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Cureus Jan 2023The dual coagulation disorder hereditary protein S deficiency and activated protein C (APC) resistance, which clinically manifests with recurrent venous thrombosis and...
The dual coagulation disorder hereditary protein S deficiency and activated protein C (APC) resistance, which clinically manifests with recurrent venous thrombosis and multifocal ischemic stroke, has only rarely been reported in the same patient. The patient is a 54-year-old male with a history of recurrent, asymptomatic ischemic stroke or transient ischemic attack (TIA) since age 14 and four episodes of deep vein thromboses (DVT), two complicated by pulmonary embolism, attributed to hereditary protein S deficiency and homozygous factor V Leiden mutation. In addition, the medical history was positive for obesity, previous chronic alcoholism, smoking, gynecomastia with left breast resection, arterial hypertension, hepatic steatosis, and cholecystolithiasis. Because of low compliance, long-term oral anticoagulation with phenprocoumon from the age of 38 was replaced by dabigatran (300 mg/d) after another stroke with bleeding at the age of 54. In summary, the simultaneous presence of two hereditary coagulation disorders can lead to multiple venous thromboses and recurrent ischemic stroke. An appealing therapeutic option in poorly compliant patients with these two hereditary clotting defects is the replacement of long-term anticoagulation with a vitamin K antagonist (VKA) by a direct oral anticoagulant.
PubMed: 36824536
DOI: 10.7759/cureus.34012 -
BioMed Research International 2015A relevant number of patients receive triple therapy with clopidogrel, aspirin, and oral anticoagulation. Clopidogrel's efficacy on ADP induced platelet function may be... (Comparative Study)
Comparative Study Randomized Controlled Trial
Impact of Dabigatran versus Phenprocoumon on ADP Induced Platelet Aggregation in Patients with Atrial Fibrillation with or without Concomitant Clopidogrel Therapy (the Dabi-ADP-1 and Dabi-ADP-2 Trials).
BACKGROUND
A relevant number of patients receive triple therapy with clopidogrel, aspirin, and oral anticoagulation. Clopidogrel's efficacy on ADP induced platelet function may be influenced by concomitant antithrombotic therapies. Data regarding the effect of dabigatran on platelet function is limited to in vitro studies and healthy individuals.
METHODS
The "Dabi-ADP-1" and "Dabi-ADP-2" trials randomized patients with atrial fibrillation to either dabigatran or phenprocoumon for a 2-week period. In Dabi-ADP-1 (n = 70) patients with clopidogrel therapy were excluded and in Dabi-ADP-2 (n = 46) patients had to be treated concomitantly with clopidogrel. The primary endpoint was ADP-induced platelet aggregation between dabigatran and phenprocoumon at 14 days. Secondary endpoints were ADPtest HS-, TRAP-, and COL-induced platelet aggregation.
RESULTS
There was no significant difference regarding the primary endpoint between both groups in either trial (Dabi-ADP-1: Dabigatran: 846 [650-983] AU × min versus phenprocoumon: 839 [666-1039] AU × min, P = 0.90 and Dabi-ADP-2: 326 [268-462] versus 350 [214-535], P = 0.70) or regarding the secondary endpoints, ADPtest HS-, TRAP-, and COL-induced platelet aggregation.
CONCLUSION
Dabigatran as compared to phenprocoumon has no impact on ADP-induced platelet aggregation in atrial fibrillation patients neither with nor without concomitant clopidogrel therapy.
Topics: Adenosine Diphosphate; Administration, Oral; Aged; Aged, 80 and over; Atrial Fibrillation; Clopidogrel; Dabigatran; Female; Follow-Up Studies; Humans; Male; Middle Aged; Phenprocoumon; Platelet Aggregation; Ticlopidine
PubMed: 26229963
DOI: 10.1155/2015/798486 -
RoFo : Fortschritte Auf Dem Gebiete Der... Nov 2015To investigate the incidence and possible risk factors of upper deep vein obstruction in patients both prior to first cardiac device implantation and before device...
Venous Obstruction in Asymptomatic Patients Undergoing First Implantation or Revision of a Cardiac Pacemaker or Implantable Cardioverter-Defibrillator: A Retrospective Single Center Analysis.
PURPOSE
To investigate the incidence and possible risk factors of upper deep vein obstruction in patients both prior to first cardiac device implantation and before device revision.
MATERIALS AND METHODS
Records of asymptomatic patients undergoing contrast venography prior to implantation or revision of a cardiac device from 09/2009 to 04/2012 were reviewed. Venograms were used to determine the presence of venous obstruction. Interrelations between the incidence of venous obstruction and patient- or device-related parameters were identified using Fisher's exact test and univariate logistic regression. Multivariate logistic regression was used to identify independent predictors of venous obstruction.
RESULTS
456 patients met the inclusion criteria (330 males, 126 females, 67.8 ± 12.9 years). 100 patients underwent first implantation, and 356 patients underwent device revision (mean time since implantation 82.5 ± 75.3 months). Venous obstruction was present in 11.0 % and 30.1 % before implantation and revision, respectively. Only presence of ventricular escape rhythm was significantly related to venous occlusion (p < 0.001) prior to first implantation. Prior to revision, significant predictors were male sex (p = 0.01), time since implantation (p < 0.0001), presence of escape rhythm (p = 0.02), compromised coagulation (p = 0.02), phenprocoumon (p = 0.005), and peripheral arterial disease (p = 0.01).
CONCLUSION
Although several risk factors could be identified, reliable prediction of venous obstruction was not possible. Therefore, we advocate performing venography in all patients prior to device revision or upgrade to avoid complications. In cases of first device implantation, the risks associated with venography should be weighed against the surprisingly high rate of deep upper vein obstruction.
Topics: Aged; Aged, 80 and over; Arm; Defibrillators, Implantable; Equipment Failure Analysis; Female; Humans; Logistic Models; Male; Middle Aged; Pacemaker, Artificial; Phlebography; Postoperative Complications; Reoperation; Retrospective Studies; Risk Factors; Statistics as Topic; Venous Thrombosis
PubMed: 26200569
DOI: 10.1055/s-0035-1553351 -
Europace : European Pacing,... Apr 2018Several studies showed reduced stroke severity in patients with atrial fibrillation (AF) if the international normalized ratio (INR) was ≥ 2 at stroke onset. There... (Comparative Study)
Comparative Study Observational Study
AIMS
Several studies showed reduced stroke severity in patients with atrial fibrillation (AF) if the international normalized ratio (INR) was ≥ 2 at stroke onset. There are no respective data for non-vitamin K-dependent oral anticoagulants (NOACs). The aim of this study was to compare the impact of NOAC or phenprocoumon intake on stroke severity.
METHODS AND RESULTS
In this single-centre observational study, 3669 patients with acute ischaemic stroke were retrospectively analysed regarding AF status and medication immediately before admission. Using multivariable regression, we analysed the association of pre-admission anticoagulation with severe stroke (National Institutes of Health Stroke Scale score ≥ 11) on admission and poor outcome at discharge (modified Rankin scale score > 2). Before the index stroke, 655 patients had known AF and a CHA2DS2-VASc score ≥ 2. While 325 (49.6%) patients were anticoagulated, 159 (24.3%) were prescribed a NOAC and 75 (11.5%) phenprocoumon patients had an INR ≥ 2 on admission. Compared with AF patients without medical stroke prevention, an INR ≥ 2 [OR 0.23 (95% CI 0.10-0.53)] or NOAC intake [OR 0.48 (95% CI 0.27-0.86)] were associated with a lower probability of severe stroke after adjustment for confounders, while an INR < 2 [OR 0.62 (95% CI 0.33-1.16)] was not. Adjusted odds ratios for poor functional outcome at hospital discharge were 0.47 (95% CI 0.27-0.84) for NOAC patients, 0.33 (95% CI 0.17-0.65) for INR ≥ 2 and 0.61 (95% CI 0.32-1.16) for INR < 2.
CONCLUSION
NOAC intake before stroke did reduce the probability of severe stroke on hospital admission and poor functional outcome at hospital discharge as similarly demonstrated for phenprocoumon patients with an INR ≥ 2 on admission.
Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Brain Ischemia; Female; Hospitalization; Humans; International Normalized Ratio; Male; Phenprocoumon; Protective Factors; Retrospective Studies; Risk Factors; Severity of Illness Index; Stroke; Time Factors; Treatment Outcome
PubMed: 28460024
DOI: 10.1093/europace/eux087 -
Journal of Thrombosis and Haemostasis :... Jan 2016ESSENTIALS: It is not known if initiation of glucose-lowering drugs alters the efficacy of vitamin K antagonists (VKA). We examined if glucose-lowering drugs affected...
UNLABELLED
ESSENTIALS: It is not known if initiation of glucose-lowering drugs alters the efficacy of vitamin K antagonists (VKA). We examined if glucose-lowering drugs affected international normalized ratio (INR) in VKA-treated patients. Upon initiating glucose-lowering drugs, 51% of patients had INR values below the therapeutic window. Monitoring of INR levels should be intensified upon initiation of glucose-lowering drugs.
BACKGROUND
It is not known whether initiation of antidiabetic treatment affects the effect of vitamin K antagonists (VKAs). It was previously shown that metformin affects the effect of one VKA, phenprocoumon.
OBJECTIVES
The aim of this study was to determine if initiation of glucose-lowering treatment affects the international normalized ratio (INR) and dose requirements of the anticoagulant VKAs warfarin and phenprocoumon.
PATIENTS/METHODS
We performed a self-controlled retrospective register-based study. A total of 118 patients commencing glucose-lowering treatment while being treated with warfarin or phenprocoumon were included in the study. We compared INR, dose/INR and proportion of patients with at least one sub-therapeutic INR measurement before and after initiation of glucose-lowering treatment.
RESULTS
Initiation of glucose-lowering treatment caused mean INR to decrease from 2.5 to 2.2 (decrease of -0.3 [95% CI: -0.1; -0.5]) and led to more than half of the patients having at least one sub-therapeutic INR measurement. Six to 12 weeks later, the VKA dose/INR was increased by 11%, indicating a weakened effect of the VKA.
CONCLUSION
Initiation of glucose-lowering treatment reduces the anticoagulant effect of VKAs to an extent that is likely to be clinically relevant. This finding needs confirmation and mechanistic explanation.
Topics: Aged; Anticoagulants; Blood Glucose; Drug Interactions; Female; Fibrinolytic Agents; Humans; Hypoglycemic Agents; International Normalized Ratio; Male; Metformin; Middle Aged; Phenprocoumon; Registries; Retrospective Studies; Vitamin K; Warfarin
PubMed: 26559049
DOI: 10.1111/jth.13187 -
PloS One 2016Risk scores for patients who are at high risk for major bleeding complications during treatment with vitamin K antagonists (VKAs) do not perform that well. BLEEDS was...
BACKGROUND
Risk scores for patients who are at high risk for major bleeding complications during treatment with vitamin K antagonists (VKAs) do not perform that well. BLEEDS was initiated to search for new biomarkers that predict bleeding in these patients.
OBJECTIVES
To describe the outline and objectives of BLEEDS and to examine whether the study population is generalizable to other VKA treated populations.
METHODS
A cohort was created consisting of all patients starting VKA treatment at three Dutch anticoagulation clinics between January-2012 and July-2014. We stored leftover plasma and DNA following analysis of the INR.
RESULTS
Of 16,706 eligible patients, 16,570 (99%) were included in BLEEDS and plasma was stored from 13,779 patients (83%). Patients had a mean age of 70 years (SD 14), 8713 were male (53%). The most common VKA indications were atrial fibrillation (10,876 patients, 66%) and venous thrombosis (3920 patients, 24%). 326 Major bleeds occurred during 17,613 years of follow-up (incidence rate 1.85/100 person years, 95%CI 1.66-2.06). The risk for major bleeding was highest in the initial three months of VKA treatment and increased when the international normalized ratio increased. These results and characteristics are in concordance with results from other VKA treated populations.
CONCLUSION
BLEEDS is generalizable to other VKA treated populations and will permit innovative and unbiased research of biomarkers that may predict major bleeding during VKA treatment.
Topics: Acenocoumarol; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Female; Fibrinolytic Agents; Follow-Up Studies; Hemorrhage; Humans; International Normalized Ratio; Longitudinal Studies; Male; Middle Aged; Phenprocoumon; Prognosis; Risk Factors; Venous Thrombosis; Vitamin K
PubMed: 27935941
DOI: 10.1371/journal.pone.0164485 -
Cardiovascular Therapeutics Jun 2016Data evaluating the complications of pulmonary vein isolation (PVI) using second-generation cryoballoons (CB) related to different anticoagulation regimes are limited.... (Comparative Study)
Comparative Study Observational Study
The Total Incidence of Complications and the Impact of an Anticoagulation Regime on Adverse Events After Cryoballoon Ablation of Atrial Fibrillation: A Single-Center Study of 409 Patients.
AIM
Data evaluating the complications of pulmonary vein isolation (PVI) using second-generation cryoballoons (CB) related to different anticoagulation regimes are limited. This study evaluates the total complications and the impact of novel oral anticoagulants (NOACs) compared to phenprocoumon on adverse events in the setting of PVI using CB.
METHODS AND RESULTS
PVI was performed using second-generation CB by two experienced investigators. A total of 409 patients (58.9% male; mean age = 61 ± 10 years) with atrial fibrillation were included in this study. In group I, 150/409 (36.7%) patients received phenprocoumon therapy, and in group II, 259/409 (63.3%) patients were treated with NOACs (rivaroxaban: n = 193; dabigatran: n = 48; and apixaban: n = 18). In both groups, the rates of major complications were similar (group I [phenprocoumon]: four pts (2.7%) vs. Group II [NOACs]: seven pts (2.7%); P = 0.999). In this cohort, 275 patients were ablated with the bonus freeze protocol, and 134 patients were ablated without bonus freezes. The procedure duration significantly decreased with the bonus freeze protocol from 102.3 ± 24.6 min to 68.5 ± 16.2 min (P < 0.001). The impact of the bonus freeze on the postprocedural increase of C-reactive protein (CRP) levels was significant compared to the postprocedural CRP levels after procedures without the bonus freeze protocol (postprocedural CRP level+ bonus protocol: 1.6 ± 1.2 mg/L vs. postprocedural CRP level+ nonbonus protocol: 1.3 ± 1.3 mg/L; P = 0.04).
CONCLUSION
The incidence of adverse events in PVI using the second-generation CB with the periprocedural administration of NAOCs was not significantly different compared to phenprocoumon. Further, large-scale randomized studies are needed to evaluate the safety of two anticoagulation regimes comparing vitamin K antagonists and NOACs, as well as different NOAC regimes, in patients undergoing PVI using cryoballoon ablation.
Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Biomarkers; Cryosurgery; Dabigatran; Female; Germany; Humans; Incidence; Inflammation Mediators; Male; Middle Aged; Phenprocoumon; Postoperative Complications; Pulmonary Veins; Pyrazoles; Pyridones; Retrospective Studies; Rivaroxaban; Treatment Outcome
PubMed: 26880220
DOI: 10.1111/1755-5922.12178 -
Circulation. Heart Failure May 2017Left ventricular assist device-supported patients are usually anticoagulated with a combination of aspirin and vitamin K antagonists. Long-term vitamin K antagonist... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Left ventricular assist device-supported patients are usually anticoagulated with a combination of aspirin and vitamin K antagonists. Long-term vitamin K antagonist therapy can be complicated by unstable international normalized ratio values and patient-related compliance problems. Therefore, direct thrombin inhibitors may represent an alternative to vitamin K antagonists.
METHODS AND RESULTS
Thirty HeartWare ventricular assist device patients with stable renal function were planned for this prospective, randomized, open-label, single-center study. Patients were randomized to receive either phenprocoumon or dabigatran in addition to aspirin for long-term anticoagulation. Treatment duration was scheduled for 1 year and stopped after observation of a primary end point. Dabigatran dose was 110 and 75 mg BID in patients with normal or impaired renal function (glomerular filtration rate >80 mL/min or between 80 and 30 mL/min, respectively). The study was stopped prematurely for safety reasons after 16 patients (61±8 years, 1 female) were randomized. Thromboembolic events occurred in 4 subjects receiving dabigatran (50%) and in 1 receiving phenprocoumon (13%; =0.28). No major bleeding was recorded, and no patient died during the study. Median time to treatment termination was significantly shorter in dabigatran patients (8.5 versus 12.0 months; =0.015).
CONCLUSIONS
Thromboembolic events on dabigatran led to early termination of a randomized controlled trial of dabigatran versus phenprocoumon in left ventricular assist device patients.
CLINICAL TRIAL REGISTRATION
https://www.clinicaltrials.gov. Unique identifier: NCT02872649.
Topics: Antithrombins; Dabigatran; Dose-Response Relationship, Drug; Equipment Failure; Female; Follow-Up Studies; Heart Ventricles; Heart-Assist Devices; Humans; Male; Middle Aged; Phenprocoumon; Pilot Projects; Prospective Studies; Thromboembolism; Time Factors; United States; Vitamin K
PubMed: 28500254
DOI: 10.1161/CIRCHEARTFAILURE.116.003709 -
Thrombosis Research Aug 2023The European Medicine Agency has authorized COVID-19 vaccination in adolescents and young adults (AYAs) from 12 years onwards. In elderly vitamin K antagonist (VKA)...
INTRODUCTION
The European Medicine Agency has authorized COVID-19 vaccination in adolescents and young adults (AYAs) from 12 years onwards. In elderly vitamin K antagonist (VKA) users, COVID-19 vaccination has been associated with an increased risk of supra- and subtherapeutic INRs. Whether this association is also observed in AYAs using VKA is unknown. Our aim was to describe the stability of anticoagulation after COVID-19 vaccination in AYA VKA users.
MATERIALS AND METHODS
A case-crossover study was performed in a cohort of AYAs (12-30 years) using VKAs. The most recent INR results before vaccination, the reference period, were compared with the most recent INR after the first and, if applicable, second vaccination. Several sensitivity analyses were performed in which we restricted our analysis to stable patients and patients without interacting events.
RESULTS
101 AYAs were included, with a median age [IQR] of 25 [7] years, of whom 51.5 % were male and 68.3 % used acenocoumarol. We observed a decrease of 20.8 % in INRs within range after the first vaccination, due to an increase of 16.8 % in supratherapeutic INRs. These results were verified in our sensitivity analyses. No differences were observed after the second vaccination compared to before and after the first vaccination. Complications after vaccination occurred less often than before vaccination (9.0 vs 3.0 bleedings) and were non-severe.
CONCLUSIONS
the stability of anticoagulation after COVID-19 vaccination was decreased in AYA VKA users. However, the decrease might not be clinically relevant as no increase of complications nor significant dose adjustments were observed.
Topics: Humans; Male; Young Adult; Adolescent; Aged; Adult; Female; COVID-19 Vaccines; Cross-Over Studies; COVID-19; Anticoagulants; International Normalized Ratio; Vitamin K
PubMed: 37321159
DOI: 10.1016/j.thromres.2023.06.005 -
BMC Medicine Jan 2015The majority of studies on quality of oral anticoagulation (OAC) therapy with vitamin K-antagonists are performed with short-acting warfarin. Data on long-acting... (Observational Study)
Observational Study
Quality of oral anticoagulation with phenprocoumon in regular medical care and its potential for improvement in a telemedicine-based coagulation service--results from the prospective, multi-center, observational cohort study thrombEVAL.
BACKGROUND
The majority of studies on quality of oral anticoagulation (OAC) therapy with vitamin K-antagonists are performed with short-acting warfarin. Data on long-acting phenprocoumon, which is frequently used in Europe for OAC therapy and is considered to enable more stable therapy adjustment, are scarce. In this study, we aimed to assess quality of OAC therapy with phenprocoumon in regular medical care and to evaluate its potential for optimization in a telemedicine-based coagulation service.
METHODS
In the prospective observational cohort study program thrombEVAL we investigated 2,011 patients from regular medical care in a multi-center cohort study and 760 patients from a telemedicine-based coagulation service in a single-center cohort study. Data were obtained from self-reported data, computer-assisted personal interviews, and laboratory measurements according to standard operating procedures with detailed quality control. Time in therapeutic range (TTR) was calculated by linear interpolation method to assess quality of OAC therapy. Study monitoring was carried out by an independent institution.
RESULTS
Overall, 15,377 treatment years and 48,955 international normalized ratio (INR) measurements were analyzed. Quality of anticoagulation, as measured by median TTR, was 66.3% (interquartile range (IQR) 47.8/81.9) in regular medical care and 75.5% (IQR 64.2/84.4) in the coagulation service (P <0.001). Stable anticoagulation control within therapeutic range was achieved in 63.8% of patients in regular medical care with TTR at 72.1% (IQR 58.3/84.7) as compared to 96.4% of patients in the coagulation service with TTR at 76.2% [(IQR 65.6/84.7); P = 0.001)]. Prospective follow-up of coagulation service patients with pretreatment in regular medical care showed an improvement of the TTR from 66.2% (IQR 49.0/83.6) to 74.5% (IQR 62.9/84.2; P <0.0001) in the coagulation service. Treatment in the coagulation service contributed to an optimization of the profile of time outside therapeutic range, a 2.2-fold increase of stabile INR adjustment and a significant decrease in TTR variability by 36% (P <0.001).
CONCLUSIONS
Quality of anticoagulation with phenprocoumon was comparably high in this real-world sample of regular medical care. Treatment in a telemedicine-based coagulation service substantially improved quality of OAC therapy with regard to TTR level, frequency of stable anticoagulation control, and TTR variability.
TRIAL REGISTRATION
ClinicalTrials.gov, unique identifier NCT01809015, March 8, 2013.
Topics: Aged; Anticoagulants; Blood Coagulation; Cohort Studies; Europe; Female; Humans; International Normalized Ratio; Male; Middle Aged; Phenprocoumon; Prospective Studies; Telemedicine; Warfarin
PubMed: 25616558
DOI: 10.1186/s12916-015-0268-9