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 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 ( <0.001) and α-thalassaemia ( = 0.0035), but not in β-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.
Blood Protein Electrophoresis ; Electrophoresis, Capillary ; Erythrocyte Inclusions ; pathology ; Erythrocyte Indices ; Female ; Genetic Testing ; Hemoglobin H ; analysis ; Humans ; Male ; Mass Screening ; Pregnancy ; Pregnancy Complications, Hematologic ; blood ; diagnosis ; Retrospective Studies ; Sensitivity and Specificity ; Singapore ; alpha-Thalassemia ; blood ; diagnosis

INTRODUCTIONDirect oral anticoagulants (DOACs) are establishing themselves as principle choices for the treatment of a variety of thrombotic disorders. DOACs are also known to affect common coagulation tests which are routinely performed for patients in clinical practice. An understanding of their varied effects is crucial for the appropriate ordering of coagulation tests and their interpretation.

MATERIALS AND METHODSLaboratories in public and private healthcare institutions and commercial sectors were surveyed on coagulation tests offered and their methods. A Medline and bibliography search, including a search on search engines, was performed for publications reporting the effects of dabigatran, apixaban and rivaroxaban on these coagulation tests. These papers were reviewed and summarised for consensus recommendations.

RESULTSProthrombin time (PT) and activated partial thromboplastin time (aPTT) are variably affected by the DOACs and dependent of the coagulation assays used. Clinicians must know which laboratory has performed these tests to logically interpret test results. A normal PT or aPTT does not exclude the presence of residual DOACs effect. The thrombin time is sensitive to dabigatran but not apixaban or rivaroxaban. Specialised coagulation tests such as thrombophilia tests are also variably affected by the DOACs. All laboratories in Singapore however, employ similar test methods permitting a common set of recommendations for specialised coagulation testing.

CONCLUSIONKnowledge of the effects of DOACs on coagulation testing is essential to determine the appropriateness of performing such tests and interpreting them coherently. Practical recommendations which are tests and location-specific are set out in this paper.

Antithrombins ; therapeutic use ; Blood Coagulation Tests ; Dabigatran ; therapeutic use ; Factor Xa Inhibitors ; therapeutic use ; Humans ; Partial Thromboplastin Time ; Practice Guidelines as Topic ; Prothrombin Time ; Pyrazoles ; therapeutic use ; Pyridones ; therapeutic use ; Rivaroxaban ; therapeutic use ; Singapore

INTRODUCTION: We aimed to describe the extrapulmonary manifestations of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, including their frequency, onset with respect to respiratory symptoms, pathogenesis and association with disease severity. METHODS: We searched the MEDLINE and Embase databases for SARS-CoV-2-related studies. Meta-analysis, observational studies, case series and case reports published in English or Chinese between 1 January 2020 and 1 May 2020 were included. Reports with only paediatric or obstetric cases were excluded. RESULTS: 169 articles were included. Early manifestations (preceding respiratory symptoms until Day 6 of onset) included olfactory and gustatory disturbance (self-reported in up to 68% and 85% of cases, respectively), gastrointestinal symptoms (up to 65.9%) and rash (up to 20.4%). From Day 7 onwards, hypercytokinaemia, paralleled multi-organ complications including acute cardiac injury (pooled incidence of 17.7% in 1,412 patients, mostly with severe disease and 17.4% mortality), kidney and liver injury (up to 17% and 33%, respectively) and thrombocytopenia (up to 30%). Hypercoagulability resulted in venous thromboembolic events in up to 31% of all patients. Uncommon disease presentation and complications comprised Guillain-Barré syndrome, rhabdomyolysis, otitis media, meningoencephalitis and spontaneous pneumomediastinum. CONCLUSION Although the systemic manifestations of SARS-CoV-2 infection are variegated, they are deeply interwoven by shared mechanisms. Two phases of extrapulmonary disease were identified: (a) an early phase with possible gastrointestinal, ocular and cutaneous involvement; and (b) a late phase characterised by multiorgan dysfunction and clinical deterioration. A clear, multidisciplinary consensus to define and approach thromboinflammation and cytokine release syndrome in SARS-CoV-2 is needed.
Humans ; Asian People ; COVID-19/complications* ; Inflammation/complications* ; SARS-CoV-2 ; Thrombosis