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The recruitment of marine species in isolated oceanic island systems can be challenged by prevailing currents, as exemplified by the Tropical Southwestern Atlantic. In this region, the Fernando de Noronha ridge hosts several seamounts, the Rocas Atoll and the Fernando de Noronha Archipelago, which are home to great marine biodiversity. However, along the ridge, the central branch of the South Equatorial Current (cSEC), flowing westward, poses a challenge to the recruitment of organisms toward Fernando de Noronha. To unveil critical insights into the intricate processes shaping biodiversity in these insular ecosystems, we use a dispersal Lagrangian tool to explore the role of diel vertical migration (DVM) to depth strata influenced by the South Equatorial Undercurrent (SEUC), which flows eastward bellow the cSEC, in shaping species dispersal and metacommunity dynamics. Our results show that while not a direct journey, the DVM into SEUC‐influenced strata increases the possibility that the seamounts and the Rocas Atoll act as stepping stones between the continental shelf and Fernando de Noronha. Propagules of organisms originating primarily from the continental shelf are transported to the western seamounts of the ridge. Upon reaching the western seamounts, organisms can find suitable habitats to recruit. The progeny of these communities that migrate to SEUC‐influenced strata have the opportunity to reach suitable habitats at the Rocas Atoll and the Eastern seamounts, ultimately connecting to the Fernando de Noronha archipelago. These results provide scientific fundaments for the development of a functional network of marine protected areas in the Tropical Southwestern Atlantic. [ABSTRACT FROM AUTHOR]

The article discusses a study conducted in Italy that evaluated the use of recombinant factor IX-albumin fusion protein (rIX-FP) as a treatment for adult patients with hemophilia B. The study found that rIX-FP prophylaxis was effective in reducing bleeding episodes and required fewer infusions compared to previous treatments. The most common dosing regimen was every 14-15 days, with one patient using a 21-day regimen. The study concluded that rIX-FP is a flexible and effective treatment option for adult patients with hemophilia B, but further research is needed to assess long-term outcomes. It is important to consider physical activity levels and lifestyle when personalizing prophylaxis regimens. [Extracted from the article]

Aims: Lymph node metastases (LNM) are one of the most important prognostic indicators in solid tumours and a major component of cancer staging. Neoadjuvant therapy might influence nodal status by induction of regression. Our aim is to determine the prevalence and role of regression of LNM on outcomes in patients with rectal cancer. Methods and results: Four independent study populations of rectal cancer patients treated with similar regimens of chemoradiotherapy were pooled together to obtain a total cohort of 469 patients. Post‐treatment nodal status (ypN) and signs of tumour regression (Reg) were incorporated to form three‐tiered (ypN− Reg+, ypN− Reg− and ypN+) and four‐tiered (ypN− Reg+, ypN− Reg−, ypN+ Reg+ and ypN+ Reg−) classifications. In our cohort, 31% of patients presented with ypN+ rectal cancer. As expected, we found significantly worse overall survival (OS) in ypN+ patients compared to ypN− patients (P = 0.002). The percentage of ypN− patients with lymph nodes with complete regression was 20% in our cohort. While node‐negative patients with and without regression had similar OS (P = 0.09), disease‐free survival (DFS) was significantly better in node‐negative patients with regression (P = 0.009). Conclusions: Regression in lymph nodes is frequent, and node‐negative patients with evidence of lymph node regression have better DFS compared to node‐negative patients without such evidence. [ABSTRACT FROM AUTHOR]

Dispersal is more intense in the ocean than on land because most marine taxa present planktonic life stages that are transported by currents even without specific morphological traits. Thus, species dispersal shapes the distribution of biodiversity along seascapes and drives the composition of biodiversity assemblages. To identify marine assembling zones which characterise spatial areas particularly prone to receive and retain similar animal assemblages from the regional pool of species through passive dispersal, we propose a community‐based approach grounded on Lagrangian simulations of plankton dispersal. This novel approach was applied to communities (coast, outer shelf, slope, seamounts and islands; 0–80 m depth) of the Tropical Southwestern Atlantic and used to assess connectivity pathways. For that, we classified the modelled particles in 15 categories according to biological traits (planktonic life duration and spawning habitat) of representative planktonic communities. From the hierarchical clustering of the multivariate matrix containing the amount of arriving particles from each category in each cell we defined 14 assembling zones. Results highlighted that the assembling zones were mostly shaped by the degree of exposure to currents and the presence of mesoscale features (eddies, recirculation) derived from the interaction between these currents and coastlines. The boundaries, dispersal and connectivity patterns of these zones consistently align with local and regional in situ spatial distribution and abundance patterns of organisms, and provide an appropriate basis for the formulation of ecological hypotheses in the metacommunity framework to be tested in situ, such as the balance between species sorting and mass effect assembling archetypes. This approach, when coupled with the knowledge of other processes shaping communities' structure and distribution, provides important insights for regions and animal groups for which knowledge is limited or absent, and more generally allows for a comprehensive overview of the distribution of distinct communities and connectivity pathways along marine environments. [ABSTRACT FROM AUTHOR]

This article examines the impact of the COVID-19 pandemic on mortality rates associated with hematological malignancies in Italy. The study found that deaths with any mention of hematological malignancies increased in 2020 compared to the previous year, while deaths classified as the underlying cause of death declined. The increase in mortality was most pronounced for chronic lymphocytic leukemia (CLL) and less prominent for non-Hodgkin lymphoma (NHL) and multiple myeloma (MM). The study highlights the importance of considering multiple causes of death in assessing the mortality burden in hematological patients during the pandemic. [Extracted from the article]

Aim: Water column acoustic backscatter is regularly registered during oceanographic surveys, providing valuable information on the composition and distribution of pelagic life in the ocean. We propose an objective approach based on functional data analysis to classify these acoustic seascapes into biogeographical regions. Location: Tropical South Atlantic Ocean off northeastern Brazil. Taxon: Sound‐scattering pelagic fauna detected with acoustic echosounders, principally small fish, crustaceans, squid and diverse gelatinous life‐forms. Methods: We use acoustic backscatter as a function of depth, simultaneously at three frequencies, to numerically describe the vertical distribution and composition of sound‐scattering organisms in the water column. This information is used to classify the acoustic seascape through functional principal component analysis. The analysis routine is tested and illustrated with data collected at 38, 70 and 120 kHz in waters affected by contrasting environmental conditions. Results: Acoustic seascape partitioning mirrored the distribution of current systems, fronts and taxonomically based regionalization. The study area was divided between slope‐boundary and open‐ocean waters, and between spring and fall hydrological regimes. Main Conclusions: The acoustic seascape consistency and the spatiotemporal coherence of the regions classified show that the method is efficient at identifying homogeneous and cohesive sound‐scattering communities. Comparisons against hydrological and biological regionalization prove that the method is reliable at delineating distinct pelagic ecosystems in a cost‐efficient and non‐intrusive way. [ABSTRACT FROM AUTHOR]

Many animal species can rapidly change their body colouration and patterning, but often the ecological drivers of such changes are unknown. Here, we explored dynamic colour change in the bluelined goatfish, Upeneichthys lineatus, a temperate marine teleost species. Upeneichthus lineatus can change in a matter of seconds, from a uniform white colour to display prominent, vertical, dark red stripes. Initial observations suggested that rapid colour change in U. lineatus was associated with feeding and may act as a signal to both conspecifics and heterospecifics that are frequently observed to follow feeding goatfish. Field observations of the colour and behaviour of individual U. lineatus were collected to (1) document the repertoire of behaviours that U. lineatus displays and categorise associated colour patterns; (2) quantify the speed of dynamic colour change; (3) establish the context in which U. lineatus changes colour and pattern; and (4) test whether the behaviour of follower fishes is influenced by colour patterning or specific behaviours of the focal goatfish. We found that U. lineatus changed colouration from white to the red banded pattern in less than 10 s. The key driver of rapid colour change in U. lineatus was feeding, particularly when the fish fed with its head buried in sediment. Conspecific followers were most likely to be white in colour and adopt searching behaviour, regardless of the focal fish colour or behaviour. Other species of follower fish spent significantly more time following U. lineatus that were displaying dark red stripes when searching or eating, implying the red stripes may be an interspecific signalling mechanism. Our findings indicate that rapid colour change in teleost fish may be used for social communication and may provide U. lineatus with increased protection from predation when feeding via a safety‐in‐numbers approach. [ABSTRACT FROM AUTHOR]

Background: Von Willebrand Disease (VWD) is a common inherited bleeding disorder. Patients with VWD suffering from severe bleeding may benefit from the use of secondary long‐term prophylaxis. Aim: Systematically summarize the evidence on the clinical outcomes of secondary long‐term prophylaxis in patients with VWD and severe recurrent bleedings. Methods: We searched Medline and EMBASE through October 2019 for relevant randomized clinical trials (RCTs) and comparative observational studies (OS) assessing the effects of secondary long‐term prophylaxis in patients with VWD. We used Cochrane Risk of Bias (RoB) tool and the RoB for Non‐Randomized Studies of interventions (ROBINS‐I) tool to assess the quality of the included studies. We conducted random‐effects meta‐analyses and assessed the certainty of the evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Results: We included 12 studies. Evidence from one placebo controlled RCT suggested that VWD prophylaxis as compared to no prophylaxis reduced the rate of bleeding episodes (Rate ratio [RR],.24; 95% confidence interval [CI],.17–.35; low certainty evidence), and of epistaxis (RR,.38; 95%CI,.21–.67; moderate certainty evidence), and may increase serious adverse events RR 2.73 (95%CI.12–59.57; low certainty). Evidence from four before‐and‐after studies in which researchers reported comparative data suggested that VWD prophylaxis reduced the rate of bleeding (RR.34; 95%CI,.25–.46; very low certainty evidence). Conclusion: VWD prophylaxis treatment seems to reduce the risk of spontaneous bleeding, epistaxis, and hospitalizations. More RCTs should be conducted to increase the certainty in these benefits. [ABSTRACT FROM AUTHOR]

Essential thrombocythemia (ET) is a myeloproliferative neoplasm characterized by enhanced platelet production and thrombotic complications. The inhibition of platelet cyclooxygenase (COX) activity by the standard once‐daily aspirin is mostly incomplete due to accelerated thrombopoiesis. The phase II Aspirin Regimens in EsSential thrombocythemia (ARES) trial has recently compared the efficacy of once‐ vs. twice‐ or three‐times daily low‐dose aspirin in inhibiting platelet thromboxane (TX) A2 production, as reflected by serum (s) TXB2 measurements. The present substudy characterized the determinants of the highly variable response to the standard aspirin 100 mg once‐daily regimen in fully compliant patients with ET and the effects of the experimental dosing regimens on response variability. By multivariable analysis, the platelet count (directly) and cytoreductive treatment (inversely) were significantly associated with sTXB2 values in 218 patients with ET. However, the platelet count positively correlated with sTXB2 in patients not being treated with cytoreductive drugs (ρ = 0.51, P < 0.01, n = 84), but not in patients on cytoreduction. Patients in the lowest sTXB2 quartile were older, more often on cytoreductive drugs, had lower platelet count and Janus‐Associated Kinase2 (JAK2)‐V617F allele frequency as compared with patients in the upper sTXB2 quartiles. After 2 weeks of a twice‐ or 3‐times daily aspirin regimen, the association between the platelet count and sTXB2 became similar in cytoreduced and non‐cytoreduced patients. In conclusion, the platelet count appears the strongest determinant of TXA2 inhibition by once‐daily low‐dose aspirin in ET, with different patterns depending of cytoreductive treatment. More frequent aspirin dosing restores adequate platelet inhibition and reduces interindividual variability, independently of cytoreduction. [ABSTRACT FROM AUTHOR]

Congenital absence of skin (CAS) is a clinical sign associated with the main types of epidermolysis bullosa (EB). Very few studies have investigated the genetic background that may influence the occurrence of this condition. Our objective was to investigate genotype‐phenotype correlations on EB with CAS through a literature revision on the pathogenic variants previously reported. A total of 171 cases (49 EB simplex, EBS; 23 junctional EB, JEB; and 99 dystrophic EB, DEB), associated with 132 pathogenic variants in eight genes, were included in the genotype‐phenotype analysis. In EBS, CAS showed to be a recurrent clinical sign in EBS with pyloric atresia (PA) and EBS associated with kelch‐like protein 24; CAS was also described in patients with keratins 5/14 alterations, particularly involving severe phenotypes. In JEB, this is a common clinical sign in JEB with PA associated with premature termination codon variants and/or amino acid substitutions located in the extracellular domain of integrin α6β4 genes. In DEB with CAS, missense variants occurring close to non‐collagenous interruptions of the triple‐helix domain of collagen VII appear to influence this condition. This study is the largest review of patients with EB and CAS and expands the spectrum of known variants on this phenomenon. [ABSTRACT FROM AUTHOR]

Introduction: Turoctocog alfa pegol is a glycoPEGylated recombinant factor VIII (FVIII) with an extended half‐life developed for prophylaxis, treatment of bleeds and perioperative management in patients with haemophilia A. Aim: Evaluate the efficacy and safety of turoctocog alfa pegol treatment for major and minor surgeries in the pathfinder 3 and 5 phase III trials. Methods: Adults/adolescents aged ≥12 years with severe haemophilia A (FVIII <1%) received perioperative turoctocog alfa pegol treatment planned to achieve FVIII activity levels >80% during major surgery (pathfinder 3). The primary end point was haemostatic efficacy during surgery; secondary end points were blood loss, haemostatic effect postsurgery, consumption, transfusions, safety and health economics. Children (0‐11 years) undergoing minor surgeries received 20‐75 IU/kg turoctocog alfa pegol at Investigator's discretion (pathfinder 5). Results: pathfinder 3 included 35 patients undergoing 49 major surgeries. Haemostasis was successful in 47/49 (95.9%) surgeries; two had moderate haemostatic responses. Median (mean) blood loss during major surgery was 75 (322.6) mL. Four bleeds were reported postsurgery; three were successfully treated with turoctocog alfa pegol (one was not evaluated). On the day of surgery, overall mean (median) dose was 75.5 (74.5) IU/kg and mean (median) number of doses was 1.7 (2.0). Five procedures required 11 transfusions on the day of surgery or days 1‐6. No safety concerns or inhibitors were identified. Forty‐five minor surgeries in 23 children were performed without complications. Conclusion: Turoctocog alfa pegol was effective for perioperative haemostatic management of major and minor surgeries in patients across age groups with severe haemophilia A. [ABSTRACT FROM AUTHOR]

Introduction Haemophilia treatment varies significantly between individuals, countries and regions and details of bleed rates, factor consumption and injection frequency are often not available. Aim To provide an overview of the FVIII/ FIX treatment practice and outcome for patients with haemophilia A ( HA) or haemophilia B ( HB) across Europe. Methods Non-interventional, 12-month retrospective study where anonymized data were retrieved from haemophilia centres/registers in Belgium, France, Germany, Italy, Spain, Sweden and the United Kingdom. Male patients (all ages) receiving coagulation factor treatment 24 months prior to the study, with basal FVIII/ FIX levels ≤5 IU dL−1, without inhibitors, were included. Data were summarized descriptively. Results In total, 1346 patients with HA and 312 with HB were included in the analysis; 75% and 57% had severe disease ( FVIII/ FIX < 1 IU dL−1) respectively. Prophylaxis was most common for severe haemophilia, especially for children, whereas on-demand treatment was more common for moderate haemophilia in most countries. The mean ( SD) prescribed prophylactic treatment ranged from 67.9 (30.4) to 108.4 (78.1) ( HA) and 32.3 (10.2) to 97.7 (32.1) ( HB) IU kg−1 per week, across countries. Most patients on prophylaxis were treated ≥3 times/week ( HA) or two times/week ( HB). The median annual bleeding rate ( ABR) for patients on prophylaxis ranged from 1.0 to 4.0 for severe HA, and from 1.0 to 6.0 for severe HB, while those with moderate haemophilia generally had slightly higher ABRs. Median ABRs for on-demand-treated severe HA ranged from 4.5 to 18.0, and for HB, 1.5 to 14.0. Conclusion Treatment practice varied greatly between centres and countries and patients treated on-demand and prophylactically both experienced bleeds, emphasizing the need for further optimization of care. [ABSTRACT FROM AUTHOR]

Introduction D-dimer assay, generally evaluated according to cutoff points calibrated for VTE exclusion, is used to estimate the individual risk of recurrence after a first idiopathic event of venous thromboembolism ( VTE). Methods Commercial D-dimer assays, evaluated according to predetermined cutoff levels for each assay, specific for age (lower in subjects <70 years) and gender (lower in males), were used in the recent DULCIS study. The present analysis compared the results obtained in the DULCIS with those that might have been had using the following different cutoff criteria: traditional cutoff for VTE exclusion, higher levels in subjects aged ≥60 years, or age multiplied by 10. Results In young subjects, the DULCIS low cutoff levels resulted in half the recurrent events that would have occurred using the other criteria. In elderly patients, the DULCIS results were similar to those calculated for the two age-adjusted criteria. The adoption of traditional VTE exclusion criteria would have led to positive results in the large majority of elderly subjects, without a significant reduction in the rate of recurrent event. Conclusion The results confirm the usefulness of the cutoff levels used in DULCIS. [ABSTRACT FROM AUTHOR]

Neutrophil/lymphocyte (NLR) and platelet/lymphocyte (PLR) ratios might represent a yet unrecognized risk factor for venous thromboembolism (VTE) in cancer out-patients receiving chemotherapy. Accordingly, this study was aimed at analyzing the significance of these novel markers in the risk prediction of a first VTE episode in a population representative of a general practice cohort. To this purpose, a mono-institutional cohort study was conducted to retrospectively analyze NLR and PLR in 810 consecutive cancer out-patients with primary or relapsing solid cancer at the start of a new chemotherapy regimen. Over a median follow-up of 9.2 months, VTE occurred in 6.7% of patients. Incidental VTE was diagnosed at time of restaging in 47% of cases. Median pre-chemotherapy NLR ( p = 0.015) and PLR ( p = 0.040) were significantly higher in patients with intermediate risk class who developed symptomatic VTE with a twofold increased VTE risk for both inflammation-based markers (NLR: p = 0.022; PLR: p = 0.037) and a worst 1-year VTE-free survival for patients with high NLR or PLR. However, only PLR (HR = 2.4, p = 0.027) confirmed to be an independent predictor of future VTE in patients in the intermediate risk class in multivariate analysis, together with ECOG performance status (HR = 3.4, p = 0.0002) and bevacizumab use (HR = 4.7, p = 0.012). We may, thus, conclude that PLR, but to a lesser extent NLR, could represent useful clinical predictors of VTE, especially in selected categories of patients such as those in the intermediate risk class in whom the assessment of PLR could allow a better risk stratification of VTE without additional costs to the national health systems. [ABSTRACT FROM AUTHOR]

Magnetic resonance imaging ( MRI) and ultrasonography ( US) are increasingly used in haemophilia A ( HA) to detect early joint changes. A total of 40 clinically asymptomatic joints, never involved by bleeding events ['healthy joints' ( HJ)], were evaluated by MRI and, in parallel, by US in 20 young subjects with severe HA (22.45 ± 2.72 years old; no history of arthritides, of viral infections or of inhibitors against factor VIII). The same joints were evaluated in 20 matched non-haemophilic (no- HA) subjects (mean age 23.90 ± 2.31 years, P = 0.078 vs. HA subjects). US images were obtained with specific probe positions according to validated procedures. A validated US score and progressive (P- MRI) and additive (A- MRI) MRI scores were employed for data collection and analysis. The US score was higher in HA than in no- HA subjects (3.40 ± 1.72 vs. 0.80 ± 1.10, P < 0.001). Taking into account only moderate/severe alterations, joint effusion was found in 55% of HA and in 5% of no- HA joints ( P < 0.001); synovial hypertrophy was found in 20% of HA and in none of the no- HA joints; cartilage erosion was found in 30% of HA and in none of no- HA joints. MRI examinations confirmed these findings and the US score correlated with the A- MRI ( r = 0.732, P < 0.001) and with the P- MRI ( r = 0.598, P < 0.001) scores. MRI and US data significantly correlated as to effusion ( r = 0.819, P = 0.002), synovial hypertrophy ( r = 0.633, P = 0.036) and cartilage erosion ( r = 0.734, P = 0.010). Despite inherent limitations, joint US examination identified subclinical abnormalities of HJ in young subjects with severe HA. [ABSTRACT FROM AUTHOR]

The A>G polymorphism at position 19911 of the prothrombin gene is associated with a mildly increased risk of venous thromboembolism, alone or in association with such common thrombophilia mutations as factor V Leiden and prothrombin 20210 GA. Its role in cerebral sinus-venous thrombosis (CSVT) is not known. The presence of prothrombin 19911 A>G was investigated in a case-control study of 107 patients with cerebral thrombosis and factor V Leiden ( n = 25), prothrombin 20210 GA ( n = 47), without known thrombophilia ( n = 35) and 842 healthy individuals with the corresponding coagulation profile. Prothrombin 19911 A>G did not increase the risk of CSVT in carriers of factor V Leiden (adjusted odds ratio 1.6, 95%CI 0.6-4.7), prothrombin 20210 GA (odds ratio 1.1, 95%CI 0.6-2.2), nor in patients without known thrombophilia (odds ratio 1.3, 95%CI 0.5-3.1). Prothrombin 19911 A>G polymorphism does not appear to be a risk factor for CSVT, alone or in association with factor V Leiden or prothrombin 20210GA. [ABSTRACT FROM AUTHOR]

The relationships between the Platelet Function Analyzer (PFA)-100 and von Willebrand factor (VWF) levels and bleeding score (BS) were evaluated within a multicentre project on Molecular and Clinical Markers for the Diagnosis and Management of type 1 von Willebrand disease (MCMDM-1VWD). PFA-100 closure time, either with epinephrine (EPI) or adenosine diphosphate (ADP)-cartridges, was measured in 107 index cases, 105 affected and 71 unaffected family members, and 79 healthy controls. By regression analysis VWF levels were strongly related to both closure times, with a non-linear progression. In a multiple stepwise regression model, age- and sex-adjusted PFA-100 ADP and VWF ristocetin cofactor activity (VWF:RCo) were independently associated with BS. Most of the variation of BS was predicted by PFA-100 ADP and VWF:RCo alone. In the subgroup of patients with subtle abnormalities of the multimeric pattern, VWF was invariably reduced and closure time prolonged in almost all of them. Neither PFA-100 ADP nor EPI closure times appeared to significantly improve the diagnostic capability of VWF antigen (VWF:Ag) measurement. Thus, in an unselected population a normal PFA-100 would be useful to exclude VWD, but whether it could replace the more specific VWF assay in patients with significant mucocutaneous bleeding symptoms remains to be investigated prospectively. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article on novel mutations of the CLCN5 gene that include a complex allele and A 5' UTR mutation in Dent disease 1.

In the last few years, there has been a growing interest in the diagnosis of mild bleeding disorders (MBD) to find reliable tools for the assessment of their inherent bleeding risk and minimum criteria for the definition of a clinically useful diagnosis. Unlike in more severe haemorrhagic disorders, in MBD, the bleeding history may overlap with that reported by normal people. This problem has required the development of strategies that could allow the assessment of bleeding symptoms from both a qualitative (presence or absence) and quantitative (bleeding severity) aspect. An example of high quality clinical research in bleeding disorders was given by the systematic approach used for the evaluation of menorrhagia. For this symptom, the most common in women with bleeding disorders, the use of pictorial charts provided many new insights. Dr Kadir will review its use in a clinical context. The assessment of the whole bleeding history requires first, the development of reproducible tools to collect symptoms and secondly, formulation of easily applicable criteria to convert the collected data into clinical information. Dr Tosetto will propose a bleeding questionnaire in which clinical criteria were developed and validated, and show how a summative, quantitative index of bleeding severity (the Bleeding Score) could be used in von Willebrand disease. Finally, Dr James will review the development of quantitative analysis in children, a particularly important and difficult application, but one that needs to be tackled urgently. [ABSTRACT FROM AUTHOR]

The diagnosis of bleeding disorders is strictly dependent on the presence of bleeding symptoms in the patient, but collection of the bleeding history and its interpretation still remains subjective. For this reason, questionnaires on bleeding history have been proposed, and validated as diagnostic tools by comparing data obtained from patients with normal controls. This effort had led, at least with respect to von Willebrand disease (VWD), to the establishment of criteria that allow discrimination of VWD carriers from normal subjects. Among the possible criteria, a promising one is represented by the bleeding score (BS), a quantitative index summarizing both the number of episodes and their severity. The BS has shown good sensitivity and specificity for the diagnosis of type 1 VWD and could be integrated in a full diagnostic algorithm that also accounts for laboratory and family data. Furthermore, the BS has been shown to be correlated with several biological variables, including VWF and FVIII:C levels, platelet function analyzer (PFA-100™) closure times, and platelet glycoprotein haplotypes. Thus, collection of the BS at the time of the diagnosis may be a useful addition in the evaluation of the bleeding patients for both the researcher and medical practitioner, although the latter should probably wait for the results of further validation studies before making more extensive use of BS as a diagnostic tool. [ABSTRACT FROM AUTHOR]

Resistance to activated protein C (APC) has been demonstrated to be a risk factor for venous thromboembolism, but it is not known whether this phenotype is consistent over time. We reinvestigated 2580 subjects from the Vicenza Thrombophilia and Atherosclerosis (VITA) Project to evaluate the prevalence of a consistent APC resistance phenotype in the population. Among the 433 subjects with an APC resistance at first visit, the phenotype was confirmed in all the 74 factor V (FV) Leiden carriers and in 124 of 359 FV Leiden negative subjects (34%). The prevalence of a confirmed phenotype, not associated with FV Leiden, was 4·8% in our population. In a subgroup of subjects previously investigated for heritability of the APC resistance, we confirmed the APC resistance phenotype in seven of 39 (17·9%) subjects with an APC resistant sibling but only in 20 of 408 (4·9%) subjects without a sibling with the same phenotype ( P = 0·005). Among the 124 FV Leiden negative subjects with a persistent APC resistance phenotype, 40 (32%) had a plasma factor VIII coagulant activity level above 150 IU/dl and eight (6·4%) were carriers of the G20210A prothrombin allele. APC resistance not due to FV Leiden is a frequent and consistent phenotype in the general population, with a possibly strong genetic influence. [ABSTRACT FROM AUTHOR]

Pseudohomozygosity for activated protein C resistance (APC-r) is a rare condition due to the association of heterozygous FV Leiden mutation and partial type I FV deficiency. To assess the risk of venous thromboembolism in these subjects, seven families including 11 pseudohomozygotes and 45 relatives were examined. Among the relatives, 16 were heterozygous FV Leiden carriers, nine showed partial FV deficiency and 20 no abnormalities. Deep vein thrombosis occurred in 4/11 (36.3%) pseudohomozygous patients versus 6/16 (37.4%) FV Leiden carriers and 1/20 (5%) normal relatives. Pseudohomozygotes and FV Leiden carriers had a significantly increased risk of venous thrombosis in comparison to normal relatives (RR 8.8 and 5.7, respectively). There was no difference between the thrombotic risk of pseudohomozygous subjects and of FV Leiden carriers (RR 1.6, 95% CI 0.43–5.7). Furthermore, there was no difference in thrombosis-free survival between pseudohomozygotes and 45 consecutive FV Leiden heterozygous outpatients, suggesting that a referral bias may explain the apparent younger age of thrombosis in the pseudohomozygotes in comparison to relatives with FV Leiden heterozygosity (27 years v 54 years; P = 0.01). Pseudohomozygosity for APC resistance carries a significantly higher risk for venous thromboembolism in comparison to normal subjects, but probably not in comparison to heterozygous FV Leiden carriers. [ABSTRACT FROM AUTHOR]

The results of a medium-chain triglyceride loading test in a patient with severe carnitine–acylcarnitine translocase deficiency clearly demonstrated impaired in vivo utilization of medium-chain triglycerides. The loading test was performed at the ages of 7 and 36 months. The diet was adjusted accordingly. The clinical course has been favourable and the child is now in very good condition at age 4 years. We conclude that the utilization of medium-chain triglycerides is only partial in carnitine–acylcarnitine translocase deficiency and cannot reasonably be considered an optimal source of energy for these patients. Careful adjustment of dietetic treatment may help to improve prognosis. [ABSTRACT FROM AUTHOR]

Only a minority of subjects with factor V (FV) Leiden mutation develop venous thromboembolism (VTE), suggesting that additional genetic risk factors may be present in symptomatic carriers. We screened 157 unrelated carriers of the FV Leiden mutation with a first episode of VTE and 291 unrelated asymptomatic FV carriers for the presence of two frequent mutations, i.e. G20210A of the prothrombin gene and C677T of the methylenetetrahydrofolate reductase gene. Carriers with other inherited or acquired thrombophilia-associated abnormalities were excluded from analysis. Heterozygotes for the G20210A mutation were more prevalent among symptomatic carriers than in asymptomatic carriers (10.8% v 2.7%, P < 0.0001); homozygotes for the C677T mutation were also more prevalent in symptomatic carriers (21.6% v 14.4%, P = 0.05). Factor V Leiden carriers who had had a VTE episode during oral contraceptive intake were more frequently carriers of the G20210A mutation (14.3%, P = 0.03). These results further support the idea that VTE in carriers of FV Leiden results from interaction with additional genetic or circumstantial risk factors, and that an accurate search for such factors is required to identify carriers at risk. [ABSTRACT FROM AUTHOR]

Essential thrombocythaemia (ET) is a chronic myeloproliferative disorder characterized by the occurrence of thromboembolic episodes, particularly in patients aged > 60 years or with a previous history of thrombosis, and/or by haemorrhages in patients with an exceedingly high platelet count. In these subgroups of patients the use of cytoreductive therapy is beneficial in terms of risk/benefit ratio. Only limited anecdotal data are available on the thrombotic or haemorrhagic risk and survival in young asymptomatic ET patients with a platelet count < 1500 × 109/l. Therefore the optimal management of these patients is unknown. To assess the incidence of thrombosis and haemorrhages in this group of patients we carried out a prospective observational study in a cohort of 65 patients with ET, aged < 60 years, with no history of thrombosis or haemorrhage and platelet count < 1500 × 109/l, and in 65 age- and sex-matched controls. Patients were not treated with cytoreductive therapy until the occurrence of thrombosis or haemorrhage. Arterial or venous thrombotic events were objectively documented both in cases and in controls. The median follow-up was 4.1 years, with an incidence of thrombosis in patients and controls of 1.91 and 1.50 cases/100 patient-years, respectively. The age- and sex-adjusted risk rate ratio was 1.43 (95% CI 0.37–5.4). Only three minor haemorrhagic episodes occurred in patients, with an incidence of 1.12 cases/100 patient-years. Pregnancy and surgery were not associated with thrombosis in these patients. We conclude that the thrombotic risk in young ET patients, with no thrombotic history and a platelet count < 1500 × 109/l, is not increased compared to the normal population and that a conservative therapeutic approach should therefore be considered in these patients. [ABSTRACT FROM AUTHOR]

The article focuses on the study that evaluates the usefulness of low dose Rituximab alone in acquired haemophilia A. The study involves a 79-year-old male patient, who was given dose of 100 milligram (mg) weekly for a total of four doses aimed at speeding up the eradication of the inhibitor. It suggests that low dos Rituximab alone could be of benefit in acquired haemophilia developing in elderly patients