Hemolytic plasma

Arginine Hyperargininemia LPI Urea cycle defects, HHH syndrome Hemolytic plasma ... 

Glutamic acid Hemolytic plasma Stored plasma Ca-levulinate treatment ... 

Knowledge of the biochemistry of the porphyrins and of heme is basic to understanding the varied functions of hemoproteins (see below) in the body. The porphyrias are a group of diseases caused by abnormalities in the pathway of biosynthesis of the various porphyrins. Although porphyrias are not very prevalent, physicians must be aware of them. A much more prevalent clinical condition is jaundice, due to elevation of bilirubin in the plasma. This elevation is due to overproduction of bilirubin or to failure of its excretion and is seen in numerous diseases ranging from hemolytic anemias to viral hepatitis and to cancer of the pancreas. 

Many of the toxins obtained from coelenterates and echinoderms, because of their hemolytic or cytotoxic actions, are assumed to have a general disruptive action on cell membranes. However, since many of these toxins are capable of forming pores or channels in the plasma membrane of cells, their cytolytic actions may be a result of this highly selective action. On the other hand, the saponins from starfish and sea cucumbers have a direct lytic action as a result of their detergent action on the integrity of cells. 

In an attempt further to elucidate the anhaptoglobinemia in patients with anemia, Nyman (N7) studied the plasma Hp in 335 cases of anemia (Hb less than 11 g/lOOml) mainly from a department of internal medicine. The partition she found (Table 2) is instructive from a pathophysiological point of view. The frequency of subnormal Hp values found within the different diagnostic groups may fairly well reflect the hemolytic trait in tire different types of anemia. Subnormal Hp possibly secondary to the increased red cell destruction is a common finding also in polycythemia. 

Although normally present in normal human plasma in abundance ( 0.6 mg/ml, 10 pM) (27-30), concentrations ofhemopexin are sensitive to a variety of pathological conditions. Decreased levels have been noted in chronic and severe hemolytic states (31) and in heme infusion of acute intermittent porphyria patients (32). On the other hand, hemopexin levels increase in the acute-phase response (33-36), and hemopexin has been designated as a type II acute-phase reactant. Plasma hemopexin also increases in certain conditions of muscle breakdown and neuromuscular disease (37). 

Immunoglobulin obtained from pooled plasma obtained from hepatitis B and HIV negative donors is used as an aspecific immunostimulant in immunodeficiency diseases, idiopathic thrombocytopenia, autoimmune hemolytic anemias, Kawasaki syndrome and to prevent infections in immune compromised patients with leukemia or multiple myeloma. Adverse effects include potentially severe hypersensitivity reactions. 

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. 

Folic acid deficiency, unlike vitamin B12 deficiency, is often caused by inadequate dietary intake of folates. Patients with alcohol dependence and patients with liver disease can develop folic acid deficiency because of poor diet and diminished hepatic storage of folates. Pregnant women and patients with hemolytic anemia have increased folate requirements and may become folic acid-deficient, especially if their diets are marginal. Evidence implicates maternal folic acid deficiency in the occurrence of fetal neural tube defects, eg, spina bifida. (See Folic Acid Supplementation A Public Health Dilemma.) Patients with malabsorption syndromes also frequently develop folic acid deficiency. Patients who require renal dialysis develop folic acid deficiency because folates are removed from the plasma during the dialysis procedure. 

Specific proteins can be covalently attached via a carbohydrate bridge to membrane-bound PI (glycosylphosphatidylinositol, or GPI). This allows GPI-anchored proteins rapid lateral mobility on the surface of the plasma membrane. A deficiency in the synthesis of GPI in hematopoietic cells results in a hemolytic disease, paroxysmal nocturnal hemoglobinuria. 

It is generally accepted that in normal subjects, most, but not necessarily all, of the bilirubin formed results from the breakdown of hemoglobin in the reticuloendothelial system. The bilirubin is then conjugated in the liver and excreted into the bile as a water-soluble pigment. The capacity of the liver to conjugate bilirubin is limited (W6), so that in cases of overproduction (e.g., hemolytic jaundice) free bilirubin will appear in the plasma. A similar result will be obtained if the ability of the liver to conjugate bilirubin is diminished (e.g., in the newborn infant). On the other hand, if the excretion of the bile is for some reason... 

In a small proportion of cases of hemolytic disease of the newborn (inspissated bile syndrome), large amounts of conjugated bilirubin as well as free bilirubin accumulate in the plasma due to obstruction (J3, L2, S16). Conjugated bilirubin is apparently nontoxic to the brain so that exchange transfusions in such infants are indicated only if the free bilirubin and not the total bile pigment concentration is rising above 20 mg/100 ml plasma. 

I. LCAT deficiency. Cholesterol associated with HDL cannot be esterified. There is a buildup of unesterified cholesterol, with comeal opacities, renal insufficiency, hemolytic anemia, and premature atherosclerosis. The diagnosis may be made on enzyme assay for plasma LCAT. 

Favorable results of exchange transfusion in a variety of diseases in adults, for example sickle cell disease, severe clotting disorders, hepatic failure, and acute hemolytic transfusion reactions, have been published (1). Today, however, machine apheresis procedures are more effective and safer for patients requiring exchange of cellular elements or plasma. Exchange transfusion is the most effective therapeutic procedure in the treatment of hemolytic disease of the newborn. Bilirubin removal prevents damage to the central nervous system caused by hyperbilirubinemia. In addition, sensitized erythrocytes are replaced by normally surviving cells and anemia is corrected. 

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