Displaying publications 81 - 100 of 186 in total

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  1. Yap SH, Ng YP, Roslan A, Kolanthaivelu J, Koh KW, P'ng HS, et al.
    Med J Malaysia, 2017 12;72(6):360-364.
    PMID: 29308774 MyJurnal
    INTRODUCTION: Atrial fibrillation (AF) is the most common cardiac arrhythmia with significant morbidity and mortality in relation to thromboembolic stroke. Our study aimed to evaluate the safety and efficacy of dabigatran in stroke prevention in elderly patient with nonvalvular AF with regard to the risk of ischemic stroke and intracranial haemorrhage (ICH) in real-world setting.

    METHODS: A retrospective cohort study of 200 patients on dabigatran and warfarin from January 2009 till September 2016 was carried out. Data were collected for 100 patients on dabigatran and 100 patients on warfarin.

    RESULTS: The mean follow-up period was 340.7±322.3 days for dabigatran group and 410.5±321.2 days for warfarin group. The mean time in therapeutic range (TTR) was 52±18.7%. The mean CHA2DS2 -VASc score for dabigatran group was 4.4±1.1 while 5.0±1.5 for warfarin group. None in dabigatran group experienced ischemic stroke compared to one patient in warfarin group (p=0.316). There was one patient in dabigatran group suffered from ICH compared to none in warfarin group (p=0.316). Four patients in warfarin group experienced minor bleeding, while none from dabigatran group (p=0.043).

    CONCLUSION: Overall bleeding events were significantly lower in dabigatran group compared to warfarin group. In the presence of suboptimal TTR rates and inconveniences with warfarin therapy, non-vitamin-K antagonist oral anticoagulants (NOAC) are the preferred agents for stroke prevention in elderly Asian patients for nonvalvular AF.

    Matched MeSH terms: Anticoagulants/therapeutic use
  2. Ngow HA, Wan Khairina WM, Teh LK, Lee WL, Harun R, Ismail R, et al.
    Singapore Med J, 2009 May;50(5):490-3.
    PMID: 19495518
    Genetic polymorphisms of CYP2C9 among different populations in different geographical regions could be different. CYP2C9 has been reported to be the enzyme responsible for the metabolism of many drugs, including warfarin and other drugs with a narrow therapeutic index. Realising the importance of inter-individual differences in the genetic profile in determining the outcome of a drug therapy, this study was conducted to explore the types and frequencies of CYP2C9 alleles in healthy and warfarin-treated Malays and Chinese, the two major ethnic groups in Malaysia. We aimed to evaluate the prevalence of the types and frequencies of common CYP2C9 alleles (*1, *2, *3 and *4) among the healthy unrelated individuals and diseased patients prescribed with warfarin.
    Matched MeSH terms: Anticoagulants/metabolism*
  3. Gwee AL
    Singapore Med J, 1963 Jun;4(2):68-80.
    PMID: 14046966
    A double-blind study with control was done to assess the effect of mono-amine-oxidase inhibitors and anticoagulant therapy in the mortality of acute myocardial infarction, in the first 4 weeks. The results show that no effect whether beneficial or adverse was seen with the use of monoamine inhibitor. On the other hand, there is a distinct decrease in mortality amongst cases not on anticoagulants. It is believed that the rarity of phlebothrombosis in local patients is the cause of the difference between local and foreign results so far as anticoagulant therapy goes. It is postulated too that one of the reasons for the difference may be due to the fact that patients are not on so strict a bed rest as elsewhere. There appears to be a definite increase of incidence in Indians, and also at least a third of myocardial infarction cases had low normal serum cholesterol readings.
    Matched MeSH terms: Anticoagulants*
  4. Thanimalai S, Shafie AA, Hassali MA, Sinnadurai J
    Int J Clin Pharm, 2013 Oct;35(5):736-43.
    PMID: 23715759 DOI: 10.1007/s11096-013-9796-6
    BACKGROUNDS: Limited evidence is available regarding pharmacist managed anticoagulation clinic in the Southeast Asian region where there is marked difference in terms of care model, genetic composition and patient demographics.

    OBJECTIVES: This study aimed at comparing the anticoagulation clinic managed by the pharmacist with physician advisory and the usual medical care provided in Kuala Lumpur Hospital (KLH) in terms of anticoagulation control and adverse outcomes.

    SETTING: A 2,302 bedded government tertiary referral hospital in Malaysia.

    METHODS: A 6-month retrospective cohort study of the effectiveness of two models of anticoagulation care, the pharmacist managed anticoagulation clinic which is known as warfarin medication therapy adherence clinic (WMTAC) and usual medical clinic (UMC) in KLH was conducted, where a random number generator was used to recruit patients. The UMC patients received standard medical care where they are managed by rotational medical officers in the physicians' clinic. As for the WMTAC with physician advisory, the pharmacist will counsel and review the patients internationalised normalization ratio at each clinic visit and also adjust the patients' warfarin dose accordingly. Patients are referred to physicians if immediate attention is required.

    MAIN OUTCOME MEASURE: The main therapeutic outcome is time in therapeutic range (TTR) both actual and expanded TTR and thromboembolic and bleeding complications.

    RESULTS: Each of the WMTAC and usual medical care recruited 92 patients, which totals to 184 patients. The patient demographics in terms of age, race and indication of treatment were comparable. At the end of the 6 months follow-up, patients in the WMTAC group had significantly higher actual-TTR (65.1 vs. 48.3 %; p < 0.05) compared to those in usual medical care group. Rates of admission were 6.5 versus 28.2 events per 100 person-years for the WMTAC and UMC groups, respectively. Though the bleeding incidences were not significantly different, it was reduced.

    CONCLUSIONS: These findings will impact local warfarin patient management services and policies because there was no available evidence supporting the role of pharmacists in the management of warfarin patients prior to this study.
    Matched MeSH terms: Anticoagulants/administration & dosage*; Anticoagulants/adverse effects; Anticoagulants/pharmacokinetics; Anticoagulants/therapeutic use
  5. Edwards F, Arkell P, Fong, Roberts LM, Gendy D, Wong CS, et al.
    J Thromb Thrombolysis, 2014;38(2):226-34.
    PMID: 24233388
    Evidence is emerging that rates of adverse events in patients taking warfarin may vary with ethnicity. This study investigated the rates of bleeds and thromboembolic events, the international normalised ratio (INR) status and the relationship between INR and bleeding events in Malaysia. Patients attending INR clinic at the Heart Centre, Sarawak General Hospital were enrolled on an ad hoc basis from May 2010 and followed up for 1 year. At each routine visit, INR was recorded and screening for bleeding or thromboembolism occurred. Variables relating to INR control were used as predictors of bleeds in logistic regression models. 125 patients contributed to 140 person-years of follow-up. The rates of major bleed, thromboembolic event and minor bleed per 100 person-years of follow-up were 1.4, 0.75 and 34.3. The median time at target range calculated using the Rosendaal method was 61.6% (IQR 44.6–74.1%). Of the out-of-range readings, 30.0% were below range and 15.4% were above. INR variability, (standard deviation of individuals’ mean INR), was the best predictor of bleeding events, with an odds ratio of 3.21 (95% CI 1.10–9.38). Low rates of both major bleeds and thromboembolic events were recorded, in addition to a substantial number of INR readings under the recommended target range. This may suggest that the recommended INR ranges may not represent the optimal warfarin intensity for this population and that a lower intensity of therapy, as observed in this cohort, could be beneficial in preventing adverse events.

    Study site: INR clinic at the Heart Centre, Sarawak General Hospital
    Matched MeSH terms: Anticoagulants/administration & dosage; Anticoagulants/adverse effects*
  6. Kakkar AK, Cimminiello C, Goldhaber SZ, Parakh R, Wang C, Bergmann JF, et al.
    N Engl J Med, 2011 Dec 29;365(26):2463-72.
    PMID: 22204723 DOI: 10.1056/NEJMoa1111288
    BACKGROUND: Although thromboprophylaxis reduces the incidence of venous thromboembolism in acutely ill medical patients, an associated reduction in the rate of death from any cause has not been shown.
    METHODS: We conducted a double-blind, placebo-controlled, randomized trial to assess the effect of subcutaneous enoxaparin (40 mg daily) as compared with placebo--both administered for 10±4 days in patients who were wearing elastic stockings with graduated compression--on the rate of death from any cause among hospitalized, acutely ill medical patients at participating sites in China, India, Korea, Malaysia, Mexico, the Philippines, and Tunisia. Inclusion criteria were an age of at least 40 years and hospitalization for acute decompensated heart failure, severe systemic infection with at least one risk factor for venous thromboembolism, or active cancer. The primary efficacy outcome was the rate of death from any cause at 30 days after randomization. The primary safety outcome was the rate of major bleeding during and up to 48 hours after the treatment period.
    RESULTS: A total of 8307 patients were randomly assigned to receive enoxaparin plus elastic stockings with graduated compression (4171 patients) or placebo plus elastic stockings with graduated compression (4136 patients) and were included in the intention-to-treat population. The rate of death from any cause at day 30 was 4.9% in the enoxaparin group as compared with 4.8% in the placebo group (risk ratio, 1.0; 95% confidence interval [CI], 0.8 to 1.2; P=0.83). The rate of major bleeding was 0.4% in the enoxaparin group and 0.3% in the placebo group (risk ratio, 1.4; 95% CI, 0.7 to 3.1; P=0.35).
    CONCLUSIONS: The use of enoxaparin plus elastic stockings with graduated compression, as compared with elastic stockings with graduated compression alone, was not associated with a reduction in the rate of death from any cause among hospitalized, acutely ill medical patients. (Funded by Sanofi; LIFENOX ClinicalTrials.gov number, NCT00622648.).
    Note: Malaysia is a study site: participating investigators: Yaw Chong Hwa (WT Ma), Najihah I, SH How, Abdul Razak AM, Law WC (ST Tie), Bharathan T, Monniaty M, Aris Chandran, Ngau Yen Yew, Aziah AM, Irene Wong, CK Chuah, Rosemi S, KK Sia, Jeyaindran S, CY Leong
    Matched MeSH terms: Anticoagulants/adverse effects; Anticoagulants/therapeutic use*
  7. Liew NC, Chang YH, Choi G, Chu PH, Gao X, Gibbs H, et al.
    Int Angiol, 2012 Dec;31(6):501-16.
    PMID: 23222928
    Venous thromboembolism (VTE) prophylaxis is under-utilized in Asia because of the misconception that its incidence is lower in Asians as compared to the Caucasians. The available data on VTE in Asia is limited due to the lack of well-designed multicenter randomized controlled trials as well as non-standardized research designs, making data comparison difficult. Emerging data indicates that the VTE incidence is not low in Asia, and is comparable to that reported in the Western literature in some instances. There is also a trend towards increasing incidence of VTE, as demonstrated by a number of hospital-based studies in Asia. This could be attributed to lifestyle changes, ageing population, increasing awareness of VTE and wider availability of Duplex ultrasound. The risk of VTE in hospitalized patients remain the same in Asians and Caucasians, even though there may be factors that are inherent to patients in Asia that influence the slight variation in incidence. The utilization rate of VTE prophylaxis remains suboptimal in Asia. The Asian Venous Thrombosis Forum (AVTF) comprises participants from various countries such as China, Hong Kong, India, Indonesia, Korea, Malaysia, Philippines, Singapore, Taiwan, Thailand and experts from Australia and Europe. The forum evaluated the available data on VTE from the Asian region and formulated guidelines tailored to meet the needs of the region. We recommend that serious considerations are given to VTE prophylaxis especially in the at-risk group and a formal hospital policy be established to facilitate the implementation. On admission to the hospital, we recommend assessing the patients for both VTE and bleeding risk. We recommend mechanical prophylaxis for patients at increased risk of bleeding and utilizing it as an adjunctive measure in combination with pharmacological prophylaxis in patients with high risk of VTE. For patients undergoing general or gynecological surgery and with moderate risk for VTE, we recommend prophylaxis with one of the following: low dose unfractionated heparin (LDUH), low molecular weight heparin (LMWH), fondaparinux or intermittent pneumatic compression (IPC). For the same group of patients at high risk of VTE, we recommend pharmacological or combination of pharmacological and mechanical prophylaxis. For patients undergoing major orthopedic surgeries like total hip replacement, total knee replacement and proximal hip fracture surgery, we recommend using one of the following: LMWH, fondaparinux, rivaroxaban, apixaban, edoxaban, dabigatran, warfarin or aspirin with IPC. For patients admitted to the hospital with acute medical illness and has moderate risk of VTE, we recommend prophylaxis with LDUH, LMWH or Fondaparinux. For the same group at high risk of VTE, we recommend combination of pharmacological and mechanical prophylaxis.
    Matched MeSH terms: Anticoagulants/adverse effects; Anticoagulants/therapeutic use*
  8. Hasan SS, Teh KM, Ahmed SI, Chong DW, Ong HC, Naina B
    Public Health, 2015 Jul;129(7):954-62.
    PMID: 26138018 DOI: 10.1016/j.puhe.2015.05.014
    OBJECTIVES: To investigate association between quality of life (QoL) and International Normalized Ratio (INR) control, with the secondary aim of assessing QoL using generic and anticoagulation-specific, the Short Form Health Survey (SF-12) and the Duke Anticoagulation Satisfaction Scale (DASS).
    STUDY DESIGN: This study assessed anticoagulation related QoL at three time intervals in two groups of patients on long-term warfarin therapy.
    METHODS: Data of 326 randomly sampled patients (163 patients each in DASS and SF-12 groups) who had been on warfarin therapy for at least one year at anticoagulation clinics were analysed. QoL was assessed at three time intervals: at the start, six months and one year of warfarin therapy. Indications and target INR ranges and subjects INR values were recorded. Time in Therapeutic Range (TTR) was estimated for four subject subgroups, based on target ranges of INR for clustered indications.
    RESULTS: Of the total, 43% of the subjects were aged between 50 and 64 years, and 51% were female. DASS assessed subjects older than 35 years perceived significant decrease in overall mean scores of anticoagulation related QoL, whilst all SF-12 assessed subjects perceived an increase in QoL. The mean percentage days in range for all INR target range subgroups did not exceed more than 60% but there was only a weak correlation (Rs = 0.104, P > 0.05) between INR control and overall QoL.
    CONCLUSION: Malaysian urban outpatients on warfarin treatment longer than one year report a significant overall decrease in QoL, as measured using a validated condition-specific instrument. These patients appeared to adapt well to lifestyle limitations imposed by long-term anticoagulation.
    KEYWORDS: Anticoagulation therapy; International Normalized Ratio; Quality of life

    Study site: anticoagulation clinics at a
    suburban tertiary Ministry of Health hospital in Peninsular
    Malaysia
    Matched MeSH terms: Anticoagulants/administration & dosage*; Anticoagulants/therapeutic use
  9. Ng SS, Lai NM, Nathisuwan S, Chaiyakunapruk N
    Clin Drug Investig, 2018 Jul;38(7):579-591.
    PMID: 29569095 DOI: 10.1007/s40261-018-0641-5
    INTRODUCTION: Anticoagulation therapy is the fundamental approach for stroke prevention in atrial fibrillation (AF) patients. Numerous systematic reviews comparing anticoagulation strategies have been published. We aim to summarize the efficacy and safety evidence of these strategies in AF patients from previously published systematic reviews.

    METHODS: We searched PubMed, EMBASE and Cochrane library from inception to Feb 24th, 2017, to identify systematic reviews and meta-analyses of randomized controlled trials that assessed interventions or strategies to improve oral anticoagulant use in AF patients.

    RESULTS: Thirty-four systematic reviews were eligible for inclusion but only 11 were included in the qualitative analyses, corresponding to 40 unique meta-analyses, as the remaining systematic reviews had overlapping primary studies. There was insufficient evidence to support the efficacy of genotype-guided dosing and pharmacist-managed anticoagulation clinics for stroke prevention in AF patients. Conversely, patient's self-management and novel oral anticoagulants (NOACs), in general were superior to warfarin for preventing stroke and reducing mortality. All interventions showed comparable risk of major bleeding with warfarin.

    CONCLUSION: Findings from this overview support the superiority of NOACs and patient's self-management for preventing stroke in AF patients. However, uncertainties remain on the benefits of genotype-guided dosing and pharmacist-managed anticoagulation clinics due to poor quality evidence, and future research is warranted.

    Matched MeSH terms: Anticoagulants/administration & dosage*; Anticoagulants/adverse effects
  10. Choi EK, Lee YS, Chern AKC, Jiampo P, Chutinet A, Hanafy DA, et al.
    Open Heart, 2020 11;7(2).
    PMID: 33184127 DOI: 10.1136/openhrt-2020-001343
    BACKGROUND AND PURPOSE: Real-world data about treatment convenience and satisfaction in Asian non-valvular atrial fibrillation (NVAF) patients after switching from vitamin K antagonists (VKAs) to non-VKA oral anticoagulants were evaluated.

    METHODS: In this non-interventional study involving 49 sites across five countries in Southeast Asia and South Korea, 379 stable NVAF patients who switched from VKA therapy to dabigatran during routine clinical practice were recruited and followed up for 6 months. Treatment convenience and satisfaction were evaluated using Perception on Anticoagulant Treatment Questionnaire-2 (PACT-Q2). Through post hoc analysis, factors associated with improved treatment convenience scores at visit 2 were described.

    RESULTS: Treatment convenience and satisfaction significantly improved after switching from VKAs to dabigatran at visit 2 and visit 3 (convenience: p<0.001 each vs baseline; satisfaction: p=0.0174 (visit 2), p=0.0004 (visit 3) compared with baseline). Factors predictive of higher (>80th percentile) response on treatment convenience were female sex, younger age (<75 years), higher baseline stroke risk, higher creatinine clearance and absence of concomitant hypertension, stroke or gastrointestinal diseases.

    CONCLUSION: Dabigatran was associated with a significant improvement in treatment convenience and satisfaction after switching from VKAs when used for stroke prevention in NVAF patients from Southeast Asia and South Korea.

    Matched MeSH terms: Anticoagulants/administration & dosage*; Anticoagulants/adverse effects
  11. Ng SS, Lai NM, Nathisuwan S, Jahan NK, Dilokthornsakul P, Kongpakwattana K, et al.
    Sci Rep, 2020 01 20;10(1):662.
    PMID: 31959803 DOI: 10.1038/s41598-019-57370-2
    Warfarin care bundles (e.g. genotype-guided warfarin dosing, patient's self-testing [PST] or patient's self-management [PSM] and left atrial appendage closure) are based on the concept of combining several interventions to improve anticoagulation care. NOACs are also introduced for stroke prevention in atrial fibrillation (SPAF). However, these interventions have not been compared in head-to-head trials yet. We did a network meta-analysis based on a systematic review of randomized controlled trials comparing anticoagulant interventions for SPAF. Studies comparing these interventions in adults, whether administered alone or as care bundles were included in the analyses. The primary efficacy outcome was stroke and the primary safety outcome was major bleeding. Thirty-seven studies, involving 100,142 patients were assessed. Compared to usual care, PSM significantly reduced the risk of stroke (risk ratio [RR] 0.24, 95% CI 0.08-0.68). For major bleeding, edoxaban 60 mg (0.80, 0.71-0.90), edoxaban 30 mg (0.48, 0.42-0.56), and dabigatran 110 mg (0.81, 0.71-0.94) significantly reduced the risk of major bleeding compared with usual warfarin care. Cluster rank plot incorporating stroke and major bleeding outcomes indicates that some warfarin care bundles perform as well as NOACs. Both interventions are therefore viable options to be considered for SPAF. Additional studies including head-to-head trials and cost-effectiveness evaluation are still warranted.
    Matched MeSH terms: Anticoagulants/administration & dosage*; Anticoagulants/adverse effects
  12. Ren X, Evangelista-Leite D, Wu T, Rajab TK, Moser PT, Kitano K, et al.
    Biomaterials, 2018 11;182:127-134.
    PMID: 30118980 DOI: 10.1016/j.biomaterials.2018.08.012
    Decellularized native extracellular matrix (ECM) biomaterials are widely used in tissue engineering and have reached clinical application as biomesh implants. To enhance their regenerative properties and postimplantation performance, ECM biomaterials could be functionalized via immobilization of bioactive molecules. To facilitate ECM functionalization, we developed a metabolic glycan labeling approach using physiologic pathways to covalently incorporate click-reactive azide ligands into the native ECM of a wide variety of rodent tissues and organs in vivo, and into the ECM of isolated rodent and porcine lungs cultured ex vivo. The incorporated azides within the ECM were preserved after decellularization and served as chemoselective ligands for subsequent bioconjugation via click chemistry. As proof of principle, we generated alkyne-modified heparin, immobilized it onto azide-incorporated acellular lungs, and demonstrated its bioactivity by Antithrombin III immobilization and Factor Xa inhibition. The herein reported metabolic glycan labeling approach represents a novel platform technology for manufacturing click-reactive native ECM biomaterials, thereby enabling efficient and chemoselective functionalization of these materials to facilitate tissue regeneration and repair.
    Matched MeSH terms: Anticoagulants/pharmacology; Anticoagulants/chemistry*
  13. Haniza MZ, Adams S, Jones EP, MacNicoll A, Mallon EB, Smith RH, et al.
    PeerJ, 2015;3:e1458.
    PMID: 26664802 DOI: 10.7717/peerj.1458
    The brown rat (Rattus norvegicus) is a relatively recent (<300 years) addition to the British fauna, but by association with negative impacts on public health, animal health and agriculture, it is regarded as one of the most important vertebrate pest species. Anticoagulant rodenticides were introduced for brown rat control in the 1950s and are widely used for rat control in the UK, but long-standing resistance has been linked to control failures in some regions. One thus far ignored aspect of resistance biology is the population structure of the brown rat. This paper investigates the role population structure has on the development of anticoagulant resistance. Using mitochondrial and microsatellite DNA, we examined 186 individuals (from 15 counties in England and one location in Wales near the Wales-England border) to investigate the population structure of rural brown rat populations. We also examined individual rats for variations of the VKORC1 gene previously associated with resistance to anticoagulant rodenticides. We show that the populations were structured to some degree, but that this was only apparent in the microsatellite data and not the mtDNA data. We discuss various reasons why this is the case. We show that the population as a whole appears not to be at equilibrium. The relative lack of diversity in the mtDNA sequences examined can be explained by founder effects and a subsequent spatial expansion of a species introduced to the UK relatively recently. We found there was a geographical distribution of resistance mutations, and relatively low rate of gene flow between populations, which has implications for the development and management of anticoagulant resistance.
    Matched MeSH terms: Anticoagulants
  14. Liew BS, Ghani AA, You X
    Med J Malaysia, 2019 Jun;74(3):246-249.
    PMID: 31256185
    Stroke is uncommon among young adults. However, the incidence of stroke among young women increases with pregnancy during peripartum and postpartum periods. The relative risk of suffering from haemorrhagic stroke was three times higher than ischemic stroke during these periods when compared with antenatal period. Neuroimaging should be prioritized in order to establish diagnosis and to facilitate treatment in a patient with suspected acute stroke. Prophylaxic anticoagulants should be used in high risk patients. Treatments of acute stroke in pregnant women include anti-platelet and thrombolytic agents. Further studies should be carried as there is lack of high level of evidences to formulate clear guideline for the management of stroke during pregnancy.
    Matched MeSH terms: Anticoagulants
  15. Balaji G, Sriharsha Y, Sharma D
    Malays Orthop J, 2019 Jul;13(2):49-51.
    PMID: 31467653 DOI: 10.5704/MOJ.1907.010
    A 58-year old female patient presented to us with a three months' old fracture of the neck of femur. She underwent bipolar hemiarthroplasty. In the immediate postoperative period, she developed deep vein thrombosis for which she was started on anticoagulant therapy. Patient had persistent discharge from the wound since then and underwent regular dressings. On the eighth post-op day, she developed sciatic nerve palsy secondary to wound haematoma. The haematoma was decompressed immediately and she had a dramatic improvement in pain but her neurological deficit persisted. The wound healed completely without any complications. At three months follow up, she had recovered completely with grade 5/5 power in ankle and foot and full sensory recovery in the sciatic nerve distribution. She was ambulating comfortably with a walker. At final follow up around 20 months post-operation, she was pain-free and walking without any support. The wound had healed completely.
    Matched MeSH terms: Anticoagulants
  16. Bawadikji AA, Teh CH, Sheikh Abdul Kader MAB, Abdul Wahab MJB, Syed Sulaiman SA, Ibrahim B
    Am J Cardiovasc Drugs, 2020 Apr;20(2):169-177.
    PMID: 31435902 DOI: 10.1007/s40256-019-00364-2
    BACKGROUND: Warfarin is prescribed as an oral anticoagulant to treat/prevent thromboembolism in conditions such as atrial fibrillation. As there is a narrow therapeutic window, treatment with warfarin is challenging. Pharmacometabonomics using nuclear magnetic resonance (NMR) spectroscopy may provide novel techniques for the identification of novel biomarkers of warfarin.

    PURPOSE: The aim was to determine the metabolic fingerprint that predicts warfarin response based on the international normalized ratio (INR) in patients who are already receiving warfarin (phase I: identification) and to ascertain the metabolic fingerprint that discriminates stable from unstable INR in patients starting treatment with warfarin (phase II: validation).

    EXPERIMENTAL APPROACH: A total of 94 blood samples were collected for phase I: 44 patients with stable INR and 50 with unstable INR. Meanwhile, 23 samples were collected for phase II: nine patients with stable INR and 14 with unstable INR. Data analysis was performed using multivariate analysis including principal component analysis and partial least square-discriminate analysis (PLS-DA), followed by univariate and multivariate logistic regression (MVLR) to develop a model to identify unstable INR biomarkers.

    KEY RESULTS: For phase I, the PLS-DA model showed the following results: sensitivity 93.18%, specificity 91.49% and accuracy 92.31%. In the MVLR analysis of phase I, ten regions were associated with unstable INR. For phase II, the PLS-DA model showed the following results: sensitivity 66.67%, specificity 61.54% and accuracy 63.64%.

    CONCLUSIONS AND IMPLICATIONS: We have shown that the pharmacometabonomics technique was able to differentiate between unstable and stable INR with good accuracy. NMR-based pharmacometabonomics has the potential to identify novel biomarkers in plasma, which can be useful in individualizing treatment and controlling warfarin side effects, thus, minimizing undesirable effects in the future.

    Matched MeSH terms: Anticoagulants/administration & dosage; Anticoagulants/adverse effects; Anticoagulants/pharmacology*
  17. Ohn MH, Ng JR, Ohn KM, Luen NP
    BMJ Case Rep, 2021 Mar 22;14(3).
    PMID: 33753396 DOI: 10.1136/bcr-2021-241955
    Coagulation predominant-type coagulopathy such as microthrombosis and macrothrombosis is a well-known recognised complication found in COVID-19 infected critically ill patients. In the context of high incidence of thrombotic events in patients with COVID-19, supplementation with anticoagulant therapy has been routinely recommended and shown to reduce mortality. However, the recommended type, dose, duration and timing of anticoagulant has not been determined yet. Spontaneous retroperitoneal haematoma secondary to anticoagulant therapy is one of the well-known but self-limiting conditions. We report a 51-year-old COVID-19 positive woman, who was taking intermediate-intensity heparin therapy for venous thromboembolism prophylaxis and died from complication of retroperitoneal bleeding. Further studies are needed to verify the risk-benefit ratio of anticoagulant therapy in patients with COVID-19. Although anticoagulant deems appropriate to use in patients with COVID-19, clinicians should be cautious about major bleeding complication such as retroperitoneal haemorrhage even when full therapeutic dosage is not used.
    Matched MeSH terms: Anticoagulants
  18. Singh V, Haque S, Kumari V, El-Enshasy HA, Mishra BN, Somvanshi P, et al.
    Sci Rep, 2019 04 24;9(1):6482.
    PMID: 31019210 DOI: 10.1038/s41598-019-42740-7
    Arterial/venous thrombosis is the major cardiovascular disorder accountable for substantial mortality; and the current demand for antithrombotic agents is extensive. Heparinases depolymerize unfractionated heparin (UFH) for the production of low molecular-weight heparins (LMWHs; used as anticoagulants against thrombosis). A microbial strain of Streptomyces sp. showing antithrombotic activity was isolated from the soil sample collected from north India. The strain was characterized by using 16S rRNA homology technique and identified as Streptomyces variabilis MTCC 12266 capable of producing heparinase enzyme. This is the very first communication reporting Streptomyces genus as the producer of heparinase. It was observed that the production of intracellular heparinase was [63.8 U/mg protein (specific activity)] 1.58 folds higher compared to extracellular heparinase [40.28 U/mg protein]. DEAE-Sephadex A-50 column followed by Sepharose-6B column purification of the crude protein resulted 19.18 folds purified heparinase. SDS-PAGE analysis of heparinase resulted an estimated molecular-weight of 42 kDa. It was also found that intracellular heparinase has the ability to depolymerize heparin to generate LMWHs. Further studies related to the mechanistic action, structural details, and genomics involved in heparinase production from Streptomyces variabilis are warranted for large scale production/purification optimization of heparinase for antithrombotic applications.
    Matched MeSH terms: Anticoagulants
  19. Schellong S, Ageno W, Casella IB, Chee KH, Schulman S, Singer DE, et al.
    Semin Thromb Hemost, 2021 May 10.
    PMID: 33971682 DOI: 10.1055/s-0041-1729169
    Isolated distal deep vein thrombosis (IDDVT) is presumed to be more benign than proximal DVT (PDVT) or pulmonary embolism (PE), suggesting a need for different management approaches. This subgroup analysis of the RE-COVERY DVT/PE global, observational study investigated patient characteristics, hospitalization details, and anticoagulant therapy in patients with IDDVT in real-world settings in 34 countries enrolled from January 2016 to May 2017. Data were analyzed descriptively according to the type and location of the index venous thromboembolism (VTE): IDDVT, PDVT ± distal DVT (DDVT), and PE ± DVT. Of the 6,095 eligible patients, 323 with DVT located outside the lower limb and no PE were excluded. Of the remaining 5,772 patients, 17.6% had IDDVT, 39.9% had PDVT ± DDVT, and 42.5% had PE ± DVT. IDDVT patients were younger and had fewer risk factors for VTE than the other groups. Other comorbidities were less frequent in the IDDVT group, except for varicose veins, superficial thrombophlebitis, and venous insufficiency. IDDVT patients were less likely to be diagnosed in an emergency department (22.3 vs. 29.7% for PDVT ± DDVT and 45.4% for PE ± DVT) or hospitalized for VTE (29.2 vs. 48.5% for PDVT ± DDVT and 75.0% for PE ± DVT). At hospital discharge or 14 days after diagnosis (whichever was later), non-vitamin K antagonist oral anticoagulants were the most commonly used anticoagulants (55.6% for IDDVT, 54.7% for PDVT ± DDVT, and 52.8% for PE ± DVT). Although differences in patient characteristics, risk factors, and clinical management were identified, anticoagulant treatment of IDDVT was almost equal to that of PDVT or PE. Prospective studies should investigate whether, in a global perspective, this is an appropriate use of anticoagulants. TRIAL REGISTRATION NUMBER:  ClinicalTrials.gov NCT02596230.
    Matched MeSH terms: Anticoagulants
  20. Phillips KP, Romanov A, Artemenko S, Folkeringa RJ, Szili-Torok T, Senatore G, et al.
    Europace, 2020 02 01;22(2):225-231.
    PMID: 31665276 DOI: 10.1093/europace/euz286
    AIMS: Clinical practice guidelines do not recommend discontinuation of long-term oral anticoagulation in patients with a high stroke risk after catheter ablation for atrial fibrillation (AF). Left atrial appendage closure (LAAC) with Watchman has emerged as an alternative to long-term anticoagulation for patients accepting of the procedural risks. We report on the long-term outcomes of combining catheter ablation procedures for AF and LAAC from multicentre registries.

    METHODS AND RESULTS: Data were pooled from two prospective, real-world Watchman LAAC registries running in parallel in Europe/Middle-East/Russia (EWOLUTION) and Asia/Australia (WASP) between 2013 and 2015. Of the 1140 patients, 142 subjects at 11 centres underwent a concomitant AF ablation and LAAC procedure. The mean CHA2DS2-VASc score was 3.4 ± 1.4 and HAS-BLED score 1.5 ± 0.9. Successful LAAC was achieved in 99.3% of patients. The 30-day device and/or procedure-related serious adverse event rate was 2.1%. After a mean follow-up time of 726 ± 91 days, 92% of patients remained off oral anticoagulation. The rates of the composite endpoint of ischaemic stroke/transient ischaemic attack/systemic thromboembolism were 1.09 per 100 patient-years (100-PY); and for non-procedural major bleeding were 1.09 per 100-PY. These represent relative reductions of 84% and 70% vs. expected rates per risk scores.

    CONCLUSION: The long-term outcomes from these international, multicentre registries show efficacy for all-cause stroke prevention and a significant reduction in late bleeding events in a population of high stroke risk post-ablation patients who have been withdrawn from oral anticoagulation.

    Matched MeSH terms: Anticoagulants
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