ABSTRACT
Deep vein thrombosis (DVT) is a common complication following traumatic fracture with a 0.5%-1% annual incidence. Low molecular weight heparin (LMWH) is the most commonly used anticoagulation drug for DVT prevention, but treatment with LMWH is invasive. Our aim is to compare the antithrombotic effect of dragon's blood, an oral botanical anticoagulant medicine approved by the Chinese FDA, with LMWH in patients undergoing hip fracture surgery and to explore the molecular mechanisms of anticoagulation treatment. Our study recruited patients and divided them into LMWH and dragon's blood treatment group. Coagulation index tests, Doppler ultrasound and mRNA sequencing were performed before and after anticoagulation therapy. There was no significant difference in postoperative DVT incidence between the two groups (23.1% versus 15.4%, P=0.694). D-dimer (D-D) and fibrinogen degradation product (FDP) showed significant reductions in both groups after anticoagulation treatments. We identified SLC4A1, PROS1, PRKAR2B and seven other genes as being differentially expressed during anticoagulation therapy in both groups. Genes correlated with coagulation indexes were also identified. Dragon's blood and LMWH showed similar effects on DVT and produced similar gene expression changes in patients undergoing hip fracture surgery, indicating that dragon's blood is a more convenient antithrombosis medicine (oral) than LMWH (hypodermic injection).
Subject(s)
Anticoagulants/therapeutic use , Heparin, Low-Molecular-Weight/therapeutic use , Plant Extracts/therapeutic use , Aged , Blood Coagulation/genetics , Female , Hip Fractures/blood , Hip Fractures/surgery , Humans , Male , Middle Aged , Postoperative Complications/blood , Postoperative Complications/prevention & control , Protein Interaction Maps , Transcriptome , Venous Thrombosis/blood , Venous Thrombosis/prevention & controlABSTRACT
AIM AND OBJECTIVE: To evaluate the efficacy and safety of Chinese herbal medicines for promoting blood circulation and removing blood stasis (PBCRBSM) for preventing deep venous thrombosis (DVT) after total hip arthroplasty (THA). MATERIALS AND METHODS: The databases were searched for studies comparing the preventive abilities of PBCRBSM and Western medicine, such as low molecular weight heparin (LMWH), rivaroxaban, and aspirin, as well as for randomized controlled trials on DVT after THA. Data were analyzed using RevMan 5.3 software. RESULTS: A total of 3254 randomized controlled trials were included, including 1630 cases in the experimental group and 1624 cases in the control group. Meta-analysis showed that compared with Western medicine, PBCRBSM reduced the incidence of DVT (OR=0.38, 95% CI [0.30, 0.48], P < 0.001); prolonged activated partial thromboplastin time (APTT) (SMD=0.44, 95% CI [0.35, 0.53], P < 0.001); reduced D-dimer (SMD=-0.75, 95% CI [-0.84,-0.65], P < 0.001), FIB (SMD=-0.61, 95% CI [-0.72, -0.50], P < 0.001), blood viscosity (P<0.01), circumference difference in lower extremities (P<0.01), venous blood flow velocity (SMD=0.97, 95% CI [0.77, 1.16], P < 0.001), and drainage volume (SMD=-1.53, 95% CI [-1.71, -1.35], P < 0.001); and reduced adverse reactions (OR = 0.32, 95% CI [0.19, 0.56], P < 0.001). There was no significant difference in prolonging prothrombin time (PT) between traditional Chinese medicine and Western medicine (SMD = 0.07, 95% CI [-0.0.01). 3, 0.16], P > 0.05. CONCLUSION: PBCRBSM is an effective method for preventing DVT after THA and has fewer adverse effects.
Subject(s)
Arthroplasty, Replacement, Hip , Blood Coagulation/drug effects , Drugs, Chinese Herbal/pharmacology , Venous Thrombosis/drug therapy , China , Humans , Medicine, Chinese Traditional , Venous Thrombosis/bloodABSTRACT
OBJECTIVE: An association between cerebral venous sinus thrombosis (CVST) and high altitude has been previously proposed, but limited published data exist to support this association. We investigated 28 cases of CVST occurring at high altitude and sought to describe patient demographics, altitude and acclimatization, hematological laboratory findings, neuroimaging, treatment, and prognosis in these cases. METHODS: Twenty-eight cases of symptomatic CVST occurring at high altitude were identified between the months of August 2017 and December 2018, in collaboration with Military Hospital, Rawalpindi and Combined Military Hospital, Skardu (Pakistan). Follow-up visits were performed at 1 and 6 months. RESULTS: Twenty-seven (96%) of the patients were males, and the mean age was 33 years. In total, 32.1% were smokers. The mean NIHSS score on presentation was 5.5. 85.7% of the cases occurred at altitude higher than 8,000 feet. On average 107.8 days were spent at a high altitude prior to CVST. Totally, 71.4% had acclimatized for >2 weeks. The mean hemoglobin (Hb) value was 16.7 g/dL and 50% had d-dimer levels higher than 1,000 ng/mL. On MRI, 25% showed signs of hemorrhage and 14.3% showed infarcts. Treatments provided include low-molecular-weight heparin and Rivaroxaban and were associated with good outcomes. CONCLUSION: CVST is not uncommon at high altitude (>8,000 feet). It is predominantly a male disease. Most patients have high Hb and high D-dimer levels. The overall outcome was good.
Subject(s)
Altitude , Anticoagulants/therapeutic use , Blood Coagulation/drug effects , Factor Xa Inhibitors/therapeutic use , Heparin, Low-Molecular-Weight/therapeutic use , Rivaroxaban/therapeutic use , Sinus Thrombosis, Intracranial/drug therapy , Venous Thrombosis/drug therapy , Acclimatization , Adult , Anticoagulants/adverse effects , Biomarkers/blood , Factor Xa Inhibitors/adverse effects , Female , Fibrin Fibrinogen Degradation Products/metabolism , Hemoglobins/metabolism , Heparin, Low-Molecular-Weight/adverse effects , Hospitals, Military , Humans , Male , Middle Aged , Military Personnel , Pakistan , Retrospective Studies , Risk Factors , Rivaroxaban/adverse effects , Sinus Thrombosis, Intracranial/blood , Sinus Thrombosis, Intracranial/diagnostic imaging , Sinus Thrombosis, Intracranial/etiology , Time Factors , Treatment Outcome , Venous Thrombosis/blood , Venous Thrombosis/diagnostic imaging , Venous Thrombosis/etiology , Young AdultABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Danhong Huayu Koufuye (DHK), a compound traditional Chinese medicine, is composed of Salvia miltiorrhiza radix (Salvia miltiorrhiza Bge.), Angelicae Sinensis radix (Angelicae Sinensis (Oliv.) Diels.), Chuanxiong rhizoma (Ligusticum chuanxiong Hort.), Persicae semen (Prunus persica (L.) Batsch), Carthami flos (Carthamus tinctorius L.), Bupleuri radix (Bupleurum chinense DC.) and Aurantii fructus (Citrus aurantium L.). DHK prevents deep vein thrombosis (DVT) through antiinflammation. However, the antiinflammatory mechanism of DHK is still unknown. OBJECTIVE: The aim of this study was to evaluate whether DHK prevented venous thrombosis through antiinflammation via Sirtuin 1 (SIRT1)/NF-κB signaling pathway. METHODS: Inferior vena cava (IVC) stenosis-induced DVT rat model was established. Rats were administered with DHK (1.6, 3.2 or 6.4â¯mL/kg/d, p.o.), heparin (200 U/kg/d, i.v.), clopidogrel (25â¯mg/kg/d, p.o.), resveratrol (50â¯mg/kg/d, p.o.) or vehicle (p.o.) once daily for two days. Blood coagulation, blood fibrinolysis, blood viscosity, blood cell counts and platelet activity were evaluated. Serum levels of inflammatory cytokines were analyzed by enzyme-linked immunosorbent assay. Pathological changes were observed by hematoxylin-eosin (HE) staining. Protein expressions in thrombosed IVCs were evaluated by Western blot and/or immunofluorescence analyses. SIRT1 mRNA expression was analyzed by real-time quantitative polymerase chain reaction. Besides, SIRT1-specific inhibitor EX527 was pretreated to confirm the role of SIRT1/NF-κB signaling pathway in the antithrombotic effect of DHK. RESULTS: DHK remarkably prevented DVT. DHK had no effects on blood coagulation, blood fibrinolysis, blood viscosity, blood cell counts or platelet activity. But DHK significantly up-regulated protein and mRNA expressions of SIRT1, and reduced leukocytes infiltration into thrombus and vein wall, serum levels of inflammatory cytokines, and protein expressions of acetylated p65 (Ace-p65), phosphorylated p65 (p-p65) and tissue factor (TF). Moreover, the antithrombotic effect of DHK was significantly abolished by EX527. CONCLUSION: DHK may prevent DVT by inhibiting inflammation via SIRT1/NF-κB signaling pathway.
Subject(s)
Anti-Inflammatory Agents/therapeutic use , Drugs, Chinese Herbal/therapeutic use , Fibrinolytic Agents/therapeutic use , Venous Thrombosis/drug therapy , Animals , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/pharmacology , Blood Cell Count , Blood Coagulation/drug effects , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/pharmacology , Female , Fibrinolytic Agents/chemistry , Fibrinolytic Agents/pharmacology , Interleukin-1beta/blood , Male , Phytochemicals/analysis , Phytochemicals/pharmacology , Phytochemicals/therapeutic use , Platelet Activation/drug effects , Rats, Sprague-Dawley , Signal Transduction/drug effects , Sirtuin 1/genetics , Sirtuin 1/metabolism , Tumor Necrosis Factor-alpha/blood , Venous Thrombosis/blood , Venous Thrombosis/genetics , Venous Thrombosis/metabolismABSTRACT
BACKGROUND/AIMS: Limited data are available regarding the efficacy of rivaroxaban for the treatment of cancer-associated venous thromboembolism (VTE). The aim of this study was to evaluate the effectiveness and safety of rivaroxaban for the treatment of VTE in active cancer patients. METHODS: In this prospective, multicenter, open-label trial (NCT01989845), we enrolled patients with active cancer and objectively diagnosed lower-extremity deep vein thrombosis, pulmonary embolism (PE), or both from November 2013 to June 2016. Active cancer was defined as a histologically confirmed malignancy, which was diagnosed or treated within the previous 6 months, or as a recurrent/ metastatic cancer. Patients received oral rivaroxaban 15 mg twice daily for first 3 weeks, followed by 20 mg once daily for 6 months. The primary outcome was the symptomatic recurrent VTE and the secondary outcomes included any recurrent VTE, major or clinically relevant non-major (CRNM) bleeding events, and overall mortality. All study outcomes were validated by blinded central adjudication. RESULTS: Of 124 patients enrolled, 110 (88.7%) had solid cancer, 93 (75.0%) had metastatic disease, and 110 (88.7%) were receiving chemotherapy or radiotherapy. During the 6-month study period, seven patients experienced symptomatic recurrent VTE (cumulative incidence, 5.9%), and two patients experienced incidental recurrent PE (cumulative incidence of any recurrent VTE, 7.6%). Major bleeding events occurred in six patients (cumulative incidence, 5.3%) and CRNM bleeding events in 11 patients (cumulative incidence, 10.2%). Twenty-eight patients (overall mortality, 24.0%) died. CONCLUSION: Rivaroxaban is effective and safe for the treatment of VTE in patients with active cancer.
Subject(s)
Blood Coagulation/drug effects , Factor Xa Inhibitors/administration & dosage , Neoplasms/epidemiology , Pulmonary Embolism/drug therapy , Rivaroxaban/administration & dosage , Venous Thromboembolism/drug therapy , Venous Thrombosis/drug therapy , Acute Disease , Adult , Aged , Aged, 80 and over , Drug Administration Schedule , Factor Xa Inhibitors/adverse effects , Female , Hemorrhage , Humans , Incidence , Male , Middle Aged , Neoplasms/diagnosis , Neoplasms/mortality , Prospective Studies , Pulmonary Embolism/blood , Pulmonary Embolism/diagnosis , Pulmonary Embolism/mortality , Recurrence , Republic of Korea/epidemiology , Risk Factors , Rivaroxaban/adverse effects , Time Factors , Treatment Outcome , Venous Thromboembolism/blood , Venous Thromboembolism/diagnosis , Venous Thromboembolism/mortality , Venous Thrombosis/blood , Venous Thrombosis/diagnosis , Venous Thrombosis/mortalityABSTRACT
BACKGROUND AND AIM: Anticoagulation therapy is the main line of treatment for acute portal vein thrombosis (PVT) in the absence of cirrhosis. However, the use of this therapy in cirrhotic PVT is still with doubtful evidence. We aimed to evaluate the efficacy and safety of rivaroxaban compared to warfarin for the management of acute non-neoplastic PVT in Hepatitis C virus (HCV)-related compensated cirrhosis. METHODS: Out of 578 patients with chronic HCV infection, 80 patients with acute PVT who had undergone splenectomy due to hypersplenism and 4 patients with acute PVT due to portal pyemia were selected. The patients were randomly assigned (1:1) to the study group (nâ¯=â¯40), in which the patients received rivaroxaban 10â¯mg/12â¯h, or the control group (nâ¯=â¯40), in which the patients received warfarin. RESULTS: In the rivaroxaban group, the resolution of PVT was achieved in 34 patients (85%) within 2.6⯱â¯0.4â¯months and delayed, partial recanalization after 6.7⯱â¯1.2â¯months (nâ¯=â¯6.15%). Complications such as major bleeding, abnormal liver functions, death, or recurrence did not occur during treatment, and patients in this group showed improved short-term survival rate (20.4⯱â¯2.2â¯months) compared to the survival rate in the control group (10.6⯱â¯1.8â¯months) in which warfarin achieved complete resolution in 45% of patients. Complications such as severe upper GI tract bleeding (43.3%), hepatic decompensation (22.5%), progression to mesenteric ischemia (12.5%), recurrence (10%), and death (20%) were observed in the control group. The duration until complete resolution of thrombus correlated with age, the extent of the thrombus, creatinine level, and MELD score. The recurrence after complete resolution of thrombus correlated with age, the extent of the thrombus, thrombogenic gene polymorphism, and the use of warfarin. CONCLUSION: Rivaroxaban was effective and safe in acute HCV-related non-neoplastic PVT with improved short-term survival rate; ClinicalTrials.gov Identifier: NCT03201367.
Subject(s)
Anticoagulants/therapeutic use , Blood Coagulation/drug effects , Factor Xa Inhibitors/therapeutic use , Portal Vein , Rivaroxaban/therapeutic use , Venous Thrombosis/drug therapy , Warfarin/therapeutic use , Adult , Anticoagulants/adverse effects , Computed Tomography Angiography , Egypt , Factor Xa Inhibitors/adverse effects , Female , Hemorrhage/chemically induced , Hepatitis C, Chronic/blood , Hepatitis C, Chronic/complications , Hepatitis C, Chronic/virology , Humans , Liver Cirrhosis/blood , Liver Cirrhosis/virology , Male , Middle Aged , Phlebography/methods , Portal Vein/diagnostic imaging , Recurrence , Rivaroxaban/adverse effects , Time Factors , Treatment Outcome , Ultrasonography, Doppler, Color , Venous Thrombosis/blood , Venous Thrombosis/diagnostic imaging , Venous Thrombosis/virology , Warfarin/adverse effectsABSTRACT
The column in this issue is supplied by Whitney Sharp, D.O., and Juan Jose Olivero, M.D. Dr. Sharp is chief medical resident in internal medicine at Houston Methodist Hospital and earned her Doctor of Osteopathic Medicine degree at Nova Southeastern University in Fort Lauderdale, Florida. Dr. Olivero is a nephrologist at Houston Methodist Hospital and a member of the hospital's Nephrology Training Program. He obtained his medical degree from the University of San Carlos School of Medicine in Guatemala, Central America, and completed his residency and nephrology fellowship at Baylor College of Medicine in Houston, Texas.
Subject(s)
Nephrotic Syndrome/complications , Venous Thromboembolism/etiology , Venous Thrombosis/etiology , Anticoagulants/therapeutic use , Humans , Nephrotic Syndrome/blood , Nephrotic Syndrome/diagnosis , Nephrotic Syndrome/therapy , Risk Factors , Treatment Outcome , Venous Thromboembolism/blood , Venous Thromboembolism/diagnosis , Venous Thromboembolism/drug therapy , Venous Thrombosis/blood , Venous Thrombosis/diagnosis , Venous Thrombosis/drug therapyABSTRACT
BACKGROUND: The aim of this study was to assess the impact of electrical calf muscle stimulation (EMS) on clinical and ultrasound outcomes in patients with post-thrombotic syndrome (PTS) and residual venous obstruction (RVO). METHODS: This was a prospective, comparative, non-randomized clinical trial involving patients who had completed a standard 6-month course of anticoagulation therapy for a first episode of unprovoked femoro-popliteal DVT and had signs of RVO in the affected veins and PTS as shown by a Villalta Score of >5. A blinded outcome assessor performed the ultrasound evaluations. A total of 60 patients in the age range from 40 to 86 years (mean 58.5±11.4) consisting of 38 men and 22 women were enrolled. They were divided into two groups of 30 participants each. Both groups (experimental and control) were treated by active walking, below-knee graduated compression stockings, and micronized purified flavonoid fraction. In the experimental group, EMS with «Veinoplus VI¼ device (three applications for 30 min every day) was also used. The patients were followed for 12 months with monthly DUS to reveal recurrent DVT and changes in RVO. The clinical criteria for treatment efficacy included changes in Villalta, VCSS and CIVIQ-20 scores. RESULTS: Recurrent DVT was found in seven of 30 patients in the control group and in zero of 30 patients in the experimental group (23.3% versus 0%, P=0.01). Through the follow-up period the degree of RVO decreased in all affected veins in both groups (P<0.01). The most significant changes were found in the popliteal vein; 60.8% decreased to 28.8% in the experimental group and 50.9% to 27.3% in the control group (P<0.01) with significant differences between the groups (P<0.01). VCSS, Villalta and CIVIQ-20 scores also significantly decreased in both groups (P<0.01). In the group with EMS, changes in the current parameters were more intensive (P<0.01). CONCLUSIONS: There is an ongoing process of deep vein recanalization during the 12 months after anticoagulant therapy cessation. Use of EMS in PTS treatment allows for reduction of recurrent DVT rates, increase the speed of deep vein recanalization and leads to additional improvement in the clinical PTS outcomes.
Subject(s)
Anticoagulants/therapeutic use , Blood Coagulation/drug effects , Electric Stimulation Therapy/methods , Muscle, Skeletal/innervation , Postthrombotic Syndrome/therapy , Venous Thrombosis/drug therapy , Adult , Aged , Aged, 80 and over , Female , Humans , Leg , Male , Middle Aged , Postthrombotic Syndrome/blood , Postthrombotic Syndrome/diagnostic imaging , Postthrombotic Syndrome/etiology , Prospective Studies , Recurrence , Russia , Time Factors , Treatment Outcome , Venous Thrombosis/blood , Venous Thrombosis/complications , Venous Thrombosis/diagnosisABSTRACT
Objective This study was performed to evaluate the efficacy of rivaroxaban versus nadroparin for preventing deep venous thrombosis (DVT) in elderly patients with osteoporosis undergoing initial total hip arthroplasty (THA) for femoral neck fractures. Methods Prospectively maintained databases were reviewed to retrospectively compare elderly patients with osteoporosis who underwent initial THA for femoral neck fractures from 2007 to 2015. The patients received peroral rivaroxaban at 10 mg/day for 2 weeks or subcutaneous injections of nadroparin at 0.3 mL/day for 2 weeks until the primary analysis cut-off date. The time to first on-study DVT was the primary endpoint. Results In total, 399 patients were included (rivaroxaban group: n=200; mean age, 70.20 ± 9.16 years and nadroparin group: n = 199; mean age, 69.90 ± 8.87 years), with a mean 3-year follow-up. The time to first on-study DVT was significantly longer in the rivaroxaban than nadroparin group (12 and 5 days, respectively). The incidence of DVT within the 2-week follow-up was significantly higher in the nadroparin than rivaroxaban group (6.8% and 19.7%, respectively), but this difference was no longer present at the final follow-up. Conclusion Rivaroxaban was associated with a significant reduction in the occurrence of first on-study DVT compared with nadroparin.
Subject(s)
Arthroplasty, Replacement, Hip/adverse effects , Femoral Neck Fractures/surgery , Nadroparin/therapeutic use , Rivaroxaban/therapeutic use , Venous Thrombosis/drug therapy , Venous Thrombosis/etiology , Aged , Blood Coagulation , Demography , Female , Femoral Neck Fractures/blood , Humans , Male , Osteoporosis/complications , Retrospective Studies , Risk Factors , Venous Thrombosis/bloodABSTRACT
Background Standard treatment for deep venous thromboembolism involves parenteral anticoagulation overlapping with a vitamin K antagonist, an approach that is effective but associated with limitations including the need for frequent coagulation monitoring. The direct oral anticoagulant rivaroxaban is similarly effective to standard therapy as a single-drug treatment for venous thromboembolism and does not require routine coagulation monitoring. The aim of this analysis was to project the long-term costs and outcomes for rivaroxaban compared to standard of care (tinzaparin/warfarin). Methods A total of 184 patients who were under anticoagulant therapy with warfarin or rivaroxaban for extended deep venous thromboembolism were retrospectively evaluated; 59 received rivaroxaban and 125 received warfarin therapy. Assessments were made on age, gender, place of residence, the duration of anticoagulation, mean international normalized ratio value, the effective rate of international normalized ratio (time in the therapeutic range), bleeding-related complication rate, duration of hospitalization due to complications, the number of annual outpatient department admission, cost for drug, cost for hospitalization, cost for outpatient department admission and international normalized ratio measurements. Results The annual outpatient cost is higher in warfarin group (147.09 ± 78 vs. 62.32 ± 19.79 USD p < 0.001). But annual drug cost is higher in rivaroxaban group (362.6 vs. 71.55 ± 31.01 USD p < 0.001). Overall cost of rivaroxaban group is higher than warfarin group (476.25 ± 36.78 vs. 364.82 ± 174.44 USD). Warfarin is not cost-effective when non-drug costs (342.5 ± 174.44 vs. 113.65 ± 36.77) and hospital costs (173.85 ± 122.73 vs. 64.9 ± 23.55 USD) were analyzed. Conclusion This analysis suggests that rivaroxaban has lower costs than warfarin in terms of outpatient department admission and hospital costs due to complications; however, warfarin was more economic when all cost parameters were considered. Time in the therapeutic range was found as 56% for warfarin that should be taken into account while analyzing costs and benefits.
Subject(s)
Anticoagulants/economics , Anticoagulants/therapeutic use , Factor Xa Inhibitors/economics , Factor Xa Inhibitors/therapeutic use , Health Care Costs , Rivaroxaban/economics , Rivaroxaban/therapeutic use , Thromboembolism/drug therapy , Thromboembolism/economics , Venous Thrombosis/drug therapy , Venous Thrombosis/economics , Warfarin/economics , Warfarin/therapeutic use , Adult , Aged , Ambulatory Care/economics , Anticoagulants/adverse effects , Blood Coagulation/drug effects , Cost Savings , Cost-Benefit Analysis , Drug Costs , Drug Monitoring/economics , Drug Monitoring/methods , Factor Xa Inhibitors/adverse effects , Female , Hemorrhage/chemically induced , Hemorrhage/economics , Hospital Costs , Humans , International Normalized Ratio/economics , Male , Middle Aged , Models, Economic , Retrospective Studies , Risk Factors , Rivaroxaban/adverse effects , Thromboembolism/blood , Thromboembolism/diagnosis , Time Factors , Treatment Outcome , Venous Thrombosis/blood , Venous Thrombosis/diagnosis , Warfarin/adverse effectsABSTRACT
We sought to investigate whether the G20210A prothrombin mutation modifies plasma fibrin clot properties in patients after venous thromboembolism (VTE) and how rivaroxaban treatment affects these alterations. We studied 34 prothrombin mutation heterozygous carriers and sex- and age-matched 34 non-carriers, all at least three months since the first VTE episode, before and during treatment with rivaroxaban. Clot permeability (Ks) and clot lysis time (CLT) with or without elimination of thrombin activatable fibrinolysis inhibitor (TAFI) were assessed at baseline, 2-6 hours (h) after and 20-25 h after intake of rivaroxaban (20 mg/day). At baseline, the prothrombin mutation group formed denser clots (Ks -12 %, p=0.0006) and had impaired fibrinolysis (CLT +14 %, p=0.004, and CLT-TAFI +13 %, p=0.03) compared with the no mutation group and were similar to those observed in 15 healthy unrelated prothrombin mutation carriers. The G20210A prothrombin mutation was the independent predictor for Ks and CLT before rivaroxaban intake. At 2-6 h after rivaroxaban intake, clot properties improved in both G20210A carriers and non-carriers (Ks +38 %, and +37 %, CLT -25 % and -25 %, CLT-TAFI -20 % and -24 %, respectively, all p<0.001), but those parameters were worse in the prothrombin mutation group (Ks -12.8 %, CLT +17 %, CLT-TAFI +13 %, all p<0.001). Rivaroxaban concentration correlated with fibrin clot properties. After 20-25 h since rivaroxaban intake most clot properties returned to baseline. Rivaroxaban-related differences in clot structure were confirmed by scanning electron microscopy images. In conclusion, rivaroxaban treatment, though improves fibrin clot properties, cannot abolish more prothrombotic fibrin clot phenotype observed in prothrombin mutation carriers following VTE.
Subject(s)
Blood Coagulation/drug effects , Blood Coagulation/genetics , Factor Xa Inhibitors/therapeutic use , Fibrin/metabolism , Mutation , Prothrombin/genetics , Pulmonary Embolism/drug therapy , Pulmonary Embolism/genetics , Rivaroxaban/therapeutic use , Venous Thromboembolism/drug therapy , Venous Thromboembolism/genetics , Venous Thrombosis/drug therapy , Venous Thrombosis/genetics , Adult , Blood Coagulation Tests , Case-Control Studies , Factor Xa Inhibitors/blood , Factor Xa Inhibitors/pharmacokinetics , Female , Fibrin/ultrastructure , Fibrinolysis/drug effects , Fibrinolysis/genetics , Genetic Predisposition to Disease , Humans , Male , Microscopy, Electron, Scanning , Middle Aged , Phenotype , Pulmonary Embolism/blood , Pulmonary Embolism/diagnosis , Rivaroxaban/blood , Rivaroxaban/pharmacokinetics , Treatment Outcome , Venous Thromboembolism/blood , Venous Thromboembolism/diagnosis , Venous Thrombosis/blood , Venous Thrombosis/diagnosisABSTRACT
Fucosylated chondroitin sulfate (FucCS) is a potent anticoagulant polysaccharide extracted from sea cucumber. Its anticoagulant activity is attributed to the presence of unique branches of sulfated fucose. Although this glycosaminoglycan exerts an antithrombotic effect following oral administration, high doses are necessary to achieve the maximum effect. The diminished activity of FucCS following oral administration is likely due to its degradation in the gastrointestinal tract and its limited ability to cross the intestinal cell membranes. The latter aspect is particularly difficult to overcome. However, gastro-resistant tablet formulation may help limit the degradation of FucCS in the gastrointestinal tract. In the present work, we found that the oral administration of FucCS as gastro-resistant tablets produces a more potent and prolonged anticoagulant effect compared with its administration as an aqueous solution, with no significant changes in the bleeding tendency or arterial blood pressure. Experiments using animal models of arterial thrombosis initiated by endothelial injury demonstrated that FucCS delivered as gastro-protective tablets produced a potent antithrombotic effect, whereas its aqueous solution was ineffective. However, there was no significant difference between the effects of FucCS delivered as gastro-resistant tablets or as aqueous solution in a venous thrombosis model, likely due to the high dose of thromboplastin used. New oral anticoagulants tested in these experimental models for comparison showed significantly increased bleeding tendencies. Our study provides a framework for developing effective oral anticoagulants based on sulfated polysaccharides from marine organisms. The present results suggest that FucCS is a promising oral anticoagulant.
Subject(s)
Anticoagulants/administration & dosage , Blood Coagulation/drug effects , Carotid Artery Diseases/prevention & control , Chondroitin Sulfates/administration & dosage , Thrombosis/prevention & control , Venous Thrombosis/prevention & control , Administration, Oral , Animals , Anticoagulants/chemistry , Anticoagulants/toxicity , Carotid Artery Diseases/blood , Chondroitin Sulfates/chemistry , Chondroitin Sulfates/toxicity , Disease Models, Animal , Drug Compounding , Female , Hemorrhage/chemically induced , Male , Rats, Wistar , Tablets, Enteric-Coated , Thrombosis/blood , Time Factors , Venous Thrombosis/bloodSubject(s)
Anticoagulants/therapeutic use , Neoplasms/drug therapy , Pulmonary Embolism/prevention & control , Rivaroxaban/therapeutic use , Stroke/drug therapy , Venous Thromboembolism/prevention & control , Venous Thrombosis/drug therapy , Consensus , Disease Management , Drug Administration Schedule , Drug Dosage Calculations , Humans , Neoplasms/blood , Neoplasms/complications , Neoplasms/pathology , Practice Guidelines as Topic , Pulmonary Embolism/blood , Pulmonary Embolism/complications , Pulmonary Embolism/pathology , Stroke/blood , Stroke/complications , Stroke/pathology , Venous Thromboembolism/blood , Venous Thromboembolism/complications , Venous Thromboembolism/pathology , Venous Thrombosis/blood , Venous Thrombosis/complications , Venous Thrombosis/pathologyABSTRACT
BACKGROUND: Statins have been reported to help prevent the development and the recurrence of deep vein thrombosis (DVT). We conducted a prospective randomized clinical trial to compare the effects of rosuvastatin plus a low-molecular-weight heparin (LMWH), bemiparin, with conventional LMWH therapy in the treatment of DVT. PATIENTS AND METHODS: In total, 234 patients were randomized into two groups, 116 in the LMWH group and 118 in the statin plus LMWH group. All patients underwent lower limb duplex ultrasound and analytic markers at diagnosis and three months of follow-up. The final analysis included 230 patients. RESULTS: No significant differences were observed in D-dimer levels after three months of follow-up between patients treated with LMWH+rosuvastatin compared to the LMWH group (802.51 + 1062.20 vs. 996.25 + 1843.37, p = 0.897). The group of patients treated with statins displayed lower levels of CRP (4.17 + 4.27 vs. 22.39 + 97.48, p = 0.018) after three months of follow-up. The Villalta scale demonstrated significant differences between groups (3.45 + 6.03 vs. 7.79 + 5.58, p = 0.035). There was a significant decrease in PTS incidence (Villalta score> 5) in the rosuvastatin group (38.3 % vs. 48.5%, p = 0.019). There were no differences in EuroQol score between groups. CONCLUSIONS: Adjuvant rosuvastatin treatment in patients diagnosed of DVT improve CRP levels and diminish PTS incidence.
Subject(s)
Anticoagulants/therapeutic use , Heparin, Low-Molecular-Weight/therapeutic use , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Rosuvastatin Calcium/therapeutic use , Venous Thrombosis/drug therapy , Adult , Aged , Aged, 80 and over , Anticoagulants/adverse effects , Biomarkers/blood , C-Reactive Protein/metabolism , Drug Therapy, Combination , Female , Fibrin Fibrinogen Degradation Products/metabolism , Heparin, Low-Molecular-Weight/adverse effects , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects , Male , Middle Aged , Postthrombotic Syndrome/prevention & control , Prospective Studies , Quality of Life , Rosuvastatin Calcium/adverse effects , Spain , Surveys and Questionnaires , Time Factors , Treatment Outcome , Ultrasonography, Doppler, Duplex , Venous Thrombosis/blood , Venous Thrombosis/diagnostic imagingABSTRACT
Objetivo. Realizar una revisión sistemática de la literatura para conocer la efectividad de la imaginería motora o práctica mental como tratamiento de pacientes con ictus en la recuperación motora del miembro superior e inferior. Estrategia de búsqueda. Se realizó una búsqueda sistemática de artículos científicos publicados, tanto en inglés como en castellano, desde octubre del 2012 hasta diciembre del 2014. Se evaluó la calidad metodológica mediante la escala de Jadad. Selección de los estudios. Se incluyeron un total de 12 artículos. La calidad metodológica de los estudios fue muy pobre en general. Solo cuatro artículos superaron la puntuación 3/5 en la escala Jadad. Síntesis de resultados. Se observó una gran heterogeneidad en la duración y en el número de participantes. El tiempo de tratamiento osciló entre los 5 y las 54 semanas. El tamaño muestral de los estudios estuvo comprendido de media entre 9 y 42 individuos. Los individuos incluidos en los trabajos presentaban hemiparesia, pudiendo afectar esta tanto a miembro superior como inferior, en una fase subaguda o crónica de la enfermedad. Conclusiones. La mayoría de los trabajos incluidos apenas detallaron los parámetros de las intervenciones. En aquellas publicaciones en las que se especificaron, el tiempo de duración por sesión osciló entre 15-20 minutos; con una frecuencia de tratamiento de tres días a la semana durante una media de cuatro semanas; en relación con el tipo de instrucciones, estas fueron principalmente auditivas y visuales; finalmente, el orden de aplicación de la terapia fue variable en relación con la terapia física convencional. Existieron elementos que no se especificaron como el número de ensayos por sesión, el tipo de imaginería empleada, el contexto o la localización de las sesiones (AU)
Objective. To conduct a systematic review of the literature to determine the effectiveness of motor imagery and mental practice as a treatment of patients with stroke for motor recovery of the upper and lower limb. Search strategy. We conducted a systematic search of scientific articles published in both English and Spanish from October 2012 to December 2014. Methodological quality was evaluated using the Jadad scale. Study selection. A total of 12 items were included. The methodological quality of the studies was generally poor. Only four articles exceeded a score of 3/5 on the Jadad scale. Synthesis of the results. There was wide heterogeneity in treatment duration and the number of participants. The treatment time ranged from 5 to 54 weeks. The average sample size of the studies included was between 9 and 42 individuals. Included individuals had hemiparesis, which could affect both the upper and lower limbs in the subacute and chronic phases. Conclusions. Most of the included studies did not describe the parameters of the interventions. In those that did specify them, the duration of each session was between 15 and 20 minutes, with a treatment frequency of three days per week for an average of four weeks. Instructions were auditory and visual. The order of application of the therapy varied in relation to conventional physical therapy. Numerous elements were not specified, such as the number of trials per session, the kind of imagery, and the context or location of the sessions (AU)
Subject(s)
Humans , Male , Female , Rehabilitation/psychology , Stroke/pathology , Upper Extremity/injuries , Paresis/pathology , Venous Thrombosis/blood , Pharmaceutical Preparations/administration & dosage , Occupational Therapy/psychology , Rehabilitation/methods , Stroke/metabolism , Upper Extremity/surgery , Weights and Measures , Paresis/metabolism , Venous Thrombosis/complications , Pharmaceutical Preparations/metabolism , Occupational TherapyABSTRACT
Results of treatment of 71 patients, suffering an acute idiopathic deep veins thrombo' sis (DVT) of lower extremities,were analyzed. In 32 (45.1%) patients rivaroxaban was applied, in 39 (54.9%) varfarin. The term of anticoagulant therapy was determined in accordance to the Ddimers level. Recurrence of the DVT, of massive hemorrhage or pulmonary thromboembolism in the followup groups were absent. In 29 (74.4%) patientsa constant dose of varfarin was lined up during minimal recommended period. For reduction of the DVT occurrence risk a rivaroxaban may serve as an alternative to varfarin.
Subject(s)
Anticoagulants/therapeutic use , Femoral Vein/drug effects , Fibrin Fibrinogen Degradation Products/metabolism , Rivaroxaban/therapeutic use , Venous Thrombosis/drug therapy , Warfarin/therapeutic use , Adult , Aged , Biomarkers/blood , Drug Administration Schedule , Female , Femoral Vein/metabolism , Femoral Vein/pathology , Humans , Leg/blood supply , Leg/pathology , Male , Middle Aged , Prospective Studies , Pulmonary Embolism/prevention & control , Venous Thrombosis/blood , Venous Thrombosis/pathologyABSTRACT
High plasma level of P-selectin is associated with the development of venous thromboembolism (VTE). Furthermore, supplementation of vitamin D could decrease thrombotic events. Hence, this study was designed to examine whether the administration of vitamin D can influence the plasma level of P-selectin in patients with VTE. In the randomized controlled trial, 60 patients with confirmed acute deep vein thrombosis and/or pulmonary embolism (PE) were randomized into the intervention (n = 20) and control (n = 40) groups. The intervention arm was given an intramuscular single dose of 300 000 IU vitamin D3 Plasma level of 25-hydroxy vitamin D, P-selectin, and high-sensitive C-reactive protein (hs-CRP) was measured at baseline and 4 weeks after. The plasma level of P-selectin (95% confidence interval = -5.99 to -1.63, P = .022) and hs-CRP (P = .024) significantly declined in vitamin D-treated group, while only hs-CRP was significantly decreased in the control group (P = .011). However, the magnitude of these reductions was not statistically significant. This study could not support the potential benefit of the high-dose vitamin D on plasma level of P-selectin and hs-CRP in patients with VTE.
Subject(s)
Cholecalciferol/administration & dosage , Venous Thromboembolism/drug therapy , Adult , Aged , C-Reactive Protein/analysis , C-Reactive Protein/drug effects , Cholecalciferol/therapeutic use , Dose-Response Relationship, Drug , Female , Humans , Male , Middle Aged , P-Selectin/blood , P-Selectin/drug effects , Pulmonary Embolism/blood , Pulmonary Embolism/drug therapy , Venous Thromboembolism/blood , Venous Thrombosis/blood , Venous Thrombosis/drug therapyABSTRACT
Warfarin is the most commonly prescribed anticoagulant drug; however, a narrow therapeutic range and a high risk of bleeding or stroke complicate its clinical use. Warfarin resistance was defined as prolonged warfarin requirements of more than 15âmg/day to achieve therapeutic anticoagulation or failure to achieve therapeutic anticoagulation with more than 20âmg/day. The resistance is associated with polymorphisms of the vitamin K epoxide reductase-oxidase complex (VKORC1) and cytochrome P450-2C9 (CYP2C9) genes, which affect warfarin pharmacodynamics and pharmacokinetics, respectively. Identification of the VKORC1 -1639 (A/G) and CYP2C9 (*1/*2/*3) allelic variants was performed using the PGX-Thrombo Strip in 41 patients with warfarin resistance compared with 30 patients with normal warfarin response out of 352 diagnosed cases of deep vein thrombosis. In warfarin-resistant patients, the VKORC1-1639 genotype frequencies were GG 0.756, GA 0.244 and AA 0.0, whereas in warfarin responder patients, they were: GG 0.333, GA 0.400 and AA 0.276 with Pâ≤â0.001. The CYP2C9 genotype frequencies showed nonsignificant difference in both group of patients (Pâ=â0.31). Our results suggest that the VKORC1-1639 GG and the wild type CYP2C9*1*1genotypes are associated with the high-dose requirement for warfarin therapy, and that VKORC1-1639 GG is responsible for warfarin resistance and failure in Egyptian patients.