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Journal of Clinical Rheumatology :... Jun 2022Performing joint aspirations and injections on patients taking long-term oral anticoagulants poses a clinical conundrum. This review aimed to quantify the safety of... (Review)
Review
Performing joint aspirations and injections on patients taking long-term oral anticoagulants poses a clinical conundrum. This review aimed to quantify the safety of performing joint procedures in these patients in terms of bleeding risk. In addition, it aimed to identify, in those receiving vitamin K antagonists, what level of international normalized ratio (INR) is the safest.A review of the medical literature was performed (electronic searches in Ovid [MEDLINE], EMBASE, and the Cochrane Library). English language original reports of patients undergoing joint injections or aspirations performed on anticoagulant therapy, published within the last 10 years, were included.Seven studies met the inclusion criteria. Patients were taking a variety of anticoagulants: warfarin, acenocoumarol, and direct oral anticoagulants. Four cases of hemorrhage were reported after 5427 procedures, over a pooled 32-year period, across 9 centers. The INR values were available for 3 cases with bleeding complications: values were 1.9, 2.3, and 3.4.Authors of all studies concluded that joint injection is safe in patients on anticoagulants. A variety of joints and approaches, reversal, or withholding of anticoagulation and bridging with low molecular weight heparin did not seem to alter bleeding risk. Bleeding complications remained low even in those with renal or hepatic impairment or those taking concomitant antiplatelets.In conclusion, joint aspiration and injection are safe in patients taking anticoagulants. Anticoagulation should not be routinely discontinued in these patients; decisions should be made on a case-by-case basis. Because of low event numbers, a recommended safe maximum INR value for joint procedures cannot be determined.
Topics: Anticoagulants; Blood Coagulation; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Warfarin
PubMed: 35616509
DOI: 10.1097/RHU.0000000000001856 -
Pharmacogenomics Jun 2022Vitamin K antagonists (VKAs) are class I oral anticoagulants that are widely prescribed following surgical heart valve implantation. The objective of this study was to...
Vitamin K antagonists (VKAs) are class I oral anticoagulants that are widely prescribed following surgical heart valve implantation. The objective of this study was to quantify the relative effects of and genotypes in predicting VKA dosing. A total of 506 South Indian patients with mechanical prosthetic heart valves who were prescribed oral VKAs, such as warfarin or acenocoumarol, were genotyped. The discriminatory ability of mutant genotypes to predict dose categories and bleeding events was assessed using regression analysis. The rs9923231, and mutant genotypes significantly influenced VKA-dose requirements and explained 27.47% of the observed dose variation. These results support pharmacogenetic screening for initial VKA dosing among South Indian patients with mechanical prosthetic heart valves.
Topics: Anticoagulants; Cytochrome P-450 CYP2C9; Genotype; Heart Valves; Humans; Pharmacogenomic Variants; Polymorphism, Single Nucleotide; Vitamin K; Vitamin K Epoxide Reductases
PubMed: 35608144
DOI: 10.2217/pgs-2022-0014 -
Combinatorial Chemistry & High... 2023Currently, there are no effective differentiation-inducing agents for gliomas. Drug repositioning is a time-saving, low-risk, and low-cost drug development strategy. In...
BACKGROUND
Currently, there are no effective differentiation-inducing agents for gliomas. Drug repositioning is a time-saving, low-risk, and low-cost drug development strategy. In this study, drugs that could induce the differentiation of glioma cells were searched by using a drug repositioning strategy.
METHODS
Data mining was used to screen for differentially expressed genes (DEGs). The STRING 11.0 database was used for enrichment analysis. The Connectivity Map database was used for drug screening. The ChEMBL and STITCH databases were used to search for drug targets. The SwissDock database was used for molecular docking.
RESULTS
A total of 45 DEGs were identified. The biological processes in which the DEGs were enriched mainly involved nervous system development and the regulation of biological processes. The enriched molecular functions mainly involved transcription-related molecular binding. The enriched cellular components mainly involved membrane-bound organelles and cellular protrusions. The enriched local network clusters mainly involved autophagy, the retinoic acid signalling pathway, and DNA methylation. The drug screening results showed that the drug with the highest score was acenocoumarol. A total of 12 acenocoumarol targets were obtained, among which histone deacetylase 1 (HDAC1) was the target with the highest degree value; the lowest ΔG value for acenocoumarol docked with HDAC1 was -7.52 kcal/mol, which was between those of the HDAC1 inhibitors romidepsin and vorinostat.
CONCLUSION
Acenocoumarol may be a potential differentiation-inducing agent for glioma cells.
Topics: Humans; Molecular Docking Simulation; Drug Repositioning; Acenocoumarol; Glioma; Cell Differentiation
PubMed: 35538833
DOI: 10.2174/1386207325666220509194428 -
International Journal of Cardiology Sep 2022Several studies have shown that in patients treated with vitamin K antagonists (VKAs) time spent in therapeutic range (TTR) is lower in females than in males. This...
BACKGROUND
Several studies have shown that in patients treated with vitamin K antagonists (VKAs) time spent in therapeutic range (TTR) is lower in females than in males. This retrospective study has evaluated a possible association among over-anticoagulation and gender, type and indications to VKAs, TTR and bleeding. Moreover, the decrease of the INR level, after VKAs withdrawal, was considered.
METHODS
From December 2020 to January 2004, 1230 patients with venous thromboembolism or atrial fibrillation were enrolled. Age, gender, type of VKAs, clinical indications, INR values and bleeding events were recorded. TTR was calculated considering the entire period of treatment.
RESULTS
A total of 1616 and 1759 over-anticoagulation episodes were found in males and females, respectively. The median INR value was 4.5 (4.0-19.04). Thirty-two percent of the patients did not have an overdose throughout the observation period. The median number of over-anticoagulation per year was significantly higher in females (0.39-year) than in males (0.28-year). After 24 h of VKAs withdrawal, INRs were similar in both genders. Logistic regression analysis showed that the episodes of over-anticoagulation per year were associated with females, atrial fibrillation, warfarin therapy, follow-up length longer than 4 years, and TTR <73%, but were not associated to bleeding episodes.
CONCLUSION
The higher number of over-anticoagulation can explain the lower TTR in females. An excess of anticoagulation is not associated with bleeding events. The recovery of INR performs better when acenocoumarol is used, therefore, in patients who present several episodes of over-anticoagulation, acenocumarolo could replace warfarin.
Topics: Acenocoumarol; Anticoagulants; Atrial Fibrillation; Female; Fibrinolytic Agents; Hemorrhage; Humans; International Normalized Ratio; Male; Retrospective Studies; Sex Factors; Vitamin K; Warfarin
PubMed: 35533748
DOI: 10.1016/j.ijcard.2022.05.003 -
Radiology Case Reports Jun 2022Vitamin K antagonists (VKA) are recommended in patients with mechanical heart valves. Major bleeding events remain the most life-threatening complication of this therapy...
Vitamin K antagonists (VKA) are recommended in patients with mechanical heart valves. Major bleeding events remain the most life-threatening complication of this therapy and sometimes it can occur in unusual anatomic areas. Spontaneous retroperitoneal hematoma is one of the rare complications of anticoagulation therapy, which needs to be recognized early and managed promptly. Here, we report a case of a 40-year-old woman with mechanical heart valve treated with acenocoumarol, who was admitted to the emergency department with abdominal pain and whose investigations came back in favor of a massive retroperitoneal hematoma. The patient was successfully treated through conservative management resulting in a good outcome. Clinicians should be careful when prescribing VKA and should always think of retroperitoneal bleeding in the event of abdominal pain or a sudden decrease in the hemoglobin levels of anticoagulated patients.
PubMed: 35515510
DOI: 10.1016/j.radcr.2022.03.099 -
Croatian Medical Journal Apr 2022To compare the Croatian and European population in terms of allele frequencies of clinically relevant polymorphisms in drug absorption, distribution, metabolism, and...
AIM
To compare the Croatian and European population in terms of allele frequencies of clinically relevant polymorphisms in drug absorption, distribution, metabolism, and excretion (ADME) genes.
METHODS
In 429 Croatian participants, we genotyped 27 loci in 20 ADME genes. The obtained frequencies were merged with the published frequencies for the Croatian population by sample size weighting. The study sample obtained in this way was compared with the average data for the European population from the gnomAD database.
RESULTS
Variant allele frequencies in the Croatian population were higher in three and lower in two polymorphisms (Benjamini-Hochberg-corrected P values: 0.0027 for CYP2B6*4 rs2279343, CYP2C9*2 rs1799853, and VKORC1 rs9923231; 0.0297 for GSTP1 rs1695; 0.0455 for CYP2A6 rs1801272) compared with the European population. The most marked difference was observed for CYP2B6*4 (9.3% in Europe vs 24.3% in Croatia). The most clinically relevant findings were higher variant allele frequencies in two polymorphisms related to lower warfarin requirements: VKORC1*2 (34.9% in Europe vs 40.1% in Croatia) and CYP2C9*2 (12.3% in Europe vs 14.7% in Croatia). This indicates that three-quarters of Croatian people have at least one variant allele at these loci. Variants in genes GSTP1 and CYP2A6 were significantly less frequently observed in Croatia.
CONCLUSIONS
Croatian population has a higher bleeding and over-anticoagulation risk, which is why we recommend the prescription of lower doses of anticoagulation drugs such as warfarin and acenocoumarol. Lower phenytoin, and higher bupropion and efavirenz doses are also recommended in the Croatian population.
Topics: Anticoagulants; Croatia; Cytochrome P-450 CYP2B6; Cytochrome P-450 CYP2C9; Humans; Pharmacogenetics; Vitamin K Epoxide Reductases; Warfarin
PubMed: 35505645
DOI: 10.3325/cmj.2022.63.117 -
Current Drug Safety 2023Acenocoumarol is an anticoagulant with numerous drug reactions. We report here, an unusual interaction between acenocoumarol and azathioprine.
BACKGROUND
Acenocoumarol is an anticoagulant with numerous drug reactions. We report here, an unusual interaction between acenocoumarol and azathioprine.
CASE PRESENTATION
A 35-year-old woman, treated with acenocoumarol for thrombosis of the superior mesenteric vein, was prescribed azathioprine for Crohn's disease. Three days later, INR values decreased from 2.36 to 1.48. The dose of acenocoumarol had to almost be doubled to reach an INR value of 2.56. The interaction between azathioprine and acenocoumarol was then suspected. Few similar cases of interactions between azathioprine and another coumarin derivative, warfarin, have been reported. To our knowledge, this is the second case of such interaction reported with acenocoumarol in literature.
CONCLUSION
Thus, despite the rarity of this interaction reporting, we draw attention to the importance of close monitoring of INR values in patients treated with acenocoumarol associated with azathioprine.
Topics: Female; Humans; Adult; Azathioprine; Crohn Disease; Acenocoumarol; Drug Interactions; Anticoagulants
PubMed: 35469571
DOI: 10.2174/1574886317666220425113613 -
Frontiers in Bioengineering and... 2022The development of a proof-of-concept point-of-care (PoC) device for the determination of oral anticoagulants determination is presented. Acenocoumarol (ACL) is...
The development of a proof-of-concept point-of-care (PoC) device for the determination of oral anticoagulants determination is presented. Acenocoumarol (ACL) is prescribed to prevent certain cardiovascular diseases related to the prevention of deep vein thrombosis, pulmonary embolism, myocardial infarction, and stroke. Oral anticoagualant treatment (OAT) represents a population of 2% under treatment which has expenditures about $ 144 million in 2011. The main drawback for OAT is the associated narrow therapeutic window and the unpredictable dose-response relationship, which is one of the main causes for visiting the emergency room at the hospitals. In a previous work, family antibodies were produced for the simultaneous detection of ACL and warfarin (W) depending on the area of application. It was developed in different formats, indirect and direct, either with similar detectabilities and both assays quantifying the oral anticoagulants with high accuracy and reproducibility. We present the implementation of the already developed immunochemical method to a point-of-care (PoC) device to assist on the patient compliance assessment programs. In order to achieve this goal, a first development was performed implementing ACL ELISA assay into a microarray format with fluorescent read-out. The assay was successfully implemented achieving a LOD of 1.23 nM of ACL directly measured in human plasma. Then, a fully integrated microfluidic system is developed which incorporates the specific immunoreagents for the detection of ACL. The immunoreagents were attached onto the glass slide in a microarray format. The system is automatic, rapid, sensitive, and disposable that could help clinicians monitor patients under OAT. According to the fluorescent label of the ACL binding, the chip can be easily read with a scanner. The microfluidic system performed good according to the robust and reproducible signals, and subsequently yielded an accurate result.
PubMed: 35425765
DOI: 10.3389/fbioe.2022.848501 -
Thrombosis and Haemostasis Mar 2022In January 2021, the Dutch vaccination program against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was started. Clinical studies have shown that...
BACKGROUND
In January 2021, the Dutch vaccination program against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was started. Clinical studies have shown that systemic reactions occur in up to 50% of vaccine recipients. Therefore, COVID-19 vaccination could affect anticoagulation control, potentially leading to an increased risk of thrombotic events and bleeding complications.
AIMS
This article investigates whether the BNT162b2 vaccine affects anticoagulation control in outpatients using vitamin K antagonists (VKAs).
METHODS
A case-crossover study was performed in a cohort of outpatient VKA users from four Dutch anticoagulation clinics who received a BNT162b2 vaccine. International normalized ratio (INR) results and VKA dosages before the first vaccination, the reference period, were compared with those after the first and second vaccination.
RESULTS
A total of 3,148 outpatient VKA users were included, with a mean age (standard deviation) of 86.7 (8.7) years, of whom 43.8% were male, 67.0% used acenocoumarol, and 33.0% phenprocoumon. We observed a decrease of 8.9% of INRs within range in the standard intensity group (target INR 2.0-3.0). There was both an increased risk of supratherapeutic (odds ratio [OR] = 1.34 [95% confidence interval [CI] 1.08-1.67]) and subtherapeutic levels (OR = 1.40 [95% CI 1.08-1.83]) after first vaccination. In the high-intensity group (target INR 2.5-3.5), the risk of a supratherapeutic INR was 2.3 times higher after first vaccination (OR = 2.29 [95% CI 1.22-4.28]) and 3.3 times higher after second vaccination (OR = 3.25 [95% CI 1.06-9.97]).
CONCLUSION
BNT162b2 was associated with an immediate negative effect on anticoagulation control in patients treated with VKAs, so it is advisable to monitor the INR shortly after vaccination, even in stable patients.
Topics: Aged; Aged, 80 and over; Ambulatory Care; Anticoagulants; BNT162 Vaccine; Blood Coagulation; Drug Monitoring; Female; Humans; International Normalized Ratio; Male; Netherlands; Predictive Value of Tests; Retrospective Studies; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Vaccination; Vitamin K
PubMed: 35245945
DOI: 10.1055/s-0042-1742628 -
Hematology (Amsterdam, Netherlands) Dec 2022Heparin-induced thrombocytopenia (HIT) is an immune-mediated adverse drug reaction associated with thrombosis. Clinical scoring systems and the presence of anti-platelet...
BACKGROUND
Heparin-induced thrombocytopenia (HIT) is an immune-mediated adverse drug reaction associated with thrombosis. Clinical scoring systems and the presence of anti-platelet factor 4 (anti-PF4)/heparin antibodies determine the diagnosis.
CASE PRESENTATION
A 57-year-old man who was treated with acenocoumarol due to a chronic left ventricular thrombus was admitted to the hospital for severe SARS-CoV-2 pneumonia and pulmonary embolism. The patient was started on bemiparin and discharged. Left lower limb acute arterial ischemia and thrombocytopenia were diagnosed 18 days later. Computed tomography angiography revealed a large left ventricular thrombus and multiple arterial thrombi. Left femoral-popliteal thromboembolectomy was performed. Anti-PF4/heparin antibodies confirmed an HIT diagnosis. Fondaparinux (7.5 mg/24 h) was initiated, but cardiac surgery was necessary. Bivalirudin was used during surgery, with an initial load (1.25 mg/kg) and maintenance infusion (2.5 mg/kg/h). The cardiac thrombus was extracted, but the patient experienced a postsurgical myocardial infarction. Percutaneous cardiovascular intervention (PCI) required a bivalirudin load (0.75 mg/kg) and maintenance infusion (1.75 mg/kg/h). No coronary lesions were detected, and argatroban was started afterwards (0.5 µg/kg/min). When the platelet count exceeded 100 × 10/L, acenocoumarol was initiated. Thereupon, acetylsalicylic acid (100 mg/24 h) was added. No other complications have been reported to date.
CONCLUSION
The clinical presentation of intraventricular and multiple arterial thrombi is remarkable. SARS-CoV-2 infection likely contributed to a hypercoagulable state. The management of patients with HIT undergoing cardiac surgery is challenging. If surgery cannot be delayed, then treatment with bivalirudin is recommended. Additionally, this drug is recommended for PCI. Bivalirudin is safe and well-tolerated in both procedures.
Topics: Acenocoumarol; Anticoagulants; Arginine; COVID-19; Heparin; Hirudins; Humans; Male; Middle Aged; Peptide Fragments; Percutaneous Coronary Intervention; Pipecolic Acids; Recombinant Proteins; SARS-CoV-2; Sulfonamides; Thrombocytopenia; Thrombosis; COVID-19 Drug Treatment
PubMed: 35231200
DOI: 10.1080/16078454.2022.2043572