Temporarily Reversing Warfarin With Low-Dose 4-Factor Prothrombin Complex Concentrate in Left Ventricular Assist Device Patients Undergoing an Invasive Procedure.

BACKGROUND: American Association for Thoracic Surgery and The International Society for Heart and Lung Transplantation (AATS/ISHLT) guidelines recommend warfarin in patients with continuous-flow left ventricular assist devices (LVADs) to reduce the risk of device thrombosis and systemic embolization. Left ventricular assist device patients often undergo elective and emergent procedures that require interrupted anticoagulation. Data and experience vary on the optimal strategy to rapidly reverse warfarin in LVAD patients when an emergent procedure is planned. OBJECTIVE: The purpose of this study was to describe the use of 4-factor prothrombin complex concentrate (PCC4) for warfarin reversal in patients with LVADs undergoing elective and emergent procedures. METHODS: This retrospective, single-center, cohort review describes the use of PCC4 in patients with LVADs who require warfarin reversal for elective or emergent procedures. The primary outcome was a composite incidence of pump thrombosis, venous thromboembolism, and ischemic stroke within 30 days of PCC4 administration. RESULTS: In total, 14 patients received 17 administrations of PCC4. One patient received 3 administrations, and 1 other patient received 2 administrations during separate encounters. The median dose was 500 units or 6.6 units/kg (range = 4.2-14.1 units/kg). Of the PCC4 administrations, 82% (14/17) were for low bleed risk procedures and 76% (13/17) were for elective procedures. There were no cases of pump thrombosis, venous thromboembolism, or stroke within 30 days of the procedure. CONCLUSIONS AND RELEVANCE: Low-dose PCC4 appears to be a safe and effective temporary reversal strategy for patients with LVADs undergoing low-bleed risk elective procedures.

Comparison of Managing Factor Xa Inhibitor to Unfractionated Heparin Transitions by aPTT Versus a Treatment Guideline Utilizing Heparin Anti-Xa Levels.

BACKGROUND: There are inadequate data on the optimal strategy for transitioning factor Xa inhibitors (FXai; apixaban, rivaroxaban) to unfractionated heparin (UFH) infusions. OBJECTIVE: In patients transitioning from an FXai to an UFH infusion, this study compared the safety and efficacy of monitoring UFH infusions using an activated partial thromboplastin time (aPTT) titration scale versus utilizing an UFH-calibrated anti-Xa titration scale aided by a novel institutional guideline. METHODS: A retrospective cohort analysis was conducted on adult patients transitioning from an FXai to an UFH infusion at 2 medical centers from June 1, 2018, to November 1, 2020. One institution utilized aPTT while the other institution primarily used UFH-calibrated anti-Xa. The primary endpoint was a composite of death, major bleeding, or new thrombosis during the hospitalization with a planned noninferiority analysis. Secondary outcomes were also collected including the amount and duration of UFH administered between cohorts. RESULTS: The incidence rate of the primary composite endpoint was 6.3% in the anti-Xa group and 11% in the aPTT group (P < 0.001 for noninferiority, P = 0.138 for superiority) meeting noninferiority criteria. No statistical differences were seen in new thrombosis, major bleeding, or any bleeding. CONCLUSION AND RELEVANCE: This represents the first report of a comparison between aPTT versus anti-Xa monitoring in relation to clinical outcomes for patients transitioning from an FXai to an UFH infusion. A transition guideline primarily utilizing an UFH-calibrated anti-Xa assay appears to be a safe alternative to aPTT monitoring and can aid facilities in the management of patients during these complex transitions.

Thromboembolic prevention and anticoagulant therapy during the COVID-19 pandemic: updated clinical guidance from the anticoagulation forum.

Thromboembolism is a common and deadly consequence of COVID-19 infection for hospitalized patients. Based on clinical evidence pre-dating the COVID-19 pandemic and early observational reports, expert consensus and guidance documents have strongly encouraged the use of prophylactic anticoagulation for patients hospitalized for COVID-19 infection. More recently, multiple clinical trials and larger observational studies have provided evidence for tailoring the approach to thromboprophylaxis for patients with COVID-19. This document provides updated guidance for the use of anticoagulant therapies in patients with COVID-19 from the Anticoagulation Forum, the leading North American organization of anticoagulation providers. We discuss ambulatory, in-hospital, and post-hospital thromboprophylaxis strategies as well as provide guidance for patients with thrombotic conditions who are considering COVID-19 vaccination.

INR Response to Low-Dose Vitamin K in Warfarin Patients.

BACKGROUND: Literature suggests that 2 mg of vitamin K intravenously (IV) provides a similar effect as 10 mg to reverse warfarin. Doses <5 mg haven't been studied in depth. OBJECTIVE: The objective was to determine the international normalized ratio (INR) reduction effect of ultra low-dose (ULD) IV vitamin K. METHODS: This retrospective, observational cohort study compared IV vitamin K doses of 0.25-0.5 mg (ULD) versus 1-2 mg (standard low dose [SLD]). The primary outcome assessed ΔINR at 36 hours; secondary outcomes assessed ΔINR at 12 hours and 30-day venous thromboembolism (VTE) and mortality rates. RESULTS: Of 88 patients identified (median baseline INR [IQR], 5.1 [3.1, 7.3] vs 4.5 [2.8, 8.2], ULD vs SLD, respectively), 59 had an INR at 12 hours. The ULD had fewer 12-hour INR values <2, with no statistical difference in the ΔINR at 12 hours between the ULD and SLD cohorts (median ΔINR, 2.2 [1.1, 3.4] vs 2.2 [1.1, 6.3]; P = 0.54; median INR, 2.3 vs 1.8). A total of 41 patients had both a 12- and 36-hour INR. No significant difference in the ΔINR between the 12- and 36-hour values occurred (median ΔINR, 0.52 [0.2, 0.91] vs ΔINR, 0.46 [0.18, 0.55]; P = 0.61), suggesting no rebound or excessive reversal and no difference in 30-day rates of VTE (P > 0.99) or death (P = 0.38). CONCLUSION AND RELEVANCE: ULD IV vitamin K reversed INR similarly to doses of 1-2 mg without rebound. A ULD strategy may be considered in patients requiring more cautious reversal.

Antibiotic Dosing for Critically Ill Adult Patients Receiving Intermittent Hemodialysis, Prolonged Intermittent Renal Replacement Therapy, and Continuous Renal Replacement Therapy: An Update.

Objective: To summarize current antibiotic dosing recommendations in critically ill patients receiving intermittent hemodialysis (IHD), prolonged intermittent renal replacement therapy (PIRRT), and continuous renal replacement therapy (CRRT), including considerations for individualizing therapy. Data Sources: A literature search of PubMed from January 2008 to May 2019 was performed to identify English-language literature in which dosing recommendations were proposed for antibiotics commonly used in critically ill patients receiving IHD, PIRRT, or CRRT. Study Selection and Data Extraction: All pertinent reviews, selected studies, and references were evaluated to ensure appropriateness for inclusion. Data Synthesis: Updated empirical dosing considerations are proposed for antibiotics in critically ill patients receiving IHD, PIRRT, and CRRT with recommendations for individualizing therapy. Relevance to Patient Care and Clinical Practice: This review defines principles for assessing renal function, identifies RRT system properties affecting drug clearance and drug properties affecting clearance during RRT, outlines pharmacokinetic and pharmacodynamic dosing considerations, reviews pertinent updates in the literature, develops updated empirical dosing recommendations, and highlights important factors for individualizing therapy in critically ill patients. Conclusions: Appropriate antimicrobial selection and dosing are vital to improve clinical outcomes. Dosing recommendations should be applied cautiously with efforts to consider local epidemiology and resistance patterns, antibiotic dosing and infusion strategies, renal replacement modalities, patient-specific considerations, severity of illness, residual renal function, comorbidities, and patient response to therapy. Recommendations provided herein are intended to serve as a guide in developing and revising therapy plans individualized to meet a patient's needs.

Thromboembolism and anticoagulant therapy during the COVID-19 pandemic: interim clinical guidance from the anticoagulation forum.

Coronavirus disease 2019 (COVID-19) is a viral infection that can, in severe cases, result in cytokine storm, systemic inflammatory response and coagulopathy that is prognostic of poor outcomes. While some, but not all, laboratory findings appear similar to sepsis-associated disseminated intravascular coagulopathy (DIC), COVID-19- induced coagulopathy (CIC) appears to be more prothrombotic than hemorrhagic. It has been postulated that CIC may be an uncontrolled immunothrombotic response to COVID-19, and there is growing evidence of venous and arterial thromboembolic events in these critically ill patients. Clinicians around the globe are challenged with rapidly identifying reasonable diagnostic, monitoring and anticoagulant strategies to safely and effectively manage these patients. Thoughtful use of proven, evidence-based approaches must be carefully balanced with integration of rapidly emerging evidence and growing experience. The goal of this document is to provide guidance from the Anticoagulation Forum, a North American organization of anticoagulation providers, regarding use of anticoagulant therapies in patients with COVID-19. We discuss in-hospital and post-discharge venous thromboembolism (VTE) prevention, treatment of suspected but unconfirmed VTE, laboratory monitoring of COVID-19, associated anticoagulant therapies, and essential elements for optimized transitions of care specific to patients with COVID-19.

Laboratory Monitoring of Parenteral Direct Thrombin Inhibitors.

Argatroban and bivalirudin are parenteral direct inhibitors of the activity of thrombin, but, unlike heparin, can inhibit both soluble as well as clot-bound thrombin. These agents do not require antithrombin as a cofactor for activity. The parenteral direct thrombin inhibitors (DTIs) can be used in a variety of settings, including heparin-induced thrombocytopenia (HIT) or an allergy to heparin, and patients requiring anticoagulation for an invasive cardiovascular intervention. Both agents have a relatively short half-life in patients without organ system failure and are typically administered by continuous infusion. Argatroban is primarily eliminated by the liver, while bivalirudin is removed by a combination of proteolytic cleavage by thrombin and renal clearance mechanisms. Several laboratory tests are available for monitoring the anticoagulant effects of the DTIs: the activated partial thromboplastin time (aPTT) and the activated clotting time (ACT) are the most commonly used assays, but on occasion, the thrombin time may be useful. Other coagulation assays such as the dilute thrombin time (dTT), chromogenic anti-IIa assays, and the ecarin clotting time (ECT) can be used. The intensity of anticoagulation with DTIs depends on the indication for use. For patients with HIT, the target aPTT is 1.5 to 3.0 and 1.5 to 2.5 times the patient's baseline value for argatroban and bivalirudin, respectively. DTI anticoagulation used during percutaneous coronary intervention can be measured using ACT. Both DTIs may cause an elevation in the international normalized ratio depending on their plasma concentration. This article will review the use of parenteral DTIs and related laboratory assays for assessing the anticoagulant effect of these drugs.

Filtering Out Use of DOACs in Hemodialysis.

Published data exploring the best approach to initiating and maintaining anticoagulation in the setting of renal support therapy are scarce, as these patients were excluded in clinical trials. When developing an anticoagulation regimen in this setting, it is important to assess thrombosis risk, identify the unique drivers for thrombosis and bleeding, and recognize the limitations of supporting evidence behind approved prescribing indications for renal impairment. Available literature and considerations for using direct acting oral anticoagulants in the setting of renal support are reviewed.

Heparin-Calibrated Chromogenic Anti-Xa Activity Measurements in Patients Receiving Rivaroxaban: Can This Test Be Used to Quantify Drug Level?

BACKGROUND: Determination of plasma rivaroxaban concentration may be necessary in certain clinical situations. Rivaroxaban concentration can be accurately and rapidly determined using a chromogenic anti-activated factor X (factor Xa) assay with specific drug calibrator material. However, there are currently no Food and Drug Administration (FDA)-approved rivaroxaban calibrators available in the United States. OBJECTIVE: To determine whether FDA-approved commercial kits for measuring heparin anti-factor Xa activity can be used to assess rivaroxaban concentrations when calibrated for unfractionated heparin or low-molecular-weight heparins. METHODS: Trough and peak samples were taken from 30 patients taking rivaroxaban as part of their routine care for atrial fibrillation or venous thromboembolism. The samples were tested using 3 different FDA-approved commercial kits for measuring heparin anti-factor Xa activity. RESULTS: There was acceptable correlation between rivaroxaban levels and heparin anti-factor Xa activity using Berichrom and COAMATIC heparin kits. The STA liquid heparin method was the most sensitive to presence of rivaroxaban. CONCLUSION: This study demonstrates a strong correlation, but variability between kits, for assessing rivaroxaban concentrations using heparin anti-factor Xa assays. The extent of the heparin calibration curve significantly limits the measurable rivaroxaban range, and this application may be useful only for trough samples. The STA liquid heparin, being exquisitely sensitive to rivaroxaban, may be suitable for ruling out presence of the drug. The routine use of heparin-calibrated anti-factor Xa assays to quantify rivaroxaban is not advocated, and when applied, it must be used with caution and limitations clearly understood.

Considerations for Systemic Anticoagulation in ESRD.

In the setting of end-stage kidney disease, the incidence and risk for thrombotic events are increased and use of anticoagulants is common. The incidence of bleeding, however, is also a frequent issue and creates additional challenges in the management of anticoagulation therapy. Patients with end-stage renal disease are typically excluded from large clinical trials exploring the use of anticoagulants, which limits our knowledge of optimal management approaches. Furthermore, varying degrees of renal failure in addition to conditions that alter the pharmacokinetics of various anticoagulants or pharmacodynamic response may warrant alternative approaches to dosing. This review will explore systemic chronic anticoagulation therapy in the setting of chronic kidney disease where hemodialysis is required. Agents discussed include vitamin K antagonists, low-molecular-weight heparins, fondaparinux, oral factor Xa antagonists, and direct thrombin inhibitors. Clinical challenges, approaches to dosing regimens, and tools for measuring responses and reversal will be explored.

Reversing dabigatran in life-threatening bleeding occurring during cardiac ablation with factor eight inhibitor bypassing activity.

OBJECTIVES: We report a case of a patient receiving dabigatran who developed a life-threatening bleeding complication during cardiac ablation that rapidly resolved after administration of Factor Eight Inhibitor Bypassing Activity (FEIBA). BACKGROUND: Therapeutic anticoagulation with warfarin during cardiac ablation has been shown to reduce the risk of stroke and systemic embolism. Cardiac tamponade is a potentially life-threatening procedural complication requiring emergent reversal of anticoagulation and pericardiocentesis. Dabigatran is superior to warfarin in preventing stroke and systemic embolism in nonvalvular atrial fibrillation, but has not been evaluated for use during cardiac ablation. Dabigatran is without a known reversal agent and, should tamponade occur during ablation, it is unclear what reversal strategy could be used to establish hemostasis. METHODS AND RESULTS: A 67-year-old man with history of atrial fibrillation with rapid ventricular rate, two previous atrial fibrillation ablations, and prescribed dabigatran 150 mg bid was admitted for an atrial fibrillation ablation procedure. The last dabigatran dose was 7 hours prior to procedure. During the procedure, a transseptal perforation occurred, requiring an emergent pericardiocentesis. Within 60 minutes, approximately 4.5 L of blood was removed via the pericardiocentesis. Low-dose FEIBA (3159 units, 26 U/kg actual body weight) over 15 minutes was administered. Hemostasis was noted within minutes of initiating the infusion with cessation of bleeding after administration was complete. CONCLUSION: This case report describes the potential ability of a low dose of the activated prothrombin complex concentrate, FEIBA, to reestablish hemostasis independent of the pharmacologic effects of dabigatran. Additional studies are warranted to confirm the findings of our observation.

Removal of dabigatran by hemodialysis.

Dabigatran is a newly available oral direct thrombin inhibitor approved for anticoagulation therapy to prevent strokes in patients with nonvalvular atrial fibrillation. Unlike warfarin, dabigatran's observed therapeutic window and minimal drug-to-drug interaction suggest that invasive laboratory testing and dose adjustment is not necessary. In circumstances of excessive anticoagulation, such as overdoses, decreased kidney function, or instances of significant bleeding, reversing dabigatran's effects may be necessary. Unlike warfarin, no rapid-acting antidote to reverse the effects of dabigatran is known. However, hemodialysis has been suggested as a method of removing dabigatran and thereby reducing its anticoagulant effect. We describe a case in which hemodialysis was used in an attempt to remove dabigatran in a patient with excessive anticoagulation from dabigatran and severe intracranial hemorrhage. Serial dabigatran levels suggested that hemodialysis removed the drug. However, given the large volume of distribution of dabigatran in the terminal phase of elimination, a rebound in drug level was noted. We suggest that a longer duration of therapy or more continuous modality of hemodialysis may be needed in conjunction with the initial hemodialysis treatment of dabigatran coagulopathy.

Safety of new oral anticoagulants with dual antiplatelet therapy in patients with acute coronary syndromes.

OBJECTIVE: To determine the safety of dabigatran, rivaroxaban, or apixaban with dual antiplatelet therapy in patients with acute coronary syndromes. DATA SOURCES: A literature search of MEDLINE (1946-January 2013) was conducted, using the search terms dabigatran, rivaroxaban, or apixaban in combination with dual antiplatelet therapy. A search of literature citations was conducted to identify additional references. STUDY SELECTION AND DATA EXTRACTION: Randomized controlled trials involving the use of one of the new anticoagulants with concomitant dual antiplatelet therapy were included in the review. DATA SYNTHESIS: Five randomized controlled trials were reviewed, including 1 trial of dabigatran, 2 trials of rivaroxaban, and 2 trials of apixaban. These studies were conducted in patients with a recent acute coronary syndrome, so most patients were receiving aspirin and clopidogrel as dual antiplatelet therapy in addition to a therapeutic dose of one of the anticoagulants. The 3 Phase 2 dose-ranging trials (1 each of dabigatran, rivaroxaban, and apixaban) found an increasing risk of major and clinically relevant nonmajor bleeding with increasing doses of the anticoagulants. The Phase 3 trial of apixaban was terminated early due to an excess of bleeding events, and the trial of rivaroxaban also found an increased risk of bleeding. CONCLUSIONS: The emerging use of dabigatran, rivaroxaban, and apixaban into clinical practice has introduced additional management options, but also safety concerns when combined with antiplatelet agents. Due to the increased risk of bleeding when combining an anticoagulant with 2 antiplatelet agents, clinicians should monitor and educate patients on avoiding potential complications. The need for continued triple regimens should be periodically reviewed.

Measuring dabigatran concentrations using a chromogenic ecarin clotting time assay.

BACKGROUND: Clinicians managing patients receiving the direct thrombin inhibitor dabigatran may benefit in being able to determine the amount of drug present in selected situations. This may include assessment of accumulation, concurrent drug interactions, or adequate removal from circulation. The ability to estimate the amount of dabigatran present using the chromogenic ecarin assay (ECA) requires further clarification. OBJECTIVE: To describe the reliability of dabigatran measurements using a chromogenic ECA. METHODS: This was an evaluation of the ECA method that incorporated assessment of imprecision, linearity, accuracy, carryover, and lower limits of detection or blank. Pooled normal plasma enriched with dabigatran at concentrations of 0, 25, 50, 75, 100, 125, 150, 200, 300, 400, and 500 ng/mL were sent blinded to 3 laboratories in the United States to compare our ECA results with those of laboratories reporting dilute thrombin time methods (HEMOCLOT thrombin inhibitor assay) for measuring dabigatran. Trough and peak levels from 35 patients were also compared with mass spectrophotometry for assessing ECA accuracy. RESULTS: The within-run or day-to-day imprecision was less than 10%, with high linearity (R (2) = 0.989) and high degree of accuracy (R (2) = 0.985; slope = 0.908) for levels ranging between 18 and 470 ng/mL and no carryover at 0 ng/mL noted. The ECA approach appeared to be more reliable at lower dabigatran concentrations. CONCLUSIONS: The chromogenic ECA appears to be an effective approach to determine the amount of dabigatran present. Further insights are necessary to determine how it can be used to reduce thromboembolic or bleeding complications in patients receiving dabigatran.

Bivalirudin in pediatric patients maintained on extracorporeal life support.

OBJECTIVE: Anticoagulation with heparin is standard of care for patients maintained on extracorporeal life support. Very limited evidence exists for the use of alternative anticoagulants during extracorporeal life support. Patients with heparin-induced thrombocytopenia, heparin resistance, and evidence of significant thrombosis while on heparin may be candidates for alternative anticoagulation. The objective of this analysis is to present evidence for the use of bivalirudin during extracorporeal life support in pediatric patients. DESIGN: Case series. SETTING: University of California, Davis Medical Center. PATIENTS: Twelve critically ill, pediatric patients receiving bivalirudin for anticoagulation during extracorporeal life support. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Twelve patients meeting entry criteria received bivalirudin during the study period. The median patient age was 8 days (range, 1 d to 6 yr). Eight patients were neonates. Eight patients were male. Nine patients were supported with venoarterial extracorporeal life support. Median duration of extracorporeal life support was 226 hours (range, 111-913) and median time on bivalirudin was 92 hours (range, 60-230). Bivalirudin bolus doses were administered to select patients without bleeding complications. The maintenance dose that corresponded with initial target activated partial thromboplastin time ranged from 0.045 to 0.48 mg/kg/hr with a median rate of 0.16 mg/kg/hr. The median dose for days 1, 3, and 5 was 0.135, 0.175, and 0.267 mg/kg/hr, respectively. The correlation (r2) between dose adjustment and activated partial thromboplastin time response was 0.264. CONCLUSIONS: This is the largest case series describing the use of a direct thrombin inhibitor in pediatric extracorporeal life support patients. The maintenance dose range reflected considerable inter-patient variability. There was an observed increase in dose requirements with time. Bivalirudin, with close monitoring, is a potential option for pediatric patients on extracorporeal life support who have developed heparin-induced thrombocytopenia, heparin resistance, or significant thrombosis while on heparin.

Approaches to Precision-based Anticoagulation management in the critically Ill.

Anticoagulant therapy is commonly associated with a high incidence of avoidable adverse events, especially in the acute care setting. This has led to several initiatives by key national health care stakeholders, including specific attention to The Joint Commission's National Patient Safety Goals, to improve anticoagulation management. The subject of special populations has long been identified as challenging by clinicians with the use of anticoagulants. This is driven in part by numerous variables that can contribute to hard outcomes such as bleeding, thrombosis, length of stay, hospital re-admission, morbidity, and mortality. Despite the notable effort to improve the use of anticoagulants with numerous clinical trials, guidelines, guidance statements, and other sources of published evidence, notable difficulties continue to challenge practitioners in managing this class of medications. This is especially the case with very diverse critically ill populations where countless variables exist, many of which were never explored in trials or have historically been frequently excluded. Trials evaluating anticoagulation therapy often can only account for small portions of variables that may affect thrombosis and hemostasis, and study methods often do not reflect the constantly changing dynamic conditions seen in unique critically ill patients. Clinicians providing care to the numerous critically ill populations are faced with conditions that lead to relatively small therapeutic windows, which makes designing safe optimal anticoagulation management plans difficult when dealing with complex patients and mechanical support devices. The approach to crafting a successful management plan for anticoagulant therapy must incorporate the numerous variables that are continuously assessed and revised during the patient's time in the intensive care unit. We explore considerations and approaches when developing, assessing, and implementing an individualized or precision-based management plan that involves the use of anticoagulants in the critically ill. The skills and thought process provided will assist clinicians in managing this unique, variable, and challenging population.

Warfarin for venous thromboembolism prophylaxis after elective hip or knee arthroplasty: exploring the evidence, guidelines, and challenges remaining.

BACKGROUND: Guidelines for the prevention of venous thromboembolism (VTE) after elective total hip or knee arthroplasty (THA/TKA) have been developed separately by the American Academy of Orthopaedic Surgeons (AAOS) and the American College of Chest Physicians (ACCP). Differences exist in approaches to preventing postoperative VTE through prophylaxis. OBJECTIVE: To compare trials using vitamin K antagonists (VKAs) and differences in guidelines to determine the benefits and drawbacks of warfarin for VTE prophylaxis following THA/TKA. DATA SOURCES: Guidelines from the AAOS published in 2009 and revised in 2011 and from the ACCP published in 2008 were compared for recommendations on the use of VKAs. A MEDLINE search from 1960 to November 2009 was conducted to identify pertinent articles on the use of warfarin or VKAs for VTE prophylaxis following THA/TKA. Search terms included warfarin, vitamin K antagonist, total hip or total knee replacement, and total hip or total knee arthroplasty. STUDY SELECTION AND DATA EXTRACTION: Only clinical trials in which warfarin was the primary agent for prophylaxis compared to other anticoagulants were included. DATA SYNTHESIS: Data on differences between guideline recommendations for the use of VKAs and the importance of a deep vein thrombosis or asymptomatic events were extracted. Thirteen comparative trials using VKAs for VTE prophylaxis and international normalized ratio (INR) targets were assessed. Overall, the incidence of bleeding tended to be lower with the use of VKAs, but thrombosis when including asymptomatic events was numerically higher when comparing INR targets. However, INR targets varied, with no comparative trials assessing the AAOS 2009 recommended INR target of 1.5-2.0. The AAOS guidelines initially recommended a longer duration of therapy and expressed stronger support for the use of aspirin for prophylaxis; however, in 2011, its guidelines were revised, with no specific recommendations as to agent, dose, or INR target goal. CONCLUSIONS: Warfarin is an effective agent to prevent VTE after elective THA/TKA. The most effective approach, including extended warfarin use up to 4 weeks or longer, has not been determined.

Vitamin K dosing to reverse warfarin based on INR, route of administration, and home warfarin dose in the acute/critical care setting.

BACKGROUND: Vitamin K is commonly used for reversal of anticoagulation of warfarin. However, the optimal dose and route of vitamin K that does not increase the duration of bridging therapy is unknown. OBJECTIVE: To determine factors influencing the extent and rate of INR reversal with vitamin K in the acute/critical care setting. METHODS: This was a chart review of 400 patients who received vitamin K for reversal of warfarin effects between February 2008 and November 2010. Data collected included international normalized ratios (INRs) 12 hours, 24 hours, and 48 hours prior to vitamin K administration; intravenous or oral vitamin K dose; and whether or not fresh frozen plasma (FFP) was administered. RESULTS: Intravenous vitamin K reduced INR more rapidly than oral vitamin K (5.09, 1.91, 1.54, and 1.41 vs 5.67, 2.90, 2.14, and 1.58) at baseline, 12, 24, and 48 hours, respectively. The dose of vitamin K (p < 0.001), route of administration (p < 0.001), and baseline INR (p < 0.001) influenced subsequent INR values. The INR reduction was similar for intravenous vitamin K doses 2 mg or greater. Home warfarin dose did not affect INR responses to intravenous (p = 0.27) or oral vitamin K (p = 0.98). FFP did not influence INR values at 48 hours. Although longer anticoagulation bridge therapy seemed to be associated with higher vitamin K doses, the incidence (p = 0.63) and duration (p = 0.61) were not significant. CONCLUSIONS: Vitamin K dose, route, and initial INR influence subsequent INR values. INR reduction is similar for intravenous vitamin K doses of 2 mg or greater. Preadministration of FFP does not alter INR values at 48 hours or more after vitamin K administration.