Ulrik Sprogøe

Report of the first nationally implemented clinical routine screening for fetal RHD in D- pregnant women to ascertain the requirement for antenatal RhD prophylaxis

BACKGROUND: A combination of antenatal and postnatal RhD prophylaxis is more effective in reducing D immunization in pregnancy than postnatal RhD prophylaxis alone. Based on the result from antenatal screening for the fetal RHD gene, antenatal RhD prophylaxis in Denmark is given only to those D− women who carry a D+ fetus. We present an evaluation of the first national clinical application of antenatal RHD screening.

Routine noninvasive prenatal screening for fetal RHD in plasma of RhD-negative pregnant women—2 years of screening experience from Denmark

Prenatal and postnatal RhD prophylaxis reduces the risk of RhD immunization in pregnancies of RhD‐negative women. Based on the result from prenatal screening for the fetal RHD gene, prenatal RhD prophylaxis in Denmark is targeted to RhD‐negative women who carry an RhD‐positive fetus. Here, we present a 2‐year evaluation of a nationwide prenatal RHD screening.

Acute antibody-mediated rejection after ABO-incompatible kidney transplantation treated successfully with antigen-specific immunoadsorption

ABO-incompatible kidney transplantation is possible after pre-treatment with rituximab, intravenous immunoglobulin and basiliximab combined with tacrolimus, mycophenolate mofetil and prednisolone. We report on the first patient treated with this protocol who developed acute antibody-mediated rejection (Banff grade II with IgG deposits) caused by ABO antibodies (anti-B). Anti-rejection treatment with anti-B-specific immunoadsorption, intravenous immunoglobulin and methylprednisolone efficiently cleared deposited IgG from the kidney allograft and re-established normal kidney function. We suggest that ABO-incompatible kidney transplantation complicated by acute antibody-mediated rejection, caused by ABO antibodies, may successfully be treated with this regime.

Measurement of platelet aggregation, independently of patient platelet count: A flow-cytometric approach

Essentials Platelet function may influence bleeding risk in thrombocytopenia, but useful tests are needed. A flow cytometric platelet aggregation test independent of the patient platelet count was made. Platelet aggregation was reduced in thrombocytopenic patients with hematological cancer. High platelet aggregation ruled out bleeding tendency in thrombocytopenic patients.

An international investigation into O red blood cell unit administration in hospitals: the GRoup O Utilization Patterns (GROUP) study

Transfusion of group O blood to non‐O recipients, or transfusion of D– blood to D+ recipients, can result in shortages of group O or D– blood, respectively. This study investigated RBC utilization patterns at hospitals around the world and explored the context and policies that guide ABO blood group and D type selection practices.

One year period prevalence of blood transfusion

Transfusion practice is reported to differ considerably between countries. Comparisons often rely on transfusion rates, incidence ‐ or prevalence rates. In this paper, the one‐year period prevalence rate (1‐YPPR) of transfusion of red cells (RBC) is presented.

Minimal variation in anti-A and -B titers among healthy volunteers over time: implications for the use of out -of- group blood components

BACKGROUND Using potentially out-of-group blood components, like low titer A plasma and O whole blood, in the resuscitation of trauma patients is becoming increasingly popular. However, very little is known whether the donors’ anti-A and/or anti-B titers change over time and whether repeated titer measurements on the same donor are required to ensure that each donation produces a low titer product. METHODS The anti-A and/or anti-B titers were measured on 56 healthy adult volunteers (47 blood donors; nine blood center personnel) every 3 months for 12 consecutive months using an automated solid phase analyzer. The results were expressed as log2 titer steps (e.g., titer 32 = 5 titer steps). RESULTS Minor variations in the average anti-A and/or anti-B titers were seen over time; the maximum individual SD in each group was 1.50 (IgG anti-A) or 1.00 (IgM anti-A, IgM, and IgG anti-B). When the SDs for the four titer measurements from all 56 volunteers were combined as appropriate, the highest overall combined SD was 0.47 titer steps for IgG anti-A. This value corresponds to a 95% confidence interval for intraindividual variation in this antibody’s titer over 12 months of 0.96 titer steps. Thus, based on one measurement, an IgG anti-A with a titer step of, for example, 6 would be expected to be in the range of titer step 5 to titer step 7 over the course of 1 year with 95% probability. CONCLUSION The titers of anti-A and/or anti-B among healthy adults are stable over at least 1 year. This suggests that repeated titer measurements within a year on the same donor are not necessary if donations are made at 3 months or longer intervals. LEVEL OF EVIDENCE Diagnostic study, level V.

Dose-time-response relationship in peanut allergy using a human model of passive cutaneous anaphylaxis

FIG 1. The number of reacting recipients (gray bars) and the median Treact (C/erythema and o/wheal) in relation to the level of sIgE. The study includes 10 recipients sensitized with serum from donor 2 (Table E1) in 5 increasing concentrations. The oral peanut challenges were carried out as single dose (10 g of whole peanut). To the Editor: The extensive use of the double-blind, placebo-controlled oral food challenge in the diagnosis of food allergy and the growing uncertainties about the appropriate time interval between dose steps highlight the need to better understand which factors govern the reaction time in anaphylaxis, that is, the time it takes for an allergic reaction to develop after a patient has ingested the allergen. The purpose of this study was to determine whether the serum level of allergen specific IgE (sIgE) and/or the oral challenge dose affect the reaction time (Treact) and the size of the wheal (Swheal) in IgE-mediated, cutaneous reactions in vivo. Details of the methods can be found in this article’s Methods section in the Online Repository at www.jacionline.org. Briefly, we used the method of passive cutaneous specific hypersensitivity to test our hypotheses in a patient-safe manner. In this technique, which Prausnitz and K€ustner were the first to describe, human serum from 4 donors with severe peanut allergy was injected intradermally into nonallergic individuals (the recipients, 41 healthy adults). The sIgE levels to peanut/Ara h2 of the donor sera were 7.5/1.7, 60.1/36.3, 61.8/45.0, and 93.1/71.0 kIU/L (see Table E1 in this article’s Online Repository at www. jacionline.org). After the serum injections, the recipients underwent oral challenges with the causal allergen (peanut) to elicit an immediate and local allergic skin reaction at the original sites of the serum injections. The oral challenges were performed either as single dose or in a titrated protocol. In this study, Treact was defined as the time from the challenge dose was swallowed to the first signs of erythema appeared at the sensitized skin site, but it was considered positive only if a wheal also subsequently developed. Swheal was measured when the wheal was at its maximal size. All donors met the specific eligibility criteria outlined by the Danish Blood Safety Directives. The Regional Scientific Ethics Committee for Southern Denmark approved the study protocol (Project-ID: S-20130086). The median Treact decreased when the serum from the same donor was less diluted, that is, when the sIgE levels to peanut and Ara h2 increased (solid lines in Fig 1). All recipients reacted at the skin sites sensitized with the 3 highest sIgE levels, whereas only 4 of 10 and 7 of 10 reacted to the 2 lowest sIgE levels (gray bars in Fig 1). The importance of the level of sIgEwas further substantiated by comparing the sera from the 4 donors with different sIgE levels (see Fig E1 in this article’s Online Repository at www. jacionline.org). In addition, themedian Treact of the serumwith the lowest sIgE to peanut (donor 1; see Table E1) and the 10% serum from the dilution experiment (Fig 1) were comparable. The median Treact also decreased with increasing oral doses of peanut in the single-dose challenges (Fig 2, A). The pattern observed for Swheal was an increasing wheal diameter with increasing doses of peanut (Fig 2, B). Finally, the titrated oral peanut challenges with 1-hour dose intervals demonstrated large variations in threshold mimicking the real-life situation in patients (see Fig E2 in this article’s Online Repository at www. jacionline.org). This study is the first to investigate the significance of the level of allergen sIgE on the reaction time (Treact) in the allergic response as well as the significance of the challenge dose in relation to Treact and the size of the resulting wheal (Swheal) of IgEmediated cutaneous reactions using a human model of passive cutaneous anaphylaxis. We found that an increase in the sIgE level as well as an increase in the challenge dose shorten Treact in the allergic response. We also found that a higher challenge dose increases the magnitude of IgE-mediated cutaneous reactions, that is, Swheal. Our findings are in keeping with those of Brunner and Walzer as well as Aoki et al. Both studies showed that a wheal-and-flare reaction first appears at the skin site sensitized with undiluted serum and then later at the sites of decreasing serum concentrations. The results from the challenges in our study indicate that a dose-time-response relationship applies for IgE-mediated reactions: a short Treact correlates with a high sIgE level and a high challenge dose, and a small Swheal correlates with a low challenge dose. However, Treact appeared to reach a maximum at a certain sIgE level seeing that there was no significant difference in Treact for the sera with Ara h2 levels from 36.3 kIU/L to 71.0 kIU/L (Fig E1). Similarly, a maximum response, that is, Swheal, appeared to be reached at 10 g of peanut in our recipients (Fig 2, B). This study also showed that the sIgE level had to be above a certain level for all recipients to respond to the same dose of peanut (Fig 1 and Fig E1) and at the lowest challenge doses several recipients did not react even though they had been sensitized with equal amounts of sIgE from the same donor (Fig E2). This between-subject biological variation could be explained by differences in the gastrointestinal absorption of peanut and that a certain serum concentration of the allergen is required for the reaction to develop given that neither body weight nor body mass index correlated with the response (data not shown). The results mimic classical pharmacokinetics and pharmacodynamics, and perhaps studies on allergen uptake, distribution,

The Crossmatch/Issue Ratio: Use of a Novel Quality Indicator and Results of an International Survey on RBC Crossmatching and Issuing Practices.

OBJECTIVES To understand the worldwide scope of RBC crossmatching and issuing practices and measure efficiency using a novel quality indicator, the crossmatch/issue (C/I) ratio. METHODS An electronic survey was disseminated to hospital transfusion services collecting details about RBC crossmatching and issuing practices. Respondents were asked to enumerate the number of RBCs crossmatched and issued at their institutions during the 2014 calendar year to calculate the C/I ratio. RESULTS Fifty-two survey responses were received, mostly from North American transfusion services (28/52, 54%). The electronic crossmatch was the most common technique (n = 29), and most respondents performed the crossmatch at the time that an order for RBCs was received in the transfusion service (even if an order to issue the RBCs was not received). Data to calculate the C/I ratio were supplied by 22 respondents, and the mean ± SD was 1.30 ± 0.34. There was no difference in C/I ratios between services that use the electronic or serologic crossmatch techniques (P = .49). The ratio was the same at the four sites that crossmatch RBCs at the time of issue compared with the time of order receipt (mean ± SD, 1.11 ± 0.09 vs. 1.35 ± 0.36, respectively; P = .19). CONCLUSIONS Electronic crossmatching is common, and the C/I ratio can be an indicator of efficiency.

Reduced platelet activation and platelet aggregation in patients with alcoholic liver cirrhosis

Abstract Results from previous studies regarding platelet function in liver cirrhosis are discordant. The aim was to investigate platelet activation and platelet aggregation in patients with alcoholic liver cirrhosis. We included 27 patients with alcoholic liver cirrhosis and 22 healthy individuals. A recently established flow cytometric approach was used to measure platelet activation and platelet aggregation independent of sample platelet count. Platelet aggregation was further investigated using light transmission aggregometry (LTA) (for platelet count >100 × 109/L). Platelet agonists were adenosine diphosphate, thrombin receptor-activating peptide, arachidonic acid, collagen, and collagen-related peptide. Patients had lower median platelet count than healthy individuals, 125 × 109/L (interquartile range [IQR] 90˗185) versus 240 × 109 (IQR 204˗285), p < 0.001. Platelet activation levels in stimulated samples were lower in patients versus healthy individuals, e.g., after collagen-related peptide stimulation, the median percentage of platelets positive for activated glycoprotein IIb/IIIa was 85% (IQR 70–94) in patients versus 97% (IQR 94–99) in healthy individuals, p < 0.001; lower platelet activation capacity being associated with low platelet count and Child–Pugh class B/C cirrhosis. Flow cytometric platelet aggregation was reduced in patients for collagen-related peptide and for adenosine diphosphate, e.g., platelet aggregation (mean ± standard deviation) was 57% ± 4 in patients versus 70% ± 1 in healthy individuals for collagen-related peptide, p = 0.01. Light LTA showed reduced collagen-induced platelet aggregation in some patients compared with healthy individuals. In conclusion, platelet function was reduced in some patients with alcoholic liver cirrhosis and the severity was associated with platelet count and severity of liver cirrhosis.