Publications by authors named "Tomáš Bolek"

33 Publications

Direct Oral Anticoagulants Plasma Levels in Patients with Atrial Fibrillation at the Time of Bleeding: A Pilot Prospective Study.

J Cardiovasc Pharmacol 2021 07;78(1):e122-e127

Department of Internal Medicine I, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovak Republic; and.

Abstract: Patients with atrial fibrillation (AF) on long-term direct oral anticoagulants (DOACs) may be at higher risk of bleeding because of higher anti-Xa or anti-IIa levels. However, there is no postmarketing study investigating these DOAC plasma levels at the time of bleeding. The aim of this study was to evaluate DOAC levels at the time of a bleeding emergency. We analyzed 5440 patients examined at our Emergency Department in from April 1, 2019, to September 30, 2019. During this period, we prospective identified 105 consecutive patients with bleeding while on long-term antithrombotic therapy; 49 patients had AF on DOACs. We compared DOAC levels in patients who bled against a control sample of 55 patients who tolerated long-term high dose DOAC therapy without any emergency. Samples of these patients were tested with drug-specific anti-Xa chromogenic analysis (rivaroxaban and apixaban) and with Hemoclot Thrombin Inhibitor assay (dabigatran). Dabigatran-treated patients who bled had significantly higher anti-IIa levels when compared with trough (261.4 ± 163.7 vs. 85.4 ± 57.2 ng/mL, P < 0.001) and peak samples of controls (261.4 ± 163.7 vs. 138.8 ± 78.7 ng/mL, P < 0.05). Similarly, there were significantly higher anti-Xa levels in rivaroxaban-treated and apixaban-treated patients with bleeding compared with trough control samples (rivaroxaban: 245.9 ± 150.2 vs. 52.5 ± 36.4 ng/mL, P <0.001 and apixaban: 311.8 ± 142.5 vs. 119.9 ± 81.7 ng/mL, P < 0.001), as well as in apixaban-treated patients when compared with peak control samples (311.8 ± 142.5 vs. 210.9 ± 88.7 ng/mL, P < 0.05). Finally, rivaroxaban anti-Xa levels in patients who bled tended to be higher compared with peak control samples (245.9 ± 150.2 vs. 177.6 ± 38.6 ng/mL, P = 0.13). This observational study showed a significant difference in anti-IIa and anti-Xa plasma levels in patients with AF with bleeding complications compared with those who tolerated long-term high-dose DOAC therapy without bleeding complications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/FJC.0000000000001038DOI Listing
July 2021

ROTEM Testing for Direct Oral Anticoagulants.

Semin Thromb Hemost 2021 Jun 15. Epub 2021 Jun 15.

Department of Internal Medicine I, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovak Republic.

Direct oral anticoagulants (DOACs) are increasingly used worldwide for the prevention of stroke in patients with atrial fibrillation and to prevent or treat venous thromboembolism. In situations such as serious bleeding, the need for urgent surgery/intervention or the management of a thromboembolic event, the laboratory measurement of DOACs levels or anticoagulant activity may be required. Rotational thromboelastometry (ROTEM) is a viscoelastic hemostatic assay (VHA) which has been used in emergencies (trauma and obstetrics), and surgical procedures (cardiac surgery and liver transplants), but experience with this assay in DOACs-treated patients is still limited. This article reviews the use of ROTEM in the setting of DOACs therapy, focusing on DOACs-associated bleeding and the use of this VHA for the management of reversal strategies for DOACs-associated anticoagulation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/s-0041-1726372DOI Listing
June 2021

How Can Rotational Thromboelastometry as a Point-of-Care Method Be Useful for the Management of Secondary Thromboprophylaxis in High-Risk Pregnant Patients?

Diagnostics (Basel) 2021 May 3;11(5). Epub 2021 May 3.

National Center of Hemostasis and Thrombosis, Department of Hematology and Transfusion Medicine, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin University Hospital, 03659 Martin, Slovakia.

Thromboprophylaxis with low-molecular-weight heparin (LMWH) for patients with a history of venous thromboembolism (VTE) is suggested. Rotational thromboelastometry (ROTEM) represents an innovative point-of-care method enabling the complex and quick evaluation of hemostasis. However, there are only episodic cases of its use for hemostasis assessment and guidance of LMWH in pregnancy. Therefore, we provide the results of unique prospective and longitudinal monitoring of hemostasis in high-risk pregnant women, which we used for the individualized optimalization of secondary thromboprophylaxis. According to the shortening of clot formation time (CFT) in EXTEM ( = 0.0007 from the 26th gestational week vs. controls) and INTEM ( = 0.002 from the 35th gestational week), increase in alpha angle (AA) in EXTEM, INTEM, and HEPTEM, and the persistence of increase in maximum clot firmness (MCF) in EXTEM, INTEM, and HEPTEM ( < 0.001 from the 26th and 35th gestational week vs. controls for EXTEM and INTEM, = 0.0012 from the 26th gestational week in HEPTEM), LMWH dose was modified. Even after the postpartum period, AA in EXTEM was steeper than in controls ( = 0.0007), indicating that hemostasis is not fully normalized after 6-8 weeks following delivery. Therefore, ROTEM may be a useful tool for the individual evaluation of the termination of anticoagulant thromboprophylaxis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/diagnostics11050828DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8147835PMC
May 2021

Does atorvastatin therapy change the anti-Xa activity in xabans-treated patients with atrial fibrillation?

Pharmacol Res Perspect 2021 May;9(3):e00730

Department of Internal Medicine I, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovak Republic.

Atorvastatin and direct oral factor Xa inhibitors (xabans) are frequently co-administrated in patients with atrial fibrillation (AF). However, no studies investigating the possibility of the pharmacologic interaction between these agents have been conducted. The aim of this prospective observational study was to determine the impact of atorvastatin therapy on anti-Xa activity in xabans-treated patients with AF. We enrolled 115 AF patients on long-term rivaroxaban (52 patients) and long-term apixaban (63 patients) therapy. Long-term atorvastatin (40 mg once daily) was administrated to 28 rivaroxaban-treated patients and to 28 apixaban-treated patients. Trough and peak samples were tested for anti-Xa activity with drug-specific anti-Xa chromogenic analysis. For rivaroxaban, there were no significant differences in trough activity (45.5 ± 39.5 ng/ml vs. 46.2 ± 30.1 ng/ml; p = .34) and peak anti-Xa activity (179.2 ± 108.8 ng/ml vs. 208.1 ± 104.1 ng/ml; p = .94) between atorvastatin-treated patients and those without atorvastatin. Similarly, atorvastatin did not impact the trough activity (127.7 ± 71.1 ng/ml vs. 100.8 ± 61.1 ng/ml; p = .12) or peak anti-Xa activity (213.8 ± 103.6 ng/ml vs. 179.3 ± 72.9 ng/ml; p = .14) among apixaban-treated patients with AF. This observational study did not show a significant impact of atorvastatin on trough and peak anti-Xa activity in xabans-treated patients with AF.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/prp2.730DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8118196PMC
May 2021

Use of Fibrinogen Determination Methods in Differential Diagnosis of Hypofibrinogenemia and Dysfibrinogenemia.

Clin Lab 2021 Apr;67(4)

Background: Fibrinogen plays an important role in hemostasis. The normal concentration of fibrinogen in blood plasma is between 1.8 - 4.2 g/L. Decreased fibrinogen levels are observed in congenital afibrinogenemia, hypofibrinogenemia, dysfibrinogenemia, disseminated intravascular coagulation, fibrinolytic therapy, some more severe hepatic parenchymal disorders, and increased blood loss. Elevated fibrinogen levels occur in inflammatory diseases and neoplastic diseases, in pregnancy, and postoperative conditions. Functional fibrinogen measurement is also one of the basic coagulation screening tests. The fibrinogen antigen assay is used to distinguish between qualitative and quantitative fibrinogen disorders.

Methods: The aim of the study was the use of fibrinogen determination methods in differential diagnosis of hypofibrinogenemia and dysfibrinogenemia, statistical evaluation and determine the relationship of fibrinogen Clauss assay, prothrombin time (PT) derived fibrinogen assay, and fibrinogen antigen in the group of 60 patients with congenital fibrinogen disorders (n = 40 dysfibrinogenemia; n = 20 hypofibrinogenemia).

Results: The results measured by the PT-derived fibrinogen assay were approximately four times higher compared to the fibrinogen Clauss assay in the group of patients with dysfibrinogenemia. In patients with hypofibrinogenemia, there is a correlation (r = 0.9016) between the fibrinogen Clauss assay and PT-derived fibrinogen assay with a statistical significance of p < 0.0001. Using a linear or quadratic interpolation function, we were able to determine the fibrinogen Clauss assay and the fibrinogen antigen assay before analysis.

Conclusions: The higher level of the PT-derived fibrinogen assay compared to the fibrinogen Clauss assay in the group of patients with dysfibrinogenemia may pose a greater risk to asymptomatic patients who require diagnosis and treatment in case of bleeding. The fibrinogen value using the PT-derived fibrinogen assay could erroneously give a normal level. The use of the interpolation function is important to estimate the value of fibrinogen activity and antigen before the analysis itself by the Clauss assay or analysis by the fibrinogen antigen assay.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7754/Clin.Lab.2020.200820DOI Listing
April 2021

Viscoelastic Hemostatic Assays and Platelet Function Testing in Patients with Atherosclerotic Vascular Diseases.

Diagnostics (Basel) 2021 Jan 19;11(1). Epub 2021 Jan 19.

Department of Internal Medicine I, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, 036 59 Martin, Slovakia.

Platelets play crucial role in acute vascular atherosclerotic diseases, including myocardial infarction and stroke. Additionally, platelet aggregation is a key target of antiplatelet agents, forming the keystone of pharmacotherapy of various atherosclerotic cardiovascular diseases. Thromboelastography and thromboelastometry, representing currently available viscoelastic hemostatic assays (VHA), are designed as whole blood, real-time analyzers of clot formation and clot resolution. These assays could, in theory, overcome some limitations of currently available platelet function testing assays. This article reviews the current experience with the use of VHA for platelet function testing and for monitoring of the response to antiplatelet therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/diagnostics11010143DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7835760PMC
January 2021

Anti-Xa Activity-Guided Edoxaban Therapy for Cancer-Associated Venous Thromboembolism?

Am J Ther 2020 Jun 1. Epub 2020 Jun 1.

Department of Internal Medicine I, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovak Republic.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MJT.0000000000001202DOI Listing
June 2020

Assessing the hemostasis with thromboelastometry in direct oral anticoagulants-treated patients with atrial fibrillation.

Thromb Res 2020 07 28;191:38-41. Epub 2020 Apr 28.

Department of Internal Medicine I, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovak republic.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.thromres.2020.04.038DOI Listing
July 2020

The Effect of Proton Pump Inhibitor Withdrawal on Dabigatran Etexilate Plasma Levels in Patients With Atrial Fibrillation: A Washout Study.

J Cardiovasc Pharmacol 2020 04;75(4):333-335

Internal Medicine I, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovak Republic; and.

Background: Several studies demonstrated that proton pump inhibitors (PPIs) co-administrated with dabigatran in patients with atrial fibrillation (AF) decreased dabigatran trough and peak plasma levels. However, it is still unknown whether this interaction is reversible or not, and whether the withdrawal of PPI would lead to normalization of dabigatran plasma levels.

Aim Of Study: The aim of this study was to determine the effect of PPI withdrawal on dabigatran plasma levels in patients with AF.

Methods: This pilot prospective study enrolled 23 AF patients on long-term dabigatran and PPI therapy (omeprazole 20 mg twice daily or pantoprazole 40 mg once daily). Dabigatran trough and peak levels (ng/mL) were tested on PPI and after a 2-week period of PPI withdrawal with Hemoclot Thrombin Inhibitor Assay.

Results: The analysis of dabigatran plasma levels demonstrated significant elevation in trough dabigatran levels after 2 weeks of PPI withdrawal (97.2 ± 79.7 vs. 163.8 ± 105.5 ng/mL; P < 0.05). Moreover, significantly higher peak dabigatran levels were observed after 2 weeks of PPI withdrawal (142.4 ± 102.8 vs. 255 ± 129.5 ng/mL; P ≤ 0.001).

Conclusions: This study showed that a 2-week period of PPI withdrawal lead to a significant increase in dabigatran trough and peak plasma levels in patients with AF.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/FJC.0000000000000791DOI Listing
April 2020

Severe hypoglycemia due to insulin self-injection as a cause of acute ST elevation myocardial infarction.

J Diabetes Metab Disord 2019 Dec 10;18(2):739-742. Epub 2019 Aug 10.

Department of Internal Medicine I, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Kollarova 2, 036 59 Martin, Slovakia.

Introduction: The role of hypoglycemia in cardiovascular disease still needs to be evaluated. Incidental case studies provide direct, but so far limited, evidence for the direct impairment of heart caused by hypoglycemia. We present a case of severe hypoglycemia manifesting with acute ST elevation myocardial infarction (STEMI).

Case Presentation: A 48-year old man committed a suicidal attempt by insulin self-injection. The emerged hypoglycemia was accompanied by ECG changes and positive troponins confirming the diagnosis of STEMI. Urgent coronary angiography was performed, but no acute coronary artery closure/critical stenosis was found. After resolution of hypoglycemia all signs of ischemia diminished. Insulin and C-peptide levels confirmed exogenous hyperinsulinemia, confirming insulin self-injection. Sadly, the patient suffered irreversible brain damage.

Conclusion: This patient case shows that severe hypoglycemia can precipitate acute STEMI.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s40200-019-00431-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6915245PMC
December 2019

Type 2 Diabetes, Atrial Fibrillation, and Direct Oral Anticoagulation.

J Diabetes Res 2019 6;2019:5158308. Epub 2019 Dec 6.

Department of Internal Medicine I, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovakia.

Type 2 diabetes (T2D) is an independent risk factor of stroke and systemic embolism in patients with atrial fibrillation (AF), and T2D patients with AF-associated stroke seem to have worse clinical outcome and higher risk of unfavorable clinical course compared to individuals without this metabolic disorder. Long-term anticoagulation is indicated in majority of T2D patients with AF to prevent adverse AF-associated embolic events. Direct oral anticoagulants (DOACs), direct oral thrombin inhibitor dabigatran, and direct oral factor Xa inhibitors, rivaroxaban, apixaban, and edoxaban, have emerged as a preferred choice for long-term prevention of stroke in AF patients offering potent and predictable anticoagulation and a favorable pharmacology with low risk of interactions. This article reviews the current data regarding the use of DOACs in individuals with T2D and AF.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2019/5158308DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6925766PMC
June 2020

Proton Pump Inhibitors and Dabigatran Therapy: Impact on Gastric Bleeding and Dabigatran Plasma Levels.

Semin Thromb Hemost 2019 Nov 19;45(8):846-850. Epub 2019 Sep 19.

Department of Internal Medicine I, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovak Republic.

Dabigatran etexilate, a direct thrombin inhibitor, is now frequently used for long-term pharmacological prevention of stroke or systemic embolism in patients with atrial fibrillation. However, such long-term dabigatran therapy (DT) significantly increases the risk of upper gastrointestinal (GI) bleeding. This increased risk of gastric bleeds might be reduced with gastroprotective agents, such as proton pump inhibitors (PPIs). PPIs coadministrated with dabigatran reduce the risk of upper GI bleeding in patients on long-term oral DT. Nevertheless, there is heated discussion regarding interactions between PPI and dabigatran that lead to decreases in dabigatran plasma levels. This article reviews up to date data about the risk of gastric bleeding on dabigatran, the impact of PPI on the reduction of gastric bleeding, and the interaction between PPI and dabigatran leading to decreased dabigatran plasma levels.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/s-0039-1695735DOI Listing
November 2019

Anti-Xa Activity in Elderly Xabans-Treated Patients With Atrial Fibrillation.

Am J Ther 2020 Sep/Oct;27(5):e507-e509

Department of Internal Medicine I, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovak Republic.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MJT.0000000000001014DOI Listing
July 2021

Direct Oral Anticoagulants: Novel Approach for the Treatment of Thrombosis in Pediatric Patients?

Pediatr Cardiol 2019 Oct 20;40(7):1431-1438. Epub 2019 Jul 20.

Department of Internal Medicine I, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Kollarova 2, 036 59, Martin, Slovak Republic.

Venous thromboembolism (VTE) is a rare, but life-threatening disease in those who have not reached their adulthood. This condition is usually treated with heparin or low molecular weight heparins which require parenteral administration and, in case of unfractionated heparin, also frequent laboratory monitoring and dose adjustment. Direct oral anticoagulants (DOACs)-direct thrombin inhibitor dabigatran, and direct oral factor Xa inhibitors rivaroxaban, apixaban, and edoxaban-are currently frequently used for the prevention and treatment of VTE in adult population. In fact, these agents offer several advantages compared to traditional agents, such as oral route of administration, short on-set and off-set of action, predictable pharmacologic profile with low risk of food and drug interactions, and no need for routine laboratory assessment of anticoagulant activity. However, clinical experience with these directly acting oral anticoagulants in pediatric population is very limited as these drugs had been tested and are used mostly in adult individuals. This article reviews the current data from pre- and post-marketing studies reporting the use of DOACs for the treatment of VTE in pediatric patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00246-019-02159-3DOI Listing
October 2019

Apixaban: a novel agent to treat heparin induced thrombocytopenia and to prevent embolism in patient with atrial fibrillation after multiple valve replacement?

J Thromb Thrombolysis 2019 Nov;48(4):619-622

Department of Internal Medicine I, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Kollarova 2, 036 59, Martin, Slovak Republic.

Very limited but promising experiences with the use of direct factor Xa inhibitors for the treatment of heparin-induced thrombocytopenia (HIT) have been reported. This contribution features our first experience with the use of apixaban (without a pre-treatment with parenteral anticoagulant) to treat a case of HIT which developed in a patient after multiple heart replacement surgery. Apixaban was effective, well tolerated and safe. An apixaban-calibrated chromogenic anti-Xa activity assessment was used to monitor apixaban activity throughout the therapy. Patient continued on apixaban for the prevention of thrombosis in the settings of atrial fibrillation. No ischemic or bleeding events occurred during the clinical follow up and the platelet count was stable. Our experience suggests that apixaban might be effectively used for the treatment of HIT and for the long-term prevention of embolism in patients after multiple valve replacement with biological prostheses and atrial fibrillation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11239-019-01910-0DOI Listing
November 2019

Dabigatran levels in omeprazole versus pantoprazole-treated patients with atrial fibrillation: is there a difference?

Eur J Clin Pharmacol 2019 Jun 12;75(6):875-877. Epub 2019 Feb 12.

Department of Internal Medicine I, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Kollarova 2, 036 59, Martin, Slovak Republic.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00228-019-02647-8DOI Listing
June 2019

How to proceed with long-term anticoagulation in patient after total gastrectomy and atrial fibrillation?

Eur J Clin Pharmacol 2019 Feb 9;75(2):285-286. Epub 2018 Oct 9.

Department of Internal Medicine I, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Kollarova 2, 036 59, Martin, Slovak Republic.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00228-018-2571-9DOI Listing
February 2019

Does proton pump inhibition change the on-treatment anti-Xa activity in xabans-treated patients with atrial fibrillation? A pilot study.

J Thromb Thrombolysis 2019 Jan;47(1):140-145

Department of Internal Medicine I, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Kollarova 2, 036 59, Martin, Slovakia.

Proton pump inhibition (PPI) reduces gastrointestinal bleeding on direct oral anticoagulants. However, PPI may affect dabigatran on-treatment levels; and there is no information regarding the effect of PPI on xabans on-treatment activity. Thus, the aim of this study was to determine the impact of PPI on therapeutic anti-Xa activity in rivaroxaban- and apixaban-treated patients with atrial fibrillation (AF). This single-centre pilot prospective study enrolled 77 consecutive xabans-treated patients (42 rivaroxaban-treated and 35 apixaban-treated patients) with AF. PPI was administrated in 44 patients. Trough and peak anti-Xa activity was assessed with factor Xa-calibrated anti-Xa chromogenic analysis. There were no significant differences in trough anti-Xa activity comparing PPI-treated patients and patients without PPI (80.5 ± 66.5 ng/mL in PPI group vs. 71.6 ± 64.1 ng/mL in non-PPI group, p = 0.57, Table 2). Similarly, there were no significant differences in peak anti-Xa activity between compared groups (175.2 ± 102.5 ng/mL in PPI group vs. 202.9 ± 84.1 ng/mL in non-PPI group, p = 0.21). This pilot study did not reveal significant changes in xabans on-treatment anti-Xa activity according the PPI status.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11239-018-1748-5DOI Listing
January 2019

Role of Thromboelastography and Rotational Thromboelastometry in the Management of Cardiovascular Diseases.

Clin Appl Thromb Hemost 2018 Nov 24;24(8):1199-1207. Epub 2018 Jul 24.

1 Department of Internal Medicine I, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovak Republic.

The monitoring of coagulation by viscoelastometric methods-thromboelastography and rotational thromboelastometry-may detect the contributions of cellular and plasma components of hemostasis. These methods might overcome some of the serious limitations of conventional laboratory tests. Viscoelastic testing can be repeatedly performed during and after surgery and thus provides a dynamic picture of the coagulation process during these periods. Several experiences with the use of these methods in cardiovascular surgery have been reported, but there is perspective for more frequent use of these assays in the assessment of platelet response to antiplatelet therapy and in the assessment of coagulation in patients on long-term dabigatran therapy. This article reviews the current role and future perspectives of thromboelastography and thromboelastometry in the management of cardiovascular diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1076029618790092DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6714776PMC
November 2018

Proton Pump Inhibition in Patients Treated With Novel Antithrombotic Drugs: Should We Worry About Thrombosis?

J Cardiovasc Pharmacol 2018 07;72(1):71-76

Department of Internal Medicine I, Jessenius Faculty of Medicine, Comenius University, Martin, Slovak Republic.

Proton pump inhibition (PPI) administered together with antiplatelet and anticoagulant agents reduces the risk of gastrointestinal hemorrhage. Several novel antithrombotic agents have been recently introduced for patients with acute coronary syndrome (prasugrel and ticagrelor) or for patients requiring long-term anticoagulation (dabigatran, rivaroxaban, apixaban, edoxaban, and betrixaban). In fact, these agents might offer even stronger inhibition of platelets or coagulation compared with older agents; therefore, the need for gastroprotection might be even stronger when these new agents are used for long-term antithrombotic therapy. On the contrary, there are several reports regarding an adverse interaction between PPI and antithrombotic agents connected with a reduction in antithrombotic therapy on-treatment levels, implicating a higher risk of thrombosis. This interaction was demonstrated in clopidogrel-treated patients and more recently also in dabigatran-treated patients. This article discusses a possible novel antithrombotic therapy/PPI interaction leading to higher risk of thrombosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/FJC.0000000000000593DOI Listing
July 2018

Dabigatran Levels in Elderly Patients with Atrial Fibrillation: First Post-Marketing Experiences.

Drugs Aging 2018 06;35(6):539-544

Department of Internal Medicine I, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Kollarova 2, 036 59, Martin, Slovak Republic.

Background: The number of elderly individuals with non-valvular atrial fibrillation (NV-AF) requiring long-term anticoagulation is rising. The pharmacokinetics of oral anticoagulants in elderly individuals may differ from that for younger patients. The aim of this study was to assess the dabigatran levels in elderly patients with NV-AF.

Patients And Methods: A pilot prospective post-marketing study in patients with NV-AF on dabigatran therapy was performed; we enrolled 21 consecutive elderly patients (aged ≥ 75 years) on a reduced dabigatran regimen (110 mg twice daily) and compared them with 13 younger (≤ 70 years) individuals on reduced dabigatran therapy due to renal impairment and with 16 younger patients on standard dabigatran therapy (150 mg twice daily). Blood samples were taken for the assessment of dabigatran trough and peak levels. Dabigatran levels were measured with the Hemoclot Thrombin Inhibitor Assay.

Results: There were significant differences in dabigatran trough levels when comparing elderly patients on reduced dabigatran with non-elderly patients on reduced dabigatran (99.3 ± 73.6 vs 51.6 ± 25.6 ng/mL; p < 0.01). Similarly, the detected dabigatran peak levels were significantly higher in elderly patients on reduced dabigatran compared with non-elderly patients on reduced dabigatran (173.4 ± 116.2 vs 116.1 ± 19.1 ng/mL; p < 0.01). No significant differences in dabigatran trough and peak levels were found when comparing elderly patients on reduced dabigatran with non-elderly patients on standard dabigatran therapy.

Conclusion: This pilot study demonstrated that elderly patients on reduced dabigatran exhibit significantly higher dabigatran levels than younger individuals on a reduced regimen, and similar levels compared with younger individuals on standard dabigatran.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s40266-018-0552-4DOI Listing
June 2018

Anti-Xa activity in oral factor Xa inhibitor-treated patients with atrial fibrillation and a higher risk of bleeding: a pilot study.

Blood Coagul Fibrinolysis 2018 Jun;29(4):369-373

Department of Internal Medicine I, Jessenius Faculty of Medicine in Martin.

: The number of patients with nonvalvular atrial fibrillation (NV-AF) who require long-term anticoagulation and also have a higher risk of bleeding is increasing. Recently, there is no information regarding real on-treatment anti-Xa activity in patients with NV-AF and a higher risk of bleeding who receive oral factor Xa inhibitors. The aim of this study was to determine trough and peak anti-Xa activity in these patients. This single-centre pilot study enrolled 41 patients with NV-AF and a higher risk of bleeding defined as Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol Concomitantly score at least 3 points. Twenty-one patients were treated with rivaroxaban and 17 patients were treated with apixaban. The trough and peak samples of these patients were tested for anti-Xa activity with factor Xa-calibrated anti-Xa chromogenic analysis. The detected trough anti-Xa activity was 63.2 ± 44.4 ng/ml. There was a significant increase in peak anti-Xa activity up to 170.3 ± 99.6 ng/ml (P < 0.001) observed. There were no significant differences in trough (52.4 ± 41.9 vs. 76.0 ± 45.4 ng/ml; P = 0.12) and peak (187.2 ± 122.5 vs. 151.5 ± 64.0 ng/ml; P = 0.27) anti-Xa activity between rivaroxaban-treated and apixaban-treated patients. This study demonstrated the anti-Xa activity in oral factor Xa inhibitor-treated patients with NV-AF and a higher risk of bleeding. No significant differences in this activity between rivaroxaban-treated and apixaban-treated patients were found.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MBC.0000000000000721DOI Listing
June 2018

Does type 2 diabetes affect the on-treatment levels of direct oral anticoagulants in patients with atrial fibrillation?

Diabetes Res Clin Pract 2018 Jan 23;135:172-177. Epub 2017 Nov 23.

Department of Internal Medicine I, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovak Republic; National Centre of Hemostasis and Thrombosis, Department of Hematology and Blood Transfusion, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovak Republic.

Aims: Type 2 diabetes (T2D) is connected with several abnormalities in haemostasis; and with higher risk of stroke and systemic embolism in patients with non-valvular atrial fibrillation (NV-AF). However, it is recently unknown whether T2D affects the activity of direct oral anticoagulants (DOACs). The aim of this study was to determine the impact of T2D on DOACs activity in patients with NV-AF.

Methods: This pilot prospective study enrolled totally 65 patients with NV-AF (20 dabigatran-treated, 110 mg/twice daily; 28 rivaroxaban-treated, 15 mg/daily; 17 apixaban-treated, 5 mg/twice daily). 25 patients had T2D (8 dabigatran-treated, 11 rivaroxaban-treated, and 6 apixaban-treated). DOAC activity was tested with Hemoclot® Thrombin Inhibitor assay in dabigatran-treated patients, and with factor Xa-calibrated anti-Xa chromogenic analysis in rivaroxaban- and apixaban-treated patients prior and two hours after drug administration.

Results: There were no significant differences in dabigatran baseline (62.1 ± 8.0 vs. 51.8 ± 38.9 ng/ml, p = .76) and 2-h-post-drug-administration (91.7 ± 57.2 vs. 72.2 ± 33.2 ng/ml, p = .48) activity comparing T2D and non-diabetic patients. Similarly, no significant differences were found in rivaroxaban baseline (35.9 ± 22.5 vs. 55.3 ± 45.1 ng/ml, p = .19) and 2-h-post-drug-administration (145.7 ± 74.1 vs. 202.6 ± 135.0 ng/ml, p = .22) anti-Xa activity. In addition, no significant differences were present in apixaban baseline (96.0 ± 54.5 vs. 63.9 ± 36.8 ng/ml, p = .24) and 2-h-post-drug-administration (151.0 ± 78.3 vs. 151.7 ± 59.1 ng/ml, p = .98) anti-Xa activity between T2D and non-diabetic patients.

Conclusions: This pilot study did not detect differences in DOACs activity according to T2D status in patients with NV-AF.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.diabres.2017.11.024DOI Listing
January 2018

Platelet Aggregation in Direct Oral Factor Xa Inhibitors-treated Patients With Atrial Fibrillation: A Pilot Study.

J Cardiovasc Pharmacol 2017 Oct;70(4):263-266

*Department of Gastroenterology, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovak Republic; †National Centre of Hemostasis and Thrombosis, Department of Hematology and Blood Transfusion, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovak Republic; and ‡Department of Internal Medicine I, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovak Republic.

Background: Activated factor X (factor Xa) plays an important role in regulation of platelets. The aim of this study was to test the effect of direct oral factor Xa inhibitors-rivaroxaban and apixaban-on platelet aggregation in patients with nonvalvular atrial fibrillation.

Patients And Methods: This single-center pilot study enrolled 21 factor Xa inhibitors-treated (9 rivaroxaban-treated and 12 apixaban-treated) patients with nonvalvular atrial fibrillation. The trough and peak samples of these patients were tested for adenosine diphosphate (ADP)-induced, epinephrine-induced, and collagen-induced platelet aggregation with light transmission aggregometry, and with factor Xa-calibrated anti-Xa chromogenic analysis.

Results: The detected trough anti-Xa activity was 57.5 ± 43.4 μg/L. There was a significant increase in peak anti-Xa activity to 175.9 ± 119.6 μg/L (P < 0.001) observed. The platelet aggregation was reduced with reduced inductor concentration. However, no significant changes in ADP-induced, or in epinephrine-induced, or in collagen-induced platelet aggregation were seen comparing trough and peak sample. There were no significant differences in anti-Xa activity or in platelet aggregation comparing rivaroxaban-treated and apixaban-treated patients.

Conclusions: This study showed that factor Xa inhibition does not affect ADP-induced, epinephrine-induced, and collagen-induced platelet aggregation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/FJC.0000000000000516DOI Listing
October 2017

The Impact of Proton Pump Inhibition on Dabigatran Levels in Patients With Atrial Fibrillation.

Am J Ther 2019 May/Jun;26(3):e308-e313

Department of Internal Medicine I, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovak Republic.

Background: Proton pump inhibition (PPI) administrated together with dabigatran reduces the risk of gastrointestinal hemorrhage. However, there is a discussion regarding possible PPI-dabigatran interaction that may reduce the efficacy of this therapy.

Study Question: To determine the impact of concomitant PPI on dabigatran plasma levels in patients with nonvalvular atrial fibrillation (NV-AF).

Study Design: A pilot prospective study in patients with NV-AF on dabigatran therapy was performed; 31 patients were enrolled. PPI with either omeprazole or pantoprazole was administrated in 19 patients.

Measures And Outcomes: Blood samples were taken for the assessment of the dabigatran trough and peak levels. Dabigatran concentration was measured with the Hemoclot Thrombin Inhibitor Assay.

Results: There were significant differences in dabigatran trough level comparing patients treated with PPI and patients without PPI (58.86 ± 36.76 ng/mL vs. 110.72 ± 88.47 ng/mL, P < 0.05). Similarly, there were significant differences in dabigatran peak level between compared groups (88.0 ± 20.5 ng/mL vs. 174.4 ± 139.64 ng/mL, P < 0.05).

Conclusions: This pilot study demonstrated the interaction between PPI and dabigatran levels in patients with NV-AF.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MJT.0000000000000599DOI Listing
November 2019

Review of the Pharmacology of the Emerging Possibilities of the Direct Oral Anticoagulants' Reversal.

Curr Drug Metab 2017 ;18(7):643-650

National Centre of Hemostasis and Thrombosis, Department of Hematology and Blood Transfusion, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin. Slovakia.

Background: Direct oral anticoagulants (DOACs) offer consistent and predictable anticoagulation, oral administration with good patient compliance and a good safety profile. Dabigatran - a direct thrombin inhibitor, apixaban and rivaroxaban - direct factor Xa inhibitors are now largely used for anticoagulation in patients with nonvalvular atrial fibrillation and in patients with venous thromboembolism. These agents have emerged as an expediential clinical choice in long-term anticoagulation for an increasing number of patients. Despite their advantages, concerns persist about a lack of rapid reversal agents in urgent clinical situations.

Methods: This review is focused on the pharmacology of nonspecific and target-specific reversal agents for DOACs-induced anticoagulation. A systemic review of preclinical and clinical studies published in peer-reviewed scientific journals was performed.

Results And Conclusions: Fresh frozen plasma and coagulation factors concentrates might be considered in bleeding emergencies; however, there is a lack of larger studies confirming the efficacy of coagulation factors concentrates for the reversal of DOACs-induced anticoagulation, and a particular risk of coagulation factors concentrates-induced thrombosis. Recently, idarucizumab has been approved commercially for acute reversal of dabigatran in emergencies as a first target-specific reversal agent. Moreover, andexanet alpha and aripazine are being extensively studied in several phase II and III clinical studies. It is likely that more target-specific agents for reversal of DOACs-induced anticoagulation will be introduced to clinical practice in near future.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2174/1389200218666170413155351DOI Listing
September 2018

Monitoring the hemostasis with rotation thromboelastometry in patients with acute STEMI on dual antiplatelet therapy: First experiences.

Medicine (Baltimore) 2017 Feb;96(6):e6045

Department of Internal Medicine I National Centre of Haemostasis and Thrombosis, Department of Hematology and Transfusiology, Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin, Martin, Slovak Republic.

Rotation thromboelastometry (ROTEM) is a viscoelastometric point-of-care-test for the complex evaluation of changes in hemostasis, performed in whole blood. However, no prospective study evaluating the efficacy of the antiplatelet therapy using ROTEM was performed.Fifty-six patients (34 men, 22 women, mean age 67.75 years, and age range 34-88 years) with acute ST-elevation myocardial infarction (STEMI), treated with dual antiplatelet therapy, undergoing urgent coronary angiography and percutaneous coronary intervention (PCI) of culprit coronary lesion were included. Three blood samples were taken (sample 1 taken before the urgent coronary angiography, sample 2 in 24 hours after the admission, and sample 3 in 30 days after acute STEMI). Twenty-one healthy blood donors (17 men, 4 women, mean age 50.38 years, and age range 40-74 years) were recruited as the control group. Blood samples were tested with ROTEM Gamma (Pentapharm GmbH, Munich, Germany) and light transmission aggregometry (LTA).Clotting time (CT) was significantly prolonged and maximum clot firmness (MCF) was significantly higher in patients compared to controls. Mean platelet aggregation after the induction with arachidonic acid (33.2% vs 74.6% in sample 1 and 21.1% vs 74.6% in sample 2), as well as adenosine diphosphate (51.4% vs 72.7% in sample 1 and 37.1% vs 72.7% in sample 2), were significantly lower in patients with acute STEMI.Significantly prolonged CT and increased MCF was found in patients with acute STEMI. This study confirmed the ability of ROTEM to identify changes in hemostasis in ACS patients on antithrombotic therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MD.0000000000006045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5313005PMC
February 2017

The Impact of Type 2 Diabetes on the Efficacy of ADP Receptor Blockers in Patients with Acute ST Elevation Myocardial Infarction: A Pilot Prospective Study.

J Diabetes Res 2016 17;2016:2909436. Epub 2016 Jul 17.

Department of Internal Medicine I, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, 03659 Martin, Slovakia.

Background. The aim of this study was to validate the impact of type 2 diabetes (T2D) on the platelet reactivity in patients with acute ST elevation myocardial infarction (STEMI) treated with adenosine diphosphate (ADP) receptor blockers. Methods. A pilot prospective study was performed. Totally 67 patients were enrolled. 21 patients had T2D. Among all study population, 33 patients received clopidogrel and 34 patients received prasugrel. The efficacy of ADP receptor blocker therapy had been tested in two time intervals using light transmission aggregometry with specific inducer and vasodilator-stimulated phosphoprotein phosphorylation (VASP-P) flow cytometry assay. Results. There were no significant differences in platelet aggregability among T2D and nondiabetic (ND) group. The platelet reactivity index of VASP-P did not differ significantly between T2D and ND group (59.4 ± 30.9% versus 60.0 ± 25.2% and 33.9 ± 25.3% versus 38.6 ± 29.3% in second testing). The number of ADP receptor blocker nonresponders did not differ significantly between T2D and ND patients. The time interval from ADP receptor blocker loading dosing to the blood sampling was similar in T2D and ND patients in both examinations. Conclusion. This prospective study did not confirm the higher platelet reactivity and higher prevalence of ADP receptor blocker nonresponders in T2D acute STEMI patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2016/2909436DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4967473PMC
June 2017

[Acute causes of sudden deaths in patients with severe hypoglycemia].

Vnitr Lek Summer 2016;62(6):462-6

Unlabelled: Hypoglycemia is a serious event, which is associated with the neurological and cardiovascular events. Hypoglycemia can be also associated with sudden death, however, the prevalence of these sudden deaths is not exactly known. Hypoglycemia is associated with the risk of sudden death in patients with type 1. and 2. type diabetes mellitus and also in critically ill patients. Sudden death can occure due to cardiovascular, neurological or metabolic disorders associated with hypoglycemia. The article provides a review of current knowledge about the prevalence of severe hypoglycemia, the association between hypoglycemia and sudden deaths and about the causes of sudden death in patients with severe hypoglycemia.

Key Words: hypoglycemia - prevalence of these sudden deaths - severe hypoglycemia.
View Article and Find Full Text PDF

Download full-text PDF

Source
June 2017