Prevalence and 6-month recovery of olfactory dysfunction: a multicentre study of 1363 COVID-19 patients.

OBJECTIVE: To investigate prevalence and recovery of olfactory dysfunction (OD) in COVID-19 patients according to the disease severity. METHODS: From 22 March to 3 June 2020, 2581 COVID-19 patients were identified from 18 European hospitals. Epidemiological and clinical data were extracted at baseline and within the 2-month post-infection. RESULTS: The prevalence of OD was significantly higher in mild form (85.9%) compared with moderate-to-critical forms (4.5-6.9%; P = 0.001). Of the 1916 patients with OD, 1363 completed the evaluations (71.1%). A total of 328 patients (24.1%) did not subjectively recover olfaction 60 days after the onset of the dysfunction. The mean duration of self-reported OD was 21.6 ± 17.9 days. Objective olfactory evaluations identified hyposmia/anosmia in 54.7% and 36.6% of mild and moderate-to-critical forms, respectively (P = 0.001). At 60 days and 6 months, 15.3% and 4.7% of anosmic/hyposmic patients did not objectively recover olfaction, respectively. The higher baseline severity of objective olfactory evaluations was strongly predictive of persistent OD (P < 0.001). CONCLUSION: OD is more prevalent in mild COVID-19 forms than in moderate-to-critical forms. OD disappeared in 95% of patients regarding objective olfactory evaluations at 6 months.

Antithrombotic medication in cancer-associated thrombocytopenia: Current evidence and knowledge gaps.

In cancer patients, antithrombotic medications (i.e. anticoagulation or antiplatelet therapy) are frequently prescribed for prior or new indications such as venous thromboembolism or stoke prevention in atrial fibrillation. Balancing the risks of bleeding and thrombosis during periods of thrombocytopenia represents a significant challenge. Management is informed mainly by expert opinion and several recent retrospective studies on venous thromboembolism. The main management options include no change, temporarily withholding antithrombotic therapy, reducing dose, changing the regimen, and increasing the platelet transfusion threshold. Important recent advances in knowledge include the prognostic importance and apparent safety of aspirin in acute myocardial infarction and thrombocytopenia and data suggesting a low risk of recurrent venous thromboembolism in autologous stem cell transplantation patients who had anticoagulation withheld. This paper will review the literature on antithrombotic medication in thrombocytopenic patients with cancer. The significant knowledge gaps will be summarized and considerations for practice and research will be provided.

The diagnostic accuracy of bleeding assessment tools for the identification of patients with mild bleeding disorders: A systematic review.

INTRODUCTION: The bleeding assessment tool (BAT) has been developed to standardize and interpret bleeding history for mild bleeding disorders. However, a critical appraisal addressing the quality and results of validation studies is lacking. AIM: We performed a systematic review of diagnostic studies assessing the performance of the BAT in patients referred for evaluation of bleeding symptoms. METHODS: The electronic database PubMed was searched from inception through July 27, 2017. Eligible publications were original studies that assessed and validated the diagnostic accuracy of bleeding questionnaires for identification of adults with mild bleeding disorders. For each study, sensitivity, specificity and diagnostic odds ratio (DOR) were calculated. Quality was assessed using the Quality Assessment of Diagnostic studies-2 tool. To assess the influence of specific study characteristics on DOR, univariate meta-regression analyses were performed. RESULTS: Nine studies were included. Five studies investigating the ISTH-BAT or other bleeding questionnaires had a moderate to low DOR. Four studies investigating Vicenza-based BATs had a high DOR, with high specificity (>90%) and sensitivity of 59%-85%. Study characteristics such as case-control design, retrospective data collection and differences in reference standard were associated with optimistic estimates of diagnostic performance. Three of four studies with a high DOR had these study characteristics. Studies with good methodological quality mainly had a low DOR. CONCLUSION: The main advantage of the BAT is that it offers a complete and structured interview. However, the BAT is of limited diagnostic value to the workup of patients referred for bleeding evaluation in clinical practice.

[Haemolysis: role of the direct antiglobulin test and eluate]. / Hemolyse: rol van directe antiglobulinetest en eluaat.

Haemolytic anaemia is the result of an abnormal breakdown of red blood cells. The direct antiglobulin test (DAT), also known as the direct Coombs test, can be used to determine the cause of the haemolysis. The DAT distinguishes between immune and non-immune causes of haemolysis. However, the DAT should not be used in screening for haemolysis. When the DAT is performed without an indication for in vivo haemolysis, there is a high risk of false-positive results. To increase the specificity of the DAT, the eluate can be tested to determine the specificity of the autoantibodies. In this article we present two cases of haemolytic anaemia in which the DAT gives further indication of the cause of haemolysis.

The practice of diagnosing and reporting transfusion-associated circulatory overload: a national survey among physicians and haemovigilance officers.

OBJECTIVES: This study aims at identifying factors that disciplines consider when diagnosing and reporting transfusion-associated circulatory overload ('TACO'). BACKGROUND: TACO is a clinical diagnosis based mainly on subjective factors. Therefore, TACO could be an underreported complication of blood transfusion. METHODS: A survey was conducted among critical care physicians, anaesthesiologists, haematologists, transfusion medicine physicians and haemovigilance officers using case vignettes and a questionnaire. Factors that may affect diagnosing TACO were investigated using conjoint analysis. A positive B-coefficient indicates a positive preference for diagnosing TACO. Participants rated factors influencing reporting TACO on a 0- to 100-point scale. RESULTS: One hundred and seven surveys were returned (62%). Vignettes showed preferences in favour of diagnosing TACO with the onset of symptoms within 2 h [ß 0·4(-0·1-1·0)], positive fluid balance [ß 0·9(0·4-1·5)] and history of renal failure [ß 0·6(0·1-1·2)]. Compared with transfusion of a single unit of red blood cells (RBC), respondents showed a preference for diagnosing TACO following a single unit of solvent/detergent (S/D) plasma or pooled platelet concentrate (PPC) [ß 0·3(-0·2-0·7) resp. 0·5(-0·1-1·2)]. Multiple transfusion (6 RBC + 4 S/D plasma) was a strong preference for diagnosing TACO compared to 1 RBC and 1 S/D plasma [ß 0·3(-0·8-1·3)]. Respondents did not fully take into account new hypertension and tachycardia when reporting TACO [median 70 (IQR 50-80) resp. 60 (IQR 50-80)]. No differences were observed between disciplines involved. CONCLUSION: When diagnosing and reporting TACO, physicians and haemovigilance officers do consider known risk factors for TACO. Reporting could be improved by increasing the awareness of haemodynamic variables in future education programmes.

OC-08 - Multiple functional defects in platelets from thrombocytopenic cancer patients undergoing chemotherapy.

INTRODUCTION: Severe thrombocytopenia (≤50×10(9) platelets/L) is often the consequence of hematological malignancies and intensive chemotherapy. The risk of clinically significant bleeding is increased in these patients, despite the use of prophylactic platelet transfusions. The fact that there is no clear correlation between the platelet count and the risk of hemorrhage, suggests that there are other contributing factors. The contribution of impairments in platelet and coagulant function remains poorly understood. AIM: In patients with chemotherapy-induced thrombocytopenia due to hematological malignancies, we evaluate platelet and coagulant functions and determine the effects of platelet transfusion. Ultimately, we can identify specific hemostatic factors that aid in the prediction of bleeding. MATERIALS AND METHODS: In total 58 patients were included and blood was collected before and, if indicated (≤10×10(9) platelets/L), 1 hour after transfusion with platelet concentrate. Platelet function was assessed using flow cytometry by determining: 1) integrin αIIbß3 activation (PAC-1 antibody), 2) P-selectin expression (anti-P-selectin antibody), 3) phosphatidylserine exposure (Annexin-V) and 4) intracellular calcium (Fluo-4 AM). Factor levels were determined in plasma. Thrombus and fibrin formation was assessed by perfusion of whole blood over a collagen-tissue factor surface at a shear rate of 1,000 s-1. RESULTS: Platelets from the thrombocytopenic patients before transfusion showed markedly reduced integrin αIIbß3 activation and P-selectin expression in response to thrombin, collagen-related peptide and ADP, compared to healthy donor platelets. Also, agonist-induced intracellular calcium fluxes were greatly reduced. However, calcium fluxes with thapsigargin, a SERCA pump inhibitor, were similar in patient and control platelets, suggesting a normal calcium store content in the patient platelets. Furthermore, phosphatidylserine exposure was increased in unstimulated patient platelets compared to control platelets (8.2 vs. 1.8%, p<0.0001). Coagulation factor levels were within the normal range, with the exception of von Willebrand factor and fibrinogen levels, which were elevated. Platelet transfusion partly recovered the platelet integrin αIIbß3 activation and P-selectin expression induced by agonists. Platelet deposition (6.7 vs. 1.7%, p<0.0001) and fibrin formation (7.6 vs. 0.9%, p=0.0005) under flow conditions were substantially improved after platelet transfusion. CONCLUSIONS: Platelets from cancer patients undergoing chemotherapy appear to display impaired functional responses to activating stimuli. Platelet transfusion partly restores these functional defects, resulting in improved thrombus and fibrin formation.

Underdiagnosing of antibody-mediated transfusion-related acute lung injury: evaluation of cellular-based versus bead-based techniques.

BACKGROUND AND OBJECTIVES: Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-related mortality. To support the diagnosis of antibody-mediated TRALI, HLA and HNA antibodies are tested in involved blood donors. Identification of antibody positive donors is important as exclusion of these donors is part of preventative strategies against TRALI. We compared cellular-based versus bead-based techniques for diagnosis of antibody-mediated TRALI. MATERIALS AND METHODS: All reported TRALI cases in the Netherlands during a 5-year period were evaluated. Donors were screened for the presence of HLA class I and class II antibodies using both cellular-based and bead-based techniques. RESULTS: In total, 100 TRALI cases were reported of which 91 were fully tested. In 113 donors, HLA antibodies were detected of which 84 were only detected by bead-based techniques, 12 only by cellular-based tests and 17 by both assays. Antibody-mediated TRALI was diagnosed in 44 of 91 reported cases. Twenty-one (48%) of these cases would not have been identified using only cellular-based assays. CONCLUSION: Bead-based techniques show a higher sensitivity for detecting incompatible donors in TRALI cases than cellular-based assays. These results suggest that the use of bead-based assays will result in a significant reduction of future TRALI reactions as more antibody positive donors will be excluded from future donations.

Increased coagulation and fibrinolytic potential of solvent-detergent plasma: a comparative study between Omniplasma and fresh frozen plasma.

BACKGROUND AND OBJECTIVES: In this study, differences in levels of proteins involved in coagulation and fibrinolysis were compared between fresh frozen (quarantine plasma) and Omniplasma. Furthermore, thawing conditions and plasma stability after thawing were studied. MATERIALS AND METHODS: 10 Omniplasma and 10 quarantine plasma units were used to study different procoagulation, anticoagulation and fibrinolytic parameters. Analysis took place at different time-points during plasma storage at 2-6°C. RESULTS: At baseline, significant reduced levels of factor V, free protein S, α2-antiplasmin and tPA-induced ROTEM lysis time were observed in Omniplasma as compared to quarantine plasma. Moreover, thrombin generation, IXa-AT complex levels and factor XIa were significantly increased in Omniplasma. The majority of the parameters studied remained stable in Omniplasma 48 h after thawing, with the exception of factor VIII (decrease) and IXa-AT (increase). CONCLUSION: Our results suggest an increased coagulation potential, presumingly as a result of contact activation during the production process and also, an increased fibrinolytic potential in Omniplasma. The stability of Omniplasma, based upon the different parameters studied, is comparable to Q-plasma. A maximum post-thawing time of 48 hfor Omniplasma can be suggested.

Triple red blood cell alloantibody formation after bone-allograft transplantation.

In this case report, we provide evidence for the possibility of red blood cell alloimmunization after bone-allograft transplantation. Here, we present a 13-year-old boy who received a bone allograft due to impending hip-luxation. Five months later he was shown to have developed three different alloantibodies: anti-D, anti-C and anti-E, which were induced by the bone allograft. Red blood cell alloimmunization is a possible adverse event when a patient is exposed to allogenic red blood cells. These antibodies may cause transfusion reactions when incompatible blood is administered. More importantly, these antibodies may cause severe, or even fatal, hemolytic disease of the fetus or newborn, stretching the importance of preventing antibody formation, especially in young women. This case demonstrates the importance of selecting rhesus phenotype compatible bone allografts.

The observation of bleeding complications in haemato-oncological patients: stringent watching, relevant reporting.

BACKGROUND: The reported percentage of haemato-oncological patients experiencing bleeding complications is highly variable, ranging from 5 to 70%, posing a major problem for comparison of clinical platelet transfusion trials using bleeding complications as a primary endpoint. In a pilot study we assessed the impact of the design of scoring of bleeding on the percentage of patients with WHO grade 2 or higher bleeding grades. STUDY DESIGN AND METHODS: We performed a prospective, observational study using a rigorous bleeding observation system in thrombocytopenic patients with haemato-oncological disorders. Endpoints of the study were the percentage of patients and days with bleeding WHO grade ≥ 2 comparing designs in which skin bleeding represent a continuation of a previous bleed or a new bleed. RESULTS: In four participating hospitals 64 patients suffering 870 evaluable thrombocytopenic days (platelet count < 80 × 10(9) L(-1)) were included. At least one episode of bleeding grade ≥ 2 occurred in 36 patients (56%). Most grade 2 bleeding complications occurred mucocutaneously. The percentage of days with bleeding of grade ≥ 2 was 16% but decreases to 8% when only newly developed skin bleeding was included. CONCLUSION: Rigorous daily observation results in a bleeding incidence that is comparable to recent reportings applying the same method. The results of this study show that censoring for stable skin bleeding has a profound effect on bleeding incidence per day. The clinical relevance of rigorous or clinically judged bleeding scores as an endpoint remains to be defined.

Allo-exposure status and leucocyte antibody positivity of blood donors show a similar relation with TRALI.

INTRODUCTION: The fraction of transfusion-related acute lung injury (TRALI) cases preventable by deferral of allo-exposed donors has previously been estimated, under the assumption this indirectly estimated the contribution of leucocyte antibodies to the occurrence of TRALI. Our aim was to estimate the fraction preventable by deferral of leucocyte antibody positive donors and to investigate the validity of allo-exposure as a marker for leucocyte antibodies. METHODS: All donors involved in a series of previously published TRALI patients were tested for leucocyte antibodies. The observed number of antibody positive donors was compared to the expected number. From this comparison we estimated the contribution of leucocyte antibodies to the occurrence of TRALI and compared this to the previously reported estimate for allo-exposed donors. RESULTS: Sixty-one TRALI patients were included. Of 288 involved donors 43 were expected and 67 were observed to be leucocyte antibody positive. The observed percentage of positive donors was 8.3% (95% confidence interval (CI): 5.1-11.5%) in excess of the expected. Overall 59% (95% CI: 34-85%) of TRALI cases was estimated to be preventable by the exclusion of all leucocyte antibody positive donors. For plasma-poor products this was 16% (95% CI: -5.0 to 36%). CONCLUSIONS: These estimates were similar to those previously published for allo-exposed donors. This suggests allo-exposure status can effectively be used in donor deferral strategies.

Colonoscopy-assisted reposition of the incarcerated uterus in mid-pregnancy: a report of four cases and a literature review.

The treatment of mid-gestational uterine incarceration remains a challenge. The success rate of manual reduction decreases with gestational age, and an operative procedure may carry important fetal, next to possible maternal morbidities. We will present four cases of uterine incarceration between the 15th and 25th week of pregnancy of which three colonoscopy-assisted manual repositions proved successful. It illustrates that conservative treatment of uterine incarceration is feasible, even during the late second trimester. That is why a review of the conservative approach of this rare condition is also presented.

[Transfusion-related acute lung injury (TRALI) in the Netherlands in 2002-2005]. / Transfusiegerelateerde acute longbeschadiging (TRALI) in Nederland in 2002-2005.

OBJECTIVE: To determine the number of reported cases of transfusion-related acute lung injury (TRALI) in the Netherlands in 2002-2005 and to determine how many cases were associated with incompatibility between leukocyte-reactive antibodies in the donor plasma and leukocytes or antigens in the recipient. DESIGN: Retrospective national case review. METHOD: Cases of TRALI reported in 2002-2005 were assessed according to the national clinical definition of TRALI, and the relationship between TRALI and transfusion was assessed. Additional clinical details were requested from the treating hospital as necessary. The results of leukocyte serological tests from donors and recipients were linked to clinical cases. For cases with positive leukocyte serological tests, the relevant blood components and the sex of the donor were recorded. RESULTS: Of the 46 cases reported, 6 had insufficient information. 8 cases did not meet the definition or had another more likely diagnosis. There was a trend toward an increase in the number of reports: 12 cases were reported in 2005, corresponding with 1:60,000 blood components. Of the 40 evaluable cases, 32 (80%) met the definition of TRALI and were deemed to be definitely (n = 16), probably (n = 5) or possibly (n = 11) related to transfusion. Severity ranged from moderate to life-threatening, and there was one TRALI-related death. Leukocyte serology was fully investigated in 18 cases: 13 (72%) had leukocyte incompatibility and in 5 cases exclusively fresh frozen plasma from a female donor was implicated.

[Stereotactic body radiotherapy (SBRT) -- an overview under special consideration of SBRT and LITT in the therapy of liver metastases]. / Extrakranielle stereotaktische Radiotherapie (ESRT) - eine Ubersicht unter besonderer Berücksichtigung von ESRT und LITT in der Behandlung von Lebermetastasen.

Stereotactic body radiotherapy (SBRT) is a high dose radiotherapy, the radiation dose is applicated one-time or in a few fractions exactly to the tumor or metastases under maximal separation from the normal tissue. Because of this a major expenditure of medical and technical efforts are necessary, a detailed description of the proceedings is following in the methodic part of this article. Indications of SBRT are especially medical irresectable lung tumors of early stages, primary liver/biliary tumors and pulmonary or liver metastases if there is an oncological benefit for the patients. The side effects are moderate, the local tumor control rate is between 78 to 100 %. Depending on the primary tumor the overall survival is prolonged statistically significant. In the Klinikum Krefeld indications of SBRT vs chemotherapy, LITT or resection are discussed by an interdisciplinary conference of gastroenterologists/oncologists, radiologists, radiooncologists and surgeons. An example of LITT will be shown also.

Clinical significance of bacteriologic screening in platelet concentrates.

BACKGROUND: Despite routine bacterial screening with a bacterial culturing system (BacT/ALERT, bioMerieux) of platelet (PLT) concentrates, two cases of life-threatening sepsis attributed to transfused PLT products contaminated with Bacillus cereus were reported to the regional hemovigilance office in the southwest region of the Netherlands. These reports necessitated a retrospective evaluation of the currently applied bacteriologic screening program. STUDY DESIGN AND METHODS: Bacteriologic screening of all PLT concentrates on production was introduced in October 2001. Aliquots (5-10 mL) of pooled PLT concentrates in additive solution were taken for cultures with the BacT/ALERT system 14 to 24 hours after donation. The total culturing period was 7 days and in case of positive signals, identification cultures were taken from the culture bottles. The results of the bacterial screening, identification, and clinical significance of possibly contaminated pooled PLT concentrates were evaluated retrospectively over a 2-year period. RESULTS: In this period, a total of 28,104 pooled PLT concentrates were produced. Positive bacterial screening was found in 0.72 percent (n = 203). Of these, in 184 pooled PLT concentrates bacteria were cultured and identified, and in the remaining 19 (9.4%) identification cultures were negative. Before a positive screening was found, 113 PLT concentrates had already been transfused without the occurrence of clinical significant transfusion reactions. CONCLUSION: Bacterial contamination of pooled PLT concentrates was not related to clinically significant transfusion reactions. Despite negative screening for bacterial contamination, life-threatening transfusion-transmitted infections by contaminated PLT products can still occur. Other strategies should be applied to guarantee a higher degree of bacteriologic safety.

[Reports of transfusion incidents: experiences from the first year of hemovigilance in the region of the former ZWN (South West Netherlands) blood bank in Rotterdam]. / Meldingen over transfusie-incidenten: ervaringen in het eerste jaar van hemovigilantie in de regio van de voormalige Bloedbank ZWN Rotterdam.

OBJECTIVE: Itemize blood transfusion incidents in the South-West Netherlands region (about 3.5 million inhabitants), where a regional reporting system for transfusion incidents was introduced in January 2001. DESIGN: Prospective, descriptive. METHOD: In the period 1 January 2001-31 December 2001, 22 hospitals voluntarily reported transfusion incidents in patients to the blood bank. All incidents were anonymously recorded in a standardised report and registered in 14 categories. RESULTS: A total of 119 transfusion incidents were reported and categorised as: incorrect blood component transfused (n = 8), mild fever 1-2 degrees C (n = 14), non-haemolytic fever > 2 degrees C (n = 36), acute haemolytic transfusion reactions (n = 3). delayed haemolytic transfusion reactions (n = 18), allergic reactions (n = 11), bacterial contamination (n = 3), transfusion-related acute lung injury (n = 1), near accidents (n = 6) and product recalls (n = 19). There were no reports in the categories anaphylactic shock, post-transfusion purpura, transfusion-acquired viral infection, and transfusion-related graft versus host disease. In the same year of haemovigilance, the blood bank issued a total of 158,000 blood products. A complication rate of 1:700 blood products was calculated. It is estimated that 53% of all incidents were reported. CONCLUSION: Despite all of the safety measures taken, severe adverse events still occurred. A well-run system for haemovigilance can contribute to the knowledge of transfusion incidents. The safety and quality of blood transfusions can be improved if this knowledge is incorporated into ongoing education about blood transfusions and in the prevention and treatment of transfusion reactions.