BACKGROUND AND OBJECTIVES: Many transgender youth experience gender dysphoria, a risk factor for suicide. Gender-affirming hormone therapy (GAHT) ameliorates this risk but may increase the risk for thrombosis, as seen from studies in adults. The aim with this study was to examine thrombosis and thrombosis risk factors among an exclusively adolescent and young adult transgender population. METHODS: This retrospective chart review was conducted at a pediatric hospital-associated transgender health clinic. The primary outcome was incidence of arterial or venous thrombosis during GAHT. Secondary measures included the prevalence of thrombosis risk factors. RESULTS: Among 611 participants, 28.8% were transgender women and 68.1% were transgender men. Median age was 17 years at GAHT initiation. Median follow-up time was 554 and 577 days for estrogen and testosterone users, respectively. Individuals starting GAHT had estradiol and testosterone levels titrated to physiologic normal. Multiple thrombotic risk factors were noted among the cohort, including obesity, tobacco use, and personal and family history of thrombosis. Seventeen youth with risk factors for thrombosis were referred for hematologic evaluation. Five individuals were treated with anticoagulation during GAHT: 2 with a previous thrombosis and 3 for thromboprophylaxis. No participant developed thrombosis while on GAHT. CONCLUSIONS: In this study, we examined thrombosis and thrombosis risk factors in an exclusively adolescent and young adult population of transgender people receiving GAHT. These data suggest that GAHT in youth, titrated within physiologic range, does not carry a significant risk of thrombosis in the short-term, even with the presence of preexisting thrombosis risk factors.
Background: Iron deficiency anemia (IDA) affects millions of children worldwide. Oral iron replacement is effective but often poorly tolerated. Intravenous iron has been demonstrated to have utility in all ages, but pediatric use remains limited. Low molecular weight iron dextran (LMWID) has a dosing range capable of replacing iron deficits in a single infusion and has been evaluated in small pediatric cohorts, but additional safety and efficacy data are limited. Here, we evaluate the safety and efficacy of LMWID in association with an electronic medical record (EMR)-based effort to optimize dosing.Procedure: A retrospective IRB-approved investigation of LMWID utilization at a tertiary pediatric hospital between January 1, 2016 and March 31, 2020 was undertaken to evaluate the therapeutic efficacy and frequency/severity of infusion-related adverse event (AE) in children and adolescents receiving LMWID. Patient demographics and LMWID dosing characteristics were collected, and primary outcome measures included laboratory response and the incidence/severity of any infusionrelated events. The utilization of an EMR-based nomogram for LMWID dosing was also evaluated.Results: A total of 254 infusions for 191 patients were included (ages 0.7-20.9 years), most with IDA. LMWID replaced at least 75% of the estimated iron deficit in a single infusion for 76% of patients. The mean hemoglobin and ferritin increases were 2.1 g/dl and >100 ng/ml, respectively. Infusion-related AEs were rare, occurring in only 12/254 (4.7%) of infusions and 67% during the test dose; each rapidly resolved without longterm sequelae. No AEs occurred in those <10 years of age. Premedication use markedly decreased with nomogram use without a change in AE rate. Conclusions:In a large institutional cohort, LMWID was well tolerated in children and adolescents, with most patients having their total iron deficits relieved in a single infusion. These data support expanded use of LMWID in the management of pediatric iron deficiency.
Increasing numbers of pediatric ventricular assist device (VAD) patients are being anticoagulated with the parenteral direct thrombin inhibitor bivalirudin because it is reportedly associated with fewer bleeding and thrombotic events. With expanded use, management is shifting from a handful of experts to a wider pool of clinicians and trainees, increasing the importance of identifying broadly acceptable, standardized monitoring assays. The pharmacokinetics of bivalirudin have not been well-studied in the pediatric population and drug monitoring in all ages has been problematic for critically ill patients who require intermediate or longer-term therapeutic anticoagulation. The dilute thrombin time (dTT), available in many clinical laboratories, has been suggested as a potentially superior alternative to the activated partial thromboplastin time (aPTT), but results have been inconsistent. As clinical use of the dTT (c-dTT) for monitoring bivalirudin increased at our institution, we sought to evaluate the performance of commercially available, "research only" functional bivalirudin assays with calibrators and controls to measure bivalirudin's anticoagulation effect, utilizing residual plasmas and clinical data from VAD patients treated with bivalirudin. Residual citrated, platelet poor plasma samples from clinically ordered laboratory tests in VAD patients were collected and stored frozen at -70 oC from February 8, 2018, to January 4, 2021. With IRB approval, the samples were analyzed in conjunction with medical record review. Two experimental assay kits were utilized, ex-dTT: a dilute thrombin time assay (Hemoclot, Hyphen-Biomed, FR) and ex-anti FIIa: a chromogenic anti-factor IIa assay (BiophenDTI, Hyphen-Biomed, FR). Bivalirudin calibrators (Biophen, Hyphen-Biomed, FR) were used to develop a standard curve for the assays. Controls of low and high (1.5 and 4 microgram/mL) bivalirudin (Biophen, Hyphen-Biomed, FR) were used for quality control of the assays. Results from the two experimental assays were compared with available standard laboratory monitoring when results were available. In total, 115 residual plasma samples from 11 different patients (up to 16 samples per patient) were analyzed. Subjects included 1 adult (37 yr.) and 10 pediatric patients (0-18 yr.). There was excellent correlation between the two experimental assays (Fig. 1A). Correlation was good between the c-dTT and each of the experimental assays; however, with a clinical laboratory platform change (instrument, reagents) midway through sample collection, the c-dTT results shifted substantially in their corresponding estimate of bivalirudin concentration (Figs 1B and C). Activated partial thromboplastin time (aPTT) had poor correlation with the c-dTT and with each of the experimental assays (Fig. 1D). Here we report results from two commercially available kits that estimate bivalirudin concentration using dTT or chromogenic anti-factor IIa assays, in comparison with clinically generated results from VAD patients treated with bivalirudin. Our findings agree with previous observations that the aPTT shows poor correlation with dTT assays (clinically used and experimental) over days and weeks of anticoagulation. The two experimental assays had excellent correlation with each other and good correlation with the c-dTT; however, the fact that the c-dTT results shifted dramatically with a clinical laboratory platform change is illustrative of the need for a bivalirudin-specific monitoring assay as an essential tool for improving outcomes at our center and across centers. More research is needed to understand which type of monitoring assay (dTT or anti-FIIa) may be better suited to particular clinical circumstances. Figure 1 Figure 1. Disclosures Lorts: Abbott: Consultancy; Medtronic: Consultancy; Berlin Heart: Consultancy; Syncardia: Consultancy; Abiomed: Consultancy.
An estimated 2-3% of US youth identify as transgender or gender non-conforming (hereafter transgender). Transgender youth may suffer from gender dysphoria, a condition associated with many health risks, including high risk of suicide. Transgender individuals have a 40% greater risk of attempting suicide than cis-gender individuals. Gender-affirming hormone therapy (GAHT) is associated with improvement of gender dysphoria and amelioration of the risk of suicide. GAHT consists of either estrogen [for transgender women (TGW)] or testosterone [for transgender men (TGM)]. However, GAHT may be associated with other risks, most notably thrombosis. Numerous studies documented increased thrombosis risk in cis-gender women using exogenous estrogen for contraception or hormone replacement therapy. Studies of GAHT suggest a risk of thrombosis with estrogen use; however, this data is not uniform. Studies of testosterone replacement in cis-gender show conflicting results with respect to thrombosis risk. All previous studies examining the risk of thrombosis with GAHT have included adults exclusively. Therefore we sought to determine the risk of thrombosis in a cohort of transgender youth receiving standardized GAHT regimens. Transgender youth have potential for a much longer exposure to GAHT, thus having different life-time risk of thrombosis than patients that start GAHT at an older age. Of all 1406 patients seen at the Cincinnati Children's Medical Center Transgender Health Clinic since its inception, 611 subjects started GAHT and were eligible for inclusion in the cohort. Of these, 176 (28.8%) identified as female, 416 (68.1%) as male, and 19 (3.1%) as non-binary. Thrombosis risks were common among the cohort: 34.5% had obesity, 15.4% used tobacco, 4.6% had migraine with aura, and 8.0% had a family history of thrombosis. Three subjects had a prior history of thrombosis: 2 with venous thromboembolism (VTE) and one with a stroke. 53.7% of the cohort had previously used hormones, most commonly for menstrual suppression. Of those with prior hormone use, the vast majority had used progesterone-only methods (5.7% previously used estrogen-containing contraceptives). All patients initiating GAHT were treated according to current guidelines with monitoring of estrogen and testosterone levels and titration of GAHT doses accordingly. Overall, 29.8% initiated estrogen therapy and 70.2% started testosterone therapy. Among the cohort, 17 individuals were referred to Hematology for evaluation for thrombosis risk prior to starting GAHT. The most common laboratory abnormality for these individuals was elevated factor VIII, elevated plasminogen-activator inhibitor 1 (PAI-1), and the PAI-1 polymorphism. Two TGW and one TGM started thromboprophylaxis prior to initiating GAHT due to thrombotic risk factors. Despite the presence of preexisting risk factors, no individual in the cohort developed a thrombosis (VTE or stroke) during GAHT. This is the first study to examine thrombosis risk of GAHT in an exclusively adolescent and young adult population. While there were no incidents of thrombosis in our cohort, we found individuals at risk for thrombosis. Careful history and counseling regarding risks are needed when discussing initiation of GAHT for transgender individuals. Additionally, further studies looking at long-term risk are needed. Disclosures Mullins: Takeda, Bayer: Other: Advisory Board.
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