Soluble Platelet Release Factors as Biomarkers for Cardiovascular Disease

Platelets are the main players in thrombotic diseases, where activated platelets not only mediate thrombus formation but also are involved in multiple interactions with vascular cells, inflammatory components, and the coagulation system. Although in vitro reactivity of platelets provides information on the function of circulating platelets, it is not a full reflection of the in vivo activation state, which may be relevant for thrombotic risk assessment in various disease conditions. Therefore, studying release markers of activated platelets in plasma is of interest. While this type of study has been done for decades, there are several new discoveries that highlight the need for a critical assessment of the available tests and indications for platelet release products. First, new insights have shown that platelets are not only prominent players in arterial vascular disease, but also in venous thromboembolism and atrial fibrillation. Second, knowledge of the platelet proteome has dramatically expanded over the past years, which contributed to an increasing array of tests for proteins released and shed from platelets upon activation. Identification of changes in the level of plasma biomarkers associated with upcoming thromboembolic events allows timely and individualized adjustment of the treatment strategy to prevent disease aggravation. Therefore, biomarkers of platelet activation may become a valuable instrument for acute event prognosis. In this narrative review based on a systematic search of the literature, we summarize the process of platelet activation and release products, discuss the clinical context in which platelet release products have been measured as well as the potential clinical relevance.

Does aspirin prevent venous thromboembolism?

Venous thromboembolism (VTE; deep vein thrombosis and/or pulmonary embolism) is a well-established cause of morbidity and mortality in the medical and surgical patient populations. Clinical research in the prevention and treatment of VTE has been a dynamic field of study, with investigations into various treatment modalities ranging from mechanical prophylaxis to the direct oral anticoagulants. Aspirin has long been an inexpensive cornerstone of arterial vascular disease therapy, but its role in the primary or secondary prophylaxis of VTE has been debated. Risk-benefit tradeoffs between aspirin and anticoagulants have changed, in part due to advances in surgical technique and postoperative care, and in part due to the development of safe, easy-to-use oral anticoagulants. We review the proposed mechanisms in which aspirin may act on venous thrombosis, the evidence for aspirin use in the primary and secondary prophylaxis of VTE, and the risk of bleeding with aspirin as compared with anticoagulation.

Potential Usefulness of D-Dimers Assay in Treated Patients with FVIII Deficiency to Detect a Prothrombotic State

Introduction The D-dimer (DD) assay represents a major biological test for the diagnosis and monitoring of thrombotic conditions. DD testing is usually not performed as part of the routine laboratory management of patients with hemophilia (PWH). There is an increasing concern about the risk of thrombotic complications in PWH, whether related to age, the presence of cardiovascular risk factors, invasive thrombogenic procedures, over-correction of FVIII or FIX, or the administration of new therapeutic agents in particular rebalancing agents such as TFPI-inhibiting molecules or Fitusiran. Arterial and venous thrombotic events have indeed recently been reported in PWH treated with these agents. It is therefore important to have simple, easily accessible biological tests available to detect and monitor the development of any prothrombotic condition in PWH with these agents and at increased risk of thrombosis. Baseline DD concentrations in PWH have not been extensively studied yet. Patients and methods We prospectively measured over a 18 months period the DD level in all consecutive PWH with hemophilia A (PWHA) in routine clinics outside bleeding episode, invasive procedure or acute medical or surgical problems. A total of 65 adult PWHA (17-76 yr) with severe (58) to moderate (n=7) disease without inhibitor on replacement therapy with FVIII were included. CRP, fibrinogen, FVIII and VWF levels were also measured at time of DD assay. Results Thirty-three patients had not measurable DD (< 250 ng/ml), 15 had levels below 500 ng/ml, 10 had levels between 500-1000 ng/ml and 7 > 1000 ng/ml. Age>70 (3), smoking (7), arterial vascular disease (2), liver cancer (2) could explain DD > 500 ng/ml in 15/17 patients. Conclusions Most PWHA on replacement therapy with FVIII had low or unmeasurable DD levels. The reasons for high DD level in PWHA do not differ from the general population. In most PWAH, the DD assay could be a useful tool to detect prothrombotic state, potentially related to hemophilia therapies. Disclosures Hermans: Bayer:Consultancy, Research Funding, Speakers Bureau;Pfizer:Consultancy, Research Funding, Speakers Bureau;Shire, a Takeda company:Consultancy, Research Funding, Speakers Bureau;Sobi:Consultancy, Research Funding, Speakers Bureau;Biogen:Consultancy, Speakers Bureau;CAF-DCF:Consultancy, Speakers Bureau;CSL Behring:Consultancy, Speakers Bureau;LFB:Consultancy, Speakers Bureau;Novo Nordisk:Consultancy, Speakers Bureau;Roche:Consultancy, Speakers Bureau;Octapharma:Consultancy, Speakers Bureau;Kedrion:Speakers Bureau;EAHAD:Other;WFH:Other.

SHOX Duplication and Tall Stature in a Patient with Xq Deletion and Vascular Disease

The anomalies of X chromosome are classified as numerical or structural. Concomitant structural anomalies in this chromosome that associate partial loss of its long arm with duplications in its short arm are uncommon. Only a few cases have been published and in most of them the reported patients present ovarian dysfunction, tall stature, and overdosage of the SHOX gene with locus Xp22.33. Considering these reports, we evaluated the case of a woman with a deletion in the long arm of the X chromosome, premature ovarian failure, tall stature, and multiple arterial vascular disease. With the aim to find a relationship between karyotype and phenotype, we explored associated anomalies in Xp and certified the overdosage of the SHOX gene in this case by MLPA. Also, taking into account the fact that the gene locus of the angiotensin-converting enzyme type 2 (ACE2) is located in Xp, our goal was to investigate the influence of this gene in the development of cardiovascular disease. The detection of the gene product of ACE2 by ELISA was undetectable. We have proposed that cytogenetic anomalies in X chromosome could contribute to decrease this protein synthesis in this gender.