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Author(s)

Mindy L. Simpson, MD

Department of Pediatrics, Hemophilia and Thrombophilia Center, Rush University Medical Center, Chicago, Illinois

Disclosures

Disclosure: Mindy L. Simpson, MD, has disclosed no relevant financial relationships.

Leonard A. Valentino, MD

Department of Pediatrics, Hemophilia and Thrombophilia Center, Rush University Medical Center, Chicago, Illinois

Disclosures

Disclosure: Leonard A. Valentino, MD, has disclosed no relevant financial relationships.

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Elisa Manzotti

Publisher, Future Science Group, London, United Kingdom

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Disclosure: Elisa Manzotti has disclosed no relevant financial relationships.

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Laurie Barclay, MD

Freelance writer and reviewer, Medscape, LLC

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Disclosure: Laurie Barclay, MD, has disclosed no relevant financial relationships.

CME Reviewer(s)

Nafeez Zawahir, MD

CME Clinical Director, Medscape, LLC

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Disclosure: Nafeez Zawahir, MD, has disclosed no relevant financial relationships.

CME

Management of Joint Bleeding in Hemophilia

Authors: Mindy L. Simpson, MD; Leonard A. Valentino, MD
CME Released: 9/20/2012
THIS ACTIVITY HAS EXPIRED FOR CREDIT
Valid for credit through: 9/20/2013, 11:59 PM EST

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Target Audience and Goal Statement

This activity is intended for hematologists, radiologists, pediatricians, and other clinicians caring for patients with joint bleeding due to hemophilia.

The goal of this activity is to review the clinical presentation and management of hemarthrosis in patients with hemophilia.

Upon completion of this activity, participants will be able to:

Describe the clinical characteristics of joint bleeding in hemophilia
Describe prophylaxis to prevent joint bleeding in hemophilia
Describe management of acute hemarthrosis in patients with hemophilia

Disclosures

Author(s)

Mindy L. Simpson, MD

Department of Pediatrics, Hemophilia and Thrombophilia Center, Rush University Medical Center, Chicago, Illinois

Disclosures

Disclosure: Mindy L. Simpson, MD, has disclosed no relevant financial relationships.

Leonard A. Valentino, MD

Department of Pediatrics, Hemophilia and Thrombophilia Center, Rush University Medical Center, Chicago, Illinois

Disclosures

Disclosure: Leonard A. Valentino, MD, has disclosed no relevant financial relationships.

Editor

Elisa Manzotti

Publisher, Future Science Group, London, United Kingdom

Disclosures

Disclosure: Elisa Manzotti has disclosed no relevant financial relationships.

CME Author(s)

Laurie Barclay, MD

Freelance writer and reviewer, Medscape, LLC

Disclosures

Disclosure: Laurie Barclay, MD, has disclosed no relevant financial relationships.

CME Reviewer(s)

Nafeez Zawahir, MD

CME Clinical Director, Medscape, LLC

Disclosures

Disclosure: Nafeez Zawahir, MD, has disclosed no relevant financial relationships.

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Outcome Measurement

Questionnaires

A major limitation in the use of questionnaires to assess outcomes following episodes of joint bleeding is that most scales are dependent on patient reports^[73] and lack objective measures, such as data from tools for evaluating psychometrics^[74] or HRQoL.^[75] One tool developed specifically to evaluate the functional wellbeing of hemophilia patients is the Hemophilia Joint Health Score, an 11-item measure administered by a physical therapist.^[76] Objective findings assessed include the presence or absence of joint swelling, preservation or loss of flexion and extension and gait changes. The outcome-predicting power of the Hemophilia Joint Health Score has been validated in boys. Other tools under study include questionnaires that assess independence^[77] and the ability to participate in regular^[78,79] and sporting activities.^[80] The use of multiple scales improves the precision of questionnaires used to assess joint outcome posthemarthroses.^[81]

Imaging Modalities

Patient-reported outcomes have traditionally been used to determine when bleeding has stopped because it has been quite difficult to detect joint bleeding with radiography. However, this situation is changing. MRI has advantages over radiography because of its ability to visualize soft tissue and cartilage changes in hemophilia joints.^[20] Two MRI scoring systems – one is a progressive system that displays the most severe joint changes, the other an additive system that depicts osteochondral and soft tissue-related changes^[82] – may enable the comparison of pathologic joint findings.

MRI has some distinct limitations, including its ability to differentiate synovial hypertrophy and hemosiderin deposition.^[83] These deficiencies may be overcome with the use of ultrasound, which has been shown to provide objective evidence of bleed resolution and can also assess joint damage.^[84] A recent study that evaluated and scored the joints of 62 consecutive patients with hemophilia A or B and compared the findings with those from 20 healthy subjects and 20 subjects with rheumatoid arthritis found the correlation between ultrasound score and the number of hemorrhages to be highly significant (p < 0.01). Furthermore, ultrasound was effective in detecting synovitis and bone and cartilage alterations, and power Doppler ultrasound identified bleeding in asymptomatic joints.

A number of novel techniques are under evaluation for soft tissue and cartilage imaging that are as follows:

Blood oxygen level-dependent MRI, which relies on MRI contrast resulting from changes in the microvascular ratio of oxyhemoglobin to deoxyhemoglobin, may determine how hypoxia affects synovial changes as arthropathy progresses.^[85]
Ultrasmall superparamagnetic iron oxide contrast-enhanced MRI, which uses nanoparticle contrast media that appear to localize in synovial macrophages, may be able to quantify hemosiderin in a joint; ^[86]
Microbubble contrast-enhanced ultrasonography may increase the sensitivity of the color and power of the Doppler signal, making it possible to detect changes in low-velocity blood flow in the hemophilic synovium;^[87]
PET, which may detect arthritis-related inflammation;^[83]
T1^[88] and T2^[89] mapping MRI, which are sensitive to changes in cartilage composition, may help to characterize the structural integrity of cartilaginous tissue and quantitatively assess the degree of cartilage degeneration;
Ultrasound biomicroscopy, which uses high-frequency probes that allow evaluation of hyaline cartilage, intra-articular fibrocartilage and ligaments.^[90]

Although not an imaging strategy, biomarkers of synovium, cartilage and bone turnover and resorption (e.g., cartilage oligomeric matrix proteins, bone-specific alkaline phosphatase, C-terminal telopeptides type 1 collagen) have the potential to monitor subclinical bleeding and early joint disease.^[91]

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Page 7 of 10

Expert Commentary

CME Information

Abstract and Introduction
FVIII & FIX Genetics
Evolution of Hemophilia Therapy
Mechanisms of Blood-induced Joint Disease
Rationale for Prophylaxis
Management of Acute Hemarthrosis
Outcome Measurement
Expert Commentary
Five-year View
Key Issues

References

CME

Management of Joint Bleeding in Hemophilia

Target Audience and Goal Statement

Disclosures

Author(s)

Mindy L. Simpson, MD

Leonard A. Valentino, MD

Editor

Elisa Manzotti

CME Author(s)

Laurie Barclay, MD

CME Reviewer(s)

Nafeez Zawahir, MD

Accreditation Statements

For Physicians

Instructions for Participation and Credit

Management of Joint Bleeding in Hemophilia: Outcome Measurement

Outcome Measurement

Questionnaires

Imaging Modalities

Table of Contents

References

Faculty and Disclosures

Author(s)

Mindy L. Simpson, MD

Leonard A. Valentino, MD

Editor

Elisa Manzotti

CME Author(s)

Laurie Barclay, MD

CME Reviewer(s)

Nafeez Zawahir, MD

CME

Management of Joint Bleeding in Hemophilia

Target Audience and Goal Statement

Disclosures

Author(s)

Mindy L. Simpson, MD

Leonard A. Valentino, MD

Editor

Elisa Manzotti

CME Author(s)

Laurie Barclay, MD

CME Reviewer(s)

Nafeez Zawahir, MD

Accreditation Statements

For Physicians

Instructions for Participation and Credit

Management of Joint Bleeding in Hemophilia: Outcome Measurement

Outcome Measurement

Questionnaires

Imaging Modalities

Table of Contents