Presentation Patterns of Adolescents With Platelet Function Disorders Affected With Heavy Menstrual Bleeding

Abstract Introduction: Platelet function disorders (PFD) clinically manifest with wide variability in mucocutaneous bleeding and significant hemorrhage post-surgery or trauma. The overall prevalence of PFD is not known, as there have not been large population-based studies. Treatment of these patients vary based on their bleeding phenotype. Additionally, the exact bleeding phenotype of many qualitative platelet defects are not well described in literature. This study aims to describe the bleeding phenotype among patients with different (PFD). Methods: This is a retrospective study among patients with PFD conducted at 3 Hemophilia Treatment centers - HOG Center for Bleeding and Clotting Disorders of CHOA, Children's Mercy hospital HTC and Rainbow babies & Children's hospital HTC. Institutional IRB approval was obtained at all 3 institutions. We collected data on demographics, bleeding symptoms at presentation, bleeding episodes, management of these bleeds over a 6-year time period (2015-2020). Results: We identified 131 patients with PFDs at 3 institutions. This included 67 males (51.2%) and 64 females (48.8%). Among 131 patients, 72 patients (55%) had a defect in platelet agonist interaction/receptor defect (ADP/Epinephrine/Collagen/TXA2/Arachidonic acid), 37 patients (28.2%) had delta storage pool defect, 8 patients (6.1%) had Glanzmann thrombasthenia, 7 patients (5.3%) had a platelet release defect, 3 patients (2.3%) with an alpha granule defect, 2 patients (1.5%) with Bernard Soulier syndrome and 1 patient (0.76%) with Wiskott Aldrich syndrome. The most common bleeding symptoms at presentation were epistaxis (40.4%), followed by easy bruising (31.3%), heavy menstrual bleeding (15.2%), gum bleeding (6.87%) and gastrointestinal bleeding (4.58%). From 2015-2020, a total of 162 bleeds were documented, and 68 patients (51.9%) with at least 1 documented episode of bleeding. 67.2% of these bleeds were spontaneous, 12.3% were secondary to trauma, 4.9% after a dental procedure, 2.5% after surgery and 0.6% after child birth. The most common type of bleeding episode in diagnosed patients included epistaxis (50%), heavy menstrual bleeding (17.9%), skin/soft tissue bleed (5.5%), gastrointestinal (5.5%) and dental/tooth related (4.9%). 93 bleeding episodes (57.4%) required some form of treatment in various settings - home (73%), clinic (15%), emergency room (7.5%), hospitalization (14%) and ICU stay (2%). Treatments included antifibrinolytics (68.8%), recombinant factor VIIa (11.8%), desmopressin (9.6%), hormonal therapy (9.6%) and platelet transfusions (5.3%). Conclusions: Our study helps characterize the bleeding phenotype and management in patients with various PFD. This data is crucial in understanding the burden of illness among different types of PFD, and to understand health care utilization to better serve the needs of these poorly characterized patients. Disclosures Sidonio: Sanofi, Takeda, Octapharma, Bayer, Biomain, Grifols, Kedrion, Genentech. Catalyst, Guardian Therapeutics, Novo Nordisk, Hema Biologics, Uniqure.: Consultancy, Honoraria. Silvey: Genentech: Speakers Bureau; Sanofi Genzyme: Membership on an entity's Board of Directors or advisory committees. Ahuja: XaTek, Inc: Patents & Royalties; Sanofi: Membership on an entity's Board of Directors or advisory committees; Takeda: Other: DSMB member ; Genentech: Membership on an entity's Board of Directors or advisory committees.

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Platelet Function Disorders in Adolescents with Heavy Menstrual Bleeding: Clinical Presentations, Laboratory Testing and Treatment Options

Journal of Blood Disorders & Transfusion ◽

10.4172/2155-9864.1000186 ◽

2014 ◽

Vol 05 (01) ◽

Author(s):

Lawrence S

Keyword(s):

Platelet Function ◽

Laboratory Testing ◽

Treatment Options ◽

Heavy Menstrual Bleeding ◽

Menstrual Bleeding ◽

Clinical Presentations ◽

Platelet Function Disorders

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Platelet function defects in adolescents with heavy menstrual bleeding

Haemophilia ◽

10.1111/hae.12293 ◽

2013 ◽

Vol 20 (2) ◽

pp. 249-254 ◽

Cited By ~ 21

Author(s):

H. L. Mills ◽

M. S. Abdel-Baki ◽

J. Teruya ◽

J. E. Dietrich ◽

M. D. Shah ◽

...

Keyword(s):

Platelet Function ◽

Heavy Menstrual Bleeding ◽

Menstrual Bleeding

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Initial Evaluation of Adolescent Females Hospitalized with Heavy Menstrual Bleeding

Blood ◽

10.1182/blood-2018-99-119576 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 1216-1216

Author(s):

Lauren E Amos ◽

Shannon L Carpenter

Keyword(s):

Board Of Directors ◽

Platelet Function ◽

Adolescent Females ◽

Bleeding Disorder ◽

Diagnostic Evaluation ◽

Heavy Menstrual Bleeding ◽

Bleeding Disorders ◽

Advisory Committees ◽

Platelet Function Disorders ◽

Von Willebrand

Abstract Background: Heavy menstrual bleeding (HMB) in adolescents can be severe and life-threatening. Up to 30% of young women who are hospitalized with anemia due to HMB have a bleeding disorder. Guidelines from the American College of Obstetrics and Gynecology (ACOG) and the National Heart, Lung, and Blood Institute (NHLBI) recommend evaluation for bleeding disorders in such patients. ACOG recommendations include testing for von Willebrand disease (VWD) and specify that consultation with a hematologist may help in interpreting results. NHLBI recommends testing for vWD be done in conjunction with a hematologist. As von Willebrand factor is an acute phase reactant, testing when patients are severely anemic and bleeding may not provide accurate results. ACOG guidelines do not include testing for platelet function disorders (PFD), though PFD may be as prevalent as VWD in females with HMB. Early and accurate diagnosis of bleeding disorders is important for health and quality of life, yet limited data exists on the diagnostic evaluation for bleeding disorders in adolescent females hospitalized for HMB. Objectives: To evaluate the diagnostic evaluation of bleeding disorders in adolescent females hospitalized for HMB. Methods: A retrospective, single center chart review of female patients aged 9-21 years hospitalized for HMB and anemia at a tertiary care children's hospital from January 1, 2000 until December 31, 2017 was done. HMB was defined as menses ≥7 days in length, use of 8 or more pads or tampons per day during menses, pictorial bleeding assessment chart (PBAC) score greater than 100, or symptomatic anemia. Patients were identified from our Hemophilia Treatment Center (HTC) registry, review of patients seen at a comprehensive clinic staffed by pediatric hematologists and gynecologists for adolescent females with HMB and bleeding disorders, and by an Electronic Medical Record (EMR) query of admission and discharge diagnoses of HMB and anemia. Data obtained included clinical features, diagnostic evaluation, and laboratory results. Results: 118 patients hospitalized for HMB and anemia were included. Inpatient Hematology consult or outpatient referral occurred in 68 (58%) of the patients; 60/68 (88%) had a bleeding disorder evaluation completed. 34 patients had a hematologic disorder. PFD was the most common (15/34; 44%) followed by VWD (9/34; 26%). 42% (50/118) of the patients did not have a Hematology consult or outpatient referral (Table 1). While hospitalized for HMB and anemia, 29 of the 50 patients had testing for vWD performed and only 4/29 (14%) had testing repeated as an outpatient once hemoglobin normalized. No patients tested for VWD while inpatient had results consistent with the diagnosis. Platelet function testing was performed in 10/50 patients using the platelet function analyzer (PFA-100) in 8 patients and platelet aggregometry in 2 patients. Conclusions: Despite national guidelines and the presence of known risk factors such as HMB since menarche and HMB causing severe anemia, the hematology service was not involved in the diagnostic process for a significant number of adolescent females. In these patients, testing often occurred while patients were hospitalized and was not repeated. Testing for platelet function disorders occurred infrequently and mainly consisted of the PFA-100 which lacks sensitivity and specificity. When patients were evaluated by Hematology and tested for bleeding disorders, a large proportion had a bleeding disorder, of which PFD were most common. This study demonstrates the need for standardization of the evaluation of adolescent females hospitalized for HMB. Guidelines should be updated to include testing for PFD. Hematologists should be involved when females are hospitalized for HMB and anemia. Disclosures Carpenter: Genentech Incorporated: Membership on an entity's Board of Directors or advisory committees; Nationwide Children's Hospital: Speakers Bureau; Bayer: Honoraria; Kedrion Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Novo Nordisk Pharmaceuticals, Inc: Consultancy; HEMA Biologics: Consultancy; American Academy of Pediatrics: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novo Nordisk: Consultancy; National Hemophilia Foundation (Impact Education): Speakers Bureau; Kane County State's Attorney: Consultancy; CSL Behring: Speakers Bureau; 4th Judicial District Attorney's Office- Colorado: Consultancy; Kedrion Biopharmaceuticals: Consultancy.

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Platelet function disorder in women with heavy menstrual bleeding in Eastern Uttar Pradesh

Journal of Medical Society ◽

10.4103/jms.jms_53_21 ◽

2021 ◽

Vol 35 (1) ◽

pp. 24

Author(s):

Madhu Jain ◽

Shuchi Jain ◽

NishaRani Agrawal ◽

Vijai Tilak ◽

Ekhlak Mohammad ◽

...

Keyword(s):

Platelet Function ◽

Uttar Pradesh ◽

Heavy Menstrual Bleeding ◽

Menstrual Bleeding ◽

Eastern Uttar Pradesh

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Heavy Menstrual Bleeding in Adolescent Females with Platelet Function Disorders

Blood ◽

10.1182/blood-2018-99-119370 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 4980-4980

Author(s):

Lauren E Amos ◽

Shannon L Carpenter

Keyword(s):

Board Of Directors ◽

Adolescent Females ◽

Heavy Menstrual Bleeding ◽

Menstrual Bleeding ◽

Line Treatment ◽

First Line ◽

Advisory Committees ◽

Platelet Function Disorders ◽

Hemostatic Therapy ◽

First Line Treatment

Abstract Background: Heavy menstrual bleeding (HMB) occurs frequently in adolescent females and a significant proportion have an underlying bleeding disorder. As diagnostic techniques for platelet function disorders (PFD) improve, these disorders are now recognized to commonly cause HMB and may be as prevalent as von Willebrand disease. Limited data exists about the prevalence of PFD in adolescents with HMB. Even less is reported on management and treatment outcomes in patients with HMB and PFD. HMB can negatively impact quality of life and cause serious adverse effects. In order to appropriately treat heavy menstrual bleeding in adolescent females with PFD, more information is needed about the prevalence, clinical manifestations, and management of these patients. Objectives: To evaluate the prevalence, clinical features, management, and outcomes of HMB in adolescent females with platelet function disorders Methods: A retrospective, single center chart review was performed of female patients aged 9-21 years with HMB and a diagnosed PFD treated at a tertiary care pediatric hospital from January 1, 2000 until December 31, 2017. Heavy menstrual bleeding was defined as menses lasting longer than 7 days, use of 8 or more pads or tampons per day during menstrual cycle, pictorial bleeding assessment chart score greater than 100, or symptomatic anemia. Patients were identified from our Hemophilia Treatment Center (HTC) registry, review of patients seen at a comprehensive clinic staffed by pediatric hematologists and gynecologists for adolescent females with HMB and bleeding disorders, and by an Electronic Medical Record (EMR) query of admission and discharge diagnoses of HMB and anemia. Data obtained included demographics, clinical features, laboratory results, treatment modalities, and outcomes. Results: 41 patients with PFD who achieved menarche were identified. 36 of these (88%) met criteria for HMB. The median age at presentation of HMB was 14 years (range 10-18). 35/36 patients had documented abnormal platelet aggregometry (PA) and the majority of patients (27/35) had at least 2 sets of abnormal PA. All patients were diagnosed with non-specific PFD. 15 of the 36 patients (41%) required hospitalization and packed red blood cell transfusion for severe anemia at time of presentation. Mean and median hemoglobin at presentation of HMB respectively were 9.5 gm/dL and 11.3 gm/dL (range 3.1-14.8) and 21 patients (58%) were anemic at presentation. 26 patients had ferritin obtained at presentation and 18 (69%) were iron deficient using our lab's reference range of ferritin less than 13 ng/dL. Half of the patients (18/36, 50%) failed first-line treatment. Successful first-line treatment included hormonal therapy alone (4 patients), hemostatic therapy alone with tranexamic acid (4 patients), hormonal plus hemostatic therapy (7 patients), and intra-uterine device plus hemostatic therapy (1 patient). The mean duration of HMB until report of resolution was 8.2 months (median 5 months; range 1-24). 8% (3/33) of patients reported continued HMB at last documented clinic visit. Conclusions: HMB occurred in the majority of adolescent female patients with PFD. These patients were frequently anemic and iron deficient. Severe and life-threatening anemia requiring hospitalization and packed red blood cell transfusion was common. First line treatment of HMB was not uniform and failed in 50% of the patients. Prospective studies are needed to standardize treatment of HMB in adolescents with PFD. Disclosures Carpenter: Kedrion Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Bayer: Honoraria; CSL Behring: Speakers Bureau; Kane County State's Attorney: Consultancy; National Hemophilia Foundation (Impact Education): Speakers Bureau; HEMA Biologics: Consultancy; Novo Nordisk: Consultancy; Nationwide Children's Hospital: Speakers Bureau; American Academy of Pediatrics: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Genentech Incorporated: Membership on an entity's Board of Directors or advisory committees; Kedrion Biopharmaceuticals: Consultancy; 4th Judicial District Attorney's Office- Colorado: Consultancy; Novo Nordisk Pharmaceuticals, Inc: Consultancy.

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Pilot study of novel lab methodology and testing of platelet function in adolescent women with heavy menstrual bleeding

Pediatric Research ◽

10.1038/pr.2017.298 ◽

2018 ◽

Vol 83 (3) ◽

pp. 693-701 ◽

Cited By ~ 2

Author(s):

Anne D Rocheleau ◽

Ayesha Khader ◽

Anh T P Ngo ◽

Colin Boehnlein ◽

Cara McDavitt ◽

...

Keyword(s):

Pilot Study ◽

Platelet Function ◽

Heavy Menstrual Bleeding ◽

Menstrual Bleeding ◽

Adolescent Women

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Iron Repletion Increases Platelet Aggregation and Reduces Platelet Count in Iron Deficient Premenopausal Women

Blood ◽

10.1182/blood-2021-154343 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 3170-3170

Author(s):

Benjamin Elstrott ◽

Hari H.S. Lakshmanan ◽

Hannah Stowe McMurry ◽

Malinda T West ◽

Sven Reid Olson ◽

...

Keyword(s):

Platelet Count ◽

Platelet Aggregation ◽

Iron Deficiency ◽

Platelet Function ◽

Platelet Reactivity ◽

Premenopausal Women ◽

Heavy Menstrual Bleeding ◽

Menstrual Bleeding ◽

Iron Deficient ◽

Post Infusion

Abstract Background: Iron deficiency, heavy menstrual bleeding, and anemia are interrelated conditions with high prevalence in women's health. Together, they impact an estimated 310 million premenopausal women worldwide. Iron deficiency has been associated with development of anemia as well as thrombocytosis. However, the effects of iron deficiency on platelet function remain unknown. Objective: We set out to investigate the impact of IV iron repletion on platelet function, platelet count, and other blood cell indices in iron deficient premenopausal women. Methods: We conducted a prospective single-center study of iron deficient premenopausal women who underwent iron repletion with a single dose of 1000 mg of low molecular weight iron. Pre-infusion and post-infusion blood samples were obtained for laboratory analysis. Standard of care monitoring of iron indices and complete blood counts were also included in the analysis. Pre-infusion rates of anemia and thrombocytosis were calculated using minimum hemoglobin and peak platelet count in the 6 months preceding iron infusion. Platelet function was quantified by Fluorescence-Activated Cell Sorting (FACS) quantification of platelet activation marker antibodies for GPIIb/IIIa (PAC1) and P-selectin (CD62P) after exposure to multiple platelet agonists. Platelet aggregation was assessed by flow of anticoagulated whole blood at a shear rate of 300 s -1 for 5 minutes through chambers coated with type I collagen, imaged with differential interference contrast optics, and quantitatively represented through computation of percent total surface coverage. Pre-infusion and post-infusion cell indices and aggregation data were compared by paired samples t-test. All statistical analyses were performed in GraphPad Prism (Version 8.0.0). Results: Thirteen patients were included in the analysis. Heavy menstrual bleeding was the suspected cause of iron deficiency in 83% of patients. Thrombocytosis was present in 15% of patients at pre-infusion and no patients at post-infusion. Average ferritin was 14 µg/L at pre-infusion and 126 µg/L at post-infusion. The peak platelet count within 6 months pre-infusion was 309 K/mm 3 (±89) vs. 274 (±64) K/mm 3 at post-infusion (p<0.05). The average change to 6-month pre-infusion peak and post-infusion platelet count was -35.2 K/mm 3 (95%CI: -66.2, -5.23). The mean 6-month minimum hemoglobin was 11.9 (±1.9) g/dL vs. 13.3 (±1.1) g/dL at post-infusion (p<0.005). Acquisition of FACS platelet reactivity data are ongoing, with preliminary results for the first 7 consecutively enrolled study patients displayed in Figure 1. Platelet aggregation measured at pre-infusion showed 14% surface coverage, with a significant increase to 29% at post-infusion (p < 0.05). None of the 13 women experienced a thrombotic event during the study period. Conclusion: Correction of iron deficiency results in decreased platelet count and improves platelet aggregation over collagen. Iron repletion may also improve platelet reactivity in response to physiologic agonists. These findings may suggest that iron deficiency impairs hemostasis and that correction of low iron may be even more critical for women with heavy menstrual bleeding. Figure 1 Figure 1. Disclosures Shatzel: Aronora Inc,: Consultancy.

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