An observational study in Bleeding Disorders, Iron and Platelet, sponsored by Nicoletta C Machin. Recruiting at 1 site in United States. Open to participants aged 15 Years and older. Per ClinicalTrials.gov, last updated 2026-10-06.
Sponsored by Nicoletta C Machin · Observational
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
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.
361 studies on the registry are indexed under Hemostatic Disorders; 65 are open to participants now.
This study's planned enrollment of 40 is below the median of 120 across 174 observational studies indexed under Hemostatic Disorders.
Browse Hemostatic Disorders studies →Nicoletta C Machin is the lead sponsor of 2 studies on the registry; 1 is open to participants now.
Counted across the registry records on this site, refreshed daily.
Patient in the outpatient setting with a bleeding disorder and Iron Deficiency planned for IV Iron as per Standard of care followed at the Hemophilia Center of Western Pennsylvania
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
Drug: IV Iron (standard of care)
Participants will receive IV iron therapy as part of standard management for iron deficiency
Change in bleeding assessment (ISTH-BAT score)
Change in bleeding severity 3 months after IV iron replacement, assessed using the ISTH-BAT (International Society on Thrombosis and Haemostasis Bleeding Assessment Tool). ISTH-BAT: Score range 0-56; higher scores indicate greater bleeding severity. Safety Issue: No
Time frame: Baseline to 3 months post-IV iron replacement
Change in Menstrual Blood Loss (PBAC Score)
Change in menstrual bleeding 3 months after IV iron replacement, measured using the Pictorial Blood Loss Assessment Chart (PBAC). Assessed only in menstruating female participants. PBAC: Score \<100 indicates normal menstrual blood loss; scores \>100 suggest heavy menstrual bleeding.
Time frame: Baseline to 3 months post-IV iron replacement
Change in Epistaxis Severity Score (ESS)
Change in epistaxis severity from baseline to 3 months post-IV iron replacement, measured using the Epistaxis Severity Score (ESS), a validated clinical tool for quantifying frequency, duration, and impact of nosebleeds. Score Range: 0 to 10 Scoring Interpretation: Higher scores indicate more severe or frequent nosebleeds. A reduction in score reflects clinical improvement.
Time frame: Baseline to 3 months post-IV iron replacement
Change in Fatigue (FACIT-F Score)
Change in fatigue levels from baseline to 3 months after IV iron replacement, as measured by the Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-F). Score Range: 0 to 160 Scoring Interpretation: Lower scores indicate greater fatigue; higher scores indicate improved energy and well-being.
Time frame: Baseline to 3 months post-IV iron replacement
Change in Physical Functioning (SF-36)
Change in physical functioning score on the SF-36 from baseline to 3 months post-IV iron. Score Range: 0 to 100 Scoring Interpretation: Higher scores indicate better physical functioning.
Time frame: Baseline to 3 months
Change in Role Limitations Due to Physical Health (SF-36)
Change in score from the Role Physical domain of the SF-36, which evaluates problems with work or daily activities due to physical health. Score Range: 0 to 100 Scoring Interpretation: Higher scores reflect fewer role limitations.
Time frame: Baseline to 3 months
Change in Role Limitations Due to Emotional Problems (SF-36)
Change in the Role Emotional domain score of the SF-36, which assesses limitations in daily activities due to emotional difficulties. Score Range: 0 to 100 Scoring Interpretation: Higher scores indicate better emotional role functioning.
Time frame: Baseline to 3 months
Change in the Vitality domain of the SF-36, measuring energy levels and fatigue.
Change in the Vitality domain of the SF-36, measuring energy levels and fatigue. Score Range: 0 to 100 Scoring Interpretation: Higher scores indicate greater energy and less fatigue.
Time frame: Baseline to 3 months
Change in Social Functioning (SF-36)
Change in the Social Functioning domain score, reflecting the extent to which physical or emotional health interferes with normal social activities. Score Range: 0 to 100 Scoring Interpretation: Higher scores indicate better social functioning.
Time frame: Baseline to 3 months
Change in Pain Score (SF-36)
Change in the Bodily Pain domain of the SF-36, evaluating intensity of pain and its effect on daily activities. Score Range: 0 to 100 Scoring Interpretation: Higher scores indicate less pain and better pain management.
Time frame: Baseline to 3 months
Change in Emotional Well-Being (SF-36)
Change in the Mental Health domain score of the SF-36, assessing psychological well-being, mood, and anxiety. Score Range: 0 to 100 Scoring Interpretation: Higher scores indicate better emotional well-being.
Time frame: Baseline to 3 months
Change in General Health Perception (SF-36)
Change in the General Health domain score of the SF-36, which assesses overall health perceptions. Score Range: 0 to 100 Scoring Interpretation: Higher scores reflect better perceived general health.
Time frame: Baseline to 3 months
Change in Mitochondrial Reactive Oxygen Species (ROS) in Platelets
Evaluate changes in mitochondrial reactive oxygen species (ROS) levels in platelet samples from baseline to 3 months post-IV iron replacement. This exploratory analysis will assess whether iron repletion alters platelet oxidative stress, potentially contributing to changes in platelet function and bleeding phenotype.
Time frame: Baseline to 3 months post-IV iron replacement
Change in Platelet Reactivity by Flow Cytometry
Evaluate changes in platelet reactivity before and after IV iron replacement, using flow cytometry to assess surface expression of activation markers (e.g., P-selectin, activated αIIbβ3 integrin) in response to standard agonists (e.g., ADP, CRP-XL). This exploratory analysis will examine whether iron repletion restores platelet responsiveness in iron-deficient individuals with inherited bleeding disorders.
Time frame: Baseline to 3 months post-IV iron replacement
Plan to share: Yes — The investigators plan to share individual participant data (IPD) that underlie the results reported in the publication, after de-identification. This may include demographic data, primary and secondary outcomes, and relevant covariates. Data will be made available to researchers who provide a methodologically sound proposal for use in academic, non-commercial research. Proposals should be directed to machinnc2@upmc.edu. Access will be granted following approval by our institutional review board or ethics committee and the execution of a data use agreement. Data will be available beginning 6 months after publication and will remain accessible for 5 years.
Supporting information: Study protocol, Statistical analysis plan, Informed consent form
Time frame: Data will be available beginning 6 months after publication and will remain accessible for 5 years.
Access criteria: Proposals should be directed to machinnc2@upmc.edu. Access will be granted following approval by our institutional review board or ethics committee and the execution of a data use agreement.
Started Aug 2025 (actual). Primary completion is estimated for Oct 2027, 25 months after the start.
Of 98 non-industry observational studies under Hemostatic Disorders, half reached primary completion within 25 months of starting (the median), counting those still running; a quarter within 12 and three quarters within 57. This study's planned 25 months is close to that.
Counting every sponsor, half of 108 studies reached it within 24 months; a quarter within 9 and three quarters within 56.
How these figures are worked out, and which studies are left out of them.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
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Nicoletta C Machin