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Biomedical subjects

N A Buskard

Publications and source records attributed to N A Buskard.

At least 19 recordsLinked to original sources

Laboratory abnormalities in thrombotic thrombocytopenic purpura. Canadian Apheresis Group.

Thrombotic thrombocytopenic purpura is an uncommon disorder that requires prompt recognition and intervention to prevent death. To date, information regarding the classic laboratory abnormalities in the disease has been derived from small numbers of patients whose laboratory tests have been done at many different sites. We report the laboratory findings in 135 patients who presented with thrombotic thrombocytopenic purpura to 17 Canadian centres. 50 men and 85 women had a mean platelet count of 25.3+/-19.4x10(9)/l. The initial platelet count correlated with mortality; 32% of patients with a platelet count of 20x10(9)/l or less died compared with 18% of patients with a platelet count >20x10(9)/l (P=0.058). The platelet-associated IgG was elevated in 88% at presentation whereas the indirect platelet suspension immunofluorescence test was positive in only 18%, 93% of the sera showed reactivity against platelets following protein blotting. All sera tested also showed reactivity against endothelial cells. Immune complexes were seen in all patients, whereas the platelet aggregating factor was detected in 59%. Although the von Willebrand factor was elevated in the majority of patients at entry, the multimer pattern was variable and showed no predictive pattern. Renal dysfunction was common (18%).

Adolescent↗

Idiopathic thrombocytopenic purpura in a liver transplant recipient with previous primary biliary cirrhosis.

The loss of immunotolerance has been implicated in the pathogenesis of both primary biliary cirrhosis (PBC) and idiopathic, immune-mediated thrombocytopenic purpura (ITP). An association between these two autoimmune diseases has been well described. We describe a 41-year-old woman in whom ITP developed 457 days after liver transplantation for PBC while receiving immunosuppressive medications sufficient to maintain allograft function. Our case report, the first to describe post-transplant ITP in association with PBC, demonstrates the persistence of the underlying immune dysregulation of PBC after transplantation. The practice of decreasing the dosage of immunosuppressive medication to maintenance levels after transplantation may unmask the effects of this defect in immunotolerance.

Adult↗

Cryosupernatant as replacement fluid for plasma exchange in thrombotic thrombocytopenic purpura. Members of the Canadian Apheresis Group.

The current established treatment of thrombotic thrombocytopenic purpura (TTP) is plasma exchange with fresh frozen plasma (FEP). With this treatment, there is a 49% response after seven exchanges and a 78% survival at 1 month. Although the exact cause of TTP is unknown, the presence of von Willebrand factor (VWF) multimers has been implicated in the disease. Accordingly, it has been suggested that cryosupernatant (plasma from which cryoprecipitate has been removed), which is relatively deficient in VWF multimers, might be an effective replacement fluid during plasma exchange. Patients from six centers were treated by plasma exchange with cryosupernatant. 18 patients who had failed a first course (average 7.7 exchanges) of plasma exchange with FFP. received a further seven exchanges with cryosupernatant. Subsequently, 40 previously untreated patients were exchanged with cryosupernatant. Of the 18 previously treated patients, 11 responded (defined as an increase in platelet count to > 150 x 10(9) /1 and no neurological events) after seven exchanges and 15 (83%) of the patients were alive at 1 month. The response rate in the 40 previously untreated patients was 75% at the end of seven exchanges and 95% of the patients were alive at 1 month. These values are significantly different (P < 0.05) from those reported in our earlier study and in other patients concurrently treated at the same centres with FFP when cryosupernatant was not available. Some patients who have failed to respond to plasma exchange with FFP replacement will respond to further exchange with cryosupernatant. Cryosupernatant replacement may be more effective as first-line treatment of TTP than FFP.

Adult↗

Therapeutic plasmapheresis.

Considerable work has been carried out over the past 25 years to define the conditions for application of plasmapheresis or plasma exchange. The use of plasma exchange in neurologic disorders such as Guillain-Barré syndrome has seen widespread application including the combination of plasma exchange with the use of intravenous immunoglobulin. Investigators have assessed the use of each therapy alone and in combination and, although both are advantageous, the relative benefits of each are still somewhat unclear. Other forms of neuropathies also seem to benefit from plasma exchange, as do some vasculitides. The use of cryosupernatant rather than frozen plasma to treat thrombotic thrombocytopenic purpura has improved outcome, but the cumulative data from many trials indicate that the mortality rate, if anything, persists at an even higher level than it did decades ago. Hemolysis, elevated liver enzymes, and low platelets syndrome, which has some characteristics similar to those of thrombotic thrombocytopenic purpura, has been shown to have variable response to plasma exchange. Plasma exchange has also been assessed as a treatment in organ failure and transplant rejection. Liver failure has shown variable response even when bioartificial livers are used. Of particular interest is the emerging use of photopheresis as an immune modulatory therapy. This is one of the newer innovative modifications of standard plasma exchange that will undoubtedly lead to interesting future therapeutic opportunities. The field continues to evolve.

Humans↗

Unrelated bone marrow transplantation in Canada, the national experience. Canadian Red Cross Society.

The Canadian Unrelated Bone Marrow Donor Registry (UBMDR) of the Canadian Red Cross Society (CRCS) was officially funded as of April 1, 1989 for an initial three year period with a mandate to recruit 50,000 unrelated bone marrow donors and to conduct the search activities for unrelated bone marrow donors worldwide on behalf of Canadian patients. Since February of 1988, 162 unrelated bone marrow transplants have been carried out in Canada. The registry now stands at an enrollment of 35,705 with approximately 1,200 donors being added monthly. Recruitment of unrelated bone marrow donors is now established in fourteen Canadian cities, and an active ethnic recruitment is now in progress.

Bone Marrow Transplantation↗

Comparison of plasma exchange with plasma infusion in the treatment of thrombotic thrombocytopenic purpura. Canadian Apheresis Study Group.

BACKGROUND: Thrombotic thrombocytopenic purpura is an uncommon disease with a high mortality rate even with current treatment. The cause of the syndrome and its optimal treatment are unknown. Although both plasma exchange and plasma infusion have been useful treatments, it is not clear which is superior. In this report we describe a prospective randomized trial comparing plasma exchange with plasma infusion for the treatment of thrombotic thrombocytopenic purpura. METHODS: One hundred two patients with thrombotic thrombocytopenic purpura were randomly assigned to receive either plasma exchange or plasma infusion with fresh-frozen plasma on seven of the first nine days after entry into the trial. The total volume of plasma received by patients undergoing plasma exchange was three times that received by patients undergoing plasma infusion. All the patients also received aspirin and dipyridamole. The outcomes in the two groups were compared at the end of the first treatment cycle (day 9) and after six months. RESULTS: At the end of the first treatment cycle patients receiving plasma exchange had a higher rate of response as defined by an increase in the platelet count (24 of 51 patients) than those who received plasma infusion (13 of 51, P = 0.025). Of the 51 patients treated with plasma exchange, 2 died, whereas 8 of the 51 patients who received plasma infusion died (P = 0.035). After six months the outcome in the plasma-exchange group was still superior, with a response observed in 40 of 51 patients, whereas 25 of 51 patients in the plasma-infusion group responded (P = 0.002). Eleven patients in the plasma-exchange group died, as did 19 patients in the plasma-infusion group (P = 0.036). The overall mortality was 29 percent. CONCLUSIONS: Plasma exchange is more effective than plasma infusion in the treatment of thrombotic thrombocytopenic purpura.

Adult↗

Safety of blood transfusion: risks and use of predonation, the Canadian experience.

A variety of measures has been introduced in Canada to improve the safety of the blood supply. An autologous blood transfusion pilot study in British Columbia indicated that this form of transfusion is well tolerated and accepted in low-risk patients undergoing elective breast reconstructive surgery. While the use of autologous blood in Canada is not common at present, with broad donor criteria and increased concern about the hazards of homologous blood transfusion autologous transfusion is likely to increase in Canada in the future.

Blood Transfusion↗

Unrelated bone marrow transplantation in Canada, the national experience.

The Canadian Unrelated Bone Marrow Donor Registry (UBMDR) of the Canadian Red Cross Society (CRCS) Blood Transfusion Service (BTS) was officially funded as of April 1, 1989 for an initial three year period with a mandate to recruit 50,000 unrelated bone marrow donors and conduct the search activities for unrelated bone marrow donors worldwide on behalf of Canadian patients (1). All provinces of Canada agreed to fund the Registry and it was unanimously adopted to locate the Canadian National Coordinating Centre (CNCC) of the Registry in Vancouver. Since February of 1988, 64 unrelated bone marrow transplants have been carried out in Canada. Over half of the unrelated donors have come from other countries. Canada has established working relationships with the United States, the United Kingdom and France. Recruitment of unrelated bone marrow donors is now established in twelve Canadian cities with more to follow. It is anticipated that the size of the registries world wide will continue to increase, that their ethnic makeup will become diversified and that the indications for unrelated bone marrow transplantation will broaden in the years to come.

Bone Marrow Transplantation↗

An anonymous seroprevalence survey of HIV infection among pregnant women in British Columbia and the Yukon Territory.

We performed an anonymous seroprevalence survey of human immunodeficiency virus (HIV) type 1 infection through HIV antibody testing of blood samples from 22,512 women aged 15 to 44 years receiving prenatal care in British Columbia and the Yukon Territory from Mar. 15 to Sept. 30, 1989. Of the samples six were confirmed to be HIV positive; this yielded a crude overall seroprevalence rate of 2.7 per 10,000 pregnant women (95% confidence interval [CI] 1.0 to 5.8). All of the positive samples were from women 20 to 29 years of age; four were from Vancouver, one was from Victoria, and one was from elsewhere. The highest seroprevalence rates were among women aged 15 to 29 years in Vancouver and Victoria (7.2 and 9.4 per 10,000 pregnant women respectively). Thus, 1 in 1300 pregnant women in that age group in the metropolitan areas of British Columbia was HIV positive. Application of seroprevalence rates to the total female population in British Columbia and the Yukon Territory revealed that as many as 401 women had HIV infection in 1989. Our estimates likely represent the minimum. As a subset of women of childbearing age pregnant women are likely at lowest risk of HIV infection, and so the true number of women 15 to 44 years of age with HIV infection is probably several times higher. Our study has provided a baseline assessment and will be repeated annually to analyse trends in HIV seroprevalence among pregnant women in British Columbia and the Yukon Territory.

Acquired Immunodeficiency Syndrome↗

Cyclosporine and methylprednisolone for prophylaxis of acute graft-versus-host disease.

Twenty-eight consecutive HLA matched patients undergoing allogeneic bone marrow transplantation received prophylaxis for acute graft-versus-host disease with combined cyclosporine and methylprednisolone. The incidence of grades II-IV acute GVHD was 28.5%, a figure similar to that reported for two other drug regimens. The incidence of chronic GVHD in patients surviving longer than 150 days was 73%. Toxicity, especially renal, was acceptable and a number of potential problems associated with the use of methotrexate were avoided. While this regimen and similar ones have reduced the incidence and severity of acute GVHD the problem remains formidable and newer approaches are clearly needed.

Adolescent↗

Post-transfusion purpura secondary to passive transfer of anti-P1A1 by blood transfusion.

A patient developed severe post-transfusion purpura (PTP) following transfusion of two units of packed red blood cells. The timing of the patient's thrombocytopenia suggested passive immunization rather than the typical anamnestic response associated with classical PTP. Investigation of the blood donors revealed one with evidence of a platelet specific antibody of high titre. This donor was typed as P1A1 negative and the antibody was shown to have anti-P1A1 specificity.

Aged↗

Allogeneic bone marrow transplantation using partially-matched related donors.

Six patients with advanced leukemia and one with severe combined immunodeficiency syndrome received allogeneic bone marrow transplantation (BMT) from HLA haploidentical donors who were compatible for one or two loci on the non-shared chromosome. Methotrexate was used for prophylaxis against acute graft-versus-host disease (GVHD). All patients engrafted but developed moderate to severe acute GVHD, and three patients died. Two leukemic patients relapsed but two others survived and were free of disease 403 and 936 days post-transplant. BMT using related partially matched donors may result in durable engraftment and long-term survivors. The implications of using such donors in expanding the application of BMT are discussed.

Bone Marrow Transplantation↗