Venous Thrombosis Biomarkers in Sickle Cell Disease and Sickle Cell Trait

NCT04349189 | Completed

• 2 other identifiers: 20006820-H-0068
• Study Type: observational
• Target: 119
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Venous thromboembolism (VTE) includes the abnormal clotting of blood in a deep vein of the upper or lower limbs (deep vein thrombosis) that may travel to and block a blood vessel in the lung (pulmonary embolism). Some people with sickle cell disease (SCD)-a red blood cell disorder-seem to be at greater risk for developing these blood clots. Researchers want to study the blood of people with SCD and VTE as well as healthy people to develop better treatments to prevent blood clots. Objective: To study blood clotting in SCD because it is the most common cause of vascular death after a heart attack or stroke. Eligibility: People ages 18-80 who have SCD (with or without a history of blood clots) or the trait for SCD, and healthy volunteers Design: Participants will be screened with medical history, physical exam, and medical records review. They will give blood samples. Participants will have phone calls either every 3 months or once a year, for 2 years. They will give updates on their health. They may give additional medical records. The phone calls may last up to 30 minutes. If participants have a VTE or pain crisis episode, they may visit the Clinical Center. These visits may last up to 4 hours. They will repeat the screening tests and give blood samples. Some participants may be invited to take part in blood studies. After 2 years, some participants will have a follow-up visit at the Clinical Center. Participation will last for about 2 years.

Conditions

Sickle Cell Disease; Venous Thrombosis; Sickle Cell Trait; Hypercoagulable State; Venous Thromboembolism

Keywords

hypercoagulable state; Recurrence; Biomarkers; Venous Thromboembolism; Vascular Mortality; Natural History

Outcome Measures

Primary Outcomes (1)

• tissue factor positive

  Number of tissue factor positive EVs/ml of plasma

  At baseline during study

Study Arms (4)

Group 1

50 Men and Women with sickle cell disease and VTE

Group 2

50 Men and Women with sickle cell disease but no VTE

Group 3

50 Men and Women with sickle cell trait

Group 4

50 ethnically matched Men and Women without sickle cell disease, sickle cell trait, or VTE

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The natural history of SCD 04-H-0161 protocol (NCT00081523) will specifically be leveraged to recruit participants with VTE. In this study we will assess feasibility of establishing a prospective natural history study of thrombosis in SCD. Establishing feasibility could lead to recruitment of SCD patients experiencing thrombosis, particularly those that are understudied including patients with HbSC disease.

You may qualify if:

• Sickle cell disease with and without VTE
• Sickle cell disease (HbSS, HbSC and HbS/beta-thalassemia genotypes) in steady state.
• Diagnosis of at least one or more VTE within 5 years of study enrolment confirmed by radiologic imaging (for SCD patients with VTE).
• Absence of clinical history of VTE (for SCD controls)
• Between 18 and 80 years of age.
• Ability to provide informed written consent.
• Sickle cell trait
• Sickle cell disease (HbAS genotype).
• Absence of clinical history of VTE
• Between 18 and 80 years of age.
• Ability to provide informed written consent.
• Ethnically matched controls
• Between 18 and 80 years of age.
• African, or of African descent.
• Ability to provide informed written consent.

You may not qualify if:

• SCD with and without VTE
• Pregnancy (test done at enrollment; if a subject becomes pregnant during the study period, samples will not be obtained while the subject is pregnant and the subject will be taken off study).
• Patients on exchange transfusion or having received a simple blood transfusion in the past 60 days.
• Active viral infection as evidenced by testing positive for hepatitis B surface antigen or hepatitis C virus (HCV) antibody (Ab) with signs of active hepatitis B or C virus infection. If the subject is positive for HCV Ab, a reverse transcriptasepolymerase chain reaction test will be conducted. Subjects with hepatitis C may be rescreened after receiving appropriate hepatitis C treatment.
• Testing positive for human immunodeficiency virus 1 or 2 Ab with evidence for ongoing active infection (i.e., CD 4 count \<400/microL and viral load \>100,000 copies/ml) on antiretroviral therapy.
• Active acute inflammatory disorders rheumatoid arthritis or systemic lupus erythematosus on disease modifying therapy.
• SCT and ethnically matched controls
• Diagnosis of any of the following chronic disease or conditions: Sickle cell disease (HbSS, HbSC and HbS/beta-thalassemia genotypes).
• Clinical history of VTE.
• Pregnancy (test done at enrollment; if a subject becomes pregnant during the study period, samples will not be obtained while the subject is pregnant and the subject will be taken off study.
• Active viral infection as evidenced by testing positive for hepatitis B surface antigen or hepatitis C virus (HCV) antibody (Ab) with signs of active hepatitis B or C virus infection. If the subject is positive for HCV Ab, a reverse transcriptasepolymerase chain reaction test will be conducted. Subjects with hepatitis C may be rescreened after receiving appropriate hepatitis C treatment.
• Testing positive for human immunodeficiency virus 1 or 2 Ab with evidence for ongoing active infection (i.e., CD 4 count \<400/microL and viral load \>100,000 copies/ml) on antiretroviral therapy.
• Active acute inflammatory disorders rheumatoid arthritis or systemic lupus erythematosus on disease modifying therapy.

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Anemia, Sickle Cell; Venous Thrombosis; Sickle Cell Trait; Thrombophilia; Venous Thromboembolism; Recurrence

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Thrombosis; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Thromboembolism; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Arun S Shet, M.D.

  National Heart, Lung, and Blood Institute (NHLBI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 15, 2020
• First Posted: April 16, 2020
• Study Start: September 1, 2020
• Primary Completion: June 20, 2024
• Study Completion: June 20, 2024
• Last Updated: August 1, 2025

Record last verified: 2025-07-22

Locations

US (1)