Anticoagulant Effect Of Warfarin Research Articles

Advances in warfarin's anticoagulation therapy in Chinese population after mechanical valve replacement

Warfarin is an irreplaceable oral anticoagulant for patients with mechanical heart valves, the stable pharmacogenetic-based warfarin dose prediction algorithms have improved the effectiveness and safety of warfarin anticoagulation therapy. Genetic factors are the main factors affecting the stable dose of warfarin. Single nucleotide polymorphisms such as VKORC1 and CYP2C9 affect the anticoagulation effect of warfarin through pharmacodynamic or pharmacokinetic pathways. Age, body surface area, combined use of drugs, and other nongenetic factors also affect the stable dose of warfarin. Previously published algorithms for warfarin dose prediction included mainly the white race, and most algorithms were constructed using traditional multiple linear regression. However, domestic studies have used machine learning methods to construct warfarin dose prediction algorithms based on the Chinese Han post-mechanical valve replacement population and have achieved better prediction efficiency. This article reviews the advances of warfarin anticoagulation influencing factors and the clinical application of stable dose prediction algorithms.

Integrated analysis of clinical and genetic factors on the interindividual variation of warfarin anticoagulation efficacy in clinical practice

AimThe anticoagulation effect of warfarin is usually evaluated by percentage of time in therapeutic range (PTTR), which is negatively correlated with the risk of warfarin adverse reactions. This study aimed to explore the effects of genetic and nongenetic factors on anticoagulation efficacy of warfarin during different therapeutic range.MethodsWe conducted an observational retrospective study aiming at evaluating the impact of clinical and genetic factors on PTTR from initial to more than six months treatment. This analysis included patients with heart valve replace (HVR) surgery who underwent long-term or life-long time treatment with standard-dose warfarin for anticoagulation control in Second Xiangya Hospital. All patients were followed for at least 6 months. We genotyped single nucleotide polymorphisms in VKORC1 and CYP2C9 associated with altered warfarin dose requirements and tested their associations with PTTR.ResultsA total of 629 patients with intact clinical data and available genotype data were enrolled in this study, and only 38.63% patients achieved good anticoagulation control (PTTR > 0.6). Clinical factors, including male gender, older age, overweight, AVR surgery and stroke history, were associated with higher PTTR. Patients with VKORC1 -1639AA genotype had significantly higher PTTR level compared with GA/GG genotype carriers only in the first month of treatment. Patients with CYP2C9*3 allele had higher PTTR compared with CYP2C9*1*1 carriers. Moreover, compared with VKORC1 -1639 AG/GG carriers, INR > 4 was more likely to be present in patients with AA genotype. The frequency of CYP2C9*1*3 in patients with INR > 4 was significantly higher than these without INR > 4.ConclusionWe confirmed the relevant factors of warfarin anticoagulation control, including genetic factors (VKORC1 -1639G > A and CYP2C9*3 polymorphisms) and clinical factors (male gender, older age, overweight, AVR surgery and stroke history), which could be helpful to individualize warfarin dosage and improve warfarin anticoagulation control during different treatment period.

Hypoglycemia possibly caused by CYP2C9-mediated drug interaction in combination with bucolome: a case report

BackgroundBucolome is a non-steroidal anti-inflammatory drug and uricosuric agent, currently used only in Japan. It is known to induce drug interactions by inhibiting cytochrome P450 (CYP) 2C9. It is often used to enhance the anticoagulant effect of warfarin by utilizing its drug interactions. There are only a few reports on drug interactions of bucolome and the mechanism remain poorly understood.Case presentationAn 81-year-old woman with a history of type 2 diabetes mellitus was taking glimepiride 2 mg/day and voglibose 0.6 mg/day. After hospitalization, the patient underwent surgical aortic valve replacement surgery (day 0). Glimepiride and voglibose were resumed on the second postoperative day (day 2), and warfarin was started to prevent thromboembolism. Since the prothrombin time-international normalized ratio on day 9 was low at 1.24, 300 mg/day of bucolome was added to enhance the effect of warfarin. A gradual decrease in blood glucose levels was observed from the day after bucolome administration was initiated. Hypoglycemia in the 56–57 mg/dL range occurred before lunch and dinner on the 6th day (day 14) of bucolome administration, due to which voglibose was discontinued. Hypoglycemia below 70 mg/dL was not observed thereafter, and the general condition of the patient was stable.ConclusionsBased on the clinical course and literature review, we believe that hypoglycemia in the present case was due to a drug interaction, caused by inhibition of CYP2C9 by bucolome and competitive inhibition of CYP2C9 by warfarin, which affected the pharmacokinetics of glimepiride. The possibility of hypoglycemia due to drug interactions should be considered by physicians, when bucolome is included to enhance the effect of warfarin, in patients taking glimepiride.

Effect of NPC1L1 polymorphism on warfarin stable dose in Chinese patients under heart valve replacement surgery.

Warfarin is the most often anticoagulant choice for preventable thromboembolism. Notably, vitamin K plays a vital role in the process of warfarin's anticoagulant effect. Therefore, we presume NPC1L1, a key transporter of vitamin K (VK) intestinal absorption, may modulate the anticoagulant effect of warfarin. Studies have shown that NPC1L1(-762T>C, rs2073548) and p53 (P72R, rs1042522) variations are implicated in influencing NPC1L1 expression. This study aimed to assess the association between these two variants and warfarin stable dose (WSD). A two-stage extreme phenotype design was used to explore the influence of these two variants (rs2073548, rs1042522) on WSD variance in 655 Chinese patients undergoing heart valve replacement surgery. NPC1L1 rs2073548, p53 rs1042522, VKORC1 rs9923231 and CYP2C9*1/*3 polymorphisms were genotyped by polymerase chain reaction-restriction fragment polymorphism (PCR-RFLP) or Sanger sequencing, respectively. WSD was identified when target monitoring international normalized ratio (INR) value at 2.0-3.0. In the discovery phase, NPC1L1 rs2073548 A allele carriers occupied a significantly higher rate in the low dose group (P=.019). However, in the validation group, warfarin dosage in patients with the rs2073548 AA, AG and GG genotypes were 2.91±0.97mg/day, 3.02±1.00mg/day and 3.00±1.06mg/day, respectively. Multiple linear regression analysis results suggested that CYP2C9*3 and VKORC1 rs9923231, but not NPC1L1 rs2073548, were independent predictors of WSD in Chinese heart valve replacement (HVR) surgical patients.

Pemafibrate does not affect the anticoagulant effect of warfarin

Pemafibrate does not affect the anticoagulant effect of warfarin

Analysis of the application and anticoagulant effect of warfarin on inpatients

Analysis of the application and anticoagulant effect of warfarin on inpatients

Decrease in Efficacy of Warfarin as a Result of Drug-Drug Interaction (Case Report)

The one of the main aims in modern clinical pharmacology is to provide safe and effective therapy considering a frequent administration of several drugs having different drug-drug interactions. Warfarin belongs to the number of popular anticoagulants which along with its efficiency not infrequently alters anticoagulant characteristics when administered with other drugs and food products. A case of a decrease in the efficacy of warfarin in a patient with mitral stenosis while taking a combined choleretic drug is presented in the article. The components of this choleretic drug (dry animal bile, dry garlic extract, dry nettle extract, activated charcoal) could impair the absorption of warfarin, increase intestinal absorption of vitamin K, and have a negative effect on the anticoagulant effect of warfarin. Management of patients receiving anticoagulants should be performed in accordance with clinical recommendations. Prescription of drugs, including multicomponent ones, without proven efficacy, for such patients should be considering the potential drug interaction.

The Effect of Warfarin Administration Time on Anticoagulation Stability (INRange): A Pragmatic Randomized Controlled Trial.

Without supporting evidence, clinicians commonly recommend that warfarin be taken in the evening. We conducted a randomized controlled trial to evaluate the effect of administration time (morning vs evening) on the stability of warfarin's anticoagulant effect. A total of 236 primary care physicians serving 54 western Canadian communities mailed letters of invitation to all their warfarin-using patients. Eligible patients were community-dwelling warfarin users (any indication) with at least 3 months of evening warfarin use and no plans for discontinuation. Participants were randomized (by web-based allocation) to morning vs continued evening warfarin ingestion. We used the Rosendaal method to determine the proportion of time within therapeutic range (TTR) of the international normalized ratio (INR) blood test month 2 to 7 postrandomization vs the 6 months prerandomization. The primary outcome was the percent change in proportion of time outside target INR range (with an a priori minimum clinically important difference of ±20%). All analyses were intention to treat. Between March 8, 2015 and September 30, 2016, we randomized 109 participants to morning and 108 to evening warfarin use. TTR rose from 71.8% to 74.7% in the morning group, and from 72.6% to 75.6% in the evening group, for a change in TTR of 2.9% in the former vs 3.0% in the latter (difference, -0.1%; P = .97; 95% CI for the difference, -6.1% to 5.9%). The difference in percent change in proportion of time outside the therapeutic INR range (obtained via Hodges-Lehmann estimation of the difference in medians) was 4.4% (P = .62; 95% CI for the difference, -17.6% to 27.3%). Administration time has no statistically significant nor clinically important impact on the stability of warfarin's anticoagulant effect. Patients should take warfarin whenever regular compliance would be easiest.

Validation of an algorithm to predict decline in INR following warfarin cessation in patients undergoing invasive procedures

Patients on warfarin are required to withdraw from treatment for a fixed period (normally 5 days) prior to an invasive procedure. However, the anticoagulant effect of warfarin subsides at different rates among different patients, exposing some to increased risk of either thrombosis or bleeding. In a recent study in patients awaiting surgery, following warfarin cessation the INR declined slower over time in those with two CYP2C9 variant alleles, increasing age, weight and number of comorbidities and that INR decline was faster in those with higher maintenance INR value. Subsequently, we developed an algorithm which predicts INR decline in individual patients after 5 days of warfarin cessation. The current study validated the algorithm. An independent cohort of patients completing a short course of warfarin took part in the study. INR values for subsequent 9 days and CYP2C9 genotype were available. The predicted INR decline (INRday 1–INRday 5) was compared to the observed one (where an INR check on day 5 was unavailable, INR was estimated using a linear approximation model). There was a strong correlation between the decline in INR by day 5 and that predicted from the algorithm for the 117 patients (r = 0.949, p < 0.001). The algorithm was precise, with low degree of bias and variance of the prediction error. The algorithm can accurately predict the INR decline following warfarin cessation in individual adult patients. The use of this easily adoptable algorithm can reduce cancellation or delays of planned surgical procedures.

A study to evaluate herb-drug interaction underlying mechanisms: An investigation of ginsenosides attenuating the effect of warfarin on cardiovascular diseases

Warfarin and ginseng have been widely used in the treatment of cardiovascular diseases. However, the clinical safety and effectiveness of herb-drug combination treatment are still controversial. Therefore, it is very essential to probe the interaction between warfarin and ginseng. In this study, in vitro and in vivo study was carried out to demonstrate that whether there is an interaction between warfarin and ginsenosides (GS), which is the main component of ginseng. In vitro study showed that the adhesion ability between endothelial cells and matrigel/platelets was enhanced due to the up-regulating expression of intercellular adhesion molecule (ICAM-1) and vascular cell adhesion molecule (VCAM-1) proteins by treatment of warfarin+GS combination compared to warfarin/GS treatment alone. Moreover, GS could weaken the anticoagulation effect of warfarin in hyperlipemia rats owning to the increased expression levels of coagulation factors and hepatic cytochrome P450 enzymes in plasma after long-term co-administration of warfarin with GS. The results of both in vitro and in vivo study demonstrated that there is a serious interaction between warfarin and ginseng, which may deteriorate atherosclerosis and thrombosis after combined use of warfarin and GS.

Impact of genetic and clinical factors on warfarin therapy in patients early after heart valve replacement surgery.

Factors influencing responsiveness to warfarin at treatment onset time were not well identified in Chinese patients undergoing heart valve replacement. We sought to select the most relevant factors that associated with patient response to warfarin early after heart valve surgery. In this observational study, 289 patients starting warfarin therapy early after heart valve replacement surgery were enrolled. CYP2C9 *1, *2, *3, and *5; VKORC1-1639 G>A, CYP4F2 V433M, and GGCX rs11676382 genotypes; clinical characteristics, response to therapy, and bleeding and thrombosis events were collected. The primary outcomes were the time to the first INR equal to or more than lower limit of therapeutic range and the warfarin dose requirements. Stepwise multiple linear regression was performed to develop a dosing algorithm to predict the warfarin dose requirements. The results of univariate analysis showed lone VKORC1-1639 G>A, CYP2C9 *1/*3, cefazolin, cefoperazone-sulbactam, increased BMI, Δhemoglobin, and white blood cell count could significantly affect patient responsiveness to warfarin in the initial period of anticoagulation. Multivariate analysis resulted in an equation: Accumulated warfarin doses (mg) = 17.068 VKORC1-1639 G>A - 4.261 hypertension + 0.593 BMI - 0.115 age - 4.852 CYP2C9 *1/*3 - 2.617 cefazolin - 4.902 cefoperazone-sulbactam - 4.537, which could explain 40.2% of the variability in warfarin dose needed to reach the first INR equal to or more than lower limit of therapeutic range. Both genetic and clinical factors contributed to anticoagulation effect of warfarin in the initial period of treatment. Our findings could provide a basis for the personalized management of warfarin use in the early stage of anticoagulation in northern Chinese patients.

Evaluation of the effects of ontogenetic or maturation functions and chronic heart failure on the model analysis for the dose-response relationship of warfarin in Japanese children.

We previously demonstrated that the rational pediatric dosage of warfarin can be well-described by a SIZE parameter that includes an allometry exponent of weight. On the other hand, allometry alone is considered to be insufficient to predict drug clearance in neonates and infants. The primary purpose of the present study was to evaluate the effects of incorporation of the maturation process into the analysis model for the dose-response relationship of warfarin in Japanese children. In addition, we evaluated the effect of chronic heart failure (CHF) on the response to warfarin as an independent risk factor for increased anticoagulant effects. Thirty-eight patients with stable anticoagulation by warfarin were enrolled. During a mean follow-up period of 4.74 ± 3.51years, 1092 data points including prothrombin time-international normalized ratio (PT-INR) were obtained. The data were subjected to multiple regression analysis to identify covariates related to the anticoagulant effects. Two different models describing the maturation process did not improve the predictive performance for the dose-response relationship in pediatric patients. In addition to the SIZE-normalized daily dose, the vitamin K epoxide reductase complex 1 (VKORC1) genotype, and concomitant use of bosentan, CHF was identified as a covariate increasing the anticoagulant effects of warfarin to 118%. The SIZE parameter was useful even without incorporation of maturation models to describe the response to warfarin in pediatric patients, and our longitudinal follow-up study design with multiple observations was beneficial to detect changes within individual subjects.

Interaction between warfarin and short-term intravenous amiodarone in intensive care unit patients after cardiac surgery

BackgroundAmiodarone and warfarin are sometimes administered immediately after cardiac surgery. Although the interaction between long-term oral amiodarone and warfarin has been reported, the interaction between warfarin and short-term intravenous amiodarone has not been reported. In this study, we investigated the effect of short-term intravenous amiodarone on the anticoagulant effect of warfarin in patients who underwent cardiac surgery.MethodsWe retrospectively reviewed the medical records of 11 patients who received oral warfarin before and after cardiac surgery, and loading doses of 125–150 mg or a 750 mg continuous infusion of amiodarone, or both in the intensive care unit (ICU) within 5 days after the surgery between July 2011 and January 2017. The prothrombin time-international normalized ratio (PT-INR)/daily warfarin dose (PT-INR/dose) was used as an indicator of anticoagulant effect. The values before surgery were considered as the baseline.ResultsThe PT-INR and PT-INR/dose values were elevated in 7 and 10 patients, respectively, after amiodarone administration. The mean PT-INR values were not significantly different before and after amiodarone administration (2.13 ± 0.58 vs 2.29 ± 0.50, respectively, p = 0.643). In contrast, the mean PT-INR/dose values were significantly elevated after the administration of amiodarone (0.93 ± 0.46 vs 1.54 ± 0.63, respectively, p = 0.002).ConclusionsShort-term intravenous amiodarone enhanced the anticoagulant effect of warfarin in patients admitted to the ICU after cardiac surgery. We suggest that the dose of warfarin should be carefully adjusted for a few days after cardiac surgery if intravenous amiodarone is coadministered.

Warfarin monitoring with viscoelastic haemostatic assays, thrombin generation, coagulation factors and correlations to Owren and Quick prothrombin time

The anticoagulant warfarin is commonly monitored with prothrombin time (PT). Viscoelastic haemostatic assays (VHA) are primarily used in situations of acute bleeding to guide haemostatic therapy. Much research has focused on VHA monitoring of new oral anticoagulants. However, many patients are still anticoagulated with warfarin and effect of warfarin anticoagulation on VHA is uncertain. The aim of this study was to assess warfarin anticoagulation on three different VHA and compare these findings with prothrombin time (PT), coagulation factor analyses and a thrombin generation assay (TGA). Citrated whole blood was drawn from 80 patients admitted for routine PT-INR Owren. VHA analysis with ROTEM (EXTEM, INTEM and FIBTEM), ReoRox (Fibscreen 1 and 2) and Sonoclot (gbACT+) was performed. Blood was also drawn for plasma analysis with PT (PT-INR Owren and PT Quick), TGA and analysis of factors I, II, VII, IX and X. Extrinsically activated VHA, including ROTEM EXTEM and FIBTEM Clotting Time (CT) and ReoRox Fibscreen1 and 2 clot onset time 1 correlated moderately with PT-INR Owren , with R 0.66–0.71. These four variables were likely to be prolonged above reference interval in patients with prolonged PT-INR Owren >1.2. Two patients with normal ROTEM CTs had Owren PT-INRs >1.5. Warfarin affects extrinsically activated VHA variables of initial clotting. The role of VHA for clinical decision-making in patients planned for invasive procedures, such as spinal/epidural anaesthesia needs further study. None of the recent guidelines on regional anaesthesia include VHA testing to define adequate haemostasis.

Warfarin Dose Adjustment After Biliopancreatic Diversion/Duodenal Switch Bariatric Surgery.

The absorption of drugs and fat-soluble vitamins is impaired after bariatric surgery on which intestinal length and function are altered. In this context, the anticoagulant effect of warfarin is difficult to predict in the postoperative period. This study aimed at describing the average weekly warfarin dose required to maintain a therapeutic international normalized ratio (INR) before and up to 1 year after sleeve gastrectomy with biliopancreatic diversion and duodenal switch (BPD/DS). Secondary end points included the number of patients requiring a minimal 20% reduction in their weekly dose of warfarin following the BPD/DS. This descriptive and retrospective longitudinal population study included 20 patients using warfarin who underwent BPD/DS. An INR was considered nontherapeutic if it was below or above 15% of the targeted therapeutic range for any given patient. One month after the surgery, the median weekly dose of warfarin was 55% lower than the preoperative dose ( P < 0.0001). In the 9 patients with full follow-up data, the warfarin dose at 1 year was still 39% lower than the preoperative dose ( P < 0.05). At that time, all patients presented a minimal dose reduction of 20%. BPD/DS robustly reduced the requirement of warfarin, which resulted in lower doses after surgery. This persisted over the first year after the surgery, likely because of enhanced sensitivity. The mechanisms for this effect remain multifactorial, and the exact extent of change in dose cannot be predicted.

Ischemic stroke in an elderly patient on apixaban

Mr. LPH, an 86 year old patient taking warfarin for atrial fibrillation (AF) is admitted for a vertebral fracture. His calculated CHADSs score was of 6. A suboptimal control of diabetes was detected. Metformin and glyburide were increased. Four days after discharge, Mr. LPH was readmitted due to diarrhea and hyperglycemia. Metformin was discontinued. Glyburide dose was adjusted. INR dosage results fluctuated during hospital stay over and under therapeutic values. Warfarin was discontinued and apixaban 2.5 mg twice daily was started. Mr. LPH was later admitted for a pulmonary severe sepsis. His infection was complicated by two AF episodes. After the last episode, Mr. LPH presented dysarthria, facial asymmetry and left hemiparesis. On the cerebral scan, we observed a right Sylvian artery stroke. Conclusion: In this case, the 2.5 mg apixaban dose was used and may explain the stroke. It occurred after two consecutive AF episodes making it the most likely cause. The choice of the low drug dosage may have been in response to caution and patient frailty. The patient was stable on warfarin for the past 14 years and the fluctuating INR episode can be explained by drug interaction. Glyburide may enhance the anticoagulation effect of warfarin.

Effects of safflower injection on the pharmacodynamics and pharmacokinetics of warfarin in rats

1. Safflower injection (SI) is extracted from Chinese herbal medicine safflower that comprises many active components. Warfarin is a common anticoagulant and has exhibited drug interactions with several herbal products. This study aimed to investigate the effects of SI on pharmacodynamics and pharmacokinetics of warfarin in rats.2. Wistar rats were randomly divided into blank control group, SI group, warfarin control group and SI + warfarin group, respectively. In SI and SI + warfarin groups, rats were injected with SI (1.6 mL/kg/d, i.p.) for 14 days. Warfarin (0.2 mg/kg) was given orally on the eighth day. Saline was given as control. The blood samples were collected at various time points. Prothrombin time (PT) and activated partial thromboplastin time (APTT) were measured. UPLC-MS/MS was used to determine the plasma concentrations of S(R)-warfarin, and the pharmacokinetic parameters were calculated.3. PT, APTT in SI and SI + warfarin rats increased significantly compared with corresponding control rats. The pharmacokinetic parameters including Cmax, t1/2, AUC0-t and AUC0-∞ of S-warfarin and R-warfarin in SI + warfarin rats were higher than those in warfarin control rats.4. These findings suggest that SI significantly increases the anticoagulant effect of warfarin by affecting its pharmacodynamic and pharmacokinetic parameters.

A retrospective study on the risk factors for bleeding events in warfarin therapy, focusing on renal function

The anticoagulant effect of warfarin used to treat stroke has been shown to vary with the concomitant use of medications and comorbidity. Concomitant use of antithrombotic drugs and underlying chronic kidney disease (CKD) represent risk factors for bleeding events. We conducted a comprehensive investigation of the background characteristics and concomitant use of drugs to identify the risk factors for warfarin-related bleeding, focusing on renal function. The study population consisted of patients prescribed warfarin at the Tokyo Women's Medical University Hospital. A retrospective review of the patient data, including bleeding events, bleeding sites, the patient's background, concomitant use of drugs, and laboratory data was carried out, and the incidence of bleeding events was compared in patient groups stratified according to CKD stage and antithrombotic drug use. Multivariate logistic regression analysis was performed to determine the risk factors for warfarin-related bleeding. Of the 3,831 patients included in the study, the incidence of warfarin-related bleeding was 3.0 events per 100 patient-years. The multivariate logistic regression analysis identified age>65years, body mass index (BMI), alanine aminotransferase (ALT), estimated glomerular filtration rate (eGFR) <30mL/min/1.73m2, prothrombin time-international normalized ratio (PT-INR), and concomitant use of antithrombotic drugs as risk factors for warfarin-related bleeding. The present analyses identified age>65years, BMI, ALT, eGFR <30mL/min/1.73m2, PT-INR, and concomitant use of antithrombotic drugs as independent risk factors for warfarin-related bleeding. We should pay attention to the risk factors associated with warfarin-related bleeding when prescribing warfarin in patients with renal impairment.

The anticoagulant effects of warfarin and the bleeding risk associated with its use in patients with chronic thromboembolic pulmonary hypertension at a specialist center in Japan: a retrospective cohort study.

Patients with chronic thromboembolic pulmonary hypertension (CTEPH) require lifelong anticoagulation therapy. However, the bleeding risk and recurrence of venous thromboembolism (VTE) in CTEPH patients who are administered warfarin have not been adequately evaluated. The purpose of this study was to evaluate the risk of clinically relevant bleeding, recurrent VTE, and clinical worsening in patients with CTEPH who were administered warfarin.The clinical records of 72 patients with CTEPH who regularly visited our institution and were administered warfarin were retrospectively reviewed between 1 January 2011 and 31 December 2015. We investigated the incidence of clinically relevant bleeding events, recurrent VTE, and hospitalization for the deterioration of pulmonary hypertension or right heart failure (RHF) during the observation period.The mean observation period for the 72 patients was 3.60 ± 1.60 person-years. Clinically relevant bleeding, RHF, and recurrent VTE occurred in 21 (29.2%), eight (11.1%), and three (4.2%) of 72 patients, respectively, and the incidence rates for these events were 8.1%/person-year, 3.1%/person-year, and 1.2%/person-year, respectively. The incidence rates for the major and non-major bleeding events were 5.0%/person-year and 3.9%/person-year, respectively. The incidence of clinically relevant bleeding events was 20.8%/person-year during medical treatment with a soluble guanylate cyclase stimulator. One of 35 patients (2.9%) during the post-pulmonary endarterectomy period experienced hemoptysis during observation period (> 6 months after pulmonary endarterectomy). No bleeding events occurred during the post-balloon pulmonary angioplasty period.In conclusion, warfarin effectively prevents VTE recurrence in CTEPH patients, but its effects may be associated with a considerable bleeding risk.

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.