This protocol permits the evaluation and treatment of subjects with hereditary and acquired hemolytic diseases, to facilitate understanding of the pathogenesis and natural history of vaso-occlusive painful crisis and pulmonary complications of sickle cell disease and related cardiopulmonary complications of other hereditary, acquired and iatrogenic hemolytic disorders. We will also investigate the polymorphisms that have been linked to pulmonary hypertension to determine whether genetic polymorphisms in candidate genes contribute to the development of pulmonary hypertension or response to treatment. Patients will be evaluated with a medical history and physical examination and routine laboratory studies will be obtained as needed to assess diagnosis, disease activity, and disease complications and to monitor for treatment-related responses and toxicities. Blood can be obtained, with subjects consent, for research studies evaluating gene/protein expression and to evaluate the role of vasodilators, vasoconstrictors, inflammatory and redox stress mediators in this population. Patients identified with pulmonary hypertension will have the option to undergo invasive hemodynamic evaluation and treatment with FDA approved drugs, according to current standards of medical practice, with signed informed consent for all offered procedures. Patients eligible for other research protocols will be offered an opportunity to participate in these studies by signed informed consent. Apart from such protocols, any medical care recommended or provided to the patient will be consistent with routine standards of practice and will be provided in consultation with the patients referring physician. In addition to the clinically indicated tests we revised the study to include peripheral arterial tonometry, an FDA approved non-invasive technology that captures a beat-to-beat plethysmographic recording of the finder arterial pulse wave activity with pneumatic probes. We also included passive infrared photography for assessment of blood flow distribution and vasomotion and are performing candidate gene analysis on the blood obtained from the subjects enrolled in this study to investigate the potential determinants or genetic risk factors for the development of pulmonary hypertension. We have successfully enrolled a total of 283 subjects to date. We continue to gather clinical data and experience related to the care of patients with sickle cell disease and other hemolytic disorders.

Project Start
Project End
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Budget End
Support Year
1
Fiscal Year
2009
Total Cost
$509,086
Indirect Cost
Name
National Heart, Lung, and Blood Institute
Department
Type
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Weir, Nargues A; Saiyed, Rehan; Alam, Shoaib et al. (2017) Prostacyclin-analog therapy in sickle cell pulmonary hypertension. Haematologica 102:e163-e165
Minniti, Caterina P; Kato, Gregory J (2016) Critical Reviews: How we treat sickle cell patients with leg ulcers. Am J Hematol 91:22-30
Baird, John H; Minniti, Caterina P; Lee, Jung-Min et al. (2015) Oscillatory haematopoiesis in adults with sickle cell disease treated with hydroxycarbamide. Br J Haematol 168:737-46
Wallen, Gwenyth R; Minniti, Caterina P; Krumlauf, Michael et al. (2014) Sleep disturbance, depression and pain in adults with sickle cell disease. BMC Psychiatry 14:207
Linguraru, Marius George; Pura, John A; Gladwin, Mark T et al. (2014) Computed tomography correlates with cardiopulmonary hemodynamics in pulmonary hypertension in adults with sickle cell disease. Pulm Circ 4:319-29
van Beers, Eduard J; Samsel, Leigh; Mendelsohn, Laurel et al. (2014) Imaging flow cytometry for automated detection of hypoxia-induced erythrocyte shape change in sickle cell disease. Am J Hematol 89:598-603
Fertrin, Kleber Yotsumoto; van Beers, Eduard J; Samsel, Leigh et al. (2014) Imaging flow cytometry documents incomplete resistance of human sickle F-cells to ex vivo hypoxia-induced sickling. Blood 124:658-60
Rowley, Carol A; Ikeda, Allison K; Seidel, Miles et al. (2014) Microvascular oxygen consumption during sickle cell pain crisis. Blood 123:3101-4
Wang, Xunde; Mendelsohn, Laurel; Rogers, Heather et al. (2014) Heme-bound iron activates placenta growth factor in erythroid cells via erythroid Krüppel-like factor. Blood 124:946-54
Lu, Kit; Cheng, Mok-Chung Jennifer; Ge, Xiaoying et al. (2014) A retrospective review of acupuncture use for the treatment of pain in sickle cell disease patients: descriptive analysis from a single institution. Clin J Pain 30:825-30

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