Methods

HTC PP

Eligibility

Eligible diagnoses include hemophilia A, hemophilia B, VWD, other rare clotting factor deficiencies or deficiencies of regulators of fibrinolysis, hereditary/functional platelet disorders, connective tissue disorders, unspecified bleeding disorders, and venous thromboembolism (VTE).

Included within the HTC PP are all patients with the above diagnoses, 89 years of age or younger, who receive care at HTCs either in person or by telemedicine.

Data Collection

Data for HTC PP are collected as a de-identified¹ data set that is compliant with the Health Insurance Portability and Accountability Act (HIPAA). The following twelve items are collected:

1. Year of Birth
2. Sex
3. Ethnicity (Hispanic versus non-Hispanic)
4. Race
5. First 3 Digits of Zip Code of Residence
6. Insurance Status
7. Primary Bleeding Disorder Diagnosis
8. Baseline Factor Activity
9. Von Willebrand Factor Activity (vWF:RCof)
10. Von Willebrand Factor Antigen Level (vWF:Ag)
11. Hepatitis C (HCV) Infection Status
12. Human Immunodeficiency Virus (HIV) Infection Status

HTC PP data are collected for each calendar year².

The Registry

Eligibility

Persons with a bleeding disorder diagnosis who receive care at an HTC are eligible for inclusion in the data collection effort. Eligible diagnoses include hemophilia A, hemophilia B, VWD, other rare clotting factor deficiencies or deficiencies of regulators of fibrinolysis, and hereditary/functional platelet disorders.

Data Collection

The Registry data are collected during a participant’s routine comprehensive clinic visits. Data are collected according to guidelines and definitions detailed in surveillance manuals. Clinical information is collected using a combination of medical record abstraction or direct patient interview by HTC staff as a part of the routine clinical assessment. Information collected includes demographics (e.g. sex, race, age, insurance status), bleeding disorder diagnoses, treatments, bleeding events, related complications (e.g. inhibitor development), healthcare utilization, and presence of other health conditions. An Initial Visit form is completed one time only for each participant to collect historic and current clinical information. Thereafter, a Subsequent Visit form is completed as often as annually³ to collect clinical information and outcomes data since the last episode of participation. CDC considers this project to be non-research public health surveillance for which disclosure of protected health information by covered entities is authorized by Title 45, Code of Federal Regulations section 164.512(b), pursuant to the Standards for Privacy of Individually Identifiable Information promulgated by HIPAA.  As such, federal regulations do not require written informed consent.  Nonetheless, written authorization is sought from all participants to ensure they are informed about the project.  A minority of participating institutions designated the project as research and require written informed consent.

From December 1, 2013 through August 23, 2015, completed Registry Initial Visit paper forms were mailed through FedEx to CDC and entered into a computer database. Data were examined upon entry into the database for missing data, inconsistencies, and unusual values that possibly represented abstraction or data-entry errors. Error reports were sent to the respective HTCs and a designated contact at each HTC used available information to resolve discrepancies and complete missing data items. Beginning on August 24, 2015, the Registry Initial Visit form data have been submitted electronically using ATHN’s web-based system for electronic data collection, the ATHN Study Manager. The data are packaged into an electronic data file that is sent to CDC daily. The ATHN information infrastructure is housed at commercial data centers that meet industry standards for security and encryption. Data from individual participants and specimens are reported to CDC using a coded, unique subject identification number and an HTC identification number. The subject identification number is generated randomly by a computer program and is not derived from any personal identifiers. As a HIPAA-compliant, limited data set, no identifiers listed as direct identifiers at section 164.514 (e) of the HIPAA Privacy Rule are sent to CDC or ATHN.

As this report represents data from the first year of data collection, only data from Initial Visit forms are included in this report. Eighty-five of 132 HTCs contributed data during the first year of data collection.

Blood Specimen Testing and Storage

Treatment of persons with bleeding disorders may involve infusion of blood products that may be contaminated with blood-borne viruses or other agents that can cause disease. Treatment also may involve use of clotting factor products, which may pose a risk for complications, including the development of an antibody (inhibitor) to the treatment product that decreases the effectiveness of the product to stop bleeding. To monitor for these complications, participants are asked to provide a serum or plasma specimen or both based on their exposure to certain treatment products, including blood products, plasma-derived factor concentrates, and recombinant factor concentrates.

A baseline serum specimen is collected and tested for hepatitis C and HIV for participants 2 years old and older regardless of treatment product exposure. If patients previously participated in the UDC surveillance project, serum specimens are collected and tested according to their previous UDC test results and interim treatment product exposure (blood bank products, plasma-derived factor concentrates or unknown interim treatment product use). Subsequent year serum collection and testing is performed if participants have had at least one relevant interim exposure.

A baseline plasma specimen is collected and tested for inhibitors to factor VIII (FVIII) or factor IX (FIX) for all participants deficient in FVIII or FIX (primarily, those with hemophilia A, hemophilia B or type 3 VWD) who have ever received blood products or FVIII/FIX concentrates (recombinant or plasma-derived) or who have an unknown treatment product history. Subsequent year plasma collection and testing is performed if participants have had at least one interim exposure to blood bank products, FVIII/FIX concentrates (recombinant or plasma-derived), or who have an unknown interim treatment product use.

Footnotes

1. De-identified means that the person’s identity cannot be connected with the information because personal identifiers, such as name, address, and birthdate, have been removed.
2. Most data for a given year are reported by February of the following year, but some records may be received later.
3. The actual interval between data collection episodes may be as little as nine months or significantly longer than a year, depending upon the participant’s routine schedule for comprehensive visits. Participants with disorders having a mild clinical course may not attend a comprehensive visit every year.