scholarly journals Surgery-Associated Bleeding Risk in Patients with Platelet Function Disorders - a Cross Sectional Study with the American Thrombosis and Hemostasis Network Dataset (ATHNdataset)

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 180-180
Author(s):  
Divyaswathi Citla Sridhar ◽  
Robert F. Sidonio ◽  
Dunlei Cheng ◽  
Sanjay Ahuja
Keyword(s):  
Board Of Directors ◽  
Platelet Function ◽  
Advisory Committees ◽  
Glanzmann Thrombasthenia ◽  
Risk Of Bleeding ◽  
Storage Pool ◽  
Dental Procedures ◽  
Platelet Function Disorders ◽  
Bleeding Episodes ◽  
Bernard Soulier Syndrome

Abstract Introduction: Platelet function disorders (PFDs) are a group of heterogenous bleeding disorders with varying bleeding phenotype. Intraoperative and post-operative bleeding are serious complications among patients with PFDs undergoing surgery. There are very few studies in literature that have specifically investigated surgery associated bleeding complications in PFDs. The aim of this study was to utilize a large national dataset to describe surgeries performed in patients with PFD, characterize the bleeding associated with these surgical procedures and outline the therapeutic approaches adopted. Methods: In this retrospective study, the ATHNdataset was queried for demographic data, PFD diagnosis, surgeries among patients with PFD, intraoperative and post-operative bleeding episodes and treatment. Descriptive statistics were used. The ATHNdataset captures information from patients with bleeding and clotting disorders from over 140 federally funded hemophilia and thrombosis treatment centers (HTCs) in the US. Patients authorize inclusion of their demographic and clinical information in this de-identified Health Insurance Portability and Accountability Act (HIPAA)-compliant data set. Results: From January 2010 to March 2020, the ATHNdataset captured 2767 patients with PFDs, of which 1769 (63.93%) were female and 998 (36.1%) were male, with 1393 patients between 0-18 years (50%) and 1374 (50%) adults >18 years. PFDs identified include 32 patients with Bernard Soulier syndrome (1.16%), 131 patients with Glanzmann thrombasthenia (4.7%), 4 patients with Gray platelet syndrome (0.14%), 29 patients with Hermansky Pudlak syndrome (1%), 1548 patients with storage pool deficiency (55.9%), and 1023 patients diagnosed as PFD (36.9%). A total of 3252 procedures were reported between 2010 and 2020; 1271 patients (46%) patients with at least one documented procedure. Figure 1 shows common procedures among patients with PFDs. Surgery-associated bleeding episodes (includes intraoperative and post-operative bleeds) were reported with 69 procedures (2.1%), which included intraoperative bleeds reported for 18 procedures (0.5%) and post-operative bleeds reported for 51 procedures (1.6%). Of the 60 procedures in patients with Glanzmann thrombasthenia, surgery-associated bleeding episodes were reported after 9 dental procedures (41%), 1 circumcision (25%) and 11 other surgeries/procedures (18.3%). Of the 6 procedures in patients with Bernard Soulier syndrome, no intraoperative or post-operative bleeding episodes were reported. Of 1688 procedures in patients with storage pool deficiency, surgery-associated bleeding episodes were reported after 26 dental procedures (1.5%) and 62 other surgeries/procedures (3.67%). No intraoperative or post-operative mortality was reported among these patients. Of 1272 patients who underwent at least 1 procedure, 646 patients (50.7%) received some form of treatment before/during/after a procedure. Among these 646 patients, 2794 exposure days of hemostasis medications were used before/during/after procedures. Among these, 49% were prior to the procedure, 0.7 % during the procedure and 49.5% after the procedure. Treatments used are shown in figure 2. Conclusion: Our study shows that patients with PFDs have a substantial risk of bleeding associated with surgery. Identifying the risk of bleeding by type and providing appropriate pre-surgical prophylaxis can decrease rates of surgery-associated bleeding in PFDs. Figure 1 Figure 1. Disclosures Sidonio: Sanofi, Takeda, Octapharma, Bayer, Biomain, Grifols, Kedrion, Genentech. Catalyst, Guardian Therapeutics, Novo Nordisk, Hema Biologics, Uniqure.: Consultancy, Honoraria. Ahuja: Genentech: Membership on an entity's Board of Directors or advisory committees; Takeda: Other: DSMB member ; XaTek, Inc: Patents & Royalties; Sanofi: Membership on an entity's Board of Directors or advisory committees.

scholarly journals A Multi-Institution Retrospective Study to Assess Bleeding Phenotype Among Patients with Platelet Function Disorders

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3033-3033
Author(s):  
Divyaswathi Citla Sridhar ◽  
Robert F. Sidonio ◽  
Michael Silvey ◽  
Dunlei Cheng ◽  
Sanjay Ahuja
Keyword(s):  
Retrospective Study ◽  
Board Of Directors ◽  
Platelet Function ◽  
Burden Of Illness ◽  
Heavy Menstrual Bleeding ◽  
Menstrual Bleeding ◽  
Advisory Committees ◽  
Post Surgery ◽  
Platelet Function Disorders ◽  
Bleeding Episodes

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.

scholarly journals Initial Evaluation of Adolescent Females Hospitalized with Heavy Menstrual Bleeding

Blood ◽  
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.

Platelet Function Disorders in Bleeding Patients without Other Coagulopathies

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4650-4650
Author(s):  
Francine R. Dembitzer ◽  
Ellinor I.B. Peerschke ◽  
Caroline Cromwell ◽  
Xiaofei Zhang ◽  
Louis M. Aledort
Keyword(s):  
Platelet Aggregation ◽  
Board Of Directors ◽  
Platelet Function ◽  
Coagulation Factor ◽  
Clinical History ◽  
Study Cohort ◽  
Advisory Committees ◽  
Normal Platelet ◽  
Platelet Function Disorders ◽  
Age Range

Abstract Introduction: We present a series of 105 patients referred for hematologic consultation to evaluate a clinical bleeding disorder. Little is known regarding the prevalence of non-genetic qualitative platelet disorders and which of these might respond to desmopressin. Methods: Patients were assessed over a two-year period, from December 2011 through December 2013. Patients, who were found to have neither von Willebrand's disease nor coagulation factor deficiencies, nor quantitative platelet defects, were tested for platelet function abnormalities by PFA-100 (Dade Behring, Marburg, Germany) and platelet aggregation and secretion studies using lumi aggregation (Chrono-Log Corp., Havertown, PA, USA). Selected patients with abnormal platelet function were given a trial of intravenous desmopressin to determine efficacy, and platelet function studies were repeated 2 hours later. Results: Of the 105 referred patients (26 males, age range 15-83 years; 79 females, age range 21-86 years), 67 with either normal (n=43) or abnormal (n=24) PFA-100 results were not evaluated further based on their clinical history and presentation. 18 patients with abnormal PFA-100 results, consisting of Collagen/ADP, Collagen/Epinephrine, or both, had platelet aggregation and secretion studies performed. 16 of these patients had abnormal platelet aggregation and secretion studies, while 2 patients had normal studies. In addition, 20 patients with normal PFA-100 results underwent platelet aggregation and secretion studies. Of these, 17 had abnormal platelet aggregation and secretion predominantly in response to two or more weak agonists, including ADP, epinephrine and/or arachidonic acid. Only 3 of these 20 patients had normal platelet aggregation and secretion. Of the 16 patients with both abnormal PFA-100 and abnormal platelet aggregation and secretion tests, 11 underwent subsequent pre- and post- desmopressin platelet function testing. 7 of the 11 patients showed improvement or complete normalization of at least one PFA-100 parameter, i.e., either Collagen/ADP, Collagen/Epinephrine, or both. However, results of platelet aggregation and secretion tests remained unchanged, irrespective of PFA-100 results. Conclusions: In the present study, platelet aggregation and secretion studies in patients with no other coagulopathies revealed platelet function defects in approximately 30% of the study cohort. Platelet function defects were in response to weak agonists, including ADP, epinephrine, and/or arachidonic acid.Our data support the recent SCC ISTH recommendations against the use of PFA-100 for platelet function screening.We recommend that the hematologist carefully assess the bleeding history, and, if significant, pursue platelet aggregation and secretion studies to identify potential platelet function defects. Disclosures Aledort: Baxter Healthcare: Membership on an entity's Board of Directors or advisory committees, Other: DSMB Participation; Kedrion BioPharma: Consultancy, Membership on an entity's Board of Directors or advisory committees.

scholarly journals Comparison of LTA Versus Wbila in Pediatric Patients with Suspected Platelet Function Disorders

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3762-3762
Author(s):  
Abigail Wax ◽  
Bhavia Doshi ◽  
Abinaya Arulselvan ◽  
Amrom Obstfeld ◽  
Michele P. Lambert
Keyword(s):  
Board Of Directors ◽  
Platelet Function ◽  
Pediatric Patients ◽  
Young Patients ◽  
Patient Characteristics ◽  
Serotonin Release ◽  
Advisory Committees ◽  
Platelet Function Disorders ◽  
Pediatric Populations ◽  
Abnormal Results

Abstract Background Diagnosis of platelet function disorders in pediatric patients is complicated by difficulties identifying at risk patients (due to young age, fewer hemostatic challenges) (Gresele, Journal of Thrombosis and Haemostasis, 2015), large quantities of blood required for standard testing, and inability to use large gauge needles to perform phlebotomy increasing the probability of false positive results. Diagnostic testing for pediatric platelet disorders has recently shifted from Light Transmission Aggregometry (LTA) with serotonin release to Whole Blood Impedance Lumi-Aggregometry (WBILA). There is a paucity of literature comparing LTA and WBILA and few studies examining bleeding assessment tools in exclusively pediatric populations. LTA is widely studied and considered the gold standard of platelet testing. However, the newer and less validated WBILA has a lower blood volume requirement making it potentially more suitable for very young patients in need of testing. Therefore, there is a significant need to validate results from WBILA testing to be able to perform platelet testing on young patients. Aims The study purpose was to analyze lab testing results and patient characteristics for patients that have had WBILA or LTA with serotonin release and compare results across testing platforms. We also compared performance characteristics for patients with access to both methods. Further, we compared Bleeding Assessment Tool (BAT) scores, age distributions and types of testing results and their occurrences for both types of testing. Methods Medical and laboratory records of children evaluated at the Children's Hospital of Philadelphia and at the Hospital of the University of Pennsylvania that were referred for a variety of causes from 1/1/2016 until 6/30/2018 were examined. Males and females referred for concerns for bleeding who are age 2 months to 21 years at time of evaluation were included. In late 2016 the coagulation laboratory at CHOP validated WBILA. Prior to this, patients were tested using LTA. Patient history and demographic information, indication for testing, aggregometry findings and final diagnosis were compared prior to and after this transition. Medical records were used to derive a bleeding score. Approximately 300 records were reviewed. Results For LTA with serotonin release, ages were distributed bimodally with peaks at 6 years and 16 years with an average of 10.6 years (SD=5.4 years). The most frequent indications for testing were epistaxis (24%) and easy bruising (20%). For WBILA, ages were distributed bimodally with peaks at 35 months and 15 years with an average of 8.6 years (SD=5.5 years). The most frequent indications for testing were epistaxis (27%) and family history (17%). Average age of patients tested with WBILA was significantly lower than LTA with serotonin release (p=0.0013). No difference in distribution or average BAT scores was seen between patients tested with LTA and WBILA. The percent of abnormal results for cases with LTA testing was 32% versus 27% for WBILA cases, a difference that was not statistically significant. This suggests that the tests have similar diagnostic performance. Additionally, there is a trend towards an association between higher BAT scores and abnormal test results, but not significantly due to few abnormal cases. Finally, comparison of WBILA with LTA results showed that for the 9 patients with both studies, 4 had normal WBILA after borderline abnormal LTA results and 5 had congruent findings. Conclusions Our data highlight the differences in results and patient characteristics between LTA and WBILA testing. The most significant difference between the two tests was age distribution, with LTA, which requires more blood, being performed in older patients. In examining test performance, our analysis of BAT scores suggests that in our population a higher BAT score may be associated with higher probability of abnormal result, but differences in scores are small and make it hard to differentiate patients appropriate for testing based on bleeding scores alone. Our rate of abnormal results is similar to that of other populations, and highlights the difficulty of diagnosis in pediatric populations. Based on the consistent frequencies of abnormal findings across test types and the analysis of BAT scores, WBILA may be an acceptable alternative to LTA with serotonin release in young patients needing evaluation for platelet function defects. Disclosures Doshi: Bayer: Research Funding. Lambert:Rigel: Consultancy; Summus: Consultancy; Shionogi: Consultancy; Novartis: Membership on an entity's Board of Directors or advisory committees; Educational Concepts in Medicine: Consultancy; Bayer: Membership on an entity's Board of Directors or advisory committees; CSL: Consultancy; Sysmex: Consultancy; Amgen: Membership on an entity's Board of Directors or advisory committees.

scholarly journals Disease Burden in Patients with Glanzmann Thrombasthenia: Perspectives from the Glanzmann Thrombasthenia Patient/Caregiver Questionnaire

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3456-3456
Author(s):  
Alexander Duncan ◽  
Angela Kellum ◽  
Shilpa Jain ◽  
Skye Peltier ◽  
Helen Smith ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Adult Patients ◽  
Factor Vii ◽  
Hormonal Contraceptives ◽  
Platelet Glycoprotein ◽  
Care Providers ◽  
Advisory Committees ◽  
Glanzmann Thrombasthenia ◽  
Female Patients ◽  
Initial Symptoms

Introduction: Glanzmann thrombasthenia (GT) is a rare bleeding disorder (~1:1,000,000) caused by impaired function of platelet glycoprotein IIb/IIIa responsible for aggregation. This novel survey was designed to identify the burden of GT through better understanding of the management of the disorder and its psychosocial impact on patients and caregivers. Methods: Participants were recruited via a rare disease specialty recruiter from Comprehensive Health Education Services. Data were collected from January 31 through March 12, 2019, via a moderator-assisted online survey. On average, the survey was completed within 45 minutes. Information regarding demographics, diagnosis, treatment history, and quality of life was collected. Results: In total, 45 respondents (24 patients and 21 caregivers; 58% female) completed the survey. Many patients were born with significant bruising (76%) or bled extensively during circumcision (47%). As a result of their early symptoms, more than 50% of those surveyed were diagnosed prior to their first birthday. For others, the average time between experiencing initial symptoms and visiting a specialist was just over 1 year and to diagnosis was just over 2 years (average age, 2.6 years, range <1-38 years). Misdiagnosis with von Willebrand disease was common. Approximately 50% of patients experienced 1 bleed every day, and 13% reported over 500 bleeds per year; Most bleeds were skin bruises and mouth bleeds, but patients also reported joint/muscle and gastrointestinal bleeds. Only 24% of respondents reported being treated at a hemophilia treatment center; 71% reported visiting their hematologist regularly. The most common treatment for bleeds was antifibrinolytics (82%), followed by recombinant activated factor VII (rFVIIa; 42%). In addition, 73% reported receiving platelets and blood transfusions in the past year. Approximately 25% reported receiving more than 20 transfusions in their lifetime. Overall, 38% of patients reported having experienced refractoriness to platelets and 32% antibodies to platelets; notably, only these patients reported receiving treatment with rFVIIa. Many feared uncontrolled bleeding due to refractoriness or antibodies to platelets and stated that their health care providers (HCPs) were too quick to treat bleeds with platelets. Many female patients struggled to find a gynecologist with some knowledge of the management of menstruation, pregnancy, and childbirth in patients with GT; 11% of respondents reported menstrual bleeding that required hospitalization and/or emergency treatment. The majority (74%) of female patients reported taking hormonal contraceptives to prevent regular menstruation; some patients not taking hormones required monthly platelet transfusions. Fifty-eight percent of patients reported issues with excessive bleeding at school as children; 38% reported missing school days and 33% were bullied during childhood. In addition, 38% of adult patients and 24% of caregivers had missed work as a result of GT, and 21% of adult patients reported that their employer did not take their condition seriously. Many respondents (65%) were satisfied with the level of support they receive from their significant other, and 76% were satisfied with the level of support they receive from their friends. Conclusions: Many patients with GT are identified early in life owing to a severe phenotype, but diagnosis remains somewhat difficult. Patients with GT experience frequent bleeding episodes, commonly as bruises and nosebleeds, with 31% experiencing more than 100 bleeds per year. Additional support from outside the GT patient community is needed. Patients desire additional education for themselves and their HCPs, especially around menstruation, childbearing, and treatment options. Disclosures Duncan: Novo Nordisk Inc: Consultancy. Kellum:Novo Nordisk Inc: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Jain:Bioverativ/Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novo Nordisk Inc: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bayer: Consultancy, Membership on an entity's Board of Directors or advisory committees; CSL Behring: Consultancy, Membership on an entity's Board of Directors or advisory committees; Octapharma: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda/Shire: Consultancy, Membership on an entity's Board of Directors or advisory committees; BPL: Consultancy, Membership on an entity's Board of Directors or advisory committees. Peltier:Novo Nordisk Inc: Membership on an entity's Board of Directors or advisory committees. Cooper:Novo Nordisk Inc.: Employment. Saad:Novo Nordisk Inc: Employment.

Severe Bleeding Events in Hemophilia Α Patients Receiving Emicizumab Prophylaxis

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1126-1126
Author(s):  
Karen L. Zimowski ◽  
Glaivy M. Batsuli ◽  
Paulette Bryant ◽  
Jenny McDaniel ◽  
Kelly Tickle ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Hemophilia A ◽  
Severe Bleeding ◽  
Severe Hemophilia ◽  
Bleeding Events ◽  
Advisory Committees ◽  
Acute Bleeding ◽  
Fviii Activity ◽  
Bleeding Episodes

Introduction : Emicizumab is a novel humanized bispecific antibody that mimics the function of activated coagulation factor VIII (fVIII). It has significantly changed the management of patients with hemophilia A and inhibitors by achieving baseline hemostatic control. Based on the HAVEN studies, emicizumab markedly reduces annualized bleeding rates and is FDA-approved for prophylaxis in hemophilia A patients of all ages, regardless of inhibitor status. In the HAVEN2 interim analysis, only 3/57 pediatric patients receiving emicizumab prophylaxis required treatment for an acute bleeding event after a 9-week median observation time. We report 3 patients with severe hemophilia A and a history of inhibitors receiving emicizumab prophylaxis with severe or refractory bleeding episodes to highlight the importance of vigilance and surveillance of children with severe hemophilia A on emicizumab. Methods: This retrospective analysis includes patients between 0-21 years of age with severe hemophilia A (fVIII activity < 1%) receiving emicizumab prophylaxis and admitted for the management of an acute bleeding episode following emicizumab's FDA approval in November 2017. Patients were followed at the Pediatric Hemophilia Treatment Center at the Hemophilia of Georgia Center for Bleeding & Clotting Disorders of Emory and the St. Jude Affiliate Clinic at Novant Health Hemby Children's Hospital. Data collected included demographics, past medical history including inhibitor status, bleeding history, and treatment modalities, and details regarding the presentation, management, and outcome of acute severe bleeding events. Due to the nature of the study, descriptive statistics were primarily used for data analysis. Results: Three patients with severe hemophilia A receiving emicizumab prophylaxis were admitted for the management of 4 severe bleeding episodes. All patients had a history of a fVIII inhibitor. Three of the 4 bleeding episodes were trauma-induced while 1 occurred spontaneously. For the traumatic episodes, all patients presented with worsening symptoms approximately 1 week following the inciting event. All patients had a normal aPTT at the time of presentation, ruling out a significant anti-drug antibody (emicizumab level not available). A patient with a low-titer inhibitor developed an epidural hematoma following a trampoline injury and was treated with continuous infusion of recombinant factor VIII (rfVIII), adjusting the rate to achieve chromogenic fVIII activity of 100% for 14 days. Following 14 days, he was started on rfVIII 50 IU/kg Q12 hours with a goal fVIII activity of 50%. His rfVIII dosing interval was gradually weaned to every other day while in inpatient rehabilitation. As outlined in Table 1, the remaining 3 bleeding events were initially managed with recombinant activated factor VII (rfVIIa) dosed at 80-90 mcg/kg/dose with escalating frequency for an average of 8 days. However, due to lack of improvement, treatment was changed to low-dose activated prothrombin complex concentrates (aPCC; 10-15 IU/kg/dose Q12-24 hours for an average of 7 days). In all 3 of these events, the hematomas improved after treatment with aPCC. No patient experienced thrombotic microangiopathy, thrombosis, or had evidence of DIC while receiving these treatment regimens. Discussion/Conclusion: Pharmacokinetic analysis of emicizumab suggests that following the standard 4-week loading phase, trough plasma emicizumab concentrations obtained prior to a 1.5 mg/kg once weekly maintenance dose correlates with at least 10-15 IU/dL equivalent fVIII activity. This degree of thrombin generation should be sufficient to prevent severe spontaneous bleeding episodes in most patients. However it does not preclude significant trauma-induced bleeding or spontaneous bleeding in inhibitor patients. Based on our cases, providers should maintain a high index of suspicion for acute bleeding in patients receiving emicizumab prophylaxis. Serious bleeding events, although rare, may have a more insidious onset in patients receiving emicizumab. Furthermore, despite the baseline hemostasis achieved with emicizumab, acute bleeding events may still require aggressive therapy. Our cases suggest that low-dose aPCC or continuous infusion fVIII may be feasible options for treating acute bleeding events in patients with hemophilia A and inhibitors receiving emicizumab prophylaxis. Disclosures Zimowski: Pfizer: Research Funding; National Hemophilia Foundation: Other: Medical Loan Reimbursement, Research Funding. Batsuli:Octapharma: Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees; Genetech: Membership on an entity's Board of Directors or advisory committees. Bryant:Novo Nordisk: Other: PI on Novo Nordisk sponsored Studies. McDaniel:Genentech: Membership on an entity's Board of Directors or advisory committees. Tickle:National Hemophilia Foundation: Research Funding. Meeks:Bayer: Membership on an entity's Board of Directors or advisory committees; Genentech: Membership on an entity's Board of Directors or advisory committees; Novo Nordisk: Membership on an entity's Board of Directors or advisory committees; Bioverativ: Membership on an entity's Board of Directors or advisory committees; Takeda-Shire: Membership on an entity's Board of Directors or advisory committees; HEMA Biologics: Membership on an entity's Board of Directors or advisory committees. Sidonio:Genetech: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda-Shire: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bioverativ: Membership on an entity's Board of Directors or advisory committees, Research Funding; Octapharma: Membership on an entity's Board of Directors or advisory committees, Research Funding; Grifols: Membership on an entity's Board of Directors or advisory committees, Research Funding; Biomarin: Membership on an entity's Board of Directors or advisory committees; Uniqure: Membership on an entity's Board of Directors or advisory committees; Novo Nordisk: Membership on an entity's Board of Directors or advisory committees; Kedrion: Research Funding.

Identification of Qualitative Platelet Disorders in Adolescent Women with Heavy Menstrual Bleeding

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4922-4922
Author(s):  
Kristina M. Haley ◽  
Susan Lattimore ◽  
Cara McDavitt ◽  
Ayesha Khader ◽  
Colin Boehnlein ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Board Of Directors ◽  
Platelet Function ◽  
Research Funding ◽  
Blood Platelet ◽  
Bleeding Disorder ◽  
Advisory Committees ◽  
Adolescent Women ◽  
Platelet Disorder ◽  
Platelet Function Assays

Abstract Introduction: Nearly 40% of adolescent women experience heavy menstrual bleeding (HMB), and identifiable bleeding disorders are diagnosed in only 20-60% of these patients. We suspect that qualitative platelet disorders contribute to HMB, but are under-diagnosed. A pilot study was conducted to evaluate platelet function in adolescent women with HMB employing four novel, small-volume, whole blood platelet function assays. In addition, primary and secondary hemostasis, bleeding phenotype, and quality of life were assessed. Methods: Patients referred to the Young Women's Hematology Clinic at Oregon Health & Science University for evaluation of HMB were offered participation in the study. Participants underwent standard review of their medical and family history and physical exam. Standard lab evaluation included CBC, PT, PTT, fibrinogen, thrombin time, Von Willebrand Panel, PFA-100, and iron studies with platelet aggregation or phenotyping performed if clinically indicated. Using less than 0.5 mL of whole blood, platelet function was assessed with four novel platelet function assays: assessment of platelet activation, secretion, and aggregation was assessed by flow cytometry analysis, while platelet adhesion and aggregation was assessed under shear in a capillary tube. Quality of life (QOL) was assessed using the PedsQL tool. Bleeding phenotype was assessed with the ISTH Bleeding Assessment Tool (ISTH BAT). Menorrhagia was assessed with the Pictorial Bleeding Assessment Chart (PBAC), the Philipp Tool and the clinical history. Results: Nine participants have enrolled on study to date, with 2 completing the 3-month visit. The median age of the cohort was 16 years (14-18 years). Eight out of nine categorized their period as heavy, 6 also had epistaxis, and 7 reported excessive bruising. The median ISTH BAT score was 4 (3-7). Of the 7 patients who had a Philipp Score obtained, 5 were positive. Median PBAC score was 161 (64-196). Median ferritin was 13 ng/mL (4-65 ng/mL). Median QOL psychosocial score was 70 (68.36-88.25), comparable to that of pediatric patients with cancer. Of the 9 participants, 6 had platelet aggregation and phenotyping. Four participants did not receive a bleeding disorder diagnosis, 1 was diagnosed with Type 1 VWD, 1 was diagnosed with bleeding disorder, NOS, and 1 was diagnosed with Ehlers Danlos Syndrome. Two participants were diagnosed with a qualitative platelet disorder (QPD): one based on platelet aggregation and one based on thromboelastography. The four novel platelet function assays confirmed platelet function abnormalities in the participants diagnosed with QPD's (Figure 1&2). Impaired platelet response to agonist stimulation was also observed in participants with non-platelet disorder bleeding disorder diagnoses and in participants without a bleeding disorder diagnosis. Conclusions: In this pilot study, the etiology of HMB in adolescent women was evaluated with four novel platelet assays in addition to standard assays of hemostasis. A bleeding disorder diagnosis was not made with standard evaluations in 4 out of 9 participants. The novel assays detected platelet abnormalities not observed using currently available clinical labs, and confirmed the presence of abnormal platelet function in participants with abnormal platelet function testing. These assays require significantly less blood volume than currently available assays and expand investigation of platelet function to platelet adhesion and platelet interactions in whole and flowing blood. Further work is needed to determine the sensitivity and specificity of the novel assays in detecting platelet dysfunction. Continued investigation into the impact of HMB on the adolescent female population is needed. Disclosures Haley: CSL Behring: Honoraria; Baxalta: Membership on an entity's Board of Directors or advisory committees. Recht:Biogen: Membership on an entity's Board of Directors or advisory committees; CSL Behring: Membership on an entity's Board of Directors or advisory committees; Biogen: Research Funding; Genentech: Research Funding; Novo Nordisk: Research Funding; Baxalta: Research Funding; Novo Nordisk: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees.

scholarly journals Risk of Major Bleeding with Ibrutinib in Patients with Thrombocytopenia - a Retrospective Single-Center Canadian Study

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4682-4682
Author(s):  
Mina Dehghani ◽  
Taylor Dear ◽  
Anthony Quint ◽  
Martha L Louzada ◽  
Selay Lam ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Major Bleeding ◽  
Univariate Analysis ◽  
Primary Objective ◽  
Canadian Study ◽  
Bleeding Events ◽  
Advisory Committees ◽  
Risk Of Bleeding ◽  
Increased Risk ◽  
Grade 3

Abstract Introduction: Ibrutinib, an oral Bruton Kinase inhibitor, is a highly effective treatment for patients with chronic lymphocytic leukemia (CLL). Previous studies reported an increased risk of bleeding due to impaired platelet function. Patients with CLL experience significant thrombocytopenia, which increases their risk for bleeding. This population was excluded from major trials and data is lacking to inform management in this setting. Methods: This is a single center retrospective study of all adult patients with CLL who received single agent ibrutinib in London, Ontario, Canada between January 2014 to December 2020. The primary objective was to investigate the risk of major bleeding associated with thrombocytopenia. Secondary objective was to investigate potential predictors of bleeding. Bleeding events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) grading system. A major bleed was defined as CTCAE grade 3 or higher as well as bleeding in the central nervous system. To assess the effect of independent variables on the outcome of bleeding, univariate analysis using chi square and t-tests was performed. Multivariate analysis was then preformed with the variables that were significant (p&lt;0.05) on univariate analysis, using logistic and cox regression models. Results: A total of 170 patients were included in this study. There were 54 bleeding events documented in 42 patients (24.7 %) of which 19(35 %) were major bleeding occurring in 17 patients. Median time to major bleeding was 2.4 months. Of the patients with major bleeding, 4(21%) were on anticoagulation, 2(10%) were on antiplatelet and 2(10%) were on combined anticoagulation and antiplatelet. There were 8 central nervous system (CNS) bleeding and 2 of them died. The mean platelet (PLT) nadir, defined as lowest PLT count at any point during ibrutinib treatment, was 73 x 10 9/Lin patients with major bleeding compared to 116 x 10 9/L in patients with minor and 91 x 10 9/L in patients with no bleeding events. On the univariate analysis, when compared patients with major bleeding to patients with no bleeding, potential predictors of major bleeding included PLT nadir (p=0.09), haemoglobin (Hb) &lt; 100 g/L at ibrutinib initiation (p=0.027) and anticoagulation (p=0.009). When compared patients with major bleeding to patients with minor or no bleeding, potential predictors of major bleeding included PLT nadir (p=0.045), Hb &lt;100 (p=0.036) and anticoagulation (p=0.06). Grade 3 thrombocytopenia, defined as PLT nadir &lt; 50 at any point during treatment with ibrutinib was not associated with increased risk of major bleeding (p=0.2). To confirm the significance of these variables, multivariate analysis was performed. When compared patients with major bleeding to patients with no bleeding, PLT nadir (OR= 0.9, p=0.008) and anticoagulation (OR=4.02, p=0.001) were confirmed to be the potential predictors of major bleeding. When compared patients with major bleeding to patients with minor or no bleeding, PLT nadir (OR=0.9 p=0.005) and Hb &lt;100 (OR=2.34, p=0.005) were the potential predictors of major bleeding. Conclusions: Although not common, Ibrutinib is associated with increased risk of bleeding and identifying high risk patients is essential to prevent major bleeding events. This retrospective Canadian study was done with the primary objective to assess the association between PLT count and major bleeding in patients on ibrutinib for treatment of CLL. In this analysis patients with major bleeding tend to have lower PLT counts compared to patients with minor or no bleeding, with mean PLT nadir of 73x 10 9/L. However, grade 3 thrombocytopenia (PLT nadir&lt;50) was not associated with increased risk of major bleeding. Other important predictors of increased risk of major bleeding while on ibrutinib include anticoagulation and anemia (Hb &lt;100). Figure 1 Figure 1. Disclosures Louzada: Amgen: Honoraria; Pfizer: Honoraria; Celgene: Honoraria; Janssen: Honoraria. Lam: AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Millennium: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Hoffmann-La Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; SeaGen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Meyers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Servier: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; Johnson & Johnson: Honoraria, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees; Beigene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees. Phua: Amgen: Honoraria; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria; NovoNordisk: Honoraria, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Honoraria.

scholarly journals Prospective Study Reveals Increased Platelet Function Associated with Multiple Myeloma and Its Treatment

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 21-21
Author(s):  
Dalia Khan ◽  
Joanne Mitchell ◽  
Rekha Rana ◽  
Neline Kriek ◽  
Amanda Unsworth ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Board Of Directors ◽  
Platelet Function ◽  
Research Funding ◽  
Platelet Reactivity ◽  
Immunoblot Analysis ◽  
Healthy Controls ◽  
Advisory Committees ◽  
Fibrinogen Binding ◽  
The Impact

Background: Multiple Myeloma (MM) is a rare incurable bone marrow cancer characterised by a malignant proliferation of plasma cells. MM is usually preceded by a premalignant and benign Monoclonal Gammopathy of Undetermined Significance (MGUS). The incidence of arterial and venous thrombosis in MM is substantially higher than in the normal population, however the cause of this increased thrombosis risk and the impact of MM on platelet function is unclear. Treatments for both newly diagnosed and relapsed/refractory patients with MM include Immunomodulatory drugs (IMiDs) such as thalidomide/lenalidomide-based combinations. These treatments improve considerably patient outcomes, however iMiD treatment also increases the risk of thrombotic complications in these patients. Aims: In this prospective study we explored the impact of MM and its treatment on platelet function. Methods: High throughput functional analysis was performed using platelets from normal healthy controls (n=31) and patients with MGUS (n=18), smouldering multiple myeloma (SMM, n= 20), and MM (26). The MM group was further divided into 3 treatment cohorts; (1) no treatment, (2) treatment with proteasome inhibitor (PI) and dexamethasone (Dex), and (3) treatment with PI, Dex, immunomodulatory drug (iMiD) and direct oral anticoagulant. Platelet aggregation and activation (fibrinogen binding and P-selectin exposure) were measured in response to a concentration range of agonists including ADP, the thrombin receptor agonist TRAP-6, collagen, collagen-related peptide (CRP), a thromboxane receptor agonist U46619 and epinephrine. Cereblon protein was detected in platelet protein extracts by immunoblot analysis. Results: Consistent with previous reports, modestly increased VWF and factor VIII levels were detected in MM patients, but no additional differences in coagulation parameters were detected in patient groups compared to normal healthy controls (other than expected due to anticoagulant usage). Platelet aggregation in response to each agonist was increased significantly in the MM patient group compared to the normal healthy controls, suggesting that platelet reactivity is elevated in MM patients through a common mechanism that is shared by different activation pathways or the involvement of multiple mechanisms. P-selectin exposure on platelets from MM patients was not significantly different from normal healthy donors, indicating that enhanced platelet reactivity in MM is specifically through modulation of integrin αIIbβ3 activation, fibrinogen binding and therefore enhanced aggregation. The effects of treatment on platelet function in patients on iMiD vs. non iMiD treatment were assessed. In the iMiD treatment group, patient platelets aggregated in response to lower concentrations of ADP, collagen, epinephrine and CRP in samples taken post-treatment compared to those taken before and during treatment. This demonstrates an increased sensitivity to platelet activation in these patients induced by treatment. Immunoblot analysis revealed that platelets contain cereblon, a therapeutic target of lenalidomide. The potential direct effects of iMiDs on platelets in vitro was therefore explored. Lenalidomide treatment (10mM) increased the ability of platelets to aggregate in response to low concentrations of each agonist tested when compared to normal controls. Conclusions: Platelet reactivity is increased in multiple myeloma and increased further upon iMiD treatment. The presence of the key therapeutic target for iMiDs in platelets and the ability of lenalidomide to modulate platelet function directly, reveals new avenues for investigation to determine the underlying mechanism of action. Disclosures Laffan: CSL: Consultancy; Pfizer: Consultancy; Sobi: Consultancy; Roche: Consultancy; LFB: Consultancy; Shire: Consultancy; Octapharma: Consultancy; Bayer: Speakers Bureau; Roche-Chugai: Speakers Bureau; Takeda: Speakers Bureau; Leo-Pharma: Speakers Bureau; Pfizer: Speakers Bureau. Shapiro:Bayer: Consultancy, Speakers Bureau; Pfizer: Consultancy, Speakers Bureau; NovoNordisk: Consultancy, Speakers Bureau; Sobi: Consultancy, Speakers Bureau; Chugai/Roche: Consultancy, Speakers Bureau; Shire/Takeda: Consultancy, Speakers Bureau. Thakurta:Oxford University: Other: visiting professor; Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Ramasamy:Takeda: Research Funding; Janssen: Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Research Funding; Amgen: Research Funding; Amgen: Honoraria; Takeda: Honoraria; Sanofi: Honoraria; Oncopeptides: Honoraria; Takeda: Speakers Bureau; Abbvie: Membership on an entity's Board of Directors or advisory committees; GSK: Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria; Bristol Myers Squibb: Honoraria; Janssen: Membership on an entity's Board of Directors or advisory committees; Bristol Myers squibb: Membership on an entity's Board of Directors or advisory committees. Gibbins:Bristol Myers Squibb: Research Funding; Arena Pharmaceuticals: Research Funding.

Sign in / Sign up

Export Citation Format

Share Document