Melanie S. Kennedy

Relationship between ADAMTS13 activity in clinical remission and the risk of TTP relapse.

Idiopathic thrombotic thrombocytopenic purpura (TTP) is characterized by frequent recurrences. Effective screening for relapses will enable intervention prior to overt episodes of TTP. The present study used a modified assay to detect ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 motif, 13) activity as low as 0·5%. This analytical improvement permits adequate measurement of ADAMTS13 activity levels in 97% of remission samples used for statistical modelling. ADAMTS13 activity and ADAMTS13 antibody (IgG) were measured in 157 serial samples prospectively collected from 24 TTP patients during periods of clinical remission. These patients were followed‐up quarterly for an average of 23 months, during which time nine episodes of TTP relapse occurred among six patients. Finally, logistic regression modelling was used to define the relationship between ADAMTS13 activity levels (0·5–100%) and the probability of TTP relapses. Our data demonstrated that lower ADAMTS13 activity and younger age were significantly associated with higher risk of relapse in the 3 months after specimens were taken. In contrast, ADAMTS13 antibody IgG levels were not predictive of TTP relapses. Identification of low ADAMTS13 activity during clinical remission as a key risk factor for TTP relapses provides a new screening strategy to identify patients who may benefit from prophylactic therapy prior to disease relapses.

An evaluation of ciclosporin and corticosteroids individually as adjuncts to plasma exchange in the treatment of thrombotic thrombocytopenic purpura

We present the results of two consecutively performed cohort studies that evaluated the clinical effects of corticosteroids or ciclosporin as an adjunct to plasma exchange (PE) for the treatment of an acute episode of thrombotic thrombocytopenic purpura (TTP). In comparing 12 corticosteroid‐treated patients with eight ciclosporin‐treated patients, none of the ciclosporin‐treated patients suffered an exacerbation or recurrence of TTP in the first 30 d after discontinuing PE compared with 6/10 (60%) of the corticosteroid‐treated patients (P = 0·042). These data suggest that ciclosporin may have advantages over corticosteroids as an adjunct to PE therapy in the initial treatment of idiopathic TTP.

Ciclosporin and plasma exchange in thrombotic thrombocytopenic purpura: long-term follow-up with serial analysis of ADAMTS13 activity

We hypothesized that ciclosporin (CSA) as adjunct to plasma exchange (PE) improves the efficacy of PE in idiopathic thrombotic thrombocytopenic purpura (TTP) via suppression of the antibody inhibitor of ADAMTS13. Our preliminary findings with CSA and PE as the upfront treatment of TTP suggested that the addition of CSA to PE significantly decreased the exacerbation (disease recurrence within 30 d of the last PE) rates compared to a cohort that received corticosteroids and PE as their upfront therapy of TTP. We present an updated analysis with long‐term follow‐up of 18 patients with idiopathic TTP treated with concurrent CSA and PE with analysis of serial measurements of ADAMTS13 activity, antigen and inhibitor concentration in the context of clinical outcome data. Overall, 16/18 (89%) patients achieved remission, similar to historical remission rates in idiopathic TTP with PE with only one patient suffering an exacerbation. Clinical responses correlated with improvements in ADAMTS13 activity and suppression of the antibody inhibitor of ADAMTS13. These data suggest that the efficacy of CSA is at least in part related to its suppression of the antibody inhibitor of ADAMTS13 and a subsequent improvement in ADAMTS13 activity and antigen.

Transfusion-Associated Graft-vs-Host Disease A Fatal Case Caused by Blood From an Unrelated HLA Homozygous Donor

Transfusion-associated graft-vs-host disease (TA-GVHD) is a rare complication of transfusion. We report fatal TA-GVHD in a 63-year-old coronary artery bypass patient of European descent after an RBC transfusion from an unrelated donor. The patient had mild lymphocytopenia and received 2 80-mg doses of methylprednisolone and 7 units of RBCs. On day 14 after the transfusion, he had fever, elevated liver enzyme levels, and a macular rash. Pancytopenia and bone marrow aplasia developed. On day 26, he had a massive gastrointestinal hemorrhage and died. At autopsy, histopathologic findings of the skin, liver, bone marrow, and gastrointestinal tract were consistent with TA-GVHD. One donor of the transfused RBCs (3 days old at transfusion) had a 1-way HLA match with the patient. A method using multiplex polymerase chain reaction is presented. This patient with TA-GVHD and mild immune suppression suggests that blood component irradiation guidelines may need to be reevaluated.

Coping with the complexities of multiple-solution problems: a case study

A model is proposed to account for the expertise of a skilled immunohematologist in solving multiple-solution problems. These problems, which he must deal with daily, are concerned with ensuring the safe transfusion of blood into patients. This model suggests that he copes with this difficult class of problems by: (1) Using patterns in the data to simplify the problem, hypothesizing the number of primitive solutions necessary to account for the test results and, when possibles, decomposing the problem into a set of less complex, single-solution problems. Such decompositions then enable more powerful reasoning processes; (2) making use of a mixture of data-driven and hypothesis-driven processes in order to reduce the chances that heuristic (and therefore error-prone) methods and cognitive biases will lead away from critical data; (3) Relying on a mixture of confirmatory and rule-out processes to provide converging evidence, thus reducing the changes of error; (4) uncovering his own errors through the use of “error models” that identify the conditions where one of his processes is likely to make an error (similar to the use of student models by expert tutors to diagnose mistakes made by students).

Severe Hemolysis Due to Passenger Lymphocyte Syndrome After Hematopoietic Stem Cell Transplantation From an HLA-Matched Related Donor

A 61-year-old white man (group A, Rh-positive) was allotransplanted for acute myelogenous leukemia from his HLA-matched related sister (group O, Rh-positive) in 2 separate infusions. Three days after the second graft infusion, the patients front blood type converted to O Rh-positive, with a negative direct antiglobulin test and elevated anti-A1 titer. Severe hemolysis developed, and the patient expired 14 days posttransplantation.

An empirical evaluation of the performance of antibody identification tasks.

Four empirical studies were conducted for better understanding of the nature of problem‐solving activities by medical technologists and medical technology students when performing antibody identification tasks. The results indicated the importance of strategies that ensure the collection of converging evidence, as these strategies protect against the fallibility of commonly used heuristics and against errors due to simple slips. The results also indicate that not only do students make significant numbers of errors, but so do practicing technologists. In one of the studies covering a 1‐year period, for instance, a group of 16 technologists made a total of 41 errors in 1057 cases. On the basis of these findings, several alternatives are proposed to reduce errors.

The effect of the source of transfused blood on the rate of consumption of transfused red blood cells in pregnancies affected by red blood cell alloimmunization

OBJECTIVE Our purpose was to compare the rate of consumption of maternally donated red blood cells with the rate of red blood cells from volunteers in fetuses affected by red blood cell alloimmunization. STUDY DESIGN The rate of hemoglobin decline was calculated in 293 fetal transfusions in 52 pregnancies, in 43 patients affected by red blood cell alloimmunization from 1987 to 1996. Fifty-eight transfusions were excluded from analysis. Hemoglobin decline was stratified by gestational age. The rates of consumption were compared with use of unpaired t tests. RESULTS The rates of hemoglobin decline (in grams per deciliter per day) were 18 to 24 weeks, 0.47 volunteer and 0.38 maternal (p = 0.174); 25 to 28 weeks 0.41 volunteer, 0.34 maternal (p = 0.46); 29 to 32 weeks, 0.35 volunteer, 0.33 maternal; > or = 33 weeks, 0.37 volunteer, 0.25 maternal, p = 0.048). Hemoglobin decline was less for the maternal donation group than for the volunteer donation group throughout gestation, becoming significant only in fetuses at > or = 33 weeks. CONCLUSION In the red blood cell-alloimmunized fetus, there is less consumption of maternal than of volunteer red blood cells. This difference reaches a statistical significance only in late gestation.

Therapeutic Apheresis: Applications and Future Directions

Abstract. The past 10–15 years have been witness to major technological achievements in the field of therapeutic apheresis. Concurrently, a large number of diseases, primarily with an immunological basis, have been treated with apheresis. In this paper, we review the various applications of therapeutic apheresis, adverse reactions associated with the mode of therapy, and future research directions. Several representative diseases are also discussed in detail.

A Pharmacokinetic Evaluation of the Effect of Plasma Exchange on Tobramycin Disposition

The effect of plasma exchange on the disposition of tobramycin was studied in three procedures done on two patients. Serum tobramycin levels were obtained when the subjects were off plasma exchange to calculate individualized tobramycin pharmacokinetic parameters. The amount of drug removed was measured and serum levels were obtained during plasma exchange. The effect of the procedure was evaluated by calculating the percentage of total body stores removed and comparing drug elimination half-life data on and off plasma exchange. The procedures resulted in the removal of 6.1%, 5.9% and 4.3% of total body stores of tobramycin. Plasma exchange provides an additional route of elimination for tobramycin which should be considered when dosing the drug in patients undergoing this procedure.