Anemia, hemolytic megaloblastic

Hematologic Hematopoietic complications, some fatal, include thrombocytopenia, leukopenia, granulocytopenia, agranulocytosis, and pancytopenia. Macrocytosis and megaloblastic anemia usually respond to folic acid therapy. Eosinophilia monocytosis leukocytosis simple anemia hemolytic anemia aplastic anemia ecchymosis. 

Different classifications of anemia are based in part on the pathophysiological factor inducing the decreased hemoglobin concentration. Anemias due to cell hy-poproliferation include aplastic anemia and iron deficiency anemia. Hemolytic anemia results from excessive destruction of red blood cells. Megaloblastic anemia, sideroblastic anemia, and iron deficiency anemia result from an abnormality in the maturation of red blood cells. 

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

Pyrimethamine (Daraprim) 25-mg tablet Malaria (see pyrimethamine-sulfadoxime) Gl Abdominal pain, vomiting, glossitis Hemat. Megaloblastic anemia, hemolytic anemia Recommended that folinic acid 1-5 mg/day be concurrently administered can cause hemolysis in patients with GbPO deficiency 9, 24, 25... 

Vitamin E may be indicated in some rare forms of anemia such as macrocytic, megaloblastic anemia observed in children with severe malnutrition and the hemolytic anemia seen in premature infants on a diet rich in polyunsaturated fatty acids. Also anemia s in malabsorption syndromes have shown to be responsive to vitamin E treatment. Finally, hemolysis in patients with the acanthocytosis syndrome, a rare genetic disorder where there is a lack of plasma jS-lipoprotein and consequently no circulating alpha tocopherol, responds to vitamin E treatment. In neonates requiring oxygen therapy vitamin E has been used for its antioxidant properties to prevent the development retrolental fibroplasia. It should be noted that high dose vitamin E supplements are associated with an increased risk in allcause mortality. 

Parenteral administration of folic acid is rarely necessary, since oral folic acid is well absorbed even in patients with malabsorption syndromes. A dose of 1 mg folic acid orally daily is sufficient to reverse megaloblastic anemia, restore normal serum folate levels, and replenish body stores of folates in almost all patients. Therapy should be continued until the underlying cause of the deficiency is removed or corrected. Therapy may be required indefinitely for patients with malabsorption or dietary inadequacy. Folic acid supplementation to prevent folic acid deficiency should be considered in high-risk patients, including pregnant women, patients with alcohol dependence, hemolytic anemia, liver disease, or certain skin diseases, and patients on renal dialysis. 

A number of toxic effects on the blood have been documented, including agranulocytosis caused by chlorpromazine, hemolytic anemia caused by methyldopa, and megaloblastic anemia caused by methotrexate. Toxic effects on the eye have been noted and range from retinotoxicity caused by thioridazine to glaucoma caused by systemic corticosteroids. 

Hematologic Megaloblastic anemia, leukopenia, and thrombocytopenia may occur all of these effects may be reversed by the concurrent administration of folinic acid (see p. 379), which protects the patient and does not enter the microorganism. Hemolytic anemia may occur in patients with glucose-6-phosphate deficiency due to the sulfamethoxazole (see p. 351). 

B9 (foUc acid/folate) Same as B2 Hemolytic and megaloblastic anemia Headache... 

Megaloblastic anemia is rare with metformin, but vitamin Bi2 concentrations can be reduced by metformin and phenformin (61) because of reduced absorption, and pre-existing deficiency can be exacerbated (41). Metformin can occasionally cause a hemolytic anemia. 

Nitrofurantoin prodnces oxidant stress and cellnlar damage by different mechanisms (43). It can distnrb folate metabolism, leading to a megaloblastic component in pre-existing (mostly hemolytic) anemia, which responds to folic acid treatment. 

Sideroblastic anemia is characterized by the accumulation of iron in the mitochondria of erythroblasts. In a Phase I study in 35 patients with refractory tumors, eight taking CMT-3 developed anemia without leukopenia or thrombocytopenia (54). Three of these patients underwent bone-marrow examination and each had ringed side-roblasts. The authors referred to several cases of aplastic anemia, megaloblastic anemia, and hemolytic anemia in which members of the tetracycline family have been implicated. However, they stated that there has been no previous reports of sideroblastic anemia associated with any tetracycline derivative and that the molecular mechanisms by which CMT-3 might cause sideroblastic anemia are unclear. 

Hemolytic Disease and Ine/fectiVe Erythropoiesis. As discussed previously, Hp levels are a sensitive indicator of in vivo hemolysis, as long as other causes of decreased levels are excluded. Splenomegaly and ineffective hematopoiesis are also associated with decreased levels. The latter, with increased hemolysis of red cells and their precursors in the bone marrow space, is seen in megaloblastic anemias... 

In iron deficiency anemia, zinc acts as an alternative substrate for FECH, leading to increased ZPP. Increased red cell protoporphyrin (mostly ZPP) may also occur in sideroblastic, megaloblastic, and hemolytic anemias. ... 

There is also a significantly increased incidence of IgA deficiency in patients with autoimmune or potentially autoimmune disorders, and usually it is not clear which came first. It can be argued that autoimmunity is a complication of immune imbalance subsequent to inborn IgA deficiency (H24). With inborn absence of IgA, exposure to normal human colostrum, plasma, and saliva can result in the production of antibodies to IgA. By the time such patients are discovered the etiological mechanisms are often obscured and IgA treatment is out of the question. The incidence of IgA deficiency is known to be 1-4% in the following conditions Still s disease, systemic lupus erythematosus, rheumatoid arthritis, Sjogren s disease, warm hemolytic anemia, megaloblastic anemia, idiopathic pulmonary hemosiderosis, thyrotoxicosis, and cirrhosis. 

Folic acid Megaloblastic anemia, diarrhea, glossitis Serum folate Decreased with increased cellular/tissue turnover (pregnancy, malignancy, hemolytic anemia) masks neurologic complications of vitamin B12 deficiency decreases risks of neural tube defects... 

FOLATE DEFICIENCY Folate deficiency is a common complication of diseases of the small intestine, which interfere with the absorption of dietary folate and the recirculation of folate through the enterohepatic cycle. In acute or chronic alcohohsm, daily intake of dietary folate may be severely restricted, and the enterohepatic cycle of the vitamin may be impaired by toxic effects of alcohol on hepatic parenchymal cells this is the most common cause of folate-deficient megaloblastic erythropoiesis. However, it also is the most amenable to therapy, inasmuch as the reinstitution of a normal diet is sufficient to overcome the effect of alcohol. Disease states characterized by a high rate of cell turnover, such as hemolytic anemias, also may be complicated by folate deficiency. Additionally, drugs that inhibit dihydrofolate reductase (e.g., methotrexate and trimethoprim) or that interfere with the absorption and storage of folate in tissues (e.g., certain anticonvulsants and oral contraceptives) can lower the concentration of folate in plasma and may cause a megaloblastic anemia. 

The number of inherited defects of the pyrimidine metabolism described so far is small, compared to that of the purine metabolism. Combined deficiency of orotate phosphoribosyltransferase (OPRT) (EC 2.4.2.10) and orotidine 5 -monophosphate decarboxylase (ODC) (EC 4.1.1.23), designated as type I hereditary orotic aciduria, presents with characteristic clinical features such as hypochromic anemia with a megaloblastic bone marrow and crystalluria. Only six patients have been described and, as far as we know, new cases have not been discovered recently. ODC deficiency with similar clinical phenomena and leading to increased urinary excretion of orotate and orotidine has been detected in only one patient (1). A third defect, a deficiency of pyrimidine 5 -nucleotidase (Py-5NX (EC 3.1.3.5.) in erythrocytes, is associated with chronic hemolytic anemia and prominent basophylic stippling of the erythrocytes due to accumulated pyrimidine nucleotides. An increasing number of patients have been reported, their detection being facilitated by the typical phenomena. We do not know whether the urinary pyrimidine profile in this condition is abnormal. 

Blood Agranulocytosis Hemolytic anemia Pancytopenia Thrombocytopenia Megaloblastic anemia Clotting and/or bleeding Eosinophilia... 

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