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S Slichter

Publications and source records attributed to S Slichter.

8 recordsLinked to original sources

Storage of platelets in additive solutions: a multicentre study of the in vitro effects of potassium and magnesium.

BACKGROUND AND OBJECTIVES: In a preliminary study, the presence of potassium and magnesium in a modified synthetic medium (PAS-III) was found to have a significant influence on platelet metabolism (using apheresis-derived, as well as buffy-coat-derived platelets) when compared with standard PAS-III. The differences included reduced glycolysis, as evidenced by lower consumption of glucose and lower production of lactate, but also better preservation of pH and hypotonic shock response reactivity. The results suggested that storage in modified PAS-III containing 20% plasma was comparable to storage in standard PAS-III containing 30% plasma. To confirm the preliminary results and to evaluate the effects of different preparation protocols, an international multicentre study, which included 11 different sites, was conducted. MATERIALS AND METHODS: Platelets from 30 pools of approximately 20 buffy coat (BC) units each and 24 pooled apheresis platelet units were aliquoted for storage in plasma (reference) or synthetic medium using either a specific additive solution (PAS-III) containing 30% plasma or a modification of PAS-III containing 5.0 mm potassium and 1.5 mm magnesium (PAS-IIIM) and either 30% or 20% plasma. Units were stored at room temperature with agitation for 7 days during which in vitro testing was carried out for biochemical, haematological and functional parameters. RESULTS: Storage of platelets in PAS-IIIM resulted in a reduction in the rate of glycolysis and better retention of pH and hypotonic shock response reactivity. Storage in PAS-IIIM containing 20% plasma appeared to result in the retention of in vitro properties, similar to those observed during storage in standard PAS-III containing 30% plasma. CONCLUSIONS: The results of this study confirm the preliminary results. Similar results were seen with platelets prepared by BC and apheresis methods, despite differences in equipment, the preparation technique and in the final platelet contents achieved in the platelet units. Storage of platelets in PAS-IIIM should be considered to improve platelet function and allow plasma reduction to 20%.

Blood Component Removal↗

Transient increase in circulating donor leukocytes after allogeneic transfusions in immunocompetent recipients compatible with donor cell proliferation.

Donor leukocytes in therapeutic blood components are implicated in transfusion-related complications ranging from alloimmunization to graft-versus-host disease (GVHD) to viral transmission and reactivation. To further characterize the kinetics of donor leukocyte clearance after allogeneic transfusion, we developed allele-specific polymerase chain reaction (PCR) assays directed at a single-copy Y chromosome gene and HLA class II alleles. These assays enable sensitive detection and quantitation of donor leukocytes at concentrations ranging from one cell to greater than 1,000 cells per 125 microL of recipient blood. When applied to serial samples from five consecutive orthopedic surgery patients who met study criteria, we observed 99.9% clearance of donor leukocytes over the initial 2 days posttransfusion, followed by a transient, 1-log increase in circulating donor leukocytes on days 3 to 5. This phenomenon was reproduced in a canine transfusion model, where the transient donor leukocyte expansion phase was prevented by gamma irradiation of donor blood, and was not observed after transfusions into alloimmunized dogs. We hypothesize that this transient increase in circulating allogeneic donor cells represents one arm of an in vivo mixed lymphocyte reaction, with activated donor T lymphocytes proliferating in an abortive GVHD reaction to HLA-incompatible recipient cells. Further investigation of this phenomenon should provide insight into the mechanisms involved in donor-recipient leukocyte interactions posttransfusion and the relationship of these interactions to leukocyte-induced complications.

Animals↗

Effects of rhIL-11 on normal dogs and after sublethal radiation.

The effects of recombinant human interleukin-11 (rhIL-11) were studied in normal dogs and dogs given otherwise sublethal total-body irradiation (TBI) without marrow transplantation. Ten normal dogs were given rhIL-11 subcutaneously, twice daily for 14 days at varying doses, two dogs at 30 micrograms/kg/day, four dogs at 60 micrograms/kg/day, two dogs at 120 micrograms/kg/day, and two dogs at 240 micrograms/kg/day. Peripheral blood platelet counts increased in all dogs. The increase in platelet counts ranged from 1.4 to 3.1 times the pre-treatment level. The greater increases of platelets were associated with higher doses (p = 0.01). No change in platelet size was evident except at the dose of 240 micrograms/kg/day. There were no changes in the total white blood cell (WBC) count or differential. A higher proportion of megakaryocytes with a DNA content of 32N/64N was observed in dogs treated with rhIL-11 at day 7 (n = 6) than for control dogs that did not receive rhIL-11 (n = 7; p = 0.01). In both peripheral blood and marrow, significantly increased hematopoietic progenitors (i.e, colony-forming unit granulocyte/macrophage [CFU-GM]) were present 7 and 14 days after the start of treatment. Concentrations of serum fibrinogen increased by a median of 155 mg/dL at day 7 of rhIL-11 (p < 0.01). Cholesterol also increased by a median of 52 mg/dL at day 14 (p < 0.01). There was a single death of a non-irradiated dog from pneumonitis on day 15 after the start of rhIL-11 administration at a dose of 120 micrograms/kg/day. All other non-irradiated dogs tolerated rhIL-11 without any significant adverse effects. Five dogs were given 200 cGy TBI without marrow grafting, followed by 240 micrograms/kg/day rhIL-11 subcutaneously in two divided doses for 28 days starting within 2 hours of TBI. The results in this group were compared with 10 dogs that had previously or concurrently been given 200 cGy without marrow grafting or hematopoietic growth factors. Two of the five treatment dogs died of pneumonitis on day 13 compared to one death among 10 control dogs on day 24. Among dogs that survived to hematologic recovery, the rhIL-11 dogs had decreased platelet counts (< 150,000) for a median of 24 days (range = 24 to 41) compared to a median of 28 days (range = 21-40) for the control group. Treatment with rhIL-11 increased platelet counts, platelet size, ploidy number of megakaryocytes, and marrow and peripheral blood CFU-GM in normal dogs.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

The first-year costs of establishing an unrelated bone marrow donor registry.

The cost of therapies like bone marrow transplantation has been an important consideration for several decades. Bone marrow transplantation is becoming increasingly accepted as an effective treatment for hematologic disorders, including acute nonlymphocytic leukemia. To find suitable donors, bone marrow donor registries are being developed. The first-year costs of establishing an unrelated bone marrow donor registry are reported here. First-year costs are largely due to personnel costs and HLA typing charges. The cost per registrant decreases over time, but further decreases due to economies of scale are limited by the continued fixed requirement for HLA typing. Data are presented by separating costs into six unique categories, thereby allowing other blood centers to estimate start-up costs based on our experience.

Bone Marrow↗

Transfusion requirements after HLA-identical marrow transplantation in 82 patients with aplastic anemia.

Red blood cell (RBC) and platelet (PLT) transfusion requirements during the first 13 weeks after HLA-identical marrow transplantation were studied in 82 patients with aplastic anemia. On the average, patients were given 9 units of RBCs (1-82) and 44 units of PLTS (6-468). The greatest need for support was during the first 4 weeks postgrafting. A multivariate statistical analysis of 22 variables showed that RBC and PLT requirements increased with age. In addition, RBC requirements increased if the patient had isohemagglutinins against the marrow donor's RBC, i.e., if the marrow transplant was across a major ABO barrier.

ABO Blood-Group System↗

Effect of six weekly transfusions on canine marrow grafts: tests for sensitization and abrogation of sensitization by procarbazine and antithymocyte serum.

We have previously shown that blood transfusions can immunize a dog and lead to rejection of a subsequent marrow graft despite lethal total body irradiation (TBI). Sensitization to histocompatibility antigens induced by two prior transfusions of whole blood could be overcome by a regimen of procarbazine and anti-thymocyte serum (ATS) preceding TBI. The current study investigated a) whether this regimen could abrogate sensitization induced by six weekly transfusions given from days --50 to --15 preceding a marrow graft, and b) whether platelet survival studies and two in vitro tests of immunity could predict marrow graft rejection. All donor-recipient pairs were histoincompatible, unrelated, and of different breed. Twenty-two recipients received platelet concentrate transfusions and eight received whole blood transfusions. Recipients were given 1200 R TBI and a graft of marrow and peripheral blood leukocytes from the transfusion donor on day 0. Three of 15 recipients (20%) given procarbazine, 12.5 mg/kg i.v. on days --8, --6, and --4, and ATS, 0.6 ml/kg subcutaneously on days --7, --5 and --3, Rejected their grafts, whereas 11 of 15 dogs (73%) not given procarbazine and ATS rejected their grafts (p less than 0.01). Serum lymphocytotoxic antibodies, peripheral leukocyte migration inhibition, and in vivo donor platelet recovery and survival were studied in those recipients receiving six weekly transfusions and in 18 other recipients receiving a single donor transfusion 3 months before marrow grafting. No significant correlation was found among these in vitro and in vivo tests of sensitization. Sensitization to marrow grafts was not reliably detected by the presence of cytotoxic antibodies or leukocyte migration inhibition. Platelet survival, however, was positively correlated with the results of marrow grafting in 12 of 15 (80%) evaluable recipients (p approximately 0.15).

Animals↗