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Biomedical subjects

Karen E King

Publications and source records attributed to Karen E King.

9 recordsLinked to original sources
PubMed2006

Prevalence of HLA antibodies in transfused patients with and without red cell antibodies.

BACKGROUND: Multiply transfused patients are at increased risk of developing red cell (RBC) antibodies, as well as antibodies to HLA. Although pretransfusion testing screens for RBC antibodies, no such testing is routinely performed for HLA antibodies. Determining which patients are more likely to make HLA antibodies may be important for patients undergoing elective surgery where platelets (PLTs) may be required. It is hypothesized that patients with RBC alloantibodies may be more likely to have HLA antibodies than previously transfused patients without RBC antibodies. STUDY DESIGN AND METHODS: Blood was collected from 53 adult male surgical patients with RBC alloantibodies and a control group of 69 similar male patients with a history of previous transfusions but no evidence of RBC alloimmunization. The samples were tested for the presence of immunoglobulin G Class I HLA antibodies by enzyme-linked immunosorbent assay. RESULTS: Of the 53 samples from patients with RBC alloantibodies, 12 (22.6%) also had HLA antibodies, whereas only 7 (10.1%) of the 69 patients in the control group had HLA antibodies (p < 0.03). CONCLUSIONS: There is a significant difference between the rates of HLA alloimmunization in male patients with RBC antibodies versus multiply transfused patients without RBC antibodies. Screening for HLA antibodies may be warranted in patients with RBC alloantibodies who might require PLT transfusion support for elective surgery.

Adult↗
PubMed2005

Treatment of autoimmune hemolytic anemia.

The appropriate therapy of autoimmune hemolytic anemia (AIHA) is dependent on the correct diagnosis and classification of this family of hemolytic disorders. Although the majority of cases are warm AIHA, there are several distinct types of cold AIHA and a number of drug-induced etiologies of AIHA, which must be investigated to determine if stopping a drug will induce a remission. In warm AIHA, corticosteroids are standard, followed by consideration of splenectomy in recalcitrant cases. If steroids and splenectomy are insufficient, other forms of immunosuppressive therapy are typically initiated. In cold AIHA, keeping the patient warm in often sufficient, but therapy directed at an underlying lympholiferative disorder may be helpful. Brisk hemolysis, inadequate responses to therapy, and worsening anemia require transfusion therapy. Although the pretransfusion workup is made difficult by the presence of the autoantibody, transfusion services can usually provide blood safe for transfusion by excluding underlying alloantibodies. When transfusion is urgently required and compatible blood cannot be located, incompatible blood may be provided as a life-saving measure. Communication between the transfusion service and the hematologist is critical to assess the risks in these settings. Hemoglobin-based oxygen carriers may provide an important bridging therapy in the future. Requests for "least incompatible" blood do not enhance transfusion safety and often result in unnecessary delays.

Anemia, Hemolytic, Autoimmune↗
PubMed2005

ABO incompatible high-titer renal transplantation without splenectomy or anti-CD20 treatment.

Most successful protocols for renal transplantation across ABO incompatible (ABOi) barriers have utilized splenectomy as part of the pre-conditioning process. We recently described successful ABOi transplantation using anti-CD20 monoclonal antibody in lieu of splenectomy. In the current study, we hypothesized that plasmapheresis (PP) and low dose CMV hyper-immunoglobulin (CMVIg) alone would be sufficient to achieve successful engraftment of ABOi kidneys. We describe four blood type incompatible patients who received live donor renal transplants from A1 (two patients), A2 (one patient), and B (one patient) donors. All patients started with antihuman globulin (AHG) phase titers of 64 or higher and were pre-conditioned with PP/CMVIg but not splenectomy or anti-CD20. All 4 patients underwent successful transplantation and have a mean current serum creatinine of 1.1 (range: 0.9-1.2). There were no episodes of antibody mediated rejection. Rapid allograft accommodation may limit the need for long-term antibody suppression provided by splenectomy or anti-CD20, thereby eliminating the added infectious risk of these modalities and removing another disincentive to ABOi transplantation.

ABO Blood-Group System↗
PubMed2004

Antibody, complement and accommodation in ABO-incompatible transplants.

Many facets of accommodation have been explored since this process was first observed in ABO-incompatible renal allografts over 17 years ago. Intriguing new pieces of the puzzle have emerged to be fitted into the picture in several places. For example, vascular endothelial cells can be stimulated to secrete substantial amounts of blood group A and B antigens linked to von Willebrand factor; the antibody response to A and B antigens stimulated by ABO-incompatible renal allografts can show epitope spreading; complement can inhibit inflammation through actions of some complement split products, particularly iC3b and C3a; endothelial cells can upregulate various cytoprotective mechanisms; and clinically, new protocols for achieving accommodation have been implemented with improved results.

ABO Blood-Group System↗
PubMed2004

Universal leukoreduction decreases the incidence of febrile nonhemolytic transfusion reactions to RBCs.

BACKGROUND: Febrile nonhemolytic transfusion reactions (FNHTR) is a relatively common complication associated with allogeneic transfusion. Because WBCs have been implicated in the mechanism of FNHTRs, it has been proposed that the transfusion of leukoreduced RBCs should be associated with a decreased incidence of FNHTRs. These reactions are generally not life threatening, but they are expensive in their management, evaluation, and associated blood-product wastage. Over the past several years, the proportion of leukoreduced RBCs has increased at Johns Hopkins Hospital in an effort to move toward complete leuko-reduction. A retrospective analysis is reported here of FNHTRs in RBC recipients as the inventory increased in percentage of leukoreduced RBC units. STUDY DESIGN AND METHODS: Between July 1994 and December 2001, all transfusion reactions (TRs) associated with the transfusion of allogeneic RBCs were retrospectively analyzed. Both computerized data and individual TR reports were reviewed. Patients who had both allergic and febrile features were included as part of both categories. TRs were reported as a percentage of total units transfused. Two time periods were selected for direct comparison. July to December 1994 represents the time period before the initiation of an increase in leuko-reduction. July to December 2001 represents a time period when almost complete leukoreduction (99.5%) had been achieved. The TR data were compared between these two time periods, comparing a time before leuko-reduction to a time period after leukoreduction had been achieved. The trends in TRs over the entire 7.5-year period of July 1994 to December 2001 were also assessed. RESULTS: In the initial period before the initiative to move toward leukoreduction, 96 percent of our RBC inventory was non-leukoreduced. In the study period after leukoreduction, 99.5 percent of our RBC inventory was leukoreduced. When comparing these two time periods, the incidence of FNHTRs decreased from 0.37 percent to 0.19 percent (p = 0.0008). The trend over the entire 7.5-year study period confirms the decrease in FNHTRs as the percentage of leukoreduced RBCs increased. The incidence of allergic TRs has remained unchanged over this time period. CONCLUSIONS: As our institution has increased its inventory of leukoreduced RBCs to approximately 100 percent, selective leukoreduced protocols have been discontinued. The incidence of FNHTRs has decreased significantly and the rate of allergic reactions has essentially remained unchanged. Leukoreduction is effective in decreasing FNHTRs associated with the transfusion of allogeneic RBCs.

Erythrocyte Transfusion↗
PubMed2004

Successful renal transplantation across simultaneous ABO incompatible and positive crossmatch barriers.

ABO incompatibility and human leukocyte antigen (HLA) sensitization remain the two largest barriers to optimal utilization of kidneys from live donors. Here we describe the first successful transplantation of patients who were both ABO incompatible and crossmatch positive with their only available donor. A preconditioning regimen of plasmapheresis (PP) and low-dose CMV hyperimmune globulin (CMVIg) was delivered every other day until donor-specific antibody (DSA) titers were reduced to a safe level and isoagglutinin titers were < or =16. Each patient received quadruple sequential immunosuppression, splenectomy and three protocol post-transplant PP/CMVIg treatments. There was no hyperacute rejection. Two of the three patients had a persistent positive cytotoxic crossmatch on the day of transplant and eliminated their DSA subsequently. Antibody-mediated rejection (AMR) in one patient was reversed by reinitiating PP/CMVIg and anti-CD20. The patients are more than 9 months post-transplant with excellent graft function. Preconditioning with PP/CMVIg results in a durable suppression of DSA and permits accommodation of the allograft to a discordant blood type. The ability to cross these two barriers simultaneously is clinically important as sensitized patients have often exhausted their blood type compatible living donors during previous transplants.

ABO Blood-Group System↗
PubMed2004

Plasmapheresis, CMV hyperimmune globulin, and anti-CD20 allow ABO-incompatible renal transplantation without splenectomy.

The majority of preconditioning protocols developed to allow ABO-incompatible (ABOi) renal transplantation include concurrent splenectomy as a prerequisite to successful engraftment. Our center has developed a preconditioning protocol that includes plasmapheresis (PP), low-dose CMV hyperimmune globulin (CMVIg), and anti-CD20 monoclonal antibody (rituximab) to allow ABOi renal transplantation without splenectomy. Our initial experience has included treatment of six recipients and successful transplantation from blood group A(1), A(2), and group B living donors. Mean (+/- SD) serum creatinine was 1.3 +/- 0.1 mg/dL among the six recipients and no episodes of antibody-mediated rejection (AMR) occurred at a median follow-up of 12 months. ABO antibody titers have remained below pretreatment levels. The absence of AMR and stable allograft function in this series show the potential of this preconditioning protocol to increase ABOi renal transplantation. The use of rituximab, allowing avoidance of splenectomy, may further remove one of the significant disincentives to ABOi transplantation, and eliminate the risk of post-splenectomy infections.

ABO Blood-Group System↗
PubMed2003

Extracorporeal photopheresis in the treatment of persistent rejection in a pediatric lung transplant recipient.

Lung transplantation is an accepted therapy for children with end-stage lung disease. One-year lung transplant survival rates of 86% have been reported by the United Network for Organ Sharing. Allograft rejection is a common cause of death following transplantation. Extracorporeal photopheresis is a novel therapy used to treat solid-organ rejection; this therapy involves separating the leukocyte-rich fraction from whole blood, treating with psoralen and ultraviolet light A exposure. The objective of therapy is to reverse progressive and persistent rejection. Working collaboratively with an institution that offers extracorporeal photopheresis may provide an alternative or additional therapy in the management of ongoing rejection following solid-organ transplantation.

Acute Disease↗