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Gender-affirming therapy involves the use of hormones to develop the physical characteristics of the identified gender and suppressing endogenous sex hormone production. Venous thromboembolism (VTE) is a known risk of exogenous estrogen therapy, and while evidence of VTE risk among transgender women using modern gender-affirming hormone therapy (GAHT) is still emerging, it is thought to affect up to 5% of transgender women. Historically, GAHT was associated with a high risk of VTE; however, modern preparations are less thrombogenic mainly due to significantly lower doses used as well as different preparations. This review presents the available literature regarding the following four topics: (1) risk of VTE among transgender women receiving estradiol GAHT, (2) how the route of administration of estradiol affects the VTE risk, (3) perioperative management of GAHT, (4) VTE risk among adolescents on GAHT. There is a need for large, longitudinal studies of transgender women using GAHT to further characterize VTE risk and how this is affected by factors such as patient age, duration of GAHT use, tobacco use, body mass index, and comorbidities. Future studies in these areas could inform the development of clinical guidelines to improve the care of transgender people., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare complication of adenovirus vector-based COVID-19 vaccines. VITT is associated with markedly raised levels of D-dimer; yet, how VITT modulates the fibrinolytic system is unknown., Objectives: We aimed to compare changes in fibrinolytic activity in plasma from patients with VITT, patients diagnosed with venous thromboembolism (VTE) after vaccination but without VITT (VTE-no VITT), and healthy vaccinated controls., Methods: Plasma levels of plasmin-antiplasmin (PAP) complexes, plasminogen, and alpha-2-antiplasmin (α2AP) from 10 patients with VITT, 10 patients with VTE-no VITT, and 14 healthy vaccinated controls were evaluated by enzyme-linked immunosorbent assay and/or Western blotting. Fibrinolytic capacity was evaluated by quantitating PAP levels at baseline and after ex vivo plasma stimulation with 50-nM tissue-type plasminogen activator (tPA) or urokinase for 5 minutes., Results: Baseline PAP complex levels in control and VTE-no VITT individuals were similar but were ∼7-fold higher in plasma from patients with VITT (P < .0001). VITT samples also revealed consumption of α2AP and fibrinogenolysis consistent with a hyperfibrinolytic state. Of interest, VITT plasma produced significantly higher PAP levels after ex vivo treatment with tPA, but not urokinase, compared to the other groups, indicative of increased fibrinolytic potential. This was not due to D-dimer as addition of D-dimer to VTE-no VITT plasma failed to potentiate tPA-induced PAP levels., Conclusion: A marked hyperfibrinolytic state occurs in patients with VITT, evidenced by marked elevations in PAP, α2AP consumption, and fibrinogenolysis. An unidentified plasma cofactor that selectively potentiates tPA-mediated plasminogen activation also appears to exist in the plasma of patients with VITT., Competing Interests: Declaration of competing interests C.B.K., H.H., F.M.M., Z.L., H.S., and R.L.M. have no conflict of interest to declare. J.D.M., P.M., S.C., and H.T. declare that they were coinvestigators on a Medical Research Future Fund (Australia; ID: 2015305) that provided the funds for this project. P.M. also declares being an associate investigator of a grant provided by AstraZeneca related to COVID-19 vaccines, being on the AstraZeneca Advisory Board (unpaid) for the Asia-Pacific Thrombosis with thrombocytopenia meeting, and being on the International Society for Thrombosis and Haemostasis Guidelines and Guidance Committee and was in receipt of the AstraZeneca vaccine exploring the differences in the response to vaccination with the AstraZeneca and Pfizer vaccines., (Copyright © 2023 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights reserved.)

C-reactive protein (CRP) is a member of the highly conserved pentraxin superfamily of proteins and is often used in clinical practice as a marker of infection and inflammation. There is now increasing evidence that CRP is not only a marker of inflammation, but also that destabilized isoforms of CRP possess pro-inflammatory and pro-thrombotic properties. CRP circulates as a functionally inert pentameric form (pCRP), which relaxes its conformation to pCRP* after binding to phosphocholine-enriched membranes and then dissociates to monomeric CRP (mCRP). with the latter two being destabilized isoforms possessing highly pro-inflammatory features. pCRP* and mCRP have significant biological effects in regulating many of the aspects central to pathogenesis of atherothrombosis and venous thromboembolism (VTE), by directly activating platelets and triggering the classical complement pathway. Importantly, it is now well appreciated that VTE is a consequence of thromboinflammation. Accordingly, acute VTE is known to be associated with classical inflammatory responses and elevations of CRP, and indeed VTE risk is elevated in conditions associated with inflammation, such as inflammatory bowel disease, COVID-19 and sepsis. Although the clinical data regarding the utility of CRP as a biomarker in predicting VTE remains modest, and in some cases conflicting, the clinical utility of CRP appears to be improved in subsets of the population such as in predicting VTE recurrence, in cancer-associated thrombosis and in those with COVID-19. Therefore, given the known biological function of CRP in amplifying inflammation and tissue damage, this raises the prospect that CRP may play a role in promoting VTE formation in the context of concurrent inflammation. However, further investigation is required to unravel whether CRP plays a direct role in the pathogenesis of VTE, the utility of which will be in developing novel prophylactic or therapeutic strategies to target thromboinflammation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Dix, Zeller, Stevens, Eisenhardt, Shing, Nero, Morton, Parker, Peter and McFadyen.)

Obesity is a well-recognised risk factor for venous thromboembolism, and increased dosing of pharmacological prophylaxis is recommended in obese inpatients. We performed a clinical decision support intervention by adjusting order sentences of prophylactic enoxaparin within our electronic medical records, which significantly improved appropriate dosing for thromboprophylaxis in obese inpatients at our institution., (© 2022 Royal Australasian College of Physicians.)

Background: Arterial and venous thromboembolic events (TEEs) have been associated with intravenous Ig use, but the risk has been poorly quantified. We aimed to calculate the risk of TEEs associated with exposure to intravenous Ig., Methods: We included participants from UK Biobank recruited over 3 years, data extracted September 2020.The study endpoints were incidence of myocardial infarction, other acute ischaemic heart disease, stroke, pulmonary embolism and other venous embolism and thrombosis.Predictors included known TEE risk factors: age, sex, hypertension, smoking status, type 2 diabetes mellitus, hypercholesterolaemia, cancer and past history of TEE. Intravenous Ig and six other predictors were added in the sensitivity analysis.Information from participants was collected prospectively, while data from linked resources, including death, cancer, hospital admissions and primary care records were collected retrospectively and prospectively.  FINDINGS: 14 794 of 502 492 individuals had an incident TEE during the study period. The rate of incident events was threefold higher in those with prior history of TEE (8 .7%) than those without previous history of TEE (3.0%).In the prior TEE category, intravenous Ig exposure was independently associated with increased risk of incident TEE (OR=3.69 (95% CI 1.15 to 11.92), p=0.03) on multivariate analysis. The number needed to harm by exposure to intravenous Ig in those with a history of TEE was 5.8 (95% CI 2.3 to 88.3).Intravenous Ig exposure did not increase risk of TEE in those with no previous history of TEE., Interpretation: Intravenous Ig is associated with increased risk of further TEE in individuals with prior history of an event with one further TEE for every six people exposed. In practice, this will influence how clinicians consent for and manage overall TEE risk on intravenous Ig exposure., Competing Interests: Competing interests: MK reports Grifols sponsorship for attendance at meeting. ASC reports Grifols sponsorship for attendance at meeting and honorarium from CSL and Lupin for an advisory role. MPL was a Primary Investigator in studies for CSL Behring, UCB Pharma, Novartis, Octapharma. He has also received ad hoc consulting fees from CSL Behring, UCB and an honorarium from Terumo BCT. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Venous thromboembolism (VTE) prophylaxis is effective in reducing VTE events; however, it is underutilized in critically ill patients. We examined trends and risk factors for omission of early thromboprophylaxis within the first 24 h after admission in Australian and New Zealand intensive care units (ICUs) between 2009 and 2020., Methods: Retrospective analysis of data from the Australian New Zealand Intensive Care Society Adult Patient Database. Data were obtained for 1,465,020 adult admissions between 2009 and 2020. Mixed effects logistic regression modeling (accounting for the random effects of the contributing ICUs) was used to identify factors associated with omission of early thromboprophylaxis., Results: A total of 107,486 (7.3%) ICU patients did not receive any form of thromboprophylaxis within the first 24 h after ICU admission without obvious reasons. Omission of early thromboprophylaxis declined from 13.7% in 2009 to 4% in 2020 (by 70.8%) (P < 0.001). Younger patients were more like to miss out on VTE prophylaxis (odds ratios (OR) per 10-year increase 0.94, 95% CI 0.95-0.99). A documented process for monitoring VTE prophylaxis (ORs 0.90, 95% CI 0.87-0.93) and having a medical lead, dedicated for coordinating ICU quality (OR per 0.1 increase in full-time equivalent 0.97, 95% CI 0.93-0.99), are associated with less omission of VTE prophylaxis., Conclusion: Omission of thromboprophylaxis within the first 24 h after ICU admission has declined steadily over the past decade. Documented process for monitoring VTE prophylaxis and having a medical lead for coordinating quality of ICU care could be potential targets for sustaining the improvement in VTE prophylaxis use., (© 2022. The Author(s).)

Important advances in the understanding and management of venous thromboembolism (VTE) have enhanced our ability to diagnose, prevent, and treat VTE. In this narrative review, we discuss how recent advances in the understanding and management of VTE are changing practice, highlight ongoing unmet needs in VTE management, and outline how novel therapeutic targets with little or no influence on hemostasis may help address these unmet needs., Competing Interests: None declared., (Thieme. All rights reserved.)

Acute venous thromboembolism (VTE) is a commonly diagnosed condition and requires treatment with anticoagulation to reduce the risk of embolisation as well as recurrent venous thrombotic events. In many cases, cessation of anticoagulation is associated with an unacceptably high risk of recurrent VTE, precipitating the use of indefinite anticoagulation. In contrast, however, continuing anticoagulation is associated with increased major bleeding events. As a consequence, it is essential to accurately predict the subgroup of patients who have the highest probability of experiencing recurrent VTE, so that treatment can be appropriately tailored to each individual. To this end, the development of clinical prediction models has aided in calculating the risk of recurrent thrombotic events; however, there are several limitations with regards to routine use for all patients with acute VTE. More recently, focus has shifted towards the utility of novel biomarkers in the understanding of disease pathogenesis as well as their application in predicting recurrent VTE. Below, we review the current strategies used to predict the development of recurrent VTE, with emphasis on the application of several promising novel biomarkers in this field. [ABSTRACT FROM AUTHOR]