Protocol - Counts of Acute Bleeds in Hemophilia
This protocol includes a bleeding log from the American Thrombosis and Hemostasis Network (ATHN) and consensus definitions from the International Societies for Thrombosis and Hemostasis (ISTH) network. The bleeding log includes six self-administered questions that capture date and location of bleed, symptoms, treatment, and response to treatment. ISTH definitions cover response to treatment (e.g., excellent, good, moderate, none) as well as classification of new bleeds, joint bleeds, and target joints. This protocol also includes guidance from the Hemophilia Inhibitors Working Group for calculating annualized bleeding rate (ABR).
The Hemophilia Inhibitor Research Working Group (WG) recommends that the calculation of annualized bleeding rate (ABR) be based on the number of bleeds instead of the number of infusions or the amount of prescribed therapeutics. Additionally, when reporting ABR, investigators should specify the methodological details, including the measures used (e.g., bleed logs, infusion logs, dispensing logs); monitoring methods (e.g., patient recall, electronic recording, administrative databases); and the time frame of data collection.
1. Date of bleed event
2. Location of bleed event
3. Which of the following symptoms did you have? (All that apply)
[ ] Unusual feeling in the joint
[ ] Warmth over the skin
[ ] Pain
[ ] Swelling
[ ] Stiffness
[ ] Loss of range of motion
[ ] None of the above
4. Did you treat your bleed with RICE?
[ ] Yes
[ ] No
[ ] Unknown
5. Did you treat your bleed with factor?
[ ] Yes
[ ] No
5a. If yes, did you take more factor than your normal prescribed dose?
[ ] Yes
[ ] No
[ ] Unknown
6. How would you describe your response* to factor treatment?
[ ] Excellent
[ ] Good
[ ] Moderate
[ ] None
RICE stands for: Rest, Ice, Compression, Elevation.
* International Society on Thrombosis and Hemostasis definition for response to treatment:
- Excellent - Complete pain relief within 8 hours and/or complete resolution of signs of bleeding after the initial injection and not requiring any further replacement therapy for relief of persistent symptoms and signs in the same joint within 72 hours.
- Good - Significant pain relief and/or improvement in signs of bleeding within approximately 8 hours after a single injection but requiring more than one dose of replacement therapy within 72 hours for complete resolution.
- Moderate - Modest pain relief and/or improvement in signs of bleeding within approximately 8 hours after the initial injection and requiring more than one injection within 72 hours but without complete resolution.
- None - No or minimal improvement, or condition worsens, within approximately 8 hours after the initial injection.
International Society on Thrombosis and Hemostasis Definitions
- After an initial moderate to excellent response to treatment, a new bleed is defined as a bleed occurring > 72 hours after stopping treatment for the original bleed for which treatment was initiated.
- An unusual sensation "aura" in the joint, in combination with any of the following:
- increasing swelling or warmth of the skin over the joint;
- increasing pain; or
- progressive loss of range of motion or difficulty in using the limb as compared with baseline.
- In infants and young children, reluctance to use the limb alone may be indicative of a joint/muscle bleed.
- Three or more spontaneous bleeds into a single joint within a consecutive 6-month period.
- Where there have been < 2 bleeds into the joint within a consecutive 12-month period, the joint is no longer considered a target joint.
Annualized Bleeding Rate (ABR)
The Hemophilia Inhibitors Working Group recommends that the calculation of annualized bleeding rate (ABR) be based on the number of bleeds instead of number of infusions or amount of prescribed therapeutics. Additionally, when reporting annualized bleeding rate, investigators should specify the methodological details including the measures used (e.g., bleed logs, infusion logs, dispensing logs); monitoring methods (e.g., patient recall, electronic recording, administrative databases); and the time frame of data collection.
Personnel and Training Required
|Specialized requirements for biospecimen collection||No|
|Average time of greater than 15 minutes in an unaffected individual||No|
Mode of Administration
Infant, Toddler, Child, Adolescent, Adult, Senior, Pregnancy
The Hemophilia Inhibitors Working Group selected the American Thrombosis and Hemostasis Network (ATHN) Bleeding Log and the consensus definitions from the International Society of Thrombosis and Hemostasis (ISTH) as the best standardized methodology for capturing and classifying bleeding events and response to treatment.
|caDSR Common Data Elements (CDE)||Hemophilia Bleeding Log Assessment Text||6706549||CDE Browser|
Process and Review
Protocol Name from Source
American Thrombosis and Hemostasis Network (ATHN) dataset Core Data Elements, Version 2.0
Source for Bleeding Log:
American Thrombosis and Hemostasis Network (ATHN). (2015, October 30). ATHNdataset Core Data Elements, Version 2.0. Bleed/Infusion Data: Bleed Events.
Source for International Society of Thrombosis and Hemostasis definitions:
Blanchette, V. S., Key, N. S., Ljung, L. R., Manco-Johnson, M. J., van den Berg, H. M., & Srivastava, A.; Subcommittee on Factor VIII, Factor IX, and Rare Coagulation Disorders of the Scientific and Standardization Committee of the International Society on Thrombosis and Hemostasis. (2014). Definitions in hemophilia: Communication from the SSC of the ISTH. Journal of Thrombosis and Haemostasis, 12(11), 1935-1939.
Berntorp, E., Astermark, J., Bj
Oldenburg, J., Mahlangu, J. N., Kim, B., Schmitt, C., Callaghan, M. U., Young, G., Santagostino, E., Kruse-Jarres, R., Negrier, C., Kessler, C., Valente, N., Asikanius, E., Levy, G. G., Windyga, J., & Shima, M. (2017). Emicizumab prophylaxis in hemophilia A with inhibitors. New England Journal of Medicine, 377(9), 809-818.
|Variable Name||Variable ID||Variable Description||dbGaP Mapping|
|PX910101010000||Date of bleed event||N/A|
|PX910101060000||How would you describe your response* to more||N/A|
|PX910101020000||Location of bleed event||N/A|
|PX910101030000||Which of the following symptoms did you have?||N/A|
|PX910101050100||If yes, did you take more factor than your more||N/A|
|PX910101050000||Did you treat your bleed with factor?||N/A|
|PX910101040000||Did you treat your bleed with RICE?||N/A|
Counts of Acute Bleeds in Hemophilia
May 7, 2019
Bleeds in hemophilia are not typically the results of massive trauma (e.g., gunshot, stabbing) but instead are most often internal bleeding events into joints, organs, mucosa, or soft tissue and involve little or no known trauma.
This measure can be used to document the occurrence, treatment, response to treatment, and classification of a bleeding event. This measure also includes guidance for calculating annualized bleeding rate (ABR).
New bleed, target joint, joint bleed, annualized bleeding rate, ABR