Diagnosis Of Bleeding Disorders Research Articles

Neuraxial Analgesia in Pregnant Individuals with Bleeding Disorders: A Comprehensive Examination of Obstetric Anesthesia Practices and Outcomes

Introduction: Neuraxial analgesia in obstetric anesthesia offers multiple advantages when compared with general anesthesia, including better pain relief and patient satisfaction, reduced opioid-related side effects, and decreased maternal morbidity and mortality. However, neuraxial analgesia carries a risk of hematoma, which can lead to permanent neurological complications, and is considered contraindicated in patients with uncorrected bleeding disorders. Hemostatic thresholds for safe neuraxial analgesia remain undetermined. Current evidence for neuraxial analgesia in pregnant individuals with bleeding disorders is limited to a few case reports or small case series, leaving significant gaps in clinical practices based on expert opinions. We sought to examine obstetric analgesia practices and outcomes in pregnant individuals with bleeding disorders. Specifically, we aimed to determine the methods used at the time of labor and delivery, the concordance with antenatal recommendations, and the outcomes in relation to the bleeding disorder, hemostatic thresholds, and hemostatic therapy support. Methods: A retrospective cohort study was conducted on all pregnant individuals with bleeding disorders who delivered between 2010-2020 at our institution, a large tertiary academic care center with high-risk obstetrical care in Ontario, Canada. We collected data on patient and disease characteristics, delivery mode, hemostatic laboratory values, hemostatic support, obstetric analgesia method, antenatal anesthesia and hematology recommendations, and post-procedure outcomes. A descriptive analysis was performed to present the findings. Results: The study cohort comprised of 56 pregnant patients, resulting in 82 deliveries. The median maternal age was 31.5 years (interquartile range (IQR): 28-34), and the median gestational age was 39 weeks (IQR: 38-40). Most patients delivered vaginally (60/82, 73.2%). von Willebrand disease type 1 (VWD-1) (28/82, 34.1%) and hemophilia A (24/82, 29.3%) were the most prevalent bleeding disorders. Neuraxial analgesia was used in most deliveries (59/82, 72.0%), followed by opioids (25/82, 30.5%), and nitrous oxide (15/82, 18.3%). Antenatal neuraxial anesthesia recommendations were documented by anesthesiology in 59.8% (50/82) and by hematology in 82.9% (68/82) of deliveries. The concordance rate between the two specialties was high at 95.7%. In two cases with discordant recommendations, neuraxial anesthesia was performed without hemostatic therapy, and no adverse events were reported. A diagnosis of bleeding disorder was established prior to the pregnancy in 79 deliveries (96.3%). Three patients were diagnosed after pregnancy: one with VWD-1 and baseline von Willebrand factor (VWF) activity at 0.34 IU/mL, one with VWD-1 and baseline VWF activity at 0.44 IU/mL, and one with Factor XIII deficiency and baseline levels at 0.42 IU/mL. They had neuraxial anesthesia administered without bleeding complications. Hemostasis laboratory values in the third trimester were considered adequate for neuraxial analgesia in 68.4% (54/79) of deliveries. Those who did not reach adequate levels received hemostatic therapy support prior to neuraxial analgesia, except for three patients (one with VWD-1 with VWF activity < 0.50 IU/mL, one with VWD type 2 with VWF activity < 0.50 IU/mL, one with factor XI deficiency and levels < 0.40 IU/mL) who fortunately did not develop post-procedural hematomas. We observed no bleeding events following neuraxial analgesia, but there were two adverse events (pain at epidural site) necessitating emergency room visits. Conclusions: Our study represents the largest cohort of pregnant individuals with bleeding disorders receiving neuraxial anesthesia and provides evidence supporting the safe administration of neuraxial analgesia, with high level of adherence to antenatal recommendations. In most cases, hemostatic laboratory values were deemed adequate, obviating the need for additional hemostatic therapy support. These findings contribute to our understanding of obstetric anesthesia practices in this population, thereby facilitating the provision of safe and effective analgesia during labor and delivery. Future prospective and multicenter studies focusing on the obstetrical management of pregnant persons with bleeding disorders, with specific emphasis on neuraxial analgesia, are warranted.

Real-World Unmet Needs in Patients with Hemophilia A without Inhibitors in the US: Results from the PicnicHealth Database

Introduction Hemophilia A is a rare X-linked bleeding disorder characterized by deficiency of the coagulation factor VIII (FVIII). The standard-of-care for hemophilia A includes prophylaxis (PPX) with factor replacement therapy or emicizumab to prevent bleeding. The World Federation of Hemophilia guidelines suggest FVIII trough levels of >3-5% or higher are adequate for PPX. While the importance of maintaining high FVIII levels is well recognized, real-world levels in patients with hemophilia A are often sub-optimal. Aim To understand unmet needs in patients with moderate or severe hemophilia A by assessing bleeding outcomes and patient-reported outcomes (PROs). Methods Patients from the United States (US) were recruited by PicnicHealth, a patient-centric data retrieval platform working with individuals who contribute their medical record data to research across various disease areas. Patients consented for PicnicHealth to retrieve their medical records from all care sites or providers and receive access to their records in the US. Patients were invited to complete bleed, treatment, and quality of life surveys. The analysis included medical record data (2015-2022) and PRO survey data (2022) from patients with moderate or severe hemophilia A (endogenous factor level ≤5%). Three cohorts were defined for the analysis of bleed outcomes, based on patients' PPX product class exposure (standard half-life [SHL] factor, extended half-life [EHL] factor, and emicizumab). Index date was defined as the first observed PPX product use within the class beginning on or after January 1, 2015, and patients were censored at the earliest of switch to another product class, end of patient data, death, or data cut-off (October 3, 2022). Patients who switched product classes during the study period were included in multiple cohorts. The PRO instrument used was the 29-item, 7-domain PROMIS-29 questionnaire (range 1-5; scale scores standardized to a general US adult population with mean [SD] score of 50 [10]). A custom instrument designed to assess patients' “worst pain intensity” was also used (from 0 = no pain to 10 = worst imaginable pain). An additional Medication and Bleed Survey was administered biweekly to collect patient-reported treatment and bleed event information. Results Of the 354 patients recruited, 293 had moderate or severe hemophilia A, of which 291 patients had a record of treatment. After excluding patients with inhibitors on index date or a non-hemophilia A bleeding disorder diagnosis on or prior to index date, 141 patients met the criteria for SHL, 88 for EHL, and 82 for emicizumab PPX cohorts (non-exclusive). Patients' mean (SD) age in years at index were as follows: SHL, 26.7 (13.3); EHL, 26.2 (11.8); and emicizumab, 29.8 (14.9). Considering only individual bleed events documented in medical records, 57.3% of the SHL cohort, 47.1% of the EHL cohort, and 55.2% of the emicizumab cohort had at least one recorded bleed within the first year post-index date. When also including bleed rates reported to the provider by the patient (for more complete data capture from the medical record) the respective values were 61.4%, 70.8% and 62.1%. Out of 293 patients with moderate or severe hemophilia A, the PROMIS-29 questionnaire was completed by 142 patients who were ≥18 years of age at the time of survey completion. Scores were similar across patients' self-reported treatment class at the time of survey ( Table). Physical functioning and ability to participate in social roles and activities were the most affected areas; the most frequently reported symptoms were sleep disturbance (84.5%) and inability to participate in social roles and activities (69.7%). Adult patients completing the custom survey (n=140/293) rated their worst pain intensity as a mean (SD) of 7.7 (2.1); in patients with a recent bleed, this was 8.4 (1.5). Overall, patients reporting a recent bleed had worse scores. Conclusion This real-word study provides insights into the unmet needs in patients with hemophilia A receiving regular PPX. Irrespective of treatment received, a majority of patients still bleed at least once a year, struggle with pain and participating in social roles and activities, and have sleep disturbances. This indicates a need for improvement in the quality of life of this population and further highlights the need for understanding the patient perspective with hemophilia A.

Incidence of Postoperative Venous Thromboembolism, Hemorrhage, and Infection in Patients with Bleeding Disorders after Hip and Knee Arthroplasty

Introduction: Patients undergoing hip or knee arthroplasty (HA or KA) developed asymptomatic postoperative (post-op) venous thromboembolism (VTE) in around 30% of cases without any pharmacologic thromboprophylaxis (ThPPx). The use of pharmacological ThPPx after HA or KA has reduced the incidence of post-op VTE within 90 days to around 0.6-1.5%. People with bleeding disorders tend to have chronic joint damage from recurrent hemarthroses and frequently require HA or KA. This was especially true in the era before chronic factor prophylaxis. The exact risk estimate of post-op VTE in this population is unclear. Furthermore, the exact risk benefit for pharmacologic ThPPx is also unknown. Methods: A retrospective cohort study was conducted by looking at patients who underwent HA or KA and stratifying them based upon whether they had bleeding disorder diagnosis. Data was collected from the Health Facts database, which contains de-identified information from the electronic medical records of all US hospitals in which Cerner© has a data use agreement. Patients with bleeding disorders included Hemophilia A, B, C and Von Willebrand disease. Incidence rates of post-op VTE, hemorrhage (Hge) and infection (Inf) were calculated and compared between patients with bleeding disorders and those without bleeding disorders regardless of pharmacologic ThPPx. The same outcomes were obtained and compared between patients with/without bleeding disorders who received ThPPx. Chi-square and Fischer exact test were used to determine statistical significance. Results: 333,584 patients underwent HA or KA. Out of these, 438 patients had bleeding disorder. The incidence rates of post-op VTE were 0.01% in patients with bleeding disorders vs 0.02% in those without (p=0.1850) regardless of ThPPx which was not statistically significant. The incidence rate of post-op Hge was higher in patients with bleeding disorders (0.01%) compared to patients without bleeding disorder (0.004%; p=0.0404). The difference in incidence rate of Inf was not statistically significant between the two groups (p=0.1768). Out of total patients, 202,936 patients who underwent KA or HA received ThPPx. The difference in incidence rates of VTE as well as Inf were not statistically significant between patients with and without bleeding disorders who received ThPPx (p=0.2357 for VTE and p=0.2519 for Inf). The incidence rate of post-op Hge in patients who received ThPPX and had bleeding disorder was 0.014% in contrast to 0.004% in patients without bleeding disorder, though, it did not reach statistical significance (p=0.0684). Conclusion: Patients with bleeding disorders have a similar risk of post-op VTE as the general population after HA or KA. Patients with bleeding disorders have higher post-op hemorrhagic complications. However, when comparing only those patients who received ThPPx, the difference in incidence of post-op Hge was not statistically significant. This implies that all patients including the ones with bleeding disorders, undergoing HA or KA may be treated with a similar ThPPx approach. Patients with bleeding disorders undergoing HA or KA do not have a higher predisposition to infections compared to the general population and may not require additional infection control measures. We did not look at the differences in factor treatment perioperatively which would have been standard for all bleeding disorder patients if they followed in a hemophilia treatment center. Our study limitation was its retrospective nature as well as all HA, KA, post-op VTE, Hge and Inf were identified by CPT and ICD codes.

Obesity and Race As Determinates of Plasma Von Willebrand and Factor VIII Levels

Introduction: Obesity has emerged as a significant public health problem in all ages in the United States. The age-adjusted prevalence of obesity and severe obesity were 42.2% and 9.2% respectively among adults aged 20 or older from 2017-2018. Overall, non-Hispanic black and Hispanic adults and youth had a higher prevalence of obesity compared with other race and Hispanic-origin groups. Obesity prevalence was lower among non-Hispanic Asian men and women compared with other race and Hispanic-origin groups based on National Center for Health Sciences- Center for Disease Control. Factor VIII (FVIII) and von Willebrand factor (vWF) are both coagulation factors that are acute phase reactants. Obesity has been associated with metabolic syndrome and resultant chronic inflammation. Obesity has previously been linked to increasing FVIII levels, however, studies have not been able to confirm a linkage between VWF and body mass index (BMI). Methods: This is a secondary analysis of a single-site retrospective review of the electronic health record of patients that had von Willebrand profiles [VWF:Antigen (Ag), VWF:Activity (Act), and/or FVIII activity] obtained within 24 hours of a hemoglobin level who had no bleeding disorder diagnosis. BMI was recorded when available in the electronic medical record at the time of laboratory testing and correlation between BMI and FVIII/vWF levels was assessed. Data was retrieved from January 1, 2012, through June 1, 2021. Results: We identified 4552 individuals who had VWF profile testing that had an associated hemoglobin level in a 24-hour period and did not carry a diagnosis of VWD. Among all subjects, a total of 2152 subjects were found to have BMI measurements, 1294 subjects <85th percentile, 379 subjects ≥85th - 95th percentile and 479 subjects ≥ 95th percentile. Demographics for the cohort with BMI measurements were White (N=1,673; mean BMI percentile 67.4±29.4), Black (N=377; mean BMI percentile 72±27.3), Asian (N=46, mean BMI percentile 48.0±33.9). There was a statistically significant difference in BMI by race (P<0.001). VWF antigen (P<0.005) and FVIII level (P<0.005) were significantly and positively correlated with increased BMI levels. Similarly, VWF activity/antigen ratio was negatively correlated (P<0.005) with increasing BMI. Further statistical modelling was performed, controlling for hemoglobin, BMI percentile, race, and age. BMI percentile remained a determinant for VWF antigen and FVIII levels. VWF antigen levels were statistically different in those with BMI <85th and ≥ 95th percentile (P<0.0001) and ≤85th-95th and ≥ 95th percentile (P<0.01). FVIII levels were significant between BMI ≤85th and ≥ 95th percentile (P<0.0001). We also examined the cohort for potential differences in VWF and FVIII levels based on race. Black race was found to be associated with higher VWF antigen levels among all races and found to be statistically significant when compared to White race (P<0.0001). Black race was also associated with a higher FVIII level versus White race (P<0.0001). Further statistical modeling was also done for race, controlling for BMI, hemoglobin, and age. VWF antigen levels were statistically significant among races (P<0.0001) with Black race having the highest mean level. Similarly, Race was a significant factor for VWF activity/antigen ratio (P<0.0001) with White race having the highest and Black race the lowest mean ratio. Race was also statistically significant (P<0.0001) for FVIII levels, with Black race having the highest levels and lowest levels in the all-other race category. Conclusions: BMI and race were independently found to be determinants of VWF:Ag and FVIII levels. As patients presenting for a bleeding disorder evaluation may be overweight or obese, the confounding effect of increased BMI should be considered during the diagnostic evaluation. We also observed racial differences in VWF antigen and FVIII levels. As this was antigen testing, it should not be affected by the known racial differences in sensitivity to ristocetin cofactor testing. Further studies to confirm these findings and the potential confounding effect of BMI are needed.

Documentation of Menstrual Concerns in Patients with Inherited Bleeding Disorders

Introduction: Inherited bleeding disorders (IBD) such as von Willebrand disease (VWD) and clotting factor deficiencies may be associated with heavy menstrual bleeding (HMB) in patients with a uterus. Identification of HMB and development of an adequate management plan is fundamental to the care of these patients. However, the frequency with which hematologists discuss, document, and recommend treatment or gynecologic (GYN) consultation in women with IBD has not been well described. In this retrospective review, our aim was to assess the frequency and breadth of documented discussions about menstrual concerns in women with IBD during initial consultative visits with a hematologist. Methods: We performed a retrospective chart review of women ages 18 to 50 with a confirmed diagnosis of VWD, hemophilia A or hemophilia B seen for an initial consultative visit at the Penn Comprehensive Hemophilia and Thrombosis Program (PCHP) between January 2017 and July 2022. We collected information regarding patient demographics and laboratory values related to the bleeding disorder diagnosis and the frequency of documentation of menstrual periods in general, as well as specific rates of discussion of concerns related to HMB (passage of clots, amount of flow), documentation of management recommendations (oral contraceptive, IUD, adjunctive antifibrinolytic agents) and/or referral to GYN. Results: Forty-two patients were included in the analysis including 39 (92.8%) with VWD, 2 (4.8%) with hemophilia A, and 1 (2.4%) with hemophilia B). Thirty-eight of 42 patients (90.5%) had a documented discussion regarding menstrual periods at the time of the initial consultative visit. Thirty-four of the 38 (89.5%) who had a documented discussion about menstruation subjectively reported having "heavy menstrual bleeding" (sHMB), although the quantity was not documented in any case with a verified tool such as the PBAC. Nineteen of 38 (50%) patients had a documented discussion regarding the amount of menstrual blood flow. Ten (52.6%) had documentation of the number of pads/tampons/products used per day. Three (15.8%) had documented menses duration (number of period days). Six (31.6%) had documentation both of period duration and the number of pads/tampons used per day. Male hematologists documented amount of flow in 41.7% of patient visits, while female hematologists did so for 53.3% of visits. Twelve of 38 (31.6%) patients had a documented discussion regarding passage of clots during their periods. Five (41.7%) had a description only of clot presence, 4 (33.3%) of clot frequency and presence and 2 (16.7%) of clot size and presence; 1 (8.3%) reported no clot passage. Male hematologists documented the presence of clots for 33.3% of visits, while female hematologists did so 26.7% of visits. There was a documented discussion of treatment options in 29 of 34 patients reporting sHMB (85.3%). Treatment options included either those in use at the time of the initial consult visit or those recommended during the initial visit in patients who reported inadequate control of sHMB with prior treatments. Treatments discussed included: 15 oral contraceptives (51.7%), 8 IUD (27.6%), 2 subdermal implant (Nexplanon) (6.9%), 1 Depo Provera (3.4%), 1 contraceptive patch (3.4%), and 2 who reported not having any response to hormonal contraception and were treated with antifibrinolytic therapy alone (6.9%). There was a documented discussion of referral to GYN in 14 of 34 (41.2%) of patients who reported sHMB. Conclusions: In this retrospective study, we found that hematologists often document menstrual bleeding concerns in female patients with IBD, but do not consistently document specific components of sHMB such as amount of menstrual blood flow and/or passage of clots. Documentation rates were similar for hematologists of both sexes. Standardized templates for evaluation of HMB (both subjectively reported and formally assessed) may improve documentation rates in the future. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Endothelium, Platelets, and Coagulation Factors as the Three Vital Components for Diagnosing Bleeding Disorders: A Simplified Perspective with Clinical Relevance.

Bleeding disorders are a major group of hematological disorders, which are highly prevalent in the world. Excessive bleeding can result in serious consequences including hypoperfusion and cardiac arrest. The body has its selfmechanism to control excessive bleeding which is termed hemostasis. Hemostasis is achieved in two major steps, the formation of the primary and secondary hemostatic plugs. Endothelium, platelets, and coagulation factors are three components involved in hemostasis. Endothelium and platelets have a major role in forming the primary hemostatic plug. Consequently, the first step in investigating a bleeding disorder is platelet count. Despite normal platelet count, abnormality in the primary hemostatic plug may arise due to functional defects of the platelets including adhesion, activation, and aggregation. Von Willebrand disease (VWD) is an endothelial defect and the most prevalent inherited defect in coagulation. Abnormalities in the secondary hemostatic plug are largely due to coagulation factor deficiencies, and, to a lesser extent, the presence of inhibitors. Techniques involving viscoelastics have been aiding in rapid diagnosis and are useful in point-of-care testing. This article discusses the investigation of bleeding disorders from the perspective of the endothelium, platelet, and coagulation factor physiology. These three components should be properly investigated to achieve the definitive diagnosis of bleeding disorders.

Saddle Pulmonary Embolism in Patients with Cancer in the Era of Incidental Events: Clinical Findings and Outcomes in a Single Centre Cohort.

Background There is scarce information regarding the prevalence and clinical impact of saddle pulmonary embolism (PE) in patients with cancer. Objectives This study aimed to assess the prevalence, clinical findings, and short-term outcomes of patients with cancer-related saddle PE including acute symptomatic and unsuspected events. Patients/Methods Consecutive patients with cancer-related PE (March 1, 2006–October 31, 2014) were retrospectively reviewed by a chest radiologist to assess PE burden and signs of right ventricular (RV) overload. The clinical outcomes within 30 days were evaluated according to saddle versus nonsaddle PE. Results Thirty-six (12%) out of 289 patients with newly diagnosed cancer-related PE presented with saddle PE. Saddle PE was found in 21 cases (58%) with acute symptomatic PE and the remaining 15 cases (42%) were found as unsuspected findings. Patients with saddle PE had more frequently experienced a previous thrombotic event (31 vs. 13%; p = 0.008), and it occurred more frequently as an acute symptomatic event (58 vs. 39%; p = 0.025) compared with those with nonsaddle PE. Signs of RV overload including RV/left ventricle ratio ≥1 (22 vs. 4%; p < 0.001) and interventricular septum displacement (53 vs. 20%; p < 0.001) were also more common in patients with saddle PE compared with nonsaddle PE. Overall, PE-related mortality, venous thromboembolism recurrence, and major bleeding within 30 days were found to be similar according to saddle versus nonsaddle PE. Conclusion Saddle PE is not uncommon in patients with cancer-related PE including in those with unsuspected PE. Similar 30-day outcomes were found according to saddle versus nonsaddle PE in our cohort.

“If I wasn't a girl”: Experiences of adolescent girls with heavy menstrual bleeding and inherited bleeding disorders

BackgroundHeavy menstrual bleeding (HMB) is a presenting symptom of an inherited bleeding disorder (BD) and results in hospitalizations, limitations of daily activities, and a reduction in quality of life. Adult women with BD report a sense of stigma, difficulties understanding their bleeding, and challenges with diagnostic labels. The experiences of adolescents with HMB and BD are unknown despite advances in medical management through the rapidly growing network of young women's hematology programs. ObjectivesThe objective of our qualitative study was to describe the experiences of adolescents with HMB with a BD and the impact on their day‐to‐day lives. Patients/MethodsOur qualitative study utilized semistructured interviews with adolescents with HMB after a BD diagnosis. We included adolescents with a BD within a multidisciplinary Young Women's Bleeding Disorders Clinic who had achieved menarche within the preceding 3 years and conducted interviews until theme saturation. All interviews were transcribed verbatim and analyzed using qualitative thematic descriptive analysis. ResultsWe identified the following themes in nine participants: anxiety and embarrassment, especially related to school; isolation and “otherness”; increased cautiousness and planning because of HMB and BD; and empowerment and identity formation because of the diagnosis of a BD. ConclusionsOur study uncovers previously unappreciated experiences of adolescents with HMB and a BD. HMB is an isolating and stressful experience in adolescents, but a BD diagnosis results in identity formation and empowerment. Psychological support and facilitating connections to others with similar life experiences soon after diagnosis represents key areas for targeted interventions.

Evaluation of the Atellica COAG 360 coagulation analyzer in a specialized coagulation laboratory.

BackgroundDiagnosis of bleeding disorders includes correct analysis of coagulation factors VIII, IX, XI, XII, XIII, II, V, VII, and X and von Willebrand antigen and activity. The aim of this study was to evaluate the analytical performance of the Atellica COAG 360 analyzer in a specialized coagulation laboratory with focus on specific coagulation parameters involved in the diagnosis of bleeding disorders.MethodsVerification included assessment of precision, reference interval, and method comparison according to local guidelines. For FVIII (Chromogenix) and FIX (Rossix), extended verifications were performed with additional assessment of linearity, detection limit, and comparability to BCS‐XP.ResultsThe precision was below 5% (normal levels) and below 10% (abnormal levels) and either improved or similar when compared to expected target values from a BCS‐XP. The locally established reference range agreed well (≥80% of measured values within manufacturer's assigned ranges) for most of the methods. The lower limit of quantification was calculated to below 0.01 IU/ml for FVIII chromogenic (Chromogenix) and FIX chromogenic (Rossix), both with acceptable linearity. Bland–Altman analyses revealed generally good agreement between Atellica COAG 360 and BCS‐XP in the determination of coagulation parameters, and differences between the two instruments did not result in any diagnostic change.ConclusionsThe results of the evaluation show that the Atellica COAG 360 analyzer performs as expected to target values and equivalent to BCS‐XP for the diagnosis of bleeding disorders in a specialized coagulation laboratory providing service to a hemophilia treatment center (HTC).

Utilization of a surgical database to provide care and assess perioperative treatment and outcomes in patients with bleeding disorders.

To describe the Indiana Hemophilia and Thrombosis Center (IHTC) surgical database, its key components, and exploratory analyses of surgeries conducted between 1998 and 2019. Surgical data across bleeding disorders collected retrospectively (1998-2006) and prospectively (2006-2019) were analyzed. Perioperative hemostasis, complications, and surgical plan deviations were compared by bleeding disorder diagnosis and data collection period. Within the 21-year period, 3246 procedures were conducted in 1413 patients with a diagnosis of von Willebrand disease (vWD), hemophilia A (HA), hemophilia B (HB), and other bleeding disorders. Majority of the procedures were minor (63.3%), and median number of surgeries per patient was 1 (range: 1-22). Adequate perioperative hemostasis was achieved in 90.9%, complications occurred in 13.6%, and surgical plan deviations occurred in 31.3% of procedures. Inadequate perioperative hemostasis and surgical plan deviations occurred more frequently in procedures involving HB compared with other bleeding disorders. Complications were not significantly different across bleeding disorders (p=.164). The prospective data collection period was associated with higher rates of hemostatic efficacy (92.4% vs. 88.3%; p<.001), complications (14.3% vs. 12.3%; p<.001), and plan deviations (34.2% vs. 25.1%; p<.001). The surgical database is an important resource in surgical management in patients with bleeding disorders. Further evaluation will facilitate use for the development of predictive models and principles of care.

Approach to the Diagnosis of Bleeding Disorders in Children

Hemostasis is the cessation of bleeding in the intravascular compartment. This occurs by the formation of clot formation at the site of injury. The intricately related system also regulates the size of the clots by the activation of fibrinolysis. The disorders that lead to the bleeding outside the intravascular space is bleeding disorder. Bleeding occurs as a result of defective quality or quantitative deficiencies of platelets, coagulation problems in the extrinsic or intrinsic or the common pathways and abnormalities in the vascular walls to contain hemorrhage. Although the values of different coagulation and fibrinlytic factors are pretty much like that of the adults yet, neonates have considerable differences in these values than their senior counterparts even in pediatric age groups. Considering all these facts the history, physical examination and laboratory investigations always provide the clinicians some important clues to reach the diagnosis. Because of the complicated relationship among the different pathways of coagulations and fibrinolytic systems the whole procedure might look complex yet methodical approach paves the way of an intelligent clinician to arrive at the diagnosis with precision and clinical perfection.&#x0D; CBMJ 2020 July: Vol. 09 No. 02 P: 45-53

Postoperative tonsil/adenoidectomy bleeding management in patients with diagnosed bleeding disorders.

ObjectiveTonsil/adenoidectomy (T/A) is a commonly performed procedure with an average post‐tonsillectomy bleed (PTB) rate between 3 and 5%. Patients with bleeding disorders (BDs) are believed to have an increased risk of PTB. We hypothesize that our medical management of BD patients using a combination of DDAVP/antifibrinolytic agents has a similar PTB rate to control patients. This study suggests a standardized protocol for patients with BDs to avoid PTB.MethodsA retrospective cohort study was completed for patients with BD who underwent tonsillectomy or T/A at Promedica Toledo or Flower Hospital between 2013 and 2020. Exclusion criteria included incomplete records, diagnosis of BD after surgery, and inability to find age and sex matched control. We defined the control group as patients who underwent T/A without BD. The following variables were collected: age, sex, medical history, BD severity, medications, type of surgery, indication for surgery, estimated blood loss (EBL), pre/postoperative medications, PTB status, and post‐PTB intervention.ResultsA total of 164 patient charts were reviewed. There were 82 patients in both cohorts. The BDs represented were platelet function disorder (80.5%), von Willebrand disease (14.6%), and others such as Factor VII and IX deficiency (4.9%). Of the BD patients included, 13.4% had severe disease. There was no significant difference between the age, sex, EBL, and PTB rates. Of the 8 BD patients with PTB, 62% bled 9‐10 days postoperatively and none had severe disease.ConclusionOur protocol to prevent PTB in patients with BDs produced similar bleed rates to control patients in this study. Further studies are required to assess postoperative length of antifibrinolytic treatment in BD patients.Level of EvidenceIII.

Abnormal Coagulation as a Risk Factor for Postoperative Complications After Primary and Revision Total Hip and Total Knee Arthroplasty

BackgroundPatients undergoing total joint arthroplasty (TJA) have an increased likelihood of having an abnormal coagulation profile compared with the general population. Coagulation abnormalities are often screened for before surgery and considered during perioperative planning. This study assesses a preoperative abnormal coagulation profile as a risk factor for postoperative complications after total hip arthroplasty (THA), revision THA (rTHA), total knee arthroplasty (TKA), and revision TKA (rTKA) and then examines specific coagulopathies to determine their influence on complication rates. MethodsPatients who underwent THA, rTHA, TKA, or rTKA from 2011 to 2017 were identified in the American College of Surgeons National Surgical Quality Improvement Program database and then assessed for preoperative abnormal coagulation profiles. Various postoperative complications were analyzed for each cohort, and two separate multivariate regression analyses were used to assess the relationship between abnormal coagulation and postoperative complications. Results403,566 THA, rTHA, TKA, or rTKA cases were identified, and 40,466 (10.0%) of patients were found to have an abnormal coagulation profile. Patients with preoperative coagulation abnormalities had higher likelihoods of postoperative complications after primary TJA than in revision TJA. An international normalized ratio>1.2 was associated with the most types of postoperative complications, followed by a bleeding disorder diagnosis. A partial thromboplastin time>35 seconds was associated with only one type of postoperative complication, while a platelet count <150,000 per μL was associated with postoperative complications only after TKA. ConclusionTJA in patients with abnormal coagulation profiles may result in adverse outcomes. These patients may benefit from preoperative intervention. Prophylactic care needs to be personalized to the specific coagulation abnormalities present.

15. Assessment of Iron Status in Adolescents Presenting to the Emergency Department with Heavy Menstrual Bleeding

<h3>Background</h3> Heavy menstrual bleeding (HMB) is experienced by many adolescents and often leads to iron deficiency (ID), which can decrease quality of life. The purpose of this study was to evaluate whether adolescent patients who present to the Emergency Department (ED) with HMB are appropriately screened and treated for ID, rather than only for anemia. <h3>Methods</h3> This was a retrospective study with IRB approval. Data was gathered from an Emergency Department and Inpatient Unit at a National Tertiary Care Hospital from 2006-2018 on adolescents aged 11-19 years with ICD-9 and 10 codes for HMB. Pregnant patients were excluded. Data included patient demographics, presenting symptomatology, past medical history, BMI, diagnosis of bleeding disorder, labs ordered and their results, treatments rendered, documented diagnosis of etiology of bleeding at time of presentation to the ED, and whether there was admission to the hospital. The main outcome measure was evaluating the number of adolescents who had iron evaluation through serum ferritin testing and how many of these met laboratory criteria for ID. ID was defined as serum ferritin <30 μg/L. Statistical analysis was performed to identify differences in symptomatology between patients who had iron levels evaluated compared to those who did not using Fishers exact and Chi square tests. A secondary outcome measure was determining the number of adolescents prescribed oral iron upon discharge. <h3>Results</h3> There were 258 adolescents who sought care for HMB in the ED, 225 (87.2%) of whom were evaluated with serum hemoglobin testing. Ninety-three (41.6%) of those tested were anemic. Only 23 (8.9%) of the 258 patients had serum ferritin testing performed. Of these, 18/23 (78.3%) were iron deficient and 21/23 (92.3%) were anemic. Patients presenting with fatigue, lightheadedness, headache, shortness of breath, and/or palpitations were more likely to have iron studies performed than those without these symptoms (p<0.01, p<0.05, p<0.01, p<0.04, p<0.01 respectively). See Figure 1. A total of 32 of the 258 patients (12.4%) were discharged on oral iron therapy. Only 15/18 (83.3%) of patients with a diagnosis of ID were discharged with iron. <h3>Conclusions</h3> Adolescents presenting to the ED with HMB are at significant risk of ID but are not appropriately screened or treated, which can have substantial consequences for their health and quality of life.

English

A 26-year-old male presented to general medicine department on 16th March 2020 with complaints of 3 episodes of epistaxis for 2 days. The epistaxis was spontaneous, sudden in onset, recurring in nature, copious in amount, not relieved on its own. No history of nasal trauma, head injury, fever, joint pain, cough, breathlessness, difficulty in swallowing, pain abdomen, haematuria, rashes. No history of bleeding diathesis from any other site. Past history revealed similar complaints of nasal bleeding for past 2 - 3 months for which he used to get admitted and administered platelets transfusions after which the symptoms used to subside. No history of any bleeding disorders or other comorbidities. Family history revealed that the younger brother is a known case of Bernard-Soulier syndrome diagnosed at the age of 15 years. Drug history was insignificant. Based on patient’s presentation and family history, a congenital bleeding disorder was considered as provisional diagnosis. On clinical examination pallor was observed in lower palpebral conjunctiva and dorsum of tongue and crusts were present in nose. Moderate splenomegaly was also observed. His laboratory data revealed presence of microcytic hypo-chromic anaemia with hyponatremia, with prolonged bleeding time, normal clotting time and coagulation time. Complete blood count revealed severe microcytic hypochromic anaemia (haemoglobin - 5.8 gram / decilitre) (Figure 1) and giant platelets (Figure 2). Bleeding time was 12 minutes and clotting time was 8 minutes. Factor VIII levels were normal in the patient. Prothrombin time was prolonged with 13.9 seconds. Liver function test revealed only hypoalbuminemia with no derangement of liver enzymes. Renal function tests were normal. Serum electrolytes revealed hyponatremia with 130 millimole / litre. Ultrasound abdomen and pelvis revealed a heterogeneous focus which was noted in spleen with peripheral colour uptake and necrotic areas within it suggesting of splenic abscess / splenic haematoma / infarct. Contrast enhanced computed tomography of abdomen and pelvis revealed mild splenomegaly with heterogeneous foci with peripheral colour uptake and necrotic areas within it measuring 6.4 * 4.8 centimeters, areas were hypo dense and few enlarged retroperitoneal lymph nodes noted in para-aortic region. Computed tomography of brain plain was normal. Contrast enhanced computed tomography of thorax was normal. Platelet function tests revealed normal aggregation with adenosine diphosphate, collagen and arachidonic acid and markedly reduced with ristocetin. Flow cytometry could not be assessed. His clinical examination revealed findings suggestive of anaemia and splenomegaly was also present with vital parameters within normal limits. He underwent thorough work-up with working diagnosis of bleeding disorder under evaluation.

Rates of Intrauterine Device Expulsion Among Adolescents and Young Women.

The objective of our study was to determine the rate of intrauterine device (IUD) expulsion and risk factors for expulsion among adolescents and young adults. Retrospective chart review. IUD insertions were performed at a single children's hospital. Eligible adolescent and young adult patients who underwent IUD insertion between August 2009 and March2019. IUD insertion. Primary outcome was the incidence of IUD expulsion in adolescents and young women. Secondary outcomes were risk factors for IUD expulsion including heavy menstrual bleeding, abnormal uterine bleeding (AUB), anemia, or a bleeding disorder diagnosis. Six hundred forty-two eligible patients underwent IUD insertion. The incidence of first IUD expulsion in this population was 58/642 (9.03%). Among those who chose to have a second IUD placed (n=29), 8/29 (27.6%) had a second expulsion. Patients who expelled their IUD were more likely to have a history of AUB, heavy menstrual bleeding, anemia, or a bleeding disorder. When controlled for body mass index and age at insertion, history of AUB and anemia remained significant risks for IUD expulsion. This study similarly showed a higher risk of primary and secondary IUD expulsion in adolescents and young women. A history of AUB, anemia, bleeding disorder, and elevated body mass index are associated with higher risk for IUD expulsion. This population should be counseled that these conditions might place them at higher risk for expulsion.

Bleeding Disorder Referrals to Hematology Clinic: A Single Institution Experience

BACKGROUND Our tertiary care pediatric hematology/oncology/BMT service receives hundreds of referrals yearly for bleeding disorder evaluation both due to bleeding symptoms and secondary to routine preoperative laboratory testing prior to elective surgery. The evaluation for a bleeding disorder can be challenging due to the wide variability of symptoms as well as the need for accurate interpretation of lab results. In 2014, Bhasin et al., Pediatric Hematology and Oncology showed that 4% of patients referred to hematology based on a preoperative coagulation evaluation had a clinically relevant bleeding disorder. Currently there is little literature about the referral patterns to pediatric hematology and the outcomes of these referrals. OBJECTIVES To characterize our hematology referrals for bleeding disorder, work up To describe the diagnostic outcomes from these referrals To estimate the proportion of bleeding disorders diagnosed from these referrals To identify referral factors that are associated with being diagnosed with a bleeding disorder DESIGN/METHOD This is a single center, retrospective chart review. Patients referred and or seen for a bleeding disorder evaluation at Children's Mercy Hospital from 07/1/2018 until 06/30/19 were evaluated for demographics, reason for consultation, referring provider, and outcome of referral. Akaike Information Criterion (AIC) was applied to logistic regression to identify factors associated with diagnosis of bleeding disorder. RESULTS A total of 373 patients were included and demographics are detailed in Table 1. Forty patients were diagnosed with a bleeding disorder, 78 patients were lost to follow up or have work up still in progress, and 255 patients had a bleeding disorder ruled out. Of our referred patient sample, 6% (21/373) were diagnosed with von Willebrand disease, 4% (14/373) were diagnosed with a platelet function disorder, and 1.3% (5/373) were diagnosed with a coagulation factor deficiency. The median time between referral and appointment was 31.5 days with a median of 2 total visits including clinic and laboratory visit for a clinical diagnosis. Forty percent of referrals were for preoperative clearance, 36% for family history, and 57% for symptoms. Of the patients referred for symptoms, 22.7% were referred for bruising and 83.9% for bleeding. Thirty eight percent had previously been treated for symptoms through hormone management, nasal cauterization, surgical intervention, or other methods. Forty four percent (164/373) of the referrals were from Otolaryngology, 30% from primary care including adolescent medicine and gynecology, and 27% from other specialties. Seventy percent of referrals were internal from specialties within our institution. The results indicate that the odds of a bleeding disorder diagnosis decrease by 8% for every year increment in age and was 3 times higher among patients having abnormal coagulation labs at the time of referral as compared to their counterpart when other variables were controlled. Logistic regression model showing referral factors that could be associated with bleeding disorder diagnosis are detailed in table 3. CONCLUSION This study characterizes the bleeding disorder referral patterns at our institution including the proportion of bleeding disorders diagnosed. This study also highlighted certain referral factors such as age, gender, referral for preoperative clearance, previous treatment with nasal cauterization and the presence of abnormal lab values that could be predictive of the presence of a bleeding disorder. Limitations of this study include the small number of patients with confirmed diagnosis and that it is conducted at a single center. Additionally, at our center, referrals are screened by a physician prior to being seen, which could have influenced the results. We illustrate that large-scale studies are needed to determine referral factors associated with the diagnosis of a bleeding disorder. Disclosures Carpenter: American Academy of Pediatrics: Other: PREP Heme/Onc editorial board; Hemostasis &amp; Thrombosis Research Society: Membership on an entity's Board of Directors or advisory committees; Shire: Research Funding; CSL Behring: Research Funding; American Thrombosis and Hemostasis Network: Membership on an entity's Board of Directors or advisory committees; Genentech, Inc.: Honoraria; Kedrion: Honoraria; Novo Nordisk: Honoraria.

Under-Diagnosed and Under-Treated Menorrhagia in Young Women Produce Suboptimal Performance

Background: Menorrhagia can have a significant impact on a woman's life. It can lead to anemia, fatigue, difficulty with physical activities, absence from work, and avoidance of social activities and may be the first sign of a bleeding disorder. We presumed that many young women with menorrhagia do not seek medical advice or are under-treated. This study aimed to document the prevalence of menorrhagia, by questionnaire, visual scores and self-assessment; its association with bleeding disorders, and the effect of menorrhagia on activity and quality of life (QoL) in young adults engaged in compulsory military service. The military service in Israel is obligatory for women as for men, making this cohort similar to the general population. Method: In this cross-sectional study we gave a short oral lecture presenting the study objective and plan to female soldiers in combat and non-combat roles. Participants were asked to consent to complete a one page coded, unidentified, initial questionnaire. After providing an additional informed consent, study participants were asked to complete additional study questionnaires, including personal and family bleeding history, pictorial bleeding assessment chart (PBAC), dysmenorrhea questionnaire, and age-appropriate PedsQL™. All forms were coded with the same number as the initial questionnaire. PBAC scores above 100 were diagnostic for menorrhagia and above 200 signified severe menorrhagia. Results: Of 422 women soldiers completing the initial questionnaire, 365 (86.5%) completed all study questionnaires. Characteristics of women not completing all study questionnaires were similar to those with complete study data except there were more soldiers in a combat role in the former (P=0.02). The median (range, 25th-75th interval) of the PBAC score was 100 (4-590, 55-189). PBAC scores &amp;gt; 100 and 200 were reported by 181 (50%) and 81 (22%), respectively. Most participants correctly self-assessed menorrhagia; still, a high PBAC score was also recorded in some who answered "no" or "unknown" in the initial questionnaire (Figure 1). Diagnosis of menorrhagia was associated with a history of bleeding, specifically cutaneous and bleeding from the oral cavity (Figure 2), yet none of the participants reported a diagnosis of a known bleeding disorder. The use of NSAIDs during menstruation was associated with a higher rate of menorrhagia (Table 1). No association was found with the current army role. However, the diagnosis of menorrhagia was related to the pre-enrolment fitness ranking [a score reflecting the overall per-recruitment health status] (Table 1). Those with menorrhagia suffered from higher pain levels and moderate to severe negative effects on activity during the days of menstruation compared to those without menorrhagia (Table 1, Figure 3). A trend for lower QoL was found in those with menorrhagia (Table 1). Discussion: Menorrhagia in young adults is a significant clinical problem effecting activity and quality of life. It is under-recognized and under-treated. The association with other bleeding manifestations may suggest an under diagnosis of bleeding disorders. In a world of women empowerment, any treatable cause, leading to suboptimal performance should be addressed. Thus, assessment for menorrhagia and dysmenorrhea should be part of well-being visit also in young adults to provide appropriate management to reduce the undesired effects of menorrhagia. Disclosures Revel-Vilk: Takeda: Honoraria; sanofi-Genzyme: Honoraria; Pfizer: Honoraria.

Iron Deficient Anemia May Obscure a Diagnosis of Low VWF, VWD or Mild Hemophilia a in Biological Females with Heavy Menstrual Bleeding

INTRODUCTION Heavy menstrual bleeding (HMB) is one of the most common disease manifestations of biological females with inherited bleeding disorders and is often accompanied by iron deficient anemia (IDA). The most common bleeding disorders identified in biological females are von Willebrand Disease (VWD)/low von Willebrand Factor levels (low VWF) and heterozygosity for factor VIII genetic defects. Several pre-analytical variables including elevated adrenergic stress and estrogen-states can make it challenging to accurately diagnose these conditions as these variables are known to influence VWF and factor VIII activity levels. We sought to investigate whether an iron depleted state impacts the results of a laboratory assessment for VWD/low VWF or mild hemophilia A. METHODS Subjects were recruited from the Spots and Dots clinic (female-identifying bleeding disorder clinic) through the University of Colorado's Hemophilia and Thrombosis Center. Eligible subjects included biological females of any age who had at least two sets of laboratory assessments for von Willebrand levels (VWF antigen, VWF activity, and factor VIII activity level) and markers for total body iron stores (complete blood count and ferritin). Age at time of first testing, iron prescriptions, and underlying bleeding disorder diagnoses were also recorded. IDA was defined as a ferritin less than 20ng/mL with accompanying anemia (Hb &amp;lt;14.3 g/dL). Descriptive statistics and Fisher's exact tests were used to evaluate the association of factor VIII/VWF activity levels and iron stores. RESULTS Thirty-seven subjects were included in the final analysis. The average age at time of first testing was 21.5 years (range 9-50 years). IDA was present in 22 patients at the time of first assessment and in 20 patients at follow up. Serum ferritin improved overall in 23 patients between assessments. Oral iron was prescribed in 20 patients and intravenous iron was prescribed in three. An improvement in serum ferritin predicted a decrease in factor VIII activity (p = 0.0092) on follow-up assessment but did not predict a significant decrease in VWF activity levels (p = 0.0819) (Figure 1). Retesting factor VIII and VWF activity levels after iron repletion led to a diagnosis of low VWF in 4 cases (10.8%) and VWD in 2 cases (5.4%) that would have otherwise been classified as normal without retesting. CONCLUSIONS IDA is frequent in women with HMB and may be insufficiently managed with oral iron therapy in adolescents and those with an underlying bleeding disorder. The fact that many patients remained iron deficient at the time of follow up testing may have blunted the results of this analysis. Despite this limitation, this study still suggests that iron deficient anemia may be a significant enough biological stressor to increase factor VIII and possibly VWF activity levels to a point that may obscure an underlying diagnosis of VWD, low VWF, or hemophilia A. Further investigations are warranted to confirm if universal retesting of VWF and factor VIII activity levels are diagnostically imperative after correction of IDA. Such a recommendation may have a significant impact on this patient population as discovery of an underlying bleeding disorder diagnosis can not only provide an explanation for a patient's HMB but also can identifying individuals who may be at increased risk for bleeding at other sites or during invasive procedures. Disclosures No relevant conflicts of interest to declare.

A Comparison of Scores from the ISTH-BAT and Self-BAT in Adolescent Biological Females with Heavy Menstrual Bleeding

INTRODUCTION Women with inherited bleeding disorders of all severities often present with heavy menstrual bleeding (HMB) during adolescence. The International Society of Thrombosis and Haemostasis Bleeding Assessment Tool (ISTH BAT) is a clinician-administered instrument that has become part of the standard initial assessment of individuals with possible bleeding diatheses and for which pediatric normal ranges have been established (Elbatarny, Haemophilila 2014). The Self-BAT is an instrument that has gained popularity due to its ability to be performed independently by the patient either on paper or electronically. While favorable intraclass correlation has been demonstrated between these tools for individuals &amp;gt;18 years of age, the Self-BAT has not been validated in an adolescent population (Punt, HT Open 2019). We therefore sought to compare the results of the physician directed ISTH-BAT with the Self-BAT in a population of biological females &amp;lt;20 years of age. METHODS Eligible subjects included biological females under 20 years of age seen at the University of Colorado's Hemophilia and Thrombosis Center's adolescent bleeding disorder (Spots and Dots) clinic for evaluation of HMB and assessment of either a known or suspected bleeding diathesis. Subjects were administered both an ISTH BAT and Self-BAT within a three-month period. All ISTH BATs were performed and scored by the same hematologist. Each subject used an iPad to enter data for the self-BAT which was collected into REDCap and scored by the same hematologist. Age at the time of assessment and underlying bleeding disorder diagnosis or etiology for HMB were also recorded. Descriptive statistics and Pearson's Correlation coefficient were used to compare the outcomes between the ISTH BAT and the Self-BAT. RESULTS Sixteen biological females met inclusion criteria and were included in our analysis (Table 1). Patients ranged in age from 11 to 19 years. Over 55% of subjects scored higher on the self-BAT than the ISTH BAT. On average, the self-BAT resulted in scores that were 2.5 points higher (range = -2 to 10). Subjects with identifiable inherited bleeding disorders and low VWF on average scored 3.09 points higher on the self-BAT while those with bleeding of unknown cause (BUC) or anovulatory bleeding scored on average 1.2 points higher. The difference in score would have resulted in a different classification in 2 patients (12.5%). The cutaneous (bruising) domain accounted for the largest contribution to higher self-BAT scores, followed by heavy menstrual bleeding (Figure 1). There did not appear to be a clear association between younger age and a greater difference between the two scores (r = 0.25, p = 0.36), though the number of available subjects did not allow for a powered assessment of this. CONCLUSIONS Based on the results of this study, we feel additional investigation is warranted to validate the tools used to screen for and confirm inherited bleeding disorders in the adolescent population of biological females with heavy menstrual bleeding. The Self-BAT may not be an optimal means of assessment in individuals under the age of 20 years and may overestimate clinical bleeding history. Disclosures No relevant conflicts of interest to declare.