Acquired hemophilia A following COVID-19 vaccine: a case report.

BACKGROUND: In the literature, reported cases of Acquired hemophilia A (AHA) induced by COVID-19 vaccination occurred after Adenoviral Vector Deoxyribonucleic Acid (DNA)- and SARS-CoV-2 Messenger Ribonucleic acid (mRNA)-Based vaccines. Here, and to the best of our knowledge, we report the first case of AHA occurring after an inactivated Sinovac-coronavac COVID-19 vaccine. CASE PRESENTATION: A 69-year-old Tunisian male patient consulted for severe left leg pain limiting physical mobility due to a 5*6 cm large ecchymosis located at the left inner thigh, having spontaneously appeared 5 days prior consultation and without notion of trauma. The patient had no known personal medical history. He had received the second dose of CoronaVac-SinoVac vaccine 30 days prior to consultation. Further physical examination revealed the presence of two other ecchymoses: one at the inner face of the right forearm, starting at the wrist reaching the elbow and the other at the left flank of the abdomen. Diagnosis of AHA was based on clinical presentation and confirmed with prolonged a PTT, Factor VIII deficiency and the presence of an FVIII inhibitor. The patient was successfully treated with corticosteroids and low dose Rituximab. CONCLUSION: Clinicians should consider AHA in front of prolonged aPTT with or without spontaneous bleedings even after inactivated virus COVID-19.

Acquired hemophilia A secondary to SARS-CoV-2 pneumonia: a case report.

The acquired hemophilia A (AHA) is a life-threatening condition. The incidence of AHA is extremely low, which requires a multidisciplinary approach to diagnosis and treatment. This is case report of 73-year-old man who presented with AHA secondary to severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) pneumonia. The patient had extensive skin bleeding and hematomas. In the coagulation screening tests activated partial thromboplastin time (APTT) was prolonged with normal prothrombin time (PT), which was indication for further investigation. The APTT in a mixing study with normal plasma did not correct so clotting factors inhibitors were suspected. With signs of bleeding, extremely low factor VIII (FVIII) activity (2%) and presence of FVIII inhibitors, AHA was diagnosed and treatment initiated. Patient was treated with factor eight inhibitor bypassing agent (FEIBA) for three days, followed by long-term corticosteroid and cyclophosphamide therapy. Malignant and autoimmune diseases as the most common causes of AHA were ruled out. The patient had a good response to therapy with gradual normalization of APTT and FVIII activity. To the best of our knowledge, the present case is the first reported case of de novo AHA after SARS-CoV-2 pneumonia. The diagnosis of AHA should be suspected in a patient with bleeding into the skin and mucous membranes without a previous personal and family history of bleeding, and with isolated prolonged APTT. It is important to investigate any isolated prolongation of APTT in cooperation with clinical laboratory experts.

Multisystem inflammatory syndrome in a neonate with severe hemophilia - a diagnostic challenge in COVID times: a case report.

BACKGROUND: Multisystem Inflammatory Syndrome in Neonates (MIS-N) can occur following antenatal COVID- 19 infection in the mother. Here we report a rare case of a neonate with Hemophilia A and MIS-N. CASE PRESENTATION: A 2-day-old baby presented with an intramuscular hematoma, neonatal seizures, and isolated activated partial thromboplastin time (APTT) prolongation. The neurosonogram showed a subdural hematoma. A diagnosis of Hemophilia A was made and was confirmed by factor 8 assay and genetic analysis. Supportive measures and Factor 8 replacement was initiated. A rising trend of inflammatory markers and an ongoing need for mechanical ventilation were noted. As there was a history of COVID-19 in the mother in the third trimester, MIS-N was diagnosed. The baby was treated with intravenous immunoglobulin (IVIG) and steroids, and there was an improvement in the clinical and laboratory markers. However, the baby developed seizures on day 16. There was an increase in the subdural hemorrhage and a further rise in inflammatory markers. A craniostomy and hematoma evacuation was done and the baby improved. CONCLUSION: The concurrent occurrence of hemophilia A with intracranial bleed, and MIS-N in a neonate is a diagnostic challenge. It is important to have a high index of suspicion to ensure timely diagnosis and treatment of MIS-N in this pandemic era.

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.

Case of acquired haemophilia a in Southeast Asia following COVID-19 vaccine.

Acquired haemophilia A (AHA) is a rare bleeding disorder with high morbidity and mortality, but it is eminently treatable if diagnosis and treatment are prompt. We report a case of AHA in Southeast Asia following the administration of the Pfizer-BioNTech COVID-19 vaccine. A man in his 80s developed multiple bruises 2 weeks after his first dose of the COVID-19 vaccine. Diagnosis was delayed due to his cognitive impairment and low clinical suspicion. This led to a representation with worsening ecchymosis, a left thigh haematoma and symptomatic anaemia. Laboratory testing was notable for an isolated prolongation of the activated partial thromboplastin time, which remained uncorrected in the mixing test. Further testing confirmed the presence of factor VIII (FVIII) inhibitors and low FVIII titres of 6.7%. He responded to treatment with intravenous methylprednisolone and recombinant activated FVII. Screening for autoimmune diseases and malignancies was negative.

Doxycycline-induced acquired haemophilia A.

An 80-year-old man with no personal or family history of bleeding, presented to hospital with extensive haematomas and skin bruising after using doxycycline. His basic lab workup was concerning for a coagulopathy with an elevated activated partial thromboplastin time and significant anaemia. Mixing studies and other factor levels were tested that led to the diagnosis of acquired haemophilia A with low factor VIII levels and high factor VIII antibodies. He was started on steroids, but his haemoglobin level continued to drop. Later, during his treatment, he was given multiple therapeutic agents, including cyclophosphamide, rituximab and recombinant factor VII (NovoSeven-R). Gradually factor VIII levels increased and haemoglobin stabilised. The hospital course was complicated by COVID-19 pneumonia leading to acute respiratory distress syndrome; the patient eventually expired due to respiratory failure.

Severe acquired haemophilia associated with asymptomatic SARS-CoV-2 infection.

A 65-year-old man presented with symptoms of severe subcutaneous bleeding in his arm, which led to compartment syndrome requiring fasciotomy and massive blood transfusion protocol. Medical history was significant for history of autoimmune thyroid disease. Workup revealed elevated partial thromboplastin time, decreased factor VIII levels and elevated factor VIII inhibitor levels. He was worked up for causes of acquired haemophilia A and was found to have an elevated SARS-CoV-2 antibody level. Given his negative workup for other secondary aetiologies, we suspect that the cause of his haemophilia A was from his SARS-CoV-2 infection, which has been observed previously in various case reports.

A case report of acquired hemophilia following COVID-19 vaccine.

Acquires hemophilia A (AHA) is rare bleeding condition commonly associated with malignancy, autoimmune disease, or pregnancy. We report a case of a 69-year-old gentleman who developed bleeding symptoms after receiving COVID-19 vaccine. Laboratory testing showed isolated prolongation of the activated partial thromboplastin time, and normal von Willebrand factor. Further testing confirmed the presence of factor VIII inhibitor. To date, no cases of AHA have been reported after exposure to COVID-19 vaccine. There have been two cases of AHA following seasonal flu and H1N1 vaccination, as well as two cases of AHA following COVID-19 infection. We present a summary of these cases and review of literature of autoimmune reactions following vaccination.

Management of COVID-19-associated coagulopathy in persons with haemophilia.

INTRODUCTION: The SARS-CoV-2 coronavirus-induced infection (COVID-19) can be associated with a coagulopathy mainly responsible for pulmonary microvasculature thrombosis and systemic thromboembolic manifestations. The pathophysiology and management of the COVID-19 coagulopathy are likely more complex in patients with inherited bleeding diseases such as haemophilia. These individuals might indeed present with both bleeding and thrombotic complications and require simultaneous antithrombotic and haemostatic treatments. OBJECTIVE: We propose practical guidance for the diagnosis and management of COVID-19 coagulopathy in persons with haemophilia. RESULTS: Continuation of regular haemostatic treatment is recommended for ambulatory patients. For patients requiring hospital admission and on replacement therapy with factors VIII or IX concentrates, prophylaxis with concentrates should be intensified according to the risk of bleeding complications and associated with prophylactic doses of LMWH. For patients on nonreplacement therapy, emicizumab should be continued and possibly combined with factor VIII and prophylactic doses of LMWH depending on the risk of bleeding and thrombosis. Dose escalation of LMWH tailored to the risk of thrombosis can be employed but not supported by evidence. CONCLUSIONS: These practical recommendations are based on the current literature on COVID-19 with its impact on haemostasis, indications and modalities for thromboprophylaxis mainly in nonhaemophilic patients and how that is likely to affect persons with haemophilia in different circumstances. They will need to be tailored to each patient's clinical status and validated in future studies.