Guidance for the practical management of warfarin therapy in the treatment of venous thromboembolism.

Venous thromboembolism (VTE) is a serious and often fatal medical condition with an increasing incidence. The treatment of VTE is undergoing tremendous changes with the introduction of the new direct oral anticoagulants and clinicians need to understand new treatment paradigms. This article, initiated by the Anticoagulation Forum, provides clinical guidance based on existing guidelines and consensus expert opinion where guidelines are lacking. Well-managed warfarin therapy remains an important anticoagulant option and it is hoped that anticoagulation providers will find the guidance contained in this article increases their ability to achieve optimal outcomes for their patients with VTE Pivotal practical questions pertaining to this topic were developed by consensus of the authors and were derived from evidence-based consensus statements whenever possible. The medical literature was reviewed and summarized using guidance statements that reflect the consensus opinion(s) of all authors and the endorsement of the Anticoagulation Forum's Board of Directors. In an effort to provide practical and implementable information about VTE and its treatment, guidance statements pertaining to choosing good candidates for warfarin therapy, warfarin initiation, optimizing warfarin control, invasive procedure management, excessive anticoagulation, subtherapeutic anticoagulation, drug interactions, switching between anticoagulants, and care transitions are provided.

Integrating electronic health records in the delivery of optimized anticoagulation therapy.

Integration of accepted practice standards into electronic health record systems can facilitate standardization of anticoagulation care delivery and result in improved anticoagulation safety. However, the majority of commonly used electronic health record systems are lacking the specialized features necessary for optimal anticoagulation management. The Task Force on Electronic Health Records of the New York State Anticoagulation Coalition provides such a Consensus Statement in this issue of the journal. The Anticoagulation Forum endorses these recommendations and advises the electronic health record industry and health information technology programmers at the institutional level to adopt these recommendations in a comprehensive and timely manner.

Double Blind Pilot Randomized Trial Comparing Extended Anticoagulation to Placebo Following Major Lung Resection for Cancer.

Venous thromboembolism (VTE), which comprises pulmonary embolus (PE) and deep vein thrombosis (DVT), is a significant cause of postoperative morbidity and mortality. This pilot randomized control trial (RCT) evaluated the feasibility of a full-scale RCT investigating extended thromboprophylaxis in patients undergoing oncological lung resections. Patients undergoing oncological lung resections in 2 tertiary centers received in-hospital, thromboprophylaxis and were randomized to receive post-discharge low-molecular-weight heparin (LMWH) or placebo injections once-daily for 30 days. At 30 days postoperatively, all patients underwent chest computed tomography with PE protocol and bilateral leg venous ultrasound. Primary outcomes included feasibility and safety; VTE incidence and 90-day survival were secondary outcomes. Between December 2015 and June 2018, 619 patients were screened, of whom 62.7% (165/263) of eligible patients consented to participate, and 133 (81%) were randomized. One-hundred and 3 patients, (77.4%), completed the 90-day study follow-up. Reasons for non-participation pre-randomization included patient discomfort and LMWH/placebo administration challenges. Post-randomization withdrawals were due to patient preference, surgeon preference and minor adverse events. Six asymptomatic VTE events (5 PE and 1 DVT) were detected within 30 days (3 in each group), for an overall incidence of 7%. There were 3 minor and no major adverse events. This study is the first to demonstrate the feasibility and safety of a full-scale extended thromboprophylaxis RCT in thoracic surgical oncology. Our results demonstrate that, while recruitment and retention rates were modest, the study design is feasible and with minimal adverse events and no intervention-related mortality.

Does the usage of digital chest drainage systems reduce pleural inflammation and volume of pleural effusion following oncologic pulmonary resection?-A prospective randomized trial.

BACKGROUND: Prolonged air leak and high-volume pleural drainage are the most common causes for delays in chest tube removal following lung resection. While digital pleural drainage systems have been successfully used in the management of post-operative air leak, their effect on pleural drainage and inflammation has not been studied before. We hypothesized that digital drainage systems (as compared to traditional analog continuous suction), using intermittent balanced suction, are associated with decreased pleural inflammation and postoperative drainage volumes, thus leading to earlier chest tube removal. METHODS: One hundred and three [103] patients were enrolled and randomized to either analog (n=50) or digital (n=53) drainage systems following oncologic lung resection. Chest tubes were removed according to standardized, pre-defined protocol. Inflammatory mediators [interleukin-1B (IL-1B), 6, 8, tumour necrosis factor-alpha (TNF-α)] in pleural fluid and serum were measured and analysed. The primary outcome of interest was the difference in total volume of postoperative fluid drainage. Secondary outcome measures included duration of chest tube in-situ, prolonged air-leak incidence, length of hospital stay and the correlation between pleural effusion formation, degree of inflammation and type of drainage system used. RESULTS: There was no significant difference in total amount of fluid drained or length of hospital stay between the two groups. A trend for shorter chest tube duration was found with the digital system when compared to the analog (P=0.055). Comparison of inflammatory mediator levels revealed no significant differences between digital and analog drainage systems. The incidence of prolonged post-operative air leak was significantly higher when using the analog system (9 versus 2 patients; P=0.025). Lobectomy was associated with longer chest tube duration (P=0.001) and increased fluid drainage when compared to sub-lobar resection (P<0.001), regardless of drainage system. CONCLUSIONS: Use of post-lung resection digital drainage does not appear to decrease pleural fluid formation, but is associated with decreased prolonged air leaks. Total pleural effusion volumes did not differ with the type of drainage system used. These findings support previously established benefits of the digital system in decreasing prolonged air leaks, but the advantages do not appear to extend to decreased pleural fluid formation.

The effect of low-dose oral vitamin K supplementation on INR stability in patients receiving warfarin. A randomised trial.

The anticoagulant effect of warfarin is influenced by variations in vitamin K intake. Concomitant use of daily low-dose oral vitamin K (LDVK) and warfarin may improve INR stability. We hypothesise that administration of LDVK improves INR control. To test this hypothesis we performed a multi-centre, placebo-controlled, randomised trial conducted at four university-affiliated hospitals in Canada. Patients on chronic warfarin therapy received oral vitamin K 150 mcg daily or a matching placebo for a total of six months after a one-month run in period. The primary outcome was a comparison of mean time in therapeutic range (TTR) in LDVK and placebo group during a six-month-period. The secondary outcome was number of INR excursions <1.5 or >4.5. There was no significant difference in the final TTR between the two groups (65.1 % vs 66 %, p =0.8). Mean TTR in both LDVK and placebo groups were statistically increased compared with prior to the study. The number of INR excursions were significantly decreased in the LDVK group (9.4 % and 5.4 %, absolute difference [pre- minus post-] = 4 %, 95 % CI, 2 to 6 %, p-value <0.001). We conclude that LDVK administration did not increase mean TTR, but did decrease the number of INR excursions. The observed improvement in mean TTR in both groups suggests that more attentive monitoring of warfarin therapy, rather than LDVK, was responsible for the improvement in TTR observed. The reduced excursions suggest that LDVK did reduce extreme INR variation. The study is registered at www.ClinicalTrial.gov# NCT00990158.

Postdischarge venous thromboembolic complications following pulmonary oncologic resection: An underdetected problem.

OBJECTIVES: To determine the prevalence of delayed postoperative venous thromboembolism (VTE) in patients undergoing oncologic lung resections, despite adherence to current in-hospital VTE prophylaxis guidelines. METHODS: Patients undergoing lung resection for malignancy in 2 tertiary-care centers were recruited between June 2013 and December 2014. All patients received guideline-based VTE prophylaxis until hospital discharge. Patients underwent computed tomography chest angiography with pulmonary embolism (PE) protocol and bilateral lower extremity venous Doppler ultrasonography at 30 ± 5 days after surgery to determine the incidence of postoperative VTE. Univariate analysis was used to compare the VTE and non-VTE groups. RESULTS: A total of 157 patients were included, 45.9% were men with a mean age of 66.7 years. VTE prevalence was 12.1% with a total of 19 VTE events, including 14 PEs (8.9%), 3 deep venous thromboses (DVTs) (1.9%), 1 combined PE/DVT, and 1 massive left atrial thrombus originating from the pulmonary vein stump after pulmonary lobectomy. PE events occurred in the operated lung 64% of the time and 4 patients (21.1%) were symptomatic at diagnosis. The 30-day mortality rate of VTE events was 5.2%, with 1 patient who died secondary to massive in situ ipsilateral PE following readmission to the hospital. Univariate analysis did not demonstrate significant differences between the VTE and non-VTE populations with regard to baseline characteristics. CONCLUSIONS: Despite adherence to in-hospital standard prophylaxis guidelines, VTE events are frequent, often asymptomatic, and with associated significant morbidity and mortality. More research into the potential role of predischarge screening and extended prophylaxis is warranted.

Oral vitamin K produces a normal INR within 24 hours of its administration in most patients discontinuing warfarin.

A randomized, blinded study in 30 patients was undertaken. This study found that low dose oral vitamin K was more effective than placebo when used to correct the INR in patients who are discontinuing warfarin. Larger studies will be required to determine if the use of oral vitamin K, for example in patients who are temporarily discontinuing warfarin to undergo interventional procedures, is safe and effective.

Oral vitamin K lowers the international normalized ratio more rapidly than subcutaneous vitamin K in the treatment of warfarin-associated coagulopathy. A randomized, controlled trial.

BACKGROUND: Excessive anticoagulation due to warfarin use is associated with hemorrhage. Subcutaneously administered vitamin K has not been evaluated for the treatment of warfarin-associated coagulopathy, yet it is widely used. OBJECTIVE: To show that oral vitamin K is more effective than subcutaneous vitamin K in the treatment of warfarin-associated coagulopathy. DESIGN: Randomized, controlled trial. SETTING: Two teaching hospitals. PATIENTS: Patients with an international normalized ratio (INR) between 4.5 and 10.0. INTERVENTION: Warfarin therapy was withheld, and 1 mg of vitamin K was given orally or subcutaneously. MEASUREMENTS: The primary outcome measure was the INR on the day after administration of vitamin K. Secondary outcome measures were hemorrhage and thrombosis during a 1-month follow-up period. RESULTS: 15 of 26 patients receiving oral vitamin K and 6 of 25 patients receiving subcutaneous vitamin K had therapeutic INRs on the day after study drug administration (P = 0.015; odds ratio, 4.32 [95% CI, 1.13 to 17.44]). CONCLUSION: Oral vitamin K lowers INR more rapidly than subcutaneous vitamin K in asymptomatic patients who have supratherapeutic INR values while receiving warfarin.

Patient preferences for capillary vs. venous INR determination in an anticoagulation clinic: a randomized controlled trial.

BACKGROUND: Patients who are receiving warfarin therapy require frequent blood testing to monitor the intensity of anticoagulation. Although previous studies suggest that capillary blood monitoring of the international normalize ratio (INR) is rapid and reliable, patient preferences for the method of blood drawing have not been investigated. METHODS: We performed a randomized controlled trial of patients attending an anticoagulation clinic in which patients were randomly allocated to undergo capillary or venous INR monitoring. Patient satisfaction with the outpatient visit, pain associated with blood drawing, and time spent in the clinic were assessed for each patient. RESULTS: Sixty patients were studied. Using a 10-point visual analogue scale to quantify patient satisfaction (0-very satisfied; 10-very dissatisfied), patients expressed a strong preference for capillary INR monitoring over venous INR monitoring (1.64 vs. 4.45; P < 0.001). Using a 10-point visual analogue scale to quantify pain with blood sampling (0-no pain; 10-very painful), patients who underwent capillary INR testing had less pain than venous INR testing (0.83 vs. 2.23; P < or = 0.004). Patients spent, on average, 33 fewer minutes in the clinic with capillary INR testing than venous INR testing (P < 0.001). DISCUSSION: Our findings support the routine use of capillary blood testing, using a portable monitor, for the management of patients in outpatient anticoagulation clinics.