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The hemolytic anemias.

Hemolytic anemias usually present with persistent reticulocytosis, a characteristic that differentiates them from other types of anemia. Once the presence of a hemolytic process has been documented, simple observation of red blood cell morphology will yield important etiologic information. Hemolysis may result from inherent defects in the red cell or from excessive environmental stress on normal cells. Immune mechanisms of hemolysis should be investigated early because of the frequency of their occurrence.

Anemia, Hemolytic

Prognostic importance of vascular lesions in acute renal failure with microangiopathic hemolytic anemia (hemolytic-uremic syndrome): clinicopathologic study in 20 adults.

Renal biopsies obtained from 20 adult patients within 30 days after onset of acute renal failure with microangiopathic hemolytic anemia ("the hemolytic-uremic syndrome") were studied. Lesions were graded independently by two observers without knowledge of the clinical history. All patients who did not have refractory hypertension were treated with heparin. Ten of the patients died, and four developed end-stage renal failure requiring chronic dialysis. Six patients, however, had a relatively good outcome: two recovered completely and four developed mild-to-moderate chronic renal failure not requiring dialysis. The six patients with a good outcome had significantly less severe arterial intimal thickening on biopsy compared with the remaining patients with a poor outcome. The patients with a good outcome and those with a poor outcome did not differ in the severity of glomerular lesions. The clinical features did not allow a prediction of late outcome. These results suggest that early renal biopsies may be helpful in predicting prognosis in the "hemolytic-uremic syndrome." This clinical syndrome may occur either in apparently healthy people, or may complicate the course of a chronic essential hypertension.

Acute Kidney Injury

Grand rounds: autoimmune hemolytic anemia.

Autoimmune hemolytic anemia (AHA) may be either primary (ie, "idiopathic," one third of all patients) or secondary (ie, associated with underlying illness, two thirds of all patients). A positive Coombs antiglobulin test is the most important criterion for diagnosis of AHA, and characterization of RBC coating (as to whether it is by IgG alone, by IgG plus complement, or by complement alone) may be valuable in ruling out certain underlying illnesses as causative in selected patients. Many limitations to the antiglobulin test must be kept in mind. As routinely performed, a positive result requires greater than 500 molecules of IgG per RBC. Red blood cells from normal subjects have less than 35 molecules of IgG per RBC. Up to 2% to 5% of patients with AHA will have RBC coating in the 50 to 500 molecules per cell range and may therefore have "false"-negative antiglobulin tests. Apparent failures of strength of antiglobulin reactions to correlate with severity of in vivo RBC destruction may result from technical factors or may reflect intrinsic differences among autoantibodies (eg, IgG subclass, affinity). A likely mechanism of in vivo RBC destruction in AHA has been demonstrated in immune-mediated in vitro RBC "rosette" formation about macrophages and lymphocytes bearing specific receptors for subclasses of IgG and for subcomponents of complement. Increased avidity of macrophages for coated RBCs in response to such stimulus as infection may play an additional role. Treatment involves control of underlying disease and the judicious use of adrenal steroids, splenectomy, and immunosuppressive agents. Transfusions, while life-saving in life-threatening anemia, carry substantially increased risks in AHA patients. Their use should be strictly limited.

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Refractory sideroblastic anemia secondary to autoimmune hemolytic anemia.

A 75-year-old woman was hospitalized with autoimmune hemolytic anemia. During a period of 22 months the patient had six hemolytic crises which responded to treatment with prednisone and azathioprine. During the last admission the patient presented a sideroblastic anemia with 98% of 'ring sideroblasts' in the bone marrow. This association has never, to our knowledge, been reported before. It is possible that the immunosuppression played a definite role in the development of this sideroblastic anemia.

Aged

Coombs--negative immune hemolytic anemia.

An immune hemolytic anemia occurs in a few patients in whom the concentration of antibody on the red cell is below the level for detection by the usual antiglobulin test. Clinically, these patients are identical to patients with warm type Coombs-positive hemolytic anemia, except for the quantity of antibody on the cell. The course of the hemolytic disease is highly variable. It is postulated that the properties of the antibody in conjunction with the sensitivity of the reticuloendothelial system for antibody-coated cells account for hemolytic anemia occurring with such low concentrations of antibody. The response to steroid therapy and splenectomy, when indicated, is usually favorable.

Anemia, Hemolytic, Autoimmune

[Immunomechanisms in drug-induced hemolytic anemias].

Among the acquired hemolytic anemias, drug-induced immune hemolytic anemias (IHA) play a significant role. Many different drugs are capable of causing IHA, alphamethyldopa and penicillins have been responsible for the greatest number of cases. For the majority of the other drugs single cases of IHA are reported. Drug-induced immune hemolysis may be mediated by different immune mechanisms including the immune cytotoxicity type (penicillins and cephalosporins) with predominantly extravascular hemolysis. Immune hemolysis of most other drugs is due to immune complexes formed by the drug and specific antibodies leading to intravascular hemolysis in the presence of complement activation. So far, the autoimmune type of IHA caused by alphamethyldopa is unexplained, serologically this form cannot be distinguished from warm antibody auto-IHA. The clinical importance of drug-induced IHA depends on the severity of anemia and the problem of diagnosis leading to adequate therapeutic measures. Only a small number of cases showing a positive direct antiglobulin (Coombs') test caused by drugs will develop IHA. Therefore this finding does not require absolutely withdrawal of the drug, but careful observation of the patient. The diagnosis of drug-induced IHA is necessary for its distinction from auto-IHA and other secondary IHA. The study of such IHA has great importance for the understanding of other drug-induced cytopenias and may give explanations of the pathogenetic mechanisms of yet unexplained autoimmune phenomena.

Anemia, Hemolytic, Autoimmune

[Hemolytic anemia].

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Anemia, Hemolytic

Hemolytic anemia in patients receiving sulfasalazine.

Hemolytic anemia is a well-recognized complication of sulfasalazine treatment. 17 of 40 (43%) patients with inflammatory bowel disease receiving sulfasalazine had evidence of hemolysis as detected by starch gel electrophoresis. Only 47% (8) of patients with hemolysis had Heinz body formation. The hemoglobin was significantly reduced in patients with hemolysis and 53% had a reticulocyte count of greater than 5%. A significant correlation was noted between hemolysis and serum sulfapyridine level, but no correlation was seen with serum sulfasalazine level. There was no significant difference in disease extent or activity in patients with hemolysis compared to those without hemolysis. Hemolysis is not a rare side-effect of sulfasalazine therapy. Heinz body formation is not invariably found in sulfasalazine-induced hemolysis.

Anemia, Hemolytic