Emicizumab in Type 3 von Willebrand Disease: Report of a Case with an Alloantibody and Literature Review.

Type 3 von Willebrand disease (VWD), the most severe form of VWD, is an inherited recessive bleeding disorder caused by the complete deficiency of von Willebrand factor (VWF). The reported prevalence is 1 per million but varies worldwide according to the frequency of consanguineous marriages. The clinical phenotype is characterized not only by mucocutaneous bleedings, but also by hemarthroses and muscle hematoma, as in patients with moderate hemophilia. Long-term prophylaxis with factor (F)VIII/VWF concentrates is recommended in patients with a history of severe and frequent bleeds. A rare complication of replacement therapy is the development of alloantibodies against VWF, with the consequences of an ineffective therapy and risk of anaphylactic reactions upon treatment. Emicizumab is the first bispecific monoclonal antibody that mimics FVIII coagulant activity and is approved for prophylaxis of bleeding in patients with inherited hemophilia A with or without inhibitors and recently also for acquired hemophilia. In this manuscript we report and discuss available data in the literature on the use of emicizumab in type 3 VWD and describe the case of a female patient with type 3 VWD with a history of alloantibodies against VWF and posttransfusion anaphylaxis, recently and successfully put on off-label prophylaxis with emicizumab.

Analytical evaluation of the novel Mindray high sensitivity cardiac troponin I immunoassay on CL-1200i.

OBJECTIVES: The current study was designed to evaluate the analytical performance of the new Mindray highly sensitive cardiac troponin I (hs-cTnI) chemiluminescent immunoassay on Mindray CL-1200i, as a thorough validation of novel hs-cTnI methods is required before introduction into clinical practice. METHODS: The evaluation of the analytical performance of this hs-cTnI immunoassay encompassed the calculation of the limit of blank (LOB), limit of detection (LOD), functional sensitivity, imprecision, linearity, 99th percentile upper reference limit (URL) and concordance with another previously validated hs-cTnI chemiluminescent immunoassay. RESULTS: The LOB and LOD were 0.32 and 0.35 ng/L, whilst the functional sensitivity (expressed as cTnI value with <10 % imprecision), was 0.35 ng/L. The linearity was excellent throughout a wide range of clinically measurable values (r=1.00 between 0.8 and 9,726.9 ng/mL). The intra-assay, inter-assay and total imprecision were 1.1-1.3 %, 5.5-8.1 % and 5.6-8.2 %, respectively. The 99th percentile URL calculated using residual plasma from 246 ostensibly healthy blood donors was 9.2 ng/L (4.3 ng/L in women vs. 12.3 ng/L in men). The Spearman's correlation between Mindray hs-cTnI and Access hs-TnI was 0.97, with mean bias of 7.2 % (95 % CI, 2.6-11.9 %). CONCLUSIONS: Although we failed to confirm the very optimistic analytical characteristics previously reported for this method, our evaluation of the novel Mindray hs-cTnI immunoassay on CL-1200i demonstrated that the overall performance is comparable to that of other commercially available hs-cTnI techniques, making it a viable alternative to other methods.

Lifestyle and dietary factors, iron status and one-carbon metabolism polymorphisms in a sample of Italian women and men attending a Transfusion Medicine Unit: a cross-sectional study.

Iron (Fe) status among healthy male and female blood donors, aged 18-65 years, is estimated. General characteristics and lifestyle factors, dietary habits and major one-carbon metabolism-related polymorphisms were also investigated. An explorative cross-sectional study design was used to examine a sample of blood donors attending the Transfusion Medicine Unit of the Verona University Hospital, Italy. From April 2016 to May 2018, 499 subjects were enrolled (255 men, 244 women, 155 of whom of childbearing age). Major clinical characteristics including lifestyle, dietary habits and Fe status were analysed. The MTHFR 677C > T, cSHMT 1420C > T, DHFR 19bp ins/del and RFC1 80G > A polymorphisms were also assayed. Mean plasma concentrations of Fe and ferritin were 16·6 µmol/l (95 % CI 16·0, 17·2) and 33·8 µg/l (95 % CI 31·5, 36·2), respectively. Adequate plasma Fe concentrations (> 10·74 µmol/l) were detected in 84·3 % and adequate ferritin concentrations (20-200 µg/l) was found in 72·5 % of the whole cohort. Among the folate-related polymorphisms analysed, carriers of the DHFR 19bp del/del mutant allele showed lower ferritin concentration when compared with DHFR 19bp ins/del genotypes. In a sample of Italian healthy blood donors, adequate plasma concentrations of Fe and ferritin were reached in a large proportion of subjects. The relationship of Fe status with lifestyle factors and folate-related polymorphisms requires more investigation to clarify further gene-nutrient interactions between folate and Fe metabolism.

Laparoscopic surgery does not reduce the need for red blood cell transfusion after resection for colorectal tumour: a propensity score match study on 728 patients.

BACKGROUND: Patients with colorectal tumour often present with anaemia, and up to 60% will receive red blood cells (RBC) transfusion. Some evidence suggests a correlation between RBC transfusion and worse outcomes. Since laparoscopy minimizes intraoperative blood loss, we retrospectively investigated its role in reducing haemoglobin (Hb) drop and requirements for postoperative RBC transfusions. METHODS: Patients were identified from consecutive cases undergone elective surgery for non-metastatic colorectal tumour between 2005 and 2019. Laparoscopic cases were matched 1:1 with open controls through propensity score matching (PSM). The main outcome measures were postoperative Hb drop and requirement for RBC. The secondary aim was evaluation of risk factors for postoperative RBC transfusions. RESULTS: After application of PSM, 364 patients treated by laparoscopy were matched with 364 patients undergone open surgery. The two groups presented similar clinical and pathological characteristics, as well as comparable postoperative outcomes. 56 patients in the open group and 47 in the laparoscopic group required postoperative RBC (P = 0.395). No difference was observed in terms of mean number of RBC units (P = 0.608) or Hb drop (P = 0.129). Logistic regression analysis identified preoperative anaemia and occurrence of postoperative complications as relevant risk factors for postoperative RBC transfusion, while surgical approach did not prove statistically significant. CONCLUSION: Laparoscopy did not influence postoperative requirements for RBC transfusions after elective colorectal surgery. Preoperative anaemia and occurrence of postoperative complications represent the major determinants for postoperative transfusions after open as well as laparoscopic surgery.

B vitamin blood concentrations and one-carbon metabolism polymorphisms in a sample of Italian women and men attending a unit of transfusion medicine: a cross-sectional study.

PURPOSE: To define blood status of folate, vitamin B12, vitamin B6, homocysteine, and major one-carbon metabolism-related polymorphisms in healthy, males and females blood donors, aged 18-65 years were evaluated. General characteristics and lifestyle factors were also investigated. METHODS: An explorative cross-sectional study design was used to evaluate a sample of blood donors attending the Unit of Transfusion Medicine of the Verona University Hospital, Italy. From April 2016 to May 2018, 499 subjects were enrolled (255 men, 244 women of whom 155 of childbearing age). Major clinical characteristics including lifestyle and dietary habits, B vitamins and homocysteine were analyzed. The MTHFR 677 C>T, cSHMT 1420 C>T, DHFR 19 bp ins/del, RFC1 80 G>A polymorphisms were also determined. RESULTS: Mean plasma concentrations of folate, vitamin B12, vitamin B6 and homocysteine were 14.2 nmol/L (95% CI 13.7-14.8), 271.9 pmol/L (95% CI 262.6-281.5), 51.0 nmol/L (95% CI 48.7-53.4) and 13.5 µmol/L (95% CI 13.1-14.0), respectively. Plasma folate, was adequate (> 15 nmol/L) in 44.7% of all subjects, 39.0% of males and 42.5% of women < 45 years. Similarly, vitamin B12 was adequate (> 350 pmol/L) in 25.1% of all subjects and in 20.3% of men ≥ 45 years. The rare allele frequencies were 0.21 for MTHFR 677TT, 0.11 for cSHMT 1420TT, 0.18 for DHFR 19 bp del/del, 0.20 for RFC1 80AA, and a gene-nutrient interaction was confirmed for folate concentrations according to MTHFR 677C>T and DHFR 19 bp del/del. CONCLUSION: An Italian sample of healthy blood donors shows that an adequate concentration of plasma folate and vitamin B12 is reached only in a limited percentage of subjects, thus encouraging consideration for specific public health strategies.

Preparedness and activities of the anti-SARS-CoV-2 convalescent plasma bank in the Veneto region (Italy): An organizational model for future emergencies.

BACKGROUND: Convalescent plasma (CP) has been used in the past in various pandemics, in particular in H1N1, SARS and MERS infections. In Spring 2020, when ongoing the SARS-CoV-2 pandemics, the Veneto Region (V-R) has proposed setting-up an anti-SARS-CoV-2 CP (CCP) Bank, with the aim of preparing a supply of CCP immediately available in case of subsequest epidemic waves. MATERIALS AND METHODS: Key-points to be developed for a quick set-up of the V-R CCP Bank have been recruitment of donors recovered from COVID-19 infection, laboratory analysis for the biological qualification of the CCP units, including titre of neutralizing antibodies and reduction of pathogens, according to National Blood Centre (CNS) Directives, adaptation of the V-R Information Technology systems and cost analysis. Some activities, including diagnostic and viral inactivation processes, have been centralized in 2 or 3 sites. Laboratory analysis upon preliminary admission of the donor included all tests required by the Italian laws and the CNS directives. RESULTS: From April to August 2020, 3,298 people have contacted the V-R Blood Transfusion Services: of these, 1,632 have been evaluated and examined as first time donors and those found to be suitable have carried out 955 donations, from which 2,626 therapeutic fractions have been obtained, at a cost around 215,00 Euro. Since October 2020, the number of COVID-19 inpatients has had a surge with a heavy hospital overload. Moreover, the high request of CCP therapy by clinicians has been just as unexpected, showing a wide therapeutic use. CONCLUSIONS: The organizational model here presented, which has allowed the rapid collection of a large amount of CCP, could be useful when facing new pandemic outbreaks, especially in low and middle income countries, with generally acceptable costs.

Mature CD10+ and immature CD10- neutrophils present in G-CSF-treated donors display opposite effects on T cells.

The identification of discrete neutrophil populations, as well as the characterization of their immunoregulatory properties, is an emerging topic under extensive investigation. In such regard, the presence of circulating CD66b+ neutrophil populations, exerting either immunosuppressive or proinflammatory functions, has been described in several acute and chronic inflammatory conditions. However, due to the lack of specific markers, the precise phenotype and maturation status of these neutrophil populations remain unclear. Herein, we report that CD10, also known as common acute lymphoblastic leukemia antigen, neutral endopeptidase, or enkephalinase, can be used as a marker that, within heterogeneous populations of circulating CD66b+ neutrophils present in inflammatory conditions, clearly distinguishes the mature from the immature ones. Accordingly, we observed that the previously described immunosuppressive neutrophil population that appears in the circulation of granulocyte colony-stimulating factor (G-CSF)-treated donors (GDs) consists of mature CD66b+CD10+ neutrophils displaying an activated phenotype. These neutrophils inhibit proliferation and interferon γ (IFNγ) production by T cells via a CD18-mediated contact-dependent arginase 1 release. By contrast, we found that immature CD66b+CD10- neutrophils, also present in GDs, display an immature morphology, promote T-cell survival, and enhance proliferation and IFNγ production by T cells. Altogether, our findings uncover that in GDs, circulating mature and immature neutrophils, distinguished by their differential CD10 expression, exert opposite immunoregulatory properties. Therefore, CD10 might be used as a phenotypic marker discriminating mature neutrophils from immature neutrophil populations present in patients with acute or chronic inflammatory conditions, as well as facilitating their isolation, to better define their specific immunoregulatory properties.

Impact of Exercise/Sport on Well-being in Congenital Bleeding Disorders.

Physical activity provides many benefits in patients with congenital bleeding disorders. Patients with hemophilia are encouraged to participate in exercise and sports, especially those patients receiving prophylaxis. Several publications and guidelines have explored this issue in hemophilia patients, evaluating in particular the impact of physical activity on patients' well-being and quality of life. The other rare congenital bleeding disorders are less studied; they are heterogeneous in terms of clinical bleeding phenotype, incidence of hemarthrosis, and arthropathy. Furthermore, prophylaxis in these patients is less common than in hemophilia patients, which must be considered when choosing the type of physical and sporting activity. In this review, the authors have analyzed the literature focusing their attention on those rare coagulation disorders that may be complicated by arthropathy and the role of exercise and sports in this context.

Clinical effectiveness of platelets in additive solution treated with two commercial pathogen-reduction technologies.

BACKGROUND: Two noninferiority, randomized, controlled trials were conducted in parallel comparing the safety and efficacy of platelets treated with Intercept or Mirasol pathogen-reduction technologies versus standard platelets. STUDY DESIGN AND METHODS: The primary endpoint was the percentage of hematology patients who developed World Health Organization Grade 2 or greater bleeding. A noninferiority margin of 11% was chosen based on expected Grade 2 or greater bleeding in 20% of controls. The study was closed for financial restrictions before reaching the planned sample size of 828 patients, and an intention-to-treat analysis was conducted on 424 evaluable patients. RESULTS: In the Intercept trial (113 treated vs. 115 control patients), the absolute risk difference in Grade 2 or greater bleeding was 6.1%, with an upper one-sided 97.5% confidence limit of 19.2%. The absolute risk difference in the Mirasol trial (99 treated vs. 97 control patients) was 4.1%, and the upper one-sided 97.5% confidence limit was 18.4%. Neither absolute risk difference was statistically significant. In both trials, posttransfusion platelet count increments were significantly lower in treated versus control patients. Mean blood component use in treated patients versus controls was 54% higher (95% confidence interval, 36%-74%; Intercept) and 34% higher (95% confidence interval, 16%-54%; Mirasol) for platelets and 23% higher (95% confidence interval, 8%-39%; Intercept) and 32% higher (95% confidence interval, 10%-57%; Mirasol) for red blood cells. Unexpected reactions and adverse events were not reported. Mortality did not differ significantly between treated and control patients. CONCLUSION: Although conclusions on noninferiority could not be drawn due to low statistical power, the study provides additional information on the safety and efficacy of pathogen-reduced platelets treated with two commercial pathogen-reduction technologies.

Analytical evaluation of the new Beckman Coulter Access high sensitivity cardiac troponin I immunoassay.

BACKGROUND: This study was aimed to evaluate the analytical performance of the novel chemiluminescent and fully-automated Beckman Coulter Access hsTnI high-sensitivity immunoassay for measurement of cardiac troponin I (cTnI). METHODS: The study, using lithium heparin samples, included assessment of limit of blank (LOB), limit of detection (LOD), functional sensitivity, linearity, imprecision (within run, between-run and total), calculation of 99th percentile upper reference limit (URL) in 175 healthy blood donors (mean age, 36±12 years; 47% women) and comparison with two other commercial cTnI immunoassays. RESULTS: The LOB, LOD and functional sensitivity of Access hsTnI were 0.14, 0.34 and 1.35 ng/L, respectively. The within-run, between-run and total imprecision was 2.2%-2.9%, 4.6%-5.4%, and 5.4%-6.1%, respectively. The linearity was excellent in the range of cTnI values between 0.95 and 4195 ng/L (r=1.00). The 99th percentile URL was 15.8 ng/L. Measurable cTnI values were found in 173/175 healthy subjects (98.9%). Good agreement of cTnI values was found with AccuTnI+3 (r=0.97; mean bias, -9.3%), whereas less satisfactory agreement was found with Siemens Dimension Vista cTnI (r=0.95; mean bias, -55%). CONCLUSIONS: The results of our evaluation of the Beckman Coulter Access hsTnI indicate that the analytical performance of this fully-automated immunoassay is excellent.

Perceived challenges and attitudes to regimen and product selection from Italian haemophilia treaters: the 2013 AICE survey.

Despite great advances in haemophilia care in the last 20 years, a number of questions on haemophilia therapy remain unanswered. These debated issues primarily involve the choice of the product type (plasma-derived vs. recombinant) for patients with different characteristics: specifically, if they were infected by blood-borne virus infections, and if they bear high or low risk of inhibitor development. In addition, the most appropriate treatment regimen in non-inhibitor and inhibitor patients compel physicians operating at the haemophilia treatment centres (HTCs) to take important therapeutic decisions, which are often based on their personal clinical experience rather than on evidence-based recommendations from published literature data. To know the opinion on the most controversial aspects in haemophilia care of Italian expert physicians, who are responsible for common clinical practice and therapeutic decisions, we have conducted a survey among the Directors of HTCs affiliated to the Italian Association of Haemophilia Centres (AICE). A questionnaire, consisting of 19 questions covering the most important topics related to haemophilia treatment, was sent to the Directors of all 52 Italian HTCs. Forty Directors out of 52 (76.9%) responded, accounting for the large majority of HTCs affiliated to the AICE throughout Italy. The results of this survey provide for the first time a picture of the attitudes towards clotting factor concentrate use and product selection of clinicians working at Italian HTCs.

Effect of peri-operative blood transfusions on long-term prognosis of patients with colorectal cancer.

BACKGROUND: Patients with colorectal cancer often present with anaemia and require red blood cell transfusions (RBCT) during their peri-operative course. Evidence suggests a significant association between RBCT and poor long-term outcomes in surgical patients, but the findings in colorectal cancer are contradictory. MATERIAL AND METHODS: The aim of this retrospective, single-centre, cohort study was to investigate the prognostic role of peri-operative RBCT in a large cohort of patients with stage I-III colorectal cancer submitted to curative surgery between 2005 and 2017. The propensity score matching technique was applied to adjust for potential confounding factors. RESULTS: Among 1,414 patients operated within the study period, 895 fulfilled the inclusion criteria: 29.6% (n=265) received peri-operative RBCT. The group that received peri-operative RBCT was significantly older (p<0.001), had more comorbidities (p<0.001), more advanced tumours (p<0.001) and more colon tumours (p=0.002) and stayed in hospital longer (p<0.001). Post-operative mortality was 7-fold higher (2.3 vs 0.3%, p=0.01) in this group. Survival outcomes were significantly worse in the group receiving RBCT than in the group not receiving RBCT for both overall (64.5 vs 80.1%, p<0.001) and cancer-specific survival (74.3 vs 85.1%, p<0.001). On multivariable analysis, peri-operative RBCT was significantly associated with poorer overall survival (hazard ratio 1.51, p=0.009). When transfused and non-transfused cases were paired through the propensity score matching technique considering main clinico-pathological features, no differences in overall and cancer-specific survival were found. DISCUSSION: Our data suggest that, after adjustment for potential confounding factors, no significant association exists between RBCT and prognosis in colorectal cancer.

Outcome of SARS CoV-2 inpatients treated with convalescent plasma: One-year of data from the Veneto region (Italy) Registry.

OBJECTIVES AND BACKGROUND: Convalescent plasma (CP) has been used worldwide to contrast SARS-CoV-2 infection. Since April 2020, it has also been used in the treatment of patients with COVID-19 in the Veneto region (Italy), along with all the other available drugs and therapeutic tools. Here we report data analysis and clinical results in 1,517 COVID-19 inpatients treated with CP containing high-titre neutralizing anti-SARS-CoV-2 antibodies (CCP). Mortality after 30 days of hospitalization has been considered primary outcome, by comparing patients treated with CCP vs all COVID-19 patients admitted to hospitals of the Veneto region in a one-year period (from April 2020 to April 2021). PATIENTS AND METHODS: Adult inpatients with a severe form of COVID-19 have been enrolled, with at least one of the following inclusion criteria: 1) tachypnea with respiratory rate (RR) ≥ 30 breaths/min; 2) oxygen saturation (SpO2) ≤ 93% at rest and in room air; 3) partial pressure of oxygen (PaO2)/fraction of inspired oxygen (FiO2) ≤ 200 mmHg, 4) radiological picture and/or chest CT scan showing signs of interstitial disease and/or rapid progression of lung involvement. Patients received a maximum of three therapeutic fractions (TFs) of CCP with a neutralizing antibody titre of ≥ 1:160, administered over a period of 3-5 days. If TFs of CCP with titre ≥ 1:160 were unavailable, 2 with antibody titre of ≥ 1:80 have been administered. RESULTS: Of the 1,517 patients treated with CCP, 209 deceased at the 30-day follow-up (14%). Death was significantly associated with an older age (p<0.001), a longer time of hospitalization before CCP infusion (p<0.001), a greater number of inclusion criteria (p<0.001) and associated comorbidities (p<0.001). Conditions significantly associated with an increased frequency of death were PaO2/FiO2 ≤ 200 (p<0.001) and tachypnea with RR>30 (p<0.05) at entry, concurrent arterial hypertension (p<0.001), cardiovascular disease (p<0.001), chronic kidney disease (p<0.001), dyslipidemia (p<0.05) and cancer (p<0.05). Moreover, factors leading to an unfavorable prognosis were a life-threatening disease (p<0.001), admission to Intensive Care Unit (p<0.001), high flow oxygen therapy or mechanical ventilation (p<0.05) and a chest X-ray showing consolidation area (p<0.001). By analyzing the regional report of hospitalized patients, a comparison of mortality by age group, with respect to our series of patients treated with CCP, has been made. Mortality was altogether lower in patients treated with CCP (14% v. 25%), especially in the group of the elderly patients (23% vs 40%,), with a strong significance (p<0.001). As regards the safety of CCP administration, 16 adverse events were recorded out of a total of 3,937 transfused TFs (0,4%). CONCLUSIONS: To overcome the difficulties of setting up a randomized controlled study in an emergency period, a data collection from a large series of patients with severe COVID-19 admitted to CCP therapy with well-defined inclusion criteria has been implemented in the Veneto region. Our results have shown that in patients with severe COVID-19 early treatment with CCP might contribute to a favourable outcome, with a reduced mortality, in absence of relevant adverse events.

Outcomes in AB0 Incompatible Living Donor Kidney Transplantation: A Case - Control Study.

Background: Patients waiting for a kidney transplant by far exceed available organs. AB0 incompatible living donor kidney transplantation (AB0i LDKT) represents an additional therapeutic strategy, but with higher risk for complications. We aimed at evaluating outcomes of AB0i LDKTs compared to compatible (AB0c) controls at our Institution. Methods: Retrospective matched case - control study (1:2) comparing AB0i vs. AB0c LDKTs from March 2012 to September 2021. Considered outcomes: graft function, acute rejection, sepsis, CMV infection, BK virus reactivation, death-censored graft survival, patient survival. Results: Seventeen AB0i LDKTs matched to 34 AB0c controls. We found excellent graft function, comparable in the two groups, at all considered intervals, with an eGFR (ml/min/1.73 m2) of 67 vs. 66 at 1 year (p = 0.41), 63 vs. 64 at 3 years (p = 0.53). AB0i recipients had a statistically significant higher incidence of acute rejection, acute antibody-mediated rejection and sepsis within 30 days (p = 0.016; p = 0.02; p = 0.001), 1 year (p = 0.012; p = 0.02; p = 0.0004) and 3 years (p = 0.004; p = 0.006; p = 0.012) after surgery. There was no difference in CMV infection, BK virus reactivation, death-censored graft survival between the two groups. Patient survival was inferior in AB0i group at 1 and 3 years (88.2 vs. 100%; log-rank p = 0.03) due to early death for opportunistic infections. AB0i LDKTs spent longer time on dialysis (p = 0.04) and 82.3 vs. 38.3% controls had blood group 0 (p = 0.003). Conclusions: AB0i LDKT is an effective therapeutic strategy with graft function and survival comparable to AB0c LDKTs, despite higher rates of acute rejection and sepsis. It is an additional opportunity for patients with less chances of being transplanted, as blood group 0 individuals.

Influence of ABO blood group on sports performance.

BACKGROUND: Despite being a recessive trait, the O blood group is the most frequent worldwide among the ABO blood types. Since running performance has been recognized as a major driver of evolutionary advantage in humans, we planned a study to investigate whether the ABO blood group may have an influence on endurance running performance in middle-aged recreational athletes. METHODS: The study population consisted of 52 recreational, middle-aged, Caucasian athletes (mean age: 49±13 years, body mass index, 23.4±2.3 kg/m2), regularly engaged in endurance activity. The athletes participated to a scientific event called "Run for Science" (R4S), entailing the completion of a 21.1 km (half-marathon) run under competing conditions. The ABO blood type status of the participants was provided by the local Service of Transfusion Medicine. RESULTS: In univariate analysis, running performance was significantly associated with age and weekly training, but not with body mass index. In multiple linear regression analysis, age and weekly training remained significantly associated with running performance. The ABO blood group status was also found to be independently associated with running time, with O blood type athletes performing better than those with non-O blood groups. Overall, age, weekly training and O blood group type explained 62.2% of the total variance of running performance (age, 41.6%; training regimen, 10.5%; ABO blood group, 10.1%). CONCLUSIONS: The results of our study show that recreational athletes with O blood group have better endurance performance compared to those with non-O blood group types. This finding may provide additional support to the putative evolutionary advantages of carrying the O blood group.

Efficacy of Haemate-P as prophylaxis of recurrent bleeding in a patient with type 2B von Willebrand's disease.

We report the case of a 58-year-old woman with type 2B von Willebrand's disease who received regular infusions of the factor VIII/von Willebrand factor concentrate Haemate-P (2000 IU every other day) for 4 months to prevent recurrent bleeding from a malignant esophageal ulcer. Prophylaxis with Haemate-P was shown to be safe and effective in this patient, thus enabling completion of radiochemotherapy.