombocytopenia and coagulopathy following total body irradiation across the dose range to induce the hematopoietic-subsyndrome of acute radiation syndrome
Published in International Journal of Radiation Biology, 2021
Isabel L. Jackson, Ganga Gurung, Yannick Poirier, Mathangi Gopalakrishnan, Eric P. Cohen, Terez-Shea Donohue, Diana Newman, Zeljko Vujaskovic
The temporal sequence of bone marrow aplasia associated with prompt radiation exposure to humans at doses 2001). The early drop in the peripheral leukocyte count is followed by a progressive decline in platelet counts and development of a severe acute anemia during the second to third week post-exposure (Liebow et al. 1949). In the absence of spontaneous recovery associated with an increase in circulating leukocytes and platelets, death due to aplastic anemia, bacterial infections, and severe hemorrhage is common (Liebow et al. 1949). After the fourth week, multiorgan failure may occur, with stepwise development of injury to late responding normal tissues (e.g. pneumonitis, nephropathy) (Liebow et al. 1949).
Related Knowledge Centers
- Anemia
- Blood Cell
- Heredity
- Pancytopenia
- Hematopoietic Stem Cell
- Bone Marrow
- Cancer
- Leukopenia
- Thrombocytopenia
- Primary Immunodeficiency