An audit of paroxysmal nocturnal haemoglobinuria (PNH) requesting at University Hospitals of North Midlands

Early identification of PNH, a rare life-threatening disease is essential to ensure appropriate management via the UK PNH service. Since testing for PNH is expensive (75.97 per test), we set out to assess the suitability of PNH requests against guidelines with the aim to feedback to colleagues and reduce unnecessary testing. To determine whether PNH requests at UHNM were in line with criteria in British Society for Haematology (BSH) guidelines. All patients over 18 years of age who had PNH testing for the first time and those who had repeat testing for monitoring between 01/04/2019 and 31/03/2020 were included. Patients were selected from electronic records of PNH sample receipt to laboratories. Hospital records were reviewed for clinical details and investigation Results. 82 requests including 79 individual patients were audited. 57% were male and 43% were female. Median age was 56 years. 97.6% of PNH tests were requested by a haematologist whilst only 2.5% requests were done by non-haematology clinicians. 52.4% requests were in keeping with BSH recommendations, whilst 47.6% tests did not meet criteria for testing. All patients tested outside of guideline recommendations were negative. Of the reasonable requests, only 23.3% (10) were positive. Of the PNH positive patients, 8 patients were known to have a PNH clone with aplastic anaemia;one patient had a hypoplastic bone marrow and a known PNH clone whilst only one patient with cytopenia had a new positivity for PNH. The frequency monitoring for aplastic anaemia and a PNH clone was 100% concordant with BSH recommendations. With appropriate testing, only one new patient was identified. Our audit has limitations. We have not been able to assess whether any patients outside of those monitored for PNH in aplastic anaemia have been overlooked for testing. Also, the time period includes the COVID-19 pandemic so our findings may not reflect usual practice. New BSH guidelines for thrombophilia testing were published in 2022 and recommend testing for PNH in patients with thrombosis at unusual sites and abnormal haematological parameters and for patients with arterial thrombosis and abnormal blood parameters. This will likely limit excess tests although the sensitivity and specificity of such an approach has not been formally evaluated. In a finite health system, it is our responsibility to rationalise investigations. The cost of a year's testing was 6229.54 and that of inappropriate testing was 2962.83. As a department, we could, therefore, save 2962.83.

Sharing the knowledge and expertise of BSH members throughout the global Haematology community

'BSH Global Speakers' was established in 2015 as a core project of the BSH Global Haematology Special Interest Group (SIG). As the project enters its eighth year, we present an update and reflection on the successes and challenges encountered. Initially known as the 'Plenary Speaker Scheme', the project was developed following a stakeholder meeting in 2015 at the inception of the SIG. Haematology colleagues from the UK and low-and middle-income countries (LMIC) came together to discuss how the BSH may be best placed to support haematologists practicing in LMICs. Sharing of expertise and building collaborative networks were identified as key priorities. The 'Plenary Speaker Project' was conceived;BSH haematologists would be supported in delivering plenaries at the meetings of colleagues in LMICs, with the aim that each visit could act as a catalyst for creating networks and developing collaborative projects in education, research, and capacity building. We established a yearly cycle of inviting applications from LMIC societies for a funded speaker at their scientific meetings, selecting the most impactful meetings, then recruiting appropriate UK-based speakers. We place emphasis on the likelihood of ongoing collaborative working or other impacts, for example engagement with local haematology trainees. To date, ten speakers have represented BSH at the meetings of LMIC societies, presenting on diverse topics, from molecularly guided interventions to prevent relapse in AML, to adapting lymphoma treatment strategies for low resource settings. Recently we have opened applications to nurse specialists and scientists, with our first scientific speaker presenting in Thailand May 2023. The COVID-19 pandemic created significant challenges for the project due to the disruption in international travel and the cancellation of many haematology meetings around the globe. We were, however, able to adapt the project to support virtual speakers at meetings in South Africa, Vietnam, and Ghana. Although virtual meetings do not naturally lend themselves to collaborative working, we were pleased that a longer term joint educational program in haemoglobinopathy care has been established with the Vietnamese Society of Haematology as a result of BSH support. The impact of BSH Global Speakers is significant. Even at smaller meetings, speakers will have the ear of the majority of practicing haematologists in a country. From the relationships built between societies and speakers we have seen the development of fellowship programmes, online education programmes, laboratory support, and numerous networks for informal advice in clinical care, research, and more.

Second wave of COVID-19 - Not a matter of great concern for pediatric hematologist/oncologist

Coronavirus disease-19 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic and is giving rise to a serious health threat globally. SARS-CoV-2 infection ranges from asymptomatic carrier state to severe illness requiring intensive care unit (ICU) management. It is postulated that with COVID-19 infection, children are less prone to develop severe symptoms as compared with adults. The data on immunocompromised children affected with COVID-19 infection is limited and not many publications are there on the effects of 2nd wave of COVID-19 infection in pediatric hematology/oncology patients till date. In our experience during second wave, 17 patients were found to be positive for SARS-CoV-2 with a male: female ratio of 2.4: 1 and median age of 8 years (range 1-18 years). Out of these 17 patients, 10 (58.8%) patients required hospital admission whereas the remaining were managed at home. Only 1 patient required ventilatory support and there was no mortality. Though the number of pediatric patients with COVID-19 infection were more during the second wave but majority had mild to moderate symptoms and were easily managed.Copyright © 2022 Pediatric Hematology Oncology Chapter of Indian Academy of Pediatrics

Impact of COVID-19 Pandemic on Treatment Decisions of Patients Treated by Hematologists in Saudi Arabia

BACKGROUND: As on March 12, 2020, the WHO declared COVID-19 as a global pandemic. Its rapid spread has posed major challenges to the management of health-care systems. Patients with hematological disorders, being immunocompromised in more ways than one, face a lot of challenges. Most of these patients require frequent visits to health-care facilities for transfusion support, infusions, surveillance, and follow-ups, which increase the risk of exposure and hence infection with severe acute respiratory syndrome coronavirus 2. AIM: We assessed the impact of the pandemic on the decisions of hematologists in Saudi Arabia. Method(s): An online survey was done through questionnaires, to understand the decisions and course of clinical treatments taken. 45 hematologist answered 20-questions structured questionnaires through online link. RESULT(S): The majority of hematologist have used virtual clinics in managing patients and have delayed or canceled well visits. Although some hematologist delayed treatment in stable patients like autologous stem cell transplantation for myeloma patients, the majority did not delay induction or consolidation therapies for patients with leukemia with curative intent plans. CONCLUSION(S): The crisis brought along with it challenges and opportunities to improve patient care through research and clinical practice. Telemedicine was sought for supporting outpatients. Malignancies were taken care of, with due precautions. Observations of decisions of hematologists resulted in the patients still being closely followed up and urgent treatments being attended to. The hematologists expressed satisfaction with the use of telemedicine. Online consultations and monitoring of patients could probably be taken as an alternative resource in such situations.Copyright © 2023 Journal of Applied Hematology Published by Wolters Kluwer - Medknow.

Progressive multifocal leukoencephalopathy, neuroradiology-neuropathology

Introduction: Progressive multifocal leukoencepha-lopathy (PmL) is an unfavorable demyelinating disease of the CNS caused by reactivation of JC virus (JCV). JCV is a double-stranded DNA human polyomavirus predominatingly acquired in childhood. Blood samples taken from healthy persons indicate that 50-90% of adults have been exposed to this virus. JCV is an opportunistic pathogen, with PmL manifesting primarily in patients with immunodefciency or taking immunomodulatory treatments or with lymphoproliferative diseases. We report a patient who developed PmL shortly after diagnosis of follicular lymphomma. Case presentation: A 70-year-old-woman admitted to the neurological departament with hemiparesis, psy-chomotor slowing down, balance problems, dizziness and in depressed mood. the patient underwent aorto-femoral transplant 12 years ago and for 10 years was under constant observation of a hematologist due to enlarged lymph nodes. Five years ago, the patient had planoepithelial cell carcinoma removed. the patient also sufered from COViD-19 infection and sufered from depression. elevated leukocytosis and D dimers, were the only abnormal results obtained in laboratory tests. However, pulmonary embolism was excluded in Ct angio. Cytometry of blood showed follicular lymphoma. Radiological fndings: mRi and Ct scans showed multiple asymmetrical pathological areas of hyperin-tense signal in t2-dependent images, hypointense in t1-dependent ones and Ct-hypodense regions which extended continuously in control examinations. they were located in the white matter of multiple lobes of both brain hemispheres subcortically and periventric-ullary. the subcortical U-fbers were involed. they did not show contrast enhancement and mass efect. they showed peripheral ring and patchy difusion restriction particularly at their leading edge. in spite of the used steroid therapy the patient's health deteriorated rapidly. the patient died of symptoms of cardio-respiratory failure 1 month after admission to hospital. Neuropathological features: the neuropathological examination revealed numerous foci of demyelination in the white matter of the frontal lobe, the parietal lobe in the pons and in the cerebellum. myelin losses were accompanied by damage to oligodendrocytes and proliferation of macrophages. the nuclei of the damaged oligodendrocytes were enlarged and hyperchromatic, and some had a "ground-glass" appearance typical of viral infection. the astrocytes were bizarre with lobulat-ed, hiperchromatic or hypochromatic nuclei and damage of cytoplasmic procesesses (clasmatodendrosis). Conclusion(s): the triad of neuropathological injuries: destruction of oligodendrocytes with intranuclear viral inclusions ("ground-glass" appearance), multifocal demyelination and bizarre astrocytes allowed for the diagnosis of late form of classical progressive multifo-cal leukoencephalopathy (cPmL), despite the short time since diagnosis of follicular lymphoma, but with many years of enlargement of the lymph nodes.

Catastrophic Antiphospholipid Crisis Triggered by Anticoagulant Switch

Case report - Introduction: The COVID-19 pandemic led to drastic changes for some patients on warfarin for venous thromboembolic (VTE) disease and atrial fibrillation. Warfarin monitoring necessitates frequent interaction with healthcare workers, which is sufficiently risky for COVID-19 transmission. As a result, selected patients were swapped over to novel oral anticoagulants (NOACs). Our patient was changed without investigating for antiphospholipid syndrome (APLS);it later transpired he was triple antibody positive. He presented in a crisis and we describe his narrative. Patients on warfarin due to presumed unprovoked venous thromboembolic disease should not be swapped to NOACs without completing, or checking, previous antiphospholipid antibody testing. Case report - Case description: A 73-year-old gentleman presented locally in August 2020 with erythema over the anterolateral surface of his left leg. He was initially treated with antibiotics for presumed cellulitis. Within a few days this lesion became necrotic and rapidly spread. At this point, he was transferred to a tertiary rheumatology centre. Within days to weeks, he developed several necrotic lesions affecting his trunk and limbs, with facial sparing noted. Approximately 30-35% of his whole-body surface became involved. He soon developed an oxygen requirement, with CTPA demonstrating lymphocytic interstitial pneumonitis without evidence of pulmonary emboli (PE). Throughout his admission, he had several other pathologies such as hyponatraemia that required level 2 care and severe noninfectious diarrhoea. Skin biopsy identified thrombotic vasculopathy. Serology confirmed triple positive antiphospholipid antibody status and a dsDNA titre of>400 iU/mL. This was the first-time serology had been undertaken despite a history of three deep vein thrombosis (DVT) episodes and two PE incidents. He had no history of SLE symptoms. His initial management for vasculitis secondary to APLS at the point of limited necrosis consisted of IV methylprednisolone followed by rituximab and PO prednisolone. While there was some delay in the progression of his disease, new areas of necrosis arose, leading to the patient receiving cyclophosphamide. Low molecular weight heparin was used for anticoagulation. This gentleman later developed proteinuria and neurological symptoms, fulfilling the criteria for catastrophic antiphospholipid syndrome. He received plasma exchange, without an improvement. He developed complications from his disease and treatment, including poor wound healing. It became apparent his condition would not improve and active treatments were stopped. He passed away 6 weeks after initial presentation. Prior to his admission to hospital, his warfarin was swapped to a NOAC. This is thought to have been the trigger behind catastrophic thrombosis. Case report - Discussion: After excluding other conditions such as necrotising fasciitis, this gentleman was rapidly started on IV methylprednisolone to halt any further progression. This is because glucocorticoids have the greatest evidence base for managing this poorly understood acute disease manifestation. After this failed to manage his condition, he was given a further immunosuppressive agent in the form of rituximab. This was used after his serology confirmed triple antibody status. It was hoped this would stop any further immunological mediated disease progression. Oral prednisolone was started at 40mg at this stage and kept under review with a tapering schedule. Cyclophosphamide was given within a few days of rituximab, with hope of a quicker onset of action. A careful MDT decision was made on these drug choices, particularly regarding their combined use and appreciating their side effect profiles. Cyclophosphamide has evidence behind its use, especially for those with APLS associated with lupus. While he did not develop any infections related to treatment, his condition progressed. Case reports suggest that plasma exchange can be useful in the management of catastrophic antiphospholipid syndrome, so the team recommen ed this. Consent at this stage became tricky due to his altered mental status, but it was felt he did demonstrate capacity for this specific decision. As his condition did not improve after this level of immunosuppression, the team reached the decision that no other treatments would likely change the outcome. He remained on oral steroids for the remainder of his admission. The other management facet of APLS crises pertains to anticoagulation. Low molecular weight heparin was recommended by the haematologists. His NOAC was stopped after the diagnosis was confirmed. Warfarin was restarted later in his admission given he had been well on this for years. Case report - Key learning points: This fascinating case exemplifies the importance of completing an antiphospholipid antibody screen for patients who present with unprovoked venous thromboembolic disease. NOACs are commonly used anticoagulant medications. Several case reports have demonstrated that patients with antiphospholipid syndrome experience breakthrough thromboembolic events when treated with NOACs. The highest risk is associated with history of arterial thrombosis and those with triple positive antibody status. Three clinical trials have either been completed or are in the process of investigating whether NOACs sufficiently prevent thromboembolic disease in these patients. The TRAPS study compared rivaroxaban to warfarin in those with triple antibody positive antiphospholipid syndrome. The study was terminated early given that higher adverse events were observed in the rivaroxaban arm (19%, n11/59) versus warfarinised patients (3%, n2/61). The RAPS study found no difference in thromboembolic risk and results from the ASTRO-APS study looking into apixaban are awaited. There is insufficient evidence to suggest that NOACs prevent VTE in a similar fashion to warfarin, so many still advocate the use of warfarin. The optimal immune management of this acute complication is not well elucidated, with a shortfall in mechanistic pathological understanding. The conference will generate discussion on this subject matter in detail. During the COVID-19 pandemic, it has been observed for patients to change anticoagulation from warfarin to NOACs. Given NOACs do not require monitoring, this medication change reduces the number of interactions patients have with healthcare services. We postulate this change triggered the crisis in our patient, where we suggest continuation of warfarin would have been ideal. This is due to the history of several unprovoked thromboembolic events without a prior antiphospholipid screen being completed. Dissemination of learning points from this case are imperative to ensure decision-making encompasses patients who may have undiagnosed antiphospholipid syndrome.

Diamond-blackfan anemia in an adult

Case Report: A 25-year-old woman with history of Diamond-Blackfan anemia (DBA) presented with a 3- week history of weakness and fatigue. The patient was in her usual state of health until 3 weeks prior when she was diagnosed with COVID-19, at which time she experienced cough, congestion, weakness, and fatigue. She reported that the cough and congestion improved after a few days, but the fatigue and weakness progressively worsened. Admission labs were notable for a hemoglobin of 5.5 g/dL with a MCV of 119.3 fL. She received 2 units of packed RBCs with improvement in hemoglobin to 8.9 g/dL. The patient was diagnosed with DBA at birth via bone marrow biopsy and had been stable on chronic prednisone with a baseline hemoglobin around 8 g/dL. Prior to this admission, she has only required one transfusion at 3 months old. Her outpatient management involved close monitoring of her hemoglobin and increasing/decreasing prednisone based on her trending hemoglobin. She had been stable on 15 mg/day of prednisone for the past few years. Her hematologist was consulted, and the decision was made to increase her dose of prednisone to 20 mg/day resulting in resolution of symptoms and stabilization of her hemoglobin level. Discussion(s): We present a rare case of DBA with worsening anemia in the setting of a recent COVID-19 infection. The literature regarding the risk and complications of COVID-19 in these patients is severely limited, with no current data on disease management, outcomes, or predictors of morbidity. DBA is a rare, congenital erythroid red cell aplasia that typically presents in infancy with an estimated incidence of 5 cases per 1 million births. DBA is characterized by progressive macrocytic anemia, congenital malformations, and increased risk of endocrine dysfunction and malignancies. Glucocorticoids are the first-line therapy for DBA, although the exact mechanism of how they stimulate erythropoiesis in DBA remains unknown. In terms of patient prognosis, approximately 40% are steroid-dependent, 40% are transfusiondependent, and 20% go into remission by age 25 years. Copyright © 2023 Southern Society for Clinical Investigation.

Timing of Multisystem Inflammatory Syndrome in Children in Relation to Index Covid-19 Infection

INTRODUCTION: Multisystem Inflammatory Syndrome in Children (MIS-C) RESULTS from Immune Dysregulation Following COVID-19 Infection. Timing of MIS-C Diagnosis in Relation to Index COVID-19 Infection Varies. The CDC Reports the Average Time Between MIS-C and COVID-19 Infection is 4 Weeks. We Aim to Determine if the Timing of MIS-C Diagnosis in Relation to the Index COVID-19 Infection Varies by Variant, and Whether Spike IgG Value Correlates with the Time Between COVID-19 and MIS-C or with Peak Ferritin. METHOD(S): Our MIS-C Team (Pediatric Cardiologists, Rheumatologists, Immunologists, Hematologists, Intensivists, and Hospitalists) Reviewed Every Suspected Case of MIS-C at our Institution, and All Confirmed Cases Were Reported to the State Health Department. Electronic Health Records Were Reviewed to Obtain Data Elements in this IRB Exempt Study. COVID-19 Variant Timeframes Were Defined by Dominant (>50% cases) Strand in the United States (Alpha/ Beta/Gamma 1/21/20-6/25/21, Delta 6/26/21-12/17/21, and Omicron 12/18/21-Present). RESULT(S): Our MIS-C Team Identified 68 Cases from 7/2/20 to 6/22/22 out of 226 (30%) Confirmed in South Carolina. We Categorized Each Case by COVID-19 Definition (Exposure, Positive Test, or Unknown). The COVID-19 Component of the Definition was Based on Exposures in 25 (37%), 25 (37%) Positive Antigen Test or PCR, and 18 (26%) Positive IgG. Mean Time Between COVID Exposure or Positive Test and MIS-C Diagnosis was 31.5d. Mean Time for Alpha/Beta/Gamma Variant was 27.3d, Delta 33.6d, and Omicron 34.2d. 100% of Cases Received IVIG, 72% IVIG and Steroids, and 13% IVIG, Steroids, and Anakinra. Relationship Between Spike IgG and Timeframe of MIS-C (r=0.61), Peak Ferritin and Anakinra (r=0.63), and Peak Ferritin and Timeframe of MIS-C (r=0.34). Only 4% of Those Vaccine-Eligible at the Time of Illness Were Fully Vaccinated. CONCLUSION(S): The Timing of MIS-C Diagnosis in Relation to the Index of COVID-19 Infection does Vary by Variant with a 6.9 Day Increase in Average Since the Start of the Pandemic. Our Overall Average of 31.5 Days (4.5 Weeks) Between COVID-19 and MIS-C Supports the Initial CDC Estimate of 4 Weeks. There was a Moderate Positive Correlation Between Spike IgG and Timeframe of MIS-C, and a Higher Peak Ferritin Indicated use of Anakinra.

HEMOLYTIC ANEMIA EXACERBATION IN CHRONIC PAROXYSMAL NOCTURNAL HEMOGLOBINURIA AFTER COVID-19 VACCINATION

SESSION TITLE: Issues After COVID-19 Vaccination Case Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematologic disorder that can lead to thrombosis, hemolytic anemia and leukemia. Though there are documented relationships between autoimmune hemolytic anemia (AIHA) and COVID-19 infection, this is the first to highlight aa potential association between PNH exacerbations and COVID vaccinations. CASE PRESENTATION: A 38 year-old female with a history of chronic paroxysmal nocturnal hemoglobinuria (PNH) currently on maintenance ravculizumab therapy presented with 3 days of generalized fatigue, chills, and worsening scleral icterus. She reports being unable to move out of the bed with concomitant somnolence. Of note, she received her second dose of the Moderna COVID-19 vaccine 2 days prior to symptom onset and not had any similar symptoms prior to this episode. Patient was hemodynamically stable on admission and afebrile. Physical exam revealed generalized lethargy/weakness and jaundice. Chest x-ray did not demonstrate any evidence of infection or pleural effusions. Initial complete blood count showed a hemoglobin of 5.9 g/dL, compared to her baseline of 9 without any evidence of bleeding. Absolute reticulocyte and bilirubin levels were elevated to 295.2 x 109 and 4.7 mg/dL respectively with a haptoglobin of <20 mg/dL. She received a total of 3 units of packed red-blood cells with subsequent stable hemoglobin levels and did not require emergent use of glucocorticoids or plasma exchange. Her lethargy improved slowly, and within a week, she returned back to her baseline functional status. She was ultimately stable and discharged for follow up with her hematologist without any complications. DISCUSSION: Though the sequelae of COVID-19 infections and associated hematologic diseases have been extensively established, the pathogenesis of COVID-19 vaccinations associated exacerbations remain unclear. Given the timing of the onset of our patient's symptoms, it is highly suggestive that her second COVID-19 vaccination was the inciting factor for her acute hemolytic anemia. It is crucial to be cognizant of the potential hematologic side effects in individuals with rare auto-immune disorders such as PNH and take into consideration the timing of vaccination or booster administrations. CONCLUSIONS: While COVID-19 vaccination benefit most likely outweighs the risks for this specific patient population, our case raises the question about the need for extra precautions in patients with known PNH associated AIHA including the timing of PNH treatment before receiving the vaccination. Reference #1: Algassim AA, Elghazaly AA, Alnahdi AS, Mohammed-Rahim OM, Alanazi AG, Aldhuwayhi NA, Alanazi MM, Almutairi MF, Aldeailej IM, Kamli NA, Aljurf MD. Prognostic significance of hemoglobin level and autoimmune hemolytic anemia in SARS-CoV-2 infection. Annals of Hematology. 2021 Jan;100(1):37-43. DISCLOSURES: No relevant relationships by Suhwoo Bae No relevant relationships by Edward Bae No relevant relationships by Joseph You

Superior Mesenteric Vein and Portal Vein Thrombosis in a Patient With COVID-19: A Rare Case

A 68-year-old man was referred to the general surgeons on account of his abdominal pain of unknown cause. He had contracted COVID-19, 9 days prior. CT chest abdomen and pelvis revealed an extensive thrombus extending from the portal vein to the superior mesenteric vein. Further investigation ruled out haematological causes, and COVID-19 was determined to be the cause. He was treated with an extended course of therapeutic dose low molecular weight heparin under the guidance of the haematology team. He was discharged once he was clinically stable and pain-free, with a plan to be followed up by both the surgeons and haematologists. This case highlights the different ways in which COVID-19 presents, and the need for clearer guidance on the treatment and prevention of thromboembolism in COVID-19.

PROSPECTIVE OBSERVATIONAL STUDY IN PATIENTS WITH IDIOPATHIC THROMBOCYTOPENIC PURPURA (ITP) TREATED WITH TPO-R AGONISTS (TPO-RA): ELTROMBOPAG (EPAG) AND ROMIPLOSTIM (ROMI) - THE PEPITE STUDY

Background: Initially, the marketing authorization (MA) of EPAG and ROMI was to adult patients (p.) with ITP ≥12 months (m.) and refractory to other treatments (t.), splenectomized or contraindicated to splenectomy. The MA was extended for EPAG in 2019 to p. aged ≥1 year with ITP ≥6 m., refractory to other t. (corticoids (CS), IgIV). In 2017, French national guidelines suggested the use of TPO-RA as an option of t. in 2nd line (L). Aims: The PEPITE study, still ongoing, aims to assess the modalities of use, effectiveness and safety of TPO-RAs in reallife. Methods: Prospective, observational, multicenter study including adult p. who initiated TPO-RA with persistent (pITP) or chronic (cITP) ITP. Inclusions occurred between 12/21/2018 and 07/17/2020. Here's the interim analysis, cut-off date: 03/22/2021. Characteristics at baseline were presented in 114 p. (analyzed pop). Efficacy analysis of TPO-RA was assessed in p. with a platelet count (PLAT) <100 G/L at TPO-RA initiation (efficacy pop 113 p.). Responses were defined as: response (R) = PLAT ≥30 G/L, complete response (CR) = PLAT ≥100 G/L and non-response (NR) = PLAT <30 G/L. Results: 123 p. included through 40 centers by 25 hematologists and 15 internists, and 77 p. were still on TPO-RA at 6 m. At baseline, mean age 62.7 ± 20.1 years, 55% men, 29% with at least 1 cardiovascular risk factor. At diagnosis: median PLAT = 26 G/L [0 to 134 G/L], 31% of p. with bleedings. 97% of p. received at least one L of t. before TPO-RA: CS 96%, IVIG 56%, rituximab 47%, dapsone 18%, hydroxychloroquine 11%, danazol 6% and 7% of p. were splenectomized. Median number L of t. = 2 and 8% of p. had more than 4 L. Median time between diagnosis and TPO-RA initiation was 2.6 years [0.3 to 49.3 years], 33% of p. with pITP (n=21 with ITP 3 -<6 months, n=16 with ITP 6 - <12 months) and 67% with cITP. At TPO-RA initiation: 9% of p. were on CS and 48% p. had PLAT <30 G/L (median PLAT = 30 G/L), 95 p. (83%) received EPAG and 19 p. (17%) ROMI. For the 77 p. still on TPO-RA at 6 m., R rate = 97% and CR = 60%. Within 6 m., 10 p. had permanently (perm.) discontinued TPO-RA, main causes were therapeutic effect deemed sufficient (TEDS) for 6 p. and NR for 2 p. For the 27 p. still treated with TPO-RA at 18 m., R rate = 93% and CR = 48%. Within 18 m., 12 p. had perm. stopped TPO-RA, including 7 p. for TEDS and 1 p. NR. P. initiated TPO-RA with ITP 3 -<6 months (N = 21), 9 (43%) p. were still on TPO-RA at 6 months, 5 (56%) in CR. Over the entire follow-up, 24p. (21%) perm. discontinued TPO-RA, main causes were TEDS for 9 p., adverse event (AE) for 5 p. and absence of R for 4 p. Of the 105 p. treated with EPAG at least once, 62 (59%) experienced at least one AE, and 26 SAE occurred in 17 p. The most common AEs were respectively 6% for headache and 3% for SARS-CoV-2 infections, diarrhea, asthenia, insomnia, arthralgia and alopecia. Of the 40 p. treated with ROMI at least once, 19 (48%) experienced at least one AE and 17 SAEs occurred in 10 p. The most common AEs: SARS-CoV-2 infections (5%) and arthralgias (5%). No deaths related to TPO-RA was reported. Summary/Conclusion: Preliminary data from the PEPITE study show that TPO-RA are prescribed in early ITP, including 33% with pITP (18% with ITP 3-<6 m.) and are used in 7% of cases after splenectomy. At 6 m. R on t. was 97% and CR on t. was 60%. Within 6 m., 6 p. had perm. stopped TPO-RA due to TEDS. The real-life effectiveness and safety data for EPAG and ROMI are consistent with data reported in extension studies, with the specificity of occurrence of SARS-CoV-2. The final analysis is scheduled after 24 m.

Anaesthetic management of a parturient with Klippel-Trenaunay syndrome

Introduction: Klippel-Trenaunay syndrome (KTS) is a rare congenital vascular disease which is characterised by capillary, venous and lymphatic malformations. We describe the anaesthetic management of a 36 year old parturient with COVID-19 and KTS, who underwent an elective caesarean section. Very few such cases have been described and the multi-system nature of condition poses various challenges to both the obstetrician and the anaesthetist. Case Report: We had a 36-year-old woman who had experienced three previous normal vaginal deliveries and an elective caesarean section (CS) four years previously under general anaesthetic(GA) at 36 weeks gestation. She was told by a vascular surgeon that she was not suitable for regional anaesthesia. There was no recent imaging of her back to rule out arteriovenous(AV) malformations. Her past history included gastric bypass surgery under GA two years ago. She also had depression, varicose veins and three previous deep venous thrombosis andwas on prophylactic lowmolecularweight heparin. She had tested positive for COVID-19 4 days previously, and had mild symptoms of cough and sore throat. After a multi-disciplinary discussion involving an obstetrician, vascular surgeon, haematologist and anaesthetist, a decision was made to proceed with GA despite recent COVID-19, because of the possibility of AV malformations, in agreement with the patient. After securing two wide bore cannulae and adequate preoxygenation, a modified Rapid Sequence Induction was performed, and a tracheal tube was secured. Anaesthesia was maintained with oxygen, nitrous oxide and sevoflurane. After delivery of the baby, oxytocin 5U, followed by an infusion, midazolam, morphine, ondansetron and dexamethasone were administered. Extubation was performed when the patient was fully awake. In recovery, further opioids were given for pain. There were no concerns for the newborn. Estimated blood loss was 200 mL. Discussion: Gestation and its physiology may further exacerbate the manifestations of KTS, with increased obstetric risk. The success in the management of these patients requires the participation of a multidisciplinary team, consisting of obstetrician, anaesthetist, urologist, haematologist and vascular surgeon, with appropriate collaboration among the professionals involved. Periodic imaging and clotting tests are recommended to evaluate the evolution of vascular malformations in the pelvis, uterus and vagina, and identify neuraxial changes, to guide the safest way of delivery and anaesthesia.

IONA - Interdisciplinary Oncological Follow-Up Clinic in Vienna

Introduction: Cancer in childhood and adolescence can be cured in many cases nowadays. In Vienna, patients are treated either in the St. Anna Children's Hospital or at the University Clinic for Pediatrics and Adolescent Medicine (Neuro-Oncology). Short-term follow-up is usually performed in the children's hospitals. Afterwards patients had to organize the necessary examinations themselves for many years. This so-called transition was not successful in many cases, as the detection and treatment of therapy and disease-associated secondary diseases requires appropriate expertise. Methods: “IONA - Interdisciplinary Oncological Follow-Up Clinic” is now offering age-appropriate, medical and psychosocial long-term follow-up since the beginning of 2020. A team of one experienced hemato/oncologist, two clinical psychologists and a social worker are offering the so-called “survivors” a specialized care, including medical check-ups tailored to the treatment and advices on risk fac-tors in order to identify and treat possible late effects early on. In addition, there is psychosocial care and, if necessary, neuropsycho-logical diagnostics. The health center where IONA is located also offers an optimal multi-professional network for this group of pa-tients. Results: More than 300 survivors have been transitioned since IONA started in early 2020. The majority of them suffered from CNS tumor, acute leukemia or lymphoma and were assigned directly by the hospitals, which guarantees continuous care. There is also reg-ular exchange between the attending physicians as well as the psy-chologists, social workers and administrative employees. During the COVID pandemic, video and audio telephony were also used to hold joint conversations. Conclusions: IONA offers interdisciplinary, standardized long-term follow-up care for patients from the age of 18 who had a hemato/oncologic disease in their childhood, adolescence or young adulthood and who have completed their medical therapy and short-term follow- up care at the responsible clinic. IONA accompanies patients in their transition process through close cooperation with the referring hospitals.

Comparing the Psychosocial Impacts of the COVID-19 Pandemic Between Haematological Cancer and Myeloma Patients: Findings From an Online Survey

Haematological cancer is a risk factor for severe COVID-19, and multiple myeloma (MM) patients may have further risk due to older age and susceptibility to infections. This study aims to understand the pandemic's psychosocial impact on people with haematological cancers, and investigate whether MM patients experience extra stress compared to non-MM patients. The IMPaCCT survey was an international, longitudinal online survey, open to cancer patients. The first survey captured the period April-July 2020 and used quantitative and qualitative measures of quality of life (QoL), including validated tools (WHOQOL-BREF and EQ-5D-5L). Overall, 944 blood cancer patients responded (173 MM, 93 leukaemia, 117 lymphoma, 561 myeloproliferative neoplasm). Most were female, resided in the United Kingdom and did not live alone. Patients with MM were older ( p < 0.001), and more of them had received their cancer diagnosis within the last 5 years ( p < 0.001) than non-MM patients. Only three participants had a COVID diagnosis and none of them had MM. In both MM and non-MM groups, most participants said they would be less concerned about COVID if they did not have cancer. Although 70% of respondents reported their QoL as good/ very good, QoL scores on WHOQOL-BREF were lower in the physical, psychological and social domains than healthy prepandemic UK norms 7 . Respondents reported more satisfaction with environmental factors, such as living arrangements and access to services, however, than prepandemic norms. In both groups there were high rates of anxiety/depression (67%, severe in 5%). MM patients reported more issues with pain and mobility than non-MM patients. Overall 84% of the respondents reported COVID had changed their lives, and 63% of them found this hard to manage. Patients' most trusted sources for information about COVID-19 were healthcare providers and scientists for MM and non-MM participants (90% and 86% with high levels of trust respectively). MM patients had more trust in their friends and family for COVID information than non-MM patients (58% with high level of trust vs. 41%;p < 0.001). Regarding services, 43% of participants had used telemedicine, with more MM than non-MM patients using this service (61% of MM vs. 39% of non-MM). Most reported it was a positive experience. Most participants experienced a changed format for their health appointments, particularly MM patients (69% of MM vs. 52% of non-MM). Appointments with oncologists or haematologists were most often affected. Thirty-four per cent of MM patients reported their treatments were changed or delayed, compared to 11% of non-MM blood cancer patients. This study summarises the self-reported impact of COVID on psychosocial health and care access during the early pandemic in vulnerable patient groups. Results indicate that MM patients are especially vulnerable. Better understanding the needs of these patients will enable healthcare providers to properly support them..

Adapting heparin monitoring in response to COVID-19

At University Hospitals of Leicester NHS Trust (UHL), unfractionated heparin (UFH) has previously been monitored using activated partial thromboplastin time (aPTT) measurements in line with international practice. Prior to the COVID-19 pandemic, heparin assays using Anti-Xa methodology were used to monitor heparin activity in selected cases following approval by a haematologist. These tests were performed in the specialist haematology laboratory by specifically trained staff. Patients diagnosed with COVID-19 have a complex coagulopathy, leading to both prolongation and shortening of aPTT and reduced reliability in heparin monitoring compared with Anti-Xa assays ( Adie & Farina, 2021;Hardy et al., 2020 ). 1,2 In response to the pandemic, to ensure reliable monitoring of treatment, UHL transitioned from using aPTT monitoring to Anti-Xa assay testing. To enable Anti-Xa assay testing in the routine fast track laboratory a new operational procedure with a simplified assay needed to be validated;the initial work had commenced in January 2020 in response to clinician request. Verification of the modified sample centrifugation procedure and a hybrid Anti-Xa assay for UFH and low molecular weight heparin (LMWH) was completed in June 2020. New protocols and staff training in the fast track laboratory took place and the transition was completed in December 2020. To compare the effect this change had at UHL, and the laboratory's ability to adapt, Anti-Xa assay request data were compared between 2018 and 2020 over a 3-month period (October-December ). The findings are presented in Table 1. The study found a 12 times increase in Anti-Xa requests in 2020. The majority of these were for patients receiving extracorporeal membrane oxygenation (ECMO) requiring UFH from our specialist centre located at Glenfield Hospital;these patients required regular monitoring and repeated Anti-Xa assays. We also found a significant increase in requests to monitor prophylactic/intermediate dose heparin treatment in 2020, again with a significant number of these patients receiving ECMO, whereas in 2018 the majority of Anti-Xa assay requests were for treatment dose heparin monitoring. By transitioning from aPTT based to Anti-Xa based heparin monitoring available 24/7 in the fast track laboratory, patients had more reliable monitoring of their heparin activity . This has changed standard of care at UHL, which was of particular benefit to the patients on ECMO and continuous heparin monitoring. Due to the fact that part of the planning and verification work occurred prior to the COVID-19 pandemic the transition of this assay was completed reasonably quickly when the clinical need for this assay to be available on a 24/7 basis became urgent. We will continue to monitor data on therapeutic impact and bleeding episodes..

MORTALITY BY COVID-19 IN ADULTS WITH ACUTE MYELOID LEUKEMIA: A SURVEY WITH HEMATOLOGISTS IN BRAZIL

On behalf of Grupo Oncoclínicas. Objectives: COVID-19 has become one of the worst pandemics in history and patients with acute myeloid leukemia (AML) seems to have high risk for severe events and death by the SARS-COV-2. Our aim is to report a survey conducted with Brazilian hematologists who attended AML patients with COVID-19 to evaluate the mortality rate and any potential risk factor for death. Methods: From May 5th to May 19th, 2021 we conducted a survey with 178 hematologists and collected data about adult patients with AML who had the COVID-19 diagnosis confirmed by RT-PCR: age, gender, possible source of contamination by SARS-COV-2 previous vaccination, moment of the AML treatment, status of AML when COVID was diagnosed and the outcomes related to COVID-19. Results: 33 patients (22 females) were recorded and the median age at the COVID-19 diagnosis was 60 years (19 to 79y). Only one had been previously vaccinated. In 21 cases (63%) in-hospital transmission was presumed to be the source of infection. In 20 patients (60,6%) COVID-19 was diagnosed when the patient had active AML, while in 13 patients (39,3%) AML was in remission. Twelve patients had diagnosis before starting AML treatment, 6 during intensive chemo induction remission, 3 during intensive chemo consolidation, 9 while in low-intensity therapy and 2 during treatment of relapse. There were 18 deaths attributed to COVID-19 (54,5%), of which 15 (83%) had active AML and 3 (17%) were in AML remission (p = 0.0052). We did not identify any other factors that could be associated to death. Among the 15 patients who survived 8 (53%) had some delay in their AML treatment. Discussion: Despite its limitations, this exploratory report addressing specifically AML and COVID-19 brings up some points to consider: 1) Most patients were presumed to be infected in the hospital, which reinforces the need for taking measures to control the dissemination of COVID-19 in the hospital enviroment.2) Our data suggests that patients with active AML possibly have a higher risk of death from COVID-19 and that patients on treatment did not have better outcomes. Beside this, 5 of 12 patients who had COVID-19 diagnosis before beginning AML treatment were alive. These findings lead us to speculate that the best strategy could be postponing the beginning of AML treatment as long as it is safe. 3) Our survey seems to confirm the high risk of death due to COVID-19 in patients with AML. 4) More than 50% of patients who survived COVID-19 had a delay in their treatment;the impact of this delay on AML survival remains uncertain and should be evaluated in future studies. Conclusion: AML patients seem to have a very high risk of death when infected by SARS-COV-2. Furthermore, even when recovered from COVID-19 those patients may suffer a delay in their treatment. Further reports are need to formulate evidence-based recommendations.

COVID-19 IN CHRONIC MYELOID LEUKEMIA PATIENTS – BRAZILIAN EXPERIENCE

Aims: To collect data about COVID-19 in CML patients from Brazilian centers and their outcomes. Methods: Observational, multicentric, ongoing register study. Hematologists from private and public CML reference centers from different regions of Brazil were invited to report their cases of COVID-19 in CML patients. Those centers are responsible for the care of approximately 3030 CML patients. Results: Between March 2020 and July 2021, 16 institutions contributed to this analysis, and reported 73 COVID-19 cases in CML patients (pts). Eight-five % were from the South and Southeast regions, 11% from Northeast. The median age was 50 years (22-79), with 33% of the pts older than 60. Male patients were predominant (60%). The median time of CML diagnosis was 9 years (0-29). Most of the pts were in first line therapy (57.5%), 27% in second line and 11% in third line. Current CML treatment at COVID-19 was: imatinib (46,5%), nilotinib (22%), dasatinib (16%), post-transplant (4%), asciminib (1%), ponatinib (1%), treatment-free remission (2%), no treatment (7%). COVID-19 grade: asymptomatic (4%), mild (66%), moderate (12%), severe/critical (16%). CML status at COVID: AP/BC (3%), CP (12,4%), hematologic response (11%), complete cytogenetic response (4%), MMR (34%), MR4.0 (8%), MR4.5 (27%). Eleven patients interrupted treatment temporarily during COVID. COVID-19 was confirmed by RT-PCR of oral and nasal swab collection (68%) or rapid/serologic test (32%). Comorbidities were present in 34 pts, most common were: hypertension (33%), diabetes (14%), chronic renal failure (4%), chronic obstructive pulmonary disease/emphysema (5.5%), pulmonary hypertension (1). Hospitalization occurred in 30% of the cases, 18% in an intensive care unit, 8% with mechanical ventilation. Treatment received for COVID-19: antibiotics (31%), steroids (16%), chloroquine (5.5%), oseltamivir (4%);ivermectin (8%): heparin (3%). Sixty-nine patients recovered, 4 died from COVID-19 (5,4%): one 42 year old newly diagnosed male patient with high leukocytes counts and with a simultaneous bacterial infection, two 70-year old patients treated with imatinib, both in MR4.5, and one 31-year old male patient treated with nilotinib, after imatinib and dasatinib failure, with hematologic response. A fifth patient in the accelerated phase died 2 months after discharge, from disease progression and pulmonary infection. All cases occurred before vaccination. There was one case of re-infection, in a patient treated with imatinib. Discussion: Conclusions: the majority of COVID-19 cases in the CML population was mild, but there were 2 deaths of young patients with active disease and two deaths in elderly patients, one of them with comorbidities. The mortality in CML was lower than observed in other hematologic cancers.

NOTTO guidelines for vaccine-induced thrombotic thrombocytopenia in organ donation and transplantation

From the context of organ donation, COVID-19 vaccine-induced thrombotic thrombocytopenia (VITT) is important as there is an ethical dilemma in utilizing versus discarding organs from potential donors succumbing to VITT. This consensus statement is an attempt by the National Organ and Tissue Transplant Organization (NOTTO) apex technical committees, India, to formulate the guidelines for deceased organ donation and transplantation in relation to VITT to help in appropriate decision-making. VITT is a rare entity, but a meticulous approach should be taken by the organ procurement organization's (OPO) team in screening such cases. All such cases must be strictly notified to the national authorities (NOTTO) as a resource for data collection and ensuring compliance with protocols in the management of adverse events following immunization. Organs from any patient who developed thrombotic events up to 4 weeks after adenoviral vector-based vaccination should be considered to be linked to VITT and investigated appropriately. The viability of the organs must be thoroughly checked by the OPO, and the final decision in relation to organ use should be decided by the expert committee of the OPO team consisting of a virologist, a hematologist, and a treating team. Considering the organ shortage, in case of suspected/confirmed VITT, both clinicians and patients should consider the riskbenefit equation based on limited experience. An appropriate written informed consent of potential recipients and family members should be obtained before the transplantation of organs from suspected or proven VITT donors.

The use of ibrutinib in Italian CLL patients treated in a real-world setting (EVIDENCE): A preliminary report

Ibrutinib is the only once-daily Bruton's tyrosine kinase (BTK) inhibitor with significant survival benefit vs. chemo- and/or immunotherapy in multiple phase 3 studies of patients (pts) with chronic lymphocytic leukemia (CLL). It has profoundly changed the treatment landscape of CLL with the longest follow-up. However, seven years (yrs) after ibrutinib was approved in Italy by regulatory agencies for CLL treatment, available data on the patterns of care of such pts in the setting of clinical practice is limited. Herein we present the first interim analysis (IA) of EVIdeNCE (ClinicalTrials.gov Identifier: NCT03720561), a multicenter, observational clinical study designed to describe the current management of pts receiving ibrutinib in a real-world setting in Italy in terms of retention rate: the study's primary end point. Methods EVIDENCE 312 treatment-naïve (TN) 38% and relapsed/refractory (R/R) 62% pts with CLL according to the iwCLL diagnosis criteria observed at 39 Italian hematological institutions in the period between November 2018 and October 2019. Inclusion criteria were treatment with ibrutinib according to the European Summary of Product Characteristics as per routine clinical practice started within the previous 3 months. The purpose of this IA is to provide demographics and disease characteristics at baseline and a preliminary evaluation of ibrutinib retention rate after one year of follow-up, along with its safety profile. The median age of pts at the time of ibrutinib initiation was 71.0 yrs (range 41.0-89.0), with 60% ≥70 yrs, 63.2% male, and 90% with Eastern Cooperative Oncology Group (ECOG) performance 0-1. Baseline Rai stage 0-I, II, and III-IV accounted for 18.3, 29.7, and 52.1% pts, respectively. Patients in stage IV were observed in 40% of the R/R and 27% in the TN subgroup. Considering 120 pts with known mutational status, del(17p) and/or TP53 mutation were present in 50.0% of pts (TN =52.1%, R/R = 48.6%), while IGHV was unmutated in 35.0% (TN =33.3% and R/R = 36.15) and mutated in 15.0% (TN =14.6%, R/R = 15.3%). At baseline, 62.9% of pts had comorbidities and 30.6% presented with a history of cardiovascular diseases (CVDs). A CIRS score ≥6 was observed in 28.5% of pts. The median time from CLL diagnosis to the start of ibrutinib was 5.1 yrs (TN 1.75 yrs vs. R/R 7.27 yrs). At least 1 treatment-emergent adverse event (TEAE) of any grade was experienced by 70.7% of pts. Frequencies were as follows: infections (30.8%;COVID-19 infections 3.2%), arthralgia (10.8%), neutropenia (9.3%), fatigue (8.4%), diarrhea (7.7%), atrial fibrillation (7.4%;grade 3-4, 4.2%), fever (7.1%), rash (6.4%), anemia (6.1%), and hypertension (4.2%). Mild bleeding TEAEs were reported in 16.1% of pts with no major bleeding event. TEAEs were more frequent in the elderly (≥65 yrs) while no significant differences in the rate of TEAEs were recorded in TN and R/R pts (69.7 vs. 71.4%, respectively). Serious TEAEs were reported in 21.9% of pts. Overall in intention to treat (ITT), 32 deaths (10%) were observed (TN =8, R/R = 24). The most common causes of death were infections (3.5%) and progressive disease (PD) (1.9%). Permanent discontinuation was observed in 56 (18%) of the pts (TN =17.2%, R/R = 18.7%) and it mostly occurred within the first 6 months. The main causes of discontinuation were toxicity (6.1%), PD (3.8%), and death (3.5%). Temporary interruptions (≤3 months without therapy and/or dose modifications) during the whole observation period occurred in 30.3% (TN =35.3%, R/R = 27.2%) and 37.7% (TN =37.5%, R/R = 37.8%) of pts, respectively, mainly determined by toxicity and clinical judgment. Finally, in this first IA after 17.3 months (range 1.1-27.0) median follow-up, the ibrutinib retention rate (calculated as the ratio between the number of patients who retained ibrutinib treatment over the total number of patients at risk) at 1-year was 81.9% [95% confidence interval (CI), 77.2-86.1%] with no difference between TN 83.2% (95% CI, 75.2-89.4%) and R/R 81.2% pts (95% CI, 74.9-86.4%). EVIDENCE is the first realw rld study of ibrutinib use in CLL clinical practice in Italy. Ibrutinib retention rate at one-year suggests a better knowledge and expertise of hematologists in the management of ibrutinib-related toxicities that may result in an improved long-term outcome of pts with CLL.