Management of abdominal pseudotumours in haemophilia: a systematic review

AIM: Haemophilic pseudotumours are complications in patients with haemophilia A or B and result from locally repetitive bleeding, mainly in the musculoskeletal system. Abdominal haemophilic pseudotumours are exceptionally rare but may cause severe complications. This systematic review aimed to evaluate therapy strategies for symptomatic abdominal haemophilic pseudotumours. METHODS: We systematically searched three databases (Medline [PubMed], Web of Science and EMBASE) for publications published between 1995 and 2023. Two reviewers independently selected the studies, extracted data and performed a quality assessment using the JBI critical appraisal checklist. RESULTS: From a total of 1199 articles, 39 articles describing 41 cases were included for final analysis. Conservative or interventional treatment was performed in 12 cases. In eight cases, a step-up to surgical therapy after interventional treatment was indicated. Primary surgical therapy was performed in 21 cases. Failure to cure was documented in 50% (n = 6) of patients treated in the first group, with a mortality rate of 16.6% (n = 2). Interventional therapy with a step-up to surgery showed no morbidity or mortality. Primary surgical resection documented favourable results in 66.6% (n = 14), with failure to cure in 9.5% (n = 2) and a mortality rate of 14.3% (n = 3). CONCLUSION: Primary surgical resection can be a first-line therapy for symptomatic, abdominal haemophilic pseudotumours, whereas preoperative embolisation could be used as a bridging therapy before surgery, especially in emergency settings. Diagnostic biopsy and percutaneous drainage should be avoided to prevent complications

Desire for biological parenthood and patient counseling on the risk of infertility among adolescents and adults with hemoglobinopathies.

BACKGROUND Both diagnosis and treatment of hemoglobinopathies have been associated with an increased risk of fertility impairment. German guidelines recommend annual monitoring of fertility parameters to enable early detection of fertility impairment and/or to offer fertility preservation (FP) when indicated. We explored the general desire for parenthood, the frequency of recalling fertility counseling and testing, and the utilization of FP in adolescents and adults with hemoglobinopathies. PROCEDURE In a cross-sectional study, patients aged 12-50 years, treated in Germany, Austria, or Switzerland, were surveyed on fertility-related aspects. Medical data, including fertility testing results, were collected from patient records. RESULTS Overall, 116/121 eligible patients, diagnosed with sickle cell disease (70.7%), thalassemia (27.6%), or other hemoglobinopathy (1.7%), participated in our study (57.8% female, median age 17.0 years, range 12-50 years). All participants required treatment of the underlying hemoglobinopathy: 68.1% received hydroxyurea, 25.9% required regular blood transfusions, and 6.0% underwent hematopoietic stem cell transplantation (HSCT). Most patients (82/108, 75.9%) stated a considerable to strong desire for (future) parenthood, independent of sex, education, diagnosis, or subjective health status. Fertility counseling was only recalled by 32/111 patients (28.8%) and least frequently by younger patients (12-16 years) or those treated with regular blood transfusions or hydroxyurea. While fertility testing was documented for 59.5% (69/116) in medical records, only 11.6% (13/112) recalled previous assessments. FP was only used by 5.4% (6/111) of patients. CONCLUSION Most patients with hemoglobinopathies wish to have biological children, yet only few recalled fertility counseling and testing. Adequate patient counseling should be offered to all patients at risk for infertility

Neonatal red blood cell transfusion practices in Switzerland:national survey and review of international recommendations

WHAT IS KNOWN ON THE SUBJECT? Red blood cell transfusions are frequently used in the care of newborns, particularly premature infants. Some countries have guidelines regarding preparation, indication and administration of red blood cells in newborns. There are no such guidelines in Switzerland. WHAT DOES THE CURRENT STUDY ADD? This study analysed the results of two national surveys, one among blood transfusion services and the other among neonatal units in Switzerland. The results demonstrate considerable heterogeneity and a lack of “unité de doctrine”. Establishment of national guidelines would be helpful and warranted. AIMS OF THE STUDY The aim of the study was to analyse Swiss practices in blood transfusion services and neonatal units for the preparation and administration of red blood cells in newborns. METHODS Two questionnaires were developed and their results analysed. A first questionnaire was developed for the Swiss blood transfusion services and local hospital haematology laboratories, and a second for the neonatal units in Switzerland. RESULTS 18/25 (72%) of laboratories and 26/29 (90%) of neonatal units performing red blood cell transfusions participated. Responses revealed a lack of consensus for the majority of questions. Differences were found in all steps of the process, from preparation (testing, irradiation, splitting, shelf life and storage of blood bags) to indication and administration (volume, speed, vascular access, patient monitoring) of red blood cells. Forty-six percent of neonatal units stated that they apply internal guidelines. Nevertheless, all but two would welcome the establishment of national recommendations. CONCLUSION This study confirmed the large variety in neonatal red blood cell transfusion practices in Switzerland. In the absence of clear evidence, national guidelines – as applied in other countries – would foster a common policy among Swiss neonatologists and facilitate the implementation of a national database for future research and comparison with international literature

Management of abdominal pseudotumours in haemophilia: a systematic review

AIM: Haemophilic pseudotumours are complications in patients with haemophilia A or B and result from locally repetitive bleeding, mainly in the musculoskeletal system. Abdominal haemophilic pseudotumours are exceptionally rare but may cause severe complications. This systematic review aimed to evaluate therapy strategies for symptomatic abdominal haemophilic pseudotumours. METHODS: We systematically searched three databases (Medline [PubMed], Web of Science and EMBASE) for publications published between 1995 and 2023. Two reviewers independently selected the studies, extracted data and performed a quality assessment using the JBI critical appraisal checklist. RESULTS: From a total of 1199 articles, 39 articles describing 41 cases were included for final analysis. Conservative or interventional treatment was performed in 12 cases. In eight cases, a step-up to surgical therapy after interventional treatment was indicated. Primary surgical therapy was performed in 21 cases. Failure to cure was documented in 50% (n = 6) of patients treated in the first group, with a mortality rate of 16.6% (n = 2). Interventional therapy with a step-up to surgery showed no morbidity or mortality. Primary surgical resection documented favourable results in 66.6% (n = 14), with failure to cure in 9.5% (n = 2) and a mortality rate of 14.3% (n = 3). CONCLUSION: Primary surgical resection can be a first-line therapy for symptomatic, abdominal haemophilic pseudotumours, whereas preoperative embolisation could be used as a bridging therapy before surgery, especially in emergency settings. Diagnostic biopsy and percutaneous drainage should be avoided to prevent complications

Donor age and red cell age contribute to the variance in lorrca indices in healthy donors for next generation ektacytometry: a pilot study

The ability of red blood cells (RBCs) to transport gases, their lifespan as well as their rheological properties invariably depend on the deformability, hydration, and membrane stability of these cells, which can be measured by Laser optical rotational red cell analyser (Lorrca® Maxsis, RR Mechatronics). The osmoscan mode of Lorrca is currently used in diagnosis of rare anemias in clinical laboratories. However, a broad range of normal values for healthy subjects reduces the sensitivity of this method for diagnosis of mild disease phenotype. In this pilot study, we explored the impact of age and gender of 45 healthy donors, as well as RBC age on the Lorrca indices. Whereas gender did not affect the Lorrca indices in our study, the age donors had a profound effect on the O_hyper parameter. To study the impact of RBC age on the osmoscan parameters, we have isolated low (L)-, medium (M)-, or high (H)- density fractions enriched with young, mature, and senescent RBCs, respectively, and evaluated the influence of RBC age-related properties, such as density, morphology, and redox state, on the osmoscan indices. As before, O_hyper was the most sensitive parameter, dropping markedly with an increase in RBC density and age. Senescence was associated with a decrease in deformability (EI_max) and tolerability to low and high osmolatites (Area). L-fraction was enriched with reticulocytes and cells with high projected area and EMA staining, but also contained a small number of cells small in projected area and most likely, terminally senescent. L-fraction was on average slightly less deformable than mature cells. The cells from the L-fraction produced more oxidants and NO than all other fractions. However, RBCs from the L-fraction contained maximal levels of reduced thiols compared to other fractions. Our study suggests that reference values for O_hyper should be age-stratified, and, most probably, corrected for the average RBC age. Further multi-center study is required to validate these suggestions before implementing them into clinical practice

Favorable pharmacokinetics in hemophilia B for nonacog beta pegol versus recombinant factor IX-Fc fusion protein: A randomized trial

Background and Objective: Nonacog beta pegol (N9-GP) and recombinant factor IX-Fc fusion protein (rFIXFc) are extended half-life rFIX compounds. We report the first single-dose pharmacokinetic trial of N9-GP and rFIXFc. Patients/Methods: Paradigm 7 was a multicenter, open-label, randomized, crossover trial in previously treated (>150 exposure days) adults with congenital hemophilia B (FIX activity ≤2%). Patients received single intravenous injections (50 IU/kg) of N9-GP and rFIXFc with at least 21 days between doses. Plasma FIX activity, predose, and at serial time points up to 240 hours postdose, was measured using validated one-stage clotting assays (SynthAFax for N9-GP; Actin FSL for rFIXFc) and a chromogenic assay (ROX factor IX) with normal human plasma as calibrator. The primary endpoint was area under the FIX activity-time curve from 0 to infinity, dose-normalized to 50 IU/kg (AUC$_{0-inf,norm}$). Results: Fifteen patients received study treatment. Based on FIX activity results from the one-stage clotting assays, estimated AUC$_{0-inf,norm}$ was significantly greater for N9-GP than rFIXFc (ratio: 4.39; P < 0.0001, based on a two-sided test on 5% significance level). In addition, N9-GP had a longer terminal half-life, two times higher incremental recovery at 30 minutes and maximum FIX activity (dose-normalized to 50 IU/kg) and six times higher FIX activity at 168 hours than rFIXFc. These findings were largely comparable with the chromogenic assay data and are consistent with published data for each compound. Conclusions: In this comparison, N9-GP demonstrated favorable pharmacokinetic characteristics versus rFIXFc, helping clinicians to understand differences between N9-GP and rFIXFc. Registration: This trial is registered with clinicaltrials.gov (NCT03075670) and the European Clinical Trials Database (EudraCT: 2016-001149-25)

The Fission Yeast Kinetochore Component Spc7 Associates with the EB1 Family Member Mal3 and Is Required for Kinetochore–Spindle Association

A critical aspect of mitosis is the interaction of the kinetochore with spindle microtubules. Fission yeast Mal3 is a member of the EB1 family of microtubule plus-end binding proteins, which have been implicated in this process. However, the Mal3 interaction partner at the kinetochore had not been identified. Here, we show that the mal3 mutant phenotype can be suppressed by the presence of extra Spc7, an essential kinetochore protein associated with the central centromere region. Mal3 and Spc7 interact physically as both proteins can be coimmunoprecipitated. Overexpression of a Spc7 variant severely compromises kinetochore–microtubule interaction, indicating that the Spc7 protein plays a role in this process. Spc7 function seems to be conserved because, Spc105, a Saccharomyces cerevisiae homolog of Spc7, identified by mass spectrometry as a component of the conserved Ndc80 complex, can rescue mal3 mutant strains

A pilot clinical phase II trial MemSID: Acute and durable changes of red blood cells of sickle cell disease patients on memantine treatment

An increase in abundance and activity of N-methyl D-aspartate receptors (NMDAR) was previously reported for red blood cells (RBCs) of sickle cell disease (SCD) patients. Increased Ca2+uptake through the receptor supported dehydration and RBC damage. In a pilot phase IIa-b clinical trial MemSID, memantine, a blocker of NMDAR, was used for treatment of four patients for 12 months. Two more patients that have enrolled into the study did not finish it. One of them had psychotic event following the invol-untary overdose of the drug, whereas the other had vertigo and could not comply to the trial visits schedule. Acute and durable responses of RBCs of SCD patients to daily oral administration of memantine were monitored. Markers of RBC turnover, changes in cell density, and alterations in ion handling and RBC morphology were assessed. Acute transient shifts in intracellular Ca2+, volume and density, and reduction in plasma lactate dehydrogenate activity were observed already within the first month of treatment. Durable effects of memantine included (a) decrease in reticulocyte counts, (b) reduction in reticulocyte hemoglobinization, (c) advanced membrane maturation and its stabilization as follows from reduction in the number of NMDAR per cell and reduction in hemolysis, and (iv) rehydration and decrease in K+leakage from patients’ RBC. Memantine therapy resulted in reduction in number of cells with sickle morphology that was sustained at least over 2 months after therapy was stopped indicating an improvementin RBC longevity