Advertisement

Topics

Anticoagulation For Pulmonary Hypertension in Sickle Cell Disease

2014-08-27 03:17:07 | BioPortfolio

Summary

Sickle cell disease (SCD) is often referred to as a hypercoagulable state. However, the contribution of coagulation activation to the pathogenesis of SCD remains uncertain. Pulmonary hypertension (PHT) is a common complication associated with significant morbidity and mortality. Autopsy studies of SCD patients with PHT show evidence of in situ thrombosis involving pulmonary vessels, similar to findings in non-sickle cell patients with PHT. Anticoagulation has been reported to be of benefit in non-sickle cell patients with PHT. With the evidence of increased coagulation activation in SCD, PHT represents a clinical endpoint that may be used to evaluate the contribution of coagulation activation to the pathophysiology of SCD. The investigators hypothesize that increased thrombin generation, as well as platelet activation are central to the pathophysiology of SCD and contribute to the occurrence of several SCD-related complications, including PHT. As a consequence, treatment modalities that down-regulate thrombin generation would be expected to delay the progression of PHT and result in improved survival in patients with SCD.

Description

As a result of the presence of large vessel thrombotic complications, as well as the biochemical evidence of ongoing coagulation activation, sickle cell disease (SCD) is often referred to as a hypercoagulable state. However, the contribution of coagulation activation to the pathogenesis of SCD remains uncertain. While the majority of clinical studies using anticoagulants have shown no convincing benefit in the prevention or treatment of acute pain episodes, most of these studies were small and poorly controlled. Furthermore, because the acute pain episode appears to result from the occlusion of postcapillary venules by the interaction of red blood cells and other cellular elements with the vascular endothelium and subendothelial matrix proteins, it may not be the ideal clinical endpoint for assessing the effect of anticoagulation in SCD patients. Pulmonary hypertension (PHT), a common complication associated with significant morbidity and mortality, and with histopathologic findings of in situ thrombosis involving pulmonary vessels, represents a clinical endpoint that is likely due, at least in part, to increased thrombin generation, and may therefore be used to evaluate the contribution of coagulation activation to the pathophysiology of SCD. Twenty patients with sickle cell anemia (HbSS) or sickle beta zero thalassemia (Sickle beta zero thalassemia) and mild PHT who meet the eligibility requirements will be enrolled, 10 patients to receive anticoagulation with warfarin and 10 to receive placebo rfor 12 months of treatment.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Conditions

Pulmonary Hypertension

Intervention

Warfarin

Location

University of North Carolina
Chapel Hill
North Carolina
United States
27599

Status

Recruiting

Source

University of North Carolina, Chapel Hill

Results (where available)

View Results

Links

Published on BioPortfolio: 2014-08-27T03:17:07-0400

Clinical Trials [2079 Associated Clinical Trials listed on BioPortfolio]

AntiCoagulant Effectiveness in Idiopathic Pulmonary Fibrosis

This study will test the effectiveness of warfarin in patients with IPF. Approximately 256 patients will be randomized 1:1 to either warfarin or placebo. Patients will return at week 1 f...

Gene Mutations in Secondary Pulmonary Hypertension

As a pulmonary hypertension center, we have created a database that prospectively tracks patients with different forms of secondary pulmonary hypertension. Records include genetic analysi...

Early Recognition of Pulmonary Arterial Hypertension in Myelodysplastic and Myeloproliferative Diseases

Myelodysplastic and myeloproliferative Disease represent conditions with increased risk for pulmonary hypertension. However, the exact prevalence of pulmonary hypertension in these conditi...

Riociguat Versus Balloon Pulmonary Angioplasty in Non-operable Chronic thromboEmbolic Pulmonary Hypertension

"Chronic thromboembolic pulmonary hypertension (CTEPH) is a severe form of pulmonary hypertension characterized by obstruction of the pulmonary vasculature by residual organized thrombi, l...

Bosentan Effects in Inoperable Forms of Chronic Thromboembolic Pulmonary Hypertension

The present trial investigates a possible use of oral bosentan, which is currently approved for the treatment of symptoms of pulmonary arterial hypertension (PAH), to patients suffering fr...

PubMed Articles [4214 Associated PubMed Articles listed on BioPortfolio]

Out of proportion pulmonary hypertension in obstructive lung diseases.

Pulmonary hypertension is common (25-90%) in chronic obstructive pulmonary diseases (COPDs). Severe pulmonary hypertension, however, is quite rare (1-3%). The term 'out of proportion' pulmonary hypert...

Adherence and medication belief in patients with pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension- A nationwide population-based cohort survey.

Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) are rare diseases with a gradual decline in physical health. Adherence to treatment is crucial in these ...

Association between Rheumatoid Arthritis and Pulmonary Hypertension: Data from the French Pulmonary Hypertension Registry.

Precapillary pulmonary hypertension (PH), and particularly pulmonary arterial hypertension (PAH), is a life-threatening complication of connective tissue diseases (systemic sclerosis, systemic lupus e...

Balloon pulmonary angioplasty in a patient with prostate cancer and chronic thromboembolic pulmonary hypertension.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a subtype of pulmonary hypertension characterized by a mean pulmonary artery pressure ≥25 mm Hg due to obstructive fibrotic thromboemboli...

Hemolysis-induced Lung Vascular Leakage Contributes to the Development of Pulmonary Hypertension.

While hemolytic anemia-associated pulmonary hypertension (PH) and pulmonary arterial hypertension (PAH) are more common than the prevalence of idiopathic PAH alone, the role of hemolysis in the develo...

Medical and Biotech [MESH] Definitions

An anticoagulant that acts by inhibiting the synthesis of vitamin K-dependent coagulation factors. Warfarin is indicated for the prophylaxis and/or treatment of venous thrombosis and its extension, pulmonary embolism, and atrial fibrillation with embolization. It is also used as an adjunct in the prophylaxis of systemic embolism after myocardial infarction. Warfarin is also used as a rodenticide.

Hypertrophy and dilation of the RIGHT VENTRICLE of the heart that is caused by PULMONARY HYPERTENSION. This condition is often associated with pulmonary parenchymal or vascular diseases, such as CHRONIC OBSTRUCTIVE PULMONARY DISEASE and PULMONARY EMBOLISM.

Familial or idiopathic hypertension in the PULMONARY CIRCULATION which is not secondary to other disease.

A prostaglandin that is a powerful vasodilator and inhibits platelet aggregation. It is biosynthesized enzymatically from PROSTAGLANDIN ENDOPEROXIDES in human vascular tissue. The sodium salt has been also used to treat primary pulmonary hypertension (HYPERTENSION, PULMONARY).

A multisystemic disorder characterized by a sensorimotor polyneuropathy (POLYNEUROPATHIES), organomegaly, endocrinopathy, monoclonal gammopathy, and pigmentary skin changes. Other clinical features which may be present include EDEMA; CACHEXIA; microangiopathic glomerulopathy; pulmonary hypertension (HYPERTENSION, PULMONARY); cutaneous necrosis; THROMBOCYTOSIS; and POLYCYTHEMIA. This disorder is frequently associated with osteosclerotic myeloma. (From Adams et al., Principles of Neurology, 6th ed, p1335; Rev Med Interne 1997;18(7):553-62)

More From BioPortfolio on "Anticoagulation For Pulmonary Hypertension in Sickle Cell Disease"

Advertisement
Quick Search
Advertisement
Advertisement

 

Relevant Topic

Pulmonary Hypertension
Pulmonary arterial hypertension (PAH) is a chronic, life-threatening disorder characterized by abnormally high blood pressure in the arteries between the heart and lungs of affected individuals. Symptoms can range from mild breathles...


Searches Linking to this Trial