Seminars in thrombosis and hemostasis最新文献

Pediatric cardiac surgery patients are predisposed to blood loss. Blood product administration can lead to complications. Prothrombin complex concentrates (PCCs) offer potential advantages of factor composition, small volume, decreased immunogenicity/infectious risks, and accessibility. The objective of this study was to describe dosing, monitoring, blood product utilization, and thromboembolic complications of administering four-factor PCC (4F-PCC) in pediatric cardiac surgery. We performed a retrospective review of patients aged <18 years undergoing cardiac surgery from June 2020 to May 2022 (inclusive) who received 4F-PCC. Outcomes of interest included 4F-PCC dosing (units/kg) and number of doses administered, chest tube output, blood product administration, donor exposure, length of stay, and thromboembolic events. Eighty-six patients met eligibility criteria. The median (range) age and weight were 0.37 (0.01-16.3) years and 5.3 (1.6-98) kg, respectively. Median (range) total 4F-PCC dose per patient was 25 (9.2-50) units/kg, with 6 patients (7%) receiving a total of two doses. Median (range) 24-hour postoperative packed red blood cells, platelet, plasma, and cryoprecipitate administration volumes were 0 (0-2.57) mL/kg/24 h, 0 (0-1.09), 0 (0-2.64), and 0 (0-0.28 mL/kg/24 h), respectively. Median (range) length of stay and 24-hour postoperative chest tube output were 10 (6-26) days and 1.1 (0.1-4.2) mL/kg/h, respectively. Two (2%) patients experienced a thromboembolic event within 30 days of 4F-PCC administration. These retrospective findings suggest no worsening of hemostatic parameters, a mild median improvement in fibrinogen, low blood product utilization, and low thromboembolism rates following 4F-PCC use in pediatric cardiac surgery.

Persistence of serum antiphospholipid antibodies (aPL) is associated with a high thrombotic risk, both arterial and venous, and with pregnancy complications. Due to the potential morbidity and mortality associated with the presence of aPL, identifying and recognizing risk factors for the development of aPL and thrombosis in aPL carriers may help to prevent and reduce the burden of disease. Multiple elements are involved in the pathomechanism of aPL development and aPL-related thrombosis such as genetics, malignancy, and infections. This review will address the role of both well-known risk factors and their evolution, and of emerging risk factors, including COVID-19, in the development of aPL and thrombosis in aPL carriers.

The incidence of venous thromboembolism (VTE) in the pediatric population has increased more than 10-fold in the last 20 years, as a consequence of the advancement of resuscitation and surgical techniques and the global increase in life expectancy of children suffering from chronic pathologies. Monitoring anticoagulant therapy to achieve outcomes within the target range in childhood VTE, parenteral administration of medications, and frequent blood tests in children are often cumbersome. Availability of safe and effective oral agents with pediatric data to support use would be of clear benefit. A physiologically based pharmacokinetic model was developed to estimate the appropriate dosing schedule for rivaroxaban in children. This incorporated growth/maturation and variability in anthropometrics (e.g., body height, weight, and body mass index), anatomy (e.g., organ weight), physiology (e.g., blood flow rates), metabolism and excretion. Rivaroxaban use in pediatric population underwent a complete investigational program, consisting mainly of one phase I pharmacokinetics/pharmacodynamics trial, three phase II trials, one phase III trial. The phase III trial enrolled 500 patients from birth to <18 years and documented the efficacy and safety of rivaroxaban regimens at dose equivalent to the adult 20 mg dose for the prevention of fatal or symptomatic nonfatal recurrent VTE and major bleeding versus heparin or vitamin K antagonists. Results were similar to those in rivaroxaban studies in adults. The efficacy and safety of rivaroxaban in children reported in the EINSTEIN JUNIOR trial provide further support to previous trials in adults (EINSTEIN Program), which demonstrate a favorable profile for the use of rivaroxaban for the management of VTE in challenging patient populations. Other clinical evidence contributing to the use of rivaroxaban among different risk groups in pediatric VTE population confirms the consistency with principal trial. Our review aims to describe the rationale for using rivaroxaban oral suspension in clinical practice and to summarize its multiple indications in each vascular bed (e.g., cerebral venous thrombosis, symptomatic or asymptomatic central venous catheter-associated thrombosis), etiology, and patients setting.

Venous thromboembolism (VTE) represents a significant global health challenge, ranking as the third leading cause of cardiovascular-related mortality. VTE pervades diverse clinical specialties, posing substantial risks to patient well-being and imposing considerable economic strains on health care systems. While platelets have long been recognized as pivotal players in hemostasis, emerging evidence underscores their multifaceted immune functions and their capacity to engage in crosstalk with other immune cells, such as neutrophils, thereby fostering immune-related thrombosis. Notably, investigations have elucidated the pivotal role of platelets in the pathogenesis of VTE. This review provides a comprehensive overview of platelet physiology, encompassing their activation, secretion dynamics, and implications in VTE. Moreover, it delineates the impact of platelet interactions with various immune cells on the initiation and progression of VTE, explores the correlation between platelet-related laboratory markers and VTE, and elucidates the role of platelets in thrombosis regression.

Preanalytical sample management is critical for a proper assessment of hemostasis parameters, and may differ depending on prescribed tests or additional tests considered to be necessary after initial results. Although there is quite vast literature on this issue, the Working Group of the French Society of Thrombosis and Haemostasis (SFTH) deemed it necessary to make an in-depth literature review and propose recommendations for the proper handling of samples prior to hemostasis assays. This extensive assessment is accessible on-line in French at the SFTH website. Here, a more synthetic view of these recommendations is proposed, supported by easy-to-use tables. The latter respectively deal with the stability of whole blood or fresh plasma, frozen samples, and proper handling of samples forwarded on dry ice. Procedures are classified as recommended, acceptable, not conformed and lacking data. This work involved the retrieval of 125 references, first screened by a working group of 6 experts, then reviewed by 20 other experts in the field. The highly detailed conditions summarized in these tables will hopefully help hemostasis laboratories to secure the conditions recommended for sample collection and transportation. Moreover, as some conditions clearly lacked recommendations, this review can open new fields of investigation for hemostasis preanalytics.

Congenital combined deficiency of factor V (FV) and factor VIII (FVIII; F5F8D, OMIM 227300) is a rare hereditary coagulopathy and accounts for approximately 3% of cases of rare coagulation disorders. The prevalence of this disease in the general population is estimated to be 1:1,000,000 and is significantly higher in regions where consanguineous marriages are permitted, such as the Mideast and South Asia. The disease has an autosomal recessive mode of inheritance and therefore occurs with an equal incidence among males and females. Heterozygous mutation carriers usually do not have clinical manifestations. The molecular basis of this disease differs from that of stand-alone congenital deficiencies of FVIII and FV. F5F8D is caused by mutations in either LMAN1 or MCFD2, which encode components of a cargo receptor complex for endoplasmic reticulum to Golgi transport of FV and FVIII, leading to defects in an intracellular transport pathway shared by these two coagulation factors. Congenital combined deficiency of FV and FVIII is characterized by decreased activities of both FV and FVIII in plasma, usually to 5 to 30% of normal. Clinical manifestations in most cases are represented by mild or moderate hemorrhagic syndrome. The simultaneous decreases of two coagulation factors present complications in the diagnosis and management of the disease. In female patients, the disease requires a special approach for family planning, pregnancy management, and parturition. This review summarizes recent progress in clinical, laboratory, and molecular understanding of this disorder.

Coagulation factor X (FX), originally named Stuart-Prower factor, plays a pivotal role in the coagulation cascade, activating thrombin to promote platelet plug formation and prevent excess blood loss. Genetic variants in F10 may lead to FX deficiency and to impaired coagulation. FX variants are phenotypically classified as being type I, with the concomitant reduction of FX coagulant activity and FX antigen levels or type II, corresponding to a reduction in activity with normal antigen plasma levels. Patients affected with FX deficiency tend to be one of the most seriously affected among those with rare bleeding disorders. They show a variable bleeding tendency strongly associated with FX coagulant activity levels in plasma and may present, in the severe form of the deficiency, life-threatening symptoms such as gastrointestinal and umbilical stump bleeding and intracranial hemorrhages or central nervous system bleeding. Treatment of FX deficiency was originally based on the replacement of the missing factor using fresh frozen plasma, cryoprecipitate and prothrombin complex concentrates; however, a plasma-derived concentrate, shown to be safe and effective in clinical trials, is now available. In addition, novel nonreplacement therapy such as small interference RNA, gene therapy, drug repurposing, and gene editing may also represent novel therapeutic approaches for FX deficiency, but further, much focused studies are needed before considering this emerging therapy in such patients.

Congenital factor VII (FVII) deficiency, the most frequent among the recessively inherited disorders of blood coagulation, is characterized by a wide range of symptoms, from mild mucosal bleeds to life-threatening intracranial hemorrhage. Complete FVII deficiency may cause perinatal lethality. Clinically relevant thresholds of plasma levels are still uncertain, and modest differences in low FVII levels are associated with large differences in clinical phenotypes. Activated FVII (FVIIa) expresses its physiological protease activity only in a complex with tissue factor (TF), which triggers clotting at a very low concentration. Knowledge of the FVIIa-TF complex helps to interpret the clinical findings associated with low FVII activity as compared with other rare bleeding disorders and permits effective management, including prophylaxis, with recombinant FVIIa, which, however, displays a short half-life. Newly devised substitutive and nonsubstitutive treatments, characterized by extended half-life properties, may further improve the quality of life of patients. Genetic diagnosis has been performed in thousands of patients with FVII deficiency, and among the heterogeneous F7 mutations, mostly missense changes, several recurrent variants show geographical distribution and identity by descent. In the general population, common F7 polymorphisms explain a large proportion of FVII level variance in plasma through FVII-lowering effects. Their combination with pathogenic variants may impact on the frequent detection of FVII coagulant levels lower than normal, as well as on mild bleeding conditions. In the twenties of this century, 70 years after the first report of FVII deficiency, more than 200 studies/reports about FVII/FVII deficiency have been published, with thousands of FVII-deficient patients characterized all over the world.