Coinheritance of hereditary spherocytosis with haemochromatosis: next-generation sequencing reveals.

We report the case of a man in his 50s with extravascular haemolysis, fluctuating indirect hyperbilirubinaemia, elevated transferrin saturation with hyperferritinaemia and normal liver enzymes. Spherocytes were detected in a blood smear and a mutation of unknown significance, c.1626+1G>A p.?, in intron 13 of the SLC4A1 gene, was identified by next-generation sequencing (NGS). The same mutation was found in his daughter, who presented with similar laboratory changes, confirming the diagnosis of hereditary spherocytosis. Abdominal MRI showed hepatosplenomegaly with hepatic iron overload. In this context of haemolysis (without anaemia) and iron overload, a diagnosis of haemochromatosis was presumed. NGS confirmed the presence of the variants p.(His63Asp) and p.(Cys282Tyr) in heterozygosity in the HFE gene. We report this case for the rarity of co-existing two haematological diseases counteracting each other.

ZAP-70 mutation: a case with familial autoimmune haemolytic anaemia and immune deficiency.

Zeta-chain associated protein kinase 70 kDa (ZAP-70) deficiency is one of the rare immunodeficiency disorders due to autosomal recessive homozygous or compound heterozygous loss-of-function mutations in the ZAP-70 GENE In the literature, patients with ZAP-70 deficiency have been reported with a broad spectrum of clinical manifestations including recurrent respiratory infections (81.8%), cutaneous involvement (57.9%), lymphoproliferation (32.4%), autoimmunity (19.4%), enteropathy (18.4%) and increased risk of malignancies (8.1%). The most common immunological phenotype in those patients was low CD8+ T cell counts (97.9%) and normal non-functioning CD4+ T cell. Haematopoietic stem cell transplantation was applied as a curative treatment for this disorder.

VEXAS syndrome presenting as diffuse alveolar haemorrhage.

We report the case of a man in his late 30s who presented with a history of breathlessness and cough with haemoptysis. Complete blood counts revealed pancytopenia. High-resolution CT showed diffuse bilateral ground glass opacities. Sequential bronchoalveolar lavage confirmed alveolar haemorrhage. Bone marrow aspiration showed vacuoles in erythroid and myeloid precursor cells. The genome was sequenced, and the UBA1 gene revealed a c.121 A>G mutation (p.Met41Val), confirming vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic syndrome. The patient was managed with high-dose prednisolone pulse therapy. He improved with the complete resolution of the alveolar haemorrhage and an improvement in lung function and cytopenias.

Rapid progression from MDS to AML with gastric submucosal tumour as an extramedullary infiltration.

We present a rare case of myeloid sarcoma in the stomach of an elderly woman initially diagnosed with anaemia. Myeloid sarcoma, an unusual extramedullary manifestation of acute myeloid leukaemia (AML), primarily affects lymph nodes, bones, spine and skin, with gastrointestinal involvement being infrequent. Despite normal results from the initial endoscopy, a follow-up examination after 4 months revealed multiple submucosal gastric tumours. These developments coincided with worsening of anaemia and an increase in peripheral myeloblasts. Pathological evaluation and immunohistochemical staining confirmed gastric extramedullary infiltration associated with AML. This case highlights the importance of comprehensive diagnostic processes when suspecting leukaemic transformations, especially in myelodysplastic syndrome (MDS). Due to financial constraints, additional critical studies such as cytogenetics and next-generation sequencing were not performed. Nonetheless, this rare case demonstrates the visual observation of rapid progression from MDS to AML and concurrent early myeloid sarcoma development in an elderly patient.

Acute deep vein thrombosis with concurrent new diagnosis of AL-amyloid-induced factor X deficiency.

Acquired factor X (FX) deficiency is a rare but well-documented clinical feature of AL amyloidosis. Patients with FX deficiency can present with clinically significant bleeding diathesis due to the adsorption of circulating FX to amyloid fibrils. Here, we report an unusual case of a man in his 60s who presented with 6 months of intermittent bruising, labs demonstrating new FX deficiency, elevated free lambda light chains for underlying AL amyloidosis and concurrent new peroneal vein thrombosis. This is the first report of concurrent thrombotic complications in the setting of AL-amyloid-induced FX deficiency. We discuss the diagnostic and therapeutic conundrum of diagnosing AL amyloidosis with bruising as the leading clinical symptom and the management of acute deep vein thrombosis in the setting of FX deficiency.

Ischaemic stroke in a patient with non-valvular atrial fibrillation (NVAF) despite non-vitamin K oral anticoagulant (NOAC) therapy.

Primary stroke prevention in non-valvular atrial fibrillation (NVAF) is primarily with non-vitamin K oral anticoagulant (NOAC) therapy. However, 20-36% of ischaemic strokes seem to occur in patients with atrial fibrillation while already on anticoagulation. We present a case of an ischaemic stroke in an elderly female in her 70s with medical history significant for hypertension and NVAF. She had a CHA2DS2-VASc score of 3 and was on apixaban for thromboprophylaxis. She presented with neurological deficits consistent with a left middle cerebral artery stroke, confirmed via head imaging; the most likely stroke aetiology was determined to be cardioembolic in the setting of NVAF. She was treated with continuation of her apixaban at the same dosage She displayed improved function, although with residual expressive aphasia at her 2-month neurology follow-up. Cardioembolic ischaemic stroke in NVAF despite current NOAC therapy does not have current management guidelines.

Primary cerebral immunoglobulin light chain amyloidoma in a patient with multiple sclerosis.

A man in his 60s, known with multiple sclerosis, presented with seizures and paresis of the left arm and leg. Brain imaging showed a white matter lesion, right parietal, which was progressive over the last 6 years and not typical for multiple sclerosis. Brain biopsy showed a B-cell infiltrate with IgA lambda monotypic plasma cell differentiation and amyloid deposits, typed as lambda immunoglobulin light chain (AL). Bone marrow biopsy and PET/CT ruled out a systemic lymphoma. Extended history taking, blood and urine testing (including cardiac biomarkers) identified no evidence of systemic amyloidosis-induced organ dysfunction.Primary cerebral AL amyloidoma is a very rare entity where optimal treatment is difficult to assess. The patient was treated with locally applied volumetric modulated arc radiotherapy, 24 Gy, divided in 12 fractions. Afterwards, the paresis of the left arm partially resolved, and the function of the left leg improved. Seizures did not occur anymore.

Aplastic anaemia following antibiotic use for urinary tract infection.

Aplastic anaemia is often associated with recent viral illnesses to include EBV and parvovirus along with certain medications such as anticonvulsants and sulfa containing antibiotics. We describe a case report of a female patient in her 70s who presented with pancytopenia after being treated with nitrofurantoin and ciprofloxacin for suspected urinary tract infection. She underwent an extensive workup to rule out alternative aetiologies of her pancytopenia to include a broad viral, autoimmune and malignancy evaluation which were unrevealing. Given her recent exposure to ciprofloxacin and nitrofurantoin and marrow recovery following removal of these agents, it was presumed that antibiotic exposure was the underlying cause of her aplastic anaemia.

Extranodal diffuse large B-cell lymphoma involving the uterine cervix.

This is a case of primary diffuse large B-cell lymphoma involving the uterine cervix which presented with irregular vaginal bleeding. The diagnosis was confirmed following multiple cervical biopsies. Treatment with a combination of immunotherapy, chemotherapy (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP)) and radiotherapy produced a good response.

Bilateral myelomatous pleural effusions: an unusual presentation in newly diagnosed multiple myeloma.

Multiple myeloma is a rare haematological malignancy characterised by the clonal proliferation of plasma cells within the bone marrow. Typical manifestations include bone pain, fatigue and monoclonal protein elevation in serum and urine. Less than 1% of cases develop myelomatous pleural effusion, a severe complication indicative of advanced disease and a very poor prognosis.Here, we present a case of a woman with a new diagnosis of multiple myeloma complicated by bilateral myelomatous pleural effusions as the initial presentation. This case underscores the diverse clinical spectrum of multiple myeloma, the significance of timely diagnosis and the threatening implications associated with myelomatous pleural effusions.

Interesting case of regional left ventricular hypertrophy.

This is an account of an interesting case with an unusual cardiac presentation. He is a man in his 60s who presented with chest tightness to the accident and emergency unit. The initial thoughts were of acute coronary syndrome or acute aortic syndrome. The initial set of investigations was non-conclusive. His echocardiogram which was done during hospital admission showed asymmetric hypertrophy of the heart muscle. It was prudent to assess that new finding with an MRI scan. The patient presented to the hospital twice during the investigation and was treated for a lower respiratory tract infection. The MRI report showed an interventricular mass lesion extending to the right ventricular free wall with angiosarcoma being high up in the differential diagnosis. Going through the heart team discussion, the decision was to go for a transcatheter biopsy. The biopsy showed B-cell lymphoma. The treatment started and interestingly with satisfactory results.

Myomatous erythrocytosis syndrome: a uterine fibroid associated with polycythaemia.

Myomatous erythrocytosis syndrome (MES) is a rare form of secondary erythrocytosis seen with myomas. Here, we present a case of a postmenopausal, nulliparous woman in her 50s incidentally found to have asymptomatic erythrocytosis on routine laboratory work. She was found to have an 18.5 cm myoma and after surgical resection, the patient's haematological values returned to normal ranges after a few weeks. This established the diagnosis as MES. The aetiology of MES continues to remain unknown but is most likely caused by an autonomous production of erythropoietin from the myomatous tissue. This case highlights obtaining a detailed history and physical examination to differentiate between the different causes of erythrocytosis, considering MES as a rare cause of secondary erythrocytosis and to prevent unnecessary procedures such as phlebotomy as surgery is the mainstay of treatment.

Aggressive precursor B cell ALL of cervix with obstructive uropathy.

Involvement of the cervix with acute lymphoblastic leukaemia (ALL) is extremely rare. In this case report, we discuss an unmarried woman in her early 20s, who presented in the emergency with lower abdominal pain and irregular vaginal bleeding for 1 month. Clinical examination and imaging revealed a large cervical mass probably neoplastic with obstructive uropathy. On evaluation, she was diagnosed incidentally with CALLA-positive precursor B cell ALL in peripheral blood flow cytometry. Involvement of B cell ALL in cervical mass was confirmed by histopathological examination of cervical biopsy and immunohistochemistry markers. Her history was not suggestive of signs and symptoms pertaining to leukaemia. Literature is sparse with only a few cases reporting cervical leukaemic infiltration. The present case report is a rarest case where the primary/initial presentation of precursor B cell ALL was seen with cervical involvement and obstructive uropathy mimicking characteristics of advanced cervical malignancy.

Hypereosinophilic syndrome: a rare cause of ST-elevation myocardial infarction and thrombus formation on the aortic valve.

We present a case of a man in his 30s presenting with ST-segment elevation myocardial infarction and eosinophilia. The patient underwent thrombus aspiration and initially echocardiographic evaluation was normal. The patient was discharged after 2 days, but was hospitalised again after 6 days. Echocardiographic evaluation now revealed a thrombus formation on the aortic valve. Laboratory data revealed increasing eosinophilia, and treatment with high-dosage corticosteroids and hydroxyurea was initiated as eosinophilic disease with organ manifestations could not be precluded. Eosinophils normalised and the patient was discharged again. The combination of hypereosinophilia and absence of infection, rheumatological disorders and malignancy, led to reactive or idiopathic hypereosinophilic syndrome being the most plausible diagnoses. The patient was closely monitored in the cardiology and haematology outpatient clinics. Echocardiographic evaluation, performed 6 weeks after the patient was discharged, showed significant regression in the size of the thrombus mass.

Extramedullary relapse of multiple myeloma presenting as space-occupying lesion in liver treated with daratumumab, pomalidomide, dexamethasone and bendamustine.

Extramedullary relapse in patients with multiple myeloma (MM) is often associated with loss of biochemical response and the appearance of measurable residual disease in the bone marrow. Fever is an unusual presenting manifestation of MM. Treatment of extramedullary relapse in patients progressing on proteasome inhibitors, anti-CD38 monoclonal antibodies and immunomodulatory drugs is challenging, as access to chimeric antigen receptor T-cells and bispecific antibodies is limited. We report a case of relapsed MM who presented with fever and hepatic space-occupying lesion mimicking hepatocellular carcinoma. In this case report, we also present our experience of using a novel combination regimen comprising Dara-Pom-Benda-Dexa (daratumumab, pomalidomide, dexamethasone and bendamustine) for relapsed MM.

Detection of novel duplication variant in ADAMTS13 gene using chromosomal microarray analysis.

We present a case of a child with congenital thrombotic thrombocytopenic purpura found to have a compound heterozygous variant in the ADAMTS13 gene with a novel variant resulting in a large duplication of exons 9-11 of ADAMTS13 This variant was identified through additional molecular testing via a chromosomal microarray analysis. To our knowledge, this assay had not previously been utilised to identify an ADAMTS13 variant and the additional testing was possible through the involvement of a genetic counsellor.

Atypical haemolytic uremic syndrome in a patient with severe Babesiosis.

Babesiosis is a tick-borne parasitic infection that can result in various haematological complications. This case report discusses a patient with severe Babesiosis complicated by an unorthodox presentation of Babesiosis-associated haemolytic uremic syndrome. Discussed here is the patient's clinical course and the management strategies employed, with an emphasis on early recognition and treatment of renal failure in the context of severe Babesiosis. Haematologic manifestations of Babesia are common and the severity of disease is dependent on parasite load. While treatment options such as red blood cell exchange have been proposed for severe cases, their impact on clinical outcomes is limited and they may not be readily available in resource-limited settings. Traditional management using antimicrobials has been proposed but there is limited discussion about managing unique presentations such as renal failure in Babesiosis. Hence, understanding the pathophysiology, early recognition and aggressive treatment strategies can optimise clinical outcomes and reduce mortality.

Falsely low glycosylated haemoglobin levels probably secondary to hypersplenism in a patient with diabetes mellitus.

A man in his 70s presented with a history of low glycated haemoglobin (HbA1c) values despite a diagnosis of type 2 diabetes. His blood glucose readings ranged between 8 and 15 mmol/L, but his HbA1c values were below 27 mmol/mol. Initial investigations demonstrated evidence of reduced red blood cell lifespan as a cause of misleadingly low HbA1c values. Further investigation revealed chronic liver disease and splenomegaly, with hypersplenism being the probable cause of increased red blood cell turnover. HbA1c estimation was no longer reliable, so ongoing diabetic care was guided by home capillary blood glucose monitoring. Healthcare providers and clinical laboratorians need to be aware of the possible clinical implications of very low HbA1c values in patients with type 2 diabetes.

Classic paroxysmal nocturnal haemoglobinuria presenting with intestinal malabsorption syndrome, acute abdomen and acute kidney injury.

A male patient in his 30s presented with complaints of acute abdominal pain, black stools and red-coloured urine. CT revealed thrombi in the splenic and left renal veins, leading to infarctions. An endoscopy displayed scalloping of the duodenal folds, indicative of intestinal malabsorption syndrome (IMS). Histopathological examination confirmed IMS. Due to the presence of intravascular haemolysis, haemoglobinuria and thrombotic complications, paroxysmal nocturnal haemoglobinuria (PNH) was suspected and subsequently confirmed by flow cytometry. Thus, a diagnosis of classic PNH with IMS and thrombotic complications was established. This unique case highlights the coexistence of PNH and IMS, resembling the complement hyperactivation, angiopathic thrombosis and protein-losing enteropathy disease, suggesting potential shared pathophysiology.

Recurrent steroid-responsive polyserositis of unclear aetiology: a possible post-COVID-19 phenomenon.

A previously healthy male patient presented with relapsing serous effusions affecting the pleural, pericardial and peritoneal membranes, along with thrombocytopaenia, following infection with COVID-19. An extensive workup was performed to rule out potential causes of polyserositis, including an infectious disease screen, autoantibody testing and imaging; however, no clear other cause was found. He exhibited a robust response to high-dose corticosteroid therapy but experienced several recurrences on tapering of treatment. His clinical course and treatment response were most suggestive of an autoimmune or autoinflammatory cause of polyserositis, though without confirmation of a specific underlying diagnosis. This report builds on existing literature on a possible link between COVID-19 and polyserositis.