Bleeding, Thrombosis and Vascular Biology
Bleeding, Thrombosis and Vascular Biology studies problems related to blood coagulation, fibrinolysis, hemostasis, physiopathology and therapy of hemorrhagic and thrombotic diseases. It encourages and promotes clinical and laboratory research on thrombosis and hemostasis, also through the institution of research awards and "travel grants" for young researchers to participate in Italian or international congresses. It develops and supports the organization of scientific congresses, conferences and educational courses on the themes of hemostasis and thrombosis, promoting the exchange of knowledge. It promotes, protects and disseminates the results of research carried out by its members, and raises awareness of these issues in the scientific world. It transfers and summarizes developments in international research in the field of hemostasis and thrombosis through the preparation of guidelines for the diagnosis and treatment of thrombotic or hemorrhagic diseases, encouraging the application of scientific data to clinical practice. Submitting articles in our journal is free of charge; even the article publication fee is not required, since the costs are covered by private funds (SISET). <!-- Editorial Rome, a summer evening, on a terrace with a few Brazilian friends, nuns, escaped during the Seventies from the military dictatorship in that Country, which did not appreciate their teaching activities. It is a prayer vigil, the eve of Pentecost. Each of us has a torch that enlightens, with its flame, the starry sky. At the end, the nuns invite us not to blow out the flame of the torches, but to put them all together in a central brazier, already rich with burning fire. We are astonished: fire on fire? Weren’t either the torches or the brazier enough? “The Spirit is fire – Paula whispers to me – it is always new and it is never enough!”. This event came back to my mind after President Paolo Gresele informed me – to my surprise – of the SISET decision to found a new journal on haemostasis and thrombosis. Yet another journal, I thought immediately, aren’t there already too many around? But the surprise was even bigger when the President asked me – on behalf of the Executive Council of the Society – if I wanted to be the Editor in Chief of the new journal. I scoff, trying to go around the question, I thank… Bleeding, Thrombosis and Vascular Biology, BTVB, it sounds like a nice acronym. We choose it at the first meeting, on Lake Maggiore, with President Gresele, the six Section Editors and the editorial manager. And here I am, trying to write my first Editorial. But didn’t we say already everything about bleeding, embolism, thrombosis, endothelial cells? Don’t we risk to be late on the market, when all the fresh fish has been already sold out? But no, it's not like that. I recall the poet Hikmet suggesting that I am wrong: The most beautiful of the seas is the one we have not sailed yet, the most beautiful of our children has not been born yet, and the newest thing I would like to say, I have not said it yet. Let’s therefore ask scientists working all around with platelets, fibrinogen, fibrinolysis or micro-circulation to open their horizons towards a larger and multidisciplinary perspective, looking for mechanisms common to apparently different phenotypes. BTVB intends to host papers that build bridges, instead of erecting walls (physiological, methodological or clinical). Haemorrhage and thrombosis are the two traditional plates of the haemostatic scale, but the pin supporting them goes in a transversal way, from genetic to nutrition, from inflammation to environment, from artificial intelligence to big data, going through gender differences, socio-economic disparities, lifestyles. The central pivot of the haemostatic scale is made up of a huge amount of people, little studied, because they are considered normal. BTVB intends to host the care (“I care”) of healthy people, an attentive and systematic exploration of the big part below the iceberg, we usually neglect, in relation to the upper part, which is small but visible. Blood circulates everywhere, it is well known, but it is not the same everywhere, also because it meets different environments. We should ‘geo-localise’ those environments in order to better understand mechanisms and events that still escape to our attention. Paraphrasing Terenzio, the ancient Roman poet, each specialist of an organ or a disease should say nihil haemostaticum a me alienum puto, I do not consider anything of hemostasis far from me. Cardiologists, neurologists, obstetricians, pharmacologists, surgeons, rehabilitators and many others can consider themselves welcome on the pages of BTVB. Let’s start a trip, old and new, with the anxiety, the curiosity and the joyfulness of a long joint experience, with the astonishment and the unpredictability of those young scientists at their first scientific adventure. Good luck to all, on behalf of SISET, Section Editors, the Editorial Board, and myself, for the attention and the cooperation the scientific community will provide us. Giovanni de Gaetano Editor-in-chief -->
PAGEPress Scientific Publications, Pavia, Italy
Persistence of functional anti-PF4 antibodies and neutrophil activation in vaccine-induced immune thrombotic thrombocytopenia
Background: Vaccine-induced immune thrombotic thrombocytopenia (VITT) is characterized by thrombosis in unusual sites triggered by anti-PF4 antibodies. To the best of our knowledge, no studies with very long follow-up on anti-PF4 antibodies persistence have been reported. Methods: We carried out a multicenter study in 16 VITT patients studied at T0 (acute episode), T1 and T2 (after 6 and 29 months) assessing the persistence of anti-PF4/heparin antibodies and of neutrophil activation. Results: At T0 80%, at T1 75%, and at T2 11% of VITT patients were positive for anti-PF4/heparin antibodies by ELISA, while 75% at T0, 56% at T1, and 0% at T2 had a positive platelet activation assay. Plasmatic MMP-9 and MMP-9/NGAL were strikingly elevated at diagnosis, but they normalized at T1. No clinical relapses were observed. Conclusions: Although anti-PF4 antibodies may persist for a long-time following an acute VITT episode, they seem to be clinically irrelevant.
the study was approved by the local Ethics Committees (CER Umbria n. 3656/20) and the Bioethics Committee of University of Perugia (n. 222848)
Copyright (c) 2025 The Author(s) https://creativecommons.org/licenses/by-nc/4.0
When a feminist platelet went to the convention of prostaglandins and thromboxanes
A satirical monologue presented in Italian at the XXVIII Meeting of the Italian Society for Haemostasis and Thrombosis, Rome, November 2024.
Executive summary of the SISET position paper on the management of antithrombotic therapy in left ventricular thrombus
Dear Editor, I wish to report that the first gene therapy procedure in Italy for the treatment of severe or moderately severe hemophilia B has been successfully administered at the Policlinico of Milan....
Medicine at the crossroads of science, compassion and ethical responsibility
Dear Editor I am pleased to attract your attention and that of the readers of BTVB to the recent message (excerpta) of Pope Leo XIV to a delegation of cardiologists from the Paris Course on Revascularization held in Rome, December 5, 2025....
The landscape of rare coagulation factor deficiency management in Italy: a national hemophilia center survey
Background: Rare bleeding disorders (RBDs) are a group of inherited conditions caused by deficiencies in specific coagulation factors, excluding hemophilia A/B and von Willebrand disease. Individually rare, they pose a significant challenge for diagnosis and management due to diverse clinical presentations and low awareness. This study aimed to provide an overview of RBDs. Methods: An online survey was sent to Italian hemophilia treatment centers. Results: Nineteen centers responded. The diagnostic approach was tiring, but key definitions showed significant variability. This included defect severity, target hemostatic levels for surgery, eligibility thresholds for rare disease exemptions. The use of prophylaxis varied, although favored in severe FII, FVII, FX, and FXIII defects. Treatment primarily involved factor-specific concentrates and tranexamic acid. While inhibitor development was considered uncommon, it was a recognized risk. Bleeding management during dental procedures, pregnancy, and delivery also showed variability. Additionally, normal factor levels in neonates differed across centers. Conclusions: This study highlights a good consensus for managing certain RBDs (FII, FVII, FX, FXIII) in Italy. However, significant heterogeneity persists, emphasizing the need for greater standardization and further research in several key areas.
Diagnostic and management practices for inherited fibrinogen disorders: a nationwide survey of Italian Hemophilia Treatment Centers
Background: inherited fibrinogen disorders are characterized by a spectrum of quantitative or qualitative fibrinogen deficiency associated with both a hemorrhagic and thrombotic risk. Methods: a nationwide survey was conducted in 19 Italian Hemophilia Treatment Centers in order to investigate current diagnostic and management practices for inherited fibrinogen disorders (afibrinogenemia, hypofibrinogenemia, and dysfibrinogenemia). Results: the survey revealed a strong consensus (95% of centers) on the necessity of both functional and antigenic fibrinogen assays for diagnosis, and a preference for fibrinogen concentrate-based treatment (used by >85% of centers). However, significant heterogeneity was observed in critical areas: for hypofibrinogenemia, the definition of a «severe» form varied among centers, and the perceived risk of spontaneous intracranial hemorrhage remained a major point of uncertainty (up to 47% of respondents answered ‘don’t know’ for this risk in hypofibrinogenemia and dysfibrinogenemia). Furthermore, intervention thresholds for major surgical procedures showed a high degree of variability across all three disorders. Conclusions: the findings highlight areas of consistent practice alongside those requiring further standardization and collaborative research to optimize the care of individuals with these rare bleeding and thrombotic conditions.
A message of science, peace and gratitude
As we approach Christmas and the New Year 2026 - which will be the fifth for our journal - we want to extend our heartfelt gratitude to our Section Editors, to every eminent Colleague of the Editorial Board, to the Authors, reviewers, readers of the Bleeding, Thrombosis and Vascular Biology (BTVB), and to all members of SISET and AICE. The contributions of you all define how we are progressing and continue to grow. The recent recognition of BTVB by both Web of Science/Clarivate and Scopus is a great success shared with our Publisher – PAGEPress Publications. To our Readers: thank you for placing your attention in us and for the time you spend with our journal. Your expectations push us to maintain and improve excellence. To our Section Editors and Reviewers: thank you for the dedication you bring to each submission. Your thoughtful evaluations, high standards, and fairness strengthen the scientific process and support the Authors working to advance knowledge. Your impact is clearly present in every issue. To our Authors: thank you for selecting BTVB as the scientific forum for your research. We appreciate the effort behind each manuscript, your openness to revising and refining your work, and your commitment to driving progress in the field. We are deeply thankful for your help to nurture a young community built on excellence, respect, curiosity, openness, fantasy and innovation. Wishing you a healthy and joyful Christmas - that would hopefully coincide with the expected time of peace in the world - and our best wishes for a fantastic New Year, we sincerely thank everything you will do to support BTVB and the science that moves our field forward. The love that moves the sun and all the stars.
PO17 | Implementation and initial validation of a new teaching and assessment platform for experts in haemostasis and thrombosis
We have developed and tested a new teaching and assessment platform for future experts in haemostasis and thrombosis. Particular attention has been paid to the inter-company guidelines describing the minimum essential skills and knowledge required. Both the clinical and laboratory aspects can be taught, refined and assessed, so as to standardise the training of haemostasis and thrombosis experts, who are increasingly in demand throughout the country.
Abstracts from the 29^ National Conference of the Italian Society for the Study of Hemostasis and Thrombosis, Bergamo, Italy | 23-25 October 2025
29th National Conference of the Italian Society for the Study of Hemostasis and Thrombosis, 2025
The National Conference of the Italian Society for the Study of Hemostasis and Thrombosis was held in Bergamo from October 23 to 25, 2025. This is a training event organized every two years by this Society, with the aim of presenting and discussing the state of the art in the pathophysiology, diagnosis, prevention, and treatment of thromboembolic and hemorrhagic diseases. The course is aimed at all those, members and non-members alike, who share a common interest in these diseases and who wish to update their knowledge, gain a deeper understanding, and exchange ideas with colleagues from different national contexts. The need for continuous updating stems from the epidemiological importance of these diseases and, consequently, from the high number of patients suffering from thromboembolic or hemorrhagic diseases who are admitted to our hospitals on a daily basis or who require long-term outpatient treatment. Secondly, the continuous production of new scientific evidence on diagnostic methodologies, therapeutic strategies, and patient management requires regular updates presented and discussed by the most experienced Italian researchers in the field. The course will open with a session organized by the SISET Youth Group on certain aspects of thrombosis, consolidating the tradition inaugurated in the Society's recent conferences/courses. The course will then be divided into seven sessions: aspects of basic research, venous thromboembolism, arterial thrombosis, congenital bleeding disorders, primary haemostasis disorders and thrombocytopenia, management of medical and surgical emergencies in thrombosis and haemostasis, and haemorrhage and thrombosis in children. In addition to illustrating some updates in basic and translational research and summarizing general knowledge on certain topics (e.g., anticoagulant therapy in venous thromboembolism, cardiovascular risk models, the diagnostic and therapeutic classification of thrombotic microangiopathies), they will focus on innovative aspects in diagnosis and therapy (e.g., VEXAS syndrome or gene therapy for hemophilia) or debated aspects (e.g., measurement of circulating direct oral anticoagulant levels). Some rare clinical situations will be explored in depth (e.g., visceral arterial thrombosis, diagnosis and treatment of rare coagulopathies/thrombocytopathies, use of antithrombotic drugs in patients with congenital coagulopathies or immune thrombocytopenia). Clinical practice aspects will also be prioritized, such as the management of medical and surgical emergencies in patients at high risk of bleeding or the management of hormone therapy in cancer patients. Much attention will also be devoted to gender medicine, with reports on the use of antithrombotic drugs in women, the cardiovascular risk associated with hormone replacement therapy, the management of pregnancy and childbirth in immune thrombocytopenia, and the management of postpartum hemorrhage. Finally, a session will be devoted to hemorrhagic and thrombotic problems in neonates, children, and adolescents. As in the last two editions, the course will last two full working days, i.e., two mornings and one full day. Scientific communications will also be presented, with oral and poster sessions. The best oral communications, selected by a panel of reviewers who worked blind to the authors, will be presented during the plenary sessions.
PO90 | Acquired hemophilia A with high-titer inhibitor in a patient with cardiovascular and metabolic comorbidities
Background: Acquired hemophilia A (AHA) is a rare autoimmune coagulopathy characterized by the development of neutralizing autoantibodies against factor VIII (FVIII). The clinical presentation can be severe, with spontaneous and recurrent bleeding, often requiring multidisciplinary management, particularly in patients with multiple comorbidities. Case Report: A 74-year-old female patient was referred to our unit for recurrent acute anemia (Hb 3 g/dL) and diffuse mucocutaneous and muscular hematomas, especially in the bilateral subscapular regions with low perfusion. The hemorrhagic picture triggered episodes of sustained ventricular tachyarrhythmia, resulting in activation of a previously implanted single-chamber ICD, placed for dilated hypokinetic cardiomyopathy of hypertensive-valvular origin (moderate mitral regurgitation). Past medical history included insulin-dependent type II diabetes mellitus with stage III chronic kidney disease, non-progressive steatotic hepatomegaly, euthyroid uninodular hyperplasia, and a long-standing calcified uterine fibroid. FVIII inhibitor testing was performed, revealing FVIII activity at 8% and an inhibitor titer of 8 BU/mL, leading to a diagnosis of AHA. The patient received intensive hemostatic treatment with recombinant activated factor VII (rFVIIa), totaling 35 vials (5 mg), which resulted in bleeding control and progressive reduction of transfusion needs (15 units of packed red blood cells). Concurrently, corticosteroid immunosuppressive therapy was initiated at 1 mg/kg, with a complete response achieved: inhibitor eradication and normalization of FVIII levels. At discharge, the patient showed hemodynamic stability, no further arrhythmic episodes, resolution of hematomas, and partial functional recovery. Conclusions: AHA may present acutely and severely, even in patients without overt autoimmune disease. Management requires a multidisciplinary approach, individualized therapy, and close monitoring of comorbidities. This case highlights the complexity of managing AHA in elderly patients with advanced cardiac disease and chronic metabolic disorders. The use of bypassing agents such as rFVIIa proved effective and safe even in a fragile cardiological context, with careful monitoring. Prompt initiation of immunosuppressive therapy was crucial, allowing for hematologic recovery without significant infectious or metabolic complications.
PO91 | Disseminated intravascular coagulation with deep vein thrombosis in a frail patient: an extreme manifestation triggered by sepsis during SGLT2i therapy
Background: Disseminated intravascular coagulation (DIC) is a life-threatening thrombotic or hemorrhagic complication, often triggered by severe sepsis. In frail patients, predisposing conditions such as dehydration, diabetic ketoacidosis (DKA), and SGLT2 inhibitor (SGLT2i) therapy may amplify the inflammatory cascade and coagulation imbalance. We report a case of severe DIC with central venous thrombosis associated with vancomycin-resistant Enterococcus faecalis (VRE) sepsis, successfully treated with antibiotics and therapeutic anticoagulation. Case Report: An 83-year-old woman with diabetes, heart failure, and cognitive impairment was admitted with fever, pyuria, hyperglycemia, metabolic acidosis, marked dehydration and acute kidney injury. Her therapy included beta blockers, ACE-inhibitors, MRA and SGLT2i. A diagnosis of SGLT2i associated urosepsis and DKA was made. Initial management included IV empirics antibiotics, fluids, and insulin infusion. To ensure stable venous access, a central venous catheter (CVC) was placed in the left subclavian vein. On day three, she continued to have fever despite antibiotic therapy and she developed monolateral upper left limb edema. Doppler ultrasound confirmed deep vein thrombosis extending from the CVC to the left subclavian vein. Laboratory tests revealed overt DIC: platelets 69,000/mm³, unmeasurable PT and aPTT, fibrinogen 37 mg/dL, D-dimer 9,770 ng/mL. Given the thrombotic phenotype and absence of active bleeding, therapeutic low molecular weight heparin was initiated. Urinoculture grew positive for Enterococcus faecalis vancomycin resistant. Previous antibiotic therapy was stopped, and Linezolid was started. Over the following days, clinical and laboratory improvement was observed: normalization of coagulation parameters (fibrinogen 190 mg/dL, platelets 129,000/mm³, D-dimer 1.11 ng/mL) and general stabilization. The patient was discharged in good condition. Conclusions: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are widely used in the treatment of type 2 diabetes and heart failure. While offering significant metabolic and cardiovascular benefits, they can pose considerable risks in vulnerable populations, particularly the elderly and frail. SGLT2i function by decreasing glucose reabsorption from the proximal convoluted tubule and increasing urinary glucose excretion. Consequently, this leads to reduced carbohydrate usage and prompts a shift toward the utilization of fatty acids, resulting in ketogenesis. Studies in rats have shown that SGLT2is can increase plasma concentrations of catecholamines and cortisol due to hypovolemia, leading to DKA. SGLT2i are also associated with an increased risk of urinary and genital tract infections, which in this instance evolved into systemic VRE sepsis. The resulting inflammatory response, gastrointestinal symptoms, likely contributed to dehydration and the onset of DKA. In turn, systemic inflammation and endothelial damage precipitated a fulminant DIC, with monolateral upper limb edema due to overt thrombosis of a CVC. Although anticoagulation in the context of DIC remains debated due to the risk of bleeding, therapeutic anticoagulation was deemed appropriate given the presence of thrombosis and the absence of hemorrhage. The clinical course confirmed both the safety and efficacy of LMWH in this case.
PO89 | Apixaban for secondary prevention of venous thromboembolism in hemodialysis patients: pharmacokinetic profile and safety outcomes
Background and Aims: The use of direct oral anticoagulants (DOACs) in patients with end-stage renal disease (ESRD) on dialysis remains controversial due to a different pharmacokinetics. To date, dialysis patients have been excluded from all randomized clinical trials and data on these setting are scanty. Among DOACs, apixaban has shown the most favorable profile in this population. We report the case of a female dialysis patient with a history of unprovoked pulmonary embolism and deep vein thrombosis, previously treated with vitamin K antagonists (VKAs), than shifted to apixaban low-dose (2.5 mg twice daily) due to hemorrhagic complications while on VKAs; we focus on apixaban plasma levels and safety outcomes during follow-up. Case Report: We present the clinical course of a 67 year-old female patient with end-stage renal disease undergoing chronic hemodialysis (three times per week), who was treated with apixaban for the secondary prevention of venous thromboembolism. The patient initially received vitamin K antagonists (VKAs) as acute-phase treatment, but this was withheld due to a spontaneous cerebral hemorrhage. She then received thromboprophylaxis with Calciparin, followed by Enoxaparin; both were poorly tolerated due to the route of administration. Apixaban was then started at the dosage of 2.5 mg twice daily. Apixaban plasma concentrations were measured using an anti-Xa assay calibrated specifically for apixaban. Clinical follow-up over six months included monitoring for symptomatic thrombotic events or bleeding complications, and laboratory parameters (i.e. hemoglobin). Apixaban plasma levels measured between day 9 and day 30 of treatment, on four separate occasions - three on non-dialysis days and one on a dialysis day - at both trough and peak times, remained within or slightly above the expected therapeutic range throughout the treatment period, both on dialysis and non-dialysis days. On non-dialysis days, peak concentrations were 95.8, 123.3, and 176.7 ng/mL (reference range: 30–153 ng/mL), while trough concentrations were 46.4 and 104.3 ng/mL (reference range: 11–90 ng/mL), with one trough sample inaccurate. On the dialysis day, peak and trough values were 196.3 ng/mL and 33.3 ng/mL, respectively (Figure 1). No thromboembolic or bleeding complications occurred during follow-up, laboratory values remained stable, and dialysis sessions proceeded without anticoagulation-related issues. Conclusions: This case supports the potential safety of low-dose apixaban in selected dialysis patients for VTE secondary prevention. In our patient, apixaban levels remained stable within therapeutic ranges, and no adverse events occurred over six months of follow-up. While based on a single case, this report contributes to growing evidence suggesting apixaban may be a viable anticoagulation option in ESRD patients, provided that close clinical and laboratory monitoring is maintained. Larger studies are needed to confirm safety and efficacy in this high-risk population. Figure 1.
PO88 | Bacterial lysate “lantigen B” induces proliferation of B and NK cells and the release of related cytokines
Background and Aims: Bacterial lysates (BLs) are medicines made from bacterial cells that are broken down and are intended to stimulate the immune system to recognize and fight infections. BLs are prescribed for the prevention of recurrent respiratory tract infections (RTIs) and, in general, almost all performed studies show that the number of RTIs and their severity decrease in BL-pretreated pa-tients, without relevant side effects. Lantigen B (Lan-B), among all the commercially available lysates is one of the most interesting. Being administered sublingually, can directly stimulate the immune cells in the site of infections as demonstrated by numerous clinical trials. The present study aimed at exploring and evaluating the ability of Lan-B to influence the proportion of various lymphocyte subpopulations and to modulate the release of selected cytokines that play a pivotal role in determining immune reactions. Also, this work was focused on evaluating these effects at the identical concentrations used in previous human studies. Methods: In this observational study PBMCs, from 7 healthy human donors, were isolated, cultured and incubated with Lan-B at 199.45 AU/mL. After incubation cells were resuspended with specific antibodies for the cytofluorimetric detection of cell surface phenotype using the following markers: CD45, CD4, CD8, CD16 and CD19. Consequently, cell culture supernatants were collected for the cytofluorimetric evaluation of cytokines concentration using LEGENDplexTM Human Inflammation Panel 1 (Figure 1). Results: Significant changes in the proportions of both CD19+ and CD56+ cells were observed in Lan-B stimulated cultures compared to unstimulated ones. In particular, both B (CD19+) and NK (CD19-/CD56+) cells proportion significantly increased from 18.20% in untreated vs. 45.27% in Lan-B-treated PBMC cultures (p=0.005). Changes were observed in the proportion of various CDs in untreated vs. Lan-B treated PBMCs, with an increase in CD19+ and in CD56+ cells. In this case, there is also an increase in CD8+ cells. Cytokines evaluation showed that, IL-1 beta, IFN-gamma, TNF-alpha, IL-17 and IL-18 are significantly increased whereas MCP1 significantly decreased upon Lan-B treatment. However, a trend for an increase of IL-12-p40, even though not significant, has been observed (p=0.052). Conclusions: This study highlighted the role of Lan-B in the modulation of the immune system by activating the innate immune system, namely NK cells, as well as the adaptive immune system, which produced considerably modified cytokines indicative of a Th1-mediated reaction. These observations can support Lan-B’s proven therapeutic efficacy. Following this first investigation, the activities of Lan-B dendritic cell maturation, epithelial cells, cytotoxic lymphocytes, and the immune response’s specificity will need future investigations. Figure 1.
PO85 | Acute retinal ischemia in hemoglobin SC disease: a case report and review of the literature
Background: Sickle cell disease (SCD) encompasses a group of hereditary hemoglobinopathies characterized by the presence of hemoglobin S (HbS), and includes homozygous sickle cell anemia (HbSS), sickle β⁰-thalassemia (HbS/β⁰), and heterozygous disorders, such as HbSC disease. The latter results from compound heterozygosity for HbS and hemoglobin C (HbC) mutations affecting the β-globin gene. Although HbSC disease generally presents with a milder clinical phenotype than HbSS, it shares the risk of vaso-occlusive complications in various organ systems, including the ocular district. Case Report: We report the case of a 28-year-old Ghanaian male with known HbSC disease under hydroxyurea treatment, who presented to the Emergency Department with sudden-onset floaters and a central scotoma in the left eye upon awakening. He reported intense physical exertion and episodes of diarrhea the previous day. His medical history included childhood hospitalization for osteomyelitis and a previous ischemic ocular event in 2020, complicated by vitreous hemorrhage and retinal detachment in the right eye, leading to profound vision loss. On examination, he was alert, afebrile, with normal vital signs. Ophthalmologic evaluation revealed left posterior vitreous detachment with vitreous strands and an area of retinal whitening and edema consistent with suspected macular retinal artery occlusion. Laboratory tests showed hemoglobin 121 g/L, hematocrit 36.8%, platelets 116 x 109/L, normal white blood cell count and inflammatory markers, and mildly elevated LDH (231 U/L) with undetectable haptoglobin. Hemoglobin electrophoresis confirmed 51% HbS and 43% HbC. Emergency erythrocytapheresis (red cell exchange transfusion) was performed, hydroxyurea was discontinued, and antiplatelet therapy with aspirin was initiated. During hospitalization, visual symptoms remained stable with no further deterioration. Additional evaluations including echocardiography, ECG-Holter, carotid ultrasound, and brain MRI/MRA revealed only a chronic right optic nerve atrophy. A mild functional protein C deficiency was noted, with normal antigen levels. The patient was discharged on a chronic monthly erythrocytapheresis regimen. Conclusions: HbSC disease can present significant clinical challenges, including vaso-occlusive episodes and proliferative retinopathy, whereas acute ischemic manifestations, such as retinal artery occlusion, are rare and lack evidence-based management guidelines. Compared to other SCD genotypes, HbSC disease remains understudied in terms of pathophysiology and treatment strategies. Unlike HbSS and HbS/β⁰, where hemolysis plays central role, HbSC-related vaso-occlusion may be more strongly influenced by increased blood viscosity. Treatment strategies align with those for HbSS, including the use of hydroxyurea, although evidence for its efficacy in HbSC is less robust and still under investigation. Alternative approaches focus primarily on minimizing the risk of further ischemic events by addressing modifiable risk factors such as hydration status and smoking. Therapeutic phlebotomy has been proposed as an adjunctive treatment for patients with HbSC disease, particularly in those with frequent vaso-occlusive episodes and elevated hemoglobin levels. Finally, red cell exchange (erythrocytapheresis) has been explored as a therapeutic option, however, evidence remains limited, and its use is generally extrapolated from experience in HbSS patients.
PO86 | Emicizumab in patients with moderate hemophilia A and severe bleeding phenotype: single-center real-world experience
Background and Aims: The role of prophylaxis in moderate hemophilia A (HA) patients is less clear than in severe HA, given their variable bleeding phenotype. A relevant portion of moderate HA patients may have a severe bleeding phenotype, characterized by frequent hemarthrosis, with a consequent high risk of developing chronic arthropathy. Therefore, this patients’ subgroup has been historically managed with factor VIII (FVIII) prophylaxis. Recently, the HAVEN 6 study has demonstrated the safety and efficacy of emicizumab prophylaxis in moderate/mild hemophilia A patients without inhibitors. In the subgroup of patients with moderate HA and severe bleeding phenotype, a significant reduction of the bleeding rate was observed, leading to the approval of emicizumab prophylaxis in this setting. Methods: Herein, we report the cases of 3 patients with moderate HA and severe hemorrhagic phenotype, treated with emicizumab prophylaxis and followed at our institution. Patients received emicizumab 3 mg/kg once weekly for 4 weeks, followed by maintenance therapy with 3 mg/kg once every 2 weeks. Data were retrospectively collected from clinical charts. Results: The median baseline FVIII activity (FVIII:C) at diagnosis was 1.5% (range 1.3 - 2.5%). The median age at the time of the first treated bleeding event was 2.01 years (range 0.27 – 2.7 years). First on-demand therapy was represented either by standard half-life recombinant FVIII (SHL-rFVIII) or plasma-derived FVIII concentrate (pdFVIII). Median duration of on-demand therapy was 50.6 years (range 9.9-63.3 years). All 3 patients required switching to a prophylaxis regimen due to frequent breakthrough bleedings; in particular the youngest patient because of very frequent invalidating hematuria and the two other because of frequent spontaneous haemarthroses. Two patients started FVIII prophylaxis at 9.9 and 50.6 years and then were switched to emicizumab for poor compliance to the i.v. infusions and persistence of spontaneous bleeds (after 6.7 and 9.5 years, respectively). A patient transitioned directly from on-demand factor therapy to emicizumab prophylaxis. During FVIII prophylaxis, the median ABR was 3.0 (range 3.0 - 5.0). At the start of emicizumab prophylaxis, the patients had a median age of 60.1 years (range 16.5-63.3) and no-one of them ever had an anti-FVIII inhibitor. At the start of emicizumab prophylaxis, HEAD-US scores were as follows: the youngest patient had a score of 0, while the two older patients—one previously managed with FVIII prophylaxis and the other with on-demand treatment—had scores of 17 and 13, respectively. The median follow-up on emicizumab is 0.5 years (0.1-0.5); during this period, all 3 patients experienced zero bleedings. The two older patients experienced a clinical improvement of hemophilic arthropathy, no longer requiring painkiller medications. The youngest patient experienced a great improvement of his social life, interacting more with his peers, and started to work out at the gym and play basketball. Conclusions: Despite the small sample size, our experience further supports the efficacy and safety of emicizumab prophylaxis in patients with moderate hemophilia A and a severe bleeding phenotype, even in a real-life setting. Therefore, emicizumab therapy represents a valid alternative to FVIII replacement therapy in this patient population, with some potential advantages in terms of compliance and quality of life.
PO87 | Intravascular leiomyomatosis extending to the right atrium: a case report with a multidisciplinary management
Background: Intravascular leiomyomatosis (IVL) is a rare condition, with approximately 400 cases reported in the literature since its first description in 1896. It is characterized by the intravascular proliferation of smooth muscle cells, often with a branching pattern that can extend from pelvic veins to thoracoabdominal vessels. Although benign in histological terms, IVL can clinically mimic a malignancy and lead to potentially fatal complications. The majority of cases of IVL have been reported in women, especially in the fourth decade of life, frequently associated with uterine leiomyomas. The treatment of choice is surgical resection, aiming to reduce morbidity and mortality associated with vascular involvement and minimize the risk of recurrence. Case Report: We report the case of a 48-year-old woman who presented in December 2022 with dyspnea and palpitations. A transthoracic echocardiogram revealed a right atrial mass, prompting further evaluation. A total-body CT scan identified a large pelvic mass, likely of uterine origin, with intravascular extension involving the ovarian veins, the right internal and common iliac veins, and the inferior vena cava (IVC), reaching the right atrium. Pelvic mass biopsy confirmed a benign leiomyoma and intravascular leiomyomatosis. Following multidisciplinary discussion, the patient underwent an initial surgery to remove the tumor from the vascular structures. In June 2023, resection was performed from the atriocaval junction up to the confluence of the suprahepatic veins. Histological examination confirmed IVL. A radiological follow-up in May 2023 revealed an increase in pelvic mass size and recurrent intravascular extension to the right atrium. After re-evaluation, a three-stage surgical procedure was performed, including complete hysteroannessiectomy and tumor removal from the right iliac vein, IVC, and right atrium. The surgery was completed without complications. Postoperative histology confirmed IVL in all specimens. A follow-up CT in July, 2023 showed no residual disease, although a focal filling defect in the IVC-just above the iliac vein confluence and at the renal vein junction-suggested chemical thrombosis. The patient was started on anticoagulant therapy, which was well tolerated, without thromboembolic recurrence or major bleeding. Complete recanalization of the thrombosis was achieved. Conclusions: This case illustrates the complex and rare nature of IVL, highlighting the critical role of a multidisciplinary management for diagnosis, treatment and follow-up. Postoperative clinical and radiological follow-up is essential to detect complications such as thrombosis and especially recurrence, which occurs in 16-30% of cases, particularly when complete surgical excision is not achieved. Additional studies are needed to define standardized surgical and therapeutic protocols for the management of IVL.
PO81 | Direct oral anticoagulants in atypical site vein thrombosis: a single centre experience focused on cancer patients
Background and Aims: Atypical sites venous thromboembolism (VTE-AL) is a rare disease has an incidence of 4% in the general population with an involvement of organ-related venous districts such as portal, mesenteric, hepatic, splenic, gonadal, renal, and cerebral venous segments. The risk of VTE in patients with cancer is increased by 12-fold compared with the general population. Major clinical trials on direct oral anticoagulants (DOACS) have excluded patients with VTE-AL. We aimed to evaluate the safety and efficacy of anti-Xa DOACs in our cancer patients with VTE-AL referred to our Centre for congenital bleeding and thrombotic disorders. Methods: We evaluated 7 cancer patients with VTE-AL (3 female and 4 male, median age 65,71 years) referred to our centre since April 2023 till March 2025: 3 (42.3%) with splenoportal axis thrombosis, 2 (28.5%) with inferior vena cava thrombosis, 1 (14%) renal thrombosis. 2/4 patients (45%) had oncohematological desease (Multiple Myeloma, Non-Hodgkin Lymphoma) and 5 patients (55%) had solid cancer (Renal Cancer, Ascending Colon Adenocarcinoma, Sigma Adenocarcinoma, Pulmonary Adenocarcinoma). All patients were diagnosed with received DOACs at full or reduced doses according to the reduction criteria in the drug label. Results: All patients underwent regular oncological follow-up of 24 months. During this follow-up period, no major bleeding or further thrombotic events were observed. Minor bleeding as to ecchymosis was observed in one patient with Non-Hodgkin Lymphomashe developed anaemia undergoing chemotherapy, resulting in discontinuation of DOAC and initiation of low molecular weight heparin (LMWH) at prophylactic dose after 5 months of treatment. 5 patients (55%) resolved the thrombotic episode and continued treatment due to disease activity, while 3 patients (33%) still present thrombosis at ultrasonographic and radiographic follow-up. 1 (11%) patient died due to the progression of the cancer. Conclusions: Our case series, limited because of the small sample size, shows that the use of DOACs in the management of VTE-AL in cancer patients is not associated with progression of VTE or major bleeding events.
PO82 | Retrospective application of the TH2 score in a multicenter cohort of ITP patients: a reliable predictive tool or a score in need of refinement?
Background: Immune thrombocytopenia (ITP) presents a dual risk of bleeding and thrombosis. While TPO receptor agonists (TPOra) effectively restore platelet counts and reduce bleeding, they may not fully prevent thrombosis. CV events, observed even with low platelet levels, suggest inflammation plays a secondary role. SYKi (e.g., fostamatinib, FST) may help by mitigating inflammation. The TH2 score (Balitsky AK et al., Blood 2018 ) was designed to help clinicians balance thrombotic and bleeding risks in treatment decisions. However, its use lacks international consensus, and its effectiveness in preventing CV events through tailored therapy remains uncertain. Aim: Retrospective evaluation of the TH2 score in ITP: its role in CV event prevention and therapy guidance. Materials and Methods: We performed a multicenter retrospective analysis of 24 patients (11 females, 13 males; median age 71, range 32–90). At diagnosis: median age 63 (11–88), treatment lines 2 (1–5), platelet count 17×109/L (3–94). 19 began first-line CCS therapy. TH2 scores were recalculated with therapy changes; non-switchers were excluded. Median CV risk factors/patient: 3 (0–5). Results: At baseline, 20/24 patients had a prothrombotic TH2 score: of them 8 started TPOra, 9 received FST, 2 IVI and 1 AZT. Detailed results are in Table 1. Conclusions: In just 3 cases (15%), an increased TH2 predicted a CV event, but the score remained unchanged; on the contrary in one instance it actually decrease after the event. However patients continued treatment safely with FST in absence of newer events. In other cases, low platelet counts likely limited score changes during therapy shifts. Although limited sample size, TH2 score didn’t optimally stratify patients, as it often indicated prothrombotic risk without translating into CV events.These findings highlight the TH2 score’s limitations in stratifying patients, suggesting the need for refinement to enhance its clinical utility in guiding personalized therapy.
PO84 | Beyond the scores: unmasking a silent pulmonary embolism in essential thrombocythemia
Background: Pulmonary embolism (PE) is a potentially fatal event, responsible for up to 300,000 deaths annually in Europe. Over 50% of patients with proximal deep vein thrombosis have concurrent PE. The Pulmonary Embolism Severity Index (PESI) and clinical prediction scores such as Wells and Geneva are commonly used for risk stratification. Essential thrombocythemia (ET) is a myeloproliferative neoplasm characterized by clonal thrombocytosis and increased thrombotic and hemorrhagic risk. Severe anemia and extreme thrombocytosis (≥1,000,000/μL) are associated with leukemic transformation. Bone marrow biopsy is key to defining disease stage. Case Report: A 79-year-old woman with ischemic heart disease and known ET on hydroxyurea (500 mg/day) was admitted for acute respiratory failure and cardiac decompensation. She showed mild tachycardia (110 bpm), tachypnea (25 breaths/min), SpO2 85%, and respiratory alkalosis (pH 7.54). Clinical signs suggested pulmonary congestion. Lab results revealed hemoglobin 10 g/dL, leukocytes 30,000/μL (>80% neutrophils), platelets 780,000/μL, and BNP 572 pg/mL. Echocardiography showed preserved systolic function, moderate mitral/tricuspid insufficiency, and pulmonary artery pressure of 45 mmHg. Despite low Wells and intermediate Geneva scores, the lack of response to therapy prompted further investigation. D-dimer was 1.75 µg/mL. CT pulmonary angiography confirmed segmental acute PE. Doppler ultrasound excluded DVT. Fondaparinux 7.5 mg/day was initiated and later switched to apixaban 5 mg BID, with gradual clinical and respiratory improvement. During hospitalization, hemoglobin declined and platelet count increased (Table 1). No circulating blasts were found on peripheral smear. The patient declined bone marrow biopsy. Genetic testing revealed the JAK2V617F mutation, while BCR-ABL rearrangements were absent. Conclusions: This case highlights the need to suspect PE in ET patients with respiratory symptoms, even when embolic risk scores are low or intermediate and other diagnoses (e.g., heart failure) are plausible. ET predisposes to thromboembolic complications, particularly in the presence of leukocytosis. Anemia, severe thrombocytosis and new thrombotic-hemorrhagic events concern for possible disease progression. A bone marrow biopsy remains essential when transformation is suspected.
PO83 | A case of deep vein thrombosis in a patient with systemic mastocytosis
Background: Systemic mastocytosis (SM) is a clonal hematological disorder characterized by the abnormal accumulation of mast cells, leading to uncontrolled degranulation (mast cell activation syndrome, MCAS) in tissues such as the bone marrow, liver, and spleen. Patients with SM may experience exacerbated or abnormal allergic reactions and may be at increased risk of thrombotic events due to coagulation disorders and the production of pro-coagulant factors, along with a reduction in anti- coagulant factors. Case Report: This case report describes a 69-year-old man with SM and left arm deep vein thrombosis (DVT) diagnosed in October 2023. The aim is to outline the therapeutic challenges in managing the underlying pathology. DVTs are common in patients with SM, and if persistent, they require long-term therapy. The patient, a 69-year-old man diagnosed with SM 8 years ago, had reported anaphylactoid crises following drug intake, food ingestion, or insect bites. In October 2023, he was diagnosed with DVT in the left femoropopliteal section, for which he began enoxaparin treatment at 100 U/Kg twice daily. To improve compliance, the patient consulted an allergist and, under strict anaesthesiology surveillance, started oral therapy with apixaban 5 mg twice daily from 17 July 2024. Over the last six months, the patient reported no bleeding or anaphylactic reactions, which contributed to an improvement in his quality of life. Conclusions: This clinical case highlights the importance of an integrated, multidisciplinary approach in managing both the underlying disease and the risk of thrombotic events. The use of anticoagulants may have an unpredictable response due to altered sensitivity to mediators released by mast cells. Direct oral anticoagulants (DOACs) are generally well tolerated, but there are no specific literature recommendations for their use in this patient population. Ongoing research is essential to better understand the mechanisms behind these complications and improve clinical management.
PO80 | Heparin-induced thrombocytopenia: a monocentric experience with danaparoid
Background: Heparin-induced thrombocytopenia (HIT) is a severe immune-mediated complication of heparin therapy, with significant thrombotic risk. Anti-PF4 antibodies may develop in up to 8% of exposed patients, but only 1–5% progress to clinical HIT. Early withdrawal of heparin and prompt initiation of a non-heparin anticoagulant are essential to manage this complication. Sodium danaparoid, a heparinoid with high anti-Xa activity and low anti-PF4 cross-reactivity, can inhibit PF4–heparin–IgG complex formation, limiting platelet (PLT) activation. It is the only anticoagulant approved for venous thrombosis prophylaxis in patients with previous HIT. Aims andMethods: We report five HIT cases diagnosed with 4T score ≥4, positive immunologic anti-PF4 IgG (HemosIL Acustar), and positive functional test (P-selectin expression by flow cytometry). Heparin was discontinued and danaparoid was initiated, followed by oral anticoagulation. Bridging with argatroban was used in unstable patients or those with high surgical risk. Case #1: 74-y.o. woman post mitral valve replacement, exposed to unfractionated heparin (UFH) and low molecular weight heparin (LMWH), developed thrombocytopenia (nadir 48 x109/L), confirmed HIT. Treated with intravenous (IV) and subcutaneous (SC) danaparoid with PLT recovery >150x109/L in 5 days and safe transition to warfarin. Case #2: 64-y.o. man after mitral valve surgery, exposed to UFH/LMWH, developed HIT (nadir 59x109/L). Initially treated with IV argatroban, then switched to SC danaparoid. PLT count normalized in 5 days, with safe warfarin initiation. Case #3: 93-y.o. woman post-hip arthroplasty, exposed to LMWH for new-onset atrial fibrillation, developed HIT (nadir 34x109/L) with concurrent deep vein thrombosis and pulmonary embolism. She was treated with IV danaparoid (PLT to 121x109/L after 5 days), then discontinued erroneously with subsequent count drop (28 x109/L), but recovered >150 x109/L in 6 days after SC danaparoid reintroduction, then safely switched to apixaban. Case #4: 74-y.o. woman post-mitral valve replacement and tricuspid repair, exposed to UFH developed severe thrombocytopenia (nadir 18x109/L), high-titer anti-PF4 antibodies (25.25 U/mL), and jugular thrombosis. Fondaparinux was started but stopped due to a further PLT drop. IV corticosteroids led to a slight rise in PLT count, allowing initiation of IV argatroban. Once clinically stable, the patientstarted SC danaparoid, with gradual PLT count recovery (at discharge was >130 x109/L) and safe transition to warfarin. Case #5: 60-y.o. man post-emergency valve surgery for myocardial infarction with papillary muscle rupture who developed HIT, exposed to UFH and LMWH, with prosthetic valve thrombosis (anti-PF4 3.93 U/mL, nadir 126 x109/L). Treated with danaparoid, PLT count rose to 202x109/L over 8 days and warfarin was then initiated safely. Results: Four patients reached PLT count >150 x109/L within 5–10 days; case #4 in 20 days. No thrombotic or bleeding complications occurred. In cases #4 and #5, repeated functional testing showed rapid loss of PLT activation after danaparoid, despite persistent immunological anti-PF4 IgG testing. This mismatch confirmed danaparoid effect on immune complex disruption. Conclusions: Danaparoid is an effective and safe drug for HIT. Despite EMA approval and guidelines support, its use in Italy remains limited. Its low cross-reactivity and ability to interfere with immune complex formation support its use as a first-line therapy.
PO79 | Trying to hit the hit in the shadow of renal failure: a complex case managed with danaparoid
Background: Heparin-induced thrombocytopenia (HIT) type II is a rare, immune-mediated adverse effect of heparin exposure, caused by antibodies against PF4-heparin complexes. These trigger platelet activation and can lead to life-threatening thrombosis. Managing HIT is challenging: anticoagulation is mandatory despite thrombocytopenia. In hemodialysis patients, who are frequently exposed to heparin and have limited alternatives due to renal clearance, clinical decisions are often complex. Early recognition is key to avoiding complications. Case Report: An 88-year-old woman was admitted for E. coli urosepsis. Her past medical history included chronic kidney disease, without any prior heparin exposure. Initial platelet count was 358×109/L. On day 12, worsening oligoanuric renal failure (eGFR 6 mL/min) required hemodialysis with unfractionated heparin. Seven days later, the platelet count started to drop (day 20: 274×109/L) rapidly reaching a nadir of 54×109/L on day 26. As infection had resolved and antibiotics were stopped, HIT was suspected (4T score: high probability). Despite the absence of overt symptoms, a Doppler ultrasound showed right femoral vein thrombosis, near the dialysis catheter. Anti-PF4 antibodies were positive (EIA: 7.4 U/mL; cutoff >1 U/mL). UFH was stopped immediately. Given ongoing dialysis needs and limited drug availability, we consulted a thrombosis expert and the HIT-THE-HIT network. The choice of drug was complicated by the fact that in our peripheral hospital access to certain medication is limited, as is the ability to monitor their activity in the laboratory. The choice fell on danaparoid. In patients on hemodialysis, danaparoid dosing depends on weight and session frequency. In our case, 3750 units were administered before each session, with prior monitoring of anti-Xa activity, which showed no evidence of drug buildup. Platelet count normalized in five days. Clinical stability improved and total body CT scan showed no signs of venous or arterial thrombosis elsewhere. As platelet levels rose – likely reflecting decreased anti-PF4 activity - warfarin was initiated on day 5. Danaparoid was stopped at day 11, when INR was therapeutic. Figure 1 illustrates the progression of platelet counts throughout the patient’s hospital stay. Unfortunately, the patient later died of septic shock unrelated to HIT. Nonetheless, thrombocytopenia and thrombosis were successfully managed without further complication. Conclusions: This case illustrates a critical diagnostic and therapeutic challenge: the need to anticoagulate a thrombocytopenic, dialysis-dependent patient in a setting with limited pharmacologic options. The simultaneous presence of thrombosis and falling platelets requires swift, structured assessment and confident clinical decision-making. Danaparoid allowed us to bridge dialysis safely while achieving hematologic recovery. Clinical suspicion, even in the absence of overt symptoms, was key. Unexplained platelet drops in dialysis patients should always prompt evaluation for HIT. Prompt recognition and tailored anticoagulation can change the course of this potentially fatal complication.
PO77 | The clinical awareness of mixing test interpretation in the era of complex reporting algorithm: do we forget the origins?
Background and Aims: Plasma mixing test is a simple laboratory procedure, which is performed on samples from patients with coagulation screening tests prolonged (mainly the activated partial thromboplastin (APTT), but also the prothrombin time (PT) or both). The prolongation has to occur in the absence of an anticoagulant therapy (heparin, anti-vitamin K antagonists (AVK) or direct oral anticoagulants (DOACs)) or a previous diagnosis that explains it (positive lupus Anticoagulant, von Willebrand disease, haemophilia, liver disease). Plasma mixing test allows to evaluate whether the 1:1 mixing with a normal pool plasma (NPP) corrects prolonged screening test, even after two hours of 37°C incubation. The principle on which this test is based is that a 50% level of a coagulation factor is sufficient to bring the altered test back to normal: - if mixing sample corrects prolonged screening test, we hypothesize factorial deficiency; - on the contrary, if mixing sample does not correct, we hypothesize presence of specific or non-specific coagulation factor antibodies (2h 37°C incubation is fundamental to evaluate the presence of specific factor inhibitor). Methods: In the era of digitalization and automation of the post-analytic phase but also in the era of privatization of healthcare, the risk of forgetting the collection of all the patient’s clinical-anamnestic information is always present. This causes the application of post-analytical complex algorithms of interpretation, resulting in time and resources lost. From many years, we have established a process to request mixing test that always starts with a discussion between the laboratory and the clinician. So, with this oral communication we want to remember that plasma mixing test requires a simple and clear process to obtain satisfactory results. Results and Conclusions: In our hospital, plasma mixing test is not requestable by hospital wards or by external patients because it is a laboratory instrument to frame the coagulation state of the patient. So, if the clinician find unexplained prolonged PT and/or APTT contacts the laboratory and discuss the case, also regarding patient physical examination (petechiae, hematomas). Exclusion of anticoagulation therapy or specific clinical conditions, such as hepatotactic patients, is fundamental to proceed with a correct evaluation of mixing test results. If we decide to proceed with the mixing test, laboratory request three 3,2% sodium citrate samples; samples are accompanied by a paper request form that include: indication of prolonged test, history of haemorrhagic or thrombotic pathologies, physical signs of haemorrhage or thrombosis and assumption of anticoagulant therapy. With one of the three samples we perform plasma mixing test always also with 2h 37°C incubation and with the others two sample we always confirm mixing test results with second level coagulation tests. For prolonged PT test, we perform extrinsic and common coagulation pathway while for prolonged APTT test, we perform intrinsic pathway, von Willebrand activity and antigen and LAC tests. Only, if the clinical examinations and mixing test are suggestive, we proceed with the study of the specific factor inhibitor. In conclusion, with this simple workflow, plasma mixing test continues to have its diagnostic orientation functionality especially in emergency situations to exclude the presence of an acquired inhibitor that represent one of the haematological emergencies.
PO76 | Thrombosis associated with midline in autoimmune patient: a case report on the use of apixaban in a real-world setting
Background: Upper extremity deep vein thrombosis (UEDVT) accounts for about 10% of all DVTs, with increasing incidence among hospitalized patients and those with central venous devices, such as PICC and midline catheters. Systemic inflammation, catheter-related infection, prolonged indwelling time, and prothrombotic comorbidities further increase the risk. While anticoagulation remains the standard treatment, the use of DOACs in catheter-related thrombosis (CRT) in non-oncologic, septic, or autoimmune patients is not well defined. We present a clinical case that highlights this therapeutic gap. Case Report: A 42-year-old woman with seronegative spondyloarthritis on biologic therapy was admitted to intensive care for septic shock. Ten days earlier, a brachial midline catheter had been placed due to poor venous access and the need for MRI with contrast. At admission, she had high-grade fever, hypotension, and acute respiratory failure. Chest CT revealed bilateral pneumonia. Peripheral and central blood cultures, as well as the catheter tip, tested positive for MRSA. Empiric intravenous vancomycin therapy was initiated. During hospitalization, she developed painful swelling of the right upper limb. Doppler ultrasound revealed acute thrombosis of the subclavian and axillary veins. Given the MRSA bacteremia and in accordance with IDSA 2009 and ESVS 2021 guidelines, the midline was promptly removed despite the concomitant thrombosis. Transthoracic echocardiography ruled out endocarditis. Thrombophilia screening, performed prior to anticoagulation, showed an isolated mild protein S deficiency, which was not confirmed on repeat testing. Initial anticoagulation with fondaparinux 7.5 mg/day was started. After internal medicine consultation, a switch to apixaban (10 mg BID for 7 days, followed by 5 mg BID) was made due to oral administration, favorable safety profile, and ease of outpatient management. There were no contraindications to DOAC use. At the 3-month follow-up, the patient was in good clinical condition, with no signs of thrombotic recurrence or bleeding. Follow-up ultrasound showed complete venous recanalization, and anticoagulation was discontinued as planned. Conclusions: Catheter-related thrombosis of the upper limb in non-oncologic, septic, or autoimmune patients remains a clinical gray area with no specific guidance in major recommendations. Current indications are often based on data from lower limb DVT or oncologic settings. This case supports the use of apixaban as an effective and well-tolerated treatment option in complex clinical scenarios, advocating for its use in selected CRT cases outside of oncology. Dedicated prospective studies and clearer guidelines are urgently needed to address this underexplored area of venous thromboembolism.
PO78 | Acquired hemophilia A as a paraneoplastic syndrome: two cases report on a rare coexistence
Background: Acquired hemophilia, meanwhile, is the most common acquired disease affecting clotting factors. Possible causes that have been empirically described include autoimmune disease (such as rheumatoid arthritis or systemic lupus erythematosus), malignancy (most frequently solid tumors), dermatologic disorders (such as psoriasis or pemphigus), postpartum changes or drug interactions. Acquired hemophilia occurs due to either acquired deficiency of factor VIII or development of factor VIII inhibitor in the body. Here, we describe a rare case of acquired hemophilia in a woman whit malignancy and in a man with pemphigus. Case Reports: The first patient is a 75-year-old female, with a history with a history of breast cancer, currently in progression of the disease with pulmonary metastases. After the initiation of atezolizumab, the patient reported experiencing diarrhea and melanotic stool, without other episodes of bleeding, such as epistaxis, ecchymosis or hematemesis. A coagulation workup was done, revealing an elevated APTT-ratio of 4.10 (normal range: 0.85 to 1.20). Other lab studies included a complete blood count, revealing a hemoglobin of 8.4 g/dL and a platelet count of 274 platelets/mL. A subsequent mixing study did not normalize the PTT, suggesting the presence of an inhibitor. The titer of the inhibitor was elevated at 129 Bethesda units (normal range: less than 0.6 Bethesda Units). The second patient is a 76-years-old man with type pemphigus presented to the local hospital with progressively more extensive discoloration of the left thigh, accompanied by worsening thigh pain and limitation of limb movement, for over 5 days. He had a hemoglobin level of 9.9 g/dL with a platelet count of 315 x 103 /µL and WBC count of 7.3 x 103 /µL. His coagulation profile was normal except for isolated prolongation of APTT-ratio which was 2.89. Failure of correction of the prolonged APTT with mixing of pooled normal plasma suggested the presence of an inhibitor. Factor assay revealed a factor VIII level of 0.5% with normal factor IX and XI levels. The Bethesda assay to quantify inhibitory antibodies was done and the titre was 691 BU. Conclusions: In these reports, two rare cases of acquired hemophilia in patients, who developed a factor VIII inhibitor as a paraneoplastic syndrome, are presented. Even though acquired haemophilia A is a rare entity, it should be considered as one of the causes of adult onset abnormal bleeding, especially in patients with underlying autoimmune disorder and malignancy. Early clinical suspicion, diagnosis and prompt management of the severe refractory form of acquired haemophilia A is lifesaving.
PO75 | Prophylaxis with RFXIII: a clinical case in a pediatric patient with congenital FXIII deficiency and delayed diagnosis
Background: Congenital factor XIII (FXIII) deficiency is a rare coagulation disorder characterized by muscular or mucocutaneous bleeding with life-threatening intracranial hemorrhages (ICHs), especially in cases with severe disease. The best treatment is the use of prophylactic plasma-derived or recombinant FXIII (rFXIII). All routine coagulation tests are normal in FXIII deficiency (FXIIID), which complicates the diagnosis of this disorder. Case Reports: A 6 years old girl affected by severe deficiency of FXIII. The patient was born at term at 36 weeks, two days after delivery she was admitted to the NICU for respiratory failure, anemia and acute thrombocytopenia, acute renal failure and hepatic hematoma. She was treated with dialysis for 2 days, assisted ventilation, transfusion with concentrated red blood cells, platelets and plasma and discharged after 40 days. In August 2021 she had a new access to the ER of Moscati Hospital in Avellino for left gluteal hematoma with difficulty in walking, treated with paracetamol and antibiotics. In August 2022 she was admitted to our hospital for the detection of an iliopsoas muscle hematoma, with severe difficulty in deambulation. Coagulation tests were normal, therefore, factor XIII assay was performed, resulting 1%. The patient was treated with rFXIII at a dose of 35 IU/kg, with resolution of the clinical symptoms in about 2 weeks. The patient has been on prophylaxis with rFXIII every 4 weeks at a dose of 35 IU/kg since August 2022 and has only experienced minor bleeding episodes (superficial post-traumatic hematomas and ecchymoses). The activity of FXIII is on average about 120% after 1 hour of drug administration. The trough level at 4 weeks is on average about 6%. Conclusions: Prophylaxis with rFXIII appears to be safe and effective in our patient with congenital FXIII deficiency: from 2022 to today, no significant haemorrhagic episodes have been recorded, only superficial manifestations of mild severity.
PO74 | Combined therapeutic approaches in a patient with hereditary hemorrhagic telangiectasia (HHT) and cardiovascular comorbidities
Background: Hereditary hemorrhagic telangiectasia (HHT), also known as Osler-Weber-Rendu syndrome, is a rare autosomal dominant genetic disorder characterized by vascular dysplasia. The condition involves mutations in genes known as ALK1, which play critical roles in the regulation of angiogenesis and vascular integrity. Case Report: A 77-year-old female patient presented with a history of recurrent massive epistaxis, since childhood, worsening in recent years. The clinical examination revealed telangiectasias on the fingertips, tongue, lips, and sublingual mucosa, in addition to systemic AVMs involving the nasal cavity, pancreas, liver, kidneys, and duodenum. Comorbidities included severe arterial hypertension, moderate aortic stenosis, type 2 diabetes mellitus, and obesity. Previous epistaxis treatments included nasal Argon plasma coagulation (2021, 2024) and right sphenopalatine artery embolization (2021), with only temporary relief. Recent and recurrent episodes of severe anterior epistaxis resulted in progressive anemia, necessitating blood cell transfusions. Medical therapy was started with antifibrinolytics (tranexamic acid at a dosage of 10 mg/kg/dose, administered intravenously -IV-every 8 hours), and vasoactive treatment with short-acting octreotide (0.1 mg subcutaneously three times daily for the initial 15 days), followed by the administration of long-acting release octreotide (octreotide LAR 20 mg intramuscularly-IM-, every 28 days), which had not been used previously. Although the literature reports benefits from antiangiogenic agents (e.g., bevacizumab) and desmopressin in managing HHT-related bleeding, these options were deemed unsuitable in this case. Desmopressin was contraindicated due to uncontrolled hypertension, while the predominant nasal bleeding phenotype limited the potential benefit of bevacizumab, which is more effective in gastrointestinal hemorrhages. Diagnostic examinations were carried out to review the distribution of angiodysplasias: brain MRI with angiographic sequences excluded cerebral AVMs, thoraco-abdominal CT angiography confirmed the multiple abdominal angiodysplasias, none bleeding, with accessory hypodensity at the left ventricular apex and myocardial scintigraphy with pharmacological stress (technetium-99m) highlighted an area of reduced coronary reserve of approximately 10% in the mid-apical segments and the lower-lateral region of the left ventricle. Although therapy with oral antifibrinolytics (tranexamic acid 15 mg/Kg/dose/8 h) and octreotide 20 mg every 28 days, and optimization of blood pressure control, a new relapse occurred with massive posterior epistaxis associated with hematemesis, resolved with octreotide 0.5 mg in IV infusion for 24 hours and parenteral antifibrinolytics (tranexamic acid 10 mg/Kg/8 h), and blood transfusions. After a new therapeutic failure, angiography was then performed with embolization of the right and left sphenopalatine and ethmoidal arteries, complicated by subacute occipital ischemia with transient cortical blindness. The patient showed progressive clinical improvement with recovery of vision and significant reduction of hemorrhagic manifestations without the need for further transfusion support. Conclusions: HHT is a rare and poorly recognized genetic bleeding disorder. The treatment must be individualized, considering all aspects of the condition, including local and systemic manifestations, and the patient’s comorbidities.
PO72 | Fondaparinux in patient with active tuberculosis
Background and Aims: Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis, an airborne-transmitted infection that primarly affects the respiratory system and potentially influences systemic phisiology and remain a leading cause of morbidity and mortality worldwide particularly in low- and middle-income countries. Thrombosis, particularly venous thromboembolism (VTE) is a notable concern in paitents with active TB; epidemiological data highlights an elevated risk of VTE and in particular of deep vein thrombosis (DVT) and pulmonary embolism (PE). The anticoagulant therapy in these patients could be very difficult to manage in particular in the long-term therapy due to interferences between warfarin and rifampin (well known from years,) but also between direct oral anticoagulants and rifampin. pathophysiology of hypercoagulability in TB arises from multiple mechanisms including systemic inflammatory response and endothelial dysfunction. Methods: Two patients from Africa, 20 and 22 years old, admitted for severe pulmonary tuberculosis. The first patient developed upper limb deep vein thrombosis (DVT) and pulmonary embolism affecting the segmental branches of the left superior lobe, the other one had peritoneal involvement of infevtion and developed DVT in the right lower limb and thrombosis of the hypogastric vein. Both patients are being treated with Fondaparinux, initially at a therapeutic dose (7.5 mg/24h for 7 days with antiXa level of 0.8 IU/ml), followed by 5 mg/24h (antiXa level of 0.6 IU/ml). Results: After one month, partial recanalization of the affected vessels was observed, and no hemorrhagic complications were noted, so the recommendation was to continue the treatment for another 30 days. The infectious condition shows clinical improvement, while the radiological findings remain unchanged. Conclusions: the anticoagulation with fondaparinux can be a valid alternative for the treatment of venous thromboembolism in patients on quadruple therapy (isoniazide, ethambutol, rifampin, pyrazinamide) for Mycobacterium tuberculosis infection proving to be safe and effective.
PO73 | False-positive CT diagnosis of DVT in a patient with severe venous sequelae: a case of bilateral cellulitis
Background: Cellulitis is an acute bacterial infection of the dermis and subcutaneous tissue, often associated with local predisposing factors such as chronic ulcers, venous insufficiency, and diabetes mellitus. A precise differential diagnosis with deep vein thrombosis (DVT) is essential, as both conditions may present with lower limb edema, erythema, and pain. Chronic alterations of the venous system, especially in patients with previous thrombotic events or diabetic microangiopathy, can mimic DVT on radiological imaging, potentially leading to diagnostic and therapeutic pitfalls. Case Report: A 70-year-old male with metabolic syndrome, bifascicular block with hypertensive heart disease, hypercholesterolemia with elevated lipoprotein(a), and type 2 diabetes mellitus was admitted to our hospital for bilateral lower limb pain, edema, and fever. His medical history was significant for recurrent lower limb skin ulcers diagnosed as pyoderma gangrenosum and chronic venous insufficiency with post-thrombotic sequelae. He had previously been hospitalized at another facility, where a CT angiography of the lower limbs suggested bilateral DVT. This led to his referral to our center for further diagnostic evaluation and management. On admission, physical examination revealed signs consistent with bilateral cellulitis, without evidence of ischemia or purulent collections. A lower limb venous Doppler ultrasound performed by our vascular team excluded acute DVT. Instead, it demonstrated severely compromised venous anatomy, characterized by thread-like lumens and significantly reduced flow, findings likely attributable to chronic post-thrombotic damage and diabetic microangiopathy. Broad-spectrum empiric antibiotic therapy was initiated, resulting in gradual clinical improvement. Anticoagulation therapy was not administered due to the absence of imaging-confirmed thrombosis. Conclusions: This case underscores the importance of thorough clinical and ultrasonographic reassessment in patients with chronic vascular disease and acute infectious symptoms. Severe structural and functional alterations of the venous system, particularly in the setting of post-thrombotic syndrome and diabetic microangiopathy, can mimic acute DVT on imaging studies. Doppler ultrasound remains the gold standard for ruling out active venous thrombosis, helping to prevent misdiagnosis and avoid unnecessary anticoagulation. Furthermore, although rare, bilateral cellulitis should be included in the differential diagnosis in patients with multiple risk factors. A careful and multidisciplinary approach is essential to ensure accurate diagnosis and appropriate management.