A 71-year-old man was stable on warfarin (2.25 mg daily) therapy with an international normalized ratio (INR) of 1.8-2.2 after a heart valve replacement surgery. Recently, he consumed the liquid-like herbal product called shengmai-yin (10 mL daily) against medical advice. Seven days after the daily consumption of shengmai-yin, he was admitted to the intensive care unit because of consciousness disturbance [Glasgow Coma Scale (GCS) score 7] with an INR of 5.08. Head computed topography revealed intracerebral hematoma in the left temporoparietal region. Both warfarin therapy and the herbal product were withdrawn. At the same time, therapy with intravenous vitamin K1 40 mg was started. On the second day of admission, craniectomy was performed to remove the intacerebral hematoma under general anesthesia. He remained confused and restless for 2 days, but then showed progressive recovery in the consciousness level as well as motor and verbal functions. Shengmai-yin contains herbal ingredients that can interact with warfarin. The Drug Interaction Probability Scale (DIPS) indicated that warfarin and shengmai-yin were highly probable causes of intracerebral hematoma. Patients on warfarin therapy should be discouraged from taking herbal medicines, especially preparations that are already known to have antiplatelet and antithrombotic effects.
Aged ; Anticoagulants/*adverse effects/therapeutic use ; Cerebral Hemorrhage/*chemically induced/drug therapy/surgery ; Drug Interactions ; Drugs, Chinese Herbal/*adverse effects ; Hematoma/*chemically induced/drug therapy/surgery ; Humans ; Male ; Treatment Outcome ; Vitamin K 1/therapeutic use ; Warfarin/*adverse effects/*therapeutic use

A 71-year-old man was stable on warfarin (2.25 mg daily) therapy with an international normalized ratio (INR) of 1.8-2.2 after a heart valve replacement surgery. Recently, he consumed the liquid-like herbal product called shengmai-yin (10 mL daily) against medical advice. Seven days after the daily consumption of shengmai-yin, he was admitted to the intensive care unit because of consciousness disturbance [Glasgow Coma Scale (GCS) score 7] with an INR of 5.08. Head computed topography revealed intracerebral hematoma in the left temporoparietal region. Both warfarin therapy and the herbal product were withdrawn. At the same time, therapy with intravenous vitamin K1 40 mg was started. On the second day of admission, craniectomy was performed to remove the intacerebral hematoma under general anesthesia. He remained confused and restless for 2 days, but then showed progressive recovery in the consciousness level as well as motor and verbal functions. Shengmai-yin contains herbal ingredients that can interact with warfarin. The Drug Interaction Probability Scale (DIPS) indicated that warfarin and shengmai-yin were highly probable causes of intracerebral hematoma. Patients on warfarin therapy should be discouraged from taking herbal medicines, especially preparations that are already known to have antiplatelet and antithrombotic effects.
Aged ; Anticoagulants/*adverse effects/therapeutic use ; Cerebral Hemorrhage/*chemically induced/drug therapy/surgery ; Drug Interactions ; Drugs, Chinese Herbal/*adverse effects ; Hematoma/*chemically induced/drug therapy/surgery ; Humans ; Male ; Treatment Outcome ; Vitamin K 1/therapeutic use ; Warfarin/*adverse effects/*therapeutic use

Nonsteroidal anti-inflammatory drugs (NSAIDs) are known to interact with the oral anticoagulant warfarin and can cause a serious bleeding complication. In this study, we evaluated the risk factors for international normalized ratio (INR) increase, which is a surrogate marker of bleeding, after addition of an NSAID in a total of 98 patients who used warfarin. Patient age, sex, body mass index, maintenance warfarin dose, baseline INR, coadministered medications, underlying diseases, and liver and kidney functions were evaluated for possible risk factors with INR increase > or =15.0% as the primary end-point. Of the 98 patients, 39 (39.8%) showed an INR elevation of > or =15.0% after adding a NSAID to warfarin therapy. Multivariate analysis showed that high maintenance dose (>40 mg/week) of warfarin (P=0.001), the presence of coadministered medications (P=0.024), the use of meloxicam (P=0.025) and low baseline INR value (P=0.03) were the risk factors for INR increase in respect to NSAID-warfarin interaction. In conclusion, special caution is required when an NSAID is administered to warfarin users if patients are taking warfarin >40 mg/week and other medications interacting with warfarin.
Adult ; Aged ; *Anti-Inflammatory Agents, Non-Steroidal/adverse effects/therapeutic use ; *Anticoagulants/adverse effects/therapeutic use ; Drug Interactions ; Female ; Hemorrhage/*chemically induced ; Humans ; International Normalized Ratio ; Male ; Middle Aged ; Retrospective Studies ; Risk Factors ; Thiazines/adverse effects/therapeutic use ; Thiazoles/adverse effects/therapeutic use ; *Warfarin/adverse effects/therapeutic use

Life-threatening in the short term and leading to a high level of morbidity in the long term, venous thromboembolism (VTE) is the most fearful complication following lower limb arthroplasty. With advances in surgical procedure, anesthetic management and postoperative convalescence have altered the risks of venous thromboembolism after total joint arthroplasty in the lower extremity. The pathogenesis of VTE is multifactorial and includes the well-known Virchow's triad of hypercoagulability, venous stasis and endothelial damage. Therefore, it is appropriate to use a multimodal approach to thromboprophylaxis. Despite extensive research, the ideal multimodal prophylaxis against venous thrombolism has not been identified. So this article reviews the recent developments in multimodal prophylaxis for thromboembolism after total joint arthroplasty.
Anesthesia, Epidural ; Arthroplasty, Replacement, Hip ; adverse effects ; Arthroplasty, Replacement, Knee ; adverse effects ; Aspirin ; therapeutic use ; Factor Xa Inhibitors ; Heparin, Low-Molecular-Weight ; therapeutic use ; Humans ; Postoperative Complications ; prevention & control ; Venous Thromboembolism ; epidemiology ; prevention & control ; Warfarin ; therapeutic use

BACKGROUNDWarfarin is the most common oral anticoagulant to decrease the stroke risk associated with atrial fibrillation (AF). There are very few prospective studies that have explored whether warfarin has an association with damage on renal function in Chinese patients with nonvalvular AF (NVAF). The aim of this study was to evaluate the effects of warfarin on renal function and study the factors associated with kidney dysfunction in Chinese adult NVAF patients without dialysis therapy.

METHODSFrom January 2011 to December 2013, a total of 951 NVAF patients from 18 hospitals were enrolled. The estimated glomerular filtration rate (eGFR) was calculated from baseline and follow-up serum creatinine levels. Kaplan-Meier survival curves compared the survival of a ≥25% decline in eGFR (hereafter, endpoint), while Cox models estimated hazard ratios (HR s) and 95% confidence intervals for this event after adjustment for age, gender, and selected potential risk factors for renal dysfunction. Cox regression analysis of the various clinical potential variables was performed to identify the predictors of a ≥25% decline in eGFR.

RESULTSAfter a 58-month follow-up, 951 NVAF patients were divided by observation into warfarin (n = 655) and no anticoagulation groups (n = 296) and 120 (12.6%) patients experienced renal endpoint. Kaplan-Meier survival curves showed that the survival period was not different in the two groups (χ2 = 0.178, log-rank P= 0.67), but patients with systolic blood pressure (SBP) <140 mmHg have significant difference with patients with SBP ≥140 mmHg (χ2 = 4.903, log-rank P= 0.03). Multivariate Cox regression analysis revealed baseline eGFR and SBP as independent predictors of the endpoint, with HR s of 1.00, and 1.02, respectively.

CONCLUSIONIn patients with NVAF, eGFR and SBP are associated with the deterioration of kidney function while Warfarin is not the risk factor of the ≥25% decline in eGFR.

TRIAL REGISTRATIONChinese Clinical Trial Registry (No. ChiCTR-OCH-13003729); http://www.chictr.org.cn/showproj.aspx?proj = 5831.

Aged ; Anticoagulants ; adverse effects ; therapeutic use ; Atrial Fibrillation ; drug therapy ; physiopathology ; Female ; Glomerular Filtration Rate ; physiology ; Humans ; Kaplan-Meier Estimate ; Kidney ; drug effects ; Male ; Middle Aged ; Prospective Studies ; Warfarin ; adverse effects ; therapeutic use

BACKGROUND/AIMS: Warfarin and aspirin are commonly used to prevent cardiovascular diseases. Aspirin was recently found to have chemopreventive effects on colon cancer and polyps by inhibiting cyclooxygenase-2. Therefore, we evaluated whether the symptoms of bleeding related with aspirin or warfarin could be a clue in early detection of colon cancer. We also assessed the effect of aspirin on the development of synchronous polyps. METHODS: A total of forty-one and 16 patients diagnosed as colon cancer, taking aspirin or warfarin respectively were enrolled. In addition, 171 patients with colon cancers were age and gender matched as a control group. We investigated the difference of clinical features and laboratory findings among three groups. RESULTS: The incidence of bleeding was 81.3% (warfarin), 53.7% (aspirin), 40.4% (control). Among three groups, location and size of cancer, number of lymph nodes involvement and stages were not different, but the number of patients in Duke stage D in warfarin group (n=1, 6.3%) were less than that of the control (n=44, 25.7%) (p=0.049). The extent of circumferencial involvement by cancer was lower in aspirin group (67%) than in the control group (80%) (p=0.035). The percentage of patients with synchronous polyps and mean number of synchronous polyps in aspirin group (34.1%, 0.68, respectively) was lower than that of control group (53.6%, 1.69, respectively) (p=0.029, 0.008, respectively). CONCLUSIONS: Bleeding related with aspirin or warfarin usage had no effect on the early diagnosis of colon cancer. However, lower incidence of Duke stage D in warfarin group might be related to anti-metastatic effect of warfarin. In addition, aspirin may have a role in suppressing the development of synchronous polyps.
Aged ; Anticoagulants/adverse effects/therapeutic use ; Aspirin/adverse effects/*therapeutic use ; Cardiovascular Diseases/prevention & control ; Colonic Neoplasms/*diagnosis/pathology ; English Abstract ; Female ; Gastrointestinal Hemorrhage/chemically induced ; Humans ; Male ; Middle Aged ; Platelet Aggregation Inhibitors/adverse effects/*therapeutic use ; Warfarin/adverse effects/*therapeutic use

PURPOSE: In this study, we investigated the stroke mechanism and the factors associated with ischemic stroke in patients with nonvalvular atrial fibrillation (NVAF) who were on optimal oral anticoagulation with warfarin. MATERIALS AND METHODS: This was a multicenter case-control study. The cases were consecutive patients with NVAF who developed cerebral infarction or transient ischemic attack (TIA) while on warfarin therapy with an international normalized ratio (INR) > or =2 between January 2007 and December 2011. The controls were patients with NVAF without ischemic stroke who were on warfarin therapy for more than 1 year with a mean INR > or =2 during the same time period. We also determined etiologic mechanisms of stroke in cases. RESULTS: Among 3569 consecutive patients with cerebral infarction or TIA who had NVAF, 55 (1.5%) patients had INR > or =2 at admission. The most common stroke mechanism was cardioembolism (76.0%). Multivariate analysis demonstrated that smoking and history of previous ischemic stroke were independently associated with cases. High CHADS2 score (> or =3) or CHA2DS2-VASc score (> or =5), in particular, with previous ischemic stroke along with > or =1 point of other components of CHADS2 score or > or =3 points of other components of CHA2DS2-VASc score was a significant predictor for development of ischemic stroke. CONCLUSION: NVAF patients with high CHADS2/CHA2DS2-VASc scores and a previous ischemic stroke or smoking history are at high risk of stroke despite optimal warfarin treatment. Some other measures to reduce the risk of stroke would be necessary in those specific groups of patients.
Aged ; Aged, 80 and over ; Anticoagulants/adverse effects/*therapeutic use ; Atrial Fibrillation/*complications ; Cardiovascular Diseases ; Case-Control Studies ; Cerebral Infarction/complications ; Female ; Humans ; Male ; Middle Aged ; Multivariate Analysis ; Risk Factors ; Stroke/etiology/*prevention & control ; Warfarin/adverse effects/*therapeutic use

PURPOSE: In this study, we investigated the stroke mechanism and the factors associated with ischemic stroke in patients with nonvalvular atrial fibrillation (NVAF) who were on optimal oral anticoagulation with warfarin. MATERIALS AND METHODS: This was a multicenter case-control study. The cases were consecutive patients with NVAF who developed cerebral infarction or transient ischemic attack (TIA) while on warfarin therapy with an international normalized ratio (INR) > or =2 between January 2007 and December 2011. The controls were patients with NVAF without ischemic stroke who were on warfarin therapy for more than 1 year with a mean INR > or =2 during the same time period. We also determined etiologic mechanisms of stroke in cases. RESULTS: Among 3569 consecutive patients with cerebral infarction or TIA who had NVAF, 55 (1.5%) patients had INR > or =2 at admission. The most common stroke mechanism was cardioembolism (76.0%). Multivariate analysis demonstrated that smoking and history of previous ischemic stroke were independently associated with cases. High CHADS2 score (> or =3) or CHA2DS2-VASc score (> or =5), in particular, with previous ischemic stroke along with > or =1 point of other components of CHADS2 score or > or =3 points of other components of CHA2DS2-VASc score was a significant predictor for development of ischemic stroke. CONCLUSION: NVAF patients with high CHADS2/CHA2DS2-VASc scores and a previous ischemic stroke or smoking history are at high risk of stroke despite optimal warfarin treatment. Some other measures to reduce the risk of stroke would be necessary in those specific groups of patients.
Aged ; Aged, 80 and over ; Anticoagulants/adverse effects/*therapeutic use ; Atrial Fibrillation/*complications ; Cardiovascular Diseases ; Case-Control Studies ; Cerebral Infarction/complications ; Female ; Humans ; Male ; Middle Aged ; Multivariate Analysis ; Risk Factors ; Stroke/etiology/*prevention & control ; Warfarin/adverse effects/*therapeutic use

BACKGROUND/AIMS: The risk of gastrointestinal (GI) bleeding with dabigatran when compared to warfarin has been controversial in the literature. The aim of our study was to assess this risk with the use of dabigatran. METHODS: We examined the medical records of patients who were started on dabigatran or warfarin from October 2010 to October 2012. The study was conducted in two hospitals. RESULTS: A total of 417 patients were included (208 dabigatran vs. 209 warfarin). GI bleeding occurred in 10 patients (4.8%) in the dabigatran group compared to 21 patients (10.1%) in the warfarin group (p=0.0375). Multivariate analysis showed that patients who were on dabigatran for < or =100 days had a higher incidence of GI bleeding than those who were on it for >100 days (p=0.0007). The odds of GI bleeding in patients who were on dabigatran for < or =100 days was 8.2 times higher compared to those who were on the drug for >100 days. The incidence of GI bleeding in patients >65 years old was higher than in those <65 years old (p=0.0453, OR=3). History of previous GI bleeding was another risk factor for GI bleeding in the dabigatran group (p=0.036, OR=6.3). The lower GI tract was the most common site for GI bleeding in the dabigatran group (80.0% vs. 38.1%, p=0.014). CONCLUSIONS: The risk of GI bleeding was lower with dabigatran. The risk factors for GI bleeding with dabigtran were the first 100 days, age >65 years, and a history of previous GI bleeding.
Age Factors ; Aged ; Aged, 80 and over ; Anticoagulants/*adverse effects/therapeutic use ; Atrial Fibrillation/drug therapy ; Dabigatran/*adverse effects/therapeutic use ; Female ; Gastrointestinal Hemorrhage/*chemically induced/epidemiology/mortality ; Humans ; Incidence ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Multivariate Analysis ; Odds Ratio ; Retrospective Studies ; Risk Factors ; Warfarin/*adverse effects/therapeutic use

Venous thromboembolism (VTE), which is manifested as deep vein thrombosis (DVT) and pulmonary embolism (PE), represents a significant cause of death, disability, and discomfort. They are frequent complications of various surgical procedures. The aging population and the survival of more severely injured patients may suggest an increasing risk of thromboembolism in the trauma patients. Expanded understanding of the population at risk challenges physicians to carefully examine risk factors for VTE to identify high-risk patients who can benefit from prophylaxis. An accurate knowledge of evidence-based risk factors is important in predicting and preventing postoperative DVT, and can be incorporated into a decision support system for appropriate thromboprophylaxis use. Standard use of DVT prophylaxis in a high-risk trauma population leads to a low incidence of DVT. The incidence of VTE is common in Asia. The evaluation includes laboratory tests, Doppler test and phlebography. Screening Doppler sonography should be performed for surveillance on all critically injured patients to identify DVT. D-Dimer is a useful marker to monitor prophylaxis in trauma surgery patients. The optimal time to start prophylaxis is between 2 hours before and 10 hours after surgery, but the risk of PE continues for several weeks. Thromboprophylaxis includes graduated compression stockings and anticoagulants for prophylaxis. Anticoagulants include Warfarin, which belongs to Vitamin K antagonists, unfractionated heparin, low molecular weight heparins, factor Xa indirect inhibitor Fondaparinux, and the oral IIa inhibitor Melagatran and ximelagatran. Recombinant human soluble thrombomodulin is a new and highly effective antithrombotic agent. Prophylactic placement of vena caval filters in selected trauma patients may decrease the incidence of PE. The indications for prophylactic inferior vena cava filter insertion include prolonged immobilization with multiple injuries, closed head injury, pelvic fracture, spine fracture, multiple long bone fracture, and attending discretion. Multiple-trauma patients are at increased risk for DVT but are also at increased risk of bleeding, and the use of heparin may be contraindicated. Serial compression devices (SCDs) are an alternative for DVT prophylaxis. Compression devices provide adequate DVT prophylaxis with a low failure rate and no device-related complications. Immobilization is one of important reasons of VTE. The ambulant patient is far less likely to develop complications of inactivity, not only venous thrombosis, but also contractures, decubitus ulcers, or osteoporosis (with its associated fatigue fractures), as well as bowel or bladder complications.
Anticoagulants ; therapeutic use ; Factor Xa Inhibitors ; Heparin ; therapeutic use ; Heparin, Low-Molecular-Weight ; therapeutic use ; Humans ; Orthopedic Procedures ; adverse effects ; Postoperative Complications ; epidemiology ; Pulmonary Embolism ; prevention & control ; Recombinant Proteins ; therapeutic use ; Risk Factors ; Thrombomodulin ; therapeutic use ; Vena Cava Filters ; Venous Thrombosis ; epidemiology ; prevention & control ; Vitamin K ; antagonists & inhibitors ; Warfarin ; therapeutic use