#8 What are sensitivity and specificity performances of a diagnostic assay?

Welcome to Ask Stago, The Podcast dedicated to provide expert answers to your expert questions in coagulation.

In today’s episode, our guest Florence Crépet will help us to understand what is behind the wording “limit of blank”, “limit of detection” and “limit of quantification”, and what it means for the clinical laboratory

Literature sources:

• Armbruster DA, Pry T. Limit of blank, limit of detection and limit of quantitation. Clin Biochem Rev. 2008 Aug;29 Suppl 1(Suppl 1):S49-52.
• CLSI. Evaluation of Detection Capability for Clinical Laboratory Measurement  Procedures; Approved  Guideline—Second  Edition. CLSI  document EP17-A2. Wayne,  PA: Clinical and Laboratory  Standards Institute; 2012.
• CLSI Evaluation of Detection Capability Implementation Guide. CLSI Document EP17-Ed2-IG. Wayne, PA: Clinical and Laboratory Standards Institute; 2021.

Content is scientific and technical in nature. It is intended as an educational tool for laboratory professionals and topics discussed are not intended as recommendations or as commentary on appropriate clinical practice.

Welcome to Ask Stago, The Podcast dedicated to provide expert answers to your expert questions in coagulation.

In this episode, to coincide with International Womens Day (March 8th), we are focusing on Gender equality in the workforce, why this is good for business and good for society overall. We meet with Eva Ohlsson Desormonts, Group HR Director for Stago and Amandine Serret International Business Support and Communications Director for Stago as well as an Executive Coach.

Literature sources:

• Women in the Workpace 2022, McKinsey & Company whitepaper
• Challenges facing early career women in thrombosis and hemostasis—meeting the needs of the next generation, Guest Editorial, J Thromb Haemost. 2022;20:2453-5455

Content is scientific and technical in nature. It is intended as an educational tool for laboratory professionals and topics discussed are not intended as recommendations or as commentary on appropriate clinical practice.

Welcome to Ask Stago, the Podcast dedicated to provide expert answers to your expert questions in coagulation.

In today’s episode, we are delighted to speak to April Matera. April experienced a stroke at the age of 39 and from there began her journey towards an anti-phospholipid syndrome diagnosis. Unfortunately it took 7 different visits to 7 different doctors to get her there. She tells us here about her APS road and how it has impacted her life and her dream to have a family.

Content is scientific and technical in nature. It is intended as an educational tool for laboratory professionals and topics discussed are not intended as recommendations or as commentary on appropriate clinical practice.

Welcome to Ask Stago, the Podcast dedicated to provide expert answers to your expert questions in coagulation.

In this series of our new season we will be covering Womens’ health and looking at the broader implications of coagulation and then speaking to a Lupus patient advocate on the impact this disease has had for her personally.

To start off, in today episode, we are delighted to speak to our Clinical Development Director, Dr Francois Depasse about the broader connection between Womens’ Health and coagulation and then a more in depth look at APS.

Links to related podcasts:

• S1E13 - Lupus anticoagulant diagnosis work-up 

  https://www.podcastics.com/podcast/episode/13-the-lupus-anticoagulant-diagnosis-work-up-54015/

• S3E7 - Hemostasis results interpretation along pregnancy 

  https://www.podcastics.com/podcast/episode/s3e7-hemostasis-results-interpretation-along-pregnancy-134753/

Literature sources:

• https://www.cdc.gov/ncbddd/blooddisorders/women/facts.html
• Miyakis S, Lockshin MD, Atsumi T, Branch DW, Brey RL, Cervera R, Derksen RH, De Groot PG, Koike T, Meroni PL, Reber G, Shoenfeld Y, Tincani A, Vlachoyiannopoulos PG, Krilis SA. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost 2006; 4: 295–306
• Devreese KMJ, Ortel TL, Pengo V, de Laat B; Subcommittee on Lupus anticoagulant/Antiphospholipid antibodies. Laboratory criteria for antiphospholipid syndrome: communication from the SSC of the ISTH. J Thromb Haemost 2018; 16: 809-813
• CLSI Laboratory testing for the Lupus anticoagulant - Approved Guideline. CLSI document H60-A. Wayne, PA; 2014.
• Devreese, KMJ, de Groot, PG, de Laat, B, et al. Guidance from the Scientific and Standardization Committee for lupus anticoagulant/antiphospholipid antibodies of the International Society on Thrombosis and Haemostasis. J Thromb Haemost. 2020; 18: 2828– 2839. https://doi.org/10.1111/jth.15047 

Content is scientific and technical in nature. It is intended as an educational tool for laboratory professionals and topics discussed are not intended as recommendations or as commentary on appropriate clinical practice.

Welcome to Ask Stago, The Podcast dedicated to provide expert answers to your expert questions in coagulation.

In today’s episode, our guest Professor Romaric Lacroix will explain us how fibrinolysis is important to the whole hemostasis process and how the sample fibrinolytic activity needs to be evaluated and sometimes monitored.

Link to previous podcasts:

• S1E15 – Disseminated Intravascular Coagulation (DIC) and fibrin related markers

  https://www.podcastics.com/podcast/episode/15-disseminated-intravascular-coagulation-dic-and-fibrin-related-markers-54016/

   

Literature sources:

• Cointe S, Vallier L, Esnault P, Dacos M, Bonifay A, Macagno N, Harti Souab K, Chareyre C, Judicone C, Frankel D, Robert S, Hraiech S, Alessi MC, Poncelet P, Albanese J, Dignat-George F, Lacroix R. Granulocyte microvesicles with a high plasmin generation capacity promote clot lysis and improve outcome in septic shock. Blood. 2022 Apr 14;139(15):2377-2391.
• Cointe S, Harti Souab K, Bouriche T, Vallier L, Bonifay A, Judicone C, Robert S, Armand R, Poncelet P, Albanese J, Dignat-George F et Lacroix R. A new assay to evaluate microvesicle plasmin generation capacity: validation in disease with fibrinolysis imbalance. J Extracell Vesicles 2018; Jul 16;7(1):1494482
• Vallier L, Cointe S, Lacroix R, Bonnifay A, Judicone C, Dignat-George F, Hau C.
• Kwaan. Microparticle and fibrinolysis. Semin Thromb Hemost. 2017 Mar;43(2):129-134

Content is scientific and technical in nature. It is intended as an educational tool for laboratory professionals and topics discussed are not intended as recommendations or as commentary on appropriate clinical practice.

Welcome to Ask Stago, the Podcast dedicated to provide expert answers to your expert questions in coagulation. In today’s episode, our guest Tom Childs will help us to understand the goal and clinical benefits of the Factor parallelism method.  

Link to previous podcasts:

• S1E11 – How to be more productive (part 1): implementation of a rules engine

  https://www.podcastics.com/podcast/episode/10-how-to-be-more-productive-part-1-implementation-of-a-rules-engine-37749/

   
• S2E8 - World Hemophilia Day

  https://www.podcastics.com/podcast/episode/s2e8-world-hemophilia-day-72341/

   
• S2E4 - How to determine factor levels in hemophilia?

  https://www.podcastics.com/podcast/episode/s2e4-how-to-determine-factor-levels-in-hemophilia-62593/

   

Literature sources:

• Ma AD, Carrizosa D. Acquired factor VIII inhibitors: pathophysiology and treatment. Hematology Am Soc Hematol Educ Program 2006: 432–7 (https://ashpublications.org/hematology/article/2006/1/432/19703/Acquired-Factor-VIII-Inhibitors-Pathophysiology).
• Morfini M. Articular status of haemophilia patients with inhibitors. Haemophilia 2008; 14 (Suppl 6): 20–2.
• Gringeri A, Mantovani LG, Scalone L, Mannucci PM; COCIS Study Group. Cost of care and quality of life for patients with hemophilia complicated by inhibitors: the COCIS Study Group. Blood 2003; 102 (7): 2358–63
• Monahan PE, Baker JR, Riske B, Soucie JM. Physical functioning in boys with hemophilia in the U.S. Am J Prev Med 2011; 41 (6 Suppl 4): S360–8.
• Collins PW, Chalmers E, Hart D et al.; United Kingdom Haemophilia Centre Doctors’ Organization. Diagnosis and management of acquired coagulation inhibitors: a guideline from UKHCDO. Br J Haematol 2013; 162 (6): 758–73 (https://onlinelibrary.wiley.com/doi/pdf/10.1111/bjh.12463).
• Riley PW, Gallea B, Valcour A. Development and implementation of a coagulation factor testing method utilizing autoverification in a high‑volume clinical reference laboratory environment. J Pathol Inform 2017; 8: 25.
• Witmer C, Young G. Factor VIII inhibitors in hemophilia A: rationale and latest evidence. Ther Adv Hematol 2013; 4 (1): 59–72
• Oldenburg J, Mahlangu JN, Kim B et al. Emicizumab prophylaxis in hemophilia A with inhibitors. N Engl J Med 2017; 377 (9): 809–18.
• Florin L, Desloovere M, Devreese KML. Validation of an automated algorithm for interpretation of lupus anticoagulant testing on the Stago STA R Max (Poster). International Society on Thrombosis and Haemostasis, 2017.

Content is scientific and technical in nature. It is intended as an educational tool for laboratory professionals and topics discussed are not intended as recommendations or as commentary on appropriate clinical practice.

Welcome to Ask Stago, The Podcast dedicated to provide expert answers to your expert questions in coagulation.

In today’s episode, our guest Gabrielle Pearl will explain us the particularities of thrombosis and hemostasis in pediatric population, and how to manage pediatric patient samples in the clinical laboratory.

Link to previous podcasts:

• S2E5 - How to collect and prepare the coagulation samples properly?

https://www.podcastics.com/podcast/episode/s2e5-how-to-collect-and-prepare-the-coagulation-samples-properly-67393/

• S2E3 - How to establish and control the reference range of my assay?

https://www.podcastics.com/podcast/episode/s2e3-how-to-establish-and-control-the-reference-range-of-my-assay-60155/

Literature sources:

• Monagle P, Barnes C, Ignjatovic V, Furmedge J, Newall F, Chan A, De Rosa L, Hamilton S, Ragg P, Robinson S, Auldist A, Crock C, Roy N, Rowlands S. Developmental haemostasis. Impact for clinical haemostasis laboratories. Thromb Haemost. 2006 Feb;95(2):362-72. doi: 10.1160/TH05-01-0047.
• Monagle P, Massicotte P. Developmental haemostasis: secondary haemostasis. Semin Fetal Neonatal Med. 2011 Dec;16(6):294-300. doi: 10.1016/j.siny.2011.07.007.
• Attard C, van der Straaten T, Karlaftis V, Monagle P, Ignjatovic V. Developmental hemostasis: age-specific differences in the levels of hemostatic proteins. J Thromb Haemost 2013; 11: 1850–4.
• Flanders MM, Phansalkar AR, Crist RA, Roberts WL, Rodgers GM. Pediatric reference intervals for uncommon bleeding and thrombotic disorders. J Pediatr. 2006 Aug;149(2):275-7. doi: 10.1016/j.jpeds.2006.04.008
• Lippi G, Franchini M, Montagnana M, Guidi GC. Coagulation testing in pediatric patients: the young are not just miniature adults. Semin Thromb Hemost. 2007 Nov;33(8):816-20. doi: 10.1055/s-2007-1000373.

Content is scientific and technical in nature. It is intended as an educational tool for laboratory professionals and topics discussed are not intended as recommendations or as commentary on appropriate clinical practice

Welcome to Ask Stago, the podcast dedicated to provide expert answers to your expert questions in hemostasis.

In today episode, our expert Lydie Nicoud, R&D reagent manager, will talk with us about the test of fibrinogen. 

As usual, don’t forget to send any question you may have to ask@stago.com, we will be glad to answer to it.

Literature sources:

• Miesbach W, Schenk J, Alesci S, Lindhoff-Last E, Comparison of the fibrinogen Clauss assay and the fibrinogen PT derived method in patients with dysfibrinogenemia .Thromb Res. 2010; 126(6): e428-33
• Karapetian H. Reptilase time (RT). Methods Mol Bio 2013; 992:273-7.
• Mackie IJ, Kitchen S, Machin SJ, Lowe GDO, Guidelines on fibrinogen assays, Br J Hematol 2003; 121: 396-404
• Cunningham MT, Olson JD, Chandler WL, Van Cott EM, Eby CS, Teruya J, Hollensead SC, Adcock DM, Allison PM, Kottke-Marchant KK, Smith MD. External quality assurance of fibrinogen assays using normal plasma: results of the 2008 College of American Pathologists proficiency testing program in coagulation. Arch Pathol Lab Med. 2012 Jul;136(7):789-95. doi: 10.5858/arpa.2011-0322-OA. PMID: 22742551.Siriez R, Dogné JM, Gosselin R, Laloy J, Mullier F, Douxfils J Comprehensive review of the impact of direct oral anticoagulants on thrombophilia diagnostic tests: practical recommendations for the laboratory. Int J Lab Hematol 2021; 43(1): 7-20

Related podcasts:

• S1E9: How to manage HIL samples in the coagulation laboratory?

  https://www.podcastics.com/podcast/episode/9-how-to-manage-hil-samples-in-the-coagulation-laboratory-37748/

   
• S1E15: Disseminated Intravascular Coagulation (DIC) and fibrin related markers.

  https://www.podcastics.com/podcast/episode/15-disseminated-intravascular-coagulation-dic-and-fibrin-related-markers-54016/

   
• S2E6: Prothrombin Time routine does not mean "simple". 

  https://www.podcastics.com/podcast/episode/s2e6-prothrombin-time-routine-does-not-mean-simple-69494/

• S2E7: APTT, not a one-for-all purposes reagent.

  https://www.podcastics.com/podcast/episode/s2e7-aptt-not-a-one-for-all-purposes-reagent-70596/

Content is scientific and technical in nature. It is intended as an educational tool for laboratory professionals and topics discussed are not intended as recommendations or as commentary on appropriate clinical practice.

Welcome to Ask Stago, The Podcast dedicated to provide expert answers to your expert questions in coagulation.

In today’s episode, our guest Dr Bryan G Fry, aka Venom Doc, will make us enter his world and understand how venom interact with coagulation and how they can prove useful for assay or drug design & development

Literature sources:

• Fry BG, Roelants K, Champagne DE, Scheib H, Tyndall JD, King GF, Nevalainen TJ, Norman JA, Lewis RJ, Norton RS, Renjifo C, de la Vega RC. The toxinogenomic multiverse: convergent recruitment of proteins into animal venoms. Annu Rev Genomics Hum Genet. 2009, 10: 483-511.
• Bittenbinder, M. A., C. N. Zdenek, B. Op den Brouw, N. J. Youngman, J. S. Dobson, A. Naude, F. J. Vonk and B. G. Fry (2018). "Coagulotoxic Cobras: Clinical Implications of Strong Anticoagulant Actions of African Spitting Naja Venoms That Are Not Neutralised by Antivenom but Are by LY315920 (Varespladib)." Toxins (Basel) 10(12): 516.
• Chowdhury, A., M. R. Lewin, C. N. Zdenek, R. Carter and B. G. Fry (2021a). "The Relative Efficacy of Chemically Diverse Small-Molecule Enzyme-Inhibitors Against Anticoagulant Activities of African Spitting Cobra (Naja Species) Venoms." Front Immunol 12: 752442.
• Seneci, L., C. N. Zdenek, A. Chowdhury, C. F. B. Rodrigues, E. Neri-Castro, M. Benard-Valle, A. Alagon and B. G. Fry (2021). "A Clot Twist: Extreme Variation in Coagulotoxicity Mechanisms in Mexican Neotropical Rattlesnake Venoms." Front Immunol 12: 612846.
• Chowdhury, A., C. N. Zdenek, J. S. Dobson, L. A. Bourke, R. Soria and B. G. Fry (2021b). "Clinical implications of differential procoagulant toxicity of the palearctic viperid genus Macrovipera, and the relative neutralization efficacy of antivenoms and enzyme inhibitors." Toxicol Lett 340: 77-88.
• Chowdhury, A., C. N. Zdenek, M. R. Lewin, R. Carter, T. Jagar, E. Ostanek, H. Harjen, M. Aldridge, R. Soria, G. Haw and B. G. Fry (2021). "Venom-Induced Blood Disturbances by Palearctic Viperid Snakes, and Their Relative Neutralization by Antivenoms and Enzyme-Inhibitors." Frontiers in Immunology 12: 2251.
• Zdenek, C. N., B. O. den Brouw, D. Dashevsky, A. Gloria, N. Youngman, E. Watson, P. Green, C. Hay, N. Dunstan, L. Allen and B. G. Fry (2019a). "Clinical implications of convergent procoagulant toxicity and differential antivenom efficacy in Australian elapid snake venoms." Toxicol Lett 316: 171-182.
• Zdenek, C. N., C. Hay, K. Arbuckle, T. N. W. Jackson, M. H. A. Bos, B. Op den Brouw, J. Debono, L. Allen, N. Dunstan, T. Morley, M. Herrera, J. M. Gutierrez, D. J. Williams and B. G. Fry (2019b). "Coagulotoxic effects by brown snake (Pseudonaja) and taipan (Oxyuranus) venoms, and the efficacy of a new antivenom." Toxicol In Vitro 58: 97-109.
• Sousa, L. F., C. A. Nicolau, P. S. Peixoto, J. L. Bernardoni, S. S. Oliveira, J. A. Portes-Junior, R. H. Mourao, I. Lima-dos-Santos, I. S. Sano-Martins, H. M. Chalkidis, R. H. Valente and A. M. Moura-da-Silva (2013). "Comparison of phylogeny, venom composition and neutralization by antivenom in diverse species of bothrops complex." PLoS Negl Trop Dis 7(9): e2442.
• Rogalski, A., C. Soerensen, B. Op den Brouw, C. Lister, D. Dashevsky, K. Arbuckle, A. Gloria, C. N. Zdenek, N. R. Casewell, J. M. Gutierrez, W. Wuster, S. A. Ali, P. Masci, P. Rowley, N. Frank and B. G. Fry (2017). "Differential procoagulant effects of saw-scaled viper (Serpentes: Viperidae: Echis) snake venoms on human plasma and the narrow taxonomic ranges of antivenom efficacies." Toxicol Lett 280: 159-170.
• Youngman, N. J., J. Llinas and B. G. Fry (2021). "Evidence for Resistance to Coagulotoxic Effects of Australian Elapid Snake Venoms by Sympatric Prey (Blue Tongue Skinks) but Not by Predators (Monitor Lizards)." Toxins (Basel) 13(9).

Content is scientific and technical in nature. It is intended as an educational tool for laboratory professionals and topics discussed are not intended as recommendations or as commentary on appropriate clinical practice.

Welcome to Ask Stago, the Podcast dedicated to provide expert answers to your expert questions in coagulation.

In today’s episode, our guest François Depasse will help us to understand the hemostasis results obtained along pregnancy, what are the related difficulties for the lab and

Link to previous podcasts:

• S1E15 Disseminated Intravascular Coagulation (DIC) and fibrin related markers:

  https://www.podcastics.com/podcast/episode/15-disseminated-intravascular-coagulation-dic-and-fibrin-related-markers-54016/

• S2E1 Whole Blood Viscoelastic Testing (VET)

  https://www.podcastics.com/podcast/episode/s2e1-whole-blood-viscoelastic-testing-vet-55204

Literature sources:

• Szecsi PB, Jørgensen M, Klajnbard A, Andresen MR, Colov NP, Stender S, Haemostatic reference intervals in pregnancy. Thromb Haemost 2010; 2013: 718-27
• Kristoffersen AH, Peters PH, Bjørge L, Røraas T and Sandberg S. Concentration of fibrin monomer in pregnancy and during the postpartum period. Annals of Clinical Biochemistry 2019; 56(6): 692-700.
• Hellgren H. Hemostasis during normal prgenancy and puerperium. Semin Thromb Hemost. 2003; 29(2): 125-30.
• Leduc L, Wheeler JM, Kirshon B, Mitchell P, Cotton DB, Coagulation profile in severe preeclampsia, Obstet Gynecol 1992 79(1); 14-8
• Gillissen A, van den Akker T, Caram-Deelder C, Henriquez DDCA, Bloemenkamp KWM, de Maat MPM, van Roosmalen JJM, Zwart JJ, Eikenboom J, van der Bom JG. Coagulation parameter during the course of severe postpartum hemorrhage: a nationwide retrospective cohort study. Blood Adv 2018; 2(19): 2433-42
• Ducloy-Bouthors AS, Mercier FJ, Grouin JM, Bayoumey F, Corouge I, Le Goueze A, Rackelboom T, Broisin F, Vial F, Luzi A, Capronnier O, Huissoud C, Mignon A, Early and systematic administration of fibrinogen concentrate in post-partum haemorrhage following vaginal delivery: the FIDEL randomized controlled trial. BJOG 2021. 128:1814-23.
• Brenner A, Ker K, Shakur-Still H, Roberts I. Tranexamic acid for post-partum haemorrhage: what, who and when. Best Pract Res Clin Obstet Gynaecol. 2019; 1:66-74

Content is scientific and technical in nature. It is intended as an educational tool for laboratory professionals and topics discussed are not intended as recommendations or as commentary on appropriate clinical practice.