warfarin genetic

Warfarin is an irreplaceable oral anticoagulant for patients with mechanical heart valves, the stable pharmacogenetic-based warfarin dose prediction algorithms have improved the effectiveness and safety of warfarin anticoagulation therapy. Genetic factors are the main factors affecting the stable dose of warfarin. Single nucleotide polymorphisms such as VKORC1 and CYP2C9 affect the anticoagulation effect of warfarin through pharmacodynamic or pharmacokinetic pathways. Age, body surface area, combined use of drugs, and other nongenetic factors also affect the stable dose of warfarin...

Vaccines against SARS-CoV-2 have been recommended across the world, yet no study has investigated whether COVID-19 vaccination influences short-term warfarin anti-coagulation levels. Patients on stable warfarin treatment who received anti-SARS-CoV-2 vaccination were prospectively enrolled and followed up for three months. INR values less than 10 days before vaccination (baseline), 3-5 days (short-term) and 6-14 days (medium-term) after vaccination were recorded as INR0, INR1, and INR2, respectively. The variations of INR values within individuals were compared, and the linear mixed effect model was used to evaluate the variations of INR values at different time points...

BACKGROUND: Venous thromboembolism(VTE)is a common multifactorial disease. Anticoagulant protein deficiency is the most usual hereditary thrombophilia in the Chinese people, which includes protein C(PC), protein S and antithrombin deficiencies. CASE PRESENTATION: A retrospective analysis was conducted on clinical manifestations, laboratory tests, genetic information, and other relevant data of siblings diagnosed with VTE in 2020 at the Department of Pediatrics of Shenzhen Second People's Hospital...

Warfarin is a widely used anticoagulant, and its S-enantiomer has higher potency compared to the R-enantiomer. S-warfarin is mainly metabolized by cytochrome P450 (CYP) 2C9, and its pharmacological target is vitamin K epoxide reductase complex subunit 1 (VKORC1). Both CYP2C9 and VKORC1 have genetic polymorphisms, leading to large variations in the pharmacokinetics (PKs) and pharmacodynamics (PDs) of warfarin in the population. This makes dosage management of warfarin difficult, especially in the case of drug-drug interactions (DDIs)...

OBJECTIVES: Genetic variation has been a major contributor to interindividual variability of warfarin dosage requirement. The specific genetic factors contributing to warfarin bleeding complications are largely unknown, particularly in Chinese patients. In this study, 896 Chinese patients were enrolled to explore the effect of CYP2C9 and VKORC1 genetic variations on both the efficacy and safety of warfarin therapy. METHODS AND RESULTS: Univariate analyses unveiled significant associations between two specific single nucleotide polymorphisms rs1057910 in CYP2C9 and rs9923231 in VKORC1 and stable warfarin dosage (P < 0...

Anticoagulants are potent therapeutics widely used in medical and surgical settings, and the amount spent on anticoagulation is rising. Although warfarin remains a widely prescribed oral anticoagulant, prescriptions of direct oral anticoagulants (DOACs) have increased rapidly. Heparin-based parenteral anticoagulants include both unfractionated and low molecular weight heparins (LMWHs). In clinical practice, anticoagulants are generally well tolerated, although interindividual variability in response is apparent...

Antiplatelets and anticoagulants are extensively used in cardiovascular medicine for the prevention and treatment of thrombosis in the venous and arterial circulations. Wide inter-individual variability has been observed in response to antiplatelets and anticoagulants, which triggered researchers to investigate the genetic basis of this variability. Data from extensive pharmacogenetic studies pointed to strong evidence of association between polymorphisms in candidate genes and the pharmacokinetics and pharmacodynamic action and clinical response of the antiplatelets clopidogrel and the anticoagulant warfarin...

BACKGROUND: The conventional markers for hepatocellular carcinoma (HCC), α-fetoprotein (AFP) and des-γ-carboxy prothrombin (DCP), have several limitations; both have low sensitivity in patients with early-stage HCC; low sensitivity for AFP with HCC after eliminating hepatitis C virus (HCV); low specificity for DCP in patients with non-viral HCC, which is increasing worldwide; low specificity for AFP in patients with liver injury; and low specificity for DCP in patients treated with warfarin...

Pharmacogenomics is the examination of how genetic variation influences drug metabolism and response, in terms of both efficacy and safety. In cardiovascular disease, patient-specific diplotypes determine phenotypes, thereby influencing the efficacy and safety of drug treatments, including statins, antiarrhythmics, anticoagulants and antiplatelets. Notably, polymorphisms in key genes, such as CYP2C9, CYP2C19, VKORC1 and SLCO1B1, significantly impact the outcomes of treatment with clopidogrel, warfarin and simvastatin...

BACKGROUND: Despite direct oral anticoagulants (DOACs) being safer than warfarin for stroke prevention in atrial fibrillation (AF), major bleeding concerns persist. Most bleeding risk scores predate DOAC approval. OBJECTIVES: This study aimed to compare the Age, history of Bleeding, and non-bleeding related Hospitalisation [ABH] score's performance-derived for DOAC-treated patients-with those of 5 other scores (Anticoagulation and Risk Factors in Atrial Fibrillation [ATRIA], Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile international normalized ratio, Elderly [>65 years], Drugs/alcohol concomitantly [HAS-BLED], Hepatic, Hepatic or Renal Disease, Ethanol Abuse, Malignancy, Older Age, Reduced Platelet Count or Function, Re-Bleeding, Hypertension, Anemia, Genetic Factors, Excessive Fall Risk and Stroke [HEMORR2 HAGES], Outcomes Registry for Better Informed Treatment of Atrial Fibrillation [ORBIT-AF], and Congestive heart failure, Hypertension, Age ≥75 [doubled], Diabetes, Stroke [doubled]-Vascular disease, Age 65-74, Sex category [CHA2 DS2 -VASc]) in predicting DOAC-related major bleeding in patients with AF...

Protein induced by vitamin K (VK) absence-II (PIVKA-II) is a sensitive marker for diagnosing hepatoma but is occasionally detected in patients without hepatoma Here, the clinical significance of serum PIVKA-II levels in patients who were not administered warfarin and did not have hepatoma or liver disease were evaluated. As VK is related to muscle and bone metabolism, PIVKA-II and clinical factors related to bone and muscle were compared. A total of 441 patients with various liver diseases were evaluated. Of these, 236 patients were female...

Despite extensive efforts to identify patients with cardiovascular disease (CVD) who could most benefit from the treatment approach, patients vary in their benefit from therapy and propensity for adverse drug events. Genetic variability in individual responses to drugs (pharmacogenetics) is considered an essential determinant in responding to a drug. Thus, understanding these pharmacogenomic relationships has led to a substantial focus on mechanisms of disease and drug response. In turn, understanding the genomic and molecular bases of variables that might be involved in drug response is the main step in personalized medicine...

Solitary Peutz-Jeghers-type polyp (SPJP) is a rare hamartomatous lesion. It is considered a different entity from Peutz-Jeghers syndrome despite similar histopathological findings. It can be found in the GI tract but rarely in the jejunum. Jejunal SPJP is susceptible to necrosis, ulceration, and intussusception, resulting in GI bleeding or small bowel obstruction. We describe a case of subacute gastrointestinal bleeding secondary to jejunal SPJP to share our approach to this challenging case using therapeutic endoscopy...

Hereditary haemorrhagic telangiectasia (HHT) is a vascular dysplasia that commonly results in bleeding but with frequent indications for therapeutic anticoagulation. Our aims were to advance the understanding of drug-specific intolerance and evaluate if there was an indication for pharmacogenomic testing. Genes encoding proteins involved in the absorption, distribution, metabolism, and excretion of warfarin, heparin, and direct oral anticoagulants (DOACs) apixaban, rivaroxaban, edoxaban, and dabigatran were identified and examined...

BACKGROUND: Congenital antithrombin deficiency is an autosomal dominant disease that results in deep venous thrombosis and pulmonary embolism, which is mainly caused by mutations in the antithrombin gene (SERPINC1). Since SERPINC1 is highly susceptible to alterations, severe structural and functional changes that promote thrombosis may occur. Clinical presentations vary from different alterations. We report a pregnant case with novel mutation in SERPINC1 presenting transient antithrombin deficiency and multiple venous thromboembolisms...

BACKGROUND: There is uncertainty regarding the clinical benefit of anticoagulant (AC) treatment in patients with cancer with atrial fibrillation (AF). We aimed to evaluate the distribution and patterns of AC use and its impact on all-cause mortality in cancer patients with AF. METHODS: A total of 1,653 patients with cancer diagnosed with AF were included in this retrospective cohort analysis. Multivariable logistic regression was applied to identify the clinical predictors of anticoagulant prescription...

Warfarin, an oral anticoagulant, has been used for decades to prevent thromboembolic events. The complex interplay between CYP2C9 and VKORC1 genotypes on warfarin PK and PD properties is not fully understood in special sub-groups of patients. This study aimed to externally validate a population pharmacokinetic/pharmacodynamic (PK/PD) model for the effect of warfarin on international normalized ratio (INR) and to evaluate optimal dosing strategies based on the selected covariates in Caribbean Hispanic patients...

BACKGROUND: The development of computational methodologies to support clinical decision-making is of vital importance to reduce morbidity and mortality rates. Specifically, prescriptive analytic is a promising area to support decision-making in the monitoring, treatment and prevention of diseases. These aspects remain a challenge for medical professionals and health authorities. MATERIALS AND METHODS: In this study, we propose a methodology for the development of prescriptive models to support decision-making in clinical settings...

Thrombosis in the inferior vena cava (IVC) is a rare but serious condition that can lead to significant morbidity and mortality. We present a case report of a 39-year-old male who presented to the emergency department with right flank pain that had progressed to severe back pain, bilateral flank pain, scrotal pain, and leg pain over the course of two days. The pain was severe enough to affect his daily activities. Laboratory investigations revealed a D-dimer level of 17 ng/mL, creatinine level of 110  µ mol/L, and a white blood cell count of 10 × 109 /L with a CRP level of 5 mg/L...

Background: Polymorphisms in the CYP2C9 , VKORC1 , MDR1 and APOE genes may impact warfarin dose. Aim: To investigate the influence of sociodemographic and clinical factors and polymorphisms *1 , *2 and *3 for CYP2C9 , -1639G>A for VKORC1 , 3435C>T for MDR1 , and ϵ2, ϵ3 and ϵ4 for APOE genes on the mean weekly warfarin maintenance dose in adults. Methods: This cross-sectional study recruited a calculated sample of 315 patients in three anticoagulation clinics in Brazil. A model containing the variables significantly associated with warfarin dose was estimated...