The psychosocial impact of haemophilia from patients' and caregivers' point of view: The results of an Italian survey.

BACKGROUD: A huge amount of data about psychosocial issues of people with haemophilia (PwH) are available; however, these materials are fragmentary and largely outdated, failing to reflect the impact of current treatment strategies. AIM: Describing the influence of illness on psychosocial aspects of adult PwH (≥18 years) and caregivers of children with haemophilia (CPwH) without inhibitors, in Italy. METHODS: Surveys (for adult PwH, CPwH and haemophilia specialists) were developed by a multidisciplinary working group and conducted from November 2019 to June 2020. RESULTS: A total of 120 PwH without inhibitors and 79 CPwH completed the survey. Adult patients reported a significant impairment in many psychosocial aspects, including working activities, relations with family members and social relations. Caregivers generally reported better scores in all aspects of the survey. Mobility, Pain and Mental health domains of EQ-5D were the most frequently impaired in both patients and caregivers, reducing the perceived quality of life. Genetic counselling was an important issue, 53% of CPwH declaring unawareness of their carrier status, as well as the psychological support offered by the reference center, 67.0% of respondents reporting that no psychological support was provided at the time of diagnosis communication. CONCLUSION: This study provides information about PwH's and CPwH's point of view in the current scenario of continuous innovations in haemophilia treatment and management furthermore, updated insights on psychosocial problems faced by patients and caregivers are reported.

Evans syndrome: Disease awareness and clinical management in a nation-wide ITP-NET survey.

Evans syndrome (ES) is rare and mostly treated on a "case-by-case" basis and no guidelines are available. With the aim of assessing disease awareness and current management of adult ES, a structured survey was administered to 64 clinicians from 50 Italian participating centers. Clinicians had to be involved in the management of autoimmune cytopenias and were enrolled into the ITP-NET initiative. The survey included domains on epidemiology, diagnosis, and therapy of ES and was designed to capture current practice and suggested work-up and management. Thirty clinicians who had followed a median of 5 patients (1-45)/15 years responded. The combination of AIHA plus ITP was more common than the ITP/AIHA with neutropenia (p < .001) and 25% of patients had an associated condition, including lymphoproliferative syndromes, autoimmune diseases, or primary immunodeficiencies. The agreement of clinicians for each diagnostic test is depicted (i.e., 100% for blood count and DAT; only 40% for anti-platelets and anti-neutrophils; 77% for bone marrow evaluation). Most clinicians reported that ES requires a specific approach compared to isolated autoimmune cytopenias, due to either a more complex pathogenesis and a higher risk of relapse and thrombotic and infectious complications. The heterogeneity of treatment choices among different physicians suggests the need for broader harmonization.

Clinical phenotype, fibrinogen supplementation, and health-related quality of life in patients with afibrinogenemia.

Due to the low prevalence of afibrinogenemia, epidemiologic data on afibrinogenemia are limited, and no data are available on health-related quality of life (HRQoL). We conducted a cross-sectional international study to characterize the clinical features, the fibrinogen supplementation modalities, and their impact on HRQoL in patients with afibrinogenemia. A total of 204 patients (119 adults and 85 children) from 25 countries were included. The bleeding phenotype was severe: 68 (33.3%) patients having at least one bleed per month and 48 (23%) a history of cerebral bleeding. About 35% (n = 72) of patients were treated with fibrinogen concentrates or cryoprecipitates as prophylaxis, 18.1% (n = 37) received ≥1 injection per week, and 16.6% (n = 34) were on home treatment. A thrombotic event was reported in venous and/or arterial territories by 37 (18.1%) patients. Thrombosis occurred even in young patients, and recurrence was frequent (7.4%). The total HRQoL was lower in children than in adults. Discomfort linked to treatment and limitations to sports and leisure were the main concerns. Women and children were particularly affected in family relationships. In multivariate analyses, younger age, residence in Asia or Africa, and a previous thrombotic event were statistically correlated with a worse HRQoL. In summary, our study underlines the severe bleeding and thrombotic phenotype and their impact on HRQoL in afibrinogenemia. The optimal strategy for fibrinogen supplementation needs to be determined. This trial was registered at www.clinicaltrials.gov as #NCT03484065.

Laying the foundations for gene therapy in Italy for patients with haemophilia A: A Delphi consensus study.

INTRODUCTION: Current treatment for haemophilia A involves factor VIII replacement or non-replacement (emicizumab) therapies, neither of which permanently normalise factor VIII levels. Gene therapy using adeno-associated viral (AAV) vectors is an emerging long-term treatment strategy for people with severe haemophilia A (PwSHA) that is likely to be available for clinical use in the near future. AIM: This article proposes practical guidelines for the assessment, treatment, and follow-up of potential PwSHA candidates for AAV-based gene therapy. METHOD: Using the Delphi method, a working group of Italian stakeholders with expertise in and knowledge of the care of adults with haemophilia A analysed literature for AAV-based gene therapy and drafted a list of statements that were circulated to a panel of Italian peers. During two rounds of voting, panel members voted on their agreement with each statement to reach a consensus. RESULTS: The Delphi process yielded 40 statements regarding haemophilia A gene therapy, across five topics: (1) organisational model; (2) multidisciplinary team; (3) patient engagement; (4) laboratory surveillance; and (5) patient follow-up and gene therapy outcomes. The consensus was reached for all 40 statements, with the second round of voting needed for five statements. CONCLUSION: Use of the hub-and-spoke organisational model and multidisciplinary teams are expected to optimise patient selection for gene therapy, as well as the management of dosing and patient follow-up, patient engagement, laboratory surveillance, and patient expectations regarding outcomes. This approach should allow the benefits of AAV-based gene therapy for haemophilia A to be maximised.

IDEAL study: A real-world assessment of pattern of use and clinical outcomes with recombinant coagulation factor IX albumin fusion protein (rIX-FP) in patients with haemophilia B in Italy.

INTRODUCTION: Factor IX replacement therapy is used for treatment and prophylaxis of bleeding in haemophilia B. rIX-FP is an extended half-life albumin-fusion protein, which, in clinical studies, has demonstrated prolonged dosing intervals up to 21 days for routine prophylaxis, providing therapeutic benefit. AIMS: To describe dosing frequency and consumption (primary endpoint), efficacy and safety of rIX-FP treatment during routine clinical practice in Italy. METHODS: Patients with moderate/severe haemophilia B on prophylaxis with rIX-FP for ≥6 months, were enrolled in this observational study from October 2017 to February 2019 and followed-up for 2 years. Descriptive analysis included prospective and retrospective data (12 months prior to switching to rIX-FP). RESULTS: Data were collected from 59 male patients (median age 30.1 years) enrolled by 23 Italian centres. Of them, 50 were on prophylaxis during the entire observation period and completed the study. The infusion frequency changed from 2-3 times/week in 86.0% of patients with previous treatment, to less than once a week in 84.0% of patients treated with rIX-FP at the 2nd-year follow-up. The annual number of infusions decreased by about 70%, whereas the mean FIX activity trough level increased from 3.8% to 14.4% (mean > 10% in all the infusion regimens). Median Annualised Bleeding Rate of .0 was achieved across all prophylaxis regimens. Subjects with zero bleedings increased from 66.0% to 78.0% with rIX-FP. CONCLUSION: Treatment with rIX-FP reduced infusion frequency, while providing higher FIX trough levels with substantial benefit in terms of annualised bleeding rate and a good safety profile.

Efficacy and safety in patients with haemophilia A switching to octocog alfa (BAY 81-8973): Final results of the global real-world study, TAURUS.

OBJECTIVES: To report the final results of the 2-year TAURUS study, assessing weekly prophylaxis dosing regimens of octocog alfa (Kovaltry®/BAY 81-8973) used in standard clinical practice in patients with moderate-to-severe haemophilia A. METHODS: TAURUS (NCT02830477) is a phase 4, multinational, prospective, non-interventional, single-arm study in patients of any age with moderate or severe haemophilia A (≤5% factor [F]VIII activity). TAURUS was designed to primarily investigate weekly prophylaxis dosing regimens used in standard clinical practice. Annualised bleeding rates (ABRs), treatment satisfaction and adherence, and safety were also assessed. RESULTS: Of 302 patients included in the full analysis set, 84.4% (n = 255) maintained their octocog alfa prophylaxis baseline regimen throughout the study, with a majority of patients (76.5%, n = 231) on two times or three times weekly regimens at the end of the observation period (≥1-≤2 years). ABRs, treatment satisfaction, and adherence remained stable during the observation period. Octocog alfa was well tolerated and there were no new or unexpected adverse events. CONCLUSIONS: These data show that a smooth transition is observed when switching to octocog alfa from a previous FVIII treatment, with no safety issues and stable bleeding rates in a real-world setting of patients with moderate-to-severe haemophilia A.

Severe maternal thrombocytopenia and prenatal invasive procedures: still a grey zone.

Management of severe thrombocytopenia, particularly of ITP, in pregnancy is mainly based on expert consensus and clinical experience while there are no clear indications about the minimum platelet count requested for prenatal diagnosis invasive procedures. Since the lack of specific recommendations we reported our clinical management of a patient suffering from severe thrombocytopenia, undergoing amniocentesis. Due to the anecdotic possibility of maternal and fetal bleeding in case of severe thrombocytopenia, prophylaxis with IVIG or even corticosteroids could be considered as a safer strategy to prevent post-procedural adverse outcomes.

Personalized Prophylaxis with myPKFiTCE: A Real-World Cost-Effectiveness Analysis in Haemophilia A Patients.

Background and Objectives: This study aimed to assess the effectiveness and costs associated with pharmacokinetics-driven (PK) prophylaxis based on the myPKFiT® device in patients affected by hemophilia A (HA) in Italy. Materials and Methods: An observational retrospective study was conducted in three Italian hemophilia centers. All patients with moderate or severe HA, aged ≥ 18 years, capable of having PK estimated using the myPKFiT device, and who had had a clinical visit between 1 November 2019 and 31 March 2022 were included. Differences in clinical, treatment, health resources, and cost data were assessed comparing post-PK prophylaxis with pre-PK. The incremental cost-effectiveness ratio (ICER) was estimated as cost (EUR) per bleed avoided. Results: The study enrolled 13 patients with HA. The mean annual bleeding rate decreased by -1.45 (-63.80%, p = 0.0055) after the use of myPKFiT®. Overall, the consumption of FVIII IU increased by 1.73% during follow-up compared to the period prior the use of the myPKFiT. Prophylaxis based on the myPKFiT resulted in an ICER of EUR 5099.89 per bleed avoided. Conclusions: The results of our study support the idea that the use of PK data in clinical practice can be associated with an improvement in the management of patients, as well as clinical outcomes, with a reasonable increase in costs.

Predictors of inhibitor eradication by primary immune tolerance induction in severe haemophilia A with high responding inhibitors.

BACKGROUND: Immune tolerance induction (ITI) is the only proven strategy to eradicate factor VIII inhibitors in patients with haemophilia A (HA). AIM: To identify patients and treatment options with the highest chance of inhibitor eradication by primary ITI. PATIENTS AND METHODS: In the frame of the Italian ITI Registry, carried out from 1995 to 2015 (last follow-up 2018), 137 primary ITI courses in severe HA patients (90/137 with poor prognosis) were analysed for predictors of outcome (complete/partial response or failure). Sixty-six of them (48%) were prospectively evaluated. RESULTS: ITI was successful in 91/137 patients (66.4%) and 70 (51.1%) achieved complete response within 11 months (median). Historical peak titres ≤200 BU/ml (P = .033), inhibitor titres ≤5 BU/ml at ITI start (P = .001), peak titres ≤100 BU/ml during ITI (P < .001) and missense mutations and small insertions/deletions of FVIII gene (P = .027) predicted complete inhibitor eradication. A score that considers the cumulative number of these variables predicted complete response with positive predictive values up to .81 at ITI start and .91 during ITI, respectively. Patients who had no bleeding (OR, 3.45, 95% CI: 1.4-8.6) nor other adverse events (OR 2.6, 95%CI: 1.3-5.3) during ITI had higher chances of complete response. During the 120-month follow-up (median), 2/70 patients who had achieved complete response relapsed (2.9%). CONCLUSIONS: This Registry, with a centralized review of outcomes, homogeneous data collection (half of which prospective) and long-term follow-up, provides insights for optimizing ITI, with a rationale for further studies in the currently evolving scenario of inhibitor management in HA patients.

Haemophilia management and treatment: An Italian survey on patients', caregivers' and clinicians' point of view.

INTRODUCTION: Haemophilia management and patients' quality of life significantly improved. However, data on current patients', caregivers' and clinicians' satisfaction and limitations of treatments and haemophilia management are limited. AIM: Assessing the management satisfaction and unmet needs from the perspective of Italian patients with haemophilia (PWH) without inhibitors (or caregivers if children) and of specialist physicians. METHODS: Surveys (for patients≥18 years, caregivers of children and haemophilia specialists) were developed by a multidisciplinary working group and conducted from November 2019 to June 2020. RESULTS: Among 275 participants, 120 (43.6%) were PWH without inhibitors, 79 (28.7%) caregivers and 37 (13.4%) clinicians. Patients and caregivers perceived a higher control of the disease compared to clinicians. However, more than 40% of patients and caregivers reported to feel significantly conditioned by the risk of bleeding during their daily life. PWH reported a 6-month mean/median (range) of bleeds 2.3/.0 (0-24) and caregivers 1.3/.0 (0-16) in children. The treatment burden (frequency of administration) was not satisfactory for more than half adults and caregivers of children treated with prophylaxis. A good access to treatment, haemophilia centres and medical service was reported, with issues associated to the multidisciplinary approach and treatment at emergency department. CONCLUSIONS: This large national study provides an updated overview of haemophilia care in Italy from different points of views, highlighting positive aspects and unmet needs. This information can guide future interventions to improve haemophilia management and the assessment of impact of new treatment options.

Direct oral anticoagulants for the treatment of atrial fibrillation in patients with hematologic malignancies.

Atrial fibrillation (AF) is common in patients with cancer due to both the proinflammatory effect of neoplastic cells and to cardiotoxicity of anti-tumor therapies. Anticoagulation is still challenging in cancer patients due to increased bleeding risk related to specific neoplasms such us hematologic malignancies. The aim of this retrospective study was to evaluate the safety and the efficacy of direct oral anticoagulants (DOACs) in AF patients affected by hematologic neoplasms. We included 97 patients on active anticancer treatment. The median follow-up was 25 months (range 10-108). No thromboembolic complications occurred, while 14 bleeding events were recorded: 1 major, 12 clinical relevant non major bleeding and 1 minor bleeding. Although retrospective and with a small number of enrolled patients, our data support the efficacy and safety of DOACs in patients affected by hematologic malignancies suggesting caution to particular situations, such as thrombocytopenia.

Italian experience with rVIII-single chain: a survey of patients with haemophilia A and their physicians.

rVIII-SingleChain is indicated for treatment and prophylaxis of bleeding in patients with haemophilia A (HA). The safety and efficacy of rVIII-SingleChain have previously been shown in the AFFINITY clinical trial programme. This survey evaluated clinical experience following a switch to rVIII-SingleChain from the perspective of both physicians and patients. A web-based survey (July-September 2019) involving 14 Haemophilia Treatment Centres (HTCs) collected data about HA patients who were under treatment with rVIII-SingleChain for ≥ 12 months, as reported by their physicians. In addition, about half of these patients were separately interviewed. Out of 91 patients receiving rVIII-SingleChain in the 14 participating HTCs, 48 had been treated for ≥ 12 months; among those 48, 38% were ≤ 18 years, 37% 19-40 years and 25 % ≥ 41 years; 73% of them had severe HA and 85% were being treated with prophylactic therapy. Twenty-six patients accepted to be separately interviewed: mean age was 30 years; 62% had severe HA and 85% were receiving prophylaxis. Focusing on those patients who were already in prophylaxis with prior FVIII (all but one with recombinant factors), infusion frequency was significantly reduced from 3-2 per week following the switch to rVIII-SingleChain (mean, 2.74 vs. 2.44, respectively; p=0.013), as reported by physicians; the rate of patients needing 3 infusions per week dropped from 74% with previous products to 44% with rFVIII-SingleChain. The annual mean factor consumption was 4740 IU/Kg (median, 4500 IU/Kg; min, 2.215 IU/Kg; max, 7.200 IU/Kg) with prior product and 4320 IU/Kg (median, 4320 IU/Kg; min, 2.215 IU/Kg; max, 6.646 IU/Kg) with rVIII-SingleChain. Both physicians and patients reported a significant reduction in annual total bleeding rates with rVIII-SingleChain compared with prior product (mean 2.15-0.96 and 2.46-0.71 events/year, p = 0.031 and p = 0.018, respectively). Mean satisfaction ratings (from 1; dissatisfied, to 5; very satisfied) for rVIII-SingleChain were quite high for both physicians (4.14, 86% satisfied/very satisfied) and patients (4.18, 86% satisfied/very satisfied). This survey suggested that switching to rVIII-SingleChain allowed patients to reduce their injection frequency without increasing factor consumption or compromising clinical results. Both physicians and patients reported a positive experience with rVIII-SingleChain after 1 year of treatment.

Eltrombopag second-line therapy in adult patients with primary immune thrombocytopenia in an attempt to achieve sustained remission off-treatment: results of a phase II, multicentre, prospective study.

Up to 30% immune thrombocytopenia (ITP) patients achieve a sustained remission off-treatment (SROT) after discontinuation of thrombopoietin receptor agonists (TPO-RAs). Factors predictive of response are lacking. Patients aged ≥18 years with newly diagnosed or persistent ITP were treated with eltrombopag for 24 weeks. Primary end-point was SROT: the proportion of responders that were able to taper and discontinue eltrombopag maintaining the response during a period of observation (PO) of six months. Secondary end-points included the association between some immunological parameters (TPO serum levels, cytokines and lymphocyte subsets) and response. Fifty-one patients were evaluable. Primary end-point was achieved in 13/51 (25%) treated patients and 13/34 (38%) patients who started the tapering. Baseline TPO levels were not associated with response at week 24 nor with SROT. Higher baseline levels of IL-10, IL-4, TNF-α and osteopontin were negative factors predictive of response (P = 0·001, 0·008, 0·02 and 0·03 respectively). This study confirms that SROT is feasible for a proportion of ITP patients treated with eltrombopag. Some biological parameters were predictive of response.

ABO Blood Group and Inhibitor Risk in Severe Hemophilia A Patients: A Study from the Italian Association of Hemophilia Centers.

Considering the profound influence exerted by the ABO blood group system on hemostasis, mainly through the von Willebrand factor and factor VIII (FVIII) complex, we have conducted a study evaluating the possible role of blood type on the risk of inhibitor development in hemophilia A. A total of 287 consecutive Caucasian patients with severe hemophilia A (202 without FVIII inhibitors and 85 with FVIII inhibitors) followed at seven Italian Hemophilia Treatment Centers belonging to the Italian Association of Hemophilia Centers (AICE) were included in the study. A higher prevalence of O blood group was detected in patients without inhibitors as compared in inhibitor patients (55 vs. 30.6%; p < 0.001). Among the other variables analyzed (age, F8 mutation, type and intensity of treatment and treatment regimen), F8 mutation class (high-risk vs. low-risk), and treatment regimen (on-demand vs. prophylaxis) were significantly correlated with inhibitor development. However, on a multivariate analysis, only the effects of F8 mutation and ABO blood type were independent of other covariates, being that non-O blood type is associated with a 2.89-fold increased risk of inhibitor development. In conclusion, our study supports the protective effect of O blood type on inhibitor risk in severely affected hemophilia A patients.

Single centre experience on Acquired Haemophilia A patients: Diagnosis, clinical management and analysis of factors predictive of response and outcome.

BACKGROUND: Acquired Haemophilia A (AHA) patients show a high response rate to immunosuppressive therapy (IST) but few information about predictors of response and outcome are reported. AIMS: We describe a large single-centre AHA cohort, investigating prognostic variables for the 'best response' (BR), time to BR (TTBR) and overall survival (OS). METHODS: A total of 61 patients were included, collecting data from clinical charts. RESULTS: A progressive increase in diagnoses, from 1978 to 2019, was observed. Fifty/56 patients (89%) underwent haemostatic therapy (rFVIIa 46%, aPCC 34%) with no significant differences in the response (rFVIIa 92.3% vs aPCC 100%) and no thromboembolic events. Sixty/61 patients underwent first-line IST with an initial response rate of 58.4%. The 12-months OS was 85%, the bleeding associated mortality rate 3% (2/61). The response rates at last observation were: CR 64%, PR 8%. We evaluated the influence of age, gender, associated conditions, IST, haemoglobin levels, FVIII:C, inhibitor titre on BR, TTBR and OS: post-partum AHA achieved the BR after a longer time than AHA related to other aetiologies or idiopathic (p = .05); in univariate analysis female sex (p = .03) and the achievement of BR (p = .001) had a positive impact on the OS while AHA secondary to neoplasms showed a shorter survival (p = .04); only the BR achievement remained significant in multivariate analysis (p = .02). CONCLUSIONS: Our data on response and survival confirmed those from the main registries. Post-partum AHA and BR achievement were significantly associated to a longer TTBR and a longer OS, respectively. Other predictors of outcome deserve to be explored in prospective studies.

Immune thrombocytopenia (ITP) World Impact Survey (I-WISh): Impact of ITP on health-related quality of life.

Immune thrombocytopenia (ITP) has a substantial, multifaceted impact on patients' health-related quality of life (HRQoL). Data describing which aspects of ITP physicians and patients perceive as having the greatest impact are limited. The ITP World Impact Survey (I-WISh) was a cross-sectional survey, including 1507 patients and 472 physicians, to establish the impact of ITP on HRQoL and productivity from patient and physician perspectives. Patients reported that ITP reduced their energy levels (85% of patients), capacity to exercise (77%), and limited their ability to perform daily tasks (75%). Eighty percent of physicians reported that ITP symptoms reduced patient HRQoL, with 66% reporting ITP-related fatigue substantially reduced patient HRQoL. Patients believed ITP had a substantial impact on emotional well-being (49%) and 63% worried their condition would worsen. Because of ITP, 49% of patients had already reduced, or seriously considered reducing their working hours, and 29% had considered terminating their employment. Thirty-six percent of patients employed at the time of the survey felt ITP decreased their work productivity, while 51% of patients with high/very high symptom burden reported that ITP affected their productivity. Note, I-WISh demonstrated substantive impact of ITP on patients' HRQoL both directly for patients and from the viewpoint of their physicians. Patients reported reduced energy levels, expressed fears their condition might worsen, and those who worked experienced reduced productivity. Physicians should be aware not only of platelet counts and bleeding but also the multi-dimensional impact of ITP on patients' lives as an integral component of disease management.

Immune thrombocytopenia (ITP) World Impact Survey (iWISh): Patient and physician perceptions of diagnosis, signs and symptoms, and treatment.

Immune thrombocytopenia (ITP) is now well-known to reduce patients' health-related quality of life. However, data describing which signs and symptoms patients and physicians perceive as having the greatest impact are limited, as is understanding the full effects of ITP treatments. I-WISh (ITP World Impact Survey) was an exploratory, cross-sectional survey designed to establish the multifaceted impact of ITP, and its treatments, on patients' lives. It focused on perceptions of 1507 patients and 472 physicians from 13 countries regarding diagnostic pathway, frequency and severity of signs and symptoms, and treatment use. Twenty-two percent of patients experienced delayed diagnosis (caused by several factors), 73% of whom felt anxious as a result. Patients rated fatigue among the most frequent, severe symptom associated with ITP at diagnosis (58% most frequent; 73% most severe), although physicians assigned it lower priority (30%). Fatigue was one of the few symptoms persisting at survey completion (50% and 65%, respectively) and was the top symptom patients wanted resolved (46%). Participating physicians were experienced at treating ITP, thereby recognizing the need to limit corticosteroid use to newly-diagnosed or first-relapse patients and espoused increased use of thrombopoietin receptor agonists and anti-CD20 after relapse in patients with persistent/chronic disease. Patient and physicians were largely aligned on diagnosis, symptoms, and treatment use. I-WISh demonstrated that patients and physicians largely align on overall ITP symptom burden, with certain differences, for example, fatigue. Understanding the emotional and clinical toll of ITP on the patient will facilitate shared decision-management, setting and establishment of treatment goals and disease stage-appropriate treatment selection.

Von Willebrand factor with increased binding capacity is associated with reduced platelet aggregation but enhanced agglutination in COVID-19 patients: another COVID-19 paradox?

Patients with Coronavirus-associated disease-2019 (COVID-19) display alterations of the hemostatic system and the presence of a prothrombotic status frequently leading to vascular complications. However, the impact of COVID-19 on platelet activity, aggregation and agglutination still needs to be clarified. We measured total levels of von Willebrand factor (vWF) and vWF binding to the platelet glycoprotein (Gp) complex (GPIb-IX-V), in a cohort of COVID-19 patients admitted to the intensive care unit of our Institution. Moreover, we evaluated platelet aggregation in response to agonists (ADP, collagen, arachidonic acid) and platelet agglutination in response to ristocetin. We found that levels of vWF antigen and the active form of vWF binding to platelets (vWF:RCo), were markedly increased in these patients. These results were associated with higher agglutination rates induced by ristocetin, thereby indirectly indicating an increased capability of vWF to bind to platelets. Conversely, we found that platelet aggregation in response to both ADP and collagen was lower in COVID-19 patients compared to healthy volunteers. This study shows that COVID-19 is associated with increased vWF-induced platelet agglutination but reduced platelet responsivity to aggregation stimuli. Our findings have translational relevance since platelet adhesion to vWF may represent a marker to predict possible complications and better delineate therapeutic strategies in COVID-19 patients.

Antithrombotic prophylaxis for surgery-associated venous thromboembolism risk in patients with inherited platelet disorders. The SPATA-DVT Study.

Major surgery is associated with an increased risk of venous thromboembolism (VTE), thus the application of mechanical or pharmacologic prophylaxis is recommended. The incidence of VTE in patients with inherited platelet disorders (IPD) undergoing surgical procedures is unknown and no information on the current use and safety of thromboprophylaxis, particularly of low-molecular-weight-heparin in these patients is available. Here we explored the approach to thromboprophylaxis and thrombotic outcomes in IPD patients undergoing surgery at VTE-risk participating in the multicenter SPATA study. We evaluated 210 surgical procedures carried out in 155 patients with well-defined forms of IPD (VTE-risk: 31% high, 28.6% intermediate, 25.2% low, 15.2% very low). The use of thromboprophylaxis was low (23.3% of procedures), with higher prevalence in orthopedic and gynecological surgeries, and was related to VTE-risk. The most frequently employed thromboprophylaxis was mechanical and appeared to be effective, as no patients developed thrombosis, including patients belonging to the highest VTE-risk classes. Low-molecular-weight-heparin use was low (10.5%) and it did not influence the incidence of post-surgical bleeding or of antihemorrhagic prohemostatic interventions use. Two thromboembolic events were registered, both occurring after high VTE-risk procedures in patients who did not receive thromboprophylaxis (4.7%). Our findings suggest that VTE incidence is low in patients with IPD undergoing surgery at VTE-risk and that it is predicted by the Caprini score. Mechanical thromboprophylaxis may be of benefit in patients with IPD undergoing invasive procedures at VTE-risk and low-molecular-weight-heparin should be considered for major surgery.

Direct oral anticoagulants in patients with hematologic malignancies.

The anticoagulant treatment for patients with hematologic malignancies is low molecular weight heparin (LMWH), which is considered the safest in this particular patients setting. Although direct oral anticoagulants (DOACs) have proven their efficacy and safety in patients with cancer, their use can be challenging in patients with hematologic malignancies due to the peculiarity of these neoplasms: high thrombotic risk, possible onset of thrombocytopenia and concomitant anticancer therapies. The aim of our study was to evaluate the efficacy and safety of DOACs for venous thromboembolism or atrial fibrillation in patients with hematologic malignancies and plasmatic DOACs level during anticancer therapy and at time of bleeding or thrombotic complications. We evaluated patients with hematologic malignancies treated with DOACs for venous thromboembolism or atrial fibrillation-therapy was maintained until the platelet count was ≥50 × 109 /L. In case of concomitant anticancer treatment and haemorrhagic or thrombotic events, we checked DOACs plasma levels (trough and peak). The patients evaluated were 135: 104/135 were on anticancer therapy. We did not observe either thrombotic or major haemorrhagic adverse events. Minor bleedings occurred in 10 patients and clinical relevant non-major (CRNM) in two patients. There was a statistically significant correlation between bleedings and myelodysplastic syndrome. DOACs resulted effective and safe in patients with hematologic malignancies. DOACs plasma level can be helpful in suggesting an early dose adjustment to prevent haemorrhagic adverse event in patients on concomitant anticancer therapy. Larger prospective studies including hematologic patients are warranted to confirm the safety and efficacy of DOACs.