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Biomedical subjects

Harvey G Klein

Publications and source records attributed to Harvey G Klein.

14 recordsLinked to original sources
PubMed2006

Apparent hemolysis following intravenous antithymocyte globulin treatment in a patient with marrow failure and a paroxysmal nocturnal hemoglobinuria clone.

BACKGROUND: Antithymocyte globulin (ATG) is a commonly used medication in the treatment of aplastic anemia. Although serum sickness has been described with the use of ATG, few cases of acute intravascular hemolysis have been reported. We report a case of apparent ATG-related hemolysis in a patient with aplastic anemia and a paroxysmal nocturnal hemoglobinuria (PNH) clone. CASE REPORT: A 62-year-old, group A, RhoD+ man with aplastic anemia and an 11.6 percent glycosylphosphatidylinositol (GPI)-anchored protein-negative population of red cells (RBCs), representing approximately 190 mL of his RBC volume, and 90 percent GPI-negative neutrophils were scheduled to receive equine ATG at 40 mg per kg per day for 4 days. After the first infusion, he developed a 1.6 g per dL decline in hemoglobin concentration and an increase in serum lactate dehydrogenase (normal, 113-226 U/L) from 284 to 1127 U per L. The hemolytic process was complicated by acute renal failure characterized by an increase in serum creatinine from 0.9 to 4.2 mg per dL and the appearance of dark-colored urine. Pre- and post-ATG direct antiglobulin tests were negative. CONCLUSION: The temporal association of intravenous ATG to lysis of complement-sensitive RBCs suggests a causal relationship. Although intravascular hemolysis after ATG administration appears to be uncommon, the clinical consequences may be severe, and determining the pathophysiology may yield clues to the mechanism of intravascular hemolysis.

Acute Kidney Injury↗
PubMed2006

In vivo efficacy of shipped HLA-matched platelets.

BACKGROUND: Platelet (PLT) concentrates are currently stored in an incubator at 20 to 24 degrees C with continuous gentle agitation. PLTs are routinely shipped for transfusion to thrombocytopenic patients, however. There is a concern that PLT concentrates may be adversely affected during the shipping process. CASE REPORT: A 40-year-old woman with severe aplastic anemia and immune refractory to unselected PLT transfusions was transferred to a distant medical center for a hematopoietic peripheral blood progenitor cell transplant where she continued to receive HLA-matched PLTs from her dedicated donors. Sixteen such components were collected and air-shipped in insulated boxes to the transplant center. Thirty-seven plateletpheresis components from the same dedicated donors had been transfused to the patient before transfer. Corrected count increments (CCIs) at the two sites were compared, with assessment of the role of HLA-match grades. The mean interruption time of controlled agitation during shipment was approximately 10.5 hours. The mean CCI of all distant transfusions was 14,450 +/- 9700 PLTs per microL x m2 per 10(11) and that of local transfusions was 10730 +/- 4870. The mean donor-paired difference between CCIs at the two sites was 1140 +/- 9940. At the remote location no clinically significant bleeding occurred and one posttransfusion febrile reaction was noted. CONCLUSION: Despite the study limitations, the effectiveness, in a single patient, of leukoreduced, irradiated apheresis PLTs shipped by lengthy combined surface and airline transport is reported, as measured by posttransfusion CCIs.

Adult↗
PubMed2004

Transfer of glycosylphosphatidylinositol-anchored proteins to deficient cells after erythrocyte transfusion in paroxysmal nocturnal hemoglobinuria.

In paroxysmal nocturnal hemoglobinuria (PNH), an acquired mutation of the PIGA gene results in the absence of glycosylphosphatidylinositol (GPI)-anchored cell surface membrane proteins in affected hematopoietic cells. Absence of GPI-anchored proteins on erythrocytes is responsible for their increased sensitivity to complement-mediated lysis, resulting in hemolytic anemia. Cell-to-cell transfer of CD55 and CD59, 2 GPI-anchored proteins, by red cell microvesicles has been demonstrated in vitro, with retention of their function. Because red cell units stored for transfusion contain many erythrocyte microvesicles, transfused blood could potentially serve as a source of CD55 and CD59. We examined whether GPI-anchored proteins could be transferred in vivo to deficient cells following transfusions given to 6 patients with PNH. All patients were group A(1) blood type. Each was given transfusions of 3 U of compatible, washed group O blood. Patient group A(1) cells were distinguished from the transfused group O cells by flow cytometry and staining with a labeled lectin, Dolichos biflorus, which specifically binds to group A(1) erythrocytes. Increased surface CD59 was measured on recipient red cells and granulocytes 1, 3, and 7 days following transfusion in all 6 patients. Our data suggest a potential therapeutic role for GPI-anchored protein transfer for severe PNH.

CD55 Antigens↗
PubMed2004

Prevalence of anemia in persons 65 years and older in the United States: evidence for a high rate of unexplained anemia.

Clinicians frequently identify anemia in their older patients, but national data on the prevalence and causes of anemia in this population in the United States have been unavailable. Data presented here are from the noninstitutionalized US population assessed in the third National Health and Nutrition Examination Survey (1988-1994). Anemia was defined by World Health Organization criteria; causes of anemia included iron, folate, and B(12) deficiencies, renal insufficiency, anemia of chronic inflammation (ACI), formerly termed anemia of chronic disease, and unexplained anemia (UA). ACI by definition required normal iron stores with low circulating iron (less than 60 microg/dL). After age 50 years, anemia prevalence rates rose rapidly, to a rate greater than 20% at age 85 and older. Overall, 11.0% of men and 10.2% of women 65 years and older were anemic. Of older persons with anemia, evidence of nutrient deficiency was present in one third, ACI or chronic renal disease or both was present in one third, and UA was present in one third. Most occurrences of anemia were mild; 2.8% of women and 1.6% of men had hemoglobin levels lower than 110 g/L (11 g/dL). Therefore, anemia is common, albeit not severe, in the older population, and a substantial proportion of anemia is of indeterminate cause. The impact of anemia on quality of life, recovery from illness, and functional abilities must be further investigated in older persons.

Age Factors↗
PubMed2003

Hemochromatosis subjects as allogeneic blood donors: a prospective study.

BACKGROUND: Persons with hemochromatosis constitute a plentiful and willing source of blood for transfusion. A program was established and evaluated for treating persons with hemochromatosis in a donor center and making their blood available for transfusion. STUDY DESIGN AND METHODS: Phlebotomy therapy was performed free of charge regardless of whether subjects met criteria for allogeneic donation. A Hb level of 12.5 g per dL was used as the threshold for performing phlebotomy, and decreases in the MCV were used to guide the endpoints of therapy. RESULTS: A total of 130 subjects were consecutively enrolled: 74 percent were homozygous for the C282Y mutation in the HFE gene, 76 percent met eligibility criteria for allogeneic donation, and 55 percent were previous blood donors. A median of 20 weekly or biweekly phlebotomies (range, 7-99) were performed before the MCV reached the targeted endpoint of 3 percent below baseline, at which time the ferritin level was less than 30 microg per L and the transferrin saturation was less than 30 percent. The median phlebotomy interval necessary to keep the MCV at this level during maintenance therapy was 10 weeks. No incident seroconversions for agents of transfusion-transmissible disease occurred during 1402 donations. All subjects testing positive for viral agents gave a prior history of deferrable risk. Twenty-seven months after starting the program, hemochromatosis donors were contributing 14 percent of the RBC units collected for allogeneic use. CONCLUSIONS: Hemochromatosis subjects can safely and significantly augment the allogeneic blood supply. Provision of phlebotomy therapy unrestricted by considerations of cost or suitability for donation can improve access to care and remove incentives for incomplete risk disclosure.

Adult↗
PubMed2002

Gene-expression profiling of the response of peripheral blood mononuclear cells and melanoma metastases to systemic IL-2 administration.

BACKGROUND: Interleukin-2 (IL-2) has direct pluripotent effects on cells with immune and inflammatory function. Which of these effects has a critical role in mediating tumor regression remains enigmatic. In this study, we compared early changes in transcriptional profiles of circulating mononuclear cells with those occurring within the microenvironment of melanoma metastases following systemic IL-2 administration. RESULTS: The results suggest that the immediate effects of IL-2 administration on the tumor microenvironment is transcriptional activation of genes predominantly associated with monocyte cell function; minimal effects were noted on migration, activation and proliferation of T cells. However, production of chemokines and markers of adhesion and migration within few hours of IL-2 administration may be responsible for a secondary recruitment of immune cells to the tumor site later. CONCLUSIONS: Our results suggest that IL-2 induces inflammation at tumor sites with three predominant secondary effects: activation of antigen-presenting monocytes; massive production of chemoattractants that may recruit other immune cells to the tumor (including MIG and PARC, which are specific for T cells); and activation of cytolytic mechanisms in monocytes (calgranulin, grancalcin) and NK cells (NKG5, NK4).

Antineoplastic Agents↗
PubMed2002

Sickle Hb polymerization in RBC components from donors with sickle cell trait prevents effective WBC reduction by filtration.

BACKGROUND: RBC components collected from donors with sickle cell trait frequently occlude WBC-reduction filters. In vitro, sickle trait RBCs have the potential for sickle Hb (Hb S) polymerization at low oxygen saturations and high Hb concentrations. STUDY DESIGN AND METHOD: To determine if the low pH and high osmolarity of the CP2D used in the collection contributed to filter failures, the filterability of sickle trait donor RBCs collected in CP2D was compared with RBCs from the same donors collected in heparin. RESULTS: Five of six sickle trait components collected in CP2D did not complete filtration, but all six RBC components collected in heparin filtered completely. RBC components collected in CP2D from four other sickle trait donors were divided in two, and one-half was treated with carbon monoxide to convert Hb S to its liganded form to prevent Hb S polymerization. All four carbon monoxide-treated components filtered within 9 minutes, but only one untreated component filtered completely. RBC components collected by apheresis contained less CP2D, and five of seven sickle trait apheresis components filtered completely; four of the five filtered rapidly (<15 min) and one filtered in 100 minutes. Hb oxygen saturation was greater in the four rapidly filtering apheresis RBC components (68 +/- 9%) than in the three that filtered slowly or incompletely (37 +/- 5%, p = 0.03). CONCLUSIONS: Hb S polymerization appears responsible for RBC WBC-reduction filter failures. Citrate anticoagulant and low oxygen saturation are responsible in part for Hb S polymerization in this setting.

Anticoagulants↗
PubMed2002

A puzzling case of anemia.

BACKGROUND: Iron deficiency anemia in adults is most frequently due to chronic blood loss. When the clinical course is complicated by sudden, severe declines in Hb concentration, the cause, nature, and lo- cation of bleeding may require an extensive clinical evaluation. CASE REPORT: A 39-year-old woman was admitted for management of refractory hypoparathyroidism related to total thyroidectomy for Graves' disease. Two weeks before admission, her Hb level was 7.0 g per dL. Despite transfusion with four units of RBCs during this interval, her admission Hb level was 5.7 g per dL. There was no evidence of blood loss or hemolysis. Laboratory values were consistent with an iron-deficient state. The patient's hospital course included repeated instances of sharp Hb drop and appropriate but unsustained response to RBC transfusion. Extensive work-up identified no occult source of bleeding. Clinical suspicion raised the possibility of self-inflicted blood loss. The patient subsequently admitted to repeatedly drawing blood from her indwelling catheter and discarding it in the lavatory. CONCLUSION: Munchausen syndrome should be considered in cases of unexplained anemia, especially in the target demographic group: young, female, healthcare professionals. Early diagnosis may prevent morbidity, multiple hospitalizations, and the risk of invasive diagnostic procedures.

Adult↗
PubMed2002

Blood substitutes: how close to a solution?

The term "blood substitute" is commonly misused when "red cell substitute" is meant. The ideal red cell substitute should deliver oxygen (O2), require no compatibility testing, cause few side effects, have prolonged storage qualities, persist in the circulation, and be available at reasonable cost. While no drug with all of these qualities is on the near horizon, several early generation red cell substitutes are approaching submission for licensure, at least for limited indications. Hemoglobin-derived red cell substitutes from human bovine and recombinant sources, as well as perfluorochemicals that dissolve O2, are in different stages of development. While each formulation has its own physical characteristics, biologic activities, and adverse reaction profile, all share one characteristic: The physiologic consequences of delivering O2 with small molecules is poorly understood, both accounting for problems seen in the clinical trials and providing therapeutic opportunities for the cancer patient. All the red cell substitutes in phase II trials have a life measured in hours and are unlikely to replace transfusions or drugs that stimulate erythropoiesis for chronic anemia, but they may play a role in cancer surgery, or even in radiation therapy, or in the management of cancer-related vascular occlusive syndromes.

Animals↗