ABO non-identical platelet transfusions, immune platelet refractoriness and platelet support.

ABO-non-identical (ABO-ni) platelets may be another risk factor for immune platelet transfusion refractoriness (i-PTR). We examined the effect of such platelets on i-PTR and subsequent platelet support through retrospective analysis of 17 322 New Zealand patients receiving ≥1 platelets. Immune PTR was defined as PTR with anti-HLA-I/HPA positivity. Univariate and multivariate analyses determined the independent risk factors for i-PTR. One hundred and eighty-eight patients (1.1%) had i-PTR and received more ABO-ni platelets than non-refractory patients (53.2% vs. 29.5%; p < 0.001). More non-O than group O patients had received ABO-ni platelets before i-PTR diagnosis (67.6% vs. 32.5%; p < 0.001). Female sex (p < 0.001), age ≤ 60 years (p = 0.004), haematology patients (p < 0.001) and ≥2 ABO-ni platelets (p < 0.001) were the independent risk factors for i-PTR. More i-PTR patients with anti-HLA-I were non-O compared to group O (90.1% vs. 75.3%; p = 0.007). More with anti-HLA-I + anti-HPA were group O than non-O (24.7% vs. 9.0%; p = 0.003). ABO-ni platelet-exposed i-PTR patients required matched platelets for longer than those receiving only ABO-i platelets (96.5 vs. 59.0 days; p = 0.02). ABO-ni platelets may be a risk factor for i-PTR with dose effect. ABO-i platelets should be considered whenever possible for at-risk patients.

Reactions to serum eye drops-New Zealand experience and review of the literature.

BACKGROUND: Serum eye drops (SED) are used to treat ocular surface disease. Reactions to SED are poorly documented. METHODS: We present our experience of self-reported reactions in New Zealand to SED (25%; autologous, allogeneic, or both) between 2003 and 2023, and a focused review of the literature. RESULTS: In total, 1067 patients received SED treatment (562 autologous, 318 allogeneic, and 187 both). Three (0.5% of those treated with allogeneic SED) reported reactions. All appeared to be allergic. All were associated with allogeneic SED. We have information on two patients: one had an eye reaction; in the other, the gastrointestinal tract was involved. The literature contains few reports of reactions to SED. They have involved both autologous and allogeneic SED, and various SED concentrations. None appears to have been severe. Notably, no eye or systemic infections have been reported. CONCLUSIONS: Information on the types and frequencies of reactions to SED is poor. This may be due to: serum being less likely to cause reactions; eyes being resistant to reactions; reactions being rare, and insufficient use of SED having occurred; under-reporting related to SED use at home and reactions being mild. More robust monitoring for reactions to SED is needed.

A critical assessment of dose effects of post-thaw CD34 on autologous stem cell transplantation treatment of haematological malignancies.

A consensus threshold of pre-cryopreservation CD34-positive cells (CD34s) has been used as the minimum dose to initiate autologous stem cell transplantation (ASCT). Advances in cryopreservation posed a debate whether post-thaw CD34s might be a superior surrogate instead. We addressed the debate in this retrospective study of 217 adult ASCTs in five different haematological malignancies treated at a single centre. We showed that post-thaw CD34s was highly correlated with pre-cryopreservation CD34s (r = 0.97) and explained ∼2.2% (p = 0.003) of the variation of the post-thaw total nucleated cell viability that however had no power to predict engraftment outcomes. After stratifying the ASCT cases into four dose groups based on post-thaw CD34s reinfused, stepwise multivariate regression analyses detected significant effects in dose group and interactions with diseases for neutrophil and platelet recovery respectively. The significant dose effects and interactions were triggered by two technical outliers in the low dose group, and disappeared in the repeated regressions after exclusion of the outliers where disease and age were the significant predictors remained. Our data clearly support the validity of the consensus threshold in ASCT applications but also highlight neglected conditions where monitoring post-thaw CD34s and clinical attributes are valuable.

Red blood cell alloantibodies in the context of critical bleeding and massive transfusion.

BACKGROUND: In the context of critical bleeding and massive transfusion (CB/MT), little is known about the development of new red blood cell (RBC) alloantibodies. We performed a retrospective, observational study to examine the frequency of RBC alloantibodies (pre-existent, anamnestic, or new) in patients with CB/MT, defined as transfusion of five or more RBC units in any 4-hour period, for any cause of CB. MATERIALS AND METHODS: Data on 2,585 New Zealand patients (date/time of MT initiation, demographic data, blood group, clinical context, and transfused RBCs) were obtained from the Australian and New Zealand Massive Transfusion Registry. RBC alloantibody screening/identification data were extracted from the New Zealand Blood Service database. We calculated summary statistics, compared proportions between different independent groups using the Chi-squared test, and performed logistic regression analysis to examine the effects of variables on alloantibody presence or formation. We also determined the immunogenicities of selected RBC antigens in the context of CB/MT. RESULTS: Of 1,234 assessable patients, 1,166 (94.5%) showed no evidence of any alloantibody. Pre-existent, anamnestic, and new alloantibodies were found, respectively, in 4.3%, 0.4%, and 7.2% of assessable patients. By multivariable regression analysis, transfusion of D-positive RBC to D-negative patients was independently associated with new alloantibody formation. Neither the quantum of RBC transfused nor trauma as clinical context were so associated although the latter trended towards a predisposition. "Antibodies of undetermined specificity" were the commonest pre-existent and new alloantibodies. The immunogenicity of Jka was the highest in this setting. DISCUSSION: RBC alloantibodies of any type were rare in this CB/MT population. Patients undergoing CB/MT appear to have low risks of re-stimulating anamnestic alloantibodies, or of developing new RBC alloantibodies.

Transfusion double whammy? Adrenaline-takotsubo-anaphylaxis-Kounis complex post transfusion?

BACKGROUND AND OBJECTIVES: The adrenaline-takotsubo-anaphylaxis-Kounis, or the ATAK complex, where there are clinical and pathophysiological overlaps between takotsubo and Kounis syndromes, in which histaminergic, adrenergic and other mediators may play roles, was recently described. The objective of this report was to describe three cases where the ATAK complex was suspected to have occurred after transfusion. MATERIALS AND METHODS: Three cases were recently reported to the New Zealand Blood Service haemovigilance programme that appeared to have features in common suggestive of the ATAK complex. RESULTS: All three patients had had a blood component transfused, an initial severe allergic reaction, treatment with adrenaline or a congener, subsequent acute left ventricular failure or transfusion-associated circulatory overload, and features suggestive of takotsubo cardiomyopathy. CONCLUSIONS: Although rarely described, transfusion-associated ATAK complex may be occurring more often than believed. Circumstances during a transfusion may predispose to it. It should be suspected if the sequence of events described above occur. Its characteristics need to be better understood. Risk factors for it may be modifiable.

Placebo and nocebo effects in transfusion medicine.

BACKGROUND: Our own observations suggested that placebo and nocebo effects may occur with transfusions. However these effects seem to have been poorly studied. OBJECTIVES: To examine published information on, and draw attention to the possibility of, placebo and nocebo effects with transfusion. METHODS: Focused literature review. RESULTS: There is some information on placebo effects with clotting factors and this effect appears modest at best. There is very little published information on this regarding other fresh blood components. Although unknown biologic effects cannot be ruled out, there are hints that placebo effects might operate - especially with red blood cell transfusions. There is practically no information on nocebo effects with transfusions. CONCLUSIONS: There are ways of surmounting the practical and ethical difficulties involved, and obtaining better information on both types of effects. Individualised, contextualised, informed consenting of transfusion recipients may help to enhance placebo, and reduce nocebo, effects. This may be supportable ethically, and desirable clinically, and financially.

Analysis of transfusion therapy during the March 2019 mass shooting incident in Christchurch, New Zealand.

BACKGROUND AND OBJECTIVE: A mass casualty incident occurred in Christchurch in March 2019. Thirty-seven patients with gunshot wounds were admitted. We describe and analyse the transfusion management of these casualties. METHODS: Data on demographics, injury and laboratory characteristics, and transfusions are summarized using descriptive statistics. Relationships between variables are examined using Pearson's and Spearman's rank correlations. Univariate analysis of explanatory variables is performed to determine the best early predictors of transfusion requirements. The characteristics of massive transfusion and non-massive transfusion cases are compared using the t- and Mann-Whitney tests. RESULTS: Sixty-five per cent received transfusions. Initial Hb, platelet counts and clotting results were mostly normal. On average, each gunshot wound patient was transfused 4, 3·1, 1·2 and 0·4 units of RBC, FFP, cryoprecipitate and platelets, respectively, on the day. Base excess was the single best predictor of transfusion requirements. CONCLUSIONS: A greater proportion of those with gunshot wounds in this incident were transfused than in other such incidents. Transfusion requirements for patients varied but were generally modest. Blood component transfusion ratios were close to that recommended. The role of base excess as a predictor of transfusion requirements in patients with similar injuries needs more study.

Improving the use and timeliness of anticoagulation reversal for warfarin related intracranial haemorrhage.

BACKGROUND: Warfarin-related intracranial haemorrhage (WRICH) is a life-threatening complication of warfarin use. Rapid and complete reversal of the coagulopathy is required. Reversal protocols which include prothrombin complex concentrates (PCC) are now recommended. We report on a quality improvement project to implement and refine such a protocol. METHODS: Retrospective and then prospective audits of all WRICH patients presenting to a single centre. The protocol development and subsequent refinements are described. Outcomes included times to scanning, treatment and overall door-needle times, as well as use of PCC. RESULTS: Across the three cohorts, use of PCC increased over time from 15% to 100% of eligible patients (p<0.001). There were significant improvements in median time to scanning (1.9 to 1.5 to 1.3 hours, p=0.03) and median door-needle times (4.5 to 2.9 to 1.9 hours, p=0.018). Key steps in the change process included (1) identifying need for change, (2) utilising senior clinical opinion leaders, (3) using "Plan-do-study-act" cycles, (4) involvement of all relevant stakeholders, (5) having a broad implementation and education plan, (6) a "change friendly" environment and (7) collaborating across departments. CONCLUSION: The introduction (and revisions) of an anticoagulation reversal strategy for WRICH has led to increased PCC use and reduced times to both diagnosis and treatment. Further work is required to improve door-needle times and monitoring.

Incidence of maternal sensitisation to Rh(D) in Christchurch, New Zealand and reasons for prophylaxis failures.

AIM: To estimate the current incidence of maternal sensitisation to Rh(D) and examine reasons for prophylaxis failures. METHOD: Retrospective chart review of new sensitisations to Rh(D) detected in antenatal records, between 2005 and 2012 in Christchurch, New Zealand and systematic examination of circumstances likely to have caused prophylaxis failures. RESULTS: Fifty-four new sensitisations in an at-risk population of about 4624 in 8 years means an incidence of roughly 1.1%. In 86.6% of 45 sensitisations where information was available, there was a recognised sensitising event including previous deliveries while in 13.3% there were none. Of those with recognised sensitising events, 46.1% had anti-D prophylaxis per local guidelines, in 12.8%, prophylaxis was given though it did not conform, entirely, to guideline. No prophylaxis at all was given to 41% despite a sensitising event being recognised. CONCLUSION: The incidence of maternal sensitisation to Rh(D) in Christchurch, New Zealand, is as expected given our prophylaxis regimen. Half the sensitisations were associated with complete or partial failure to follow local guidelines. Better adherence to this may reduce incidence of sensitisation. It is also thrice as high as might be expected with a routine antenatal anti-D prophylaxis (RAADP) program. An economic analysis of RAADP in New Zealand will be useful.

Phlebotomy patterns in haemochromatosis patients and their contribution to the blood supply.

AIMS: To determine venesection patterns in hereditary haemochromatosis (HC) patients in Christchurch, New Zealand, their contribution to the blood supply, and reasons for deferral. METHODS: Review of clinical records of 412 HC patients venesected by the NZ Blood Service at least once during 2009. RESULTS: Of 275 males and 137 females, 384 had been tested for HFE gene mutations--76% were C282Y homozygotes, 12.8%, C282Y/H63D compound heterozygous, 8.6%, either H63D homozygotes, C282Y heterozygotes or H63D heterozygotes. Small numbers had no detectable mutations, were not iron overloaded but had been venesected for isolated hyperferritiniaemia. 53% were donors. C282Y homozygotes required significantly more venesections than patients of other genotypes. Eligible HC patients donated 3 units/donor/year compared to 1.63/person/year by healthy donors (p<0.001). HC patients contributed 3.4% of whole blood collections in 2009. There were 212 permanent or temporary donation deferrals--common reasons were abnormal liver functions, chronic or malignant disease, or immigration from vCJD risk countries. CONCLUSIONS: HC donors donate at nearly twice the rate of healthy donors but contribute only a small amount to the blood pool. Revision of selection criteria may increase this contribution without compromising blood safety.

Iron status and risk-profiling for deficiency in New Zealand blood donors.

AIM: To assess the iron status of New Zealand blood donors using the serum ferritin (ferritin) assay and the impact of gender, age, and donation history on iron status. METHODS: Ferritin levels were measured in 5006 subjects attending two New Zealand Blood Service (NZBS) blood donor sites between October and December 2006. The influence of three major determinants of iron status (gender, age, and blood donation history) in the previous 12 months was assessed. RESULTS: Ferritin levels tended to be lower in younger people, females, and those with more intensive blood donation history. Levels lower than 12 mcg/L were found in 14.1% of subjects overall, 19.9% of females, 19.0 % of those aged under 20 years, and 25.1% of those who had donated 3-4 whole blood units during the previous 12 months had ferritin levels lower than 12 mcg/L. Risks were additive and total risk correlated inversely with ferritin levels. CONCLUSIONS: Iron deficiency is a significant problem in New Zealand blood donors. Prevention or treatment, as appropriate, would help both donors and the long-term supply of blood. A stratified approach to testing, prevention and treatment taking into account risk factors, ferritin and Hb levels is likely to be the most effective strategy.