Platelet Function in Patients With Hemophilia A

Decreased Platelet Function as a Cause of Increased Bleeding in Patients With Hemophilia A

Abnormalities in the gene encoding Factor VIII (FVIII) results in hemophilia A, an X-linked recessive bleeding disorder with a prevalence of 1 in 5000 males. Hemophilia A patients are classified into 3 different categories based on residual FVIII activity compared to normal: mild (6-40%), moderate (1-5%) and severe (<1%). This categorization correlates to some degree with bleeding phenotype, but does not completely define it. Some patients with hemophilia A bleed less often than others despite identical plasma FVIII levels. The cause(s) of this phenotype heterogeneity in hemophilia A remains largely unknown, despite a number of studies of possible factors.

Activated platelets, in addition to their role in primary hemostasis, play a major role in secondary hemostasis (coagulation) by providing a phospholipid surface to which coagulation factors bind. A role for platelets in the hemorrhagic propensity of hemophilia A has been suggested in the past, but only a small number of studies have been performed with limitations in assays performed and numbers of patients. The purpose of the present study is to determine whether platelet reactivity in severe hemophilia A patients is associated with past bleeding frequency and/or predicts future bleeding frequency.

Study Overview

• Status: Completed
• Conditions: Hemophilia A

• Study Type: Observational
• Enrollment (Actual): 36

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital, Boston Hemophilia Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

• Sampling Method: Non-Probability Sample

Study Population

Patients with severe hemophilia A who do not have inhibitors against FVIII and who have a bleeding history of at least 6 months.

Description

Inclusion Criteria:

• Patients with severe hemophilia A who are being prophylactically treated with FVIII.
• Age of at least 2 years.
• Bleeding history of at least 6 months.
• IRB-approved informed consent.

Exclusion Criteria:

• Presence of FVIII inhibitors.
• Greater than 7 days since active bleeding.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The percentage of coated platelets.	2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Platelet reactivity.	2 years
The number of procoagulant platelet-derived microparticles.	2 years

Collaborators and Investigators

• Sponsor: Boston Children's Hospital
• Collaborators: Baxter Healthcare Corporation
• Investigators: Principal Investigator: Alan D Michelson, MD, Boston Children's Hospital

Study record dates

Study Major Dates

• Study Start: March 1, 2015
• Primary Completion (Actual): June 1, 2018
• Study Completion (Actual): February 1, 2020

Study Registration Dates

• First Submitted: March 19, 2014
• First Submitted That Met QC Criteria: March 19, 2014
• First Posted (Estimate): March 20, 2014

Study Record Updates

• Last Update Posted (Actual): July 14, 2020
• Last Update Submitted That Met QC Criteria: July 10, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: bleeding; severe hemophilia A; coated platelets
• Additional Relevant MeSH Terms: Hematologic Diseases; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Blood Coagulation Disorders; Hemophilia A
• Other Study ID Numbers: BCH-CPRS-hemophilia A