| Literature DB >> 33200086 |
Michaël Hardy1,2, Isabelle Michaux3, Sarah Lessire2, Jonathan Douxfils4,5, Jean-Michel Dogné4, Marion Bareille1, Geoffrey Horlait3, Pierre Bulpa3, Celine Chapelle6,7, Silvy Laporte6,7, Sophie Testa8, Hugues Jacqmin1, Thomas Lecompte9, Alain Dive3, François Mullier1.
Abstract
This data article accompanies the manuscript entitled: "Prothrombotic Disturbances of hemostasis of Patients with Severe COVID-19: a Prospective Longitudinal Observational Cohort Study" submitted to Thrombosis Research by the same authors. We report temporal changes of plasma levels of an extended set of laboratory parameters during the ICU stay of the 21 COVID-19 patients included in the monocentre cohort: CRP, platelet count, prothrombin time; Clauss fibrinogen and clotting factors II, V and VIII levels, D-dimers, antithrombin activity, protein C, free protein S, total and free tissue factor pathway inhibitor, PAI-1 levels, von Willebrand factor antigen and activity, ADAMTS-13 (plasma levels); and of two integrative tests of coagulation (thrombin generation with ST Genesia) and fibrinolysis (global fibrinolytic capacity - GFC). Regarding hemostasis, we used double-centrifuged frozen citrated plasma prospectively collected after daily performance of usual coagulation tests. Demographic and clinical characteristics of patients and thrombotic and hemorrhagic complications were also collected from patient's electronic medical reports.Entities:
Keywords: COVID-19; D-dimers; Fibrinolysis; Hemostasis plasma proteins; Intensive care unit; Thrombin generation; Thrombosis
Year: 2020 PMID: 33200086 PMCID: PMC7654236 DOI: 10.1016/j.dib.2020.106519
Source DB: PubMed Journal: Data Brief ISSN: 2352-3409
Demographic and clinical characteristics of observed patients.
| All patients( | |
|---|---|
| Age (years), median (IQR) | 60 [57–64] (48–74) |
| Male gender, n (total) | 18 (21) |
| BMI (kg/m²), median (IQR) | 30 [27–32] (21–42) |
| Caucasian ethnicity, n (total) | 18 (21) |
| Obesity (BMI ≥30 kg/m²), n (total) | 11 (21) |
| Hypertension, n (total) | 11 (21) |
| COPD, n (total) | 4 (21) |
| Asthma, n (total) | 3 (21) |
| CAD, n (total) | 3 (21) |
| On arrival at the ICU | |
| APACHE II, median (IQR) | 14 [12–20] (9–22) |
| SOFA score, median (IQR) | 6 [4–8] (3–12) |
| Time-interval between symptoms onset and ICU admission, median (IQR) | 9 [8–11] (4–15) |
| PAFI, median (IQR) | 91 [67–135] (44–260) |
| During ICU stay | |
| ICU stay duration, median (IQR) | 15 (7–26) (5–28) |
| Patients having received UFH | 13 (21) |
| UFH daily dose (IU/kg/day), median (IQR) | 441 [338–587] (0–800) |
| Patients having received LMWHa, n (total) | 19 (21) |
| LMWH daily dose (IU/kg/day), median (IQR) | 100 [53–149] (0–230) |
| Non-invasive ventilation, n (tot) | 3 (21) |
| Invasive ventilation support, n (tot) | 19 (21) |
| ECMO, n (tot) | 5 (21) |
| Vasopressor use, n (tot) | 16 (21) |
| New renal replacement therapy, n (tot) | 6 (21) |
| Thrombotic complications | 10 (21) |
| Major bleeding according to the ISTH | 6 (21) |
| Death, n (tot) | 3 (21) |
| Discharged from ICU at the end of observation period, n (tot) | 9 (21) |
Patients may have received UFH or LMWH at different periods of ICU stay.
See the companion paper for the descriptions of the events.
IQR, interquartile range; BMI, body mass index; COPD, chronic obstructive pulmonary disease; CAD, coronary artery disease; ICU, intensive care unit; IQR, interquartile range; APACHE II score, acute physiology and chronic health disease classification system II; SOFA, sepsis-related organ failure assessment; PAFI, PaO2/FiO2 ratio; UFH, unfractionated heparin; LWMH, low molecular weight heparin; ECMO, extracorporeal membrane oxygenation; ICU, intensive care unit.
Changes over time of hemostasis parameters along intensive care unit stay.
| Variable and reference ranges | D1–D10 ( | D11–D20 ( | D21–D30 ( |
|---|---|---|---|
| CRP (mg/dL) <5 | 211 [160–267] (9–485) | 97 [63–126] (2–451) | 95 [64–114] (14–256) |
| Platelet count (109/L) 150 to 450 | 246 [177–387] (73–701) | 337 [187–454] (89–672) | 252 [153–412] (87–583) |
| vWF antigen (%) 50 to 160 | 438 [357–534] (204–803) | 476 [380–548] (161–846) | 475 [424–702] (211–795) |
| vWF activity (%) 46 to 176 | 294 [228–452] (151–845) | 344 [280–400] (107–927) | 429 [383–676] (152–779) |
| ADAMTS-13 (IU/mL) 0.4 to 1.3 | 0.61 [0.40–0.65] (0.13–0.86) | 0.45 [0.39–0.61] (0.24–0.83) | 0.45 [0.43–0.50] (0.41–0.62) |
| Prothrombin time (%) 75 to 100 | 81 [75–89] (28–100) | 80 [77–87] (51–100) | 80 [78–84] (62–100) |
| Fibrinogen (mg/dL) 200 to 400 | 722 [588–820] (177–1122) | 680 [555–723] (64–985) | 631 [592–682] (198–851) |
| Factor II (%) 70 to 120 | 82 [74–97] (34–126) | 88 [70–96] (30–113) | 94 [79–103] (37–119) |
| Factor V (%) 70 to 120 | 127 [91–158] (21–218) | 140 [112–175] (64–245) | 126 [114–145] (42–299) |
| Factor VIII (%) 60 to 150 | 292 [239–317] (100–522) | 326 [263–354] (99–603) | 333 [268–404] (128–576) |
| AT (%) 80 to 120 | 91 [68–100] (33–131) | 82 [71–105] (51–130) | 92 [78–94] (53–107) |
| Protein C activity (%) 70–120 | 85 [78–120] (46–169) | 113 [105–117] (51–178) | 107 [98–158] (90–187) |
| Free protein S antigen (%) Men: 70 to 148 Women: 50 to 134 | 80 [65–124] (39–150) | 114 [88–129] (44–150) | 110 [96–149] (45–150) |
| Total TFPI (ng/mL) 20.4 to 142 | 107 [82–168] (60–292) | 98 [90–158] (57–396) | 128 [92–140] (50–186) |
| Free TFPI (ng/mL) 0.4 to 19.6 | 42 [28–75] (9–173) | 32 [22–83] (12–175) | 38 [23–57] (14–102) |
| Thrombin generation lag time (ratio) 1.1 to 1.3 | 2.0 [1.5–2.4] (1.0–10.3) | 2.2 [1.7–3.0] (1.1–9.9) | 2.5 [1.9–3.3] (1.4–7.6) |
| Thrombin generation time to peak (ratio) 1.2 to 1.3 | 1.7 [1.4–2.0] (1.0–6.5) | 1.8 [1.5–2.4] (1.0–6.5) | 2.0 [1.7–2.5] (1.1–5.1) |
| Thrombin generation peak height (%) 45 to 66 | 78 [53–105] (13–139) | 67 [48–78] (21–137) | 54 [42–73] (19–174) |
| Thrombin generation ETP (%) 59 to 80 | 111 [70–139] (23–208) | 81 [66–89] (37–210) | 73 [56–95] (31–158) |
| D-dimers (ng/mL) ISTH criterion for DIC, ≥3500 (2 pts) or ≥11,100 (3 pts) | 4860 [2336–12,260] (750–20,000) | 3425 [2557–4710] (540–13,750) | 3120 [1960–4420] (800–16,430) |
| PAI-1 (AU/mL) <16 | 23.6 [20.3–25.4] (2.3–58.7) | 19.5 [16.5–28.8] (1.6–52.0) | 15.6 [13.9–57.2] (6.8–52.2) |
| GFC (min) 30 to 60 | 57 [53–64] (31–240) | 55 [49–69] (34–240) | 57 [44–73] (37–240) |
CRP, C-reactive protein; vWF antigen, von Willebrand factor antigen; vWF activity, von Willebrand factor activity, ristocetin cofactor; ADAMTS-13 (also known as von Willebrand factor cleaving protease); TFPI, tissue factor pathway inhibitor; DIC, disseminated intravascular coagulopathy; t-PA, tissue-type plasminogen activator; PAI-1, plasminogen activator inhibitor; AU, arbitrary units; GFC, global fibrinolysis capacity (Lysis Timer instrument); ETP, endogenous thrombin potential.
Results of ST Genesia TGA are relative to reference plasma and expressed as ratios (temporal parameters) or percentages (thrombin concentration-related parameters).
Fig. 1Temporal changes in C-reactive protein plasma levels during Namur ICU stay for the 21 patients. Each point represents the result of the test of the day. The blue line represents the reference range according to the manufacturer (5 mg/dL). Grey stars represent the inclusion period and orange stars the day of thrombosis diagnosis.(For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
Fig. 2Temporal changes in platelet count during Namur ICU stay for the 21 patients. Each point represents the result of the test of the day. Blue lines represent the reference range (150–450 × 109/L). Grey stars represent the inclusion period and orange stars the day of thrombosis diagnosis.(For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
Fig. 3Temporal changes in prothrombin time (expressed as percentage activity) during Namur ICU stay for the 21 patients. Each point represents the result of the test of the day. Blue lines represent the reference range locally determined (75–100%). Grey stars represent the inclusion period and orange stars the day of thrombosis diagnosis.(For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
Fig. 4Temporal changes in Clauss fibrinogen during Namur ICU stay for the 21 patients. Each point represents the result of the test of the day. Blue lines represent the reference range according to the manufacturer (200–400 mg/dL). Grey stars represent the inclusion period and orange stars the day of thrombosis diagnosis.(For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
Fig. 5Temporal changes in clotting factor II levels during Namur ICU stay for the 21 patients. Each point represents the result of the test of the day. Blue lines represent the reference range according to the manufacturer (70–120%). Grey stars represent the inclusion period and orange stars the day of thrombosis diagnosis.(For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
Fig. 6Temporal changes in clotting factor V levels during Namur ICU stay for the 21 patients. Each point represents the result of the test of the day. Blue lines represent the reference range according to the manufacturer (70–120%). Grey stars represent the inclusion period and orange stars the day of thrombosis diagnosis.(For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
Fig. 7Temporal changes in clotting factor VIII levels during Namur ICU stay for the 21 patients. Each point represents the result of the test of the day. Blue lines represent the reference range according to the manufacturer (60–150%). Grey stars represent the inclusion period and orange stars the day of thrombosis diagnosis.(For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
Fig. 8Temporal changes in D-dimers plasma levels during Namur ICU stay for the 21 patients. Each point represents the result of the test of the day. Grey stars represent the inclusion period and orange stars the day of thrombosis diagnosis.(For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
Fig. 9Temporal changes in thrombin generation (ST Genesia with ThromboScreen reagent) lag time (LT) normalized using a reference plasma (provided with ThromboScreen reagent) during Namur ICU stay for the 21 patients. Each point represents the result of the test of the day. Blue lines represent the reference range according to Calzavarini et al (1.1–1.3) [3]. Grey stars represent the inclusion period and orange stars the day of thrombosis diagnosis. The ordinate is represented using a logarithmic scale.(For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
Fig. 10Temporal changes in thrombin generation (ST Genesia with ThromboScreen reagent) time to peak (ttP) normalized using a reference plasma (provided with ThromboScreen reagent) during Namur ICU stay for the 21 patients. Each point represents the result of the test of the day. Blue lines represent the reference range according to Calzavarini et al. (1.2–1.3) [3]. Grey stars represent the inclusion period and orange stars the day of thrombosis diagnosis. The ordinate is represented using a logarithmic scale.(For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
Fig. 11Temporal changes in thrombin generation (ST Genesia with ThromboScreen reagent) peak height (pH) normalized using a reference plasma (provided with ThromboScreen reagent) during Namur ICU stay for the 21 patients. Each point represents the result of the test of the day. Blue lines represent the reference range according to Calzavarini et al. (45–66%) [3]. Grey stars represent the inclusion period and orange stars the day of thrombosis diagnosis.(For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
Fig. 12Temporal changes in thrombin generation (ST Genesia with ThromboScreen reagent) endogenous thrombin potential (ETP) normalized using a reference plasma (provided with ThromboScreen reagent) during Namur ICU stay for the 21 patients. Each point represents the result of the test of the day. Blue lines represent the reference range according to Calzavarini et al (59–80%) [3]. Grey stars represent the inclusion period and orange stars the day of thrombosis diagnosis.(For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
Fig. 13Temporal changes in PAI-1 activity during Namur ICU stay for the 21 patients. Each point represents the result of the test of the day. The blue line represents the reference range according to the manufacturer (<16AU/mL). Grey stars represent the inclusion period and orange stars the day of thrombosis diagnosis.(For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
Fig. 14Temporal changes in global fibrinolytic capacity (GFC) measured with the Lysis Timer instrument during Namur ICU stay for the 21 patients. Each point represents the result of the test of the day. Blue lines represent the reference range locally determined (30–48 min). Grey stars represent the inclusion period and orange stars the day of thrombosis diagnosis. The ordinate is represented using a logarithmic scale.(For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
Fig. 15Temporal changes in antithrombin activity during Namur ICU stay for the 21 patients. Each point represents the result of the test of the day. Blue lined represent the reference range according to the manufacturer (80–120%). Grey stars represent the inclusion period and orange stars the day of thrombosis diagnosis. Exogenous antithrombin supplementations are represented by red hashes.(For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
Fig. 16Temporal changes in protein C activity during Namur ICU stay for the 21 patients. Each point represents the result of the test of the day. Blue lines represent the reference range according to the manufacturer (70–130%). Grey stars represent the inclusion period and orange stars the day of thrombosis diagnosis.(For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
Fig. 17Temporal changes in free protein S levels during Namur ICU stay for the 21 patients. Each point represents the result of the test of the day. Blue lines represent the reference range according to the manufacturer (60–140%). Grey stars represent the inclusion period and orange stars the day of thrombosis diagnosis.(For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
Fig. 18Temporal changes in total tissue factor pathway inhibitor (TFPI) levels during Namur ICU stay for the 21 patients. Each point represents the result of the test of the day. Blue lines represent the reference range according to the manufacturer (21.3–142.9 ng/mL). Grey stars represent the inclusion period and orange stars the day of thrombosis diagnosis.(For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
Fig. 19Temporal changes in free tissue factor pathway inhibitor (TFPI) levels during Namur ICU stay for the 21 patients. Each point represents the result of the test of the day. Blue lines represent the reference range according to the manufacturer (0.4–19.6 ng/mL). Grey stars represent the inclusion period and orange stars the day of thrombosis diagnosis.(For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
Fig. 20Temporal changes in von Willebrand factor (vWF) antigen levels during Namur ICU stay for the 21 patients. Each point represents the result of the test of the day. The blue line represents the reference range according to the manufacturer (< 160%). Grey stars represent the inclusion period and orange stars the day of thrombosis diagnosis.(For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
Fig. 21Temporal changes in von Willebrand factor (vWF) activity (ristocetin cofactor) during Namur ICU stay for the 21 patients. Each point represents the result of the test of the day. The blue line represents the reference range according to the manufacturer (< 176%). Grey stars represent the inclusion period and orange stars the day of thrombosis diagnosis.(For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
Fig. 22Temporal changes ADAMTS-13 activity during Namur ICU stay for the 21 patients. Each point represents the result of the test of the day. Blue lines represent the reference range according to the manufacturer (0.4–1.3IU/mL). Grey stars represent the inclusion period and orange stars the day of thrombosis diagnosis.(For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
Summary of percentages of available data over the observation period per laboratory parameter.
| Parameter | Percentage of days with available data (%) |
|---|---|
| C-reactive protein | 97 |
| Platelet count | 99 |
| Prothrombin time | 85 |
| Fibrinogen | 84 |
| Factor II | 82 |
| Factor V | 82 |
| Factor VIII | 85 |
| D-dimers | 84 |
| Thrombin generation LT | 58 |
| Thrombin generation ttP | 58 |
| Thrombin generation pH | 58 |
| Thrombin generation ETP | 58 |
| Plasminogen activator inhibitor 1 | 84 |
| Global fibrinolytic capacity | 83 |
| Antithrombin activity | 84 |
| Protein C activity | 44 |
| Free protein S antigen | 44 |
| Total TFPI | 33 |
| Free TFPI | 33 |
| Anti-Xa activity | 82 |
| von Willebrand factor antigen | 21 |
| von Willebrand factor activity | 21 |
| ADAMTS-13 | 22 |
LT, lag time; ttP, time to peak, pH, peak height; ETP, endogenous thrombin potential; TFPI, tissue factor pathway inhibitor.
| Subject | Hematology |
| Specific subject area | Hemostasis, Coronavirus disease 2019 |
| Type of data | Tables and Figures |
| How data were acquired | Blood samples prospectively collected daily from intensive care unit (ICU) patients admitted for coronavirus disease 2019 (COVID-19). Corresponding instruments and reagents of laboratory hematology for: platelet count, prothrombin time, Clauss fibrinogen and clotting factors II, V and VIII levels, D-dimers levels, PAI-1 levels, antithrombin activity, protein C activity, free protein S antigen, total and free tissue factor pathway inhibitor antigens, von Willebrand factor antigen and activity, ADAMTS-13 levels), thrombin generation, and global fibrinolytic capacity (GFC); and C-reactive protein. |
| Data format | Raw: Public repository. Analyzed: Tables and figures |
| Parameters for data collection | Laboratory data: Clinical laboratory tests that describe disturbances of hemostasis of ICU patients, severely affected with CoViD-19: primary hemostasis (platelet count, von Willebrand factor antigen and activity; ADAMTS-13 activity); coagulation (prothrombin time, Clauss fibrinogen, clotting factors II, V and VIII levels, in vitro thrombin potential), natural anticoagulants (antithrombin activity, protein C activity, free protein S antigen, total and free tissue factor pathway inhibitor antigens); and fibrinolysis (D-dimers levels, PAI-1 activity, global fibrinolytic capacity). Clinical data: complications of hemostasis disturbances (thrombosis and hemorrhages) and relevant data for characterization of the cohort (age; sex, BMI, ethnicity, comorbidities, APACHE II, SOFA scores and PaO2/FiO2 ratios at ICU admission, ICU stay duration, anticoagulation regimen, ICU length of stay, need for respiratory, cardiocirculatory or renal support; death). |
| Description of data collection | The following laboratory tests were performed with a STA-R Max (Diagnostica Stago, Asnières-sur-Seine) and reagents from Stago: prothrombin time (STA-NeoPTimal), Clauss fibrinogen (STA-Liquid FIB), clotting factor II (STA-NeoPTimal and STA – Deficient II), V (STA-NeoPTimal and STA – Deficient V) and VIII (STA-CK Prest and STA – Immunodef VIII), D-dimers (STA – LIATEST D-Di Plus), PAI-1 (STACHROM PAI-1), antithrombin (STA-Stachrom ATIII), protein C activity (STA – Stachrom Protein C), free protein S antigen (STA-LIATEST Free Protein S), total (Asserachrom total TFPI) and free TFPI (Asserachrom free TFPI), heparin anti-Xa activity (STA - Liquid anti-Xa), von Willebrand factor antigen (STA – LIATEST VWF:Ag). CRP levels were measured on a Vitros 5600 Integrated System with CRP Gold Latex reagents (DiAgam, Ghislenghien, Belgium) and platelet count on a Sysmex |
| XN-20 analyzer with Cellpack reagent (Sysmex). Thrombin generation was measured on a ST Genesia with STG-ThromboScreen reagent (Stago) after neutralizing heparin with hexadimethrine bromide (25 μg/mL; polybrene, Sigma Aldrich, Saint-Louis, United States). Global fibrinolytic capacity was measured using the Lysis Timer instrument with dedicated reagents (Hyphen Biomed). ADAMTS13 activity was measured using the Technozym® ADAMTS-13 Activity ELISA kit (Technozym, Technoclone, Vienna, Austria). Von Willebrand activity was measured on an AcuStar analyser with HemosIL AcuStar VWF:RCo reagent (Instrumentation Laboratory). Laboratory data were retrieved from laboratory files. Clinical data were retrieved from patients’ medical charts. | |
| Data source location | Institution: CHU UCL Namur – Godinne site. City: Yvoir. Country: Belgium. |
| Data accessibility | Repository name: Mendeley Data Data identification number: |
| Related research article | M. Hardy, I. Michaux, S. Lessire, J. Douxfils, J.-M. Dogné, M. Bareille, G. Horlait, P. Bulpa, C. Chapelle, S. Laporte, S. Testa, H. Jacqmin, T. Lecompte, A. Dive and F. Mullier. Prothrombotic hemostasis Disturbances in Patients with Severe COVID-19: a Prospective Longitudinal Observational Cohort Study. Thromb Res. 2020; 197:20-23. |