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.
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.
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.
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.