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203. Centers for Disease Control and Prevention. Summary report of UDC national activity. Treatment/clinical characteristics (hemophilia). www2a.cdc.gov/ncbddd/htcweb/UDC_Report/UDC_Report.asp (Accessed 3 December 2011)

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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.

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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

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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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Mechanisms of Blood-induced Joint Disease

The progression from normal joint to synovitis and then to arthropathy is attributed to undefined mediators in blood,^[27,28] which is not normally found in the joint space.^[29] Following an isolated hemarthrosis, blood in the joint cavity is gradually resorbed by synovial tissue over a period of 3–4 weeks, resulting in complete resolution of the hemorrhage.^[30] By contrast, recurrent bleeding into a joint overwhelms the synovium. Iron (hemosiderin), the degradation product of red blood cells, accumulates in the tissue, leading to synovial hypertrophy and hyperplasia and the proliferation and persistence of inflammatory cells.^[31] Chronic inflammation triggers the release of tissue-destructive enzymes and cytokines that contribute to progressive joint damage.^[32,33]

Vascular development and angiogenesis are an essential component of blood-induced joint disease. Just as angiogenesis is required for tumor growth, angiogenesis also appears to be necessary for synovial expansion.^[34] Neovascularization causes the synovial membrane to thicken and develop friable fronds and villous projections. A network of capillaries forms under the hypertrophied synovium in response to joint irritation and in an effort to increase blood flow to remove blood breakdown products.^[30] Any attempt at joint rehabilitation may cause the synovial fronds and villi to become trapped in the joint space and torn with joint motion, severing the subsynovial vessels and causing bleeding. New hemorrhaging further irritates the synovium, increasing the likelihood of subsequent synovial entrapment and bleeding directly resulting in a self-perpetuating cycle of bleeding, synovitis and joint bleeding.^[30]

Articular cartilage is composed of chondrocytes embedded in an extracellular matrix that produce collagen, proteoglycans and metabolism-regulating enzymes.^[35] The continuous presence of blood in a joint changes the composition of the articular cartilage, possibly owing to the loss of proteoglycans and the production of degradative enzymes from iron-laden synovial or subsynovial macrophages.^[36] As joint disease progresses, bone remodeling occurs, and osteoclastic activity increases, resulting in a loss of bone mineral density that culminates in osteoporosis.^[27,28]

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Page 4 of 10

Rationale for Prophylaxis

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: Mechanisms of Blood-induced Joint Disease

Mechanisms of Blood-induced Joint Disease

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: Mechanisms of Blood-induced Joint Disease

Mechanisms of Blood-induced Joint Disease

Table of Contents