Displaying publications 1 - 20 of 22 in total

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  1. Liew NC, Sim KH, Ng SC, Suhail A, Premchandran N
    Med J Malaysia, 2011 Aug;66(3):278-80; quiz 281.
    PMID: 22111463 MyJurnal
    Venous thromboembolism is a rising concern in Asia especially among patients after surgery where this complication is readily preventable. Despite the availability of several treatment options, the acceptance of prophylaxis and usage of these methods remain low. A possible explanation to this behavior is the limitations attached to the available treatment options: narrow therapeutic window of warfarin and parenteral administration of low molecular weight as well as unfractionated heparins. Newer agents have been researched and introduced to overcome these limitations in the hope of improving the adaptation towards post surgical thromboprophylaxis. Dabigatran and rivaroxaban are two such new agents that are promising in view of efficacy and ease of administration.
    Matched MeSH terms: Venous Thromboembolism/prevention & control*
  2. Sivananthan DK
    J Orthop Surg (Hong Kong), 2013 Aug;21(2):139.
    PMID: 24014768
    Matched MeSH terms: Venous Thromboembolism/prevention & control*
  3. Chow TWP, Wong YM
    Med J Malaysia, 2001 Dec;56(4):418-27.
    PMID: 12014760
    Thromboembolic disease remains an important cause of maternal mortality worldwide. The risk assessments for prevention of thromboembolism in pregnancy are controversial due to lack of large-scale randomised controlled trials. Unfractionated heparin is at present, the anticoagulant of choice during pregnancy. However, it may be superseded by low-molecular-weight heparin in the near future because of its safety and efficacy.
    Matched MeSH terms: Thromboembolism/prevention & control*
  4. Prasannan S, Chin LN, Gul YA
    Asian J Surg, 2005 Apr;28(2):125-30.
    PMID: 15851367
    OBJECTIVE: The aim of this study was to analyse the current practice of venous thromboembolism (VTE) prophylaxis among general surgeons in Malaysia.

    METHODS: A questionnaire survey was conducted among general surgeons attending the annual Malaysian College of Surgeons meeting in 2002. A total of 110 questionnaires were distributed to specialist-grade general surgeons with varying subspecialty interests.

    RESULTS: Seventy-seven (70%) surgeons returned the questionnaire. Of these, 43% were of the opinion that VTE was as common in Asian patients as in the West. Selective VTE prophylaxis was used by 99% in their practice. The indications for use, in order of frequency, were: previous VTE disease, risk grading, prolonged surgery, obesity, malignancy and age. Low molecular weight heparin was the most common type of prophylaxis used. VTE-related morbidity was reported by 44 surgeons (57%) over the past year, and 39% of these cases were fatal.

    CONCLUSION: The high incidence of VTE-related complications indicates that the use of thromboprophylaxis is either insufficient or not matched to the level of risk. Updated guidelines on VTE prophylaxis should be used so that a standardized approach can ensure that patients receive adequate prophylaxis where indicated.

    Matched MeSH terms: Thromboembolism/prevention & control*
  5. Gan GG, Teh A, Goh KY, Chong HT, Pang KW
    Int J Hematol, 2003 Jul;78(1):84-6.
    PMID: 12894858
    Warfarin is a drug commonly used in the prevention of thromboembolic events. There have been reports suggesting that racial background may influence warfarin dose requirements. Malaysia is a multiracial country in which there are 3 major races, Malay, Chinese, and Indian. We examined 100 patients from our hospital on stable maintenance doses of warfarin, with international normalized ratio (INR) of 2.0 to 3.5. We found that the mean warfarin dose for Indian patients (n = 19) was 6.9 mg, for Chinese patients (n = 55) was 3.6 mg, and for Malay patients (n = 26) was 3.2 mg. The results showed that the Indian patients required a statistically significantly higher warfarin dose than did patients of the other 2 races (P < .0005). Age was also found to affect the daily warfarin maintenance dose.
    Matched MeSH terms: Thromboembolism/prevention & control
  6. Zairul-Nizam ZF, Gul YA
    J Orthop Surg (Hong Kong), 2003 Dec;11(2):178-83.
    PMID: 14676344
    To survey Malaysian orthopaedic surgeons' attitudes to and use of venous thromboembolic disease prophylaxis.
    Matched MeSH terms: Thromboembolism/prevention & control*
  7. Kow CS, Hasan SS
    Rev Esp Cardiol (Engl Ed), 2021 01;74(1):114-115.
    PMID: 32933883 DOI: 10.1016/j.rec.2020.08.009
    Matched MeSH terms: Venous Thromboembolism/prevention & control*
  8. Liew NC, Alemany GV, Angchaisuksiri P, Bang SM, Choi G, DE Silva DA, et al.
    Int Angiol, 2017 Feb;36(1):1-20.
    PMID: 27606807 DOI: 10.23736/S0392-9590.16.03765-2
    The Asian venous thromboembolism (VTE) prophylaxis guidelines were first published in 2012. Since its first edition, the Asian Venous Thrombosis Forum (AVTF) working group have updated the Asian VTE epidemiology and reviewed issues that were not addressed in the previous guidelines. The authors noted that the rising incidence of VTE across Asia may be attributable to aging population, dietary changes, and increasing incidence of obesity and diabetes. The new additions in the guideline include role of thrombophilia in VTE, bleeding risk in Asians, individual risk assessment, updates in the prevention of VTE in medically ill, bariatric surgery, cancer, orthopedic and trauma patients. The influence of primary thrombophilia in perioperative VTE is still unclear. The secondary risk factors, however, are similar between Asians and Caucasians. The group found no evidence of increased risk of bleeding while using pharmacological agents, including the use of novel anti-coagulants. At present, Caprini risk assessment model is widely used for individual risk assessment. Further validation of this model is needed in Asia. In medically ill patients, pharmacological agents are preferred if there is no bleeding risk. Intermittent pneumatic compression device (IPC) is recommended in patients with bleeding risk but we do not recommend using graduated compressive stockings. In bariatric patients, data on VTE is lacking in Asia. We recommend following current international guidelines. A high index of suspicion should be maintained during postbariatric surgery to detect and promptly treat portomesenteric venous thrombosis. Different cancer types have different thrombotic risks and the types of surgery influence to a large extent the overall VTE risk. Cancer patients should receive further risk assessment. In patients with higher thrombotic risk, either due to predisposing risk or concomitant surgery, low molecular weight heparin is indicated. Different countries appear to have different incidence of VTE following trauma and major orthopedic surgery. We recommend mechanical prophylaxis using IPC as the main method and additional pharmacological prophylaxis if the thrombotic risk is high. As for obstetric practice, we propose adherence to the UK Greentop guideline that is widely accepted and utilized across Asia. To improve VTE thromboprophylaxis implementation in the region, we propose that there should be better health education, establishment of hospital-based guidelines and multidisciplinary collaboration.
    Matched MeSH terms: Venous Thromboembolism/prevention & control*
  9. Voon HY, Chai MC, Hii LY, Amin R, Suharjono HN
    J Obstet Gynaecol, 2018 May;38(4):493-497.
    PMID: 29433369 DOI: 10.1080/01443615.2017.1389867
    Strategies to prevent mortality from obstetric venous thromboembolism begin with identification, risk stratification and subsequently, implementation of prophylactic measures. We sought to identify the burden of pharmacologic thromboprophylaxis in postpartum women, including the main clinical indications and its uptake in a multireligious population, with Islam as the official religion. A total of 2514 deliveries between 1st January to 31st December 2016, across three centres in Malaysia were reviewed retrospectively from hospital-based registries. 770 (30.62%) patients fulfilled the criteria for thromboprophylaxis based on the revised 2015 criteria proposed by the Royal College of Obstetricians and Gynaecologists. A combination of age, parity, BMI, caesarean section and preterm births were the main indications. One out of the five patients who delivered vaginally required thromboprophylaxis. In our setting with a sizable Muslim population, low molecular weight heparin was the thromboprophylaxis of choice in more than two-third of the patients. The information obtained from this study allows better local resource planning. Impact statement What is already known on this subject: Risk factors for venous thromboembolism in pregnancy and puerperium are largely drawn from registries due to the rarity of the index event. Up to 7% of women require antenatal thromboprophylaxis based on the criteria proposed by the Royal College of Obstetrician and Gynaecologists in 2009. What do the results of this study add: Using the RCOG guideline revised in 2015, a significant proportion of women delivering vaginally would require postnatal thromboprophylaxis based on age, parity and BMI. When either age or parity, both with relatively low odds ratio for thrombosis were omitted, a substantial proportion of women would not achieve the threshold for prophylaxis. Despite a sizable Muslim population in the country, the uptake of low molecular weight heparin was relatively high. What are the implications of these findings for clinical practice and/or future research: Cost-benefit studies should consider the adjusted odds ratio of individual indications on a VTE event. While uptake and acceptability is high, prospective studies on medication adherence is equally pertinent.
    Matched MeSH terms: Venous Thromboembolism/prevention & control*
  10. Chong HY, Saokaew S, Dumrongprat K, Permsuwan U, Wu DB, Sritara P, et al.
    Thromb Res, 2014 Dec;134(6):1278-84.
    PMID: 25456732 DOI: 10.1016/j.thromres.2014.10.006
    Pharmacogenetic (PGx) test is a useful tool for guiding physician on an initiation of an optimal warfarin dose. To implement of such strategy, the evidence on the economic value is needed. This study aimed to determine the cost-effectiveness of PGx-guided warfarin dosing compared with usual care (UC).
    Matched MeSH terms: Thromboembolism/prevention & control*
  11. Saheb Sharif-Askari F, Syed Sulaiman SA, Saheb Sharif-Askari N, Al Sayed Hussain A, Railey MJ
    PLoS One, 2014;9(9):e106517.
    PMID: 25181525 DOI: 10.1371/journal.pone.0106517
    Anticoagulation therapy is usually required in patients with chronic kidney disease (CKD) for treatment or prevention of thromboembolic diseases. However, this benefit could easily be offset by the risk of bleeding.
    Matched MeSH terms: Thromboembolism/prevention & control
  12. 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: Thromboembolism/prevention & control
  13. 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: Venous Thromboembolism/prevention & control
  14. 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: Venous Thromboembolism/prevention & control*
  15. Lee L, Liew NC, Gee T
    Int Angiol, 2012 Dec;31(6):526-33.
    PMID: 23222930
    This survey was conducted to determine the opinions and practices of peri-operative venous thromboembolism (VTE) prophylaxis among surgical and intensive care specialists in Asia.
    Matched MeSH terms: Venous Thromboembolism/prevention & control*
  16. Lu HT, Nordin R, Othman N, Choy CN, Kam JY, Leo BC, et al.
    J Med Case Rep, 2016 Aug 10;10(1):221.
    PMID: 27510438 DOI: 10.1186/s13256-016-1018-0
    BACKGROUND: Many cases of cardiac masses have been reported in the literature, but in this case report we described a rare case of biatrial cardiac mass that represented a challenge for diagnosis and therapy. The differentiation between cardiac masses such as thrombi, vegetations, myxomas and other tumors is not always straightforward and an exact diagnosis is important because of its distinct treatment strategy. Transthoracic/esophageal echocardiography and cardiac magnetic resonance play an important role in establishing the diagnosis of cardiac masses. However, no current noninvasive diagnostic tool has the ability to absolutely diagnose cardiac masses; obtaining a pathological specimen by surgical resection of cardiac masses is the only reliable method to diagnose cardiac masses accurately. Our case report is an exception in that the final diagnosis was affirmed by empirical anticoagulation therapy based on clinical judgment and noninvasive characterization of biatrial mass.

    CASE PRESENTATION: We described a 54-year-old Malay man with severe mitral stenosis and atrial fibrillation who presented with a biatrial mass. Transthoracic/esophageal echocardiography and cardiac magnetic resonance detected a large, homogeneous right atrial mass typical of a thrombus, and a left atrial mass adhering to interatrial septum that mimicked atrial myxoma. The risk factors, morphology, location, and characteristics of the biatrial cardiac mass indicated a diagnosis of thrombi. However, our patient declined surgery. As a result, the nature of his cardiac masses was not specified by histology. Of note, his left atrial mass was completely regressed by long-term warfarin, leaving a residual right atrial mass. Thus, we affirmed the most probable diagnosis of cardiac thrombi. During the course of treatment, he had an episode of non-fatal ischemic stroke most probably because of a thromboembolism.

    CONCLUSIONS: Noninvasive characterization of cardiac mass is essential in clarifying the diagnosis and directing treatment strategy. Anticoagulation is a feasible treatment when the clinical assessment, risk factors, and imaging findings indicate a diagnosis of thrombi. After prolonged anticoagulation therapy, complete resolution of biatrial thrombi was achievable in our case.

    Matched MeSH terms: Venous Thromboembolism/prevention & control*
  17. Kotirum S, Chongmelaxme B, Chaiyakunapruk N
    J Thromb Thrombolysis, 2017 Feb;43(2):252-262.
    PMID: 27704332 DOI: 10.1007/s11239-016-1433-5
    To analyze the cost-utility of oral dabigatran etexilate, enoxaparin sodium injection, and no intervention for venous thromboembolism (VTE) prophylaxis after total hip or knee replacement (THR/TKR) surgery among Thai patients. A cost-utility analysis using a decision tree model was conducted using societal and healthcare payers' perspectives to simulate relevant costs and health outcomes covering a 3-month time horizon. Costs were adjusted to year 2014. The willingness-to-pay threshold of THB 160,000 (USD 4926) was used. One-way sensitivity and probabilistic sensitivity analyses using a Monte Carlo simulation were performed. Compared with no VTE prophylaxis, dabigatran and enoxaparin after THR and TKR surgery incurred higher costs and increased quality adjusted life years (QALYs). However, their incremental cost-effectiveness ratios were high above the willingness to pay. Compared with enoxaparin, dabigatran for THR/TKR lowered VTE complications but increased bleeding cases; dabigatran was cost-saving by reducing the costs [by THB 3809.96 (USD 117.30) for THR] and producing more QALYs gained (by 0.00013 for THR). Dabigatran (vs. enoxaparin) had a 98 % likelihood of being cost effective. Dabigatran is cost-saving compared to enoxaparin for VTE prophylaxis after THR or TKR under the Thai context. However, both medications are not cost-effective compared to no thromboprophylaxis.
    Matched MeSH terms: Venous Thromboembolism/prevention & control*
  18. Indirayani I, Kalok A, Nik Ismail NA, Shah SA, Lim PS, Mohamed Ismail NA, et al.
    J Obstet Gynaecol Res, 2018 Aug;44(8):1458-1465.
    PMID: 29845672 DOI: 10.1111/jog.13686
    AIM: Sodium pentosan polysulfate (Na-PPS) is a plant-based agent that has similar action with low-molecular-weight heparin. It inhibits factor Xa, preventing blood clot formation. To date, its use in clinical practice as thromboprophylaxis agent is still limited. In addition, the efficacy and safety profile of this agent was not robustly reported globally, especially for countries with major Muslim population. We hypothesized that Na-PPS was equally effective as the standard thromboprophylaxis. We aim to compare the efficacy and safety of Na-PPS against standard agent (fondaparinux or enoxaparin).

    METHODS: This was a randomized control, open-label trial. Women underwent major gynecological surgery were randomized to receive either subcutaneous 50 mg of Na-PPS twice daily or subcutaneous enoxaparin 40 mg once daily. Fondaparinux 2.5 mg once daily was given to Muslim women as an alternative to enoxaparin. The treatment was started 6 h postoperatively, for at least 3 days. All the patients received thromboembolic deterrent stockings. The primary efficacy outcome was venous thromboembolism up to 3 days postsurgery. The main safety outcomes were minor and major bleeding.

    RESULTS: Among 109 participants, there was no incidence of venous thromboembolism. None of the women developed major bleeding. Minor bleeding was observed in 28.3% (15/53) and 5.4% (3/56) of Na-PPS and standard thromboprophylaxis group, respectively (P = 0.001).

    CONCLUSION: Na-PPS was associated with increased risk of minor bleeding. There was insufficient data to conclude its efficacy as thromboprophylaxis. Further research is needed to evaluate Na-PPS safety as a standard thromboprophylactic agent.

    Matched MeSH terms: Thromboembolism/prevention & control*
  19. 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: Thromboembolism/prevention & control*
  20. 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: Thromboembolism/prevention & control
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