Anticoagulants

Background and Purpose— Hyperperfusion syndrome is a rare but well-described complication after endarterectomy or stenting in the carotid circulation. Summary of Case— A 66-year-old man who had vertebrobasilar insufficiency refractory to medical treatment because of an intracranial right side vertebral stenosis was referred to our institution for endovascular treatment. Stenting was performed, and after 24 hours, he became extremely agitated, and this was followed by a period of apathy without focal neurological deficits. MRI showed bilateral thalamic hemorrhage. Conclusion— To our knowledge, this is the first report of hyperperfusion syndrome with hemorrhagic presentation after intracranial vertebral artery stenting.

SummaryA score that can accurately determine the risk of major bleeding during anticoagulant therapy may help to make decisions on anticoagulant use. RIETE is an ongoing registry of consecutive patients with acute venous thromboembolism (VTE). We composed a score to predict the risk for major bleeding within three months of anticoagulant therapy. Of 19,274 patients enrolled, 13,057 (67%) were randomly assigned to the derivation sample, 6,572 to the validation sample. In the derivation sample 314 (2.4%) patients bled (fatal bleeding, 105). On multivariate analysis, age >75 years, recent bleeding, cancer, creatinine levels >1.2 mg/dl, anemia, or pulmonary embolism at baseline were independently associated with an increased risk for major bleeding. A score was composed assigning 2 points to recent bleeding, 1.5 to abnormal creatinine levels or anemia, 1 point to the remaining variables. In the derivation sample 2,654 (20%) patients scored 0 points (low risk); 9,645 (74%) 1–4 poin...

Aliment Pharmacol Ther 31, 375-386Aliment Pharmacol Ther 31, 375-386SummaryBackground  The administration of parnaparin sodium as oral colon-release tablets (CB-01-05 MMX®) has been proposed as a novel approach for the treatment of ulcerative colitis (UC).Aim  To assess the efficacy and the tolerability of 8 weeks’ oral daily administration of 210 mg of parnaparin sodium compared with placebo in subjects treated with stable-doses of oral aminosalicylates.Methods  This multicenter, randomized, double-blind proof of concept trial compared the efficacy of CB-01-05 MMX® 210 mg tablets to placebo in 141 subjects with mild to moderately active left-sided UC treated with stable-doses of aminosalicylates. The efficacy was assessed by clinical activity index (CAI), endoscopic index (EI) and histological score (HS).Results  A total of 121 subjects (61 in test group and 60 in control group) formed the per protocol (PP) population. After 8 weeks of treatment, clinical remission was achieved in 83.6% of the CB-01-05 MMX® group, and in 63.3% in the comparator group (P = 0.011). This effect was also significantly evident in the test group at week 4 (P = 0.028). A significant difference was also detected in rectal bleeding, (disappeared respectively in 75.4% and 55.0%; P = 0.018), and in mucosal friability (recovered respectively in 80.3% and in 56.7%; P = 0.005).Conclusions  CB-01-05 MMX® was safe and significantly effective in treating subjects with mild-to-moderate left-sided UC treated with stable-doses of aminosalicylates.Background  The administration of parnaparin sodium as oral colon-release tablets (CB-01-05 MMX®) has been proposed as a novel approach for the treatment of ulcerative colitis (UC).Aim  To assess the efficacy and the tolerability of 8 weeks’ oral daily administration of 210 mg of parnaparin sodium compared with placebo in subjects treated with stable-doses of oral aminosalicylates.Methods  This multicenter, randomized, double-blind proof of concept trial compared the efficacy of CB-01-05 MMX® 210 mg tablets to placebo in 141 subjects with mild to moderately active left-sided UC treated with stable-doses of aminosalicylates. The efficacy was assessed by clinical activity index (CAI), endoscopic index (EI) and histological score (HS).Results  A total of 121 subjects (61 in test group and 60 in control group) formed the per protocol (PP) population. After 8 weeks of treatment, clinical remission was achieved in 83.6% of the CB-01-05 MMX® group, and in 63.3% in the comparator group (P = 0.011). This effect was also significantly evident in the test group at week 4 (P = 0.028). A significant difference was also detected in rectal bleeding, (disappeared respectively in 75.4% and 55.0%; P = 0.018), and in mucosal friability (recovered respectively in 80.3% and in 56.7%; P = 0.005).Conclusions  CB-01-05 MMX® was safe and significantly effective in treating subjects with mild-to-moderate left-sided UC treated with stable-doses of aminosalicylates.

OBJECTIVES: A case of delayed popliteal artery injury (PA-INJ) onset after total knee arthroplasty (TKA) in a patient under postoperative anticoagulation therapy is reported. The role of anticoagulation both in late PA-INJ presentation and in PA-INJ management is discussed.ReportAn obese 76-year-old woman was presented with a common femoral vein thrombosis coupled with pulmonary embolism five days after TKA. She was immediately placed under anticoagulation therapy. Four days later, during physiotherapy-supervised mobilization, she developed a calf haematoma and large retro-articular pseudoaneurysm. Angiography revealed a minor PA-INJ successively treated with a covered stent-graft. CONCLUSIONS: In cases of initially undetected and staunched TKA-related PA-INJs, postoperative anticoagulation therapy may act as a potential trigger for final arterial rupture during mobilization exercises, followed by acute bleeding; in these cases, endovascular management represents an excellent treatm...

The Neuromodulation Appropriateness Consensus Committee (NACC) of the International Neuromodulation Society (INS) evaluated evidence regarding the safety and efficacy of neurostimulation to treat chronic pain, chronic critical limb ischemia, and refractory angina and recommended appropriate clinical applications. The NACC used literature reviews, expert opinion, clinical experience, and individual research. Authors consulted the Practice Parameters for the Use of Spinal Cord Stimulation in the Treatment of Neuropathic Pain (2006), systematic reviews (1984 to 2013), and prospective and randomized controlled trials (2005 to 2013) identified through PubMed, EMBASE, and Google Scholar. Neurostimulation is relatively safe because of its minimally invasive and reversible characteristics. Comparison with medical management is difficult, as patients considered for neurostimulation have failed conservative management. Unlike alternative therapies, neurostimulation is not associated with medi...

The Asian venous thromboembolism (VTE) prophylaxis guidelines was 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, orthopaedic and trauma patients. The influence of primary thrombophilia in perioperative VTE is still unclear. The secondary risk factors however, is 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, ...

Results: Early postoperative mortality (in the first 30 days) was 3.4% (n = 1). The overall estimated Kaplan–Meier survival was 56.7% at 36 months, 46.7% at 60 months, and 43.3% at 96 months. HD program was discontinued for two patients after renal transplantation in the ...

SummaryThe natural history of patients with venous thromboembolism (VTE) who develop a major bleeding complication while on anticoagulant therapy is not well known. RIETE is a prospective registry of consecutive patients with symptomatic, objectively confirmed, acute VTE. The clinical characteristics, treatment decisions and outcome of all VTE patients who had major bleeding during the first three months of anticoagulant therapy were retrospectively studied. As of January 2007, 17,368 patients were included in RIETE. Of these, 407 (2.3%) had major bleeding during the study period: 144 gastrointestinal, 119 haematoma, 51 intracranial, 43 genitourinary, 50 other. In 286 (69%) patients anticoagulant therapy was discontinued, in 74 (18%) not modified, in 38 (9.1%) a vena cava filter was inserted. During the first 30 days after bleeding, 24 (5.9%) patients re-bled, 20 (4.9%) had recurrent VTE, 133 (33%) died. Of these, 75 died of bleeding, 12 of recurrent pulmonary embolism. Most deaths ...

Interaction thermodynamics between warfarin, a very popular anticoagulant, and Sudlow I binding site of human (HSA) or bovine (BSA) serum albumin have been examined in strictly controlled experimental conditions (HEPES buffer 50 mM, pH 7.4 and 25 °C) by means of isothermal titration calorimetry (ITC), fluorescence spectrometry (FS) and frontal analysis capillary electrophoresis (FA/CE). Each technique is based on measurements of a different property of the biochemical system, and then the results allow a critical discussion about the suitability of each approach to estimate the drug-protein binding parameters. The strongest interaction step is properly evaluated by the three assayed approaches being the derived binding constants strongly consistent: from 4 × 104 to 7 × 104 for HSA and from 0.8 × 105 to 1.2 × 105 for BSA. Binding enthalpy variations also show consistent results: -5.4 and -5.6 Kcal/mol for HSA and -4.3 and -3.7 Kcal/mol for BSA, as measured by ITC and FS, respectively...

Aim  To determine the attitude of Spanish general dentists in relation to dental extraction in patients with heart valve prostheses subjected to acenocoumarol anticoagulation.Material and methods  A telephone survey was made of Spanish general dentists, asking about the indicated approach in the case of performing dental extractions in patients with heart valve prostheses subjected to acenocoumarol (Sintrom®) anticoagulation.Results  Of the 271 dentists answered, 175 were male (64.6%) and 96 were female (35.4%), with a mean professional experience of 20.17 ± 9.3 years. A total of 228 dentists (84.1%) indicated the need to refer the patient to a specialist for establishing the required approach, while 43 dentists (15.9%) did not consider such a measure to be necessary. Among this latter group of 43 dentists, 26 (60.5%) considered that acenocoumarol should be withdrawn or replaced by low-molecular weight heparin, while 17 (39.5%) were of the opinion that the anticoagulation regimen should not be modified. In relation to the international normalized ratio, 36 (83.7%) did not consider it necessary to request this parameter. As regards the prevention of endocarditis, 11 (25.6%) specified the need for prophylaxis, although only eight (72.7%) did so correctly. There were no statistically significant differences in behaviour in relation to either gender or years of professional experience.Conclusions  This study identifies a lack of knowledge on the part of the dentists regarding the approach to dental extraction in patients with heart valve prostheses subjected to anticoagulation. Due educational measures therefore should be reinforced among these professionals.

Background— Dabigatran, an oral thrombin inhibitor, and rivaroxaban and apixaban, oral factor Xa inhibitors, have been found to be safe and effective in reducing stroke risk in patients with atrial fibrillation. We sought to compare the efficacy and safety of the 3 new agents based on data from their published warfarin-controlled randomized trials, using the method of adjusted indirect comparisons. Methods and Results— We included findings from 44 535 patients enrolled in 3 trials of the efficacy of dabigatran (Randomized Evaluation of Long-Term Anticoagulation Therapy [RELY]), apixaban (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation [ARISTOTLE]), and rivaroxaban (Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation [ROCKET-AF]), each compared with warfarin. The primary efficacy end point was stroke or systemic embolism; the safety end poi...

Many investigators have demonstrated the short-term and midterm efficacy of minimally invasive direct coronary artery bypass (MIDCAB). However, the influence of heparin dosing during MIDCAB on postoperative and immediate graft patency is less well defined. This report outlines our experience with MIDCAB employing a variety of heparinization protocols. The traditional MIDCAB approach was used in 152 patients who underwent single-vessel off-pump coronary artery bypass. Before the left internal mammary artery was divided, a 150-U/kg bolus of heparin sodium was given to 76 patients (group 1), and 300 U/kg was given to another 76 patients (group 2). Additional heparin was given during the procedures to maintain an activated clotting times of greater than 300 seconds for group 1 and greater than 400 seconds for group 2. On average, patients in group 1 required more boluses of heparin during treatment than patients in group 2. A larger standard deviation from the mean was observed for the ...

To identify optimum international normalized ratio (INR) levels and required warfarin doses and anticoagulation-related complications in patients following mechanical prosthetic valve replacement. Five hundred and seven patients were prospectively followed up for 10 years (2008.5 patient-years). Anticoagulation-related complications were classified into hemorrhage and thromboembolism. Two hundred and ninety-two (57.6%) were males and 215 (42.4%) were females with a mean age of 29.5 +/- 11.32 years. A total of 268 (52.9%) patients had mitral, 96 (18.9%) had aortic and mitral, and 76 (15%) had aortic valve replacement (AVR). Valves implanted totaled 345 (68%) ball and cage, 126 (24.9%) bileaflet, and 36 (7.1%) single disc. There were 10,669 total visits, with mean INR 2.6 +/- 0.59 and mean warfarin 5.17 +/- 1.6 mg. Sixty-four (3.2% per patient-years) events occurred during follow-up, of which 23 (1.13% per patient-years) events were due to thromboembolism and 41 (2.04% per patient-yea...

The term thrombophilia describes an increased tendency to develop thrombosis and many laboratory markers with different strengths of association with thrombosis have been identified. The main causes of maternal mortality and morbidity in developed countries is venous thromboembolism (VTE) and obstetric complications. During pregnancy and puerperium the risk for VTE increases due to hemostatic imbalance towards a prothrombotic state, and it is further increased in women carriers of thrombophilia; recent studies have also demonstrated an association between thrombophilia and obstetric complications. These complications are, therefore, considered potentially preventable with the prophylactic administration of anticoagulant drugs, although their efficacy is not proven by data from randomized controlled trials. After a systematic comprehensive literature review and using a rigorous methodology, the expert panel formulated recommendations regarding the usefulness of screening for thrombophilia in pregnancy to identify high-risk women and for the management of antithrombotic prophyalxis. When evidence is lacking, consensus-based recommendations are provided.

The genus Citrus of the family Rutaceae includes many species e.g. Citrus indica, Citrus aurantifolia and Citrus limon, among which Citrus limon L. Burm. f. has been reported to have highest antimicrobial activity. It is used as antidote against certain venom, due to its platelet inhibitory effect and also reported to have hypocholesterolemic effect. However its anticoagulant and thrombolytic effect were not been investigated, hence a prospective in-vitro/in-vivo study was designed to determine the effect of Citrus limon on blood parameters, coagulation and anticoagulation factors. In-vitro tests revealed highly significant increase in thrombin time and activated partial thromboplastin time by Citrus limon, whereas fibrinogen concentration was significantly reduced in comparison to control, however prothrombin time was not affected significantly. In-vivo testing of Citrus limon was done at three different doses i.e. 0.2ml/kg, 0.4ml/kg and 0.6ml/kg in healthy rabbits. Significant cha...