Acquired Haemophilia associated with SARS-CoV2 infection

We present the case of a 73-year-old man, with a history of SARS-CoV2 infection ( January 2021), who came to the emergency department three months post infection, with complaints of left hip and knee pain, that turned out to be a substantial thigh hematoma. Analysis showed a normocytic/normochromic anaemia (9,0 g/dL), prolonged aPTT (63.2 seconds;normal range 24.7-39.0 sec.), with normal prothrombin time. We arrived at a diagnosis of Acquired Haemophilia A. Treatment was promptly started, with clinical and laboratory improvement. After the vaccination to SARS-CoV2, a relapse was observed. Acquired Haemophilia A is a rare, autoimmune disease, distinguished by the presence of inhibitors against factor VIII. It's characterised by subcutaneous hematomas and muscle bleeding, with prolonged aPTT. SARS-CoV2 infection has already been mentioned as a possible cause.

Abnormal postpartum uterine bleeding in adolescence associated with SARS-CoV-2 infection

Background: With a prevalence of 1-3 cases per million, acquired haemophilia A (AHA) is a rare autoimmune bleeding disorder caused by the presence of neutralizing antibodies against factor VIII. Even though diagnosis of this bleeding disorder is rarely established among children and adolescents, AHA may lead to severe, life-threatening hemorrhage in this age group, and therefore it requires special caution. Case report: 19 year old primigravida with confirmed SARS-CoV-2 infection was admitted to hospital due to prolonged vaginal bleeding six weeks postpartum. All gynaecological causes of uterine bleeding were excluded, Foley catheter was placed, but the bleeding still persisted. Coagulation tests revealed isolated deranged aPTT values. Further haematology evaluation demonstrated factor VIII deficiency, presence of factor VIII inhibiting factors, and the diagnosis of AHA was proposed. The anti-inhibitor coagulant complex drug was introduced and patient has responded positively to the treatment. Conclusion(s): Due to disturbance of immune system, pregnancy and postpartum period represent predilection time for AHA development. Furthermore, viral infection in pregnancy, such as COVID-19, might be considered as an additional risk factor for AHA development and several reported cases of AHA after COVID-19 infection support this hypothesis. Even though AHA is a rare disease, due to its high mortality rate of more than 20%, it should be considered in all cases of unusual bleeding of unknown cause in all age groups. Publication of this case report is approved by Institutional Review Board.Copyright © 2023

A cross-sectional follow-up study of physical activity in adults with moderate and severe haemophilia.

AIM: To conduct a cross-sectional follow-up assessment of physical activity (PA) in people with moderate and severe haemophilia (PwMSH) from the Irish Personalised Approach to the Treatment of Haemophilia (iPATH) study. METHODS: Between June-December 2021, participants' PA was measured over one week using accelerometery, and was compared with their previously measured data from the original iPATH assessment. Self-awareness of PA and the impact of the Covid-19 pandemic on PA, pain, mobility and function were retrospectively examined using a survey. RESULTS: Of 30 participants who returned surveys [n = 19, severe (FVIII, <.01 IU/mL); n = 4, moderate (FVIII, .01-.05 IU/mL); n = 7, severe (FIX, <.01 IU/mL); age: 47 (36, 55) years], 28 completed accelerometery (follow-up time: 3 years). There were no significant differences in accelerometer PA (all p > .05), but achievement of World Health Organisation guidelines increased (67.9%-75.0%; p = .646). Increased self-awareness of PA was reported by 76.7%, and 66.7% reported desires to become more physically active. Compared to normal, most reported either no differences or lower levels of PA during lockdown restrictions. Self-reported PA increased for most when restrictions eased from April 2021 onwards. Beyond the pandemic, concerns included pain and access to exercise resources. CONCLUSION: Self-reported PA throughout the pandemic was variable, whilst there were no significant differences in objectively measured PA between assessment periods, despite reports of increased self-awareness and desires to be physically active at follow-up. Further qualitative research is needed to design personalised PA and health interventions, capturing perspectives of patients, their families, and multi-disciplinary haemophilia healthcare providers.

Management of acquired haemophilia A in severe Covid-19: Haemostatic bridging with emicizumab to keep the balance between bleeding and thrombosis.

Acquired haemophilia A (AHA) is an autoimmune bleeding disorder caused by autoantibodies blocking coagulation factor VIII (FVIII). Haemostatic management of AHA and concomitant thrombotic risk is difficult. We cover the management of a 75-year-old male with severe Covid-19, a prothrombotic disease, and de novo AHA with severe muscle bleeding, a disease requiring highly thrombogenic haemostatic therapy and immunosuppression-a challenging combination. FVIII activity was measured using human and bovine reagents to differentiate between endo- and exogenous FVIII activity. For haemostatic control, recombinant human activated FVII was given, followed by emicizumab, as a less thrombogenic long-term haemostatic agent. Steroids were used as initial immunosuppressive therapy. Later, rituximab was used for inhibitor eradication. No thromboembolic events occurred, and bleeding was effectively controlled. Emicizumab achieved haemostatic balance in a patient under haemorrhagic and thrombogenic conditions. Individual risk assessment is needed to guide treatment decisions in patients threatened by simultaneous bleeding and thrombosis.

Validation of the patients-specific functional scale in patients with haemophilia.

INTRODUCTION: A complete functional assessment is essential to measure health status and treatment effects in patients with haemophilia. The Patient-Specific Functional Scale (PSFS) is a reliable, valid, simple and quick scale that measures physical function in patients with musculoskeletal disorders. However, the reliability and validity of the PSFS have not been evaluated in patients with haemophilia. AIM: The aim of this study was to validate the Patient-Specific Functional Scale in patients with haemophilia. METHODS: Twenty-eight patients with haemophilia participated in the study. They completed the PSFS and the Haemophilia Activity List (HAL) scales by telephone during an initial session, and then repeated the assessment in a follow-up session 1 week apart. Reliability was analysed by the internal correlation coefficient (ICC), the standard error of measurement (SEM) and the smallest detectable change (SDC). The concurrent validity of the PSFS was determined by correlating the initial score of the PSFS scale to the initial score of the HAL scale. Correlations were calculated by means of scatter plots and Pearson product-moment r correlation coefficient. RESULTS: ICC and SEM values showed excellent reliability for the PSFS scale, with a SDC of 1. A significant moderate correlation was found between the results of the PSFS and the HAL (r = .57, P < .001). CONCLUSION: The PSFS is a reliable and valid scale to measure the functionality of people with haemophilia.

Total Hip Replacement in Severe Haemophilia A: Challenges and Feasibility.

The management of haemophilic patients is complicated due to multiple comorbidities. A dedicated haemophilia treatment centre with a multidisciplinary team can plan and execute elective orthopaedic surgery in such haemophilic individuals. A cementless total hip arthroplasty (THA) was performed in a 26-year-old male patient with haemophilic arthropathy of the right hip under factor VIII replacement therapy based on activated partial thromboplastin time levels. The patient received a preoperative dose of recombinant anti-haemophilic factor. Venous thromboembolic event prophylaxis was not given. Postoperative radiographs demonstrated successful prosthesis placement. The patient could bear weight and walk unassisted two weeks after surgery. THA in patients with haemophilia leads to significant improvement in joint function with a relatively low incidence of complications with modern techniques and haematological management.

Haemophilia management programme: Transformation during COVID-19.

Background & objectives: Haemophilia is a debilitating bleeding disorder with significant comorbidities affecting the quality of life. In India, the management of these individuals is still limited to on-demand institutional treatment with coagulant factors. In this study, we highlighted the problems faced by these patients in the COVID-19 period due to nationwide lockdown. Methods: A retrospective study was done to ascertain the trend in the number of patients with haemophilia A and B visiting the hospital, those succumbing to haemophilic complications and indications for factor requirement in the pre-COVID (October 2019-March 2020) and during the COVID-19 period (April-September 2020). Representative cases with unusual complications were described along with significant challenges faced in providing standard care of treatment to these individuals due to the COVID-19 pandemic. Results: A total of 818 and 162 individuals with haemophilia A and B, respectively, were registered with the department. The overall number of patient visits to the hospital significantly reduced from an average of 6.9 outpatient department (OPD) visits per patient in the pre-COVID-19 period to an average of 3.9 OPD visits per patient and admissions reduced to 50 per cent during the COVID-19 period. This led to a reduction in utilization of factors VIII and IX except VIIa for haemophilia with inhibitors. There was no factor utilization for elective surgeries during the COVID-19 period. A total of eight patients succumbed to haemophilia-related complications during the COVID-19 period due to delay in reaching the hospital. The challenges faced in the management of three cases with musculoskeletal bleeds, one case with scrotal haematoma and one with haemothorax during the COVID-19 period were also highlighted. Interpretation & conclusions: COVID-19 pandemic has unveiled the need for on-demand home treatment with coagulant factors and has also brought to light the existing need for primary prophylaxis, especially for younger individuals with haemophilia.

Case Report: Acquired Haemophilia A Following mRNA-1273 Booster Vaccination Against SARS-CoV-2 With Concurrent Diagnosis of Pleomorphic Dermal Sarcoma.

While the global pandemic caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is still ongoing and new virus variants are emerging, there is a universal need for vaccines to protect individuals from severe complications and ideally control the pandemic by enabling herd immunity. Several vaccines against SARS-CoV-2 have been approved and are widely used to stem the recurring waves of coronavirus disease 2019 (COVID-19). Post-marketing surveillance is essential to record even rare safety issues related to these new vaccines. Among these issues, several autoimmune phenomena have been recorded in temporal association with and feasibly triggered by a vaccination. Acquired haemophilia A (AHA) is a rare condition characterized by new-onset haemorrhagic diathesis caused by an inhibitor of blood clotting factor VIII (FVIII), often in the elderly and most commonly associated with autoimmune or malignant disease. There have been a small number of AHA cases triggered by vaccinations, including those against SARS-CoV-2. We report the first case of AHA in temporal association with an mRNA-1273 booster vaccination. The diagnosis was made promptly, and the patient received appropriate care including immunosuppression using glucocorticoids, cyclophosphamide (CYC) and rituximab (RTX). The haemorrhage ceased after escalation of treatment, and the patient is recovering. Concurrent malignancy was initially ruled out using a wide scope of diagnostic tests, but pleomorphic dermal sarcoma (PDS) of the forehead occurred after initiation of specific AHA immunosuppressive treatment. Since large vaccination programs are ongoing worldwide and potential adverse events during post-marketing surveillance have been reported following vaccination against SARS-CoV-2, this case illustrates challenges in rare events occurring in association with SARS-CoV-2 vaccination and to proof a causal relationship. Therefore, there is an urgent need for reporting any events in association with SARS-CoV-2 vaccination, but also a crucial discussion about possible concurrent triggers and follow-up information about individual patients.

Spontaneous suprachoroidal haemorrhage in haemophilia coincident with ChAdOx1 nCoV-19 vaccine.

PURPOSE: To report a case of spontaneous suprachoroidal haemorrhage in a haemophilia patient immediately following ChAdOx1 nCoV-19 vaccination. CASE PRESENTATION: A 60-year-old man with haemophilia developed painful vision loss in his left eye a day following the ChAdOx1 nCoV-19 vaccination due to acute angle-closure glaucoma from a massive suprachoroidal haemorrhage. He had an extremely deranged coagulation profile; activated partial thromboplastin time (APTT): 89 s, normal range 29-35 s After factor VIII transfusion, ocular hypotensive therapy and systemic/topical steroids, the suprachoroidal haemorrhage and glaucoma resolved, but the vision remained poor. CONCLUSION: Spontaneous suprachoroidal haemorrhage may be seen in haemophiliacs with deranged coagulation profiles. In our case, it followed ChAdOx1 nCoV-19 vaccination, and we recommend caution and checking the coagulation profile in such patients apriori.

Severe COVID-19 Infection Management in a Patient with Mild Haemophilia-A Case Report.

Patients with haemophilia present a significant challenge when admitted into the intensive care unit. To prevent haemorrhagic complications related to the infection or due to invasive procedures factor (F) VIII/IX must be substituted. As thromboembolic complications are frequent among critically ill COVID-19 patients, thromboprophylaxis is also applied to patients with haemophilia. This requires careful monitoring of FVIII/IX activity as well as other haemostatic parameters, such as D-dimer and antiXa. We describe a 44-year old patient with mild haemophilia A (FVIII activity of 6%), who required a prolonged intensive care unit stay due to a severe SARS-CoV-2 infection. FVIII was substituted via boluses, and dalteparin was given according to recommendations. The patient successfully recovered from the disease.

Safety and effectiveness of telerehabilitation program in people with severe haemophilia in Chile. A qualitative study.

INTRODUCTION: Little is known about how people with haemophilia (PWH) perceive and assess the usefulness, safety and effectiveness of telerehabilitation. OBJECTIVE: To describe usefulness, safety, effectiveness and limitations of a telerehabilitation program applied in people with severe haemophilia implemented during the COVID-19 pandemic in Chile. DESIGN AND METHODS: A qualitative study was conducted based on a focus group. Four analytical categories were predefined, three of which involved elements of Donabedian's model for quality assessment in health care (structure, process and results). RESULTS: One of the most important aspects according to all of the participants is the sense of safety they experienced while being taken care of by a physiotherapist specializing in PWH rehabilitation. This facilitated trust in the professional and adherence to treatment. All participants reported improvements in their physical condition and sense of well-being. The lack of adequate equipment at home, the limited length of the sessions, the perception that the physiotherapist may not be able to perform an appropriate physical examination and the lack of direct supervision were described as disadvantages. CONCLUSIONS: The findings underscored that telerehabilitation had high satisfaction among PWH. Telerehabilitation was perceived by PWH as a safe and effective intervention to improve physical condition. Telerehabilitation could be further supported and improved, and coverage could be enhanced, including rural and remote areas, which suffer from chronic inequalities in access to rehabilitation. The lack of face-to-face supervision and physical examination were perceived as the principal disadvantages. These results may help to improve telerehabilitation programs in PWH elsewhere.

Impact of first COVID-19 lockdown on paediatric and adult haemophilia patients treated in a French Haemophilia Comprehensive Care Centre.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic has created an unprecedented global health crisis. AIM: To investigate the impact of the 1st COVID-19 lockdown on haemophilia patients in terms of symptoms, management, medication adherence, mental health and lifestyle behaviours. METHODS: A prospective cross-sectional phone survey using a two-part questionnaire was conducted in haemophilia patients (adults and children) followed-up in a French Haemophilia Comprehensive Care Centre between May 5, 2020 and June 2, 2020 (CLEO CD study: NCT04390126). RESULTS: Among 284 haemophilia A or B patients with FVIII or FIX < 40% contacted for the study, 239 (84%) including 183 adults and 56 children participated to the survey. In 81% of children and 78% of adults, bleeding episodes remained unchanged or decreased. Medication adherence was 82.0% in adults and 98.2% in children. Non-adherence concerned haemostatic agents in six patients and analgesics in three. Overall, 67% of adults and 71% of children felt as good as before lockdown. In both adults and children, the three major changes in lifestyle behaviours were: increase in screen time (49% and 57%), decrease in physical activity (43% and 48%), and weight gain (32% and 27%), respectively. CONCLUSIONS: Encouraging results were observed in terms of haemophilia symptoms, medication adherence, and mental health. Conversely, a negative impact was observed on lifestyle behaviours in a cohort of French haemophilia patients during the 1st lockdown.

Digital haemophilia: Insights into the use of social media for haemophilia care, research and advocacy.

INTRODUCTION: The haemophilia community on Twitter is diverse, consisting of advocacy groups, patients, physicians, researchers and other users. However, the scope of this community is uncharacterized, and limited data is available regarding effective participation in this community. AIM: To assess the types of users active in the haemophilia community on Twitter, as well as major themes present in haemophilia-related tweets. METHODS: Forty-nine thousand five hundred and twelve tweets between September 2019 and September 2021 were classified using regular expressions. A subset of the classified tweets was manually analysed to identify prevalent discussion themes. RESULTS: Among the top 250 users by post count, the largest categories of users were support and advocacy groups, people with bleeding disorders and healthcare providers. The largest thematic categories of tweets were gene therapy, contaminated haemophilia blood products, haemophilia research, clinical management of haemophilia and COVID-19. While misinformation was rare, negative and incorrect perceptions of haemophilia were present among the general public. CONCLUSION: Our results demonstrate patterns of effective Twitter usage for patient care, research and advocacy purposes among the haemophilia community.

Anticoagulation for Stroke Prevention after Restoration of Haemostasis with Emicizumab in Acquired Haemophilia A.

Acquired haemophilia A (AHA) is a rare haemorrhagic disorder caused by the development of autoantibodies inhibiting factor VIII function. It predominantly affects the elderly, who are often burdened with a considerable number of comorbidities, and can result in life-threatening bleeding. The management of AHA consists of two aspects: inhibitor eradication with an immunomodulator and bleed control with a bypassing agent. Here we present a case of AHA with a high titre inhibitor in a patient with extensive comorbidities and atrial fibrillation in whom inhibitor eradication could not be achieved within a few weeks using corticosteroids alone. Due to coronavirus disease (COVID)-19 restrictions and complications of care, emicizumab offered an effective and convenient therapy, not only sparing the need for continued and intensified inhibitor eradication, but also allowing anticoagulation for stroke prophylaxis. LEARNING POINTS: Emicizumab may offer a suitable option for bleeding prophylaxis when inhibitor eradication is not achievable with immunotolerance treatment, especially in the age of the COVID-19 pandemic when the consequences of immunosuppression can be detrimental.Bleeding prophylaxis with emicizumab may enable long-term anticoagulation in patients with acquired haemophilia A during inhibitor eradication.The prothrombotic risks of emicizumab are not yet sufficiently characterized.

Excess weight gain in the paediatric bleeding disorders population: Impact of the COVID-19 Pandemic.

INTRODUCTION: The COVID-19 pandemic has resulted in lifestyle changes for children. The aim of this study was to evaluate the impact of the pandemic on weight/BMI in children with severe bleeding disorders. METHODS: We conducted a retrospective review of patients age 3-18 years with severe bleeding disorders on prophylactic therapy treated at SickKids Hospital (Toronto, Canada) between February 01, 2018 and March 31, 2021. We evaluated the following pre- and post-COVID variables: weight (kg), weight percentile, BMI (kg/m2 ), BMI percentile, HJHS score, and prophylactic dosing (units/kg). RESULTS: One hundred and four patients were included in the final analysis. Diagnoses were as follows:  haemophilia A (n = 92; 70.8%), haemophilia B (n = 17; 13.1%), type 3 von Willebrand disease (n = 11; 8.5%), the remainder were diagnosed with rare factor deficiencies.  Median interval time from pre-COVID measurements to latest follow-up was 12.4 months (IQR 10.32-14.52 months) during which there was a statistically significant increase in median weight percentile +5.75 centiles (from 63rd centile to 68.75th centile). There was a statistically significant increase in mean BMI of +1.03 kg/m2 (P = < .001) while median BMI percentile increased +8.82 centiles (from 53.9th centile to 62.72nd centile) and mean BMI percentile increased 3.42 centiles (from 57.5 centile to 60.9 centile). The group that gained the most weight centiles, BMI and BMI centiles were 5-14 years old. CONCLUSION: There was a trend to weight gain over the study period. More long-term data is required to evaluate the impact of this increase in weight and BMI on children with bleeding disorders.