Warfarin Research Articles

Review: In AF, direct oral anticoagulants reduce all-cause and vascular mortality compared with warfarin.

Source Citation Gomez-Outes A, Lagunar-Ruiz J, Terleira-Fernandez AI, et al. Causes of death in anticoagulated patients with atrial fibrillation. J Am Coll Cardiol. 2016;68:2508-21. 27931607

Uninterrupted Dabigatran as Safe as Warfarin During AF Ablation

As prevalence of atrial fibrillation (AF) and its risk factors rises, the number of individuals undergoing catheter ablation of AF, already one of the

Rivaroxaban vs. Aspirin to Prevent Recurrent Venous Thromboembolism

The duration of guideline-recommended antithrombotic therapy for patients with venous thromboembolism (VTE) ranges from 3 months to indefinite, depending on whether the VTE is provoked or unprovoked and on patients' bleeding risks (NEJM JW Emerg Med Feb 2016 and Chest 2016; 149:315). For long-term prevention of recurrent VTE, options include warfarin, direct-acting oral anticoagulants, and aspirin; among the anticoagulants, guidelines recommend direct-acting anticoagulants over warfarin, unless substantial renal impairment …

Clinical features and microsurgical treatment of warfarin-associated intracerebral hemorrhage (a report of 65 cases)

Objective To discuss the clinical features and surgical outcome of warfarin-associated intracerebral hemorrhage (WICH). Methods Sixty-five consecutive patients with WICH were admitted to Department of Neurosurgery, Beijing Anzhen Hospital, Capital Medical University, from January 2005 to May 2016. Their clinical presentation, therapies and outcomes were retrospectively analyzed and discussed with reference to the relevant literatures. Among these patients, 7 cases underwent drilling and drainage, intracranial hematomas were removed by small craniotomy in 50 cases, and both hematoma and bone were removed in the remaining 8 cases. Results The average volume of hematomas in 65 patients was (46.8±13.7) ml.The mean dose of warfarin was 1.5-6.0 mg/d and the average dose was(3.5±1.5) mg/d. The medication time was 3-72 with a mean of 27.8±3.4 months. When the intracerebral hemorrhage occurred, the international normalized ratio (INR) was 1.2-5.6 (mean, 2.7±1.2). WICH occurred in 48 (73.8%) patients within the recommended range of anticoagulation (INR: 2.0-3.0). There were no operative complications in the 65 patients. Based on the Glasgow coma scale (GOS), 28 cases (43.1%) were in grade Ⅴ, 15 cases (23.1%) in grade Ⅳ, 8 cases (12.3%) in grade Ⅲ, 5 cases (7.7%) in grade Ⅱ, and 9 cases (13.8%) in grade Ⅰ (13.8%). Nine cases (13.8%) died, among which 4 cases died due to rebleeding and multiple systemic organ failure occurred in the remaining 5 cases. Conclusion Appropriate surgical timing and surgical treatment of WICH could help prevent the enlargement of hemotomas, improve the prognosis and reduce its mortality. Key words: Intracerebral hemorrhage; Warfarin; Neurosurgical procedures; Anticoagulants

Large Saddle Embolus: An Unusual Cause of Collapse

Background Pulmonary embolisms are a relatively common and potentially life threatening cardiovascular disorder Diagnosis can be difficult due to variation in presentation therefore suspicion should always be high for a venous thromboembolic cause for any unusual presentations such as an unprovoked collapse Treatment for pulmonary embolisms remains somewhat conflicted particularly in cases with complex comorbidities Case presentation A year old Caucasian male was admitted with a new history of multiple collapses over the past three days He had had a small GI bleed a month ago which was being managed with proton pump inhibitors A CTPA was performed and showed a large saddle thrombus Despite the radiological diagnosis the patient was haemodynamically stable so he was not thrombolysed Considering his recent history of a GI bleed he was started on Warfarin due to its reversibility Previous studies have suggested that the incidence of bleeding while being anticoagulated depends on the site of bleeding and the time elapsed between bleeding and thrombotic event It has been suggested previously that the benefits of anticoagulation therapy outweigh the risks for those with GI bleeds The patient was loaded on Warfarin and was discharged without complication Conclusion This case demonstrates an unusual presentation of a pulmonary embolism The corresponding radiological image shows a very significant saddle embolus which shows how the acuity of the clinical presentation may not match the severity of the pathology seen radiologically In addition the treatment used for the patient was somewhat equivocal due to the patient rsquo s recent history of a small upper GI bleed resulting in Warfarin being prescribed Recent evidence has been unclear and conflicting about what management option is best for managing venous thromboembolisms on a background of GI bleeding This case highlights the need for further RCTs comparing management and clearer guidelines in regards to anticoagulation

Warfarin affects acute inflammatory response induced by subcutaneous polyvinyl sponge implantation in rats

Purpose: Warfarin (WF) is an anticoagulant which also affects physiological processes other than hemostasis. Our previous investigations showed the effect of WF which gained access to the organism via skin on resting peripheral blood granulocytes. Based on these data, the aim of the present study was to examine whether WF could modulate the inflammatory processes as well. To this aim the effect of WF on the inflammatory response induced by subcutaneous sponge implantation in rats was examined.Materials and methods: Warfarin-soaked polyvinyl sponges (WF-sponges) were implanted subcutaneously and cell infiltration into sponges, the levels of nitric oxide (NO) and inflammatory cytokines tumor necrosis factor (TNF) and interleukin-6 (IL-6) production by sponge cells were measured as parameters of inflammation. T cell infiltration and cytokine interferon-γ (IFN-γ), interleukin-17 (IL-17) and interleukin-10 (IL-10) were measured at day 7 post implantation.Results: Warfarin exerted both stimulatory and suppressive effects depending on the parameter examined. Flow cytometry of cells recovered from sponges showed higher numbers of granulocytes (HIS48+ cells) at days 1 and 3 post implantation and CD11b+ cells at day 1 compared to control sponges. Cells from WF-sponges had an increased NO production (Griess reaction) at days 1 and 7. In contrast, lower levels of TNF (measured by ELISA) production by cells recovered from WF-soaked sponges were found in the early (day one) phase of reaction with unchanged levels at other time points. While IL-6 production by cells recovered from WF-soaked sponges was decreased at day 1, it was increased at day 7. Higher T cell numbers were noted in WF sponges at day 7 post implantation, and recovered cells produced more IFN-γ and IL-17, while IL-10 production remained unchanged.Conclusions: Warfarin affects some of the parameters of inflammatory reaction induced by subcutaneous polyvinyl sponge implantation. Differential (both stimulatory as well as inhibitory) effects of WF on inflammatory response to sponge implants might affect the course and/or duration of this reaction.

Clinical experience reversing factor Xa inhibitors with four-factor prothrombin complex concentrate in a community hospital.

Clinical experience reversing factor Xa inhibitors with four-factor prothrombin complex concentrate in a community hospital.

Effectiveness case of Jidabokuippo (traditional Japanese Kampo medicine) on pain, venous thrombosis, and subcutaneous hematoma after percutaneous femoral catheterization in a hemodialysis patient

BackgroundThe authors herein report a case of pain, femoral vein thrombosis, and inguinal subcutaneous hematoma caused by percutaneous femoral vascular catheterization in a hemodialysis (HD) patient complicated with vascular access occlusion. The pain was well-controlled without using analgesics such as non-steroidal anti-inflammatory drugs (NSAIDs). The thrombosis and hematoma increased in size and was also treated by conservative treatment using traditional Japanese Kampo medicine (jidabokuippo: JDI) to resolve oketsu: a sign of microcirculating disorder. JDI improves the blood circulation in the affected lesion and alleviates contusion-induced blood flow and repairs blood flow without forming thrombosis. These catheter-related complications were successfully treated by JDI.Case presentationA 41-year-old man under HD was admitted because of permanent vascular access failure. He had a history of side effects of gastrointestinal bleeding associated with use of NSAIDs and accompanied with femoral vein thrombosis and inguinal subcutaneous hematoma caused by percutaneous femoral vascular catheterization. The hematoma increased in size and was treated using JDI. In the present case, pain, venous thrombosis, and subcutaneous hematoma surprisingly improved with use of JDI in addition to combination therapy with anticoagulant (warfarin potassium) and antibiotic (meropenem hydrate), without using analgesics such as NSAIDs.ConclusionsThe present case indicated as follows: JDI controls the pain associated with hematoma without analgesics such as NSAIDs; JDI also has an effect of improving the complications associated with venous thrombosis and subcutaneous hematoma caused by catheterization in HD patients safely. JDI, one of Kampo drugs, has few side effects and can be used as needed.

Electrochemical microfluidic chip based on molecular imprinting technique applied for therapeutic drug monitoring

In this work, a novel electrochemical detection platform was established by integrating molecularly imprinting technique with microfluidic chip and applied for trace measurement of three therapeutic drugs. The chip foundation is acrylic panel with designed grooves. In the detection cell of the chip, a Pt wire is used as the counter electrode and reference electrode, and a Au–Ag alloy microwire (NPAMW) with 3D nanoporous surface modified with electro-polymerized molecularly imprinted polymer (MIP) film as the working electrode. Detailed characterization of the chip and the working electrode was performed, and the properties were explored by cyclic voltammetry and electrochemical impedance spectroscopy. Two methods, respectively based on electrochemical catalysis and MIP/gate effect were employed for detecting warfarin sodium by using the prepared chip. The linearity of electrochemical catalysis method was in the range of 5×10−6–4×10−4M, which fails to meet clinical testing demand. By contrast, the linearity of gate effect was 2×10−11–4×10−9M with remarkably low detection limit of 8×10–12M (S/N=3), which is able to satisfy clinical assay. Then the system was applied for 24-h monitoring of drug concentration in plasma after administration of warfarin sodium in rabbit, and the corresponding pharmacokinetic parameters were obtained. In addition, the microfluidic chip was successfully adopted to analyze cyclophosphamide and carbamazepine, implying its good versatile ability. It is expected that this novel electrochemical microfluidic chip can act as a promising format for point-of-care testing via monitoring different analytes sensitively and conveniently.

Use of Low-dose Oral Warfarin in Three Cases of Livedoid Vasculopathy.

We hereby present our experience of low-dose oral warfarin in the management of three cases of livedoid vasculopathy.

Impact of the Number of Anti-Thrombosis Agents in Hemodialysis Patients: BOREAS-HD2 Study

Background/Aims: Relationships between the number of anti-thrombosis agents, clinical benefits and adverse events in hemodialysis (HD) patients are unclear. Methods: All patients on HD in 22 institutes (n = 1,071) were enrolled and followed up for 3 years. After exclusion of patients with missing data, kidney transplantation or retraction of consent during the follow-up period (n = 204), mortality rate and ischemic and hemorrhagic events were compared between different regimens of anti-thrombosis agents. Results: The use of dual or triple antiplatelet (AP) agents (HR:2.03, 95% CI:1.01-4.13, p = 0.04) and the combination of an AP agent and warfarin (WF) (HR:4.84, 95%CI 1.96-11.96, p < 0.001) were associated with an increase in hemorrhagic events compared with no use of anti-thrombosis agents. No anti-thrombosis regimen was associated with a significant change in risk of ischemic stroke. The use of dual or triple AP agents, but not WF, was associated with an increase in cardiovascular mortality (HR:2.48, 95% CI:1.24-4.76, p = 0.01). Conclusion: A significant increase in hemorrhagic events by the use of dual or more AP agents and by co-administration of an AP agent and WF in patients on HD should be considered in planning their anti-thrombosis regimen.

Warfarin Guide: Co-Design of a Mobile Computer-Assisted Anticoagulant Therapy.

Patients with some types of cardiovascular disease are prescribed anticoagulation therapy with Warfarin in order to control the ability of blood clotting. This work presents a co-designed mobile application, called Warfarin Guide, for a computer-assisted anticoagulant therapy. The application addresses the challenges that unexperienced patients may find when having to remember to regularly check their INR values and make temporary adjustments for INR value fluctuations that are not easy to interpret without direct medical advice.

A short infrapectineal buttress plate fixing posterior column for complex acetabular fractures through Ilioinguinal approach

Objective To evaluate the clinical outcomes of ilioinguinal approach with short infrapectineal buttress plate fixing posterior column for patients with complex acetabular fractures. Methods Data of 29 consecutive patients (male 22, female 7, age range 25-72 years, average age 53±6.3 years) with complex acetabular who had operated by single ilioinguinal approach with infrapectineal buttress plate from September 2008 to August 2012 were retrospectively analyzed. According to Letournel-Judet classifications, there were 4 cases of anterior column and posterior hemi-transverse, 11 cases of associated both-column, 4 of T-shaped and 6 with seagull sign. The acetabular fractures model was printed preoperatively by 3D printing technique for surgical simulation, open reduction and internal fixation through single ilioinguinal approach with a short infrapectineal plate fixing posterior column, particularly an ox horn shape K-wire sleeve was developed for drilling and screw insertion using flexible screw-driver. Clinical, radiographic, and functional outcomes assessed by the modified Merle d' Aubigne score were collected. Results Two patients were lost to follow-up, including one patient who died at 15 days postoperative because of pulmonary embolism, and the other one who had moved abroad at 12 months postoperative. The remaining 27 (93%) had a mean follow-up of 40 months (range, 24-75 months). The operating time was 180±35.5 min; the time for the fracture union was 3.5±0.9 month; blood loss during the operating was 500±43.9 ml; no case had fracture re-displacement. At the latest follow-up, radiographic grades were excellent in 17, good in 8, poor in 4, including one poor patient who had a total hip arthroplasty (3%) at 35 months after the internal fixation. The average modified Merle d’Aubigne score was 16 (range, 10-18), and categorized as excellent in 12, good in 8, fair in 5, and poor in 2. Three patients had developed deep venous thrombosis of the lower extremities, and one of them died of pulmonary embolism 15 days after operation; two cases of deep venous thrombosis of the lower extremity were found 3-4 days after operation. Thrombosis disappeared 6 months after anticoagulant therapy by warfarin. One case who had superficial wound infection after operation was treated by anti-infection and VSD negative pressure, and incision was healed after one month. One case with poor quality of fracture reduction and seagull sign was treated with total hip arthroplasty after 35 months because of traumatic arthritis. The total complication rate was 24% (7/29). Conclusion In the patient with complex acetabular fractures combining posterior column medial displacement, single Ilioinguinal approach with infrapectineal buttress plates could achieve a stable concentric hip joint, and immediate postoperative ambulation can result in reasonable clinical, radiographic, and functional outcomes. Key words: Acetabulum; Fractures, bone; Internal fixators

Synthesis of Anticogulant Warfarin and Its Derivatives by the Crude Earthwarm Extract

Synthesis of Anticogulant Warfarin and Its Derivatives by the Crude Earthwarm Extract

Nasal Drug Absorption from Powder Formulations: Effect of Fluid Volume Changes on the Mucosal Surface.

The effect of changes in the mucosal fluid volume on the nasal drug absorption of powder formulations was evaluated using warfarin (WF), piroxicam (PXC), and norfloxacin (NFX) as model drugs. Lactose and sodium chloride (NaCl), which are water soluble and small-sized chemicals that increase osmotic pressure after dissolution, were used as excipients to change the mucosal fluid volume. The in vitro study using a Madin-Darby canine kidney (MDCK) cell monolayer indicated that lactose and NaCl, sprayed over the surface of air interface monolayers, increased the fluid volume on the monolayer surface and enhanced the transepithelial transport of the model drugs. The in vivo animal study indicated that the nasal absorption of PXC is enhanced by lactose and NaCl after nasal administration of the powder formulations. This is likely due to the enhanced dissolution of PXC on fluid-rich nasal mucosa and an increase in the effective surface area for drug permeation, which lead to better nasal absorption. However, both excipients failed to increase the nasal absorption of WF and NFX. To clarify the mechanism of the drug-dependent effect of lactose and NaCl, the nasal residence of the formulation was examined using FD70 as a non-absorbable marker. The nasal clearance of FD70 was enhanced by lactose and NaCl, leading to a decrease in the nasal drug absorption. Lactose and NaCl caused no damage to the nasal tissue. These results indicate that the addition of water-soluble excipients such as lactose to powder formulations can enhance the nasal absorption of highly permeable but poorly soluble drugs.

Simultaneous Determination of Warfarin and Aspirin Contents in Biological Fluids Using Excitation-Emission Matrix Fluorescence Coupled with a Second-order Calibration Method.

In the present work, a practical method that combines excitation-emission matrix fluorescence with a second-order calibration method based on an alternating trilinear decomposition (ATLD) algorithm was developed in order to simultaneously and directly determine the contents of warfarin (WAR) and aspirin (ASA) in human plasma and urine samples, even in the presence of unknown interferences. With the pre-estimated component number of 4, the obtained average spiked recoveries were 105.4 ± 7.8 and 104.2 ± 8.3% for WAR, 96.5 ± 2.8 and 91.2 ± 2.3% for ASA in human plasma and urine samples, respectively. Furthermore, the figures of merit were calculated and also inter- and intra-day experiments were performed that proved the proposed method is of great significance to the monitoring of clinical administration and also being a simple sample pretreatment at low-cost.

Quality control of Warfarin Sodium tablets marketed in Syria

There are several generics of Warfarin Sodium available in Syrian drug market. The aim of this study is to evaluate the physicochemical properties of three brands of Warfarin Sodium(5mg) tablets marketed in Syria. The physicochemical equivalence of three brands of warfarin sodium tablets were assessed through the evaluation of weight variation, friability, hardness, content uniformity, and dissolution rate. All the brands complied with the specifications for hardness, friability, and weight variation tests. Two brands had values within the range specified (95-105%) for content uniformity in the USP while brand C failed the test. Also brands A, B released more than 80% of drug in 30 minutes while brand C release less than 80%, so brands A, B passed USP specifications, While brand C failed this test.

Study of competitive binding of amlodipine besylate and benazepril hydrochloride to bovine serum albumin and their displacement interaction at the binding site

The present experiment shows how clinically two important drugs, amlodipine besylate (AB) and benazepril hydrochloride (BH), bind with serum protein and their mutual effect to displace each other from their binding sites. Binding chemistry of amlodipine besylate and and benazepril hydrochloride to bovine serum albumin (BSA) was evaluated by equilibrium dialysis method at pH 7.4 and 37°C temperature. The binding of these two drugs have been characterized by two sets of association constant: high affinity constant (K1) with low capacity (n1) and low affinity association (k2) constant with high capacity (n2). The non-linear curve of the scatchard plot suggested high affinity binding sites (K1 = 8.47x105 M-1, n1=1.9) and low affinity binding sites (K2 = 0.33 x105 M-1 , n2=11.7) for amlodipine besylate. On the other hand for benazepril hydrochloride high affinity constant (K1) was 14 x105 M-1 (n1 =1) and low affinity constant (K2) was 0.31 x105 M-1 (n2 = 16 ). Site specific probe displacement data showed that amlodipine besylate primarily binds to site – I (the warfarin sodium site), while the low affinity site of this drug is site II (diazepam site) on BSA. On the other hand, benazepril hydrochloride primarily binds to site – II (diazepam site) on BSA. The investigated drugs compete for different site (site-I amlodipine besylate and site-II – benazepril hydrochloride) and they do not displace each other on bovine serum albumin, hence concurrent administration of these two drugs will not alter the therapeutic efficacy of each other and co-administered of these two drugs can be effective as a combination dosage form in the management of hypertension.

An Assessment of Osteoporotic Conditions among Users and Non-Users of Warfarin: A Case-Control Study.

Warfarin is an oral anticoagulant which is associated with a decrease in Bone Mass Density (BMD). The study aimed to explore the prevalence of osteoporosis conditions in Malaysians with chronic warfarin patients using calcaneal quarter of Quantitative Ultrasound (QUS) machine and to investigate whether long-term sodium warfarin therapy that antagonizes vitamin K is affecting the increasing rate of osteoporosis in Penang and to find the risk factors of getting osteoporosis among warfarin users and its non users. A case-control study was conducted among 130 patients using warfarin, attending the outpatient clinic at Hospital Pulau Pinang. A convenience sampling method was used to recruit the required sample. Another 140 subjects were selected from the community as a control group (non-users of warfarin). This study showed that more than three-quarter patients (82%) were at high risk of abnormal BMD. The warfarin users were two times more likely to have a higher osteoporosis risk compared to control group. Moreover, BMD has a negative correlation with age, but has a positive correlation with Body Mass Index (BMI). Patients showed a negative correlation with a higher dose of warfarin intake. This study concluded that osteopenia and osteoporosis are serious problems between users and non-users warfarin in Penang. Therefore, it should be taken into consideration in the Malaysian Health Ministry's agenda.

Daclatasvir・asunaprevir併用療法中にワルファリンカリウムの効果減弱を来した大動脈解離術後のC型慢性肝炎の一例

57歳・男性，C型慢性肝炎（genotype 1b）．急性大動脈解離術後でワルファリンカリウム（ワルファリン）を内服していた．Y93・L31薬剤耐性変異なし．腎機能障害があるため，daclatasvir（DCV）・asunaprevir（ASV）併用療法を選択した．治療開始前のPT-INRは目標範囲内（1.8-2.2）で安定していたが，内服開始後PT-INRは経時的に短縮し，ワルファリン必要量が増加した．DCV/ASVとワルファリンの薬物相互作用は報告されていないが，最近，海外でDirect Acting Antivirals（DAA）治療中に本例に類似した報告がある．薬物相互作用の関与は完全には否定出来ないが，ウイルスが消失し，肝機能が改善し薬物代謝能が改善したことや凝固因子の産生能力改善も一因ではないかと推測した．DAA投与時は薬物相互作用だけでなく，肝機能改善による代謝能力向上も念頭に入れる必要があると考え報告する．