Hemolytic Bone marrow

The life span of the normal red blood cell is 120 days this means that slightly less than 1% of the population of red cells (200 billion cells, or 2 million per second) is replaced daily. The new red cells that appear in the circulation still contain ribosomes and elements of the endoplasmic reticulum. The RNA of the ribosomes can be detected by suitable stains (such as cresyl blue), and cells containing it are termed reticulocytes they normally number about 1% of the total red blood cell count. The life span of the red blood cell can be dramatically shortened in a variety of hemolytic anemias. The number of reticulocytes is markedly increased in these conditions, as the bone marrow attempts to compensate for rapid breakdown of red blood cells by increasing the amount of new, young red cells in the circulation. 

HbSS) hallmark of SCD Chronic hemolytic anemia is common Patients may develop infarction of the spleen, liver, bone marrow, kidney, brain, and lungs Gallstones and priapism also may develop Slow healing lower extremity ulcers may develop usually after infection or trauma Hgb 7-10 g/dL (70-100 g/L or 4.4-6.2 mmol/L)... 

Gelman et al. (1978) found that the interaction between lead and phenylhydrazine produced an additive effect in the acute hemolytic phase of anemia and a probable synergistic effect during the compensatory phase of anemia in rabbits. The mechanism postulated for anemic interaction appears to be primarily related to depressed bone marrow production of erythrocytes rather than to increased hemolysis. 

Mitomycin C -antitumor antibiotic inhibits RNAand DNA synthesis -bone marrow suppression -nausea and vomiting—mild to moderate -mucocutaneous effects (mucositis, stomatitis, diarrhea) -vesicant if extravasated -nephrotoxicity -veno-occlusive disease (VOD) of the liver -hemolytic-uremic syndrome... 

Gl Melena anorexia nausea vomiting constipation taste alteration diarrhea. Hematologic Bone marrow depression thrombocytopenia thrombocytopenic purpura hemolytic anemia leukopenia pancytopenia agranulocytosis. 

Hematologic/Lymphatic Anemia hemolytic anemia thrombocytopenia thrombocytopenic purpura eosinophilia leukopenia granulocytopenia neutropenia bone marrow depression agranulocytosis reduction of hemoglobin or hematocrit prolongation of bleeding and prothrombin time decrease in WBC and lymphocyte counts increase in lymphocytes, monocytes, basophils, and platelets. Hypersensitivity Adverse reactions (estimated incidence, 1% to 10%) are more likely to occur in individuals with previously demonstrated hypersensitivity. In penicillin-sensitive individuals with a history of allergy, asthma, or hay fever, the reactions may be immediate and severe. 

Hematologic- Eosinophilia transient neutropenia leukocytosis leukopenia thrombocythemia thrombocytopenia agranulocytosis granulocytopenia hemolytic anemia bone marrow depression pancytopenia decreased platelet function anemia aplastic anemia hemorrhage. 

Capsules/Tablets/Oral solution-There are significant adverse events caused by ribavirin capsules/interferon alfa-2b or peginterferon alfa-2b therapy, and ribavirin tablets/peginterferon alfa-2a therapy, including severe depression and suicidal ideation, hemolytic anemia, suppression of bone marrow function, autoimmune and infectious disorders, pulmonary dysfunction, pancreatitis, and diabetes. 

Bone marrow depression may be manifested as aplastic anemia, thrombocytopenia, thrombocytopenic purpura, leukopenia, agranulocytosis, hemolytic anemia. 

Hemolytic anemia, porphyria, bone marrow depression, superinfections (especially with fungi), metabolic acidosis occurs rarely. 

Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS) has occurred in patients with advanced HIV disease and also in allogeneic bone marrow transplant and renal transplant recipients taking valacyclovir at doses of 8 g/day. 

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. 

Sulfasalazine has a high incidence of adverse effects, most of which are attributable to systemic effects of the sulfapyridine molecule. Slow acetylators of sulfapyridine have more frequent and more severe adverse effects than fast acetylators. Up to 40% of patients cannot tolerate therapeutic doses of sulfasalazine. The most common problems are dose-related and include nausea, gastrointestinal upset, headaches, arthralgias, myalgias, bone marrow suppression, and malaise. Hypersensitivity to sulfapyridine (or, rarely, 5-ASA) can result in fever, exfoliative dermatitis, pancreatitis, pneumonitis, hemolytic anemia, pericarditis, or hepatitis. Sulfasalazine has also been associated with oligospermia, which reverses upon discontinuation of the drug. Sulfasalazine impairs folate absorption and processing hence, dietary supplementation with 1 mg/d folic acid is recommended. 

The most dangerous adverse reaction of sulfonylureas is agranulocytosis. Aplastic anemia (79), red cell aplasia (80), pure white cell aplasia (81), bone marrow aplasia, and hemolytic anemia have been described during treatment with chlorpropamide (82), glibenclamide (83), or tolbutamide (84). 

Antibodies Names vary according to specific lymphocyte targets see Table 37-2 Bone marrow, other organ transplants (see Table 37-2) Idiopathic thrombocytic purpura, other hemolytic disorders... 

Glucocorticoids See text for listing Heart, kidney, liver, bone marrow Multiple sclerosis, rheumatoid arthritis, SLE, inflammatory bowel disease, hemolytic disorders, others. 

Azathioprine is an effective agent in suppressing the immune system in patients undergoing renal transplantation and in patients suffering from acute glomerulonephritis, the renal component of systemic lupus erythematosus, prednisone-resistant idiopathic thrombocytopenic purpura, and functioning autoimmune hemolytic anemia. Azathioprine depresses bone marrow functioning, which is its chief side effect. 

Trimellitic anhydride, used in chemical synthesis. Type II hypersensitivity manifested by adverse effects on blood, including hemolytic anemia and bone marrow depression, may be caused by exposure to trimellitic anhydride. This agent may also cause type III hypersensitivity, resulting from deposition of antigen-antibody complexes in tissue and causing symptoms such as rheumatoid disease or pneumonitis. 

The hematopoietic system is affected by both short- and long-term arsenic exposure. Arsenic is known to cause a wide variety of hematological abnormalities like anemia, absolute neutropenia, leucopenia, thrombocytopenia, and relative eosinophilia - more common than absolute esino-philia, basophilic stippling, increased bone marrow vascularity, and rouleau formation (Rezuke et al, 1991). These effects may be due to a direct hemolytic or cytotoxic effect on the blood cells and a suppression of erythropoiesis. The mechanism of hemolysis involves depletion of intracellular GSH, resulting in the oxidation of hemoglobin (Saha et al, 1999). Arsenic exposure is also known to influence the activity of several enzymes of heme biosynthesis. Arsenic produces a decrease in ferrochelatase, and decrease in COPRO-OX and increase in hepatic 5-aminolevulinic acid synthetase activity (Woods and Southern, 1989). Subchronic... 

The defect also results in an excess synthesis of a chains. These chains precipitate and are observed as inclusion bodies. Cells with these precipitates are predisposed to a preferential destruction in the bone marrow or the peripheral circulation and a characteristic hemolytic anemia will result. 

Acquired hemolytic reactions due to anti-A or anti-B can be caused by group O allografts in renal transplantation (80-83) and can be prevented by prophylactic irradiation of the kidney (84). Cases of immune hemolytic anemia have also been attributed to donor-derived red cell antibodies after allogeneic bone marrow transplantation (85,86). 

Sulfonamides have adverse effects on all bone marrow-derived cell lines. The resulting disturbances include hemolytic anemia, folate deficiency anemia, neutropenia, thrombocytopenia, and pancytopenia. While adverse effects on erythrocytes are rare, the rates of leukopenia, neutropenia, and thrombocytopenia are highly variable. In a hospital drug monitoring program, leukopenia or neutropenia occurred in 0.4% of 1809 patients treated with co-trimox-azole (54), and thrombocytopenia of mild-to-moderate degree in 0.1% (54,55), similar to figures recorded in other studies (56,57). Pancytopenia is an extremely rare form of adverse reaction to sulfonamides (58). 

Agranulocytosis (probably due to toxicity rather than hypersusceptibility) can be caused by sulindac (13), as can bone marrow aplasia (14) and severe thrombocytopenia (15,16), which may be the consequence of autoimmune platelet destruction in the presence of sulindac or its metabolite (SEDA-7, 109). Immune-mediated hemolytic anemia with a positive direct antiglobulin test has been reported (SEDA-18,103). 

Starzl T. Acute hemolytic anemia in liver and bone marrow transplant patients under FK 506 therapy. Transplant Proc 1991 23(6) 3190-2. 

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. 

Adverse effects of thiacetazone include bone marrow depression and hemolytic anemia. It can also cause serious skin rashes. Continuous laboratory and clinical observations are required (1). 

Adverse effects of thiacetazone include bone marrow depression, with anemia, leukopenia, agranulocytosis, and thrombocytopenia (2-4). Hemolytic anemia has also been described (5). 

Zeigler ZR, Rosenfeld CS, Andrews DF 3rd, et al. Plasma von Willebrand Factor Antigen (vWF AG) and thrombomodulin (TM) levels in Adult ThromboticThrombocytopenic Purpura/Hemolytic Uremic Syndromes (TTP/HUS) and bone marrow transplant-associated thrombotic microangiopathy (BMT-TM). Am J Hematol 53 213-20,1996. 

Unusual immune side-effects have also been reported in association with IFNa therapy. Chronic hemolytic uremic syndrome was observed in a patient with multiple myeloma treated with IFNa (De Broe ME, personal communication). The post bone marrow transplantation course was complicated and he received several nephrotoxic antibiotics. Three months later a treatment with IFNa was started. Towards the end of the treatment renal function deteriorated. There was partial renal recovery after cessation of therapy. Renal biopsy showed focal mesangio-capillary lesions, mesangiolysis and intracapillary thrombosis consistent with a chronic form of hemolytic uremic syndrome. Ra-vandi-Kashani et al. [49] and Harvey et al. [50] reported 3 other cases of HUS/TTP. Two patients developed renal failure requiring dialysis. E. coli OH157.H7 was grown from the stool of one patient. 

D Ribavirin causes dose-related hemolytic anemia. Metabolites of ribavirin accumulate within the RBG, which cause cell damage. Although interferon can cause anemia, it is usually the result of bone marrow suppression. Hemolytic anemia tends to occur within 1 to 2 weeks after initiation of therapy. It is recommended that a baseline hematocrit and hemoglobin be checked prior to therapy and then regularly during therapy. 

Bone marrow depression peripheral neuropathy hearing loss transient cortical blindness hemolytic anemia... 

Chemically induced hemolytic anemia, bone marrow depression, thrombocytopenia Hypersensitivity pneumonitis, rheumatoid disease, sarcoidosis, vasculitis Contact dermatitis, sarcoidosis, energy, delayed hypersensitivity... 

Adverse/Toxic Long-term therapy may result in acidotic state. Nephrotoxicity/hepatotoxicity occurs occasionally, manifested as dark urine/stools, pain in lower back, jaundice, dysuria, crystalluria, renal colic/calculi. Bone marrow depression may be manifested as aplastic anemia, thrombocytopenia, thrombocytopenic purpura, leucopenia, agranulocytosis, hemolytic anemia. 

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... 

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