Genotype and Phenotype Correlation in Hereditary Thrombotic Thrombocytopenic Purpura (Upshaw-Schulman Syndrome)

Description

Hereditary thrombotic thrombocytopenic purpura (Upshaw-Schulman syndrome) is a rare disorder characterized by thrombocytopenia as a result of platelet consumption, microangiopathic hemolytic anemia, occlusion of the microvasculature with von Willebrand factor-platelet-thrombic and ischemic end organ damage. The underlying patho-mechanism is a severe congenital ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 motif, 13) deficiency which is the result of compound heterozygous or homozygous ADAMTS13 gene mutations. Although considered a monogenic disorder the clinical presentation in Upshaw-Schulman syndrome patients varies considerably without an apparent genotype-phenotype correlation. In 2006 we have initiated a registry for patients with Upshaw-Schulman syndrome and their family members to identify possible triggers of acute bouts of TTP, to document individual clinical courses and treatment requirements as well as possible side effects of long standing plasma substitution, e.g. alloantibody formation or viral infections.

Conditions

Thrombotic Thrombocytopenic Purpura, Congenital Thrombotic Thrombocytopenic Purpura, Familial Thrombotic Thrombocytopenic Purpura, Thrombotic Thrombocytopenic Purpura, Congenital, Upshaw-Schulman Syndrome

Study Overview

Study Details

Study overview

Hereditary thrombotic thrombocytopenic purpura (Upshaw-Schulman syndrome) is a rare disorder characterized by thrombocytopenia as a result of platelet consumption, microangiopathic hemolytic anemia, occlusion of the microvasculature with von Willebrand factor-platelet-thrombic and ischemic end organ damage. The underlying patho-mechanism is a severe congenital ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 motif, 13) deficiency which is the result of compound heterozygous or homozygous ADAMTS13 gene mutations. Although considered a monogenic disorder the clinical presentation in Upshaw-Schulman syndrome patients varies considerably without an apparent genotype-phenotype correlation. In 2006 we have initiated a registry for patients with Upshaw-Schulman syndrome and their family members to identify possible triggers of acute bouts of TTP, to document individual clinical courses and treatment requirements as well as possible side effects of long standing plasma substitution, e.g. alloantibody formation or viral infections.

Thrombotic Thrombocytopenic Purpura Registry - A Prospective Observational Study for Patients Suffering From Hereditary Thrombotic Thrombocytopenic Purpura (Upshaw-Schulman Syndrome)

Genotype and Phenotype Correlation in Hereditary Thrombotic Thrombocytopenic Purpura (Upshaw-Schulman Syndrome)

Condition
Thrombotic Thrombocytopenic Purpura
Intervention / Treatment

-

Contacts and Locations

Oklahoma City

University of Oklahoma Health Sciences Center, Department of Medicine, PO Box 26901, Oklahoma City, Oklahoma, United States, 73126-0901

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

For general information about clinical research, read Learn About Studies.

Eligibility Criteria

  • * Severe ADAMTS13 deficiency ( ≤ 10% activity) and no ADAMTS 13 inhibitor on two or more occasions at least one month apart
  • * Being a family member of a confirmed or suspected patient
  • * Molecular analysis of ADAMTS13 gene with one or more mutations and/or positive infusion trial (full recovered ADAMTS13 activity after infused fresh frozen plasma (FFP) with a plasma half-life of 2-4 days)

Ages Eligible for Study

to

Sexes Eligible for Study

ALL

Accepts Healthy Volunteers

No

Collaborators and Investigators

Insel Gruppe AG, University Hospital Bern,

Johanna A Kremer Hovinga, MD, STUDY_CHAIR, University Clinic of Hematology and Central Hematology Laboratory, Bern University Hospital and the University of Bern, Inselspital

Bernhard Lämmle, M.D., STUDY_CHAIR, University Medical Center, Center for Thrombosis and Hemostasis, Mainz, Germany

Yoshihiro Fujimura, M.D., STUDY_CHAIR, Department of Blood Transfusion Medicine, Nara Medical University, Kashihara, Japan

Ingrid Hrachovinova, Ph.D., STUDY_CHAIR, Institute of Hematology and Blood Transfusion, Coagulation Laboratory, Prague, Czech Republic

Petter Quist-Paulsen, M.D., Ph.D., STUDY_CHAIR, Department of Hematology, St Olavs Hospital, 7006 Trondheim, Norway

Reinhard Schneppenheim, M.D., Ph.D., STUDY_CHAIR, Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

James N. George, MD, STUDY_CHAIR, University of Oklahoma Health Sciences Center, Department of Medicine, United States of America

Paul N Knoebl, MD, STUDY_CHAIR, Medical University of Vienna, Div. Hematology and Hemostasis, Austria

Study Record Dates

2030-10