Medicine and Health Sciences Commons^™

Incremental Dialysis For Preserving Residual Kidney Function—Does One Size Fit All When Initiating Dialysis?, A. T. Mathew, Y. Obi, C. M. Rhee, J. A. Chou, K. Kalantar-Zadeh

Journal Articles

© 2018 Wiley Periodicals, Inc. While many patients have substantial residual kidney function (RKF) when initiating hemodialysis (HD), most patients with end stage renal disease in the United States are initiated on 3-times per week conventional HD regimen, with little regard to RKF or patient preference. RKF is associated with many benefits including survival, volume control, solute clearance, and reduced inflammation. Several strategies have been recommended to preserve RKF after HD initiation, including an incremental approach to HD initiation. Incremental HD prescriptions are personalized to achieve adequate volume control and solute clearance with consideration to a patient's endogenous renal function. …

Evaluation Of Extracellular Matrix Composition And Rheology As Determinants Of Growth, Invasion, And Response To Photodynamic Therapy In 3d Cell Culture Models Of Pancreatic Ductal Adenocarcinoma, Gwendolyn M. Cramer

Graduate Doctoral Dissertations

Pancreatic ductal adenocarcinoma (PDAC) is a notoriously lethal disease characterized by prominent stromal involvement, which plays complex roles in regulating tumor growth and therapeutic response. The extracellular matrix (ECM)-rich stroma has been implicated as a barrier to drug penetration, although stromal depletion strategies have had mixed clinical success. It remains less clear how biophysical interactions with the ECM regulate invasive progression and susceptibilities to specific therapies. Here, an integrative approach combining 3D cell culture and quantitative imaging techniques is used to evaluate invasive behavior and motility as determinants of response to classical chemotherapy and photodynamic therapy (PDT), in which light …

Vaksinasi Pada Lansia, Iris Rengganis

Jurnal Penyakit Dalam Indonesia

No abstract provided.

Association Between Disease Activity And Depression Inrheumatoid Arthritis Patients, E Mudjaddid, Myra Puspitasari, Bambang Setyohadi

Jurnal Penyakit Dalam Indonesia

Introduction. Rheumatoid Arthritis (RA) is a chronic, systemic disease that cause synovialinflammation and progressive destruction to cartilages and deformities. Prevalence of depressionin RA patients is 20 to 30%. Disease activity is considered to have association with depression. This study aims to identify the prevalence of depression in RA patients and the associationbetween disease activity index and depression in RA patients. Methods. A cross-sectional study of 145 RA patients that fulfilled the inclusion criteria was conducted in Rheumatology Outpatient Clinic at Cipto Mangunkusumo Hospital Jakarta from January to March 2017.Evaluation of Disease Activity Score - 28 (DAS 28) and Back Depression …

Predictor Factors Affecting Seroconversion Post-Influenzavaccination In The Elderly, Saskia Aziza Nursyirwan, Sukamto Koesnoe, Edy Rizal Wahyudi

Jurnal Penyakit Dalam Indonesia

Introduction. The influenza vaccine as the most effective method for preventing influenza virus infection currently has lower efficacy in the elderly than younger adults due to change of immune response as well as other risk factors. This study aims to identify predictor factors affecting seroconversion post-influenza vaccination in elderly. Methods. retrospective cohort study in the elderly population in East Jakarta Posyandu who got the influenza vaccine. A total of 277 subjects with antibody titre pre and one month post-vaccination influenza were examined. Risk factors such as age, gender, exercise status, smoking status, type 2 diabetes, pulmonary, and cardiovascular disease, nutritional …

Cardiotoxicity Complication Of Radiotherapy, Beta Agustia Wisman, Sally Aman Nasution, Marulam M. Panggabean

Jurnal Penyakit Dalam Indonesia

Radiation is an important modality in the management of malignancy. Some cases of malignancy requiring radiotherapy in the chest include breast cancer, Hodgkin's lymphoma, or lung cancer.Cardiotoxicity due to radiotherapy can occur within 3 to 29 years after radiotherapy, mostly in the second or third decade after therapy. Some cardiovascular complications resulting from radiotherapy may affect pericardial, myocardial, vascular, heart valves and conduction disturbances. Symptomatic cardiotoxicity may occurs 10% in patients undergoing radiotherapy in the chest area. It is important for clinicians to understand the cardiotoxicity of radiotherapy for educational purposes, therapeutic and dosing considerations, treatment monitoring and early detection. …

The Relationship Between Age And Activity Of Daily Living Withthe Fall Risk Of Patients In Geriatric Outpatient Installation, Agustin Junior Nanda Deniro, Nuniek Nugraheni Sulistiawati, Novira Widajanti

Jurnal Penyakit Dalam Indonesia

Introduction. Fall is one of the physical problems that happened quite frequently and resulted in morbidity and mortality of old people. There are several factors related to fall risk, among others are age and independence in activity of daily living. Methods. This research is an observational analytical study with cross sectional approach, by collecting free variable data (age and activity of daily living) through interview and Barthel index score, dependent variable (fall risk) by direct observation using Timed Up and Go test that analyzed by Rank Spearman correlation test. The number of samples with incidental sampling technique was 55 patients …

Photodermatoses In Children, Siti Nurani Fauziah, Wresti Indriatmi, Lili Legiawati

Journal of General - Procedural Dermatology & Venereology Indonesia

Photodermatoses cover the skin’s abnormal reactions to sunlight, usually to its ultraviolet (UV) component or visible light. Etiologically, photodermatoses can be classified into 4 categories: (1) immunologically mediated photodermatoses (idiopathic photodermatoses); (2) drug- or chemical-induced photosensitivity; (3) hereditary photodermatoses; and (4) photoaggravated dermatoses. The incidence of photodermatoses in the pediatric population is much lower than in adults, Polymorphous light eruption (PMLE) is the most common form of photodermatoses in children, followed by erythropoietic protoporphyria. Early diagnosis and investigations should be performed to avoid long-term complications. Photoprotection is the mainstay of photodermatoses management, including use of physical protection and sunscreen.

Seroprevalence Of Syphilis And Herpes Simplex Virus Type 2 And Its Association With Sexual Behaviour Factors (A Cross-Sectional Study Among Men Who Have Sex With Men In Manado, Indonesia), Nurdjanah J. Niode, Hendra Minarto, Andravita F. Mitaart, Grace M. Kapantow, Renate T. Kandou

Journal of General - Procedural Dermatology & Venereology Indonesia

Aims: This study investigated the seroprevalence and sexual risk behavior factors associated with syphilis and herpes simplex virus type 2 (HSV-2) among men who have sex with men (MSM), in Manado, Indonesia.

Methods: Serum samples and questionnaires regarding their socio-demographic and sexual behaviour were collected from 60 MSM in Manado. Samples were screened for anti-HSV-2 IgG for herpes, the Venereal Disease Research Laboratory (VDRL) and the Treponema Pallidum Haemagglutination (TPHA) test for syphilis. A cross sectional method was used in this study.

Results: Of 60 MSM (median age was 20 years), 35% had homosexual orientation and 65% …

Allergic Contact Dermatitis Due To Nickel In Household Detergent, Dewi Utami Putri, Irma Damayanti Roesyanto-Mahadi

Journal of General - Procedural Dermatology & Venereology Indonesia

Allergic contact dermatitis (ACD) is a cutaneous inflammatory reaction caused by contact with specific exogenous allergen to which a person has developed allergic sensitization. Nickel was reported as one of the most common causes of ACD worldwide, particularly affecting females. It is associated with a variety of nickel-containing products, from jewelry to detergent.

A 32-year-old female was presented with pruritic eruption consist of erythematous papules and vesicles on both hands and extensor forearms since 2 weeks before admission. The patient is a housewife who did handwashing clothes and kitchenware with detergent and soap every day. At first, there were erythematous …

Antiphospholipid Antibody Profile In Hiv/Aids Patients, Inolyn Pandjaitan, Nanang Sukmana, Shufrie Effendy

Jurnal Penyakit Dalam Indonesia

Introduction. Through the process of molecular mimicry, human immunodeficiency virus (HIV) infection can increase the concentration of antiphospholipid antibody (APA) which has possible association with thrombosis. The molecular mimicry in this HIV/AIDS patients is influenced by several factors, such as immunocompromised condition, the use of antitretroviral (ARV) therapy, hepatitis B and C coinfection, use of other drugs, and history of intravenous drug user (IDU). We conducted this study to determine the profile and prevalence of antiphospholipid antibody in patients with HIV/ AIDS in Dr. Cipto Mangunkusumo General Hospital. Further, we explored the relationship between APA in HIV/AIDS patients with the …

Diagnosis And Treatment Of Pneumocystis Carinii Pneumonia (Pcp)/Pneumocystis Jirovecii Pneumonia In Hiv Patient: A Case Report, Dewi Rizki Agustina, Christy Efiyanti, Evy Yunihastuti

Jurnal Penyakit Dalam Indonesia

Pneumocystis carinii pneumonia (PCP) or pneumocystis jirovecii pneumonia is an opportunistic infection that can occur in immunocompromised patients. In patients with HIV, PCP is the most common opportunistic infection especially in patients with CD4 cell counts less than 200 cell /ul. To diagnose a PCP is very difficult because symptoms, blood tests, and thoracic radiography are not pathognomonic for PCP. However, untreated PCP is almost always fatal. Trimethroprimsulfamethoxazole (TMX-SMX) orally or intravenously for 21 days is the drug of choice for managing PCP with or without HIV. This article discusses a case with patients with symptoms of dyspneu, unproductive cough, …

Validity Of Simple Risk Index And Evaluation Of Methods Andmanagement Of Acute Coronary Events To Predict Mortality Inacute Coronary Syndrome Patients In Intensive Coronary Careunit Cipto Mangunkusumo Hospital, Rahmah Safitri Meutia, Sally Aman Nasution, Lukman H. Makmun

Jurnal Penyakit Dalam Indonesia

Introduction. Risk stratification is an important part in the management of patients with an Acute Coronary Syndrome (ACS) to avoid overtreatment or undertreatment. Although Simple Risk Index (SRI) and Evaluation of Methods and Management of Acute Coronary Events (EMMACE) have been validated in other countries, no study of its applicability has been performed in Indonesia with different patients’ characteristics. This study aims to obtain the calibration and discrimination performance of SRI and EMMACE to predict 30 days mortality in ACS patients in ICCU of Cipto Mangunkusumo Hospital. Methods. A retrospective cohort study with consecutive sampling was conducted in ACS patients …

The Patterns Of Primary Cotrimoxazole Prophylaxis In Adult Hivpatients In Hiv Integrated Clinic Cipto Mangunkusumo Hospitaljakarta In 2004-2013, Ken Ayu Mastini, Zubair Djoerban, Evy Yunihastuti

Jurnal Penyakit Dalam Indonesia

Introduction. Low rate use of cotrimoxazole which is a standard of primary prevention against toxoplasmosis infection and Pneumocystis jirovecii pneumonia (PCP) in patients with CD4 <200 cell>/mm3 was found. This study aims to describe prescription pattern of cotrimoxazole primary prophylaxis in adult HIV patients in RSCM. Methods. A cohort retrospective study was conducted in HIV Integrated Clinic Cipto Mangunkusumo Hospital patients from 2004 to 2013. Individuals were eligible for this study if they were ≥18 years old and had indication of primary cotrimoxazole prophylaxis. Variable analyzed in this study were initiation, discontinuation, dosage, duration, duration percentage, and adverse events of primary …

Efficacy Of Topical Estradiol Compared To Topical Glycolic Acid For Skin Aging Treatment In Postmenopausal Women, Shannaz Nada Yusharyahya, Marsha Bianti

Journal of General - Procedural Dermatology & Venereology Indonesia

Skin aging is a complex biological process in human being, as a result from intrinsic factors (genetic, hormonal, metabolism) and extrinsic factors (UV exposure, pollution, smoking, life style). In postmenopausal women, physiologically, the amount of estrogen are decreased, causing deterioration of their skin’s appearance.

Along with the changes that occur, skin care require more attention. A holistic approach can increase epidermal thickness, therefore, reducing the depth of wrinkles, as well as improving skin texture and moisture. There are various treatments available to improve skin appearance due to aging.

This EBCR is aimed to compare the efficacy of topical estradiol and …

Venous Ulcer, Irene Dorthy Santoso, Hanny Nilasari, Shannaz Nadia Yusharyahya

Journal of General - Procedural Dermatology & Venereology Indonesia

Leg ulcers one common problem in the adult population to geriatric with a prevalence about 1-2%. The pattern of life which tends to be sedentary, less activity, obesity, increased the incidence of leg ulcers. The duration of healing and recurrence occurs in majority of patients contributed the decline in quality of life for patients with venous ulcers. Diagnosis, latest treatment and prevention are essential to discuss.

The Effect Of Injection Of Adsc Compared To Appe On Collagen Density In Aging Skin (Animal Study), Erlina Pricilla, Indah Julianto, Harijono Kariosentono, Dyah R. Budiani, Yuda Heru Fibrianto, Yuyun Rindiastuti, Ainun Veraida

Journal of General - Procedural Dermatology & Venereology Indonesia

Introduction: Aging is a biological process that can induces changes to the structural integrity and physiological function of skin. Structural changes of skin are a result of dermal atrophy, decreased collagen, the loss of subcutaneous fat, the loss of inherent elasticity, and increased melanogen.1,5,6 From the definition itself, a stem cell characterized by its ability to self-renew and also have an ability to differentiate along multiple lineage pathways.2,4 ADSC which is a kind of mesenchymal stem cell from human adipose tissue, have some potential properties as stem cells derived from bone marrow.4,7

Objective: The aim of this study …

Molecular Characterization Of Multidrug-Resistant Klebsiella Pneumoniaeand Escherichia Coliharbouring Extended Spectrum Beta-Lactamases Andcarbapenemases Genes At A Tertiary Hospital, Kenya, Daniel Maina, Gunturu Revathi, Andrew C. Whitelaw

Pathology, East Africa

Background: Multidrug-resistant (MDR) Gram negative rods are increasingly being reported in sub-Saharan Africa. Molecular investigations play an important role, alongside other measures, in controlling nosocomial infections attributed to these organisms.

This study aimed to determine the common extended spectrum beta-lactamases (ESBL) and carbapenemases genes, and clonal relationship in MDR Klebsiella pneumoniae and Escherichia coli.

Methods: Fifty-four MDR isolates collected at the Aga Khan University hospital, Nairobi in the month of August 2012 formed the study. These were picked after an increase in the number of resistant strains during the said period was experienced.

Results: blaCTXM was present in 41 (74%) …

Ovarian Cancer Screening: Lessons About Effectiveness, Edward J. Pavlik

Obstetrics and Gynecology Faculty Publications

No abstract provided.

Discovery Of Novel, Orally Bioavailable, Antileishmanial Compounds Using Phenotypic Screening, Diana Ortiz, W. Armand Guiguemde, Jared T. Hammill, Angela K. Carrillo, Yizhe Chen, Michele Connelly, Kayla Stalheim, Carolyn Elya, Alex Johnson, Jaeki Min, Anang Shelat, David C. Smithson, Lei Yang, Fangyi Zhu, R. Kiplin Guy, Scott M. Landfear

Pharmaceutical Sciences Faculty Publications

Leishmaniasis is a parasitic infection that afflicts approximately 12 million people worldwide. There are several limitations to the approved drug therapies for leishmaniasis, including moderate to severe toxicity, growing drug resistance, and the need for extended dosing. Moreover, miltefosine is currently the only orally available drug therapy for this infection. We addressed the pressing need for new therapies by pursuing a two-step phenotypic screen to discover novel, potent, and orally bioavailable antileishmanials. First, we conducted a high-throughput screen (HTS) of roughly 600,000 small molecules for growth inhibition against the promastigote form of the parasite life cycle using the nucleic acid …

P5l Mutation In Ank Results In An Increase In Extracellular Inorganic Pyrophosphate During Proliferation And Nonmineralizing Hypertrophy In Stably Transduced Atdc5 Cells, Raihana Zaka, David Stokes, Arnold S. Dion, Anna Kusnierz, Fei Han, Charlene J. Williams

Charlene Williams

Ank is a multipass transmembrane protein that regulates the cellular transport of inorganic pyrophosphate. In the progressive ankylosis (ank) mouse, a premature termination mutation at glutamic acid 440 results in a phenotype characterized by inappropriate deposition of basic calcium phosphate crystals in skeletal tissues. Mutations in the amino terminus of ANKH, the human homolog of Ank, result in familial calcium pyrophosphate dihydrate deposition disease. It has been hypothesized that these mutations result in a gain-of-function with respect to the elaboration of extracellular inorganic pyrophosphate. To explore this issue in a mineralization-competent system, we stably transduced ATDC5 cells with wild-type Ank …

An Investigation Of Factors Predicting The Type Of Bladder Antimuscarinics Initiated In Medicare Nursing Homes Residents, Daniela C. Moga, Qishan Wu, Pratik Doshi, Amie J. Goodin

Pharmacy Practice and Science Faculty Publications

Background: To examine factors predicting type of bladder antimuscarinics (BAM) initiated in nursing home (NH) residents.

Methods: Incident BAM initiators following NH admission were identified by constructing a retrospective cohort from Medicare files and Minimum Data Set (MDS). Participants included all residents 65 years and older admitted in Medicare-certified NH between January 1, 2007 and December 31, 2008 who were prescribed BAM and had continuous Medicare (Part A, B, and D) enrollment. Patient characteristics, medications, and comorbidities were derived from Medicare enrollment and claims. NH characteristics and health status were derived from MDS assessments. The outcome was defined as type …

Immune Checkpoint Inhibitors In Neuroendocrine Tumors: A Single Institution Experience With Review Of Literature, Aman Chauhan, Millicent Horn, Gray Magee, Kurt Hodges, B. Mark Evers, Susanne Arnold, Lowell B. Anthony

Markey Cancer Center Faculty Publications

This unique case series and review of literature suggests that immune checkpoint inhibitors may have clinical activity in neuroendocrine tumors.

Objective: Summarize advances of immuno-oncology in neuroendocrine tumors with the help of a case series.

Design: Case series and review of literature.

Intervention or Exposure: The patients were treated with immune checkpoint inhibitors (pembrolizumab or nivolumab).

Main Outcome(s) and Measures(s): Life expectancy, quality of life, disease progression.

Results: Maximum durable response of 16 months in one of the patients so far. All patients showed improvement in quality of life before disease progression. Two out of four are still on therapy. …

Multicenter, Randomized Study To Optimize Bowel For Colon Capsule Endoscopy, David Kastenberg, Wilmot C. Burch Jr, David P. Romeo, Pankaj K. Kashyap, David C. Pound, Neophytos Papageorgiou, Ignacio Fernández-Urien Sainz, Carly E. Sokach, Douglas K. Rex

Division of Gastroenterology and Hepatology Faculty Papers

AIM To assess the cleansing efficacy and safety of a new Colon capsule endoscopy (CCE) bowel preparation regimen. METHODS This was a multicenter, prospective, randomized, controlled study comparing two CCE regimens. Subjects were asymptomatic and average risk for colorectal cancer. The second generation CCE system (PillCam^® COLON 2; Medtronic, Yoqneam, Israel) was utilized. Preparation regimens differed in the 1^st and 2^nd boosts with the Study regimen using oral sulfate solution (89 mL) with diatrizoate meglumine and diatrizoate sodium solution (“diatrizoate solution”) (boost 1 = 60 mL, boost 2 = 30 mL) and the Control regimen oral sulfate …

Epilepsy, Hippocampal Sclerosis And Febrile Seizures Linked By Common Genetic Variation Around Scn1a., Dalia Kasperaviciute, Claudia B Catarino, Mar Matarin, Costin Leu, Jan Novy, Anna Tostevin, Bárbara Leal, Ellen V S Hessel, Kerstin Hallmann, Michael S Hildebrand, Hans-Henrik M Dahl, Mina Ryten, Daniah Trabzuni, Adaikalavan Ramasamy, Saud Alhusaini, Colin P Doherty, Thomas Dorn, Jörg Hansen, Günter Krämer, Bernhard J Steinhoff, Dominik Zumsteg, Susan Duncan, Reetta K Kälviäinen, Kai J Eriksson, Anne-Mari Kantanen, Massimo Pandolfo, Ursula Gruber-Sedlmayr, Kurt Schlachter, Eva M Reinthaler, Elisabeth Stogmann, Fritz Zimprich, Emilie Théâtre, Colin Smith, Terence J O'Brien, K Meng Tan, Slave Petrovski, Angela Robbiano, Roberta Paravidino, Federico Zara, Pasquale Striano, Michael R Sperling, Russell J Buono, Hakon Hakonarson, João Chaves, Paulo P Costa, Berta M Silva, António M Da Silva, Pierre N E De Graan, Bobby P C Koeleman, Albert Becker, Susanne Schoch, Marec Von Lehe, Philipp S Reif, Felix Rosenow, Felicitas Becker, Yvonne Weber, Holger Lerche, Karl Rössler, Michael Buchfelder, Hajo M Hamer, Katja Kobow, Roland Coras, Ingmar Blumcke, Ingrid E Scheffer, Samuel F Berkovic, Michael E. Weale, Uk Brain Expression Consortium, Norman Delanty, Chantal Depondt, Gianpiero L Cavalleri, Wolfram S Kunz, Sanjay M Sisodiya

Russell Buono

Epilepsy comprises several syndromes, amongst the most common being mesial temporal lobe epilepsy with hippocampal sclerosis. Seizures in mesial temporal lobe epilepsy with hippocampal sclerosis are typically drug-resistant, and mesial temporal lobe epilepsy with hippocampal sclerosis is frequently associated with important co-morbidities, mandating the search for better understanding and treatment. The cause of mesial temporal lobe epilepsy with hippocampal sclerosis is unknown, but there is an association with childhood febrile seizures. Several rarer epilepsies featuring febrile seizures are caused by mutations in SCN1A, which encodes a brain-expressed sodium channel subunit targeted by many anti-epileptic drugs. We undertook a genome-wide association …

Home-Based Pre-Exposure Prophylaxis (Prep) Services For Gay And Bisexual Men: An Opportunity To Address Barriers To Prep Uptake And Persistence, Steven A. John, H Jonathon Rendina, Christina Grov, Jeffrey T. Parsons

Publications and Research

Gay, bisexual, and other men who have sex with men (GBM) are disproportionately affected by the HIV epidemic. Despite the promise of pre-exposure prophylaxis (PrEP) in reducing HIV transmission risk, barriers for uptake and persistence exist. We sought to identify whether GBM in a nationwide cohort who have not yet initiated PrEP (n = 906) would prefer to get PrEP-related care from a primary care provider (PCP) compared to a specialist clinic or provider. We then sought to identify their level of interest and factors associated with preference for using home-based PrEP services (i.e., HB-PrEP), defined to participants as conducting …

An Assessment Of Emotional Intelligence In Emergency Medicine Resident Physicians., Dimitrios Papanagnou, Kathryn Linder, Anuj Shah, Kory Scott London, Shruti Chandra, Robin Naples

Department of Emergency Medicine Faculty Papers

OBJECTIVES: To define the emotional intelligence (EI) profile of emergency medicine (EM) residents, and identify resident EI strengths and weaknesses.

METHODS: First-, second-, and third-year residents (post-graduate years [PGY] 1, 2, and 3, respectively) of Thomas Jefferson University Hospital's EM Program completed the Emotional Quotient Inventory (EQ-i 2.0), a validated instrument offered by Multi-Health Systems. Reported scores included total mean EI, 5 composite scores, and 15 subscales of EI. Scores are reported as means with 95% CIs. The unpaired, two-sample t-test was used to evaluate differences in means.

RESULTS: Thirty-five residents completed the assessment (response rate 97.2%). Scores were normed …

Nuclear Spindles Pave The Way To Metastasis, Patrick J. Hensley, Natasha Kyprianou

Urology Faculty Publications

No abstract provided.

An Assessment Of Emotional Intelligence In Emergency Medicine Resident Physicians., Dimitrios Papanagnou, Kathryn M Linder, Anuh Shah, Kory Scott London, Shruti Chandra, Robin Naples

Department of Emergency Medicine Faculty Papers

Objectives: To define the emotional intelligence (EI) profile of emergency medicine (EM) residents, and identify resident EI strengths and weaknesses.

Methods: First-, second-, and third-year residents (post-graduate years [PGY] 1, 2, and 3, respectively) of Thomas Jefferson University Hospital's EM Program completed the Emotional Quotient Inventory (EQ-i 2.0), a validated instrument offered by Multi-Health Systems. Reported scores included total mean EI, 5 composite scores, and 15 subscales of EI. Scores are reported as means with 95% CIs. The unpaired, two-sample t-test was used to evaluate differences in means.

Results: Thirty-five residents completed the assessment (response rate 97.2%). Scores were normed …

Tfpiα Interacts With Fva And Fxa To Inhibit Prothrombinase During The Initiation Of Coagulation, Jeremy P. Wood, Helle H. Petersen, Bingke Yu, Xiaoai Wu, Ida Hilden, Alan E. Mast

Gill Heart & Vascular Institute Faculty Publications

Tissue factor pathway inhibitor α (TFPIα) inhibits prothrombinase, the thrombin-generating complex of factor Xa (FXa) and factor Va (FVa), during the initiation of coagulation. This inhibition requires binding of a conserved basic region within TFPIα to a conserved acidic region in FXa-activated and platelet-released FVa. In this study, the contribution of interactions between TFPIα and the FXa active site and FVa heavy chain to prothrombinase inhibition were examined to further define the inhibitory biochemistry. Removal of FXa active site binding by mutation or by deletion of the second Kunitz domain (K2) of TFPIα produced 17- or 34-fold weaker prothrombinase inhibition, …