Acquired Hemophilia A following Pfizer-BioNTech SARS CoV-2 mRNA vaccine, successfully treated with prednisolone and rituximab.

INTRODUCTION: Acquired haemophilia A (AHA) is a rare bleeding disorder, characterised by the presence of autoantibodies to clotting factor VIII (FVIII). AHA can be idiopathic or occur in the context of malignancy, autoimmune disease, drugs, or pregnancy. Recently, cases of AHA following both COVID-19 infection and vaccination have been reported. CASE REPORT: We report the case of a 95-year-old female who was immunised with the Pfizer-BioNTech SARS CoV-2 mRNA vaccine, with doses given three weeks apart. Spontaneous bruising over her extremities appeared one week after the initial dose, with hospital admission occurring three weeks after the second. Examination revealed a large haematoma on the dorsum of the right hand with resultant bleeding and widespread ecchymoses. Investigations confirmed a diagnosis of AHA. MANAGEMENT AND OUTCOME: Initial management included high dose prednisolone, recombinant Factor VIII and tranexamic acid. There was no significant clinical improvement after three days, so intravenous rituximab 100 mg weekly for four weeks was commenced. The activated partial thromboplastin time (aPTT) normalised after two doses and Factor VIII level reached 0.68U/ml on day + 22. The patient was successfully discharged from hospital after 37 days. DISCUSSION: Four cases of AHA following administration of COVID mRNA vaccines (Pfizer and Moderna) have been documented. AHA should be a differential in patients presenting with bleeding following COVID-19 vaccination, in the presence of a normal platelet count. Rapid recognition, prompt initiation of immunosuppressive treatment and rigorous supportive cares are required to minimise morbidity and mortality.

Temozolomide-induced aplastic anaemia: Case report and review of the literature.

INTRODUCTION: Temozolomide (TMZ) is an oral alkylating agent principally indicated for neurological malignancies including glioblastoma (GBM) and astrocytoma. Most common side effects are mild to moderate, and include fatigue, nausea, vomiting, thrombocytopenia and neutropenia. Severe or prolonged myelosuppression, causing delayed treatment or discontinuation, is uncommon. Major haematological adverse effects such as myelodysplastic syndrome or aplastic anaemia (AA) have rarely been reported. CASE REPORT: We report a 68-year old female with GBM treated at a tertiary hospital with short-course radiotherapy and concurrent temozolomide following craniotomy. On treatment completion she was transferred to our hospital for rehabilitation. She was thrombocytopenic on admission. Platelets continued falling with significant pancytopenia developing over the next two weeks. Blood parameters and a markedly hypocellular bone marrow confirmed the diagnosis of very severe AA, probably due to TMZ. MANAGEMENT AND OUTCOME: Treatment consisted of repeated platelet transfusions, intravenous antibiotics, antiviral and antifungal prophylaxis, and G-CSF 300 mcg daily. Platelet and neutrophil counts had returned to normal at 38 days following the completion of TMZ treatment. DISCUSSION: Whilst most cases of AA are idiopathic, a careful drug, occupational exposure and family history should be obtained, as acquired AA may result from viruses, chemical exposure, radiation and medications. Temozolomide-induced AA is well documented, though only 12 cases have been described in detail. Other potential causes were eliminated in our patient. Physicians should be aware of this rare and potentially fatal toxicity when prescribing. Frequent blood tests should be performed, during and following TMZ treatment, to enable early detection.

Diagnosis and management of adult patients with von Willebrand disease in South Australia.

We have analyzed the databases for von Willebrand disease (VWD) from the hemophilia center for adult patients with bleeding disorders in South Australia. We define the prevalence of types of VWD to determine the proportion of who would be treated with factor (F) VIII/von Willebrand factor (VWF) concentrate to prevent or control hemorrhage. In severe or moderately severe patients, we use plasma-derived FVIII/VWF concentrate, and for mild to severe cases, we use desmopressin plus tranexamic acid. There are 103 patients with VWF ristocetin (RCo) ≤50 IU/dL: 38 (37%) severe (VWF:RCo <10 IU/dL), 28 (27%) moderate (VWF:RCo 10 to 29 IU/dL), and 37 (36%) mild (VWF:RCo 30 to 50 IU/dL). Hence in 66 (64%), FVIII/VWF concentrate is the mainstay of treatment. The prevalence of VWD in our region according to data from our center is ~1 per 12,000. A total of 52% of patients are type 1, 44% type 2, and 5% type 3. In our experience, type 2M (45% of type 2) is much more common than types 2A and 2B (each 9% of type 2). Mutation detection is useful for identifying some subtypes of VWD.

Benign FGB (148Lys→Asn, and 448Arg→Lys), and novel causative γ211Tyr→His mutation distinguished by time of flight mass spectrometry in a family with hypofibrinogenaemia.

We describe a novel procedure for the direct analysis of plasma fibrinogen by HPLC time of flight (TOF) mass spectrometry and apply it to the investigation of a family with hypofibrinogenaemia. Electrospray TOF analysis provided much higher resolution than was possible with our previous quadrupole analyser and revealed three different mass changes within the fibrinogen Bß and γ chains of the family. It also demonstrated the actual hypofibrinogenaemia phenotype was caused by an aberrantγ chain (-23 Da) which was expressed at a diminished ratio of 0.2:1 relative to γ(A) and co-inherited with a second coequally expressed Bß variant (Bß(M) /Bß(A), 1:1). Co-segregation was confirmed by gene analysis that showed the affected father and son had a very rare Bß148Lys→Arg mutation (-14 Da) inherited together with a unique new γ211Tyr→His mutation (-26 Da). This latter causative substitution occurs at a site that is absolutely conserved across all fibrinogen chains and preserved across all species. TOF analysis also identified a variant Bß chain (54,186 Da) that was coequally expressed with normal Bß chains (54,213 Da) in the unaffected mother.

Successful treatment of transplant-associated microangiopathy with rituximab.

The microangiopathic anaemia with thrombocytopenia--which can occur after haematopoietic stem cell transplant--resembles thrombotic thrombocytopenic purpura but has different pathophysiology and does not respond to plasma exchange. We describe a patient with severe manifestations of this disorder who recovered promptly following treatment with rituximab, an anti-CD20 antibody.