Impact of IV Iron on Bleeding Symptoms in Iron Deficient Patients With Inherited Bleeding Disorders

NCT ID: NCT07083583

Last Updated: 2025-10-03

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 40 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2025-08-08
• Study Completion Date: 2027-10-01

Brief Summary

This is a prospective, single-arm, single-center observational study evaluating the impact of intravenous (IV) iron replacement in patients with inherited bleeding disorders and iron deficiency (ferritin <50ng/dL). Subjects will undergo baseline bleeding assessments, quality-of-life measures, and laboratory tests before receiving standard-of-care IV iron. Follow-up blood work and questionnaires will be conducted post-replacement to assess for changes

Detailed Description

Iron deficiency is one of the most prevalent nutritional deficiencies globally. In particular, patients with an inherited bleeding disorder are at increased risk of iron deficiency/ iron deficiency anemia given the propensity of this patient population to bleed. The impact of iron deficiency on hemoglobin synthesis is well established as it remains the leading cause of anemia worldwide, especially among menstruating women. Studies have shown a prevalence of iron deficiency as high as 93% in Hemophilia B Carriers , and iron deficiency anemia in 75% of females with von Willebrand Disease. However, platelets are also affected by iron deficiency. The effect of iron deficiency, as described in the past, is primarily seen in platelet production, where iron deficiency anemia (IDA) leads to increased platelet production or thrombocytosis. This is achieved through increased megakaryopoietic differentiation. Nonetheless, little is known about the effect of iron deficiency on platelet function and the mechanism by which it happens. In addition to that, it is unknown whether iron deficiency in patient with an underlying bleeding disorder could mitigate worsening bleeding symptoms.

Studies in mice have demonstrated that platelet function was suppressed in iron-deficient mice, with evidence of iron-dependent platelet activation promoted through calcium mobilization and αIIbβ3 activation. A recent study in women with IDA demonstrated that iron levels may affect platelet function. Flow cytometry showed that women with IDA have quiescent platelets circulating in a degranulated state, which might be refractory to hemostatic activation. That same study showed that iron repletion decreased P-selectin levels and enhanced degranulation of quiescent platelets when exposed to CRP-XL or ADP. That translated into increased adhesion to collagen. A study done in children, adolescents, and young adults highlighted that mean PFA-100 closure times were significantly longer in patients with IDA, with reduced Platelet aggregation with ADP, epinephrine, and ristocetin. That same study showed that treatment with Iron improved platelet aggregation tests and significantly decreased PFA-100.

The clinical relationship between bleeding, platelet function, and iron deficiency remains poorly understood. It is hypothesized that patients with iron deficiency may experience increased bleeding, with anecdotal evidence suggesting that bleeding improves as iron levels are restored. This effect is believed to be mediated by alterations in platelet function. However, the specific cellular and molecular mechanisms underlying platelet hyporesponsiveness in iron deficiency are poorly elucidated. This would particularly impact patients with an underlying inherited bleeding disorder who are at an increased risk of blood loss.

This study addresses the critical gap in understanding the bleeding phenotype in iron-deficient patients with inherited bleeding disorders. To date, no studies have comprehensively evaluated this relationship. The investigator proposes a prospective study to assess bleeding phenotypes through validated bleeding assessment scores and quality of life metrics, pre and post IV iron replacement. Additionally, the investigator will analyze platelet samples pre- and post-treatment to investigate the impact of iron replenishment on platelet function and hemostatic parameters. These findings will provide valuable insights into the interplay between iron deficiency, platelet function, and bleeding severity, advancing our understanding and management of this unique patient population.

Conditions

Bleeding Disorders; Iron; Platelet; Bleeding

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Iron Deficient patients with underlying bleeding disorders

Subjects ≥15 years old with a history of an inherited bleeding disorder (including von Willebrand disease, platelet disorders, factor deficiencies, or bleeding disorder of unknown cause) and ferritin \<50 ng/mL identified during routine clinic evaluation.

IV Iron (standard of care)

Intervention Type: DRUG

Participants will receive IV iron therapy as part of standard management for iron deficiency

Interventions

IV Iron (standard of care)

Participants will receive IV iron therapy as part of standard management for iron deficiency

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Males and Females > 15 years of age

2. Diagnosed with an Inherited Bleeding Disorder (Von Willebrand disease, platelet disorders, factor deficiencies, or bleeding disorder of unknown cause)

3. Evidence of Iron Deficiency (Ferritin < 50 ng/mL)

4. Receiving IV iron at Hemophilia Center of Western Pennsylvania

5. Willingness to have blood drawn

6. Willing to return to clinic 3 months post infusion for final blood draw, bleeding and quality of life assessments.

Exclusion Criteria

1. Previous thrombosis, VTE History.

2. Platelet count < 100,000 * 109/L

3. Concomitant use of antiplatelet drugs, anticoagulants, aspirin, NSAIDs.

• Minimum Eligible Age: 15 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Health Resources and Services Administration (HRSA)

FED

Sponsor Role: collaborator

Nicoletta C Machin

OTHER

Sponsor Role: lead

Responsible Party

Nicoletta C Machin

Assistant Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Nicoletta Machin, DO

Role: PRINCIPAL_INVESTIGATOR

University of Pittburgh

Locations

Hemophilia Center of Western Pennsylvania

Pittsburgh, Pennsylvania, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Nicoletta Machin, DO

Role: CONTACT

MANCHINN@pitt.edu

(412) 209-7280

Facility Contacts

Deborah Vehec

Role: primary

dvehec@vitalant.org

(412) 209-7564

Anuj Kaul

Role: backup

akaul@vitalant.org

(412) 209-7563

References

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

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Other Identifiers

STUDY25020144

Identifier Type: -

Identifier Source: org_study_id