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  1. Article ; Online: Évaluation d’un test d’orientation diagnostique de thrombopénie induite à l’héparine : validation d’un délai différé de réalisation du test.

    Billoir, Paul / Barbay, Virginie / Fresel, Marielle / Brunel, Sabine / Duchez, Véronique Le Cam

    Annales de biologie clinique

    2023  Volume 81, Issue 3, Page(s) 248–254

    Abstract: Heparin-induced thrombocytopenia (HIT) is a rare, iatrogenic condition, characterized by its potential severity and diagnostic difficulties. The diagnosis is based on a set of arguments allowing the calculation of a pre-test score pointing to HIT. There ... ...

    Title translation Evaluation of a diagnostic test for heparin-induced thrombocytopenia: validation of a delayed test time.
    Abstract Heparin-induced thrombocytopenia (HIT) is a rare, iatrogenic condition, characterized by its potential severity and diagnostic difficulties. The diagnosis is based on a set of arguments allowing the calculation of a pre-test score pointing to HIT. There are rapid diagnostic tests for suspected HIT. Among these, the STic Expert® HIT has a good sensitivity to detect HIT. However, it must be performed within 2 hours after sampling. The aim of this study was to evaluate a delayed STic Expert® HIT test at 8 hours and in frozen plasma. Thirty-six patients were prospectively included for HIT testing between April 01, 2018, and July 1, 2022, at the University Rouen Hospital. For any request for HIT testing, an analysis by STic Expert® HIT was performed within 2 hours and 8 hours post-sampling. Any positive result was confirmed by a functional test, platelet aggregation with heparin, release of 14C-serotonin assay (SRA), and immunological assay by a research for anti-platelet factor 4 IgG antibodies. Twenty-three patients had a STic Expert® HIT. Sixteen presented platelet aggregations in the presence of heparin and had a positive anti-PF4 test, 17 had a positive SRA. Six patients had no HIT. For the test performed within 2 hours of collection, the Se = 100%, Sp = 68.42%, PPV = 73.91%, and NPV = 100%. The X2 = 18.21 with p < 0.001. For the test performed at 8 hours post sampling, the Se = 100%, Sp = 68.42%, PPV = 73.91% and NPV = 100%. The X2 = 18.21 with p < 0.001. In conclusion, we have demonstrated that the STic Expert® can be used to perform an HIT diagnostic test 8 hours after sampling and on thawed plasma. However, this study needs to be confirmed on a larger number of samples.
    MeSH term(s) Humans ; Thrombocytopenia/chemically induced ; Thrombocytopenia/diagnosis ; Heparin/adverse effects ; Antibodies/pharmacology ; Platelet Aggregation ; Platelet Factor 4/adverse effects ; Serotonin ; Diagnostic Tests, Routine ; Anticoagulants/adverse effects
    Chemical Substances Heparin (9005-49-6) ; Antibodies ; Platelet Factor 4 (37270-94-3) ; Serotonin (333DO1RDJY) ; Anticoagulants
    Language French
    Publishing date 2023-04-14
    Publishing country France
    Document type English Abstract ; Journal Article
    ZDB-ID 418098-7
    ISSN 1950-6112 ; 0003-3898
    ISSN (online) 1950-6112
    ISSN 0003-3898
    DOI 10.1684/abc.2023.1810
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Evaluation of thrombin generation assay in factor XI deficiency.

    Kasonga, Fiston / Feugray, Guillaume / Chamouni, Pierre / Barbay, Virginie / Fresel, Marielle / Chretien, Marie Hélène / Brunel, Sabine / Le Cam Duchez, Véronique / Billoir, Paul

    Clinica chimica acta; international journal of clinical chemistry

    2021  Volume 523, Page(s) 348–354

    Abstract: Introduction: Factor XI (FXI) deficiency is characterized by a lack of correlation between FXI plasma levels and the occurrence of hemorrhagic events. The main objective of our study was to determine whether thrombin generation assay (TGA) could be used ...

    Abstract Introduction: Factor XI (FXI) deficiency is characterized by a lack of correlation between FXI plasma levels and the occurrence of hemorrhagic events. The main objective of our study was to determine whether thrombin generation assay (TGA) could be used to assess the hemorrhagic phenotype of patients with FXI deficiency.
    Material and methods: All patients had confirmed laboratory measurement of FXI < 50% in two plasma samples. Relevant bleeding history was evaluated by a senior physician. TGA was performed with Calibrated Automated Thrombography, in platelet poor plasma, from patients and healthy controls. The assay was performed with PPP low reagent (1 pM of human tissue factor).
    Results: Seventy-six patients with FXI deficiency were included between 2011 and 2020. Among them, eight patients had severe deficiency (FXI < 15%). Mean age was 34 years [range: 9-77]. Endogenous thrombin potential (ETP) was significantly lower in patients with FXI deficiency and bleeding (573 nM·min [225-1214]) or no bleeding (732 nM·min [222-1435]), compared to healthy controls (1184 nM·min [933-1518]). No difference was observed for ETP and peak between patients with FXI deficiency and bleeding and patients with FXI deficiency and no bleeding. No difference was observed for ETP (923 nM·min [377-1497] vs 1063 nM·min [252-2529]), peak (82 nM [28-154] vs 131 nM [20-330]) or velocity (13.7 nM/min [3.6-29.6] vs 26.5 nM/min [2.5-90]) in women with (n = 4) and without history (n = 17) of post-partum bleeding. No difference of thrombin generation was observed in pregnant women with FXI deficiency (ETP: 1395 nM·min [351-2529]; peak: 154 nM [26-330]; velocity: 29.6 nM/min [4.1-90.0]), compared to healthy controls and a control group of healthy pregnant women.
    Conclusion: In conclusion, under our experimental condition, a non-significant decrease of thrombin generation was observed in plasma samples of patients with FXI deficiency and bleeding. Our results suggest an increase of coagulation parameters during pregnancy in women with FXI deficiency. A larger sample size or other experimental conditions are required to evaluate the use of TGA in FXI deficiency.
    MeSH term(s) Adolescent ; Adult ; Aged ; Blood Coagulation ; Blood Coagulation Tests ; Child ; Factor XI ; Factor XI Deficiency/diagnosis ; Female ; Humans ; Male ; Middle Aged ; Pregnancy ; Thrombin ; Young Adult
    Chemical Substances Factor XI (9013-55-2) ; Thrombin (EC 3.4.21.5)
    Language English
    Publishing date 2021-10-17
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 80228-1
    ISSN 1873-3492 ; 0009-8981
    ISSN (online) 1873-3492
    ISSN 0009-8981
    DOI 10.1016/j.cca.2021.10.021
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Thrombin generation profile in non-thrombotic factor V Leiden carriers.

    Billoir, Paul / Duflot, Thomas / Fresel, Marielle / Chrétien, Marie Hélène / Barbay, Virginie / Le Cam Duchez, Véronique

    Journal of thrombosis and thrombolysis

    2019  Volume 47, Issue 3, Page(s) 473–477

    Abstract: Factor V Leiden (FVL) mutation is the most common genetic risk factor for venous thromboembolism. In families with a history of thrombosis, FVL can be present in 18%. Thrombin generation test is commonly used as an evaluation tool of thrombotic risk. The ...

    Abstract Factor V Leiden (FVL) mutation is the most common genetic risk factor for venous thromboembolism. In families with a history of thrombosis, FVL can be present in 18%. Thrombin generation test is commonly used as an evaluation tool of thrombotic risk. The objective of this study was to evaluate the thrombogenic potential of FVL in asymptomatic carriers and in patients with personal or familial history of thrombosis. This was a retrospective single center study including 160 patients. Among them, 43 had personal history of thrombosis and 117 had familial history of thrombosis. Thrombin generation (TG) was realized in frozen platelet poor plasma with 1 pM of tissue factor and 4 µM of phospholipid. FVL mutation was associated with a global increase of TG. No difference was observed between patients with provoked thrombosis and patients with first-degree familial history of thrombosis (endogenous thrombin potential (ETP): 1501.0 ± 316.4 nM min and thrombin peak: 253.4 ± 71.5 nM vs. 1520.4 ± 283.8 nM min and 268.6 ± 68.0 nM). An increase of TG was observed in patients with unprovoked thrombosis (n = 23) and in patients with provoked thrombosis (n = 20) (ETP: 1819.5 ± 319.8 nM min and peak: 332.3 ± 55.8 nM). In the unprovoked thrombosis group, patients with a pulmonary embolism had a higher ETP than patients with deep vein thrombosis (DVT) (2036 ± 343 nM min vs. 1707 ± 261 nM min). With a predictive score formula (s = 0.1315 × Age + 0.0105 × ETP) with a threshold of 22.1 as risk to develop an unprovoked thrombosis among patients with second-degree familial history. The results of our analysis suggest that measurement of thrombin generation in patients with FVL mutation may identify subjects with an increased risk of unprovoked thrombosis. Further studies are needed to examine the usefulness of predicting thrombotic presentation in asymptomatic carriers.
    MeSH term(s) Adult ; Aged ; Factor V/genetics ; Female ; Heterozygote ; Humans ; Male ; Medical History Taking ; Middle Aged ; Mutation ; Predictive Value of Tests ; Pulmonary Embolism ; Retrospective Studies ; Risk Assessment ; Thrombin/biosynthesis ; Thrombophilia ; Thrombosis/etiology
    Chemical Substances factor V Leiden ; Factor V (9001-24-5) ; Thrombin (EC 3.4.21.5)
    Language English
    Publishing date 2019-01-30
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 1230645-9
    ISSN 1573-742X ; 0929-5305
    ISSN (online) 1573-742X
    ISSN 0929-5305
    DOI 10.1007/s11239-019-01821-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Factor XII deficiency evaluated by thrombin generation assay.

    Feugray, Guillaume / Kasonga, Fiston / Chamouni, Pierre / Barbay, Virginie / Fresel, Marielle / Hélène Chretien, Marie / Brunel, Sabine / Le Cam Duchez, Véronique / Billoir, Paul

    Clinical biochemistry

    2021  Volume 100, Page(s) 42–47

    Abstract: Introduction: Coagulation factor XII (FXII) plays a role in thrombin generation, fibrinolysis, inflammation, angiogenesis, chemotaxis and diapedesis. FXII deficiency is not associated with bleeding risk unlike other coagulation factors.: Materials/ ... ...

    Abstract Introduction: Coagulation factor XII (FXII) plays a role in thrombin generation, fibrinolysis, inflammation, angiogenesis, chemotaxis and diapedesis. FXII deficiency is not associated with bleeding risk unlike other coagulation factors.
    Materials/methods: We investigated thrombin generation assay (TGA) profile modification in FXII deficiency and the correlation with TGA and deficiency severity. TGA was performed in platelet poor plasma (PPP) with tissue factor (1 pmol/L) and phospholipid (4 µmol/L) standardized concentration. Thrombin generation profiles were compared in 54 patients with FXII deficiency, 25 healthy controls and 23 patients with hemophilia A (factor VIII (FVIII) deficiency. Patients with FXII deficiency were classified in three groups based on FXII activity (30-50%, 10-29%, <10%). FVIII deficiency was included as a bleeding control group.
    Results: As expected, we found a correlation between FXII deficiency and activated partial thromboplastin time (aPTT). A decrease of thrombin generation was observed in healthy controls and all FXII deficiency groups. A decrease of endogenous thrombin potential (ETP), peak and velocity was observed in patients with FVIII deficiency compared to FXII deficiency. A decrease of thrombin generation was noted in patients with FXII deficiency and bleeding history compared to patients with FXII deficiency and thrombosis history.
    Conclusion: In this study, thrombin generation profiles were not sensitive to FXII deficiency. TGA could distinguish bleeding and thrombotic tendency in FXII deficiency. Our results should therefore be considered as exploratory and deserve confirmation.
    MeSH term(s) Adult ; Aged ; Factor XII Deficiency/blood ; Female ; Humans ; Male ; Middle Aged ; Partial Thromboplastin Time ; Retrospective Studies ; Thrombin/metabolism
    Chemical Substances Thrombin (EC 3.4.21.5)
    Language English
    Publishing date 2021-11-26
    Publishing country United States
    Document type Clinical Trial ; Journal Article
    ZDB-ID 390372-2
    ISSN 1873-2933 ; 0009-9120
    ISSN (online) 1873-2933
    ISSN 0009-9120
    DOI 10.1016/j.clinbiochem.2021.11.014
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Anti-Xa Oral Anticoagulant Plasma Concentration Assay in Real Life: Rivaroxaban and Apixaban Quantification in Emergency With LMWH Calibrator.

    Billoir, Paul / Barbay, Virginie / Joly, Luc Marie / Fresel, Marielle / Chrétien, Marie Hélène / Le Cam Duchez, Véronique

    The Annals of pharmacotherapy

    2018  Volume 53, Issue 4, Page(s) 341–347

    Abstract: Background: Oral anti-Xa inhibitors have demonstrated noninferiority to vitamin K antagonists (VKAs) for the prevention of stroke in patients with atrial fibrillation and recurrent venous thromboembolism. They are associated with a decrease in major ... ...

    Abstract Background: Oral anti-Xa inhibitors have demonstrated noninferiority to vitamin K antagonists (VKAs) for the prevention of stroke in patients with atrial fibrillation and recurrent venous thromboembolism. They are associated with a decrease in major bleeding. In contrast with VKA, no coagulation monitoring is required. However, in clinical practice, determination of drug concentration is sometimes necessary.
    Objective: The objective of this study was to evaluate a low-molecular-weight heparin (LMWH) calibrated anti-Xa assay for the quantification of rivaroxaban and apixaban plasma concentration in emergency.
    Methods: The anti-Xa plasma concentration of rivaroxaban and apixaban were measured in emergency in 210 patients using STA anti-Xa liquid assay. For each plasma concentration <150 ng/mL of rivaroxaban or apixaban, an anti-Xa assay calibrated with LMWH was performed.
    Results: We demonstrated a significant correlation between LMWH anti-Xa activity and rivaroxaban ( R
    MeSH term(s) Aged ; Atrial Fibrillation/drug therapy ; Blood Coagulation/drug effects ; Blood Coagulation Tests/methods ; Calibration ; Factor Xa Inhibitors/blood ; Factor Xa Inhibitors/therapeutic use ; Female ; Hemorrhage/prevention & control ; Heparin, Low-Molecular-Weight/blood ; Humans ; Male ; Predictive Value of Tests ; Pyrazoles/blood ; Pyrazoles/therapeutic use ; Pyridones/blood ; Pyridones/therapeutic use ; Retrospective Studies ; Rivaroxaban/blood ; Rivaroxaban/therapeutic use ; Sensitivity and Specificity ; Stroke/prevention & control ; Venous Thromboembolism/prevention & control
    Chemical Substances Factor Xa Inhibitors ; Heparin, Low-Molecular-Weight ; Pyrazoles ; Pyridones ; apixaban (3Z9Y7UWC1J) ; Rivaroxaban (9NDF7JZ4M3)
    Language English
    Publishing date 2018-10-31
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1101370-9
    ISSN 1542-6270 ; 1060-0280
    ISSN (online) 1542-6270
    ISSN 1060-0280
    DOI 10.1177/1060028018811657
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Management of dabigatran after overdosage: two case reports and suggestions for monitoring.

    Billoir, Paul / Girault, Christophe / Barbay, Virginie / Boyer, Deborah / Grangé, Steven / Fresel, Marielle / Chrétien, Marie Hélène / Le Cam Duchez, Véronique

    Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis

    2018  Volume 29, Issue 7, Page(s) 653–655

    Abstract: Bleeding is the main complication of anticoagulant treatments as dabigatran etexilate. In patients with atrial fibrillation, dabigatran, at certain doses, has been associated with similar rates of stroke and embolism, and a lower rate of major ... ...

    Abstract : Bleeding is the main complication of anticoagulant treatments as dabigatran etexilate. In patients with atrial fibrillation, dabigatran, at certain doses, has been associated with similar rates of stroke and embolism, and a lower rate of major hemorrhage compared to warfarin. Before the recent possibility of reversing the anticoagulant effect of dabigatran with idarucizumab, prothrombin complex concentrate (PCC) was the main available treatment in cases of severe bleeding or emergency surgery . We describe two different cases with very high overdosage in which PCC or idarucizumab was used to reverse the effect of dabigatran etexilate.
    MeSH term(s) Antibodies, Monoclonal, Humanized/therapeutic use ; Antithrombins/adverse effects ; Blood Coagulation Factors/therapeutic use ; Dabigatran/adverse effects ; Dabigatran/therapeutic use ; Drug Monitoring ; Drug Overdose/drug therapy ; Emergency Treatment ; Hemorrhage/chemically induced ; Hemorrhage/drug therapy ; Humans
    Chemical Substances Antibodies, Monoclonal, Humanized ; Antithrombins ; Blood Coagulation Factors ; prothrombin complex concentrates (37224-63-8) ; idarucizumab (97RWB5S1U6) ; Dabigatran (I0VM4M70GC)
    Language English
    Publishing date 2018-07-24
    Publishing country England
    Document type Case Reports ; Journal Article
    ZDB-ID 1033551-1
    ISSN 1473-5733 ; 0957-5235
    ISSN (online) 1473-5733
    ISSN 0957-5235
    DOI 10.1097/MBC.0000000000000763
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Évaluation du citrate théophylline adénosine dipyridamole (CTAD) et du citrate comme anticoagulant dans la surveillance du traitement par héparine non fractionnée : validation d’une centrifugation différée pour le dosage de l’anti-Xa.

    Billoir, Paul / Clavier, Thomas / Guilbert, Arnaud / Barbay, Virginie / Chrétien, Marie Hélène / Fresel, Marielle / Abriou, Caroline / Girault, Christophe / Le Cam Duchez, Véronique

    Annales de biologie clinique

    2020  Volume 78, Issue 1, Page(s) 27–34

    Abstract: Unfractionated heparin (UFH) is the main anticoagulante used in intensive care unit. The anticoagulant effect is monitored by activated partial thrombin time (aPTT) and anti-Xa activity (anti-Xa) measurement. However, delayed centrifugation induces ... ...

    Title translation Theophylline adenosine dipyridamole (CTAD) and citrate evaluation to survey unfractionated heparin treatment: a delayed centrifugation validation for anti-Xa measurement?.
    Abstract Unfractionated heparin (UFH) is the main anticoagulante used in intensive care unit. The anticoagulant effect is monitored by activated partial thrombin time (aPTT) and anti-Xa activity (anti-Xa) measurement. However, delayed centrifugation induces platelet factor 4 (PF4) release and anti-Xa decrease. Several studies have concluded that aPTT and anti-Xa measurement should be performed within 2 hours in citrated anticoagulant but may be delayed longer in citrate theophylline adenosine and dypiridamol (CTAD) anticoagulant. The objective of this study was to compare the stability of both aPTT and anti-Xa in citrate and CTAD samples, and to determine the effect of delayed centrifugation on both aPTT, anti-Xa results, and PF4 release in citrate samples only.
    Methods: aPTT and anti-Xa were measured in citrate and CTAD anticoagulant samples from 93 patients. Delayed centrifugation was performed in citrate samples from 31 additional patients, with hourly aPTT and anti-Xa measurement from 1 to 6 hours. In 14 of these last patients, PF4 release was also evaluated with Human CXCL4/PF4 Quantikine ELISA Kit.
    Results: We observed a significant correlation between citrate and CTAD anticoagulant for aPTT (r
    Conclusion: We have demonstrated that anti-Xa measurement for unfractionated heparin should be done 4 hours in citrated plasma and that CTAD was not better than citrate. However, these initial findings require confirmation using other aPTT and calibrated anti-Xa assays.
    MeSH term(s) Adenosine/chemistry ; Adenosine/pharmacology ; Anticoagulants/chemistry ; Anticoagulants/pharmacology ; Anticoagulants/therapeutic use ; Blood Coagulation Tests/methods ; Blood Preservation/methods ; Blood Specimen Collection/methods ; Centrifugation/methods ; Chemical Fractionation/methods ; Citric Acid/chemistry ; Citric Acid/pharmacology ; Dipyridamole/chemistry ; Dipyridamole/pharmacology ; Drug Monitoring/methods ; Factor Xa/metabolism ; Factor Xa Inhibitors/analysis ; Factor Xa Inhibitors/blood ; Heparin/analysis ; Heparin/therapeutic use ; Humans ; Partial Thromboplastin Time ; Theophylline/chemistry ; Theophylline/pharmacology ; Thrombin Time ; Time Factors
    Chemical Substances Anticoagulants ; Factor Xa Inhibitors ; Citric Acid (2968PHW8QP) ; Dipyridamole (64ALC7F90C) ; Heparin (9005-49-6) ; Theophylline (C137DTR5RG) ; Factor Xa (EC 3.4.21.6) ; Adenosine (K72T3FS567)
    Language French
    Publishing date 2020-02-27
    Publishing country France
    Document type Evaluation Study ; Journal Article
    ZDB-ID 418098-7
    ISSN 1950-6112 ; 0003-3898
    ISSN (online) 1950-6112
    ISSN 0003-3898
    DOI 10.1684/abc.2020.1525
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Is citrate theophylline adenosine dipyridamole (CTAD) better than citrate to survey unfractionated heparin treatment? Has delayed centrifugation a real impact on this survey?

    Billoir, Paul / Clavier, Thomas / Guilbert, Arnaud / Barbay, Virginie / Chrétien, Marie Hélène / Fresel, Marielle / Abriou, Caroline / Girault, Christophe / Le Cam Duchez, Véronique

    Journal of thrombosis and thrombolysis

    2019  Volume 48, Issue 2, Page(s) 277–283

    Abstract: Unfractionated heparin (UFH) is the main anticoagulant used in intensive care unit. The anticoagulant effect is monitored by activated partial thrombin time (aPTT) and anti-Xa activity (anti-Xa) measurement. However, delayed centrifugation induces ... ...

    Abstract Unfractionated heparin (UFH) is the main anticoagulant used in intensive care unit. The anticoagulant effect is monitored by activated partial thrombin time (aPTT) and anti-Xa activity (anti-Xa) measurement. However, delayed centrifugation induces platelet factor 4 (PF4) release and anti-Xa decrease. Several studies have concluded that aPTT and anti-Xa measurement should be performed within 2 h in citrated anticoagulant but may be delayed longer in Citrate Theophylline Adenosine and Dypiridamol (CTAD) anticoagulant. The objective of this study was to compare the stability of both aPTT and anti-Xa in citrate and CTAD samples, and to determine the effect of delayed centrifugation on both aPTT, anti-Xa results, and PF4 release in citrate samples only. aPTT and anti-Xa were measured in citrate and CTAD anticoagulant samples from 93 patients. Delayed centrifugation was performed in citrate samples from 31 additional patients, with hourly aPTT and anti-Xa measurement from 1 to 6 h. In 14 of these last patients, PF4 release was also evaluated with Human CXCL4/PF4 Quantikine ELISA Kit. We observed a significant correlation between citrate and CTAD anticoagulant for aPTT (r
    MeSH term(s) Anticoagulants/pharmacology ; Blood Coagulation Tests ; Blood Preservation/methods ; Centrifugation ; Citrates/pharmacology ; Dipyridamole/pharmacology ; Drug Monitoring/methods ; Heparin/pharmacokinetics ; Heparin/therapeutic use ; Humans ; Phosphodiesterase Inhibitors/pharmacology ; Theophylline ; Time Factors
    Chemical Substances Anticoagulants ; Citrates ; Phosphodiesterase Inhibitors ; Dipyridamole (64ALC7F90C) ; Heparin (9005-49-6) ; Theophylline (C137DTR5RG)
    Language English
    Publishing date 2019-05-16
    Publishing country Netherlands
    Document type Comparative Study ; Journal Article
    ZDB-ID 1230645-9
    ISSN 1573-742X ; 0929-5305
    ISSN (online) 1573-742X
    ISSN 0929-5305
    DOI 10.1007/s11239-019-01882-1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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