About Pathology Uncertainty

A laboratory result is useful when its performance is understood in relation to the decision it supports. Pathology Uncertainty helps laboratory professionals ask the right questions about measurement, choose suitable evidence and recognise the limits of a conclusion.

The site connects measurement uncertainty, analytical performance specifications, method verification, method comparison, internal quality control and external quality assessment. Its focus is practical reasoning across laboratory disciplines: what does this number mean, what evidence supports it, and what should happen next?

Stephen is a Consultant Clinical Scientist in Specialist Haemostasis at Cambridge University Hospitals NHS Foundation Trust. His clinical and research work brings together assay performance, measurement uncertainty and the interpretation of laboratory results.

He completed his PhD at the University of Hertfordshire in December 2025. His research examined imprecision, analytical performance and measurement uncertainty in the laboratory assessment of thrombotic thrombocytopenic purpura. The thesis is available through the University’s research archive, where it was deposited in 2026.

Stephen tutors applied haemostasis and thrombosis and medical laboratory statistics at the University of Greenwich. He also writes educational articles for Pathology in Practice and develops online learning material. His specialist clinical background informs the examples and questions, while this website addresses principles relevant across laboratory medicine.

Research by Stephen MacDonald, including journal articles, laboratory guidance, conference abstracts, preprints and his doctoral thesis. Expand a year to browse its entries.

65 entries · 2005–2026

202613 entries

• UK laboratory consensus on coagulation testing of patients receiving marstacimab: findings from the first structured review of BASIS clinical trial dataBowyer A, Riddell A, Baker P, MacDonald S. Research and Practice in Thrombosis and Haemostasis. 2026;10.Conference abstract · ISTH poster PB2142
• The Laboratory Monitoring of Altuvoct (Efanesoctocog Alfa): Recommendations From the Laboratory Working Party of the United Kingdom Haemophilia Centres Doctor’s OrganisationBowyer AE, Khan M, Lawrence C, MacDonald S, Martin J, Platton S, et al. Haemophilia. 2026;32(1):279–283.Laboratory recommendations · First published online in 2025
• A reflex mixing strategy reduces VKA-related false positives without compromising detection of weak lupus anticoagulantCox-Morton S, MacDonald S, White D. Research and Practice in Thrombosis and Haemostasis. 2026;10.Conference abstract · ISTH poster PB1197
• Point‐Of‐Care Testing of Fibrinogen by the qLab FIB System in Patients Taking Direct Oral Anticoagulants (DOACs)Long C, MacDonald S, Myers A, Rodiera C, Agrawal S, Falter F. International Journal of Laboratory Hematology. 2026;48(5):1158–1164.
• How certain is your international normalized ratio? Measurement uncertainty, the new WHO thromboplastin standard, and what we should knowMacDonald S. Research and Practice in Thrombosis and Haemostasis. 2026;10(3):103453.Commentary
• Measurement uncertainty in the hemostasis laboratoryMacDonald S. Seminars in Thrombosis and Hemostasis. 2026;52(8):899–907.Review · First published online in 2025
• Reanchoring the international normalized ratio: the sixth World Health Organization thromboplastin standard and the next stage of prothrombin time standardizationMacDonald S. Research and Practice in Thrombosis and Haemostasis. 2026;10(6):106896.Commentary
• Diagnosis and monitoring of thrombotic thrombocytopenic purpura: Guidance for laboratories from the British Society for HaematologyMacDonald S, Pitchford T, Singh D, Fretwell R, Jenkins PV, Lawrence C, et al. British Journal of Haematology. 2026;209(3):928–938.Guideline
• Advancing the implementation of standardised reporting units for haemostasis factor assays through collaborative effortsMacDonald S, Williams S, Platton S. Clinical Chemistry and Laboratory Medicine. 2026;64(9):e201–e205.
• Studies of Imprecision, Performance and Measurement Uncertainty in Laboratory Assessment of Thrombotic Thrombocytopenic PurpuraMacDonald SG. University of Hertfordshire. 2026.Doctoral thesis · Deposited in 2026
• Influence of intra-cuvette stir-speed on light transmission platelet aggregometry on an automated haemostasis analyserPlatton S, Alaoye F, Baker P, Harper S, Jones R, Kirby R, et al. International Journal of Laboratory Hematology. 2026;48.Conference abstract · Presented at ISLH 2025 · Conference proceedings
• Evaluation of the Prevalence of Occult Fibrin in Donor Organs, Its Origins, and Consequences: Insights From the COPE StudiesWatson CJE, Jochmans I, MacDonald S, White D, Bridgeman C, Butler AJ, et al. Transplant International. 2026;39:15547.
• A pilot, two-center, sequential dose escalation safety study of alteplase with fresh frozen plasma during normothermic liver perfusionWatson CJE, MacDonald S, White D, Bridgeman C, Gaurav R, Swift L, et al. Liver Transplantation. 2026;32(7):978–990.

20253 entries

• Clinical Significance of APTT Tests and Their Correlation with Heparin Anti-Xa and Anti-IIa Activities is Transformed by Pairing with a Heparin-Resistant Recalcification Solution (HRRS)Attrill G, MacDonald S, Favaloro EJ, Dangol M, Exner T. Preprints.org. 2025.Preprint
• Deep generative classification of blood cell morphologyDeltadahl S, Gilbey J, Van Laer C, Boeckx N, Leers MPG, Freeman T, et al. Nature Machine Intelligence. 2025;7(11):1791–1803.
• How to Measure Uncertainty in Laboratory TestsMacDonald S. International Journal of Laboratory Hematology. 2025;47.Conference abstract

20243 entries

• Assessing the impact of different heparin dosing regimens for cardiopulmonary bypass on anticoagulation: the HepDOSE pilot studyLwin TN, Mudannayake R, MacDonald S, Arrowsmith JE, Burt C, Besser M, et al. Canadian Journal of Anesthesia. 2024;71(2):234–243.
• Taipan snake venom time has high sensitivity for lupus anticoagulants in non‐anticoagulated, triple positive antiphospholipid syndrome patientsMoore GW, Platton S, Yartey N, Foxton E, White D, MacDonald SG. International Journal of Laboratory Hematology. 2024;46(3):538–545.
• Practical considerations for the use of the rapid AcuStar® ADAMTS13 activity assay in the diagnosis of acute thrombotic thrombocytopenic purpura (TTP)Yong J, MacDonald S, Downey C, Fretwell R, Lawrence C, Murphy P, et al. Journal of Clinical Medicine. 2024;13(15):4462.

20235 entries

• Measurement uncertainty in the VWF-ADAMTS13 axis: the challenges of adding a calculated measurand in the haemostasis laboratoryMacDonald S. Journal of Laboratory and Precision Medicine. 2023;8:5.Review
• Triple-positive antiphospholipid syndrome does not guarantee positivity in each lupus anticoagulant assayMoore GW, Foxton E, Platton S, Yartey N, White D, MacDonald SG. Journal of Thrombosis and Haemostasis. 2023;21(12):3539–3546.
• Ex situ fibrinolytic therapy during normothermic perfusion before transplantation clears intravascular fibrin and is associated with minimal cholangiopathyWatson C, Bridgeman C, MacDonald S, Fear C, Swift L, Webster R, et al. Transplantation. 2023;107(9):188–189.Conference abstract
• Occult fibrin in deceased donor livers is associated with transplant failure and cholangiopathyWatson C, MacDonald S, Bridgeman C, Fear C, Swift L, Gaurav R, et al. Transplantation. 2023;107(9):179.Conference abstract · Conference poster
• D-dimer release from livers during ex situ normothermic perfusion and after in situ normothermic regional perfusion: evidence for occult fibrin burden associated with adverse transplant outcomes and cholangiopathyWatson CJE, MacDonald S, Bridgeman C, Brais R, Upponi SS, Foukaneli T, et al. Transplantation. 2023;107(6):1311–1321.

20222 entries

• Elucidating mechanisms of genetic cross-disease associations at the PROCR vascular disease locusStacey D, Chen L, Stanczyk PJ, Howson JMM, Mason AM, Burgess S, et al. Nature Communications. 2022;13(1):1222.
• Direct oral anticoagulants‐Remove versus Taipan snake venom time for detection of a lupus anticoagulant in patients taking oral direct factor Xa inhibitorsWhite D, Moore GW, Besser M, MacDonald S, Thomas W. Research and Practice in Thrombosis and Haemostasis. 2022;6(1):e12648.

20215 entries

• Investigation of platelet function in patients with chronic kidney disease stages IV‐VKhalid A, White D, Sharp M, Duff E, MacDonald S, Fry A, et al. International Journal of Laboratory Hematology. 2021;43(6):1606–1611.
• Direct oral anticoagulant concentrations in obese and high body weight patients: a cohort studyMartin AC, Thomas W, Mahir Z, Crowley MP, Dowling T, Breen K, et al. Thrombosis and Haemostasis. 2021;121(2):224–233.
• Current practice and registration patterns among United Kingdom Haemophilia Centre Doctors’ Organisation centers for patients with unclassified bleeding disordersThomas W, Downes K, Evans G, Gidley G, Lowe G, MacDonald S, et al. Journal of Thrombosis and Haemostasis. 2021;19(11):2738–2743.
• Thrombin generation measured by two platforms in patients with a bleeding tendency: commentThomas W, White D, MacDonald S. Journal of Thrombosis and Haemostasis. 2021;19(11):2896–2899.Comment
• Evaluation of COVID‐19 coagulopathy; laboratory characterization using thrombin generation and nonconventional haemostasis assaysWhite D, MacDonald S, Edwards T, Bridgeman C, Hayman M, Sharp M, et al. International Journal of Laboratory Hematology. 2021;43(1):123–130.

202012 entries

• Updated hospital associated venous thromboembolism outcomes with 90-days follow-up after hospitalisation for severe COVID-19 in two UK critical care unitsDoyle AJ, Thomas W, Retter A, Besser M, MacDonald S, Breen KA, et al. Thrombosis Research. 2020;196:454–456.
• Evaluation of point-of-care ACT coagulometers and anti-Xa activity during cardiopulmonary bypassFalter F, MacDonald S, Matthews C, Kemna E, Cañameres J, Besser M. Journal of Cardiothoracic and Vascular Anesthesia. 2020;34(11):2921–2927.
• Significant levels of endogenous formaldehyde in humans–a potential driver of Fanconi anaemia?Glover L, Dingler F, Cordell R, Baxter J, MacDonald S, Symington E, et al. British Journal of Haematology. 2020;189:132–133.Conference abstract · Conference supplement
• A case of acquired Glanzmann thrombasthenia post multivisceral transplantGriffin J, MacDonald S, Thomas W. British Journal of Haematology. 2020;189:262–263.Conference abstract
• Investigation of patients with unclassified bleeding disorder and abnormal thrombin generation for physiological coagulation inhibitors reveals multiple abnormalities and a subset of patients with increased tissue factor pathway inhibitor activityMacDonald S, White D, Langdown J, Downes K, Thomas W. International Journal of Laboratory Hematology. 2020;42(3):246–255.
• Characterization of a large cohort of patients with unclassified bleeding disorder; clinical features, management of haemostatic challenges and use of global haemostatic assessment with proposed recommendations for diagnosis and treatmentMacDonald S, Wright A, Beuche F, Downes K, Besser M, Symington E, et al. International Journal of Laboratory Hematology. 2020;42(2):116–125.
• Elucidating mechanisms of genetic cross-disease associations: an integrative approach implicates protein C as a causal pathway in arterial and venous diseasesStacey D, Chen L, Howson JMM, Mason AM, Burgess S, MacDonald S, et al. medRxiv. 2020.Preprint · Later journal article listed under 2022
• Does age‐adjusted D‐dimer have a role in assessment of VTE recurrence rates? CommentThomas W, Mindlina I, MacDonald S, Besser M. International Journal of Laboratory Hematology. 2020;42(5):e240.Comment
• Heparin failure and COVID-19: should we explore other anticoagulants? An observational report regarding in-vitro recovery of anticoagulant action in COVID-19 patients in intensive careThomas W, White D, Cox-Morton S, MacDonald S, Besser M. Thrombosis Research. 2020;195:226–227.
• Diagnostic work up of patients with increased bleeding tendency: CommentThomas W, White D, MacDonald S, Downes K, Obaji S, Desborough M. Haemophilia. 2020;26(4):e209–e210.Comment
• Correction to: Heparin resistance in COVID-19 patients in the intensive care unitWhite D, MacDonald S, Bull T, Hayman M, de Monteverde-Robb D, Sapsford D, et al. Journal of Thrombosis and Thrombolysis. 2020;50(2):478.Correction
• Heparin resistance in COVID-19 patients in the intensive care unitWhite D, MacDonald S, Bull T, Hayman M, de Monteverde-Robb D, Sapsford D, et al. Journal of Thrombosis and Thrombolysis. 2020;50(2):287–291.

20193 entries

• Single centre audit of testing F8 genetics and identifying the p. Tyr365Cys mutation in mild haemophilia A: implications for patient care and resourcesChengal R, MacDonald S, Symington E, Thomas W. British Journal of Haematology. 2019;185:135.Conference abstract · Conference supplement
• A diagnostic solution for haemostasis laboratories for patients taking direct oral anticoagulants using DOAC‐RemoveCox‐Morton S, MacDonald S, Thomas W. British Journal of Haematology. 2019;187(3):377–385.
• Utility of the DASH score after unprovoked venous thromboembolism; a single centre studyMacDonald S, Chengal R, Hanxhiu A, Symington E, Sheares K, Besser M, et al. British Journal of Haematology. 2019;185(3):631–633.

20182 entries

• Multiple centre evaluation study of ADAMTS13 activity and inhibitor assaysLangley K, Fretwell R, Kitchen S, MacDonald S, Dutt T, Baker P, et al. International Journal of Laboratory Hematology. 2018;40(1):21–25.
• Clinical bleeding and thrombin generation in admissions to critical care with prolonged prothrombin time: an exploratory studyStanworth SJ, Desborough MJR, Simons G, Seeney F, Powter G, MacDonald S, et al. Transfusion. 2018;58(6):1388–1398.

20162 entries

• Acquired hypofibrinogenemia: current perspectivesBesser MW, MacDonald SG. Journal of Blood Medicine. 2016;7:217–225.Review
• Impedance platelet aggregometry for surveillance of ibrutinib therapy in chronic lymphocytic leukaemiaThomas W, Kazianka L, MacDonald S, Ringshausen I, Follows G, Pabinger I, et al. Journal of Thrombosis and Haemostasis. 2016;14:81.Conference abstract · Conference proceedings

20151 entry

• The risk of a first and a recurrent venous thrombosis associated with an elevated D‐dimer level and an elevated thrombin potential: results of the THE‐VTE studyvan Hylckama Vlieg A, Baglin CA, Luddington R, MacDonald S, Rosendaal FR, Baglin TP. Journal of Thrombosis and Haemostasis. 2015;13(9):1642–1652.

20145 entries

• Pharmacokinetics of a new high purity factor X concentrate in subjects with severe or moderate factor X deficiencyAustin S, Alvarez MT, Auerswald G, Bermejo N, Kavakli K, Mitchell W, et al. Haemophilia. 2014;20:20.Conference abstract
• Safety and efficacy of a new high purity factor X concentrate in subjects with factor X deficiency undergoing surgeryEscobar M, Millar C, Austin S, Auerswald G, MacDonald S, Norton M, et al. Haemophilia. 2014;20:23.Conference abstract · NHS evidence review
• Efficacy and safety of a new high purity factor X concentrate in the treatment of severe or moderate factor X deficiencyKavakli K, Austin S, Alvarez MT, Auerswald G, Bermejo N, Mitchell W, et al. Haemophilia. 2014;20:20.Conference abstract · NHS evidence review
• ISO 15189:2012, uncertainty of measurement and laboratory haematologyMacDonald S. International Journal of Laboratory Hematology. 2014;36:129–130.Conference abstract
• Safety of a new high purity factor X concentrate in the management of hereditary factor X deficiencyNorton M, Mitchell WB, Alvarez MT, Austin S, Auerswald G, Bermejo N, et al. Haemophilia. 2014;20 Suppl 2:53.Conference abstract · EAHAD poster PO064

20132 entries

• Determination of fibrinogen level to guide replacement therapy in patients undergoing cardiopulmonary bypass with direct thrombin inhibitorsMacDonald SG, Bannister N, Ortmann E, Jenkins D, Falter F, Gray S, et al. Journal of Thrombosis and Haemostasis. 2013;11 Suppl 2:29.Conference abstract
• Point of care heparin monitoring: combined use of clot rate and clot timeMacDonald SG, Luddington R, Sharples L, Besser M. Journal of Thrombosis and Haemostasis. 2013;11 Suppl 2:966.Conference abstract · Congress proceedings

20122 entries

• Pharmacokinetics, safety, and efficacy of a high purity factor X in patients with severe and moderate hereditary factor X deficiencyAlvarez M, Auerswald G, Austin S, Bermejo N, Kavakli K, Oner A, et al. Haemophilia. 2012;18 Suppl 3:182.Conference abstract · WFH abstract FP-TU-04.3-2 · Conference proceedings
• The Papworth Plug – successful use of high dose fibrinogen concentrate and platelet concentrate in potential life-threatening complication after cardiopulmonary bypass surgery in a patient with Type 2M Vicenza von Willebrand diseaseAmerikanou R, MacDonald S, Lawrence K, Large S, Besser MW. Perfusion. 2012;27(4):307–310.

20101 entry

• Critical factors contributing to the thromboelastography traceMacDonald SG, Luddington RJ. Seminars in Thrombosis and Hemostasis. 2010;36(7):712–722.

20081 entry

• Investigation of the role of platelets in clot bound thrombin assays and their contribution to clot procoagulant activityPlayer PM, Luddington R, MacDonald S. Haematologica. 2008;93:149.Conference abstract · Conference proceedings

20062 entries

• An interactive navigation tool to promote recruitment to health care science in haematology in school students between 14-19 years oldMacDonald SG. British Journal of Haematology. 2006;133 Suppl 1:38.Conference abstract · Conference proceedings
• Fibrin bound thrombin is pivotal in the initiation of the thrombin burst and is a key determinant of the amplification phase of clot formationMacDonald SG, Luddington R, Baglin TP. British Journal of Haematology. 2006;133 Suppl 1:9–10.Conference abstract

20051 entry

• Development of an assay for the determination of the quantity and activity of clot bound thrombin in a plasma systemMacDonald SG, Luddington R, Baglin TP. British Journal of Haematology. 2005;129 Suppl 1:58.Conference abstract

Stephen’s educational articles on laboratory quality, measurement and statistics. Expand a series to browse its articles. A free Pathology in Practice account is required to read the full articles.

45 articles · 6 series | View the standalone catalogue

Practical statistics in laboratory medicine (2026)5 articles

• Distributions, outliers and confidence intervals in laboratory data25 May 2026
• Practical statistics: hypothesis testing – t-tests, ANOVA, and others27 July 2026
• Precision studies: common mistakes, limitations and points of caution31 August 2026
• Linearity and measuring interval: a practical guide for biomedical scientists21 September 2026
• Detection capability at the low end: three related but different limits2 November 2026

Risk management in laboratory medicine (2025–2026)8 articles

• Introduction to risk management frameworks in clinical laboratories1 April 2025
• Process mapping, FMEA and FTA: practical approaches to risk assessment6 May 2025
• Risk-based validation and verification in medical laboratories: an overview10 June 2025
• Risk-based quality control: planning, defining, linking and evaluating5 August 2025
• Risk-based turnaround time management: a look at some important issues19 August 2025
• Monitoring of lot changes, delta checks, critical results and reference range22 September 2025
• Risk-based audit schedules and periodic review of examinations27 October 2025
• Management of risk: an action plan for pulling everything together20 January 2026

Measurement uncertainty update (2024)8 articles

• Evaluation of measurement uncertainty: Where we were and where we are going16 January 2024
• Metrological traceability: examining the way to give our results meaning25 March 2024
• Setting measurement uncertainty limits: a brief introduction to the issues23 April 2024
• Intermediate imprecision: challenges and benefits using a simpler method13 May 2024
• Bias and measurement uncertainty: a duo rarely handled correctly30 July 2024
• Measurement uncertainty in results with no numbers: an overview10 September 2024
• Reviewing and reporting measurement uncertainty in medical laboratories23 September 2024
• Unseen risks: how MU affects much more than just assays26 November 2024

Method comparison studies (2020–2021)8 articles

• Method comparison studies in biomedical science: an introduction5 October 2020
• Method comparisons: the importance of study design and requirements17 November 2020
• Method comparison studies: an introduction to acceptability criteria28 January 2021
• Method comparisons with quantitative data I: a look at basic summaries23 March 2021
• Method comparisons with quantitative data II: a look at statistics28 April 2021
• Method comparisons with quantitative data III: difference plots5 May 2021
• Qualitative method comparisons: examining a binary transformation8 June 2021
• Method comparison studies: a review of the process and report1 September 2021

Statistical quality control (2018–2020)9 articles

• Statistical quality control: overview of applications in the clinical laboratory9 October 2018
• Statistical quality control: a look at process design – the materials involved29 November 2018
• Statistical quality control: a look at process design – setting IQC targets12 February 2019
• Statistical quality control: defining goals by measuring performance9 April 2019
• Statistical quality control: error identification and control procedure complexity5 June 2019
• Statistical quality control: an overview of monitoring process with rules10 August 2019
• Statistical quality control: an initial assessment of common QC charting3 October 2019
• Statistical quality control: further assessment of more-complex QC charting26 November 2019
• Statistical quality control: IQC management and troubleshooting errors11 February 2020

Measurement uncertainty fundamentals (2017–2018)7 articles

• Measurand: the first step to measurement uncertainty evaluation2 February 2017
• Assay modelling: the next step in measurement uncertainty evaluation5 May 2017
• Standard uncertainty, the building block of measurement uncertainty9 August 2017
• Internal quality control as the means of determining measurement uncertainty4 November 2017
• Expression of uncertainty in measurement: combining standard uncertainties6 February 2018
• Expression of uncertainty in measurement: more budget topics9 April 2018
• Putting it all together, building the measurement uncertainty budget4 June 2018