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Biomedical subjects

S G Sandler

Publications and source records attributed to S G Sandler.

At least 19 recordsLinked to original sources

Human platelet alloantigen systems in three Chinese ethnic populations.

Knowledge of the prevalence of human platelet antigens (HPA) in different populations is important for effective diagnosis and management of immune-mediated platelet disorders. The purpose of this study was to determine HPA gene frequencies in the majority Han ethnic population of China and in ethnic She and Tajik minority populations. Using PCR sequence specific primers, HPA- 1, -2, -3, -4, -5, and -6, we determined genotypes for ethnic Han, She, and Tajik blood donors. HPA gene frequencies for Chinese Han were found to be similar to those of She, reflecting the historic affinities of these two populations. HPA gene frequencies for Tajik were closer to those for Caucasians than to Chinese Han, She, or other Asian populations, reflecting their disparate origin and historic geographic isolation. HPA gene frequencies in these Chinese populations reflect their historic origins. Knowledge of these findings may be used to better understand and treat immune-mediated platelet disorders in these populations.

Antigens, Human Platelet↗

Treatment of immune thrombocytopenic purpura in children : current concepts.

Treatment of immune thrombocytopenic purpura (ITP), the most common bleeding disorder of childhood, is a controversial subject for most practitioners. Diagnosis and management of ITP has historically been based primarily on expert opinion rather than on evidence. Due to a paucity of carefully conducted clinical trials in children, the management of ITP varies widely, ranging from observation only, to aggressive management with intravenous immunoglobulin (IVIG), intravenous anti-D rhesus (Rh)0 immunoglobulin (IV RhIG), corticosteroids, and splenectomy. To address the controversies, the American Society of Hematology (ASH) and the British Society for Hematology (BSH) have developed ITP practice guidelines. These guidelines, based on expert opinion, differ in their recommendations for treatment. The ASH guidelines favor therapy based on a low platelet count, and the more current BSH guidelines recommend a more conservative 'wait and watch' approach. In addition to treating children with severe bleeding symptoms, there is a tendency (not evidence based) to treat early in order to prevent a life-threatening bleeding episode, including intracerebral hemorrhage. Corticosteroids are a highly effective therapy, inexpensive, and can usually increase the platelet count within hours to days. However, chronic or prolonged use is associated with toxicity. In the US, based on the knowledge of known toxicities of corticosteroids, as well as the efficacy of alternative treatments (IV RhIG, IVIG), many pediatricians prefer to treat with IVIG and IV RhIG, reserving corticosteroid treatment for serious bleeding or refractory disease. However, in the UK, for the most part, corticosteroids are used as first-line therapy in children with ITP. Splenectomy is rarely indicated in children except for those with life-threatening bleeding and chronic, severe ITP with impairment of quality of life. For children who develop chronic or refractory ITP, immunosuppressive drugs and/or chemotherapy agents may offer some promise. However, the long-term effects of these drugs in children are unknown and they should not be considered unless there is unequivocal evidence that the patient is refractory to IV RhIG, IVIG, and corticosteroids. To date, virtually all of the randomized clinical trials conducted in children with ITP have focused on platelet counts as the sole outcome measure. Only carefully designed, multicenter, randomized clinical trials comparing the effects of different treatment modalities in terms of bleeding, quality of life, adverse effects, and treatment-related costs will be able to address the controversies surrounding childhood ITP treatment and allow management of this condition to be based on scientific data rather than treatment philosophy.

Adrenal Cortex Hormones↗

Bar code technology improves positive patient identification and transfusion safety.

As a result of human error, an estimated 1 in 12,000 blood transfusions is given to the wrong patient. The cause of nearly all of these errors is failure of hospital personnel to identify positively intended transfusion recipients, their blood samples for cross-matching, or their correct blood components. We describe our experience using a point-of-care bar code transfusion safety system that links patients' bar-coded wristbands, with bar-coded labels on blood sample tubes, blood component bags, and nurses' identification badges. The result was 100 % accuracy of matching patients, their blood samples, and components for transfusions. For verifying information before starting blood transfusions, nurses preferred bar code "double checks" to conventional visual "double checks" by a second nurse. Methods are needed to reinforce nurses' proficiency with technological approaches to transfusion safety, such as software-driven bar code scanning, in situations where transfusions are administered infrequently.

Blood Banks↗

Review: immune thrombocytopenic purpura: an update for immunohematologists.

Immune thrombocytopenic purpura (ITP) is an acquired disease in which autoantibodies to platelets cause their sequestration and destruction by mononuclear macrophages, principally in the spleen. If increased production of platelets by megakaryocytes does not compensate for platelet destruction, the number of circulating platelets decreases (thrombocytopenia), resulting in a characteristic bleeding tendency (purpura). While most children with the disease experience a relatively short and benign clinical course, ITP in adults often lasts more than 6 months (chronic ITP) and is resistant to conventional treatment (corticosteroids, intravenous immune globulin, or splenectomy). The goal of medical management is to increase the platelet count to a safe level, without the risks of bacterial infections associated with splenectomy or toxicity from prolonged corticosteroid therapy. Splenectomy increases platelet counts in hours to days in most patients with acute ITP, but nearly 50 percent experience recurrent thrombocytopenia by 5 years postsplenectomy.

Autoimmune Diseases↗

Equivalence of spray-dried K2EDTA, spray-dried K3EDTA, and liquid K3EDTA anticoagulated blood samples for routine blood center or transfusion service testing.

We compared the results of routine blood tests for 102 blood donors' samples and 100 patients' samples collected in spray-dried K2EDTA, spray-dried K3EDTA, and liquid K3EDTA blood collection tubes to evaluate the impact of changes in formulation of the anticoagulant (K2EDTA vs.K3EDTA), its application (liquid vs. spray-dried), and tube material (glass vs. plastic). Methods for ABO/D testing, antibody screening, and antibody identification included direct hemagglutination/microplate (Olympus(R) PK 7200) and gel column methods (Ortho ID-Micro Typing System/Gel Test). Additional studies on blood donors' samples included time delayed antigen testing and antibody identification and half-draw/half-evacuated collections. Also, we compared the results of routine ABO/D testing and antibody screening for 50 patients' samples collected in spray-dried K2EDTA and spray-dried K3EDTA and for an additional 50 patients' samples collected in spray-dried K2EDTA tubes from two different manufacturers. All patients' samples were tested in parallel by solid phase/microplate method (Immucor ABS 2000) and the standard manual tube method. All test results for routine blood bank tests on donors' and patients' samples were concordant, demonstrating the equivalence of spray-dried K2EDTA, spray-dried K3EDTA, and liquid K3EDTA blood collection tubes for routine donor center or transfusion service testing.

Journal Article↗

Intravenous Rh immune globulin for treating immune thrombocytopenic purpura.

Intravenous Rh [corrected] immune globulin was licensed by the U. S. Food and Drug administration in 1995 for the treatment of acute and chronic immune thrombocytopenic purpura in children and chronic immune thrombocytopenic purpura in adults. In 1996, the American Society of Hematology published a practice guideline for immune thrombocytopenic purpura, but treatment recommendations of necessity were formulated using only results of early clinical trials with intravenous Rh immune globulin. To date, there are no published results of large-scale clinical trials comparing conventional doses of intravenous immune globulin with the most promising dose range for intravenous Rh immune globulin (50-75 microg/kg). However, clinical experience is accumulating to indicate that intravenous Rh immune globulin is as effective, probably safer, and easier to administer than intravenous immune globulin. Acute intravascular hemolysis after infusions of intravenous Rh immune globulin for immune thrombocytopenic purpura has been reported with an estimated incidence of 1 in 1,115 patients. The risk factors for this adverse event have not been defined.

Adult↗

Serologic aspects of treating immune thrombocytopenic purpura using intravenous Rh immune globulin.

In patients with immune thrombocytopenic purpura (ITP), IgG autoantibody-coated platelets are phagocytized by mononuclear macrophages, primarily in the spleen. Intravenous Rh immune globulin (IV RhIG) has been used since 1983 to treat D(+), nonsplenectomized patients with ITP. The beneficial therapeutic effect of IV RhIG is attributed to competitive inhibition of phagocytosis of IgG-coated platelets by IgG anti-D-coated D(+) red blood cells (reticuloendothelial or Fc receptor blockade). Following infusions of IV RhIG in D(+) ITP patients, the direct and indirect antiglobulin tests become transiently positive, reflecting passively transferred anti-D and other alloantibodies that were present in the infused IV RhIG. These consistent and predictable serologic findings contrast with the inconsistent and weak anti-D reactivity observed when D(-) women are treated with relatively small doses of intramuscular RhIG for Rh immunoprophylaxis. The pathophysiology of ITP and the effect of infusing IV RhIG in patients with ITP are illustrated in this review, using computer-generated figures.

Journal Article↗

The cost of treating immune thrombocytopenic purpura using intravenous Rh immune globulin versus intravenous immune globulin.

Multiple factors, including efficacy, toxicity and cost, may influence the decision to treat immune thrombocytopenic purpura (ITP) with intravenous immune globulin (IVIG) or intravenous Rho (D) immune globulin (IV RhIG). We conducted a survey of 50 hospitals in 31 states to determine the costs for treating ITP using conventional doses for IVIG or IV RhIG, based on package insert recommendations. The average cost for a dose of IVIG ($2,771) was 71.7% ($1,157) more than that for a dose of IV RhIG ($1,614). In the absence of clearly defined differences in clinical outcomes when treating ITP with IVIG or IV RhIG, the difference in cost may be an important factor in selecting the treatment.

Data Collection↗

Platelet transfusions: utilization and associated costs in a tertiary care hospital.

We implemented a prospective study to evaluate platelet transfusion utilization, resource use, and costs in a tertiary care hospital over a 6-month period. All hospitalized patients receiving platelet transfusions between July and December 1996 were followed prospectively to determine platelet use and costs. Clinical and financial data were collected, evaluated, and compared to identify trends in resource utilization based on admitting service and platelet-refractory status. One thousand nine hundred forty-four platelet units were transfused to 245 hospitalized patients (50.6% male, mean age 49 years) during the study period. The majority of platelet units transfused were single donor (N = 1,460, 75%) and administered to bone marrow patients and patients with a hematological malignancy/disorder. Median hospitalization costs per admission were $27,750, ranging from a high of $58,729 for admission to the Bone Marrow Transplant service to $13,856 per admission to the Internal Medicine/Other service. Patients were refractory to platelet transfusions during 21.6% of hospitalizations. Hospital stays were longer (35.0 days vs. 14.4 days, P < 0.001) and inpatient hospital costs ($103,956 vs. $37,817, P < 0.001) were more than two and a half times higher for patients refractory to platelet transfusions. Platelet utilization, resource use, and costs vary by admitting service. Refractoriness to platelet transfusion was associated with significantly greater costs and lengths of stay. Monitoring platelet transfusion practices, particularly for patients refractory to platelet transfusions, may be beneficial for limiting costs and improving efficacy.

Adult↗

The spleen and splenectomy in immune (idiopathic) thrombocytopenic purpura.

The benefits of surgical splenectomy in patients with immune (Idiopathic) thrombocytopenia purpura (ITP) probably reflect the combined effects of eliminating a source of antiplatelet antibody synthesis as well as the primary site of platelet destruction. The recent availability of intravenous Rho(D) Immune globulin (WinRho SDF; Nabi, Boca Raton, FL) presents an opportunity to extend the duration of nonsurgical (spleen-sparing) management of chronic ITP by inducing reversible Fc blockade. While new methods for laparoscopic splenectomy may offer improved surgical outcomes and reduced costs for ITP patients in the near-term, the long-term consequences of splenectomy remain to be determined. Partial splenectomy has been shown to be effective in the management of anemia in hereditary spherocytosis and elliptocytosis, while preserving vital splenic phagocytic and immune functions. The concept that cell destruction occurs in reticuloendothelial cells has been updated with recognition that the mononuclear phagocyte is neither a reticular nor an endothelial cell. Immune phagocytosis is now understood to be mediated by macrophage IgG Fc and complement receptors. A key factor for devising a strategy for selecting medical or surgical splenectomy, or postponing splenectomy, is an assessment of the relative importance of splenic immune versus phagocytic function in the pathogenesis of ITP.

Humans↗

A fully automated blood typing system for hospital transfusion services. ABS2000 Study Group.

BACKGROUND: The results of routine blood bank testing by a fully automated blood typing system (ABS2000) were compared with those obtained by standard manual methods in six hospital transfusion services. STUDY DESIGN AND METHODS: The ABS2000 system uses microtiter plates for determining ABO and D types, solid-phase red cell adherence (SPRCA) assays for antibody detection, and modified SPRCA plates for IgG crossmatches. The transfusion services used their standard manual test tube methods. RESULTS: Of 3779 donors' samples tested for ABO types (red cell typings only), 3.0 percent could not be interpreted by the ABS2000 system's neural network, because of clots, hemolysis, or lipemic samples. The results for ABO types were concordant for 99.8 percent of the remaining samples. Of 3779 donors' samples tested for D types, the results were concordant for 98.7 percent. Of 7580 patients' samples tested for ABO types (red cell and plasma typings), 5.8 percent could not be interpreted by the ABS2000 system. There was 100-percent concordance of ABO typing results for the remaining 7140 samples. There was 99. 7-percent concordance of results for patients' D types. The results of 96.7 percent of antibody detection tests and 98.8 percent of crossmatches were concordant. Neither method failed to detect a serologically incompatible crossmatch that was associated with a specific, clinically significant alloantibody. The ABS2000 system performed 45 confirmatory donor ABO and D types in 115 minutes, 22 antibody detection tests in 116 minutes, 16 patients' ABO/D types in 149 minutes, and 40 crossmatches in 140 minutes. CONCLUSION: The ABS2000 blood typing system automates routine blood bank tests with accuracy comparable to that of hospital transfusion services' standard manual methods.

Automation↗

Detection of multiple passively acquired alloantibodies following infusions of IV Rh immune globulin.

BACKGROUND: Passively acquired blood group alloantibodies are detected regularly after infusions of IV Rh immune globulin (RhIG) for the treatment of immune thrombocytopenic purpura (ITP) in D+ patients. STUDY DESIGN AND METHODS: Blood samples from 16 D+ patients with ITP were tested after treatment with IV RhIG for the presence of passively acquired alloantibodies. Similar studies were conducted for three D- patients after injections of IM RhIG for Rh immunoprophyl-axis. Four production lots of IV RhIG and 2 lots of IM RhIG were tested for the presence of alloantibodies. RESULTS: All 16 D+ patients with ITP developed a positive DAT, as well as positive antibody detection test results, after infusions of IV RhIG. All postinfusion plasma samples contained anti-D, as well as one or more additional antibodies, usually anti-C, -E, -G, -V, or -Fy(a). Eluates from patients' RBCs with positive DAT results contained multiple passively acquired alloantibodies. Multiple alloantibodies were detected in samples of different production lots of IV RhIG or IM RhIG. No acute transfusion reactions were observed in five D+ patients with ITP who had been treated with IV RhIG and had been given serologically incompatible D+ RBCs. After injections of IM RhIG, the only passively acquired alloantibody detected was anti-D. CONCLUSION: Plasma samples from D+ patients with ITP treated with IV RhIG regularly contained anti-D and multiple other passively acquired Rh, Duffy, or Kidd system alloantibodies. Postinfusion RBC samples all had positive DAT results with eluates containing anti-D and multiple other Rh, Duffy, or Kidd system antibodies. The consistent detection of multiple passively acquired alloantibodies after IV RhIG, in contrast to the detection of anti-D only after IM RhIG, reflects the immediate effect of the entire (bolus) dose of RhIG by the IV route, the dose for treating ITP that is approximately 10 times the dose for Rh immunoprophylaxis, and the expected serologic incompatibility with recipients' D+ RBCs.

Erythrocyte Transfusion↗

A solid phase and microtiter plate hemagglutination method for pretransfusion compatibility testing.

Most hospital blood transfusion services perform routine pretransfusion compatibility tests (ABO/D typings, antibody detection tests and crossmatches) using standard test tube methods. Recently, alternative technologies, including microtiter plate methods, solid phase red cell adherence (SPRCA) assays, gel tests, microbead columns and affinity column assays have become available. While the increased sensitivity of these new serological technologies is an important advantage, cost savings and automated testing are also important benefits. Our hospital's Transfusion Service converted from manual test tube methods for compatibility testing to manual microtiter plate and SPRCA methods and, subsequently, to automated microtiter plate and SPRCA methods. The conversion was facilitated by using commercially-marketed reagent kits and a fully-automated blood typing analyzer. The automated blood typing system was linked electronically to a hand-held combination bar code reader/portable data terminal that enabled positive identification of patients' bar code wrist bands, personal identification badges, and bar code labels on patients' blood samples and blood components. This bar code identification system has been implemented in the hospital's outpatient Infusion Service. Thus, the conversion to microtiter plate and SPRCA assays enhanced transfusion safety not only by increasing the sensitivity of serological testing, but also by standardizing compatibility testing, supporting electronic record keeping, and linking the laboratory analyzer to a bar code identification system.

Blood Grouping and Crossmatching↗

Improving transfusion safety by electronic identification of patients, blood samples, and blood units.

To evaluate the feasibility of using an electronic identification system to improve safety and documentation of blood transfusions, a hand-held bar code scanner and data terminal, portable label printer, and related software were integrated into all phases of the blood transfusion process, including sample collection, laboratory testing, and administration of blood components. The study was conducted in two hospitals, one in Italy and the other in the United States. Each hospital used different laboratory analysers and information systems. A total of 621 blood components were transfused to 177 patients using 331 blood samples with 100 percent accuracy and electronic documentation of all pertinent patient, staff, sample, testing, and component information. Bar code reading and related electronic technology can be adapted to improve transfusion safety and reduce the risk of human errors at all steps of the blood transfusion process.

Journal Article↗