Clinical and health-related quality of life outcomes of transfusion-dependent thalassaemia patients in Singapore.

INTRODUCTION: Transfusion-dependent thalassaemia is associated with complications related to iron overload from frequent red cell transfusions which affect quality of life. We collected data on the clinical outcomes, complications, socioeconomic status and health-related quality of life (HRQoL) of transfusion-dependent thalassaemia patients in Singapore, and analysed the associations between clinical and socioeconomic factors with development of transfusion-related complications and HRQoL scores. MATERIALS AND METHODS: This was a cross-sectional study of transfusion-dependent thalassaemia patients treated at four major public hospitals in Singapore. Clinical information was obtained from retrospective reviews of medical records. Socioeconomic data and patient-reported compliance to iron chelators were obtained from prospective interviews of patients or caregivers using a questionnaire. A validated, disease-specific HRQoL instrument, the TranQOL, was administered to patients and caregivers during a routine clinic or transfusion visit. RESULTS: Liver iron loading was the most common transfusion-related complication and occurred in 79% of patients. Cardiac iron loading was noted in 28.3% and endocrine complications were present in 34.2%. Liver iron loading was significantly associated with higher mean ferritin level. Cardiac iron loading was significantly associated with increasing age, higher mean ferritin level and type of iron chelator. Endocrine complications were associated with increasing age, higher mean ferritin level, type of iron chelator and poorer patient-reported compliance to iron chelators. The lowest TranQOL scores were reported by caregiver parents of patients aged less than 18 years. Lower TranQOL scores were significantly associated with increasing age, especially in the 31-50 age cohort, and with reception of social assistance. CONCLUSION: The main morbidities noted in transfusion-dependent thalassaemia patients in Singapore are from complications associated with iron loading. The cohort of older thalassaemia patients aged 31-50 experienced significantly higher rates of cardiac iron loading, endocrine complications and lower TranQOL scores compared to younger age cohorts.

An unusual presentation of Idiopathic hypereosinophilic syndrome.

Hypereosinophilic syndrome (HES) is a rare but life-threatening multi-organ disease which can be complicated by stroke, with devastating outcomes. Eosinophils can accumulate in multiple organs, most commonly involving the heart, skin, lungs, spleen, and liver. Neurological end-organ complications in hypereosinophilic syndrome are unusual and have been established to be of three types: brain infarction, encephalopathy and sensory polyneuropathy. We present a case where acute ischaemic stroke and encephalopathy are early manifestations of Idiopathic HES. It is important to consider HES as an aetiology for stroke and a high eosinophil count is an initial diagnostic clue. Early initiation of steroid therapy can potentially prevent disease progression.

Coinheritance of High Oxygen Affinity Hb Helsinki [HBB: c.248A>T; ß82(EF6)Lys→Met] with Hb H Disease.

Hb Helsinki [HBB: c.248A>T; ß82(EF6)Lys→Met] is a high oxygen affinity hemoglobin (Hb) causing polycythemia, whereas Hb H (ß4) disease causes mild to severe chronic hemolytic anemia. The clinical characteristics, gel electrophoresis, capillary electrophoresis (CE) and molecular genotyping of a case of Hb Helsinki coinherited with Hb H disease in an ethnic Malay is described, illustrating the interaction between the ß-globin variant and coinheritance of three α gene deletions. The proband was asymptomatic, exhibited microcytosis and a normal with Hb value.

Bitten by a bug or a bag? Transfusion-transmitted dengue: a rare complication in the bleeding surgical patient.

BACKGROUND: Blood-borne infections remain a risk of blood transfusions. While routine screening of donated blood products has greatly reduced the risk of human immunodeficiency virus, hepatitis B, and hepatitis C transmission, arboviruses such as dengue, chikungunya, and the West Nile virus remain significant risks especially during outbreaks. CASE REPORT: We report a rare case of dengue documented to be acquired through a blood transfusion, which resulted in severe thrombocytopenia prolonging admission in hospital in a neurosurgical patient. RESULTS: The donor of one of the units of red blood cells presented with dengue fever 2 days after donating. Sanger sequencing confirmed DENV-2 (dengue virus, Serotype 2) in both the donor and the patient samples and showed 100% nucleotide sequence identity between the two viruses, confirming transfusion-transmitted dengue infection. CONCLUSION: This case highlights the importance of arboviral screening of donor blood, especially for populations in endemic areas during outbreaks.

Venous thromboembolism in an Asian COVID-19 cohort across 3 infection waves-a retrospective observational study.

Background: A high incidence of venous thromboembolism (VTE) in COVID-19 has led to international recommendations for thromboprophylaxis. With limited data on Asian patients with COVID-19, the role of thromboprophylaxis remains unclear. Objectives: To investigate the in-hospital incidence of VTE in an Asian COVID-19 cohort, describe the VTE trend through successive COVID-19 waves (wild-type, delta, and omicron), and characterize the risk factors for VTE. Methods: We performed a retrospective observational cohort study of hospitalized COVID-19 adults from January 2020 to February 2022. Objectively confirmed VTE were reviewed to obtain VTE incidence and trend. Subset analysis of critical (intensive care), moderate (oxygen supplementation), and mild cases hospitalized ≥5 days was performed to investigate risk factors and in-hospital hazards of VTE. Results: Sixteen VTE events occurred among 3574 patients. Overall, VTE incidence was 0.45%, or 0.21% in mild, 3.60% in moderate, and 5.38% in critical infection. The maximum cumulative risk of VTE was 1.14% at 14 days for mild, 8.13% at 21 days for moderate, and 11.55% at 35 days for critical infection. Thromboprophylaxis use in mild, moderate, and critical cases was 5.7%, 28.8%, and 81.7%, respectively. In multivariable analysis, the severity of infection remained the strongest independent predictor of VTE. Compared with mild infection, the relative risk was 8.26 (95% CI, 2.26-30.16) for critical infection and 6.29 (95% CI, 1.54-25.67) for moderate infection. Conclusion: Overall, VTE incidence in Asian patients with COVID-19 is <1% across successive waves. Patients with moderate and critical infections are at greater risk for VTE and should be considered for routine thromboprophylaxis.

Severe Thrombocytopenia, Thrombosis and Anti-PF4 Antibody after Pfizer-BioNTech COVID-19 mRNA Vaccine Booster-Is It Vaccine-Induced Immune Thrombotic Thrombocytopenia?

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a serious and life-threatening complication occurring after adenovirus-vector COVID-19 vaccines, and is rarely reported after other vaccine types. Herein, we report a case of possible VITT after the Pfizer-BioNTech mRNA vaccine booster, who presented with extensive lower limb deep vein thrombosis, severe thrombocytopenia, markedly elevated D-dimer and positive anti-PF4 antibody occurring 2 weeks post-vaccination, concurrent with a lupus anticoagulant. A complete recovery was made after intravenous immunoglobulin, prednisolone and anticoagulation with the oral direct Xa inhibitor rivaroxaban. The presenting features of VITT may overlap with those of antiphospholipid syndrome associated with anti-PF4 and immune thrombocytopenia. We discuss the diagnostic considerations in VITT and highlight the challenges of performing VITT confirmatory assays in non-specialized settings. The set of five diagnostic criteria for VITT is a useful tool for guiding initial management, but may potentially include patients without VITT. The bleeding risks of severe thrombocytopenia in the face of thrombosis, requiring anticoagulant therapy, present a clinical challenge, but early recognition and management can potentially lead to favorable outcomes.

Image Analysis Using Machine Learning for Automated Detection of Hemoglobin H Inclusions in Blood Smears - A Method for Morphologic Detection of Rare Cells.

BACKGROUND: Morphologic rare cell detection is a laborious, operator-dependent process which has the potential to be improved by the use of image analysis using artificial intelligence. Detection of rare hemoglobin H (HbH) inclusions in red cells in the peripheral blood is a common screening method for alpha-thalassemia. This study aims to develop a convolutional neural network-based algorithm for the detection of HbH inclusions. METHODS: Digital images of HbH-positive and HbH-negative blood smears were used to train and test the software. The software performance was tested on images obtained at various magnifications and on different scanning platforms. Another model was developed for total red cell counting and was used to confirm HbH cell frequency in alpha-thalassemia trait. The threshold minimum red cells to image for analysis was determined by Poisson modeling and validated on image sets. RESULTS: The sensitivity and specificity of the software for HbH+ cells on images obtained at ×100, ×60, and ×40 objectives were close to 91% and 99%, respectively. When an AI-aided diagnostic model was tested on a pilot of 40 whole slide images (WSIs), good inter-rater reliability and high sensitivity and specificity of slide-level classification were obtained. Using the lowest frequency of HbH+ cells (1 in 100,000) observed in our study, we estimated that a minimum of 2.4 × 106 red cells would need to be analyzed to reduce misclassification at the slide level. The minimum required smear size was validated on 78 image sets which confirmed its validity. CONCLUSIONS: WSI image analysis can be utilized effectively for morphologic rare cell detection. The software can be further developed on WISs and evaluated in future clinical validation studies comparing AI-aided diagnosis with the routine diagnostic method.

Getting patient blood management Pillar 1 right in the Asia-Pacific: a call for action.

Preoperative anaemia is common in the Asia-Pacific. Iron deficiency anaemia (IDA) is a risk factor that can be addressed under patient blood management (PBM) Pillar 1, leading to reduced morbidity and mortality. We examined PBM implementation under four different healthcare systems, identified challenges and proposed several measures: (a) Test for anaemia once patients are scheduled for surgery. (b) Inform patients about risks of preoperative anaemia and benefits of treatment. (c) Treat IDA and replenish iron stores before surgery, using intravenous iron when oral treatment is ineffective, not tolerated or when rapid iron replenishment is needed; transfusion should not be the default management. (d) Harness support from multiple medical disciplines and relevant bodies to promote PBM implementation. (e) Demonstrate better outcomes and cost savings from reduced mortality and morbidity. Although PBM implementation may seem complex and daunting, it is feasible to start small. Implementing PBM Pillar 1, particularly in preoperative patients, is a sensible first step regardless of the healthcare setting.

Evaluation of Thalassaemia Screening Tests in the Antenatal and Non-Antenatal Populations in Singapore.

INTRODUCTION: Haemoglobinopathy testing is performed for carrier screening and evaluation of microcytic anaemia. We evaluated the effectiveness of thalassaemia screening tests at our institution and suggest ways of improving the testing algorithm. MATERIALS AND METHODS: A total of 10,084 non-antenatal and 11,364 antenatal samples with alkaline gel electrophoresis (AGE), capillary electrophoresis (CE), haemoglobin H (HbH) inclusion test, mean corpuscular haemoglobin (MCH) and mean corpuscular volume (MCV) were retrospectively reviewed. A subgroup of 187 samples with genetic testing was correlated with HbH inclusions and MCH/ MCV. The effect of iron deficiency on percentage hemoglobin A2 (HbA2) was studied. RESULTS: HbH inclusion test showed low sensitivity of 21.43% for α-thalassaemia mutations but higher sensitivity of 78.95% for --SEA deletion. By receiver operating characteristic (ROC) analysis, MCH ≤28 pg or MCV ≤80 fl for non-antenatal samples and MCH ≤27 pg or MCV ≤81 fl for antenatal samples had >98% sensitivity for HbH inclusions. Above these thresholds, the probability that HbH inclusions would be absent was <99% (negative predictive value [NPV] >99%). MCH ≥28 pg had 100% sensitivity (95% CI 95.63%-100%) for α-thalassaemia mutations and 97.68% calculated NPV in the antenatal population. Detection of haemoglobin variants by CE correlated highly with AGE (99.89% sensitivity, 100% specificity). Severe iron deficiency reduced HbA2 in hemoglobin (P <0.001) and α-thalassaemia (P = 0.0035), but not in ß-thalassaemia. CONCLUSION: MCH/MCV thresholds have adequate sensitivity for α-thalassaemia in the antenatal population, and genotyping plays an important role as HbH inclusion test shows low sensitivity. CE without AGE, may be used as initial screening for haemoglobin variants. Our study provides contemporary data to guide thalassaemia screening algorithms in Singapore.

Plasmodium knowlesi infection: a diagnostic challenge.

Plasmodium knowlesi malaria is an uncommon, but highly prevalent parasitic infection in parts of Malaysia. This is the case of a 14-year-old Singaporean boy presenting to our emergency department with an 11-day history of fever following a school trip to Malaysia. Hepatosplenomegaly was the only clinical finding; laboratory tests showed thrombocytopaenia, lymphopaenia, mild anaemia and liver transaminitis. Specific malaria antigen tests were negative, but the peripheral blood film showed plasmodia with atypical features, with a parasite load of 0.5%. PCR confirmed the diagnosis of P knowlesi. The patient was successfully treated with chloroquine. The clinical course of P knowlesi malaria is indistinguishable from that of Plasmodium falciparum. This case highlights the importance of taking detailed travel history, careful examination of malaria blood films and judicious use of molecular techniques. Antigen tests alone may have missed a malaria diagnosis altogether, while blood film examination may wrongly identify the species as Plasmodium malariae or P falciparum. Third-generation PCR assays can be used to reliably identify P knowlesi.

Monkey malaria in humans: a diagnostic dilemma with conflicting laboratory data.

Plasmodium knowlesi has recently been recognized as the fifth Plasmodium species causing malaria in humans. Diagnosis is difficult morphologically, and currently, available rapid tests have not been comprehensively evaluated with this pathogen. We report a case of P. knowlesi malaria that was confirmed after the initial clue of discordant microscopy and immunochromatographic results, highlighting the importance of molecular diagnostics in cases with the relevant clinical and epidemiologic history.