warfarin and Hypertension--Pulmonary

The usual differential diagnoses of nocturnal events in children include parasomnias, nocturnal seizures, nocturnal reflux (Sandifer syndrome), hypnic jerks, periodic limb movements of sleep, and sleep disordered breathing. We report a previously healthy young girl who presented to the sleep clinic for evaluation of nocturnal events which were diagnosed as medically refractory nocturnal seizures. It was not until a syncopal event occurred in the daytime, which prompted referral for cardiac evaluation, the diagnosis of idiopathic pulmonary arterial hyper-tension (IPAH) was made. Sleep physicians should consider IPAH in the differential diagnosis of nocturnal events in children.

Topics: Carbolines; Cardiac Output, Low; Child, Preschool; Diagnosis, Differential; Drug Therapy, Combination; Epoprostenol; Female; Humans; Hypertension, Pulmonary; Oxygen Inhalation Therapy; Parasomnias; Seizures; Severity of Illness Index; Sleep Apnea Syndromes; Tadalafil; Treatment Outcome; Warfarin

Topics: Anticoagulants; Diuretics; Drug Therapy, Combination; Dyspnea; Female; Humans; Hypertension, Pulmonary; Middle Aged; Phosphodiesterase 5 Inhibitors; Phosphodiesterase Inhibitors; Piperazines; Practice Guidelines as Topic; Purines; Sildenafil Citrate; Sulfones; Warfarin

Vascular thrombosis implicates in the pathogenesis of pulmonary arterial hypertension (PAH). Anticoagulation therapy (warfarin) has been recommended by many experts in the treatment of PAH. However, the long-term effectiveness of anticoagulation therapy remains controversial. Because of the various drugs, such as epoprostenol, bosentan, and sildenafil, for the treatment of PAH recently, warfarin alone is not a realistic therapy for PAH. Accordingly we reviewed the previous manuscript regarding anticoagulation therapy for PAH, and looked at the current role of anticoagulation therapy in Japan.

Topics: Anticoagulants; Drug Therapy, Combination; Humans; Hypertension, Pulmonary; Warfarin

Thrombotic arteriopathy has been implicated in the pathophysiology of pulmonary arterial hypertension (PAH). However, the role of anticoagulants in the treatment of PAH is uncertain. Through a qualitative systematic review of epidemiological studies, the effectiveness of anticoagulation therapy with warfarin on survival was evaluated in patients with PAH. MEDLINE (1966 to November 2005), EMBASE (1966 to November 2005), bibliographies of included studies and published reviews were searched without language restriction. Epidemiological studies evaluating the effectiveness of warfarin in PAH were included. Studies had to report mortality as an outcome. Seven observational studies evaluating the effectiveness of warfarin comprising 488 patients were identified. Five studies support the effectiveness of anticoagulation therapy, whereas two do not. Data from observational studies suggest that anticoagulation therapy may be an effective intervention in pulmonary arterial hypertension. However, given the methodological limitations and the small number of existing observational studies, a randomised controlled trial is needed in order to definitively address this important clinical issue.

Topics: Anticoagulants; Epidemiologic Studies; Humans; Hypertension, Pulmonary; International Normalized Ratio; Warfarin

Pulmonary arterial hypertension (PAH) is a progressive arteriopathy of the pulmonary circulation that can affect a wide group of patients. Presentation and natural history of PAH are intimately linked to progressive right ventricular failure. Historically, survival in PAH has been poor, especially for patients with PAH associated with progressive systemic sclerosis and human immunodeficiency virus. Oral, subcutaneous, and intravenous therapies that have emerged during the last decade can improve symptoms and hemodynamics. This review explores the impact of these therapies on prognosis in PAH, which ultimately rests on the ability to reverse the pulmonary arteriopathy and preserve right ventricular function.

Topics: Anticoagulants; Antihypertensive Agents; Bosentan; Calcium Channel Blockers; Clinical Trials as Topic; Epoprostenol; Humans; Hypertension, Pulmonary; Piperazines; Prognosis; Purines; Sildenafil Citrate; Sulfonamides; Sulfones; Survival Analysis; Warfarin

A case of well tolerated secundum atrial septal defect in a woman who died at 86 years of age is described and the lesions responsible for pulmonary hypertension are discussed. Previous reports of over-70-year-old patients with untreated secundum atrial septal defect are also reviewed.

Topics: Aged; Aged, 80 and over; Atrial Fibrillation; Diuretics; Echocardiography, Transesophageal; Fatal Outcome; Female; Heart Septal Defects, Atrial; Humans; Hypertension, Pulmonary; Warfarin

Pulmonary arterial hypertension in children can occur secondary to shunt lesion like ventricular septal defect, patent ductus arteriosus or it may be idiopathic, the so called primary pulmonary hypertension (PPH). The progression of PPH is usually rapid in children as compared to adults and the mean survival is 2-3 years after the diagnosis is made. Histological changes in the form of medical muscular hypertrophy, intinal hyperplasia and later angiomatous, plexiform lesions occur in pulmonary vasculature. The pulmonary vasculature normally is a high flow, low resistance circuit and allows large blood flow without marked increase in pulmonary arterial pressure. However, with prolonged increased flow or any other vasoconstrictor stimulus, histological changes start occurring in the pulmonary bed resulting in increasing pressure in pulmonary artery. Right ventricular hypertension follows resulting in right ventricular hyypertrophy and later dysfunction. Life threatening arrhythmias may result in sudden death in some of these patients. Clinical presentation is in the form of exertional dyspnoea with syncope at times. Over 50% of children with PPH are helped by vasodilators. They may be treated with calcium channel blockers (e.g. nifedipine, dose titrated to blood pressure) orally. Those not responding to oral vasodilators can be put on chronic inhaled nitric oxide or continuous intravenous prostacyclin infusion. Chronic anticoagulation therapy may also increase survival. In symptomatic cases, blade/balloon atrial septostomy may increase survival in patients of PPH with intact atrial sptum. For children not responding to medical therapy, lung transplantation may be the answer in near future.

Topics: Adult; Anticoagulants; Child; Diagnosis, Differential; Humans; Hypertension, Pulmonary; Survival Analysis; Vasodilator Agents; Warfarin

Topics: Cardiotonic Agents; Dihydropyridines; Epoprostenol; Humans; Hypertension, Pulmonary; Mass Screening; Risk Factors; Vasodilator Agents; Warfarin

Although lung transplantation is considered a definitive treatment of patients with advanced pulmonary vascular disease and pulmonary hypertension, advances in the success of the medical management of patients with pulmonary hypertension make it less clear as to when to refer a patient for transplantation. Coumadin anticoagulation is associated with improved survival in all patients, and calcium channel blockers therapy with improved survival in very select patients. Chronic prostacyclin represents a newer therapy that seems to have a dramatic impact on patients' functional class and survival. As improvements continue in the medical management in pulmonary hypertension, and in survival of patients undergoing lung transplantation, the guidelines for patient selection should be constantly evolving.

Topics: Anticoagulants; Antihypertensive Agents; Calcium Channel Blockers; Epoprostenol; Humans; Hypertension, Pulmonary; Lung Transplantation; Patient Selection; Warfarin

Efforts aimed at assessing pharmacotherapy of pulmonary arterial hypertension (PHT) have largely focused on patients with primary PHT, PHT associated with selected connective tissue diseases, and various forms of hypoxic secondary PHT. Part I of this review discusses the value and limitations of a wide variety of vasodilator drugs, oxygen, and warfarin in the treatment of primary PHT with special reference to their effects on pulmonary and systemic hemodynamics, functional capacity, and survival.

Topics: Acetylcholine; Adrenergic alpha-Agonists; Adrenergic beta-Agonists; Angiotensin-Converting Enzyme Inhibitors; Calcium Channel Blockers; Epoprostenol; Female; Humans; Hypertension, Pulmonary; Male; Oxygen; Vasodilator Agents; Warfarin

Topics: Aminophylline; Coumarins; Drug Therapy; Humans; Hypertension; Hypertension, Pulmonary; Lung; Nitroglycerin; Pulmonary Embolism; Pulmonary Heart Disease; Thromboembolism; Thrombosis; Warfarin

Chronic thromboembolic pulmonary hypertension (CTEPH) is caused by the obstruction of the main pulmonary artery due to thrombosis and vascular remodeling. Regarding the need for anticoagulant therapy in CTEPH patients, this study aimed to compare rivaroxaban with warfarin in terms of its efficacy and safety in patients undergoing endarterectomy surgery.. The study was a parallel clinical trial in patients who underwent endarterectomy following CTEPH. A total of 96 patients were randomly selected and assigned to two groups: warfarin-treated (control) and rivaroxaban-treated (intervention). Patients were clinically assessed for re-thrombosis, re-admission, bleeding, and mortality in the first, third, and sixth months after surgery.. There was no significant difference in the occurrence of thrombosis between the two groups within the first, third-, and sixth-months post-surgery (p=0.52, 1, 0.38 respectively). Moreover, the mortality rate (p=0.9), bleeding rate (p=0.06), and re-admission rate (p=0.15) showed no significant differences between the two groups.. Rivaroxaban may be as effective as warfarin in treating CTEPH patients after endarterectomy in the short term and can be used as an anticoagulant in these patients. However, studies with long-term follow-ups are needed to consolidate the strategy of treating these patients with rivaroxaban.

Topics: Anticoagulants; Chronic Disease; Endarterectomy; Hemorrhage; Humans; Hypertension, Pulmonary; Pulmonary Embolism; Rivaroxaban; Thrombosis; Treatment Outcome; Warfarin

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

Long-term anticoagulation is recommended in idiopathic pulmonary arterial hypertension (IPAH). In contrast, limited data support anticoagulation in pulmonary arterial hypertension (PAH) associated with systemic sclerosis (SSc-PAH). We assessed the effect of warfarin anticoagulation on survival in IPAH and SSc-PAH patients enrolled in Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL), a longitudinal registry of group I PAH.. Patients who initiated warfarin on study (n=187) were matched 1:1 with patients never on warfarin, by enrollment site, etiology, and diagnosis status. Descriptive analyses were conducted to compare warfarin users and nonusers by etiology. Survival analyses with and without risk adjustment were performed from the time of warfarin initiation or a corresponding quarterly update in matched pairs to avoid immortal time bias. Time-varying covariate models were used as sensitivity analyses. Mean warfarin treatment was 1 year; mean international normalized ratios were 1.9 (IPAH) and 2.0 (SSc-PAH). Two-thirds of patients initiating warfarin discontinued treatment before the last study assessment. There was no survival difference with warfarin in IPAH patients (adjusted hazard ratio, 1.37; P=0.21) or in SSc-PAH patients (adjusted hazard ratio, 1.60; P=0.15) in comparison with matched controls. However, SSc-PAH patients receiving warfarin within the previous year (hazard ratio, 1.57; P=0.031) or any time postbaseline (hazard ratio, 1.49; P=0.046) had increased mortality in comparison with warfarin-naïve patients.. No significant survival advantage was observed in IPAH patients who started warfarin. In SSc-PAH patients, long-term warfarin was associated with poorer survival than in patients not receiving warfarin, even after adjusting for confounders.. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00370214.

Topics: Adult; Aged; Anticoagulants; Disease Management; Female; Humans; Hypertension, Pulmonary; Male; Middle Aged; Registries; Survival Rate; Time Factors; Treatment Outcome; Warfarin

The prognosis of patients with severe pulmonary hypertension (PHT) is poor. To determine prognosis and guide therapy, an acute hemodynamic trial of selective pulmonary vasodilators, usually inhaled nitric oxide (iNO), was performed. We hypothesized that oral sildenafil, a phosphodiesterase-5 inhibitor, is a safe and effective alternative to iNO.. We studied 13 consecutive patients (mean+/-SEM, 44+/-2 years of age; 9 women) referred for consideration of heart-lung transplantation or as a guide to medical therapy. All but one were functional class III or IV. Patients had primary PHT (n=9), pulmonary arterial hypertension (n=2), or secondary PHT (n=2). Hemodynamics and serum cyclic guanosine-monophosphate levels (cGMP) were measured at baseline and at peak effects of iNO (80 ppm), sildenafil (75 mg), and their combination. The decrease in pulmonary vascular resistance was similar with iNO (-19+/-5%) and sildenafil (-27+/-3%), whereas sildenafil+iNO was more effective than iNO alone (-32+/-5%, P<0.003). Sildenafil and sildenafil+iNO increased cardiac index (17+/-5% and 17+/-4%, respectively), whereas iNO did not (-0.2+/-2.0%, P<0.003). iNO increased, whereas sildenafil tended to decrease, pulmonary capillary wedge pressure (+15+/-6 versus -9+/-7%, P<0.0007). Systemic arterial pressure was similar among groups and did not decrease with treatment. cGMP levels increased similarly with iNO and sildenafil, and their combination synergistically elevated cGMP (P<0.0001).. A single oral dose of sildenafil is as effective and selective a pulmonary vasodilator as iNO. Sildenafil may be superior to iNO in that it increases cardiac output and does not increase wedge pressure. Future studies are indicated to establish whether sildenafil could be effective over a longer duration.

Topics: Administration, Oral; Adult; Cyclic GMP; Diuretics; Drug Therapy, Combination; Female; Headache; Hemodynamics; Humans; Hypertension, Pulmonary; Male; Middle Aged; Nitric Oxide; Phosphodiesterase Inhibitors; Piperazines; Predictive Value of Tests; Pulmonary Artery; Pulmonary Circulation; Pulmonary Wedge Pressure; Purines; Sildenafil Citrate; Sulfones; Treatment Outcome; Vascular Resistance; Vasodilator Agents; Warfarin

Thrombosis in situ related to endothelial cell injury may contribute to the development of pulmonary hypertension (PH). P-selectin, a leukocyte adhesion receptor present in endothelial cells and platelets, reflects endothelial injury and platelet activation, and thrombomodulin (TM), a receptor for thrombin and a major anticoagulant proteoglycan on the endothelial membrane, reflects the anticoagulant activity of the endothelium.. To assess abnormal coagulation due to endothelial injury in patients with PH, plasma levels of soluble P-selectin and TM were measured in 32 patients with primary PH (PPH), 25 with secondary pulmonary arterial hypertension (sPAH), 31 with pulmonary venous hypertension (PVH), and 17 healthy subjects (Control). These measurements were repeated after continuous infusion of prostacyclin in 15 patients with PPH and 3 with sPAH. P-selectin levels in both the sPAH and PPH groups were significantly higher than those in the Control and PVH groups (P<0.05). Plasma TM level in the PPH group was significantly lower than those in the other groups (P<0.01). After prostacyclin therapy, the lower TM level was increased and the higher P-selectin level was decreased (P<0.05).. Decreased TM and increased P-selectin in PPH and sPAH may reflect in situ thrombosis due to endothelial injury. Prostacyclin may act not only as a vasodilator but also as an agent that improves endothelial injury and altered hemostasis in pulmonary arterial injury.

Topics: Adult; Aged; Anticoagulants; Antihypertensive Agents; Epoprostenol; Female; Hemodynamics; Humans; Hypertension, Pulmonary; Male; Middle Aged; P-Selectin; Thrombomodulin; Warfarin

Primary pulmonary hypertension is a progressive, fatal disease of unknown cause. Vasodilator drugs have been used as a treatment, but their efficacy is uncertain.. We treated 64 patients with primary pulmonary hypertension with high doses of calcium-channel blockers. Patients who responded to treatment (defined as those whose pulmonary-artery pressure and pulmonary vascular resistance immediately fell by more than 20 percent after challenge) were treated for up to five years. Their survival was compared with that of the patients who did not respond and with patients enrolled in the National Institutes of Health (NIH) Registry on Primary Pulmonary Hypertension. Warfarin was given to 55 percent of the patients as concurrent therapy, on the basis of a lung scan showing nonuniformity of pulmonary blood flow (47 percent of patients who responded and 57 percent of those who did not respond).. Seventeen patients (26 percent) responded to treatment, as indicated by a 39 percent fall in pulmonary-artery pressure and a 53 percent fall in the pulmonary-vascular-resistance index (P less than 0.001). Nifedipine (mean [+/- SD] daily dose, 172 +/- 41 mg) was given to 13 patients, and diltiazem (mean daily dose, 720 +/- 208 mg) was given to 4 patients. After five years, 94 percent of the patients who responded (16 of 17) were alive, as compared with 55 percent of the patients who did not respond (26 of 47, P = 0.003). The survival of the patients who responded was also significantly better than that of the NIH registry cohort (P = 0.002) and patients from the NIH registry who were treated at the University of Illinois (P = 0.001). The use of warfarin was associated with improved survival (P = 0.025), particularly in the patients who did not respond.. This study suggests that high doses of calcium-channel blockers in patients with primary pulmonary hypertension who respond with reductions in pulmonary-artery pressure and pulmonary vascular resistance may improve survival over a five-year period.

Topics: Adult; Blood Pressure; Calcium Channel Blockers; Diltiazem; Humans; Hypertension, Pulmonary; Nifedipine; Prospective Studies; Pulmonary Artery; Survival Rate; Vascular Resistance; Warfarin

Topics: Adolescent; Adult; Angiocardiography; Blood Circulation; Child; Child, Preschool; Clinical Trials as Topic; Female; Heart Defects, Congenital; Humans; Hypertension, Pulmonary; Infant; Male; Pulmonary Artery; Pulmonary Valve Stenosis; Radiography, Thoracic; Tolazoline; Warfarin

Chronic thromboembolic pulmonary hypertension (CTEPH) requires lifelong anticoagulation. Long-term outcomes of CTEPH under current anticoagulants are unclear.. The CTEPH AC registry is a prospective, nationwide cohort study comparing the safety and effectiveness of direct oral anticoagulants (DOACs) and warfarin for CTEPH.. Patients with CTEPH, both tre atment-naïve and on treatment, were eligible for the registry. Inclusion criteria were patients aged ≥20 years and those who were diagnosed with CTEPH according to standard guidelines. Exclusion criteria were not specified. The primary efficacy outcome was a composite morbidity, and mortality outcome comprised all-cause death, rescue reperfusion therapy, initiation of parenteral pulmonary vasodilators, and worsened 6-minute walk distance and WHO functional class. The safety outcome was clinically relevant bleeding, including major bleeding.. Nine hundred twenty-seven patients on oral anticoagulants at baseline were analyzed: 481 (52%) used DOACs and 446 (48%) used warfarin. The 1-, 2-, and 3-year rates of composite morbidity and mortality outcome were comparable between the DOAC and warfarin groups (2.6%, 3.1%, and 4.2% vs 3.0%, 4.8%, and 5.9%, respectively; P = .52). The 1-, 2-, and 3-year rates of clinically relevant bleeding were significantly lower in DOACs than in the warfarin group (0.8%, 2.4%, and 2.4% vs 2.5%, 4.8%, and 6.4%, respectively; P = 0.036). Multivariable Cox proportional-hazards regression models revealed lower risk of clinically relevant bleeding in the DOAC group than the warfarin group (hazard ratio: 0.35; 95% CI: 0.13-0.91; P = .032).. This registry demonstrated that under current standard of care, morbidity and mortality events were effectively prevented regardless of anticoagulants, while the clinically relevant bleeding rate was lower when using DOACs compared with warfarin.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Chronic Disease; Cohort Studies; East Asian People; Hemorrhage; Humans; Hypertension, Pulmonary; Prospective Studies; Retrospective Studies; Thromboembolism; Warfarin

We describe the case of a 72-year-old gentleman who was referred to our institution for management of cardiogenic shock from a massive pulmonary embolism. Right heart catheterization revealed a low cardiac index and markedly elevated pulmonary pressures, suggested long-standing venous thromboembolic (VTE) disease that evolved into chronic thromboembolic pulmonary hypertension (CTEPH). The patient was cannulated to veno-arterial extra-corporeal membrane oxygenation and eventually treated with pulmonary embolectomy and thromboendarterectomy. Subsequently discovered inferior vena cava clot and left iliac deep vein thrombosis were treated with suction and mechanical thrombectomy. Intravascular ultrasound of the left lower extremity venous system identified iliac vein compression syndrome (IVCS) as the culprit of the patient's VTE and CTEPH. A left iliac stent was placed and the patient was discharged on Warfarin for anticoagulation. The case illustrates the rapidly expanding armamentarium for VTE treatment and proposes IVCS as a new, potentially underrecognized risk factor for CTEPH.

Topics: Aged; Anticoagulants; Embolectomy; Endarterectomy; Endovascular Procedures; Extracorporeal Membrane Oxygenation; Hemodynamics; Humans; Hypertension, Pulmonary; Male; May-Thurner Syndrome; Pulmonary Embolism; Risk Factors; Stents; Thrombectomy; Treatment Outcome; Venous Thromboembolism; Venous Thrombosis; Warfarin

Antiphospholipid syndrome (APS) is a cause of chronic thromboembolic pulmonary hypertension (CTEPH) and it is associated with an increased risk of postoperative neurological complications. We experienced a case of reversible parkinsonism after pulmonary endarterectomy (PEA) and subsequent multiple cerebral infarctions under standard anticoagulation therapy in a patient with CTEPH associated with APS. Strict management using a combination of antiplatelet and anticoagulation therapy should be considered in patients with a high titer of triple antiphospholipid antibodies in the perioperative period. We should be aware of the high risk of postoperative neurologic manifestations in patients with APS.

Topics: Adult; Anticoagulants; Antiphospholipid Syndrome; Cerebral Infarction; Chronic Disease; Endarterectomy; Heparin; Humans; Hypertension, Pulmonary; Male; Parkinsonian Disorders; Postoperative Complications; Pyridines; Thiazoles; Treatment Outcome; Warfarin

Chronic thromboembolic pulmonary hypertension (CTEPH) is a form of pulmonary arterial hypertension (PAH) in which the pulmonary thrombus fails to resolve, resulting in occlusion and remodelling of pulmonary arteries.

Topics: Adult; Angiography; Anticoagulants; Chronic Disease; Dyspnea; Electrocardiography; Humans; Hypertension, Pulmonary; Male; Pulmonary Artery; Pulmonary Embolism; Tomography, X-Ray Computed; Treatment Outcome; Warfarin

Topics: Anticoagulants; Disease Management; Female; Humans; Hypertension, Pulmonary; Male; Registries; Warfarin

ABCA3 is highly expressed in alveolar epithelial type 2 cells and is associated with surfactant homeostasis. Patients with ABCA3 mutations develop various respiratory complications, such as fatal respiratory distress syndrome or interstitial lung disease. We describe a patient with pulmonary fibrosis and emphysema with pulmonary hypertension, associated with compound heterozygous mutations of the ABCA3 gene. This is the first report showing that mutations in the ABCA3 gene lead to pulmonary fibrosis and emphysema, including combined pulmonary fibrosis and emphysema, in childhood. Treatment with prostacyclin analogue, warfarin, and inhaled oxygen was effective to improve patient's hemodynamic condition as well as pulmonary fibrosis and emphysema. Pediatr Pulmonol. 2016;51:E21-E23. © 2016 Wiley Periodicals, Inc.

Topics: Anticoagulants; ATP-Binding Cassette Transporters; Calcium Channel Blockers; Child; Female; Home Care Services; Humans; Hypertension, Pulmonary; Mutation; Oxygen Inhalation Therapy; Pulmonary Emphysema; Pulmonary Fibrosis; Treatment Outcome; Warfarin

Pulmonary arterial hypertension (PAH) is a rare, progressive, fatal vascular disorder. Genetic predisposition plays vital roles in the development of PAH, with most mutations being identified in genes involved in the transforming growth factor beta (TGF-β) signaling pathways. Defects in the BMP9 gene have been documented in hereditary hemorrhagic telangiectasia (HHT), the most common inherited vascular disorder, which is occasionally associated with PAH. Selective enhancement of endothelial BMPR2 with BMP9 reverses pulmonary arterial hypertension.. We report the case of a 5-year-old Hispanic boy who was diagnosed with severe PAH and right heart failure at 3 years of age. During his stay in the pediatric intensive care unit, treatment was initiated with inhaled nitric oxide and intravenous epoprostenol; he subsequently was transitioned to treprostinil, sildenafil, and prophylactic enoxaparin. Now, two years later, the child is asymptomatic on sildenafil, bosentan, subcutaneous treprostinil, and warfarin. Genetic screening revealed a novel homozygous nonsense mutation in the BMP9 gene (c.76C > T; p.Gln26Ter). The child had no telangiectasias or arteriovenous malformations; family history also was negative. Subsequent parental testing showed both parents were heterozygous for the same mutation, indicating that the child inherited the BMP9 mutant allele from each parent.. To our knowledge, this is the first report of a BMP9 mutation in a patient with PAH. The homozygous nonsense mutation may account for the early onset and severity of PAH in this patient and also fit the 'two-hit' model we proposed previously. The absence of clinical symptoms for PAH in the parents may be due to incomplete penetrance or various expressivities of the BMP9 mutations. Our study expands the spectrum of phenotypes related to BMP9 mutations.

Topics: Anticoagulants; Antihypertensive Agents; Bosentan; Child, Preschool; Codon, Nonsense; Epoprostenol; Growth Differentiation Factor 2; Growth Differentiation Factors; Homozygote; Humans; Hypertension, Pulmonary; Male; Mexican Americans; Sildenafil Citrate; Sulfonamides; Vasodilator Agents; Warfarin

Topics: Adult; Age Distribution; Aged; Anticoagulants; Bosentan; Chronic Disease; Female; Humans; Hypertension, Pulmonary; Incidence; Latvia; Male; Middle Aged; Phenylpropionates; Prevalence; Pulmonary Embolism; Pyrazoles; Pyridazines; Pyridones; Registries; Rivaroxaban; Sex Distribution; Sildenafil Citrate; Sulfonamides; Vasodilator Agents; Warfarin; Young Adult

Treatment of children and adults with pulmonary hypertension (PH) with or without cardiac dysfunction has improved in the last two decades. The so-called pulmonary arterial hypertension (PAH)-specific medications currently approved for therapy of adults with PAH target three major pathways (endothelin, nitric oxide, prostacyclin). Moreover, some PH centres may use off-label drugs for compassionate use. Pulmonary hypertensive vascular disease (PHVD) in children is complex, and selection of appropriate therapies remains difficult. In addition, paediatric PAH/PHVD therapy is vastly based on experience and trial data from adult rather than paediatric studies; however, the first randomised paediatric PAH trials have been conducted recently. We present consensus recommendations for the treatment of children with PH. Class of recommendation and level of evidence were assigned based on paediatric data only or on adult studies that included >10% children. After a systematic literature search and analysis of the published data, we developed treatment strategies and algorithms that can guide goal-oriented PH therapy. We discuss early combination therapy (double, triple) in patients with PAH in functional class II-IV and in those with inadequate response to the initial pharmacotherapy. In those children with progressive, severe PAH and inadequate response, advances in drug development, and interventional and surgical approaches provide promising new strategies to avoid, reverse or ameliorate right heart failure and left ventricular compression. In particular, first follow-up data indicate that Potts shunt (left pulmonary artery to descending aorta anastomosis) may be an alternative destination therapy, or bridge to bilateral lung transplantation, in end-stage paediatric PAH.

Topics: Adolescent; Anticoagulants; Aspirin; Calcium Channel Blockers; Child; Consensus; Contraceptives, Oral; Diuretics; Endothelin Receptor Antagonists; Endothelium-Dependent Relaxing Factors; Humans; Hypertension, Pulmonary; Mineralocorticoid Receptor Antagonists; Nitric Oxide; Oxygen Inhalation Therapy; Phosphodiesterase 5 Inhibitors; Platelet Aggregation Inhibitors; Prostaglandins; Vasodilator Agents; Warfarin

Topics: Disease Management; Familial Primary Pulmonary Hypertension; Humans; Hypertension, Pulmonary; Registries; Survival Rate; Warfarin

Topics: Disease Management; Familial Primary Pulmonary Hypertension; Humans; Hypertension, Pulmonary; Registries; Survival Rate; Warfarin

The use of oral anticoagulation in patients with heart failure in sinus rhythm remains controversial as previous large randomized controlled trials (RCTs) have not shown a survival benefit. However, heterogeneity exists among heart failure patients and it is possible that high-risk subgroups may benefit from anticoagulation (warfarin). We hypothesize that one such subgroup are patients with heart failure and pulmonary hypertension (PH), conditions associated with coagulation abnormalities.. We conducted a retrospective, population-based, longitudinal cohort study in patients with left ventricular systolic dysfunction (LVSD) and PH [defined as a right ventricular systolic pressure (RVSP) >35 mmHg] identified from echocardiograms performed between January 1994 to May 2011. This data was linked using a unique patient-specific identifier to community-dispensed prescriptions, hospital admissions, and mortality data. For comparison, we included patients with LVSD and no PH.. A total of 2619 subjects with LVSD and a measurable RVSP were identified (mean ± SD age of 73 ± 12 years); 1606 out of 2619 had PH and 1013 out of 2619 had no PH. The overall mean follow-up period was 2.56 ± 3.0 years. In patients with LVSD and PH, the use of warfarin was associated with an improved survival [hazard ratio (HR) = 0.72 95% confidence interval (CI) 0.58-0.90, P = 0.0003], fewer non-cardiovascular disease-related deaths (HR = 0.65, 95%CI 0.49-0.87, P = 0.0033 and showed a trend towards reduced cardiovascular disease-associated mortality (HR = 0.72, 95%CI 0.51-1.02). Warfarin did not improve survival in those with LVSD with no PH.. In patients with both LVSD and PH, the use of warfarin is associated with a 28% reduction in mortality. Further prospective trials are required to confirm our findings.

Topics: Aged; Aged, 80 and over; Anticoagulants; Case-Control Studies; Cohort Studies; Female; Heart Failure; Humans; Hypertension, Pulmonary; Longitudinal Studies; Male; Middle Aged; Proportional Hazards Models; Retrospective Studies; Systole; Ventricular Dysfunction, Left; Warfarin

Topics: Anticoagulants; Aspirin; Cardiac Tamponade; Diastole; Heart Failure; Heart-Assist Devices; Humans; Hypertension, Pulmonary; Male; Middle Aged; Postoperative Complications; Pulsatile Flow; Sternotomy; Systole; Thoracotomy; Warfarin

To establish the rat model of acute pulmonary embolism, and study the changes of vascular active substances in pulmonary embolism rats, and investigate the interventive effect of anticoagulant drugs on vascular active substances.. One hundred and twenty-eight rats were randomly divided into four groups: control group, model group, low-molecular-weight heparin and warfarin treated group and rivaroxaban-treated group (n = 32 in each group). The method of autologous thrombosis was used to establish the animal model of acute pulmonary embolism. The animals were treated with saline or different anticoagulant drugs. The physiological and biochemical parameters were detected at different time points after embolization. The rats were killed after embolism of 24 h, 3 d, 5 d or 1 week respectively and the pathologic samples of lung tissues were collected to analyze the pulmonary pathological changes in different groups.. Rats in embolization group after blood clots injection showed shortness of breath, oral cyanosis; quicken heart rates and other symptoms. All embolization groups had pulmonary hypertension, the levels of type B natriuretic peptide (BNP) were increased significantly. The ratio of endothelin-1 (ET-1)/NO and thromboxane (TXB2) and prostacyclin (6-k-PGFla) were abnormal. After treated with effective anticoagulant drugs, the levels of BNP, ET-1, NO, TXB2 and 6-k-PGF1a were tended to the normal levels in the control group. The pulmonary hypertensions were gradually decreased. The efficacy of rivaroxaban on pulmonary embolism was the same as that of the low molecular weight heparin or warfarin.. Anticoagulation therapy can effectively improve endothelial function after pulmonary embolism, reduce pulmonary hypertension, and revise the increased BNP levels to normal levels. The efficacy of rivaroxaban is not inferior to that of low molecular weight heparin and warfarin.

Topics: Animals; Anticoagulants; Disease Models, Animal; Endothelin-1; Heparin, Low-Molecular-Weight; Hypertension, Pulmonary; Lung; Morpholines; Pulmonary Embolism; Rats; Rivaroxaban; Thiophenes; Warfarin

Topics: Anticoagulants; Disease Management; Female; Humans; Hypertension, Pulmonary; Male; Registries; Warfarin

Although warfarin is often recommended for pulmonary arterial hypertension (PAH) management to mitigate thrombotic risk and improve survival, limited information exists to guide anticoagulation therapy. The purpose of this study was to compare and contrast warfarin therapy monitoring requirements and outcomes in patients with PAH and atrial fibrillation (AF) receiving long-term anticoagulation.. Patients initiated on warfarin for PAH between January 1, 2000 and December 31, 2008 were matched by warfarin initiation date (±90 days), age (±5 years), chronic disease score (±1 points), and sex to patients initiated for AF. The primary study endpoint was frequency of INR monitoring per 30 days of observation. Secondary endpoints included indicators of INR control and warfarin-related adverse events.. A total of 84 patients were included - 18 and 66 in the PAH and AF groups, respectively. Patients with PAH had a higher median rate of INR measurements per 30 days compared to patients with AF (median=2.0, interquartile range [IQR]=1.5 - 2.3 vs. median=1.6, IQR=1.3 - 2.0, p=0.046). There were no differences between groups with respect to percent of INR measurements in range, overall time in therapeutic range (TTR), or warfarin-related adverse events (all p>0.05). Study results suggest that patients with PAH may be more difficult to manage as seen through more frequent INR monitoring. Potential management difficulties did not translate to a lower performance on indicators of INR control or increased risk of warfarin-related adverse events.

Topics: Anticoagulants; Cohort Studies; Female; Humans; Hypertension, Pulmonary; International Normalized Ratio; Male; Middle Aged; Retrospective Studies; Warfarin

Topics: Adult; Anticoagulants; Chronic Disease; Dyspnea; Edema; Endarterectomy; Female; Heparin; Humans; Hypertension, Pulmonary; Lower Extremity; Pulmonary Embolism; Recurrence; Respiratory Insufficiency; Thromboembolism; Warfarin

Topics: Adult; Anticoagulants; Antihypertensive Agents; Bosentan; Chronic Disease; Diuretics; Drug Therapy, Combination; Humans; Hypertension, Pulmonary; Male; Pulmonary Embolism; Sulfonamides; Tomography, X-Ray Computed; Warfarin

Warfarin is recommended in systemic sclerosis-associated pulmonary arterial hypertension (SSc-PAH) and idiopathic PAH (IPAH) to improve survival. There is no evidence to support this in SSc-PAH and the evidence in IPAH is conflicting. We evaluated the ability of warfarin to improve survival using 2 large SSc-PAH and IPAH cohorts.. The effect of warfarin on all-cause mortality was evaluated. Bayesian propensity scores (PS) were used to adjust for baseline differences between patients exposed and not exposed to warfarin, and to assemble a matched cohort. Bayesian Cox proportional hazards models were constructed using informative priors based on international PAH expert elicitation.. Review of 1138 charts identified 275 patients with SSc-PAH (n = 78; 28% treated with warfarin) and 155 patients with IPAH (n = 91; 59% treated with warfarin). Baseline differences in PAH severity and medications were resolved using PS matching. In the matched cohort of 98 patients with SSc-PAH (49 treated with warfarin), the posterior median hazard ratio (HR) was 1.06 [95% credible interval (CrI) 0.70, 1.63]. In the matched cohort of 66 patients with IPAH (33 treated with warfarin), the posterior median HR was 1.07 (95% CrI 0.57, 1.98). The probability that warfarin improves median survival by 6 months or more is 23.5% in SSc-PAH and 27.7% in IPAH. Conversely, there is a > 70% probability that warfarin provides no significant benefit or is harmful.. There is a low probability that warfarin improves survival in SSc-PAH and IPAH. Given the availability of other PAH therapies with demonstrable benefits, there is little reason to use warfarin to improve survival for these patients.

Topics: Anticoagulants; Bayes Theorem; Cause of Death; Cohort Studies; Familial Primary Pulmonary Hypertension; Female; Humans; Hypertension, Pulmonary; Male; Proportional Hazards Models; Scleroderma, Systemic; Treatment Outcome; Warfarin

Pulmonary arterial hypertension (PAH) is a major cause of mortality in connective tissue disease (CTD). We sought to quantify survival and determine factors predictive of mortality in a cohort of patients with CTD-associated PAH (CTD-PAH) in the current era of advanced PAH therapy.. Patients with right heart catheter proven CTD-PAH were recruited from six specialised PAH treatment centres across Australia and followed prospectively. Using survival methods including Cox proportional hazards regression, we modelled for all-cause mortality. Independent variables included demographic, clinical and hemodynamic data.. Among 117 patients (104 (94.9%) with systemic sclerosis), during 2.6 ± 1.8 (mean ± SD) years of follow-up from PAH diagnosis, there were 32 (27.4%) deaths. One-, two- and three-year survivals were 94%, 89% and 73%, respectively. In multiple regression analysis, higher mean right atrial pressure (mRAP) at diagnosis (hazard ratio (HR) = 1.13, 95% CI: 1.04 to 1.24, P = 0.007), lower baseline six-minute walk distance (HR = 0.64, 95% CI: 0.43 to 0.97, P = 0.04), higher baseline World Health Organization functional class (HR = 3.42, 95% CI: 1.25 to 9.36, P = 0.04) and presence of a pericardial effusion (HR = 3.39, 95% CI: 1.07 to 10.68, P = 0.04) were predictive of mortality. Warfarin (HR = 0.20, 95% CI: 0.05 to 0.78, P = 0.02) and combination PAH therapy (HR = 0.20, 95% CI: 0.05 to 0.83, P = 0.03) were protective.. In this cohort of CTD-PAH patients, three-year survival was 73%. Independent therapeutic predictors of survival included warfarin and combination PAH therapy. Our findings suggest that anticoagulation and combination PAH therapy may improve survival in CTD-PAH. This observation merits further evaluation in randomised controlled trials.

Topics: Aged; Australia; Blood Pressure; Cohort Studies; Connective Tissue Diseases; Female; Follow-Up Studies; Humans; Hypertension, Pulmonary; Male; Middle Aged; Pericardial Effusion; Prognosis; Proportional Hazards Models; Survival Rate; Walking; Warfarin

Warfarin use in scleroderma (SSc)-associated pulmonary arterial hypertension (PAH) and idiopathic PAH (IPAH) is controversial. A prerequisite for a trial is the demonstration of community uncertainty. We evaluated experts' beliefs about the effect of warfarin on 3-year survival in SSc-PAH and IPAH, and factors that influence warfarin use.. PAH experts attending the 2008 American College of Rheumatology or American Thoracic Society meetings expressed the probability of 3-year survival without and with warfarin and their degree of uncertainty by applying adhesive dots, each representing a 5% weight of probability, in "bins" on a line, creating a prior probability distribution or prior. Using a numeric rating scale, participants rated factors that influence their use of warfarin.. Forty-five experts (44% pulmonologists, 38% rheumatologists, 16% cardiologists, 2% internists) underwent the belief elicitation interview. In SSc-PAH, the mean probabilities of 3-year survival without and with warfarin were 54% and 56%, respectively. Pessimistic experts believe that warfarin worsens survival by 7%. Optimistic experts believe that warfarin improves survival by 13%. In IPAH, the mean probabilities of 3-year survival without and with warfarin were 68% and 76%. Factors (mean rating out of 10, 0 = not at all important, 10 = extremely important) that influence experts' use of warfarin were functional class (5.4), age (5.4), pulmonary artery pressure (5.2), peripheral vascular disease (3.6), disease duration (2.8), and sex (1.7).. Bayesian priors effectively quantify and illustrate experts' beliefs about the effect of warfarin on survival in SSc-PAH and IPAH. This study demonstrates the presence of uncertainty about the effect of warfarin, and provides justification for a clinical trial.

Topics: Anticoagulants; Bayes Theorem; Familial Primary Pulmonary Hypertension; Humans; Hypertension, Pulmonary; Male; Practice Patterns, Physicians'; Scleroderma, Systemic; Surveys and Questionnaires; Survival Rate; Warfarin

Chronic thromboembolic pulmonary hypertension (CTEPH) is a chronic progressive disease of pulmonary circulation characterised by indistinct ethiopathogenesis. We present a case of a 50 year-old male with thrombophilia of unknown origin leading to the formation of multiple thrombi within venous circulation followed by episodes of acute pulmonary embolism resulting ultimately in acute heart failure in the course of developing CTEPH. Unfortunately, despite the wide range of haemostasis laboratory tests we were not able to define the type of coagulation abnormality. Owing to the efficient cooperation between cardiologists and cardiosurgeons it was possible to save patient's life.

Topics: Acenocoumarol; Anticoagulants; Cardiac Surgical Procedures; Coronary Thrombosis; Echocardiography, Doppler; Humans; Hypertension, Pulmonary; Intestine, Small; Male; Middle Aged; Myocardial Infarction; Necrosis; Pulmonary Embolism; Stroke; Time Factors; Treatment Outcome; Warfarin

Anticoagulation with warfarin is recommended for the treatment of patients with pulmonary arterial hypertension (PAH). However, the therapeutic benefit of anticoagulation has not yet been demonstrated experimentally or clinically. Here, rivaroxaban, an oral, direct factor Xa (FXa) inhibitor, was compared with warfarin and enoxaparin in the prevention of right ventricular (RV) dysfunction and hypertrophy in the monocrotaline (MCT) model of pulmonary hypertension.. Sprague-Dawley rats (n = 10 per group) were randomized to receive rivaroxaban, warfarin, enoxaparin, or placebo before receiving a subcutaneous injection of MCT 60 mg/kg or saline. Rivaroxaban and enoxaparin were administered for 28 days starting 4 h before MCT injection; warfarin was given for 35 days initiated 7 days before MCT injection. RV haemodynamics and hypertrophy were assessed 28 days after MCT administration. Rivaroxaban dose-dependently reduced systolic and end-diastolic RV pressure increase and RV hypertrophy. Warfarin reduced RV pressure increase only. Enoxaparin had no effect on either parameter. Severe bleeding occurred in four and five rats treated with warfarin and enoxaparin, respectively, whereas no overt bleeding was observed in rats treated with rivaroxaban.. Selective, direct inhibition of FXa by rivaroxaban effectively prevented RV dysfunction and hypertrophy in MCT-injected rats, indicating a role for coagulation factors in experimental pulmonary hypertension. Clinical investigation of the impact of early and continued administration of a specific FXa inhibitor such as rivaroxaban on the course of PAH should be considered.

Topics: Animals; Blood Coagulation; Enoxaparin; Factor Xa; Factor Xa Inhibitors; Familial Primary Pulmonary Hypertension; Hemodynamics; Hypertension, Pulmonary; Hypertrophy, Right Ventricular; Male; Monocrotaline; Morpholines; Rats; Rats, Sprague-Dawley; Rats, Wistar; Rivaroxaban; Thiophenes; Thrombosis; Warfarin

Interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH) represent the leading causes of death in systemic sclerosis (SSc). Screening for these complications has assumed greater importance, but is not universal. The aim of this study is to determine the self-reported screening, diagnosis and treatment practices of rheumatologists and respiratory physicians for SSc-related lung disease.. Email survey of 270 rheumatologists and 600 respiratory physicians.. Responses were received from 42 (16%) rheumatologists and 68 (11%) respiratory physicians. Of SSc patients seen by rheumatologists, 17% had ILD and 7.5% had a diagnosis of PAH compared with 31% and 21% for respiratory physicians. Forty per cent of all physicians screened asymptomatic SSc patients without a known diagnosis of ILD or PAH less than annually or not at all. The most commonly used screening investigations were pulmonary function tests (PFT) (95%) and transthoracic echocardiogram (TTE) (78%). In suspected ILD, both groups used high-resolution computed tomography scans and PFT in >90% of patients. In suspected PAH, both used TTE and PFT (>90%); right heart catheterisation was used by only 50% of physicians. In treatment of ILD, rheumatologists used intravenous (IV) cyclophosphamide more often (CYC) (59% vs 28%, P= 0.003) and more respiratory physicians used oral CYC (44% vs 28%, P= 0.012). In PAH, more respiratory physicians used warfarin (68% vs 40%, P= 0.006). Only approximately 65% of physicians had used specific PAH therapy, which may reflect lack of access to a designated PAH treatment centre.. The heterogeneity of responses revealed in this study raises the importance of screening, diagnosis and treatment algorithms in the management of this potentially life-threatening disease.

Topics: Cyclophosphamide; Data Collection; Diagnosis, Differential; Disease Management; Humans; Hypertension, Pulmonary; Lung Diseases, Interstitial; Mass Screening; Physicians; Respiration Disorders; Rheumatology; Scleroderma, Systemic; Treatment Outcome; Warfarin

Bayesian inference has the advantage of formally incorporating prior beliefs about the effect of an intervention into analyses of treatment effect through the use of prior probability distributions or "priors." Multiple methods to elicit beliefs from experts for inclusion in a Bayesian study have been used; however, the measurement properties of these methods have been infrequently evaluated. The objectives of this study were to evaluate the feasibility, validity, and reliability of a belief elicitation method for Bayesian priors.. A single-center, cross-sectional study using a sample of academic specialists who treat pulmonary hypertension patients was conducted to test the feasibility, face and construct validity, and reliability of a belief elicitation method. Using this method, participants expressed the probability of 3-year survival with and without warfarin. Applying adhesive dots or "chips," each representing 5% probability, in "bins" on a line, participants expressed their uncertainty and weight of belief about the effect of warfarin on 3-year survival.. Of the 12 participants, 11 (92%) reported that the belief elicitation method had face validity, 10 (83%) found the questions clear, and 11 (92%) found the response option easy to use. The median time to completion was 10 minutes (5-15 minutes). Internal validity testing found moderate agreement (weighted kappa=0.54-0.57). The intraclass correlation coefficient for test-retest reliability was 0.93.. This method of belief elicitation for Bayesian priors is feasible, valid, and reliable. It can be considered for application in Bayesian clinical studies.

Topics: Anticoagulants; Bayes Theorem; Bias; Canada; Cross-Sectional Studies; Humans; Hypertension, Pulmonary; Probability; Reproducibility of Results; Surveys and Questionnaires; Treatment Outcome; Warfarin

Bosentan is an endothelin-receptor antagonist that reportedly induces both cytochrome P450 (CYP) 3A4 and CYP2C9 enzymes, which are also involved in warfarin metabolism. We present a case report describing a probable drug interaction between warfarin and bosentan in a patient with pulmonary hypertension.. A 52-year-old black female (weight, 77 kg) diagnosed with pulmonary hypertension secondary to bilateral pulmonary emboli had a stable international normalized ratio (INR; target range, 2-3) with a weekly warfarin dose of 52.5 mg for 2 months before the initiation of bosentan therapy. Other concurrent medications included telmisartan/ hydrochlorothiazide 40/12.5 mg once daily and a daily multivitamin (which contained no vitamin K). Three weeks after starting bosentan 62.5 mg BID, a therapeutic INR concentration was reached with a weekly warfarin dose 14% higher (an increase of 7.5 mg/wk) than her weekly warfarin dose before initiation of bosentan. After a brief discontinuation (7 days) and retitration of bosentan and warfarin, the final weekly warfarin dose (75 mg/wk) was 43% greater (an increase of 22.5 mg/wk) than the previously stable dose, which enabled the patient to reach her therapeutic INR goal range of 2 to 3.. Bosentan has CYP3A4- and CYP2C9-inducing properties and is therefore likely to cause decreased concentrations of warfarin. We describe here a probable drug interaction between bosentan and warfarin that resulted in a 43% increase in warfarin dose to maintain the patient's therapeutic INR.

Topics: Anticoagulants; Antihypertensive Agents; Aryl Hydrocarbon Hydroxylases; Bosentan; Cytochrome P-450 CYP2C9; Cytochrome P-450 CYP3A; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Interactions; Female; Humans; Hypertension, Pulmonary; International Normalized Ratio; Middle Aged; Pulmonary Embolism; Sulfonamides; Treatment Outcome; Warfarin

Topics: Administration, Inhalation; Contrast Media; Follow-Up Studies; Humans; Hypertension, Pulmonary; Imaging, Three-Dimensional; Male; Middle Aged; Nitric Oxide; Oximetry; Piperazines; Purines; Radiographic Image Enhancement; Radiography, Thoracic; Risk Assessment; Severity of Illness Index; Sildenafil Citrate; Sulfones; Tomography, X-Ray Computed; Treatment Outcome; Warfarin

We describe the case of an 83-year-old man with a family history of pulmonary hypertension (PH) who presented with severe pulmonary arterial hypertension (PAH) and later tested positive for a novel bone morphogenetic protein receptor 2 (BMPR2) gene mutation. To our knowledge, this may be the oldest reported patient with PAH in whom a BMPR2 mutation was initially identified.

Topics: Aged, 80 and over; Amlodipine; Bone Morphogenetic Protein Receptors, Type II; Bosentan; Digoxin; Dyspnea; Humans; Hypertension, Pulmonary; Male; Pulmonary Artery; Sulfonamides; Warfarin

Selective right pulmonary arteriography and 3-dimensional computed tomography revealed multiple severe stenoses of the peripheral pulmonary artery associated with poststenotic aneurysms in a 65-year-old woman. She was referred to the hospital for evaluation of dry cough, gradually increasing dyspnea and multiple nodular shadows on a chest radiograph. Echocardiography and cardiac catheterization showed severe pulmonary hypertension, though other structural heart diseases or well-characterized congenital syndromes were ruled out. She was diagnosed as isolated peripheral pulmonary artery branch stenosis. Recent advances in CT technology enable a less-invasive assessment of pulmonary artery, and can be useful in the management of pulmonary arterial hypertension.

Topics: Aged; Aneurysm; Arterial Occlusive Diseases; Cardiac Catheterization; Constriction, Pathologic; Cough; Dyspnea; Epoprostenol; Female; Humans; Hypertension, Pulmonary; Imaging, Three-Dimensional; Oxygen Inhalation Therapy; Piperazines; Pulmonary Artery; Purines; Sildenafil Citrate; Sulfones; Tomography, X-Ray Computed; Ultrasonography; Vasodilator Agents; Warfarin

Topics: Adenoidectomy; Anesthetics, Intravenous; Anticoagulants; Antihypertensive Agents; Bosentan; Child; Down Syndrome; Elective Surgical Procedures; Epoprostenol; Female; Follow-Up Studies; Humans; Hypertension, Pulmonary; Intubation, Intratracheal; Piperazines; Piperidines; Propofol; Purines; Remifentanil; Severity of Illness Index; Sildenafil Citrate; Sleep Apnea, Obstructive; Sulfonamides; Sulfones; Tonsillectomy; Treatment Outcome; Vasodilator Agents; Warfarin

Topics: Anticoagulants; Antihypertensive Agents; Bosentan; Diagnostic Imaging; Drug Therapy, Combination; Electrocardiography; Female; Heart Defects, Congenital; Humans; Hypertension, Pulmonary; Middle Aged; Pulmonary Artery; Sulfonamides; Warfarin

Pulmonary arterial hypertension (PAH) remains a debilitating and life-threatening disease despite improvements in hemodynamics, exercise capacity and survival with recent therapeutic advances. Health-related quality of life (HRQOL) has, therefore, been proposed as an important outcome for evaluating care. Relatively little, however, is known regarding HRQOL or its determinants in PAH. The Minnesota Living with Heart Failure questionnaire was recently adapted and validated for HRQOL measurement in PAH. We applied this pulmonary hypertension-specific version (MLHF-PH) to a larger population of PAH patients.. Ninety-three consecutive outpatients with PAH completed the MLHF-PH. Scores were assessed for correlations with demographics, symptoms, hemodynamics and treatments.. Patients with PAH had significantly impaired HRQOL as assessed by the disease-specific MLHF-PH. Each physical and emotional component, as well as total scores on the MLHF-PH indicated severely depressed HRQOL. As compared to other diagnoses, PAH associated with scleroderma had the worst HRQOL. Patients with WHO functional Class II symptoms reported better HRQOL than Class III patients. Fatigue, weakness and abdominal discomfort were each associated with more severely depressed HRQOL, as was current epoprostenol use. With the sole exception of the right atrial pressure, hemodynamic measurements did not correlate with HRQOL scores. Simultaneous evaluation of HRQOL with a non-disease-specific questionnaire (SF-36) revealed a similarly impaired status, although identified fewer associations with patient-specific factors.. Severely impaired HRQOL is present in this population of patients with PAH evaluated with a disease-specific questionnaire. The availability of a pulmonary hypertension-specific HRQOL questionnaire may enable further targeted investigations of factors that might improve outcomes.

Topics: Activities of Daily Living; Adolescent; Adult; Aged; Aged, 80 and over; Analysis of Variance; Chest Pain; Epoprostenol; Fatigue; Female; Health Status; Hemodynamics; Humans; Hypertension, Pulmonary; Male; Middle Aged; Quality of Life; Sickness Impact Profile; Warfarin; Young Adult

In pulmonary arterial hypertension (PAH), thrombosis and thromboembolism occurs as a consequence of pulmonary microvasculopathy with a change of pulmonary vascular microenviroment toward a procoagulant, prothrombotic and antifibrinolytic pattern. Circulating antiphospholipid antibodies, increased plasma levels of platelet aggregating agents (serotonin, thromboxane), adhesion molecules (P selectin, von Willebrand factor), antifibrinolytic enzymes (plasminogen activator inhibitor 1) and prothrombotic cytokines have been identified in PAH patients so far. Thrombogenic pulmonary vasculopathy has been documented in many patients with PAH. Furthermore, most patients will not be diagnosed until right heart enlargement and impaired right ventricular function has developed. Thus, there is clear rationale for a treatment with anticoagulation. In four uncontrolled studies Warfarin improved the prognosis of patients with idiopathic and other forms of PAH. However, so far there are no prospective randomised studies evaluating the role of anticoagulants in the treatment of PAH. This review summarizes the current data and guidelines concerning anticoagulation in PAH.

Topics: Anticoagulants; Blood Platelets; Cardiomegaly; Cerebrovascular Disorders; Fibrinolysis; Humans; Hypertension, Pulmonary; Warfarin

Topics: Administration, Oral; Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Arginine; Aspirin; Hemolysis; Humans; Hypertension, Pulmonary; Male; Middle Aged; Spherocytosis, Hereditary; Vasodilator Agents; Warfarin

Pulmonary arterial hypertension (PAH) is characterized by elevated pulmonary vascular resistance which leads to right ventricular failure. Serotonin and the serotonin transporter play an important role in animal and human studies of PAH. We therefore hypothesized that PAH patients treated with high-affinity selective serotonin reuptake inhibitors (SSRIs) would have a reduced risk of death compared to PAH patients not treated with SSRIs.. We performed a retrospective cohort study of 84 consecutive adult PAH patients who underwent initial evaluation from January 1994 to June 2002 at the Pulmonary Hypertension Center of the New York Presbyterian Hospital. Patient-time while receiving high-affinity SSRIs (K(d)<1nmol) (paroxetine, sertraline, or fluoxetine) was considered "exposed". Patient-time while receiving tricyclic, atypical, or no antidepressants was considered "unexposed".. Thirteen of the 84 patients (15%) used high-affinity SSRIs during the study period. Five patients were taking high-affinity SSRIs at baseline and 8 initiated high-affinity SSRIs during the follow-up period. The median time from baseline evaluation until initiation of high-affinity SSRIs was 125 (0-1227) days. The median duration of high-affinity SSRI use was 482 (110-1624) days and the total at-risk time on high-affinity SSRIs was 18.1 person-years. Seventy-nine (94%) patients were treated with warfarin; 38 (45%) received continuous intravenous epoprostenol; 12 (14%) received continuous subcutaneous treprostinil, and 23 (27%) were treated with oral bosentan. The median follow-up was 764 days. Twenty-four patients died and one underwent lung transplantation during the study period. There were no differences in age, gender, diagnosis, hemodynamics, or incidence of acute vasoreactivity between SSRI users and non-users. The risk of death for high-affinity SSRI users was lower but not statistically significantly different from that of non-users (hazard ratio=0.53, 95% CI 0.07 to 3.9, p=0.53). Adjustment for demographics, diagnosis, hemodynamics, or other therapies did not significantly change this result.. SSRI use was associated with a 50% reduction in the risk of death in a cohort of PAH patients which was not statistically significant. Larger cohort studies may better define this relationship; an adequately powered trial of high-affinity SSRIs in PAH patients may be warranted.

Topics: Adult; Bosentan; Cardiac Catheterization; Cohort Studies; Digoxin; Drug Administration Routes; Epoprostenol; Female; Follow-Up Studies; Hemodynamics; Humans; Hypertension, Pulmonary; Lung Transplantation; Male; Pulmonary Circulation; Retrospective Studies; Selective Serotonin Reuptake Inhibitors; Sulfonamides; Survival Analysis; Treatment Outcome; Vasodilation; Warfarin

Unfractionated heparin has been a near universal anticoagulant for cardiac surgery; however it is contraindicated in heparin-induced thrombocytopenia type II. Alternative anticoagulants such as bivalirudin (a direct thrombin inhibitor) are being utilized. Bivalirudin was successfully used in an immunologically complex patient (diagnoses of heparin-induced thrombocytopenia type II, systemic lupus erythematosus, antiphospholipid syndrome, and dialysis-dependent renal failure) requiring cardiopulmonary bypass. Thrombotic events are common in antiphospholipid syndrome patients undergoing cardiac surgery utilizing high-dose heparin. This may represent unrecognized heparin-induced thrombocytopenia type II. Our patient did not experience perioperative thrombotic or bleeding complications. The possible cross-reactivity between heparin induced thrombocytopenia type II and antiphospholipid syndrome has not been investigated.

Topics: Adult; Antibody Specificity; Anticoagulants; Antiphospholipid Syndrome; Autoantibodies; Cross Reactions; Drug Evaluation; Drug Therapy, Combination; Female; Heart Failure; Heparin; Hirudins; Humans; Hypertension, Pulmonary; Kidney Failure, Chronic; Lupus Erythematosus, Systemic; Mitral Valve Insufficiency; Peptide Fragments; Platelet Count; Platelet Factor 4; Recombinant Proteins; Renal Dialysis; Thrombocytopenia; Thrombophilia; Warfarin

Patients with heparin-induced thrombocytopenia requiring urgent cardiac surgery present a unique challenge that must be addressed by the use of nonheparin alternatives for anticoagulation during cardiopulmonary bypass. Although isolated cases have been presented involving the use of antithrombin III independent thrombin inhibitor hirudin in this situation, its ability to completely inhibit thrombin activity has not been demonstrated. In this report we describe the efficacy of this drug in inhibiting thrombin during a case requiring prolonged cardiopulmonary bypass.

Topics: Aged; Anticoagulants; Blood Coagulation; Cardiopulmonary Bypass; Chondroitin Sulfates; Contraindications; Dermatan Sulfate; Endarterectomy; Female; Heparin; Heparitin Sulfate; Hirudins; Humans; Hypertension, Pulmonary; Plasma; Platelet Transfusion; Pulmonary Embolism; Recombinant Proteins; Thrombectomy; Thrombin; Thrombocytopenia; Time Factors; Warfarin

The present study describes a case of pulmonary arterial hypertension (PAH) associated with multicentric Castleman's disease in a patient infected with HIV type 1 and human herpes virus 8. Therapy included highly active antiretroviral therapy, warfarin, diuretics, continuous i.v. epoprostenol and 12-monthly pulses of cyclophosphamide. The patient's condition improved dramatically with complete reversibility of PAH, allowing weaning of continuous i.v. epoprostenol therapy. After 5 yrs, both Castleman's disease and PAH have not relapsed. This supports the hypothesis that control of inflammation and retroviral replication may be of interest in the context of PAH, complicating the course of an inflammatory condition associated with viral infection. In conclusion, further studies should help in characterising the best candidates for anti-inflammatory treatment in the setting of pulmonary arterial hypertension.

Topics: Adult; Anti-Retroviral Agents; Castleman Disease; Cyclophosphamide; Diuretics; Epoprostenol; Female; HIV Infections; HIV-1; Humans; Hypertension, Pulmonary; Treatment Outcome; Warfarin

Topics: Acute Kidney Injury; Adult; Anticoagulants; Biopsy; Female; Glomerulosclerosis, Focal Segmental; Hematuria; Humans; Hypertension, Pulmonary; International Normalized Ratio; Lupus Erythematosus, Systemic; Lupus Nephritis; Pneumonia; Pulmonary Embolism; Warfarin

Inflammatory processes seem to be involved in pulmonary arterial hypertension (PAH). CD40 ligand (L) may promote inflammation and thrombus formation, and we hypothesized that CD40L could be involved in the pathogenesis of PAH.. Several significant findings were revealed when examining the possible role of CD40L in PAH. (1) Patients with primary (n=13) and secondary (n=11) PAH but not those with chronic thromboembolic pulmonary hypertension (n=8) had increased plasma levels of soluble (s) CD40L compared with control subjects (n=8). (2) PAH patients using warfarin had markedly lower sCD40L levels than those without such therapy. (3) sCD40L levels were higher in arterial (femoral artery) compared with mixed venous blood (pulmonary artery), suggesting enhanced release or reduced clearance in the pulmonary vasculature. (4) Platelets from PAH patients showed enhanced spontaneous and SFLLRN-stimulated release of sCD40L compared with control subjects. (5) In vitro, recombinant sCD40L induced monocyte chemoattractant protein (MCP)-1 and interleukin-8 gene expression in endothelial cells, and plasma levels of these chemokines were raised in all PAH groups, significantly correlated to sCD40L and hemodynamic parameters. (6) Although prostacyclin therapy (3 months) showed clinical benefit, this therapy had no effect on sCD40L and increased MCP-1 levels in PAH patients, and prostacyclin enhanced MCP-1 in CD40L-stimulated endothelial cells.. Our findings suggest a role for CD40L in the pathogenesis of PAH, possibly operating through an interaction between platelets and endothelial cells involving chemokine-related mechanisms.

Topics: Aged; Anticoagulants; Blood Platelets; CD40 Ligand; Cells, Cultured; Chemokine CCL2; Collagen Diseases; Endothelial Cells; Endothelium, Vascular; Epoprostenol; Female; Femoral Artery; Gene Expression Regulation; Heart Defects, Congenital; HIV Infections; Humans; Hypertension, Pulmonary; Interleukin-8; Liver Cirrhosis; Male; Middle Aged; Peptide Fragments; Pulmonary Artery; Recombinant Proteins; Solubility; Thromboembolism; Umbilical Veins; Warfarin

We report the case of a 48-year-old woman with a diagnosis of pulmonary hypertension and hyperthyroidism (Graves' disease) in whom pulmonary artery pressures became normal after treatment of thyroid disease. The possible pathogenic mechanisms involved in this association include the presence of hyperdynamic heart failure and/or the presence of immune alterations underlying both conditions.

Topics: Anticoagulants; Antithyroid Agents; Autoimmunity; Cardiotonic Agents; Digitalis Glycosides; Female; Graves Disease; Humans; Hypertension, Pulmonary; Hyperthyroidism; Middle Aged; Spain; Warfarin

Pulmonary hypertension (PH) sometimes occurs in patients with systemic lupus erythematosus (SLE). We report a case of 51-year-old-woman with PH associated with SLE. She had been diagnosed as SLE on the basis of pericardial effusion, hematological disorder, positive antinuclear antibody, and hypocomplementemia. Despite minimal lupus activity, she had marked elevation of pulmonary arterial pressure (101/53 mmHg) and decreased cardiac index (1.5 l/min/m2). Symptoms related to PH were progressive under treatment with oral corticosteroids, oxygen, calcium antagonists, and warfarin. After 17 months of epoprostenol treatment, she died of pulmonary infarction. SLE-associated PH is often severe and progressive even in association with minimal activity.

Topics: Anticoagulants; Autoimmune Diseases; Calcium Channel Blockers; Disease Progression; Epoprostenol; Fatal Outcome; Female; Hemodynamics; Humans; Hypertension, Pulmonary; Hypertrophy, Right Ventricular; Lupus Erythematosus, Systemic; Middle Aged; Oxygen; Prednisolone; Pulmonary Embolism; Warfarin

Topics: Adult; Anticoagulants; Female; Fluorescein Angiography; Humans; Hypertension, Pulmonary; Isosorbide Dinitrate; Retinal Vein Occlusion; Vasodilator Agents; Visual Acuity; Warfarin

Pregnancy associated with primary pulmonary hypertension is an uncommon observation, with maternal mortality > 50%. Experience treating this condition is limited. Past reports have emphasized the need for pregnancy termination. In the last few years there has been considerable interest in long-term intravenous use of epoprostenol (prostacyclin) in patients with primary pulmonary hypertension.. A woman with severe primary pulmonary hypertension who was on long-term epoprostenol therapy became pregnant with twins and was treated with high doses of epoprostenol and nitric oxide during delivery and the postpartum period. She was well six months later on continuous epoprostenol therapy. The one viable infant was alive and still hospitalized at this writing.. Epoprostenol therapy may be continued during pregnancy in patients with severe primary pulmonary hypertension for long-term pulmonary vasodilatation.

Topics: Abnormalities, Drug-Induced; Adult; Anticoagulants; Antihypertensive Agents; Bronchodilator Agents; Epoprostenol; Face; Female; Humans; Hydrocephalus; Hypertension, Pulmonary; Nitric Oxide; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy Outcome; Pregnancy, Multiple; Syndrome; Twins; Warfarin

A 15 year-old girl was admitted to the hospital because of fever, polyarthlargia, dry cough, dyspnea, butterfly rash and multiple oral aphthas. The diagnosis of systemic lupus erythematosus (SLE) was made based on renal disorders, pancytopenia, positive antinuclear antibody and positive for antibodies to double-stranded DNA. On admission, she developed progressive dyspnea with highly active SLE. The patient was complicated with both pulmonary hypertension (PH) and interstitial pneumonitis (IP), judging from increased pulmonary sound by an auscultation, interstitial shadows especially at bilateral lower lung and enlarged shadow of right atrium in a chest rentgenogram, ground glass pattern of bilateral middle to lower lung in a chest computed tomographic scan, increased pulmonary artery pressure, 53 mmHg, by an ultrasound cardiograph (UCG). Combination of methylprednisolone pulse therapy, cyclosporin A and plasma exchanges was effectively administered, which resulted in improvement of disease activity of SLE, IP and PH. However, two months later, although disease activity of SLE was completely reduced, recurrence of PH by UCG and multiple pulmonary embolism (PE) which was observed by a chest rentgenogram and a pulmonary blood flow scintigraphy was further complicated. Administration of cyclophosphamide pulse therapy and warfarin therapy improved both PE and PH. The patient had PH at the different clinical course of SLE; 1) PH maybe induced by severe IP at the active phase of SLE and 2) PH brought about from multiple PE at the inactive phase of SLE. Thus, the case is thought to be suggestive of elucidating the pathogenesis of PH of several systemic autoimmune diseases including SLE.

Topics: Adolescent; Cyclophosphamide; Female; Humans; Hypertension, Pulmonary; Lung Diseases, Interstitial; Lupus Erythematosus, Systemic; Plasma Exchange; Pulmonary Embolism; Pulse Therapy, Drug; Recurrence; Treatment Outcome; Warfarin

Severe pulmonary hypertension (PHT) occurring in patients with systemic lupus erythematosus (SLE) is uncommon. Different modalities have been tried in the treatment for this condition but have not been effective because of progressive increase of pulmonary resistance over time. Our patient with SLE and PHT with antiphospholipid syndrome (APS), a condition which has previously never been described, responded rapidly to combination treatment with immunosuppression, anticoagulation and vasodilator therapy.

Topics: Adult; Anticoagulants; Antiphospholipid Syndrome; Cyclophosphamide; Diltiazem; Female; Humans; Hypertension, Pulmonary; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Prednisone; Vasodilator Agents; Warfarin

In a retrospective study, we tested the hypothesis that anticoagulant therapy with warfarin sodium (Coumadin) has a beneficial influence on the long-term prognosis in patients with primary pulmonary hypertension (PPH) and aminorex-induced plexogenic pulmonary hypertension. The study included a total of 173 patients from two European cities. One hundred four of these patients took the anorectic drug aminorex (Menocil), which was available in some European countries almost 30 years ago; 69 patients had pulmonary hypertension of unexplained etiology, ie, PPH. Fifty-six of the 104 aminorex-treated patients and 24 patients in the PPH group received warfarin after diagnosis was established. For analysis, patients were divided into four groups according to their history of aminorex intake and anticoagulant therapy. Survival time, changes in hemodynamics (pulmonary arterial pressure), and improvement in quality of life (scored by the New York Heart Association [NYHA] classification) were compared and analyzed. We found that aminorex-treated patients had a better long-term prognosis than those with PPH (7.5 vs 3.9 years; p < or = 0.001). The best mean survival time of 8.3 years was found in anticoagulated aminorex-treated patients, compared to 6.1 years in nonanticoagulated aminorex-treated patients. Moreover, aminorex-treated patients who received anticoagulant therapy soon after the onset of symptoms showed significantly better prognosis (10.9 years) than those who commenced treatment 2 years thereafter (5.9 years) (p < or = 0.05). In patients with PPH, systolic pulmonary pressure was shown to influence survival time significantly (p < or = 0.0005); however, this correlation was not found in aminorex-treated patients. An improvement of symptoms like dyspnea on exertion was seen in 44.8% of the anticoagulated aminorex-treated patients, while deterioration was evident in 72.2% of the nonanticoagulated aminorex-treated patients. In conclusion, our study has shown that anticoagulant therapy had a positive influence on long-term survival and a significant improvement in quality of life in patients with PPH, in particular in patients with a history of anorectic drug intake.

Topics: Adolescent; Adult; Aged; Aminorex; Analysis of Variance; Anorexia; Anticoagulants; Appetite Depressants; Blood Pressure; Dyspnea; Female; Hemodynamics; Humans; Hypertension, Pulmonary; Longitudinal Studies; Male; Middle Aged; Physical Exertion; Prognosis; Proportional Hazards Models; Pulmonary Artery; Quality of Life; Retrospective Studies; Survival Rate; Systole; Time Factors; Warfarin

To improve the identification of chronic thromboembolic pulmonary hypertension. We restrospectively analysed clinical data of 72 patients with chronic thromboembolic pulmonary hypertension (CTEPH). The levels of arterial blood gases appeared to be decrease in PaO2 and PaCO2, and increase in P(A-a)O2. There were 80.3% of unsymmetrical pulmonary hyperlucencies on chest radiograph and 76.4% of right ventricular hypertrophy on electrocardiograph, 92.5% and 97.1% of right atrial and right ventricular enlargement, respectively. 11.1% of pericardial effusion was noted on echocardiograph, and 98.5% of rise in pulmonary arterial pressure calculated by Doppler. The mean pulmonary arterial pressure was 6.50 +/- 1.80 kPa (48.75 +/- 13.50 mmHg), in part, by right cardiac catheterazation. Both the incidences of pulmonary embolism were 100.0% on pulmonary angiography and on radionuclide lung perfusion scan. There were 43.1% of the history of deep venous disorders and 75.0% of the positive findings by radionuclide venography in the lower extremities, respectively. The misdiagnostic and the lost diagnosis rate of prehospitalization accounted for 90.3%. The understanding of clinical manifestations and laboratory findings of CTEPH is important to promote diagnostic sense and level of CTEPH.

Topics: Adolescent; Adult; Aged; Anticoagulants; Blood Gas Analysis; Diagnostic Errors; Female; Humans; Hypertension, Pulmonary; Male; Middle Aged; Pulmonary Embolism; Retrospective Studies; Warfarin

Patients with pulmonary embolism may have no definitive predisposing factors for thrombi. The clinical entity of chronic pulmonary embolism is also uncertain. This study clarified the clinical characteristics of pulmonary embolism without definitive predisposing factors. During the last 10 years, 36 consecutive patients were diagnosed as having pulmonary embolism (mean age 61 years, female 75%). Twenty-four patients (67%) had definitive predisposing factors ("definitive" group). Patients without definitive predisposing factors had the following characteristics. The onset of symptoms was out-hospital and insidious. The main symptom was exertional dyspnea without acute episode compatible with an embolism. In four patients (33%) there was a delay of over 2 years form the onset of symptoms to the diagnosis. Three patients had been treated for depression. Thrombolytic therapy caused an inadequate fall in mean pulmonary artery pressure from 41 +/- 11 to 24 +/- 8 mmHg and in three patients it remained over 30 mmHg. Deep vein thrombosis were found in four of nine patients in whom venography were performed 10 days after thrombolytic therapy, but only one patient showed thrombus in the "definitive" group. During the convalescent stage, all patients were treated with prophylactic warfarin. Home oxygen therapy was indicated in three patients and an inferior vena caval filter was implanted in two patients. One third of patients with pulmonary embolism in our institute had no definitive predisposing factors. In these patients, even with thrombolytic therapy, recovery of pulmonary hypertension was often insufficient and deep vein thrombosis persisted. Clinicians should be aware of this disease to avoid undue delay in its diagnosis.

Topics: Aged; Female; Humans; Hypertension, Pulmonary; Male; Middle Aged; Neoplasms; Obesity; Prognosis; Pulmonary Embolism; Thrombolytic Therapy; Thrombophlebitis; Warfarin

We report about the history of a 53-year-old female who suffered from dyspnea as well as leg and chest pain for six months; in addition she experienced two syncopal events. Recurrent pulmonary embolism was suspected, which was subsequently confirmed by positive scintigraphical findings. Acute cor pulmonale may have caused the syncopes. Therapy with heparin and oral warfarin was started. Within few days the patients condition improved markedly. Signs of pulmonary hypertension disappeared within five months.

Topics: Chest Pain; Dyspnea; Female; Humans; Hypertension, Pulmonary; Leg; Middle Aged; Pulmonary Embolism; Thrombosis; Warfarin

This is the report of a series of eight patients with pulmonary hypertension (primary and secondary) who delivered at the McMaster University Medical Centre between 1978 and 1987. Seven of the eight patients delivered vaginally and had a successful outcome. The eighth patient was admitted as an emergency and died shortly after Caesarean section under general anaesthesia, performed to save the infant. The other seven patients were all managed by a team, including anaesthetists, cardiologists and obstetricians, from about 25 wk. The patients were hospitalized pre-partum and received oxygen therapy and anticoagulation with heparin. Analgesia in labour was managed, once anticoagulation was reversed, by low concentrations of epidural bupivacaine (0.125%-0.375%) and fentanyl. The patients were monitored during labour and delivery with oximetry and arterial and central venous pressure lines. Pulmonary arterial lines were not used because of increased risk and questionable usefulness. Vaginal delivery was managed with vacuum extraction or forceps lift-out to minimize the stress of pushing. After delivery, all patients were monitored in an intensive care unit for several days, anticoagulation was restarted, and all patients were discharged home taking oral anticoagulant therapy. The successful management of pulmonary hypertension in pregnancy should include team management started early in pregnancy and controlled vaginal delivery utilizing epidural analgesia.

Topics: Adult; Anesthesia, Epidural; Anesthesia, Obstetrical; Delivery, Obstetric; Ductus Arteriosus, Patent; Eisenmenger Complex; Female; Heart Septal Defects, Atrial; Heart Septal Defects, Ventricular; Heart Valve Diseases; Heparin; Humans; Hypertension, Pulmonary; Mitral Valve; Monitoring, Physiologic; Obstetric Labor Complications; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy Outcome; Warfarin

The purpose of this study was to examine the influence of treatment on long-term prognosis of patients with aminorex-induced plexogenic pulmonary hypertension. The study included 104 patients (13 males, 91 females) with an aminorex (menocil) intake between 1966 and 1968. All patients were treated with digitalis and diuretics, 52% received an anticoagulant medication with warfarin after pulmonary hypertension was diagnosed. During follow-up, a second right-heart catheterization was performed in 37 patients with a mean interval of 5 years. The longest mean survival time, 8.3 years, was found in patients treated with anticoagulant medication, compared to the 6.1 years found in the non-anticoagulated aminorex patients. Also, in the 5- and 10-years survival rate, patients with an anticoagulant therapy have shown better results (62.9 vs. 38% and 39 vs. 20%, respectively). Patients who received anticoagulant therapy soon after the onset of symptoms showed a better mean survival (10.9 years) than those who commenced treatment more than 1 year thereafter (mean survival 5.9 years). In 57% of the patients who had a second right-heart catheterization a decrease of pulmonary pressures could be diagnosed. Two-thirds of these patients with pulmonary pressure decrease were under anticoagulant therapy. An improvement in the NYHA-classification was seen in 44.8% of the patients treated with warfarin, in comparison to 22.2% of those who did not receive anticoagulant therapy. Although this study is retrospective, it shows a positive influence of anticoagulant therapy on survival in patients with a history of anorectic drug intake.

Topics: Adrenal Cortex Hormones; Adrenergic alpha-Antagonists; Aged; Aminorex; Digitalis Glycosides; Diuretics; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Hypertension, Pulmonary; Male; Pulmonary Wedge Pressure; Quality of Life; Retrospective Studies; Survival Rate; Warfarin

A therapy consisting of a combination of an anticoagulant and a vasodilator was investigated to determine its effects on the long-term prognosis of primary pulmonary hypertension (PPH). Twenty patients with PPH who had undergone diagnostic catheterization in our hospital were studied. The mean follow-up period after the initial catheterization was 6 years, with the longest follow-up being 24.4 years. Seven patients were treated with warfarin as an anticoagulant, combined with either isoproterenol (3 patients) or nifedipine (4 patients) as a vasodilator (AV group). The remaining 13 patients were not treated (control group). Although there were no significant differences in the physical activity or hemodynamics between the groups, improvement was seen in 43% of the AV group and in only 7.6% of the controls. The 5 year survival rate was significantly higher in the AV group (57% vs 15%; P < 0.05). Hemodynamics were evaluated repeatedly in 8 patients and improvement was seen only in the AV group. These results suggest that a therapy consisting of a combination of an anticoagulant and a vasodilator may improve the long-term prognosis of PPH.

Topics: Adolescent; Adult; Drug Combinations; Female; Hemodynamics; Humans; Hypertension, Pulmonary; Isoproterenol; Male; Middle Aged; Nifedipine; Prognosis; Survival Rate; Warfarin

Chronic hypoxia produces pulmonary hypertension and pulmonary vascular remodeling. Heparin partially prevents the rise in right ventricular pressure and vascular remodeling in chronically hypoxic mice. To determine if this is due to the anticoagulant property of heparin or another property, we compared the effect of oral warfarin given at an anticoagulating dose (0.5 mg/kg/day) to heparin given by continuous infusion at a dose that does not prolong the partial thromboplastin time (PTT) (20 units/kg/h) on hypoxic pulmonary hypertension and vascular remodeling in the guinea pig. Normoxic control animals either untreated or treated with heparin or Coumadin were all alike in blood gases, pulmonary vascular resistance, right heart weights, and pulmonary histology. Hypoxia (10% 0(2) for 10 days) induced similar and significant increases in mean pulmonary artery (PA) pressure in both the hypoxic control and warfarin groups (19 +/- 1 mm Hg (mean +/- SEM) in both groups versus 11 +/- 0.1 mm Hg in the normoxic control group; p less than 0.05). Total pulmonary vascular resistance (TPR) was also increased from 0.041 +/- 0.002 in the normoxic control group to 0.087 +/- 0.007 and 0.071 +/- 0.003 mm Hg/ml/min/kg in the hypoxic control and warfarin groups, respectively (p less than 0.05). Whereas anticoagulation with warfarin did not protect the guinea pig from developing pulmonary hypertension, heparin markedly reduced PA and TPR (15 +/- 1 mm Hg and 0.052 +/- 0.002 mm Hg/ml/min/kg, respectively; p less than 0.05 versus hypoxic control or warfarin).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Blood Coagulation; Blood Vessels; Chronic Disease; Guinea Pigs; Hemodynamics; Heparin; Hypertension, Pulmonary; Hypoxia; Male; Partial Thromboplastin Time; Prothrombin Time; Pulmonary Circulation; Warfarin

Primary pulmonary hypertension carries a poor prognosis, with a 5 year survival rate of less than 25%. However, a previous study of more than 100 patients with tissue-proved primary pulmonary hypertension suggested that antithrombotic therapy may have a beneficial effect on survival, especially in patients with the thromboembolic type of primary pulmonary hypertension. This report describes a 54 year old white man with primary pulmonary hypertension of the thromboembolic type (proved by right upper lobe lung biopsy) who, after long-term antithrombotic therapy, showed resolution of symptoms of dyspnea and fatigue, regression of electrocardiographic signs of right ventricular hypertrophy and regression of elevated pulmonary artery pressure. Base-line cardiac catheterization in January 1982 revealed elevated pulmonary artery pressure (104/37 mm Hg) and pulmonary vascular resistance (14.6 units/m2) that did not decrease with 100% oxygen or intravenous hydralazine (12 mg). The patient was treated with warfarin and dipyridamole, 100 mg four times daily. The most recent cardiac catheterization in January 1984 revealed a pulmonary artery pressure of 50/15 mm Hg and a pulmonary vascular resistance of 8.7 units/m2. It is believed that this is the first report of regression of the symptoms and signs of biopsy-proved primary pulmonary hypertension. In view of the lack of a response to vasodilators in 1982, it is suggested that antithrombotic therapy is partially responsible for the improvement of this patient.

Topics: Cardiac Catheterization; Dipyridamole; Follow-Up Studies; Hemodynamics; Humans; Hypertension, Pulmonary; Male; Middle Aged; Pulmonary Embolism; Warfarin

A patient with a circulating lupus anticoagulant in the absence of systemic lupus erythematosus developed recurrent deep venous thromboses and pulmonary emboli. Pulmonary emboli recurred despite prolonged oral anticoagulant therapy and resulted in fatal pulmonary arterial hypertension. Extended anticoagulant therapy alone may not prevent recurrent thromboembolism in patients with a lupus anticoagulant. Pulmonary thromboembolism may be an important factor in the pathogenesis of pulmonary hypertension in patients with a lupus anticoagulant.

Topics: Adult; Blood Coagulation Disorders; Blood Coagulation Factors; Humans; Hypertension, Pulmonary; Lupus Coagulation Inhibitor; Male; Pulmonary Embolism; Thrombophlebitis; Warfarin

Topics: Adult; Aged; Fibrinolytic Agents; Humans; Hypertension, Pulmonary; Male; Middle Aged; Pulmonary Embolism; Recurrence; Warfarin

Topics: Aged; Female; Fibrinolytic Agents; Heparin; Humans; Hypertension, Pulmonary; Pulmonary Embolism; Recurrence; Warfarin

Fourteen patients were treated with anticoagulants during 15 pregnancies. Eleven had venous thrombosis, three with pulmonary embolism; three had prosthetic heart valves; and one had mitral stenosis with pulmonary hypertension. All 15 were treated with heparin and 10 with warfarin. The mean duration of heparin therapy was 4.5 weeks and of warfarin 14 weeks. There were two minor episodes of recurrent thromboembolism and three minor haemorrhagic episodes during anticoagulant therapy. No fetal or neonatal complications occurred.There appears to be no ideal anticoagulant regimen for treating thromboembolic disease in pregnancy. A compromise approach based on experimental and clinical findings is suggested, which is considered to offer reasonable protection to the mother without undue risk to the fetus. This is heparin when an anticoagulant is indicated in the first trimester, after 37 weeks' gestation, and for the treatment of the initial thromboembolic episodes. Oral anticoagulants are used at other times when long-term anticoagulant therapy is indicated.

Topics: Adolescent; Adult; Female; Fetal Diseases; Fetus; Heart Valve Prosthesis; Hemorrhage; Heparin; Humans; Hypertension, Pulmonary; Infant, Newborn; Mitral Valve Stenosis; Pregnancy; Pregnancy Complications, Cardiovascular; Pulmonary Embolism; Thrombophlebitis; Warfarin

Topics: Anticoagulants; Embolism; Humans; Hypertension, Pulmonary; Myocardial Infarction; Phenindione; Renal Artery Obstruction; Rheumatic Heart Disease; Thrombosis; Warfarin