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Biomedical subjects

D Goldfinger

Publications and source records attributed to D Goldfinger.

72 records · Page 4Linked to original sources

The phenotypes En(a-), Wr(a-b-), and En(a+), Wr(a+b-), and further studies on the Wright and En blood group systems.

In 1975, we showed 18, 19 an En(a-) blood sample to be phenotypically Wr(a-b-). In the current report, we describe tests that show that three En(a-) members of a single family, not believed to be related to the family of the previously tested En(a-) person, are also Wr(a-b-). They have red blood cells that neither react with nor adsorb anti-Wra or anti-Wrb. In addition, we have shown that the red blood cells of six EnaEn heterozygotes, in the family tested, are Wr(a-b+) but carry only a single dose of Wrb antigen. Tests on anti-Ena have shown conclusively that one example is a mixture of separable anti-Ena and anti-Wrb and that a second example may well contain the same two antibodies. By various methods, we have demonstrated that the red blood cells of the only known Wr(a+b-) individual are En(a+) and do not display any of the physicochemical abberations of the En(a-) phenotype. It is further shown that neuraminidase and trypsin do not denature the Wra or Wrb antigens in vitro, but that the protease ficin does have a limited ability to denature Wrb. Additional observations on the first reported example of anti-Wrb are included. These various findings have been considered in the light of gene linkage of, or gene interaction between, the En and Wright system genes. It is concluded that the evidence does not exclude the possibility that En is a silent allele at the WraWrb locus so that the genotype EnEn (or WrWr) might result in the phenotype En(a-), Wr(a-b-). However, it is also pointed out that the evidence equally well supports the postulation that the Wra and Wrb genes are unable to function in the absence of an Ena gene. If this latter theory is proved correct, the interaction between Ena and the Wright genes can be thought of as similar to that between the H and ABO or X1r and CDE genes. It is pointed out that if En is a silent allele at the MN locus (current evidence on this point is not conclusive,) En and Wr cannot be synonymous for it is known that the Wra and M and N genes segregate independently. Location of En at the MN locus would not, however, refute the theory that Wra and Wrb cannot function in the absence of En. Finally, it is pointed out that the supposed anti-Wrb is probably just what its name implies but that even if this assumption is later disproved, the high incidence antigen defined by the antibody presently called anti-Wrb is unequivocally associated with Ena.

Blood Group Antigens↗

Acute hemolytic transfusion reactions--a fresh look at pathogenesis and considerations regarding therapy.

A review of our knowledge of acute hemolytic transfusion reactions indicates that we have learned much in recent years about the pathogenetic mechanisms involved. An approach to effective therapy for patients suffering such reactions should be based on our latest understanding of the pathophysiology of this syndrome. However, changes in our therapeutic approach have not kept abreast of our increased awareness of the etiologic factors, and the patient, therefore, is not getting the benefit of our increased knowledge in this area. The primary pathogenetic mechanisms involved in these reactions appear to be disseminated intravascular coagulation and a series of hemodynamic alterations leading to ischemic necrosis of tissues. Therapy would best be aimed at interfering with these primary pathophysiologic pathways.

Acute Kidney Injury↗

Autoimmune hemolytic anemia associated exclusively with IgA of Rh specificity.

A nine-year-old boy had typical clinical, hematologic and blood group serologic findings of autoimmune hemolytic anemia except for one important exception; with most commercially available broad spectrum anti-human sera the direct antiglobulin tests were negative. With reagents prepared in the laboratory which were found to be relatively less potent in and anti-IgG and IgM activity but which utilize a short period of incubation after mixing with the washed cells, the tests were all clearly positive. If incubation were employed with the commercial reagents, the tests were positive. Further studies showed that the patient's cells were coated exclusively with IgA and that a commercial reagent, although potent in anti-IgG and anti-IgM, was relatively deficient in anti-IgA. It is proposed that incubation compensates for the latter and is cautioned that incubation, with reagents potent in anti-IgG, could lead to false negative reactions with weakly IgG sensitized cells due to antibody surplus prozones of inhibition. This case illustrates that the rare instances of "Coombs negative immune hemolytic anemias" may be based on mechanisms such as those reported here and, that to be ideal, a broad spectrum anti-human serum should have balanced anti-immunoglobulin activities in relation to its incubation time.

Anemia, Hemolytic, Autoimmune↗

Long-term plateletpheresis in the management of primary thrombocytosis.

We attempted to control the platelet count of a patient with primary thrombocytosis utilizing long-term plateletpheresis therapy. The patient previously could not be controlled with chemotherapy, because of rapid development of leukopenia. Although intensive pheresis at the rate of four to five procedures per week produced rapid lowering of the patient's platelet count, continued therapy at the rate of two to three procedures a week failed to maintain these counts, and platelets gradually rose to pretreatment levels. We conclude that while plateletpheresis can produce acute lowering of elevated platelet counts, the rate of platelet production in primary thrombocytosis may be too rapid to allow for long-term control by pheresis alone, utilizing an acceptable treatment schedule of one of three procedures per week.

Blood Transfusion↗

Treatment of renal allograft rejection by exchange plasma-lymphocytapheresis.

Therapy for acute renal allograft rejection generally consists of administration of high doses of corticosteroids along with cytotoxic drugs. Failure of this treatment usually dictates removal of the graft. We describe a patient who was rejecting a renal transplant from his HLA-identical, mixed lymphocyte culture-compatible brother. This acute rejection episode was unresponsive to three days of therapy with high doses of steroids, azathioprine and coumadin. The patient rapidly improved following intensive exchange plasmapheresis and lymphocytapheresis. This therapy produced depletion of immunoglobulins, complement components, coagulation factors and circulating lymphocytes, and resulted in dramatic improvement in renal function and reversal of the rejection crisis. We suggest that intensive pheresis may represent an important adjunct to currently available therapy for the treatment of acute renal allograft rejection.

Adult↗

Use of long-term leukapheresis in the treatment of chronic lymphocytic leukemia.

We used repeated leukapheresis in the long-term management of chronic lymphocytic leukemia. Twelve patients with far-advanced disease that was refractory to standard forms of therapy, were studied. Six patients completed a predefined course of therapy. Although a single patient responded favorably for a period of time, no other patient was benefited by this treatment. While circulating lymphocyte counts in these patients always could be reduced, generally, this was not associated with improvements in pancytopenia, hypogammagobulinemia, adenopathy, organomegaly, or constitutional symptoms of lethargy, fevers and night sweats. Mean survival was only ten months from onset of therapy. We conclude that long-term leukapheresis is ineffective in the management of far-advanced chronic lymphocytic leukemia.

Agammaglobulinemia↗

Prevention of adverse reactions to blood transfusion by the administration of saline-washed red blood cells.

We prospectively compared the incidence of complications following saline-washed versus packed red blood cell transfusions, to determine whether routine use of washed red blood cells could reduce significantly the incidence of transfusion reactions. Clinical reports of reactions were evaluated carefully to confirm whether the reaction was caused by transfusion. In 3,799 washed red blood cell transfusions, there were eight confirmed reactions (0.21%). Of 6,359 packed red blood cell transfusions, 31 reactions occurred (0.49%). The difference in incidence of confirmed complications was statistically significant (p less than 0.03). Administration of washed red blood cells to all patients requiring transfusions can thus be seen to reduce significantly the incidence of adverse reactions. This is likely the result of the removal of leukocytes and plasma achieved by the washing process. The increased safety of washed red blood cells must be weighed against their extra expense to determine their cost-effectiveness in transfusion therapy.

Blood Preservation↗

Exchange red blood cell pheresis in a pediatric patient with severe complications of sickle cell anemia.

Exchange transfusion is a well-established procedure for the treatment of severe complications of sickle cell anemia. However, large-volume exchange is a difficult, time-consuming technique, and therefore rarely used. Exchange red blood cell pheresis, using automated equipment, can accomplish red blood cell exchange more rapidly and efficiently, and can be easily performed by a skilled team of nursing personnel. The recent introduction of a pediatric centrifuge bowl allows this technique to be applied to pediatric patients. This procedure was used in a 13-year-old male with sickle cell anemia, who presented with bilateral pulmonary infiltrates, respiratory distress, and hypoxemia, unresponsive to antibiotics and other means of conservative therapy. A one and one-half volume red blood cell exchange reduced the hemoglobin S concentration to 13 per cent. The patient experienced dramatic improvement within 24 hours, progressing to complete recovery within a few days.

Adolescent↗

Safety of autologous blood donation prior to elective surgery for a variety of potentially "high-risk" patients.

We studied 342 potentially "high-risk" patients, including patients with severe heart disease, elderly patients, children, and pregnant women, to determine the incidence of complications related to phlebotomy. Our patients had an adverse reaction rate associated with blood donation of 4 percent, which is no greater than would be expected among normal volunteer blood donors. No patient experienced a dangerous complication associated with phlebotomy. We conclude that many patients currently denied the opportunity to donate blood preoperatively are actually suitable candidates for autologous blood transfusion programs.

Adult↗

Preparation and in vitro function of granulocyte concentrates for transfusion to neonates using the IBM 2991 blood processor.

Clinical studies have suggested that granulocyte transfusions may be of value in the treatment of septic neonatal patients who present with severe granulocytopenia. We have developed a protocol for the preparation of granulocyte concentrates from freshly collected units of whole blood, using an automated blood cell processor. The red cells were washed with saline. Then, the buffy coats were collected from the washed red cells and studied for their suitability as granulocyte concentrates for neonatal transfusion. The mean number of granulocytes per concentrate was 1.6 X 10(9) in a mean volume of 25 ml. Studies of granulocyte function, including viability, random mobility, chemotaxis, phagocytosis and nitro-blue tetrazolium reduction, demonstrated that the granulocytes were functionally unimpaired following preparation of the concentrates. These studies suggest that concentrates of functional granulocytes, suitable for transfusion to neonatal patients, can be prepared from fresh units of whole blood, using a cell processor. This procedure is more cost-effective than leukapheresis and allows for delivery of granulocytes for transfusion in a more timely fashion.

Blood Transfusion↗

Transfusion-associated noncardiogenic pulmonary edema. Report of a case and a warning regarding treatment.

Although noncardiogenic pulmonary edema (NCPE) is a recognized complication of blood transfusion, the precise etiology is not well understood. NCPE may be secondary to complement-mediated pulmonary capillary injury initiated by either donor or recipient anti-leukocyte antibodies. It is not caused by simple volume overload. Recent blood banking texts and published case reports continue to suggest diuretics as part of the initial therapy for this complication. We report a case of transfusion-associated NCPE in which empirical diuretic therapy clearly was detrimental and suggest that the use of diuretics for treatment of this condition is not warranted. Reversal of progressive hypoxemia is the mainstay of therapy. Hemodynamic monitoring is important in differentiating NCPE from pulmonary edema secondary to cardiac failure or volume overload and should be used as a guide for further therapy.

Adult↗

Clinical significance of anti-Yt(b). Report of a case using a 51chromium red cell survival study.

Several published reports have documented the variable survival of Yt(a+) red cells (RBC) in patients with anti-Yt(a) as measured by 51Chromium (Cr)-labeled RBC survival studies. Similar studies with anti-Yt(b) have not been reported. A 51Cr-labeled RBC survival study was performed using Yt(b+) RBCs and a monocyte monolayer assay in a young hemodialysis patient who required chronic transfusion therapy and who had developed anti-Yt(b). The survival of the transfused RBCs was 100 and 93 percent at 1 and 24 hours, respectively, with a half life of 21 days at termination of the study (normal, 28 to 32 days). These results showed no evidence of rapid destruction of the Yt(b+) RBCs, indicating that this patient could be transfused safely with blood from Yt(b+) donors. Long-term survival of the 51Cr-labeled Yt(b+) RBCs was shortened moderately, however, a finding that correlated with a slightly abnormal monocyte monolayer assay test.

Adult↗

Cisplatin-induced nonimmunologic adsorption of immunoglobulin by red cells.

Antibodies to cisplatin, an extensively used anticancer chemotherapeutic agent, have been implicated previously as a cause of immune hemolytic anemia. Investigation of a suspected case of cisplatin-induced hemolytic anemia in a 40-year-old man demonstrated that IgG could be adsorbed nonimmunologically by reagent red cells in vitro. This phenomenon was found to be a source of possible error in the interpretation of studies identifying specific cisplatin antibodies. Furthermore, cisplatin was found to be capable of producing a positive direct antiglobulin test (DAT), owing to the nonspecific adsorption of immunoglobulin and complement in vivo. Although this finding did not result in acute hemolysis, it may cause confusion in the investigation of DAT-positive hemolytic anemias. We question whether previous reports of cisplatin-induced hemolytic anemia are accurate in their assessment that such hemolysis was mediated immunologically. Future studies of suspected cases of hemolysis induced by this drug should include serologic investigation adequate to demonstrate the presence of specific cisplatin antibodies. A positive DAT in such patients should not be considered proof of drug-induced immune hemolytic anemia.

Absorption↗

Microaggregates in frozen and saline washed red blood cells.

The microaggregates which accumulate in stored blood have been implicated in the development of posttraumatic pulmonary insufficiency. These particles are known to be composed of degenerated leukocytes and platelets. Because frozen and saline washed red blood cells contain small numbers of leukocytes and platelets, they were studied as a possible source of microaggregate-free red blood cells. Using a Model T Coulter Counter to quantitate all particles 13-80 microns in size, it was shown that freezing and deglycerolization, or simple saline washing (manual or automated), could reduce the number of microaggregates in stored blood by 80 to 90 per cent. These findings add to a growing list of potential advantages in the routine use of frozen red cells for patients requiring transfusion.

Erythrocyte Aggregation↗

Ammonia accumulation in platelet concentrates during storage.

Newly prepared platelet concentrates (PC) and platelet poor plasma (PPP) stored at either room temperature (RT) or 4 C were analyzed for ammonia content initially, and after storage at 24, 48, and 72 hours. These studies demonstrate that ammonia rapidly accumulates in PC stored at RT. This accumulation appears to be temperature dependent, as evidenced by the observed differences in ammonia accumulation in PC stored at 4 C and RT. Whether ammonia acts as a toxic metabolite in the inhibition of platelet function and the development of the "storage lesion," which occurs in PC stored at RT, needs further clarification. Additional studies are also necessary to establish the clinical efficacy of transfusing ammonia-containing platelet concentrates into premature neonates with immature functioning livers, and perhaps into adults with severe liver disease.

Ammonia↗