Hemolysis intravenous

Homogenates of MetruUum senile, possibly the world s most common large sea anemone, yield extracts that are powerfully hemolytic for washed mammalian erythrocytes (22). The active substance, metridiolysin, is a protein of molecular weight approximately 80,000. In contrast to the sphingomyelin-inhibitable toxins, metridiolysin is an acidic protein having a pi of about 5. It is thermolabile and is inactivat by proteolytic enzymes. The optimal pH for hemolysis is between 5 and 6, and at pH 8 the lysin is inactive. It can be dissociated into two subunits of unequal size. Besides being cytolytic in vitro, metridiolysin is lethal when injected intravenously into mice. As shown in Table IV erythrocytes from the horse or dog are about a hundred times as sensitive to lysis as those from the mouse, and erythrocytes from other animals tested are intermediate in sensitivity. 

It is important that injectable solutions that are to be given intravenously are isotonic, or nearly so. Because of osmotic pressure changes and the resultant exchange of ionic species across red blood cell membranes, nonisotonic solutions, particularly if given in quantities larger than 100 mL, can cause hemolysis or cre-nation of red blood cells (owing to hypotonic or hypertonic solutions, respectively). Dextrose, sodium chloride, or potassium chloride is commonly used to achieve isotonicity in a parenteral formula. 

Embolism is another possible complication of the IV route. Particulate matter may be introduced if a drug intended for intravenous use precipitates for some reason, or if a particular suspension intended for IM or SC use is inadvertently given into a vein. Hemolysis or agglutination of erythrocytes may be caused by injection of hypotonic/hypertonic solutions, or by more specific mechanisms (Gray, 1978). 

Osmotic diuretics are used to increase water excretion in preference to sodium excretion. This effect can be useful when avid Na + retention limits the response to conventional agents. It can be used to maintain urine volume and to prevent anuria that might otherwise result from presentation of large pigment loads to the kidney (eg, from hemolysis or rhabdomyolysis). Some oliguric patients do not respond to osmotic diuretics. Therefore, a test dose of mannitol (12.5 g intravenously) should be given before starting... 

Typically, in this Lrstn vivo pharmacokinetic screening, both intravenous and oral formulations are administered to a rodent species, predominantly rats. If it is possible, the same formulation should be used for both intravenous and oral arms. Although in the discovery phase it is preferable to use low volume, high-concentration cosolvent formulations to increase solubility and hence the amount of drug dosed, it does have increased risks of hemolysis and tissue irritation when administered intravenously. Therefore, cautions need to be taken not to exceed the toxicity levels for the cosolvent. 

It was found that unloaded PEBPBLA micelles cause no hemolysis, even at a level of 0.70 mg/mL. PECb-PBLA has an extremely low critical micelle concentration (Kwon et al., 1993), and thus, there is little monomeric PBEPBLA for the lysis of lipid bilayer membranes. In addition, PEO-bPBLA micelles may break apart slowly to monomers. The lack of hemolytic activity of PEO-bPBLA contrasts strongly with other amphiphiles used for drug solubilization and intravenous drug administration. Sodium deoxycholate causes 100% hemolysis at a level of 0.32 mg/mL. This is due to disruption of lipid bilayer membranes of red blood cells. 

Inhibition of immune hemolysis by berberine was described by Tanaka (505). Subcutaneous or intravenous injections of berberine either in single doses or repeatedly did not affect the number of erythrocytes, leukocytes, and the hemoglobin level of intact rabbits (506). In rabbits, with anemia induced by phenylhydrazine and toluenedia-mine, berberine had an antianemic effect. Hasegawa and Tanaka (507) did not observe any effect of berberine on the production of plasma cells. It decreased the anticoagulant action of heparin in dog and human blood in vitro (508). Morthland (509) carried out a spectrophotometric study of the interaction of nucleic acids with aminoacridine or with other basic stains including berberine. 

Quinine is a cinchona alkaloid that acts rapidly against all four species of Plasmodium. It is used to treat protozoal infections and leg cramps, and as a bitter and flavoring agent. However, the drug is not used prophylactically for malaria. Quinines are contraindicated in patients with a history of hypersensitivity to quinine or quinidine. They should not be used in the presence of hemolysis and should be used with caution in patients with atrial fibrillation, cardiac conduction defects, or heart block. Quinine administration in myasthenia gravis may aggravate the disease, hence it should be avoided. Quinine can be used in pregnancy.37 Intravenous infusion of quinine should be slow, and the patient should be monitored for cardiotoxicity.38 Cinchonism, which is characterized by tinnitus, GI disturbances, and impaired vision may occur with therapeutic doses of quinine.39... 

Chlorhexidine occasionally causes skin sensitivity. Hemolysis has been reported following accidental intravenous administration.1123 It may damage safe tissues such as the eye. Chlorhexidine is an irritant and should not be used for sensitive tissues. Contact with the eyes should be avoided, as it will cause corneal damage. Syringes sterilized with chlorhexidine must be cleaned perfectly before using for other purposes. Aqueous solutions of chlorhexidine used for the storage of instruments should contain sodium nitrite (0.1%) to inhibit metal corrosion and should be required to be changed every week. 

These observations have several important practical implications. First, hospitals must store red blood cells in a plasma solution which has the correct proportions of salts and proteins. The plasma solution is made to be slightly hypertonic to the red cells so that the integrity of the cells is preserved and hemolysis is prevented. Second, when doctors inject a drug intravenously into a patient, the drug is suspended in a saline solution which is slightly hypertonic to red blood cells. Intravenous injection of a drug in pure water will cause some of the patient s red blood cells to hemolyze because water is hypotonic to the red blood cells. 

Non-IgE-antibody-mediated immunological reactions Modification of erythrocyte surface components due to binding of beta-lactams or their metabolic products is thought to be the cause of the formation of antierythrocyte antibodies and the development of a positive Coombs test implicated in the development of immune hemolytic anemia (211). About 3% of patients receiving large doses of intravenous penicillin (10-20 million units/ day) will develop a positive direct Coombs test (212). However, only a small fraction of Coombs positive patients will develop frank hemolytic anemia (213). Antibody-coated erythrocytes are probably eliminated by the reticuloendothelial system (extravascular hemolysis) (214), or less often by complement-mediated intravascular erythrocyte destruction (215). Another mechanism implicates circulating immune complexes (anti-beta-lactam antibody/beta-lactam complexes), resulting in erythrocyte elimination by an innocent bystander mechanism (82). Similar mechanisms have been implicated in thrombocytopenia associated with beta-lactam antibiotics (216,217). 

A 76-year-old Japanese man, who had been given 23 courses of intravenous antibiotic therapy over 2 years for chronic bronchitis, was given intravenous ceftizoxime 1 g/day. He developed anaphylactic shock and hemolysis. Despite very extensive therapy he died 2 weeks later. 

Ceftriaxone has been associated with autoimmune hemolytic anemia, erythroblastocytopenia, and acute hepatitis (56). The ceftriaxone in this case was given intravenously and not orally, as erroneously published (written communication from the authors). Other cases of hemolysis have been reported after ceftriaxone (57). 

A 14-year-old girl, perinatally infected with HIV, had a medical history of recurrent infections that had been treated with several antibiotics, including ceftriaxone. She was given ceftriaxone (60 mg/kg intravenously) for pneumonia and 30 minutes later complained of severe back pain, became nauseated, vomited, and collapsed. Despite intensive medical care she died within a few hours with massive intravascular hemolysis and disseminated intravascular coagulopathy. Autopsy was refused. 

A 47-year-old multiparous Hispanic woman received a living-unrelated kidney transplant for end-stage renal disease secondary to polycystic kidney disease. On the day of transplantation she received intravenous daclizumab 1 mg/kg plus methylprednisolone 300 mg and mycophenolate mofetil 3 g/day, and on day 3 ciclosporin emulsion 4 mg/kg/day. On day 8 she developed thrombotic microangiopathy without evidence of rejection. Ciclosporin was withdrawn. Plasmapheresis with fresh frozen plasma was started. Daclizumab on day 14 was postponed for 24 hours and plasmapheresis was stopped to avoid clearance of daclizumab. Thereafter she was given tacrolimus, without recurrence of hemolysis. 

A patient who had been taking dapsone inappropriately instead of an antispasmodic that had been prescribed for a spinal condition, because of incorrect labeling in a pharmacy, developed methemoglobinemia (24). Methylene bine was given intravenously and may have contribnted to the severe hemolysis that followed. 

Intravenous dimethylsulfoxide poses the greatest problems and causes transient systemic hemolysis with hemoglobinuria, but without gross hematuria. The hemolysis is dose-dependent and appears within several minutes after infusions of dimethylsulfoxide 20-40% (11). There was no evidence of kidney damage because of handling higher amounts of hemoglobin after hemolysis. 

The most common adverse effects of fusidic acid are minor and are related to the gastrointestinal tract (discomfort, diarrhea). Rare adverse events include granulocytopenia, thrombocytopenia, venous spasm, and skin reactions (4). Fusidic acid has detergent properties and can cause hemolysis when injected intravenously or can induce tissue damage when given intramuscularly. However, its systemic toxicity is relatively low. 

Intravascular hemolysis occurred during intravenous glycerol therapy in patients with acute stroke (12). 

Propylene glycol causes acute hemolysis with raised lactate dehydrogenase activity, and raised bilirubin and plasma hemoglobin concentrations after use of a stock solution during intravenous administration of glyceryl trinitrate (11). 

Severe acute hemolysis due to acquisition of red cell alloantibodies from donor serum has been reported (67-69). In other cases, the suggested mechanism of hemolytic anemia after high dosages of intravenous immunoglobulin was the presence of anti-A and/or anti-B antibodies in the plasma product (70). 

Comenzo RL, Malachowski ME, Meissner HC, Fulton DR, Berkman EM. Immune hemolysis, disseminated intravascular coagulation, and serum sickness after large doses of immune globulin given intravenously for Kawasaki disease. J Pediatr 1992 120(6) 926-8. 

Intracranial hypertension associated with glyceryl trinitrate has been reported and attributed to cerebral vasodilatation (47). However, it may occasionally be a consequence of hyperosmolality, hemolysis, and lactic acidosis caused by the excipient ethylene glycol used with intravenous isosorbide dinitrate. The risk of this may be greatest in patients with renal impairment (48). 

Hemolysis after intravenous streptokinase is rare (33). Transient lymphopenia, possibly related to immunological destruction of T-helper cells by streptokinase, has been described (34). 

The toxic effects on the kidneys occur via the induction of acute intravascular hemolysis with the development of acute tubular necrosis. One of the cases mentioned above, who administered the copper sulphate intravenously, had a kidney biopsy 8 weeks following on from presentation and this showed... 

Intravascular hemolysis and biochemical changes and reversible neurological deterioration have been reported following intravenous administration however, it has been questioned whether these findings were directly attributable to dimethyl sulfoxide rather than to concomitant drug therapy or contaminants. " Recently, a hypersensitivity reaction attributed to dimethyl sulfoxide has been reported. ... 

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