Innovance is a laboratory equipment product by Siemens. It is designed to perform automated analysis and measurements for various applications in the laboratory setting. The core function of Innovance is to provide reliable and accurate data through its analytical capabilities.
Data collection was performed retrospectively from electronic medical records and laboratory information systems by two researchers for each hospital. For eligible patients, we extracted the demographics (age and gender), preexisting comorbidities (hypertension, chronic kidney disease (CKD), chronic obstructive pulmonary disease (COPD), cardiovascular disease (CVD) and diabetes mellitus) and laboratory tests. For measurement of D-dimer levels, four immunoturbidimetric assays were used (Table 1). The primary outcome of interest was all-cause in-hospital mortality.
Assays for measurement of D-dimer in BIOCOVID study
García de Guadiana-Romualdo L., Morell-García D., Favaloro E.J., Vílchez J.A., Bauça J.M., Alcaide Martín M.J., Gutiérrez Garcia I., de la Hera Cagigal P., Egea-Caparrós J.M., Pérez Sanmartín S., Gutiérrez Revilla J.I., Urrechaga E., Álamo J.M., Hernando Holgado A.M., Lorenzo-Lozano M.C., Canalda Campás M., Juncos Tobarra M.A., Morales-Indiano C., Vírseda Chamorro I., Pastor Murcia Y., Sahuquillo Frías L., Altimira Queral L., Nuez-Zaragoza E., Adell Ruiz de León J., Ruiz Ripa A., Salas Gómez-Pablos P., Cebreiros López I., Fernández Uriarte A., Larruzea A., López Yepes M.L., Sancho-Rodríguez N., Zamorano Andrés M.C., Pedregosa Díaz J., Sáenz L., Esparza del Valle C., Baamonde Calzada M.C., García Muñoz S., Vera M., Martín Torres E., Sánchez Fdez-Pacheco S., Vicente Gutiérrez L., Jiménez Añón L., Pérez Martínez A., Pons Castillo A., González Tamayo R., Férriz Vivancos J., Rodríguez-Fraga O., Díaz-Brito V., Aguadero V., García Arévalo M.G., Arnaldos Carrillo M., González Morales M., Núñez Gárate M., Ruiz Iruela C., Esteban Torrella P., Vila Pérez M., Acevedo Alcaraz C., Blázquez-Manzanera A.L, & Galán Ortega A. (2021). Harmonized D-dimer levels upon admission for prognosis of COVID-19 severity: Results from a Spanish multicenter registry (BIOCOVID-Spain study). Journal of Thrombosis and Thrombolysis, 53(1), 103-112.
D-dimer plasma levels were assessed 2days (À2) preoperatively and on the 3rd, 7th, and 10th days after surgery with the Siemens Innovance (Siemens Healthcare Diagnostics Products GmbH, Marburg, Germany). In order to minimize bias, all qualified laboratory technologists interpreting the results of D-dimer assays were unaware of the patients' clinical presentation or the results of other objective tests.
Yang Y., Zan P., Gong J, & Cai M. (2017). d-Dimer as a Screening Marker for Venous Thromboembolism After Surgery Among Patients Younger Than 50 With Lower Limb Fractures. Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis, 23(1).
ETP (INNOVANCE®, Siemens Healthcare Diagnostics, Marburg, Germany) assesses plasma’s capacity to generate thrombin (total amount and time course) [19 (link)]. The measured parameters of this assay are:
The time needed until the start of thrombin generation (lag time/tlag),
The total amount of thrombin generated (area under the curve/AUC),
The maximum thrombin concentration (Cmax), and
The time needed to reach maximum thrombin generation (tmax).
In this assay, phospholipids, calcium ions, and human recombinant tissue factor are utilized to activate coagulation and, thus the generation of thrombin. The process is recorded with the aid of a slow reacting chromogenic substrate (at 405 nm) and a fibrin aggregation inhibitor.
Vrigkou E., Tsantes A., Konstantonis D., Rapti E., Maratou E., Pappas A., Halvatsiotis P, & Tsangaris I. (2022). Platelet, Fibrinolytic and Other Coagulation Abnormalities in Newly-Diagnosed Patients with Chronic Thromboembolic Pulmonary Hypertension. Diagnostics, 12(5), 1238.
A Sysmex XE-2100 analyzer (Roche, Chicago, IL, USA) was used to determine complete blood counts. Fibrinogen levels were measured by a modified Clauss method (Siemens Healthcare Diagnostics, Marburg, Germany). A particle-enhanced immunoturbidimetric method (Innovance, Siemens Healthcare Diagnostics, Marburg, Germany) was utilized for the detection of the D-dimers. Lastly, aPTT, PT and INR were processed by a BCS® XP System Hemostasis analyzer (Siemens Healthcare Diagnostics, Marburg, Germany).
Vrigkou E., Tsantes A., Konstantonis D., Rapti E., Maratou E., Pappas A., Halvatsiotis P, & Tsangaris I. (2022). Platelet, Fibrinolytic and Other Coagulation Abnormalities in Newly-Diagnosed Patients with Chronic Thromboembolic Pulmonary Hypertension. Diagnostics, 12(5), 1238.
Complete blood count (leukocyte count, platelet count, hemoglobin, and hematocrit) was performed on a Sysmex XN-9000 analyzer (Sysmex Corporation, Kobe, Hyogo, Japan) using EDTA blood. PT (Dade Innovin; Siemens, Marburg, Germany), aPTT (Dade Actin FSL; Siemens), fibrinogen concentration (Clauss method, Dade Thrombin Reagent; Siemens), D-dimer concentration (Innovance; Siemens), and Anti-Xa activity (Biophen Heparin LRT; Hyphen Biomed, Neuville-Sur-Oise, France) were measured on a Sysmex CS2100i (Sysmex Corporation) in 3.2% citrated blood. For the anti-Xa measurement, COVID-19 patient samples (18 μl) were three times diluted with reference pooled plasma (36 μl). Anti-Xa activity was determined using an LMWH calibration line (aXa-LMWH; Hyphen Biomed). UFH activity was subsequently calculated with a previously determined formula: UFH anti-Xa = 1.55 * LMWH anti-Xa (26 (link)). Bilirubin (Bilirubin Total, third-generation; Roche Diagnostics, Basel, Switzerland) and creatinine (Enzymatic Reagent; Roche Diagnostics) were determined in serum on a COBAS® 8000 (Roche Diagnostics).
Hulshof A.M., Brüggemann R.A., Mulder M.M., van de Berg T.W., Sels J.W., Olie R.H., Spaetgens B., Streng A.S., Verhezen P., van der Horst I.C., Ten Cate H., Spronk H.M., van Bussel B.C, & Henskens Y.M. (2021). Serial EXTEM, FIBTEM, and tPA Rotational Thromboelastometry Observations in the Maastricht Intensive Care COVID Cohort—Persistence of Hypercoagulability and Hypofibrinolysis Despite Anticoagulation. Frontiers in Cardiovascular Medicine, 8, 654174.
All data were collected prospectively in-line with clinical routine and were recorded in a structured database. Regular visits were scheduled until 24 months. At the first visit of the CCP, structured history was taken as well as physical examination. Clinical risk factors were assessed. Laboratory tests were performed 1 months after stop anticoagulant treatment (e.g., D-dimer, factor VIII). Clinical outcomes were assessed until the last visit. Patients were additionally followed over the course of further outpatient visits and accessing MUMC and general practitioner records. Observer were not aware about outcomes while assessing predictors and predictors while assessing outcomes, respectively. Laboratory tests were conducted at pre-specified time points as previously described (35 (link)). A protocol was implemented to ensure adequate pre-analytical conditions (15 (link)). D-dimer levels were determined using the Vidas assay (bioMérieux Clinical Diagnostics, Marcy-l'Etoile, France) or Innovance, respectively (Siemens Healthcare, Marburg, Germany). Factor VIII was analyzed using a one-stage assay (Actin FS, Siemens Healthcare, Marburg, Germany) on a Sysmex CA7000 (distributed by Siemens Healthcare, Marburg, Germany).
Nagler M., Van Kuijk S.M., Ten Cate H., Prins M.H, & Ten Cate-Hoek A.J. (2021). Predicting Recurrent Venous Thromboembolism in Patients With Deep-Vein Thrombosis: Development and Internal Validation of a Potential New Prediction Model (Continu-8). Frontiers in Cardiovascular Medicine, 8, 655226.
Effects of dextran relative to those of albumin in equipotent doses on fibrinogen plasma concentration, vWF antigen concentration, and activity were analyzed in separate animals. Blood was collected in citrated tubes as described above and centrifuged for 20 min at 2,000 × g. Plasma was separated and immediately frozen at −70°C. This plasma was analyzed with commercial available tests adopted for human plasma (see below). Plasma concentration of fibrinogen was analyzed using an ELISA according to the instructions by the manufacturer (Zymutest Fibrinogen, Aniara Diagnostica, West Chester, Ohio). The vWF antigen concentration was analyzed with a latex immunoassay: vWF Ag (Siemens) on a BCS-XP (Siemens). Latex-particles are coated with antibodies against vWF. Upon binding, agglutination occurs, which is measured optically. The function of vWF was analyzed with latex vWF glycoprotein 1b (GP1b) activity test Innovance (Siemens). It relies on a monoclonal antibody that recognizes the functional GPIb-binding epitope on vWF and reflects vWF effects on platelet adhesion and aggregation (27 ).
Schött U., Kander T, & Bentzer P. (2018). Effects of Dextran-70 and Albumin on Coagulation in Experimental Hemorrhage in the Guinea Pig. Shock (Augusta, Ga.), 50(3), 366-372.
VWF:RCo (BC von Willebrand reagent [Siemens]) and VWF glycoprotein Ib (GpIb) binding activity (Innovance, Siemens) were determined by commercially available assays as described previously.23, 24
Zhu S., Gilbert J.C., Hatala P., Harvey W., Liang Z., Gao S., Kang D, & Jilma B. (2020). The development and characterization of a long acting anti‐thrombotic von Willebrand factor (VWF) aptamer. Journal of Thrombosis and Haemostasis, 18(5), 1113-1123.
The aPTT (Dade Actin FSL; Siemens, Marburg, Germany), PT (Dade Innovin; Siemens), fibrinogen level (Clauss method, Dade Thrombin Reagent; Siemens), FVIII activity (Dade Actine FS and FVIII deficient plasma; Siemens), D-dimer (INNOVANCE D-dimer; Siemens), antithrombin (INNOVANCE; Siemens), and anti-Xa (Biophen Heparin LRT; Hyphen Biomed, Neuville-Sur-Oise, France) were measured on a Sysmex CS2100i (Sysmex Corporation, Kobe, Hyogo, Japan) hemostasis analyzer. Samples for the anti-Xa test were first diluted 2x with pooled reference plasma containing ∼100% ATIII and the anti-Xa activity was subsequently determined using specific calibration lines for UFH (aXa-UFH) (Biophen UFH Calibrator; Hyphen Biomed) or low-molecular-weight heparin (LMWH) (aXa-LMWH) (Biophen Heparine Calibrator; Hyphen Biomed). The aPTT (Cephascreen; Stago, Paris, France) was also performed on a STA-R Max2 analyzer (Stago). Thrombocyte count was determined using a Sysmex XN-9000 analyzer (Sysmex). C-reactive protein (CRP, third generation, Roche Diagnostics, Basel, Switzerland) and ferritin (Elecsys ferritin, Roche) were performed on the COBAS8000 by Roche Diagnostics.
Streng A.S., Delnoij T.S., Mulder M.M., Sels J.W., Wetzels R.J., Verhezen P.W., Olie R.H., Kooman J.P., van Kuijk S.M., Brandts L., ten Cate H., Lorusso R., van der Horst I.C., van Bussel B.C, & Henskens Y.M. (2020). Monitoring of Unfractionated Heparin in Severe COVID-19: An Observational Study of Patients on CRRT and ECMO. TH Open: Companion Journal to Thrombosis and Haemostasis, 4(4), e365-e375.
Venous blood was collected from all subjects at the time of enrollment into 1 : 10 final volume of 3.8% sodium citrate. Platelet-poor plasma was obtained by centrifugation at 1550 9g for 20 min at 20 °C, and samples were stored at À80 °C until testing. Laboratory assays ADAMTS-13 activity was measured using the method of Kokame et al. [33] with commercial recombinant FRETS-VWF73 peptide (Peptide Institute Inc., Osaka, Japan) according to the manufacturer's instructions. ELISA methods were used to assess protein antigen (Ag) levels: ADAMTS-13 (Immubind ADAMTS-13 ELISA; American Diagnostica Inc., Stanford, CA, USA), VWF (Asserachrom Ò vWF:Ag; STAGO, Asni eres-sur-Seine, France), F1 + 2 (Enzygnost monoclonal; Dade Behring, Marburg, Germany) and soluble P-sel (R&D Systems Inc., Minneapolis, MN, USA). D-dimer was measured with Innovance (Siemens Healthcare Diagnostics, Marburg, Germany).
Pépin M., Kleinjan A., Hajage D., Büller H.R., Di Nisio M., Kamphuisen P.W., Salomon L., Veyradier A., Stepanian A, & Mahé I. (2016). ADAMTS-13 and von Willebrand factor predict venous thromboembolism in patients with cancer. Journal of thrombosis and haemostasis : JTH, 14(2).
Our mission is to provide scientists with the largest repository of trustworthy protocols and intelligent analytical tools, thereby offering them extensive information to design robust protocols aimed at minimizing the risk of failures.
We believe that the most crucial aspect is to grant scientists access to a wide range of reliable sources and new useful tools that surpass human capabilities.
However, we trust in allowing scientists to determine how to construct their own protocols based on this information, as they are the experts in their field.
Ready to
get started?
Sign up for free.
Registration takes 20 seconds.
Available from any computer
No download required
