Transfusion/Hemostasis Clinical Research Network
Barbara A Konkle, Associate Professor Of Medicine
University Of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104
Grant 5U01HL072346-05 from National Heart, Lung, And Blood Institute IRG: ZHL1
Abstract: This is an application from University of Pennsylvania School of Medicine faculty to participate in the planned Transfusion Medicine/Hemostasis Clinical Trial Network. This group includes the resources of the University of Pennsylvania Health System (UPHS), the Children s Hospital of Philadelphia (CHOP) and the Penn-Jersey Division of the American Red Cross (PJ-ARC). UPHS and CHOP have ongoing large collaborative programs led by Barbara A. Konkle, M. D., the P.I. of this application, and Catherine Manno, M.D., a co-investigator, respectively, for the care of patients with inherited and acquired disorders of hemostasis. These programs have a long-standing record of participation in clinical trials. In addition, the institutions provide transfusion services, including the provision of cellular components and plasma, to large pediatric and adult bone marrow and stem cell transplantation programs, liver transplantation programs and trauma programs, among other specialized programs. The transfusion services provide plasmapheresis for disorders such as thrombotic thrombocytopenic purpura. Scott Murphy, M.D., a co-investigator in this proposal, lends his experience in clinical trial networks in hematology, having been a long standing member of the Polycythemia Vera study group and an internationally recognized expert in platelet transfusion. Dr. Murphy, a faculty member of the University of Pennsylvania is the Medical Director of the PJ-ARC. Two randomized clinical trials are proposed 1) Comparision of Platelet Concentrates Derived from Platelet Rich Plasma and Buffy Coats and, 2) Anticoagulation with Unfractionated Heparin Versus the Direct Thrombin Inhbitor Argatroban and the Risk of Thrombosis, Thrombocytopenia and Adverse Clinical Outcomes Following Cardiopulmonary Bypass Surgery. The University of Pennsylvania can provide extensive resources for this Network including patients for enrollment and experience in clinical trial design and enrollment. The investigators look forward to the opportunity to actively participate in such a network which will significantly advance the care of children and adults requiring transfusion or suffering from inherited or acquired disorders of hemostasis.
Keywords: blood /lymphatic pharmacology, blood disorder chemotherapy, blood transfusion, hemostasis, antibody, anticoagulant, aspartate transaminase, blood coagulation, clinical trial phase I, cooperative study, erythrocyte, heart /lung bypass, hematology, heparin, human therapy evaluation, inhibitor /antagonist, plasma, plasmapheresis, platelet, thrombocytopenia, blood cell count, clinical research, enzyme linked immunosorbent assay, human subject, patient oriented research
Project start date: 2002-09-30
Project end date: 2007-08-31
5U01HL072346-05 (2006): $285018
Sponsored Links Excellgen http://Excellgen.com
Transfusion/Hemostasis Clinical Research Network
Barbara A Konkle, Associate Professor Of Medicine
University Of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104
Grant 5U01HL072346-04 from National Heart, Lung, And Blood Institute IRG: ZHL1
Abstract: This is an application from University of Pennsylvania School of Medicine faculty to participate in the planned Transfusion Medicine/Hemostasis Clinical Trial Network. This group includes the resources of the University of Pennsylvania Health System (UPHS), the Children s Hospital of Philadelphia (CHOP) and the Penn-Jersey Division of the American Red Cross (PJ-ARC). UPHS and CHOP have ongoing large collaborative programs led by Barbara A. Konkle, M. D., the P.I. of this application, and Catherine Manno, M.D., a co-investigator, respectively, for the care of patients with inherited and acquired disorders of hemostasis. These programs have a long-standing record of participation in clinical trials. In addition, the institutions provide transfusion services, including the provision of cellular components and plasma, to large pediatric and adult bone marrow and stem cell transplantation programs, liver transplantation programs and trauma programs, among other specialized programs. The transfusion services provide plasmapheresis for disorders such as thrombotic thrombocytopenic purpura. Scott Murphy, M.D., a co-investigator in this proposal, lends his experience in clinical trial networks in hematology, having been a long standing member of the Polycythemia Vera study group and an internationally recognized expert in platelet transfusion. Dr. Murphy, a faculty member of the University of Pennsylvania is the Medical Director of the PJ-ARC. Two randomized clinical trials are proposed 1) Comparision of Platelet Concentrates Derived from Platelet Rich Plasma and Buffy Coats and, 2) Anticoagulation with Unfractionated Heparin Versus the Direct Thrombin Inhbitor Argatroban and the Risk of Thrombosis, Thrombocytopenia and Adverse Clinical Outcomes Following Cardiopulmonary Bypass Surgery. The University of Pennsylvania can provide extensive resources for this Network including patients for enrollment and experience in clinical trial design and enrollment. The investigators look forward to the opportunity to actively participate in such a network which will significantly advance the care of children and adults requiring transfusion or suffering from inherited or acquired disorders of hemostasis.
Keywords: blood /lymphatic pharmacology, blood disorder chemotherapy, blood transfusion, hemostasis, antibody, anticoagulant, aspartate transaminase, blood coagulation, clinical trial phase I, cooperative study, erythrocyte, heart /lung bypass, hematology, heparin, human therapy evaluation, inhibitor /antagonist, plasma, plasmapheresis, platelet, thrombocytopenia, blood cell count, clinical research, enzyme linked immunosorbent assay, human subject, patient oriented research
Project start date: 2002-09-30
Project end date: 2007-08-31
5U01HL072346-04 (2005): $289250
5U01HL072346-03 (2004): $128012
Grants awarded to Barbara A Konkle
NOVEL BIOMARKERS PREDICTIVE OF HEPARIN-INDUCED THROMBOCYTOPENIA
Barbara A Konkle
Puget Sound Blood Center, 921 Terry Ave, Seattle, Wa 98104
Grant 5RC1HL099973-03 from National Heart, Lung, And Blood Institute
Abstract: This proposal addresses the Broad Challenge Area of (03) Biomarker Discovery and Validation, specifically (03-HL-101), to identify and validate clinically relevant, quantifiable biomarkers of diagnostic and therapeutic responses for blood, vascular, cardiac and respiratory tract dysfunction. Thrombosis is the major cause of death in the United States and heparin, in unfractionated (UFH) or low molecular weight form, is uniformly used for anticoagulation in the hospital setting. Heparin-induced thrombocytopenia (HIT) occurs in 1-5% of patients exposed to heparin, can have severe consequences with loss of limbs or life, and often occurs in elderly patients with advanced atherosclerotic disease and increased baseline risks of both thrombosis and hemorrhage. While alternative anticoagulants are available, they are associated with increased risks of bleeding and increased costs, and have not replaced UFH for common surgeries requiring cardiopulmonary bypass (CPB). If patients who are at greatest risk of HIT can be identified prior to heparin exposure, targeted alternative anticoagulation could be used. HIT is caused by antibodies against a complex of heparin/platelet factor 4 (PF4). Our laboratory studies, including animal models and human ex-vivo studies of platelet and vascular PF4 and glycosoaminoglycan/PF4 complex immunogenicity, support our ability to utilize novel biomarkers and clinical factors to determine the risk of HIT. We are currently studying platelet biomarkers of risk in patients undergoing cardiac catheterization and are now poised to validate these biomarkers, and markers of incipient antibody development, in a patient population at high risk of forming antiheparin/ PF4 antibodies. We hypothesize that a constellation of biomarkers and clinical factors will predict risk of heparin/PF4 antibody formation and HIT, and propose studies to evaluate this through Specific Aims 1) To determine if novel platelet biomarkers and clinical factors predict anti-heparin/PF4 antibody formation post- CPB; 2) To evaluate expression of antigen-specific B cells and evolution of antiheparin/PF4 antibody isotype and titer as precursors of HIT; and, 3) To observe if anti-heparin/PF4 antibody formation or platelet biomarkers predict in-hospital and 30 day cardiovascular and all cause morbidity and mortality. The University Of Pennsylvania School Of Medicine contributes substantially to the local economy. In 2008, the School of Medicine created 37,000 jobs and $5.4 billion in regional economic activity, with the areas highly trained workforce producing more than 24,600 applications for just 840 open Penn staff research positions. Through the proposed studies we will retain and increase staff employment (2.5 jobs) and our studies should improve use of a commonly prescribed medication and decrease adverse clinical events and medical costs. These goals are consistent with the purpose of the American Recovery and Reinvestment Act of 2009 to preserve and create jobs, and to promote economic recovery by spurring advances in science and health. Heparin is a commonly used blood thinner in all hospitals in the U.S. Heparin-induced thrombocytopenia (HIT) is a serious adverse effect of heparin that can result in loss of limbs or death. This study will help identify patients most at risk of developing HIT with heparin therapy so that the approach to their care can be altered, and thus, improved
Keywords: ATGN; Address; Adverse effects; American; Animal Model; Animal Models and Related Studies; Antibodies; Antibody Formation; Antibody Production; Antibody Response; Anticoagulant Agents; Anticoagulant Drugs; Anticoagulants; Anticoagulation; Antigens; Antiheparin Factor; Area; B blood cells; B-Cells; B-Lymphocytes; Bizzozero`s corpuscle/cell; Bleeding; Blood; Blood Platelet Factor IV; Blood Platelets; Blood Vessels; Blood platelet factor 4; Bursa-Dependent Lymphocytes; Bursa-Equivalent Lymphocyte; Cardiac; Cardiac Catheterization Procedures; Cardiopulmonary Bypass; Cardiovascular; Cardiovascular Body System; Cardiovascular system; Cardiovascular system (all sites); Caring; Catheterization, Cardiac; Cause of Death; Cessation of life; Chemokine (C-X-C motif) Ligand 4; Clinical; Clinical Treatment; Complex; Death; Deetjeen`s body; Development; Diagnostic; Disease; Disorder; Drugs; Dysfunction; Economics; Employment; Event; Evolution; Extremities; Factor 4; Functional disorder; Future; Goals; HOSP; Hayem`s elementary corpuscle; Health Sciences; Heart Catheterization; Heart Catheterization Pocedure; Heart-Lung Bypass; Hemorrhage; Heparin; Heparin Neutralizing Protein; Heparinic Acid; Hospitals; Human; Human, General; Insertion of catheter into heart chamber; Jobs; Laboratory Study; Life; Limb structure; Limbs; Man (Taxonomy); Man, Modern; Marrow platelet; Medical; Medication; Molecular Weight; Morbidity; Morbidity - disease rate; Mortality; Mortality Vital Statistics; Non-Trunk; Occupations; Operation; Operative Procedures; Operative Surgical Procedures; Organ System, Cardiovascular; Patients; Pennsylvania; Pharmaceutic Preparations; Pharmaceutical Preparations; Physiopathology; Platelet Factor 4; Platelets; Position; Positioning Attribute; Principal Investigator; Professional Postions; Programs (PT); Programs [Publication Type]; Pulmonary Body System; Pulmonary Organ System; Recombinant Platelet Factor 4; Recovery; Research; Respiratory System; Respiratory system (all sites); Respiratory tract structure; Reticuloendothelial System, Blood; Reticuloendothelial System, Platelets; Risk; Small Inducible Cytokine B4; Small Inducible Cytokine Subfamily B, Member 4; Surgical; Surgical Interventions; Surgical Procedure; Therapeutic; Thrombocytes; Thrombocytopenia; Thrombopenia; Thrombosis; Tracts, Respiratory; Training; Treatment Side Effects; United States; Universities; Validation; Vascular, Heart; antibody biosynthesis; biomarker; blood loss; blood thinner; circulatory system; clinical relevance; clinically relevant; cost; disease/disorder; drug/agent; elderly patient; gamma-Thromboglobulin; heart bypass; high risk; immunogen; immunogenicity; immunoglobulin biosynthesis; improved; medical schools; model organism; novel; older patient; pathophysiology; patient population; platelet factor IV; programs; randomized trial; respiratory tract; response; side effect; surgery; therapy adverse effect; thrombocyte/platelet; thrombopoiesis inhibitor; treatment adverse effect; trial regimen; trial treatment; vascular
Relevance: Principal Investigator/Program Director (Last, first, middle): KONKLE, Barbara A. : Heparin is a commonly used blood thinner in all hospitals in the U.S. Heparin-induced thrombocytopenia (HIT) is a serious adverse effect of heparin that can result in loss of limbs or death. This study will help identify patients most at risk of developing HIT with heparin therapy so that the approach to their care can be altered, and thus, improved
Project start date: 2009-09-30
Project end date: 2011-08-31
Budget start date: 1-SEP-2010
Budget end date: 31-AUG-2011
PFA/PA: RFA-OD-09-003
5RC1HL099973-03 (2010): $499110
7RC1HL099973-02 (2009): $497473
Transfusion/Hemostasis Clinical Research Network
Barbara A Konkle, Associate Professor Of Medicine
University Of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104
Grant 1U01HL072346-01 from National Heart, Lung, And Blood Institute IRG: ZHL1
Abstract: This is an application from University of Pennsylvania School of Medicine faculty to participate in the planned Transfusion Medicine/Hemostasis Clinical Trial Network. This group includes the resources of the University of Pennsylvania Health System (UPHS), the Children s Hospital of Philadelphia (CHOP) and the Penn-Jersey Division of the American Red Cross (PJ-ARC). UPHS and CHOP have ongoing large collaborative programs led by Barbara A. Konkle, M. D., the P.I. of this application, and Catherine Manno, M.D., a co-investigator, respectively, for the care of patients with inherited and acquired disorders of hemostasis. These programs have a long-standing record of participation in clinical trials. In addition, the institutions provide transfusion services, including the provision of cellular components and plasma, to large pediatric and adult bone marrow and stem cell transplantation programs, liver transplantation programs and trauma programs, among other specialized programs. The transfusion services provide plasmapheresis for disorders such as thrombotic thrombocytopenic purpura. Scott Murphy, M.D., a co-investigator in this proposal, lends his experience in clinical trial networks in hematology, having been a long standing member of the Polycythemia Vera study group and an internationally recognized expert in platelet transfusion. Dr. Murphy, a faculty member of the University of Pennsylvania is the Medical Director of the PJ-ARC. Two randomized clinical trials are proposed 1) Comparision of Platelet Concentrates Derived from Platelet Rich Plasma and Buffy Coats and, 2) Anticoagulation with Unfractionated Heparin Versus the Direct Thrombin Inhbitor Argatroban and the Risk of Thrombosis, Thrombocytopenia and Adverse Clinical Outcomes Following Cardiopulmonary Bypass Surgery. The University of Pennsylvania can provide extensive resources for this Network including patients for enrollment and experience in clinical trial design and enrollment. The investigators look forward to the opportunity to actively participate in such a network which will significantly advance the care of children and adults requiring transfusion or suffering from inherited or acquired disorders of hemostasis.
Keywords: blood /lymphatic pharmacology, blood disorder chemotherapy, blood transfusion, hemostasis, antibody, anticoagulant, aspartate transaminase, blood coagulation, clinical trial phase I, cooperative study, erythrocyte, heart /lung bypass, hematology, heparin, human therapy evaluation, inhibitor /antagonist, plasma, plasmapheresis, platelet, thrombocytopenia, blood cell count, clinical research, enzyme linked immunosorbent assay, human subject, patient oriented research
Project start date: 2002-09-30
Project end date: 2007-08-31
1U01HL072346-01 (2002): $300000
2U01HL072346-06 (2007): $214236
Mentored Career Development In Clinical Research In Non-malignant Hematology
Barbara A Konkle, Associate Professor Of Medicine
University Of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104
Grant 1K12HL087064-01 from National Heart, Lung, And Blood Institute IRG: ZHL1
Abstract: This application describes plans at the University of Pennsylvania and Children s Hospital of Philadelphia to train the next generation of leaders in clinical and translational research in non-malignant hematology. The breadth and depth of the hematology programs, along with additional resources at the University, provide an ideal setting for this career development program, which will be structured to cover four areas including Hemostasis, Red Cell Disorders, Immune Hematology and Transfusion Medicine, and Stem Cells and Myeloproliferative Disorders. Experienced faculty members will lead each area and aid the Director and Co- Directors in developing a comprehensive curriculum in benign hematology. These faculty will serve as Primary Mentors, and with Secondary Mentors, will train scholars in their areas of expertise. In addtion, the program will utilize the resources within the recently developed Institute for Translational Medicine and Therapeutics. The specific training goals of this program are 1) To provide broad-based clinical training and exposure to all aspects of pediatric and adult non-malignant hematology; 2) To guide the Scholar in acquiring the knowledge and tools necessary to be a successful clinical or translational researcher, including training in biostatistics, epidemiology, clinical trials design, and in the responsible conduct of research; 3) To develop scholars with a thorough understanding of advances in basic molecular and cell biology relevant to their areas of clinical research focus, and in methodologies used in these areas; 4) To ensure knowledge and understanding of ethical issues in both basic and clinical biomedical research; and, 5) To provide close mentoring of the scholars with defined timelines to meet goals in education, research, and scientific and grant writing, and to provide positive clinical research role models in a supportive academic environment. The program will train future clinical and translational researchers in benign hematology who are equipped with a sophisticated background in basic science and clinical research methodologies. It is anticipated that graduates of this program will be at the leading edge of their research field and ideally situated to compete for further NIH funding and to serve as faculty members in non-malignant hematology in academic centers, training the next generation of non-malignant hematologists.
Keywords: career, clinical research, curriculum, health science research potential, hematology, mentoring /mentor, training, blood transfusion, epidemiology, ethics, hematopoietic stem cell, hemostasis, immunohematology, statistics /biometry
Project start date: 2006-09-28
Project end date: 2011-08-31
1K12HL087064-01 (2006): $399984
5K12HL087064-03 (2008): $397189
5K12HL087064-02 (2007): $397589
PLASMINOGEN ACTIVATOR INHIBITOR 1 GENE EXPRESSION
Barbara A Konkle, Associate Professor Of Medicine
Medicinethomas Jefferson University
201 South 11th St
philadelphia, Pa 191075587
Grant 5R29HL044956-05 from National Heart, Lung, And Blood Institute IRG: HEM
Abstract: Plasminogen activator inhibitor - 1(PAI-1) is the primary physiologic inhibitor of tissue plasminogen activator (tPA) and also inhibits urokinase (UK). Studies suggest that PAI-1 is the major regulator of tPA induced fibrinolysis and may also be involved in other processes including matrix degradation and tissue remodeling. Elevated levels of plasma PAI-1 are associated with thrombosis in man. Controversy exists whether liver or vascular endothelium is the major source of plasma PAI-1 and studies suggest that PAI-1 synthesis is regulated differently in these two tissues. We have preliminary evidence in rat that PAI-1 mRNA is expressed primarily in the hepatic endothelium and not the hepatocyte. Studies outlined in this proposal will compare PAI-1 mRNA and protein synthesis in freshly isolated rat hepatic fractions and aortic endothelium and in cultured cells from these same tissues. Cultures will be treated with modulators known to affect PAI-1 expression in endothelium or hepatocyte/hepatoma cultures to evaluate differential regulation. PAI-1 expression in human endothelium is modulated by a number of factors including cAMP elevating compounds and phorbol esters. We had previously shown that the class I heparin binding growth factor, endothelial cell growth factor (HBGF-1), decreased PAI-1 expression in human endothelial cell culture. Recent studies in my laboratory have shown that cAMP elevation and the phorbol ester PMA modulate the HBGF-1 effect on PAI-1. Studies are outlined to further investigate cellular pathways involved in this growth factor modulation of PAI-1 expression. Human PAI-1 expression is regulated, at least in part, at the level of gene transcription. We have evidence that it is also modulated at the level of mRNA stability. An "AU" rich sequence in the 3´ untranslated region of PAI-1 mRNA may be involved in these processes. Studies are outlined in this proposal to investigate mRNA sequences and RNA binding protein that may be involved in regulating PAI-1 mRNA stability
Project start date: 1990-07-01
Project end date: 1996-06-30
5R29HL044956-05 (1994): $130940
PLASMINOGEN ACTIVATOR INHIBITOR-1 GENE EXPRESSION
Barbara A Konkle, Associate Professor Of Medicine
Thomas Jefferson University
201 South 11th St
philadelphia, Pa 191075587
Grant 5R29HL044956-04 from National Heart, Lung, And Blood Institute IRG: HEM
Abstract: Plasminogen activator inhibitor - 1(PAI-1) is the primary physiologic inhibitor of tissue plasminogen activator (tPA) and also inhibits urokinase (UK). Studies suggest that PAI-1 is the major regulator of tPA induced fibrinolysis and may also be involved in other processes including matrix degradation and tissue remodeling. Elevated levels of plasma PAI-1 are associated with thrombosis in man. Controversy exists whether liver or vascular endothelium is the major source of plasma PAI-1 and studies suggest that PAI-1 synthesis is regulated differently in these two tissues. We have preliminary evidence in rat that PAI-1 mRNA is expressed primarily in the hepatic endothelium and not the hepatocyte. Studies outlined in this proposal will compare PAI-1 mRNA and protein synthesis in freshly isolated rat hepatic fractions and aortic endothelium and in cultured cells from these same tissues. Cultures will be treated with modulators known to affect PAI-1 expression in endothelium or hepatocyte/hepatoma cultures to evaluate differential regulation. PAI-1 expression in human endothelium is modulated by a number of factors including cAMP elevating compounds and phorbol esters. We had previously shown that the class I heparin binding growth factor, endothelial cell growth factor (HBGF-1), decreased PAI-1 expression in human endothelial cell culture. Recent studies in my laboratory have shown that cAMP elevation and the phorbol ester PMA modulate the HBGF-1 effect on PAI-1. Studies are outlined to further investigate cellular pathways involved in this growth factor modulation of PAI-1 expression. Human PAI-1 expression is regulated, at least in part, at the level of gene transcription. We have evidence that it is also modulated at the level of mRNA stability. An "AU" rich sequence in the 3´ untranslated region of PAI-1 mRNA may be involved in these processes. Studies are outlined in this proposal to investigate mRNA sequences and RNA binding protein that may be involved in regulating PAI-1 mRNA stability
Keywords: anticoagulant, gene expression, plasminogen activator RNA binding protein, cell growth regulation, cyclic AMP, genetic transcription, growth factor, heparin, messenger RNA, nucleic acid sequence, urokinase, vascular endothelium human tissue, liver cell, tissue /cell culture
Project start date: 1990-07-01
Project end date: 1995-06-30
5R29HL044956-04 (1993): $122402
5R29HL044956-03 (1992): $115807
Sponsored Links Excellgen http://Excellgen.com
Age Dependent Thrombotic Risk Factors In Heparin-induced Thrombocytopenia
Barbara A Konkle, Associate Professor Of Medicine
Medicineuniversity Of Pennsylvania
3451 Walnut Street
philadelphia, Pa 19104
Grant 5R21HL092748-02 from National Heart, Lung, And Blood Institute IRG: ZAG1
Abstract: Heparin-induced thrombocytopenia (HIT) is a prototypic, common, iatrogenic thrombotic disorder characterized by inflammation, platelet activation and venous thromboembolism (VTE). It occurs in 1-5% of heparinized patients and often in elderly patients with advanced atherosclerotic disease. Recent studies demonstrate a strong link between atherosclerosis and venous thromboembolism. We believe that both disorders share certain fundamental features in their pathophysiology, i.e. inflammation and platelet dependent acceleration of vascular procoagulant pathways. We propose studies below to better understand the mechanistic basis of HIT, explaining why atherosclerosis is central as a risk factor for the development of this disorder. Specific Aim 1 To examine the relationship between platelet PF4 content, severity of atherosclerosis and HIT antigen expression. We have demonstrated that platelet PF4 content correlates with development of atherosclerosis in a murine model, and that PF4 accumulates in human atherosclerotic lesions and forms HIT-like antigenic complexes. We now propose that high levels of platelet PF4 predispose to progression of atherosclerosis and lead to development of HIT antibodies even prior to heparin exposure. To test whether these findings are relevant to the clinical setting, two patient populations (ages 25-45 and >60) undergoing cardiac catheterization prior to valve replacement surgery will be examined. The severity of atherosclerosis on cardiac catheterization will be recorded and blood will be obtained to assess total platelet PF4 content and HIT antibody level. In addition, a subset of patients will undergo skin punch biopsies that will be analyzed for vascular damage and PF4 and HIT antigenicity. Specific Aim 2 To examine the relationship between platelet PF4 content and total surface PF4 and HIT antigenic complexes. We have also shown, mostly in murine models, but again with supportive studies in humans, that surface-bound PF4/glycosaminoglycan (GAG) complexes on platelets are antigenic targets in HIT. We posit that patients with high platelet PF4 and more severe atherosclerosis (see above) will have more extensive chronic platelet activation and PF4 release and higher levels of platelet-bound surface PF4 and HIT antigenic PF4/GAG complexes. We propose to show that such a population with high surface PF4 and HIT PF4/GAG antigenic complexes can be detected in the general population. We therefore propose to measure the level of platelet PF4 content and total surface PF4 and HIT antigenicity in these two populations and also in well children. These studies should allow us to identify high risk patients, and lay the groundwork for clinical trial(s) evaluating outcomes in patients stratified by risk and/or receiving targeted therapy. This should result in decreased morbidity and mortality in elderly patients requiring heparin anticoagulation. Patients who are hospitalized frequently receive the blood thinner heparin to prevent or treat blood clotting. These patients are at risk of a blood clotting condition called heparin-induced thrombocytopenia. These studies will clarify whether older patients are at increased risk for this disorder and help us target individuals at greater risk of this complication so that their treatment can be modified. This should improve the outcome of patients needing blood thinning with the medication heparin
Project start date: 2007-09-25
Project end date: 2009-08-31
5R21HL092748-02 (2008): $239050
1R21HL092748-01 (2007): $214050