vitamin-k-semiquinone-radical and Hypertension--Pulmonary

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Fibrinolytic Agents; Humans; Hypertension, Pulmonary; Vitamin K

Pulmonary hypertension (PH), in particular pulmonary arterial hypertension and chronic thromboembolic PH, burdens patients with relevant morbidity and mortality. The use of oral anticoagulants (OACs) seems able to mitigate the risk of adverse outcomes and death in these patients. Despite scarce evidence, the use of OAC is recommended to treat PH patients, mainly based on observational data. So far, data are still unclear about the impact of direct oral anticoagulant (DOACs), whereas vitamin K antagonists are the main drugs recommended. More data are needed to fully clarify the role of OAC and DOACs in PH patients.

Topics: Administration, Oral; Anticoagulants; Fibrinolytic Agents; Humans; Hypertension, Pulmonary; Vitamin K

Life-long anticoagulation is the recommended management for chronic thromboembolic pulmonary hypertension (CTEPH). Evidence regarding the use of direct oral anticoagulants (DOAC) for CTEPH is yet to be established. We performed a systematic review and meta-analysis to clarify the outcomes of CTEPH in patients who used DOAC or vitamin K antagonists (VKA).. We reviewed literature in PubMed and EMBASE through March 2023. We included studies involving patients with CTEPH where DOAC and VKA were compared. We collected data including intervention history for CTEPH, bleeding events, recurrence of VTE (venous thromboembolism), and mortality. We performed a meta-analysis using the Mantel-Haenszel method with a fixed-effects model.. We included one randomized clinical trial and six observational studies, with a total of 2969 patients. Six studies investigated major bleeding outcomes, and seven investigated all bleeding outcomes. There were no differences in major bleeding (RR 0.59, 95 % CI [0.34-1.02], I. DOAC compared to VKA was associated with a significantly lower mortality and higher risk of recurrent PE. Since most of the included studies are observational, we must consider the existence of multiple biases and confounding factors.

Topics: Administration, Oral; Anticoagulants; Blood Coagulation; Fibrinolytic Agents; Hemorrhage; Humans; Hypertension, Pulmonary; Pulmonary Embolism; Randomized Controlled Trials as Topic; Venous Thromboembolism; Vitamin K

Direct oral anticoagulants (DOACs) are being increasingly used in patients with chronic thromboembolic hypertension (CTEPH), however, the data on their safety and efficacy are scarce and contradictory. We systematically searched MEDLINE and Google Scholar databases from January 2010 to January 2021 for studies of DOACs in CTEPH. Three observational studies, 2 abstracts and one case series met our inclusion criteria. While these studies reported similar or even less rates of major bleeding in patients receiving DOACs compared with vitamin K antagonists, there were concerns about the possibility of increased risk of venous thromboembolism recurrence with DOAC therapy. Further studies are warranted to better define the role of DOACs in CTEPH.

Topics: Administration, Oral; Anticoagulants; Hemorrhage; Humans; Hypertension, Pulmonary; Venous Thromboembolism; Vitamin K

Chronic thromboembolic pulmonary hypertension (CTEPH) represents the later stage consequence of at least one or more unresolved episodes of acute pulmonary embolism; thus, indefinite anticoagulation is strongly recommended by current practice guidelines. Historically, vitamin K antagonists have been widely used in these patients. However, recent data indicate a shift toward direct oral anticoagulants (DOACs), despite lack of data on the safety and efficacy in this patient population. Herein, we briefly discuss the current rationale for oral anticoagulation use in CTEPH, addressing important issues and controversies involved with the use of DOACs, opening a strategy for further clinical research in the field of oral anticoagulation.

Topics: Administration, Oral; Anticoagulants; Humans; Hypertension, Pulmonary; Pulmonary Embolism; Venous Thromboembolism; Vitamin K

Pulmonary hypertension (PH) comprises a cluster of severe conditions characterized by elevated mean pulmonary arterial pressure. While targeted therapies have been approved over the last twenty years for pulmonary arterial hypertension (PAH) and chronic-thrombo-embolic PH (CTEPH), the possible role of anticoagulant therapy as a supportive treatment PAH is still debated. In PAH, anticoagulant use remains frequent, although evidence appear to be poor (recommendation class IIb-C in international guidelines). In CTEPH treatment, anticoagulants are highly recommended, because it often involves thrombosis (recommendation class I-C in international guidelines). Historically, PH patients have been treated with vitamin K antagonists (VKA), which are the only available oral anticoagulants. In this context, risk/benefit ratio of VKA is affected by the risk of major bleeding events. This drawback could be mitigated with direct oral anticoagulants (DOACs): in addition to being less constraining for patients, DOACs have shown a lower risk of major bleeding events in their already approved indications (venous thromboembolism, atrial fibrillation). However, DOACs have never been specifically assessed in PAH and CTEPH patients. Bioaccumulation risk should be considered if DOACs are prescribed in PAH and CTEPH patients, especially the risk of drug-drug interaction mediated by P-glycoprotein and cytochrome 3A4 with targeted therapies.

Topics: Administration, Oral; Anticoagulants; Female; Humans; Hypertension, Pulmonary; Male; Risk Factors; Vitamin K

In this review, we present some different and special conditions that are generally being treated with anticoagulants such as cerebral vein thrombosis (CVT), mesenteric vein thrombosis (MVT), Budd-Chiari syndrome (BCS), and Pulmonary Hypertension (PH) despite the lack of controlled clinical trials. While either low molecular weight heparins (LMWHs) or unfractioned heparin (UFH) are used in the acute phase of the first three conditions, the potential chronic use of warfarin in PH is controversial. What is not completely known in the management of CVT, MTV, and BCS is whether (a) LMWHs are similar to UFH in terms of efficacy and safety, and (b) a fibrinolytic drug could be employed in the acute phase. The timing at which warfarin should be started, and the duration of its employment are two additional crucial points that deserve to be examined. In the course of PH, the role of warfarin is controversial, but it could be employed after a careful balance of the hemorrhagic and thromboembolic risk. In conclusion, we tried to simplify the approach to this sometimes problematic task considering the available literature with the aim of providing some practical skills to be used by physicians in their daily clinical practice. Since it is improbable that in the future controlled clinical trials will be designed to find the optimal anti-thrombotic management of these conditions, we believe that a physician should be aware of the lack of solid data in the field but at the same time should always exert clinical judgment when considering an aggressive anticoagulant approach. The duration of oral anticoagulant treatment is left to the clinical judgment of the balance between the hemorrhagic and thrombotic risks in any single patient.

Topics: Anticoagulants; Chronic Disease; Decision Making; Female; Follow-Up Studies; Humans; Hypertension, Pulmonary; Intracranial Thrombosis; Male; Mesenteric Vascular Occlusion; Mesenteric Veins; Patient Selection; Risk Assessment; Treatment Outcome; Vitamin K

Pulmonary embolism (PE) is common and the majority of patients survive the acute event. Survivors are at increased risk for adverse outcomes, including persistent thrombi, recurrent embolism, chronic thromboembolic pulmonary hypertension (CTEPH), and death. Anticoagulation protects against recurrence, which has a high mortality rate. The recommended duration of anticoagulation for patients with reversible PE risk factors is 3 months. For patients with idiopathic PE or persistent risk factors, extended duration of anticoagulation is preferred, balanced with an individual patient's risk of hemorrhage, which in itself is a major cause of morbidity and mortality. Among patients with malignancy who develop venous thromboembolism (VTE), low-molecular-weight heparin is preferred over oral vitamin K antagonists in the first 6 months. Thereafter, anticoagulation should be continued indefinitely with either low-molecular-weight heparin or oral vitamin K antagonists. Inferior vena cava filters are not routinely recommended and should only be used in patients who have a contraindication to anticoagulation. Patients who have had VTE and with persistent or recurrent dyspnea should be evaluated for recurrence of VTE or development of CTEPH. Patients with recurrent VTE should be anticoagulated indefinitely. Routine screening for CTEPH in asymptomatic patients is not recommended. Echocardiography often provides the first indication of the presence of pulmonary hypertension. Once presence of CTEPH is established by right-sided heart catheterization and perfusion imaging (ie, ventilation/perfusion scintigraphy, computed tomography angiography, or pulmonary angiography), patients should be referred early to a center with expertise, as it is potentially surgically curable by pulmonary endarterectomy. Those who are deemed inoperable after being evaluated may gain symptomatic benefit from drugs approved for idiopathic pulmonary arterial hypertension. Lung transplantation may also be an option for patients who are not candidates for pulmonary endarterectomy.

Topics: Anticoagulants; Blood Coagulation Tests; Chronic Disease; Drug Administration Schedule; Dyspnea; Heparin, Low-Molecular-Weight; Humans; Hypertension, Pulmonary; Neoplasms; Pulmonary Embolism; Risk Factors; Vena Cava Filters; Venous Thrombosis; Vitamin K

The optimal course of oral anticoagulant therapy is determined according to the risk of recurrent venous thromboembolism after stopping therapy and the risk of anticoagulant-related bleeding. Clinical risk factors appear to be important in predicting the risk of recurrence whereas the influence of biochemical and morphological tests is uncertain. The risk of recurrent venous thromboembolism is low when the initial episode was provoked by a reversible major risk factor (surgery): 3 months of anticoagulation is sufficient. Conversely, the risk is high when venous thromboembolism was unprovoked or associated with persistent risk factor (cancer): 6 months or more prolonged anticoagulation is necessary. After this first estimation, the duration of anticoagulation may be modulated according to the presence or absence of certain additional risk factors (major thrombophilia, chronic pulmonary hypertension, massive pulmonary embolism): 6 months if pulmonary embolism was provoked and 12 to 24 months if pulmonary embolism was unprovoked. If the risk of anticoagulant-related bleeding is high, the duration of anticoagulation should be shortened (3 months if pulmonary embolism was provoked and 3 to 6 months if it was unprovoked). Lastly, if pulmonary embolism occurred in association with cancer, anticoagulation should be conducted for 6 months or more if the cancer is active or treatment is on going. Despite an increasing knowledge of the risk factors for recurrent venous thromboembolism, a number of issues remain unresolved. Randomised trials comparing different durations of anticoagulation are needed.

Topics: Age Factors; Anticoagulants; Antiphospholipid Syndrome; Cohort Studies; Drug Administration Schedule; Female; Fibrin Fibrinogen Degradation Products; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Hypertension, Pulmonary; Male; Neoplasms; Prospective Studies; Pulmonary Embolism; Randomized Controlled Trials as Topic; Recurrence; Risk Factors; Sex Factors; Thrombophilia; Time Factors; Vena Cava Filters; Venous Thrombosis; Vitamin K

Despite limited evidence from clinical studies, anticoagulant drugs such as vitamin K antagonists (VKA) (e.g., warfarin or phenprocoumon) are widely used in the background treatment of patients with pulmonary arterial hypertension (PAH). According to current guidelines, they are generally accepted as efficacious drugs, although their efficacy is neither supported by randomised controlled trials, nor formally approved by regulatory agencies for use in the specific PAH indication. The use of these drugs is not without problems, as a paradoxical situation has to be managed in the treatment of this condition. On one hand, thrombosis is one of the key pathophysiologic features of PAH (besides vasoconstriction, proliferation and inflammation). On the other hand, the incidence of bleeding events is increased in PAH patients. This applies particularly to PAH that is related to connective tissue diseases, congenital heart disease and chronic thromboembolic pulmonary hypertension. In patients receiving VKA, caution must be observed in particular when concomitantly using prostanoids or sildenafil. Similarly, VKA doses have to be adjusted according to the labelling when using sitaxentan concomitantly. Regular International Normalized Ratio monitoring contributes to the safety of PAH patients on VKA.

Topics: Anticoagulants; Antihypertensive Agents; Endothelin Receptor Antagonists; Hemorrhage; Humans; Hypertension, Pulmonary; Thrombosis; Vitamin K

Chronic thromboembolic pulmonary hypertension (CTEPH) is a complication of prior pulmonary thromboembolism (PE), caused by incomplete clot dissolution after PE. In patients with CTEPH, lifelong anticoagulation is mandatory to prevent recurrence of PE and secondary in situ thrombus formation. Warfarin, a vitamin K antagonist, is commonly used for anticoagulation in CTEPH based on historical experience and evidence. The anticoagulant activity of warfarin is affected by food and drug interactions, requiring regular monitoring of prothrombin time. The lability of anticoagulant effect often results in haemorrhagic and thromboembolic complications. Thus, lifelong warfarin is a handicap in terms of safety and convenience. Currently, the use of direct oral anticoagulants (DOACs) in CTEPH has increased with the advent of four DOACs. The safety of DOACs is superior to warfarin, with less intracranial bleeding in patients with non-valvular atrial fibrillation and venous thromboembolism. Edoxaban, the latest DOAC, also has proven efficacy and safety for those diseases in two large clinical trials; the ENGAGE-AF trial and HOKUSAI-VTE trial. The present trial seeks to evaluate whether edoxaban is non-inferior to warfarin in preventing worsening of CTEPH.. The KABUKI trial (is an investigator-initiated, multicentre, phase 3, randomised, single-blind, parallel-group, warfarin-controlled, non-inferiority trial to evaluate the efficacy and safety of edoxaban versus warfarin (vitamin K Antagonist) in subjects with chronic thromBoembolic pUlmonary hypertension taking warfarin (vitamin K antagonIst) at baseline) is designed to prove the non-inferiority of edoxaban to warfarin in terms of efficacy and safety in patients with CTEPH.. This study is approved by the Institutional Review Board of each participating institution. The findings will be published in a peer-reviewed journal, including positive, negative and inconclusive results.. NCT04730037.. This paper was written per the study protocol V.4.0, dated 29 January 2021.

Topics: Anticoagulants; Atrial Fibrillation; Humans; Hypertension, Pulmonary; Multicenter Studies as Topic; Randomized Controlled Trials as Topic; Single-Blind Method; Stroke; Venous Thromboembolism; Vitamin K; Warfarin

Chronic thromboembolic pulmonary hypertension (CTEPH) remains an underdiagnosed disease. Anticoagulation is essential in its therapy to prevent recurrent venous thromboembolism (VTE). According to some international guidelines, vitamin K antagonists (VKA) remain the gold standard. Nevertheless, direct oral anticoagulants (DOAC) are widely used, partly because of numerous advantages. The objective of this study was to determine if DOAC is an effective and safe alternative to VKA in CTEPH patients.. A retrospective observational study was conducted between 2001 and 2021 in a CTEPH Clinic of a tertiary care hospital. We recorded demographic characteristics, anticoagulant therapies and pulmonary hypertension treatments received. Safety outcomes were bleeding events and deaths while efficacy outcomes were recurrent VTE events.. Among the study population (N = 205), the distribution of anticoagulant used transitioned from majority on VKA to majority on DOAC. In 2020, 23 (19 %) were on VKA and 97 (78 %) on DOAC. Among 11 VTE events occurring during follow-up, 7 were in the VKA group (1.10 %/person-year) and 1 in the DOAC group (0.32 %/person-year). Rates of VTE recurrence were not significantly different in those treated with DOAC compared to VKA (P = 0.21). Total bleeding rate on VKA (2.52 %/person-year) and DOAC (2.52 %/person-year) were the same (P = 1.00). Among 27 patients who died, no deaths occurred as a consequence of bleeding or VTE events.. Bleeding and VTE events were not higher in CTEPH patients receiving DOAC compared to VKA which adds confidence to considering DOAC as an effective and safe alternative for long term anticoagulation in CTEPH patients.

Topics: Administration, Oral; Anticoagulants; Blood Coagulation; Fibrinolytic Agents; Hemorrhage; Humans; Hypertension, Pulmonary; Venous Thromboembolism; Vitamin K

EXPERT was an international, multicenter, prospective, uncontrolled, non-interventional cohort study in patients with pulmonary hypertension treated with riociguat. Patients were followed for 1-4 years, and the primary outcomes were adverse events (AEs) and serious AEs (SAEs), including embolic/thrombotic and hemorrhagic events. Here we report data on patients with chronic thromboembolic pulmonary hypertension (CTEPH) receiving a vitamin K antagonist (VKA; n = 683) or a non-vitamin K antagonist oral anticoagulant (NOAC; n = 198) at baseline. AEs and SAEs were reported in 438 patients (64.1%) and 257 patients (37.6%), respectively, in the VKA group, and in 135 patients (68.2%) and 74 patients (37.4%) in the NOAC group. Exposure-adjusted hemorrhagic event rates were similar in the two groups, while exposure-adjusted embolic and/or thrombotic event rates were higher in the NOAC group, although the numbers of events were small. Further studies are required to determine the long-term effects of anticoagulation strategies in CTEPH.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Cohort Studies; Hemorrhage; Humans; Hypertension, Pulmonary; Prospective Studies; Vitamin K

Chronic thromboembolic pulmonary hypertension (CTEPH) is an uncommon complication of acute pulmonary emboli necessitating lifelong anticoagulation. Despite this, few data exist on the safety and efficacy of vitamin K antagonists (VKAs) in CTEPH and none for direct oral anticoagulants (DOACs).. To evaluate outcomes and complication rates in CTEPH following pulmonary endarterectomy (PEA) for individuals receiving VKAs or DOACs.. Consecutive CTEPH patients undergoing PEA between 2007 and 2018 were included in a retrospective analysis. Postoperative outcomes, recurrent venous thromboembolism (VTE), and bleeding events were obtained from patient medical records.. Seven hundred ninety-four individuals were treated with VKAs and 206 with DOACs following PEA. Mean observation period was 612 (standard deviation: 702) days. Significant improvements in hemodynamics and functional status were observed in both groups following PEA (P < .001). Major bleeding events were equivalent (P = 1) in those treated with VKAs (0.67%/person-year) and DOACs (0.68%/person-year). The VTE recurrence was proportionately higher (P = .008) with DOACs (4.62%/person-year) than VKAs (0.76%/person-year), although survival did not differ.. Post-PEA functional and hemodynamic outcomes appear unaffected by anticoagulant choice. Bleeding events were similar, but recurrent VTE rates significantly higher in those receiving DOACs. Our study provides a strong rationale for prospective registry data and/or studies to evaluate the safety of DOACs in CTEPH.

Topics: Administration, Oral; Anticoagulants; Humans; Hypertension, Pulmonary; Retrospective Studies; Venous Thromboembolism; Vitamin K

Topics: Anticoagulants; Humans; Hypertension, Pulmonary; Vitamin K

The pathophysiology of chronic thromboembolic pulmonary hypertension (CTEPH) is not fully understood. Poor-quality anticoagulation may contribute to a higher risk of CTEPH after acute pulmonary embolism (PE), partly explaining the transition from acute PE to CTEPH. We assessed the association between the time in therapeutic range (TTR) of vitamin-K antagonist (VKA) treatment and incidence of CTEPH after a PE diagnosis.. Case-control study in which the time spent in, under and above therapeutic range was calculated in 44 PE patients who were subsequently diagnosed with CTEPH (cases). Controls comprised 150 consecutive PE patients in whom echocardiograms two years later did not show pulmonary hypertension. All patients were treated with VKA for at least 6 months after the PE diagnosis. Time in (TTR), under and above range were calculated. Mean differences between cases and controls were estimated by linear regression.. Mean TTR during the initial 6-month treatment period was 72% in cases versus 78% in controls (mean difference -6%, 95%CI -12 to -0.1), mainly explained by more time above the therapeutic range in the cases. Mean difference of time under range was 0% (95%CI -6 to 7) and 2% (95CI% -3 to 7) during the first 3 and 6 months, respectively. In a multivariable model, adjusted odds ratios (ORs) for CTEPH were around unity considering different thresholds for 'poor anticoagulation', i.e. TTR <50%, <60% and <70%.. Subtherapeutic initial anticoagulation was not more prevalent among PE patients diagnosed with CTEPH than in those who did not develop CTEPH.

Topics: Aged; Anticoagulants; Case-Control Studies; Female; Humans; Hypertension, Pulmonary; Incidence; Male; Middle Aged; Pulmonary Embolism; Risk; Treatment Outcome; Vitamin K

Chronic thromboembolic pulmonary hypertension is one of the most prevalent forms of pulmonary hypertension and is a major complication of acute pulmonary embolism. One mainstay of chronic thromboembolic pulmonary hypertension treatment is lifelong anticoagulation. The recent advent of direct oral anticoagulants for acute pulmonary embolism treatment has provided a viable and effective alternative for treating this condition. However, little is known about the efficacy of this new class of drugs for treating chronic thromboembolic pulmonary hypertension. We aimed to evaluate the safety and efficacy of direct oral anticoagulants in the treatment of chronic thromboembolic pulmonary hypertension.. A cohort of chronic thromboembolic pulmonary hypertension patients who initiated treatment with direct oral anticoagulants between June 2015 and November 2016 were enrolled in this study.. Sixteen patients used rivaroxaban, three used dabigatran and one used apixaban for a mean follow-up of 20.9 months. The mean age was 51 years, and eighteen patients were classified as functional class II/III. Eight patients underwent a pulmonary endarterectomy and exhibited clinical, hemodynamic and functional improvement and currently continue to use direct oral anticoagulants. No episode of venous thromboembolism recurrence was identified during the follow-up period, but there was one episode of major bleeding after a traumatic fall.. Although direct oral anticoagulants appear to be a safe and effective alternative for treating chronic thromboembolic pulmonary hypertension, larger studies are needed to support their routine use.

Topics: Administration, Oral; Adult; Aged; Antithrombins; Chronic Disease; Dabigatran; Female; Humans; Hypertension, Pulmonary; Male; Middle Aged; Pulmonary Embolism; Pyrazoles; Pyridones; Reproducibility of Results; Treatment Outcome; Vitamin K

Patients treated for pulmonary arterial hypertension (PAH) frequently receive vitamin K antagonists (VKAs) for PAH or validated indications (such as atrial fibrillation or venous thromboembolism). In these latter indications, VKAs are challenged by direct oral anticoagulants (DOAs). Decreased dosage of DOAs has been proposed in patients at risk of bioaccumulation.. We aimed to evaluate the frequency of bioaccumulation risks in patients treated with PAH-targeted therapy, particularly regarding the presence of validated indications.. We conducted a retrospective study in three different PAH referral centers. All patients receiving PAH-targeted therapy were classified according to demographics, prescription and indications of VKAs, and the presence of major bioaccumulation risk factors (renal failure, low body weight, strong P-glycoprotein or cytochrome P3A4 inhibitors).. Two hundred and thirty-nine of the 366 patients included received VKAs, 94 for validated indications. At least one major risk factor was found in 231 (63.1%) of the whole study population, and in 54 (57.4%) of the patients anticoagulated for a validated indication. No specific patient phenotype could be individualized.. About 1 in 2 patients treated with PAH therapy has at least one of the three major risk factors for DOA bioaccumulation. DOAs in the PH setting could be associated with bioaccumulation and should be individualized, mainly in patients with confirmed indication.

Topics: Administration, Oral; Anticoagulants; Biological Availability; Creatinine; Female; Humans; Hypertension, Pulmonary; Male; Retrospective Studies; Risk Factors; Vitamin K

The aetiology of chronic thromboembolic pulmonary hypertension (CTEPH) is not clearly understood. In some patients, the disease is preceded by acute pulmonary embolism (APE), and is characterised by intravascular thrombosis, vasoconstriction, inflammation and remodelling of pulmonary arteries. Ensuing pulmonary hypertension leads to potentially fatal chronic right ventricle failure. Both inborn and acquired risk factors were identified. Pathogenesis of haemostatic disorders is not completely explained, and extrinsic coagulation pathway disorders may play a role in CTEPH aetiology.. To evaluate levels of tissue factor (TF) and tissue factor pathway inhibitor (TFPI) in CETPH, and to delineate their role in the disease pathogenesis.. Plasma concentrations of TF and TFPI were evaluated in 21 CTEPH patients, in 12 patients with pulmonary arterial hypertension (PAH), in 55 APE survivors without persistent pulmonary hypertension after at least 6 months from the acute episode, and in 53 healthy volunteers (control group C). Most patients were treated with vitamin K antagonists (VKA), and some with unfractionated or low molecular weight heparin. Exclusion criteria included malignancy, inflammation, and recent operation.. Tissue factor concentration was lower in CTEPH and in post-APE patients, not stratified by anticoagulation modality, as compared to control group (p = 0.042; p = 0.011) and PAH group (p = 0.024, p = 0.014). Patients with CTEPH and post-APE on adequate VKA-anticoagulation had similar TF concentration to group C. TFPI concentration was similar in CETPH and post-APE patients irrespective of anticoagulation, and higher as compared to group C (respectively, p = 0.012; p = 0.024; p = 0.004). TFPI concentration was similar in patients with CETPH and in post-APE group, both on adequate VKA-anticoagulation when compared to group C. In the post-APE group, there was no significant difference in TFPI concentration between patients receiving adequate and subjects without anticoagulation. Group C was significantly (p = 0.000) younger than any other group, and showed correlation (r = 0.31) between age and TFPI concentration.. In CTEPH there is a high consumption of TF, leading to reduction in plasma concentration of TF and increase in TFPI. Adequate VKA-anticoagulation normalises TF and TFPI plasma concentrations, as is the case of APE survivors.

Topics: Adult; Aged; Anticoagulants; Humans; Hypertension, Pulmonary; Lipoproteins; Middle Aged; Pulmonary Embolism; Thromboplastin; Vitamin K; Young Adult

Topics: Administration, Oral; Algorithms; Anticoagulants; Biomarkers; Chronic Disease; Clinical Laboratory Techniques; Diagnostic Imaging; Embolectomy; Endovascular Procedures; Female; Fibrin Fibrinogen Degradation Products; Fibrinolytic Agents; Heart Failure; Home Care Services; Humans; Hypertension, Pulmonary; Long-Term Care; Neoplasms; Pregnancy; Pregnancy Complications, Cardiovascular; Prognosis; Pulmonary Embolism; Risk Factors; Vasoconstrictor Agents; Vasodilator Agents; Vitamin K

Topics: Anticoagulants; Female; Hemorrhage; Humans; Hypertension, Pulmonary; Male; Vitamin K

Vitamin K antagonists are advised in pulmonary arterial hypertension patients despite a lack of safety data. We reviewed major bleeding in three classes of pulmonary hypertension patients, all receiving vitamin K antagonists. Bleeding event rates were 5.4 per 100 patient-years for patients with idiopathic pulmonary arterial hypertension, 19 per 100 patient-years for connective tissue disease related pulmonary arterial hypertension patients and 2.4 per 100 patient-years for chronic thromboembolic pulmonary hypertension patients. Life tables analysis showed that event-free survival was worse in patients with connective tissue disease related pulmonary hypertension than in patients with idiopathic pulmonary arterial hypertension (Wilcoxon=12.8; p<0.001), and patients with chronic thromboembolic pulmonary hypertension (Wilcoxon=23.2; p<0.001). Patients with idiopathic pulmonary arterial hypertension suffered more events than patients with chronic thromboembolic pulmonary hypertension (Wilcoxon=7.2; p<0.01). Major bleeding was independent of age, sex, target international normalised ratio (INR) range, documented INR, vitamin K antagonist type, or right atrial pressure, but was associated with use of prostacyclin analogues. Major bleeding risk during vitamin K antagonist therapy differs among groups of patients with pulmonary hypertension. Further research regarding optimal anticoagulant therapy is needed, as well as risk-benefit analyses for pulmonary hypertension patients with a higher bleeding propensity.

Topics: Administration, Oral; Adult; Aged; Anticoagulants; Disease-Free Survival; Female; Fibrinolytic Agents; Hemorrhage; Humans; Hypertension, Pulmonary; International Normalized Ratio; Male; Middle Aged; Platelet Count; Retrospective Studies; Vitamin K

The risk of thromboembolic events related to travel is not exclusively due to air travel. We report the case of a patient who presented pulmonary embolism after prolonged train travel.. An 82 Year-old patient had a significant past history of ischemic heart disease. He traveled by train, in a sitting position, for around 12 hours from Barcelona (Spain) to Paris (France). Approximately 24 hours after the journey, he presented pain in the right leg and dyspnea, which increased during the following 48 hours. Ultrasonographic cardiac examination revealed pulmonary arterial hypertension (54mm Hg), acute right ventricular failure and showed a thrombus located in the pulmonary artery, confirming the diagnosis of pulmonary embolism. Ultrasonography diagnosed deep venous thrombosis of the right leg. Treatment with heparin and oral anticoagulant was initiated. Evolution was favorable and the patient was discharged home 14 days later. No further medical event occurred during the Year that followed.. The mechanisms that precede the development of a venous thrombosis are not specific to the method of transport. Blood vessel wall lesions, venous stasis and blood clotting component abnormalities, principle elements in the development of thrombosis according to Virchow's triad, are enhanced by prolonged sitting position, during travel, whether in planes or not. The role of other risk factors, personal or depending on the condition of travel, remains unknown. Simple prophylactic measures should be widely proposed during long travel, whatever the mode of transport.. The development of a venous thrombosis, enhanced by prolonged sitting position, can occur whatever the form of travel. Prophylactic measures should be widely prescribed for prolonged travel, taking in consideration personal thromboembolic risk factors and circumstances of travel.

Topics: Aged; Aged, 80 and over; Anticoagulants; Echocardiography; Follow-Up Studies; Heparin; Humans; Hypertension, Pulmonary; Male; Pulmonary Embolism; Railroads; Risk Factors; Travel; Venous Thrombosis; Ventricular Dysfunction, Right; Vitamin K

Topics: 4-Hydroxycoumarins; Anticoagulants; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Hypertension, Pulmonary; Indenes; Myocardial Infarction; Risk Factors; Thrombocytopenia; Thrombophlebitis; Vitamin K