Hematologic disorders anemia

Adverse Effects. The primary problem associated with foscarnet is impaired renal function, including acute tubular necrosis. Hematologic disorders (anemia, granulocytopenia, leukopenia), gastrointestinal disturbances (cramps, nausea, vomiting), and CNS toxicity (confusion, dizziness) may also occur during foscarnet treatment. 

R. W. "Hematology", Chapter 11, "Erythrocyte Disorders -Anemias Related to Abnormal Globln", McGraw-Hill Book Company, New York, 1972. 

Several reports identified nonlethal effects in humans acutely exposed to arsine. These reports, however, lacked definitive exposure data but verified hematologic disorders leading to renal failure as critical effects of arsine exposure. Bulmer et al. (1940) (as cited in Elkins 1959) reconstructed an exposure incident at a gold extraction facility and estimated that subchronic (up to 8 mon) exposure to 0.12 ppm arsine resulted in jaundice and anemia (see Section 2.2.1). The lack of definitive exposure data for humans necessitates the use of animal data for quantitative estimation of AEGL values. Derivation of AEGL-2 values based upon limited human data (Flury and Zernik 1931) was considered but rejected because the data were poorly documented and inconsistent with other data showing lethality at lower cumulative exposures. 

Following intravenous injection of Thorotrast, cirrhosis of the liver was the primary systemic effect in humans and animals. Hematological disorders (aplastic anemia, leukemia, myelofibrosis, and splenic cirrhosis), cardiovascular effects (myocardial infarction, severe coronary luminal narrowing and internal alteration of the carotid artery), and Thorotrastoma (localized fibrosis surrounding deposits of Thorotrast) were also found in patients injected with Thorotrast. The effects of Thorotrast were a result of the radiological toxicity of thorium. 

Alcohol indirectly affects hematopoiesis through metabolic and nutritional effects and may also directly inhibit the proliferation of all cellular elements in bone marrow. The most common hematologic disorder seen in chronic drinkers is mild anemia resulting from alcohol-related folic acid deficiency. Iron deficiency anemia may result from gastrointestinal bleeding. Alcohol has also been implicated as a cause of several hemolytic syndromes, some of which are associated with hyperlipidemia and severe liver disease. 

Hematologic disorders Acquired hemolytic anemia, acute allergic purpura, leukemia, autoimmune hemolytic anemia, idiopathic thrombocytopenic purpura, multiple myeloma... 

Hematologic disorders Immunosuppression Autoimmune hemolytic anemia, congenital hypoplastic anemia, erythroblastopenia, thrombocytopenia... 

Adverse Effects. The most serious problems associated with ganciclovir include anemia, granulocytopenia, thrombocytopenia, and related hematologic disorders. Ganciclovir may also cause gastrointestinal disturbances (nausea, loss of appetite) and CNS disturbances (mood changes, nervousness, tremor). 

Other causes of gastric atrophy, such as those due to Helicobacter pylori,AIDS, or radiation injury, can lead to a similar outcome but from different pathogenic mechanisms. Therefore, vitamin B12 deficiency, resulting in neurological, psychiatric, metabolic, and hematological disorders, can arise from any one of the many causes listed in Table 28-1. For this reason, the term pernicious anemia (PA) is used here to describe only the classical disease that is associated with IF deficiency due to autoimmune gastritis. 

Hexachlorobenzene (a fungicide) has caused porphyria cutanea tarda in humans. It does not cause convulsions. Lindane, chlordane, and dieldrin have been associated anecdotally with certain rare hematologic disorders, including aplastic anemia the incidence of these effects appears to be extremely low. 

One of the rare studies of the excretion of tryptophan metabolites, both spontaneous and after load, by patients with hematological disorders, is the work of Altman and Miller (A4). They reported an elevated urinary excretion of anthranilic acid in 9 children with an unusual congenital anemia referred to as erythrogenesis imperfecta (A4). Oral administration of 1.6 g L-tryptophan to one patient led to increased urinary excretion of anthranilic acid as well as other intermediary metabolites of tryptophan. Massive doses of riboflavin per os during 30 days caused no change in the hematological status, but there appeared to be a decrease in the amount of anthranilic acid excreted. 

Hematological Disorders. Seventeen boys under 4 years of age were studied by Rabe and Plonko (Rl) for evidence of pyridoxine need. Four of the children had hypochromic microcytic anemia, 4 had convulsions, and 9 suffered from miscellaneous acute infectious illnesses. 

M2. Marver, H. S., Studies on tryptophan metabolism. I. Urinary tryptophan metabolites in hypoplastic anemias and other hematologic disorders. J. Lab. Clin. Med. 58, 425-436 (1961). 

Fig. 7. The minor hemoglobin components of patients with various hematological disorders. From left to right hemolytic anemias, polycythemia vera, leukemias, iron-deficiency anemia, lupus erythematosus, malabsorbed vitamin Bu., Post splenectomy. From Horton and Huisman (H24) with permission of the authors and publisher.

There are several acquired hematological disorders which have an increased synthesis of Hb-F [summarized in (H37, K13)], Thus, an elevated level of Hb-F is frequently observed in, for example, Fanconi s anemia, megaloblastic anemia, polycythemia vera, various types of leukemia, multiple myeloma and lymphomas, macroglobulinemia, and metastatic disease of the bone marrow. The chemical heterogeneity of the Hb-F in some of these disorders (aplastic anemia, Fanconi s anemia, and various forms of leukemia) has been studied (H60, R29). In many instances, the to ratio is similar to that found in the normal newborn. This is particularly striking for patients with various forms of leukemia, and the Hb-F which is produced in increased quantities in these disorders invariably has a °y to y ratio of about 3 1. This newborn ratio of °y to y chains in Hb-F may be a common factor in these diseases as perhaps another example of fetal characteristics in red cells of patients with leukemia, it supports the hypothesis that these cells may be of fetal origin (H25). 

Singer, H., Chemoff, A. I., and Singer, L., Studies on abnormal hemoglobin. I. Their demonstration in sickle cell anemia and other hematologic disorders by means of alkali denaturation. Blood 6, 413-428 (1951). 

Interferon alfa has direct myelosuppressive effects and can also cause hematological disorders by immune blood cell destruction, as suggested by reports of immune-mediated thrombocytopenia, immune hemolytic anemia (205,206), or a positive direct Coombs test, with or without hemolysis (207-209). 

NSAIDs have been reported to cause potentially severe hematological disorders thrombocjdopenia, agranulocytosis, aplastic anemia, and hemolytic anemia (50). Thrombocytopenia is generally mild and reversible and has a low case-fatahty rate, but deaths from bleeding have been reported, particularly with indometacin, oxjrphen-butazone, and phenylbutazone (50). 

The most common drug-induced hematologic disorders in- elude aplastic anemia, agranulocytosis, megaloblastic anemia, thrombocytopenia, and hemolytic anemia. 

By most reports, idiosyncratic drug-induced hematologic disorders are rare. Relatively few epidemiologic studies have addressed the actual incidence of these adverse reactions. A report from The Netherlands estimated the incidence of drug-associated agranulocytosis as 1.6 to 2.5 cases per million inhabitants per year. Similar results were found in epidemiologic studies conducted in Thailand and BraziU Older data from a study conducted in Europe and Israel estimated the incidences of aplastic anemia and agranulocytosis to be 0.5 and 3.1 cases per million per year, respectively. ... 

Epoetin alfa has received orphan drug status from the FDA for the treatment of the anemia of prematurity, HIV infection, and myelodysplasia. In the latter case, even very high doses or more than 10(X) units/kg two to three times a week have had limited success. The utility of very high-dose therapy in other hematological disorders, such as sickle cell anemia, still is under study. Highly competitive athletes have used epoetin alfa to increase their hemoglobin levels ( blood doping ) and improve performance. 

Hematologic disorders (e.g., idiopathic thrombocytopenic purpura, acquired hemolytic anemia)... 

Erslev AJ (1986) Erythrocyte Disorders — Anemias related to unknown or multiple mechanisms. In Williams WJ, Beuler E, Ersley AJ and Hchtman DA, eds. Hematology, 3rd edn. Chapter 51, pp. 522-528. McGraw-Hill Book Co, New York. 

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