Acute haemolytic transfusion reaction after transfusion of fresh frozen plasma in a neonate-Preventable by using solvent/detergent-treated pooled plasma?

BACKGROUND: Plasma is a commonly used blood product and is available in the form of fresh frozen plasma (FFP) or pooled solvent/detergent-treated plasma. In the Netherlands, solvent/detergent-treated plasma has become the standard product in the adult population since several years, but for neonatal use, FFP remains the product of preference. DESCRIPTION: A preterm neonate developed lung bleeding at day 8 postpartum, for which intubation and mechanical ventilation was required and transfusions with packed red blood cells and plasma, in the form of FFP, were given. Five hours after transfusion, a red discoloration of the urine occurred. An acute haemolytic transfusion was suspected, confirmed by laboratory investigations (fast decrease in haemoglobin, increased free haemoglobin, decreased haptoglobin, increased lactate dehydrogenase and a positive direct antiglobulin test [IgG 2+]). Additional research showed that the FFP product contained nonspecific auto-antibodies that reacted with the transfused erythrocytes, most test erythrocytes and the donor's own erythrocytes. CONCLUSION: A neonate experienced an acute haemolytic reaction, most probably caused by administrating a FFP product containing auto-antibodies. If transfused with solvent/detergent-treated plasma, such antibodies would have been diluted or captured. This case adds a new argument to the discussion on expanding the use of solvent/detergent-treated plasma to the paediatric population.

The effect of extended c, E and K matching in females under 45 years of age on the incidence of transfusion-induced red blood cell alloimmunisation.

Maternal alloantibodies directed against fetal red blood cell (RBC) antigens may cause potentially life-threatening haemolytic disease of the fetus and newborn (HDFN). Dutch transfusion guidelines therefore prescribe preventive cEK matching for all (pre-)fertile females. To quantify the impact of cEK matching, we compared overall and antigen-specific cumulative RBC alloimmunisation incidences in females and males aged <45 years. Among a multicentre cohort comprised of patients who received their first and subsequent RBC unit between 2005 and 2019, first-formed RBC alloantibodies were detected in 47 of 2998 (1·6%) females and 49 of 2507 (2·0%) males. Comparing females and males, overall alloimmunisation incidences were comparable (3·1% [95% confidence interval (CI) 2·1-4·4] versus 3·5% (95% CI 2·4-4·9, P = 0·853) after 10 units transfused). However, cEK alloimmunisation incidences were significantly lower among females (0·6% (95% CI 0·3-1.5) versus 2·2% (95% CI 1·5-3·4, P = 0·001) after 10 units transfused). Yet, despite cEK-matching guidelines being in effect, 6·5%, 3·6% and 0·2% of all RBC units remained mismatched for c, E or K antigens respectively. Most of these mismatches were almost always due to emergency settings. Even though cEK alloimmunisation was not prevented completely, implementation of cEK matching resulted in an alloantigen-exposure risk reduction of up to 98%.

Designing a diagnostic Total Testing Process as a base for supporting diagnostic stewardship.

To more comprehensively support clinical management of patients in our hospital, we redesigned the diagnostic Total Testing Process (TTP) from request to report. To that end, clinical needs were identified and a vision on Total Laboratory Automation (TLA) of the TTP was developed. The Delft Systems Engineering Approach was used for mapping a desirable laboratory testing process. The desirable "To Be" diagnostic process was tendered and the translation of a functional design into a specific TLA-configuration - compliant with the vision and the predefined functional design - was accomplished using a competitive dialogue tender variant (based on art. 29 of the EU guideline 2014/24). Realization of this high-end TLA-solution enabled a high-quality testing process with numerous improvements such as clear and supportive digital request forms, specimen consolidation, track and trace and non-conformity registration at the specimen level, better blood management (∼40% less blood sampled), lean and in line processing with increased productivity (42% rise in test productivity per capita), and guaranteed total turn-around-times of medical tests (95% of TLA-rooted in line tests are reported <120 min). The approach taken for improving the brain-to-brain loop of medical testing, as fundament for better diagnostic stewardship, is explained.

Sunitinib-associated pseudothrombocytopenia induced by IgM antibody.

Thrombocytopenia is a well-documented adverse reaction of sunitinib. Thrombocytopenia was observed in a patient with metastatic renal clear-cell carcinoma undergoing sunitinib treatment. Platelet count in an ethylenediaminetetraacetic acid (EDTA) sample was 19 × 10(9)/l. To exclude pseudothrombocytopenia (PTCP), a platelet count in citrate-anticoagulated blood was performed, showing a platelet count of 6 × 10(9)/l. Due to the apparent thrombocytopenia, the patient received platelet concentrates. Subsequent analyses revealed PTCP whereby platelet clumping was most abundant in citrate - followed by EDTA- and heparin-anticoagulated blood samples. This effect was partially reversed after placing blood samples at 37°C. The IgM antiplatelet autoantibodies responsible for in vitro agglutination are temperature and multianticoagulant dependent and did not react to amikacin pre-supplementation. Remarkably, the antibody revealed specificity to platelet antigens other than GPIIb/IIIa, GPIb/IX, GPIa/IIa, GPIV, and GPV. After 16 days of discontinuing sunitinib, no PTCP and no platelet reactive antibodies could be detected. We report a case of PTCP with clear time-relation with sunitinib, strongly suggesting the mechanism to be sunitinib dependent. Since this finding has not been described before, non-recognition of PTCP during sunitinib treatment might lead to dose reduction or unwarranted therapy.

A case of consistent discrepancies between urine and blood human chorionic gonadotropin measurements.

BACKGROUND: Our laboratory was confronted with two successive urine samples from a single patient which tested positive for human chorionic gonadotropin (hCG) when tested with both qualitative and quantitative assays, combined with no detectable hCG in corresponding plasma samples. METHODS: Serial dilution and recovery experiments were performed in order to investigate the presence of interfering substances or a high-dose hook effect. The ovarian cysts that were removed from this patient were immunohistochemically stained using polyclonal anti-human hCG antibodies. Furthermore, a urine sample was sent to the USA hCG Reference Service for hCG variant analysis. RESULTS: Dilution and recovery experiments in urine and plasma samples were unremarkable. The biopsy stained negative for human hCG and free ß-subunit. hCG isoform analysis in the urine sample revealed that approximately 87.5% of the immunoreactive hCG lacked the ß-subunit C-terminal peptide (CTP). CONCLUSIONS: We report a rare case in which two successive urine samples test positive for hCG whereas in corresponding plasma samples hCG is undetectable. The majority of the total hCG contained a degraded form of ß-subunit that lacks the CTP. This hCG variant, possibly of pituitary origin, is thought to have an extreme fast clearance rate possibly explaining the discordance between the hCG results in urine and plasma samples.

[High prevalence of vitamin D deficiency in the south-west Netherlands]. / Hoge prevalentie van vitamine D-deficiëntie in Zuidwest-Nederland.

OBJECTIVE: To determine how often vitamin D deficiency occurs in the populations of a city, the countryside and urbanised areas of the countryside, and also the influence of the seasons. DESIGN: Cross-sectional study carried out in the winter and summer of 2013. Trend analysis from requests for determination of vitamin D levels by general practitioners between January 2010 and August 2012. METHOD: In a random sample survey of all blood samples received by SHL-Groep (diagnostic center for primary care) between 21-01-2013 - 10-03-2013 (winter period) and 01-08-2013 - 30-08-2013 (summer period), Vitamin D levels of the residual material were measured. We reported the results by age group, gender and postal code area in the following areas: The Hague (city), Province of Zeeland (countryside) and West Brabant (urbanised countryside). In addition, the average vitamin D concentration obtained from all the requests for determination of vitamin D levels between January 2010 and August 2012 was measured against the time of year. RESULTS: During the winter period 58.8% of the 2503 participants had a vitamin D serum concentration of < 50 nmol/l (The Hague: 65.6%; Zeeland: 50.9%). A total of 29.9% had vitamin D levels of < 30 nmol/l. In men under the age of 50 years, this was 38.2%. Of the 1910 people tested during the summer, 35.4% had a vitamin D level of < 50 nmol/l (The Hague: 43.7%; Zeeland: 33.5%). 11.6% had a vitamin D level < 30 nmol/l. General practitioners requested the vitamin D levels of 50,441 patients. The average vitamin D level varies considerably with the seasons. CONCLUSION: Vitamin D deficiency occurs frequently, even in relatively young people and more so in cities than in the countryside. The average vitamin D concentration varies with the seasons.