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Annales de Biologie Clinique Nov 2023The ordering of clinical haemostasis tests is increasing in Burkina Faso due to the newly emergence of cardiovascular and metabolic diseases. However, appropriate local...
The ordering of clinical haemostasis tests is increasing in Burkina Faso due to the newly emergence of cardiovascular and metabolic diseases. However, appropriate local reference values (RV) are lacking. Our study aimed to establish RV for prothrombin time (PT), activated partial thromboplastin time (aPTT) and fibrinogen assays. In 2020, we carried out a cross-sectional study at the transfusion centre of Ouagadougou and included 280 healthy blood donors (140 males and 140 females) as reference subjects (RS) according to CLSI guidelines (C28 A3). From each RS a 5 mL blood sample had been withdrawn in citrated tubes. We performed PT, aPTT and fibrinogen assays using the Sysmex™ CA660 coagulometer and Siemens™ reagents. RV were calculated using the "central 95 percentile" method. Reference values of PT, aPTT and Fibrinogen were respectively [73.84%-117.50%], [20,01-29.45] seconds and [2.04-3.83] g/L for females and [58.81%-112,31%] seconds, [20,9-29,98] seconds and [1.58-3.35] g/L for males. We report for the first time locally appropriate haemostasis RV for the Burkina Faso adult's population. They will be of clinical use to our health care professionals.
PubMed: 37987309
DOI: 10.1684/abc.2023.1835 -
Life (Basel, Switzerland) Jul 2023This study aimed to explore the effects of raloxifene (Rx) and estradiol (E) on prothrombin time (PT), partial thromboplastin time (APTT), coagulation factors (VII, X,...
This study aimed to explore the effects of raloxifene (Rx) and estradiol (E) on prothrombin time (PT), partial thromboplastin time (APTT), coagulation factors (VII, X, XI), and fibrinogen concentrations in rats. Female rats were ovariectomized 11 days prior to starting the treatment. Afterward, they received Rx or E (1, 10, 100, and 1000 µg/kg) or propylene glycol (0.3 mL; vehicle, V) subcutaneously for 3 consecutive days. Plasma was collected to measure the hemostatic parameters. Rx significantly increased PT (8%, at 1000 µg/kg; < 0.05) and APTT at all doses evaluated (32, 70, 67, 30%; < 0.05, respectively). Rx (1, 10, 100, and 1000 µg/kg) decreased the activity of factor VII by -20, -40, -37, and -17% ( < 0.05), respectively, and E increased it by 9, 34, 52, and 29%. Rx reduced factor X activity at 10 and 100 µg/kg doses (-30, and -30% < 0.05), and E showed an increment of 24% with 1000 µg/kg dose only. Additionally, Rx (1, 10, 100 µg/kg) diminished FXI activity (-71, -62, -66; < 0.05), E (1 and 10 µg/kg) in -60 and -38, respectively ( < 0.05), and Rx (1000 µg/kg) produced an increment of 29% ( < 0.05) in fibrinogen concentration, but not E. Our findings suggest that raloxifene has a protective effect on hemostasis in rats.
PubMed: 37511987
DOI: 10.3390/life13071612 -
Haemophilia : the Official Journal of... Nov 2023Mim8 is a next generation bispecific antibody developed for the treatment of haemophilia A (HA). Mim8 has an increased potency compared to first generation molecules....
INTRODUCTION AND AIMS
Mim8 is a next generation bispecific antibody developed for the treatment of haemophilia A (HA). Mim8 has an increased potency compared to first generation molecules. The impact on Mim8 on non-FVIII measuring haemostasis assays was assessed in plasma containing Mim8.
METHODS
Congenital severe HA plasma was spiked with increasing concentrations of Mim8 (0-20 μg/mL). 28 routine and specialist haemostasis assays were used to measure activities. These included tests for prothrombin time (PT), fibrinogen, thrombin, D-dimer, anti-Xa, heparin induced thrombocytopenia (HIT), clotting factors II-XII, factor XIII, von Willebrand factor (VWF), thrombophilia and DRVVT.
RESULTS AND CONCLUSIONS
Less than 10 % difference was calculated between plasma without Mim8 and plasma spiked to 15 μg/mL Mim8 in all assays except thrombin time (-10.5%), APTT-based factor IX, XI and XII, Werfen VWF:RCo (10.6%) and Siemens LA1 (-26.4%) and LA2 (-16.9%). At the expected therapeutic steady state levels of Mim8 (5-8 μg/mL), less than 10% difference was calculated for thrombin time and Werfen VWF:RCo. APTT-based assays of FIX, XI and XII are significantly elevated in the presence of Mim8 and should not be performed. A chromogenic FIX assay could be used to accurately measure FIX activity in the presence of Mim8. There was some interference in the DRVVT method we used so local assessment of other DRVVT methods is advised. Differences in all other tests would not be predicted to affect patient management.
Topics: Humans; Blood Coagulation; von Willebrand Factor; Hemostasis; Blood Coagulation Tests; Prothrombin Time; Hemophilia A
PubMed: 37824563
DOI: 10.1111/hae.14884 -
Annals of Hematology Oct 2023Hemophagocytic lymphohistiocytosis (HLH) has a low incidence and high mortality. In order to improve our understanding of the clinical features and prognostic risk...
Hemophagocytic lymphohistiocytosis (HLH) has a low incidence and high mortality. In order to improve our understanding of the clinical features and prognostic risk factors of adult HLH, we analyzed the clinical characteristics and prognostic risk factors of adult HLH and developed a prognostic model to predict the overall survival (OS) of adult HLH. The clinical characteristics and survival statistics of adult patients with HLH identified at The Second Affiliated Hospital of Chongqing Medical University between February 2012 and October 2020 were retrospectively analyzed to constitute the primary cohort, while patients between 25 October 2020 and 20 March 2023 were collected at the same institution as a validation cohort for the prospective study. A total of 142 patients met the inclusion criteria, with 72 and 70 in the primary cohort and validation cohort respectively. In the primary cohort, the median OS was 102 days, with 37.5%, 34.5%, and 28.7% 1-, 2-, and 3-year OS, respectively. Univariate analysis showed that age, interleukin-10 (IL-10), interleukin-2 receptor (IL-2R), prothrombin time (PT), and indirect bilirubin (IBiL) were correlated with prognosis. Multivariate analysis showed that IL-10 and PT were independent factors affecting OS in adult patients with HLH. A prognostic model consisting of IL-2R, PT, and IL-10 and a corresponding prognostic nomogram were developed adopting the principle of minimum value of Akaike information criterion(AIC). The model has a high prediction accuracy letter (C-index = 0.708). The AUC values of 1-year, 2-year, and 3-year were 0.826, 0.865, and 0.882, correspondingly. In the validation cohort, all patients were divided into high-risk and low-risk groups, and the risk of death was significantly higher in the high-risk group than in the low-risk group (p < 0.01). The calibration curve for the model shows that the Nomogram constructed in this study is very reliable to predict the OS of HLH patients. IL-10 and PT have significant prognostic value in adult HLH. The prognostic model and the nomogram built in this study can forecast the OS of adult HLH patients.
Topics: Humans; Adult; Lymphohistiocytosis, Hemophagocytic; Prognosis; Retrospective Studies; Interleukin-10; Prospective Studies; Receptors, Interleukin-2
PubMed: 37464139
DOI: 10.1007/s00277-023-05368-2 -
The Science of the Total Environment Aug 2023Association linking polycyclic aromatic hydrocarbons (PAHs) to blood coagulation function during pregnancy remains absent. Hence, we conducted a cross-sectional study...
Association linking polycyclic aromatic hydrocarbons (PAHs) to blood coagulation function during pregnancy remains absent. Hence, we conducted a cross-sectional study including 679 late pregnant women (27.2 ± 5.1 years old) drawn from Zunyi birth cohort, Southwest China. During late pregnancy, ten urinary PAHs metabolites and four clinical blood coagulation parameters were measured, including activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT), and fibrinogen (FIB). Multiple linear regression, Restricted cubic spline (RCS) regression, Bayesian kernel machine regression (BKMR), and quantile g-computation (Q-g) regression were used to investigate their single, nonlinear, and mixed associations. Each 2.7-fold increment in 2-hydroxyfluorene (2-OHFlu), 9-hydroxyfluorene (9-OHFlu), 1-hydroxyphenanthrene (1-OHPhe), 2-hydroxyphenanthrene (2-OHPhe), and 3-hydroxyphenanthrene (3-OHPhe) were associated with 0.287 s, 0.190 s, 0.487 s, and 0.396 s shorter APTT, respectively; each 2.7-fold increment in 2-OHPhe was associated with a 0.047 s longer PT; each 2.7-fold increment in 9-hydroxyphenanthrene (9-OHPhe) and 1-hydroxypyrene (1-OHPyr) were associated with 0.087 s and 0.031 s shorter TT, respectively; and each 2.7-fold increment in 1-hydroxynaphthalene (1-OHNap) was associated with 0.032 g/L higher FIB level. The nonlinear association of 2-OHPhe with APTT and 1-OHNap with FIB were also observed. Furthermore, the shortened APTT and TT associated with PAHs mixture were indicated by BKMR and Q-g model. BKMR also revealed a nonlinear association of 2-OHPhe with PT and an interaction effect of 2-OHPhe and 3-OHPhe on APTT. Our results indicate that urinary PAHs was associated with shortened coagulation time and increased FIB. Therefore, more attention should be paid for late pregnant women to prevent PAHs-associated risk of thrombosis. Future perspective studies to confirm our findings and explore the underlying biological mechanism are warranted.
Topics: Humans; Female; Pregnancy; Young Adult; Adult; Polycyclic Aromatic Hydrocarbons; Cross-Sectional Studies; Bayes Theorem; Prothrombin Time; Blood Coagulation; Biomarkers
PubMed: 37149174
DOI: 10.1016/j.scitotenv.2023.163949 -
The Journal of the Association of... Oct 2023Warfarin has been the most extensively used oral anticoagulant (OAC) in medical settings for over 60 years. Its uses, potential adverse effects, and methods for... (Review)
Review
Warfarin has been the most extensively used oral anticoagulant (OAC) in medical settings for over 60 years. Its uses, potential adverse effects, and methods for reversing its effects have been firmly established, rendering it a routine medication in medical settings where most professionals feel at ease employing it. Compared to other vitamin K antagonists (VKAs), such as acenocoumarol, warfarin offers benefits like diminished prothrombin time (PT) assays leading to enhanced oral anticoagulation. Observations over the past few years have seen the inclusion of novel/direct OACs (NOACs/DOACs) in the anticoagulant armamentarium. Although DOACs have several advantages, warfarin still has an important role in subsets of patients where DOACs are contraindicated, not well-tolerated, or cannot afford DOACs due to higher costs. Moreover, there are patient profiles where warfarin is still considered a superior choice compared to DOACs, such as age group of >75 years, kidney failure with creatinine clearance (CrCl) below 30 mL/minute, and prosthetic mechanical valve replacement. Precise management of the international normalized ratio (INR) is crucial for the effectiveness of warfarin treatment. INR monitoring is the major concern in the Indian context due to the lack of laboratories for standardized measurement. Adopting strategies such as point-of-care INR monitoring devices and anticoagulation clinics can help to improve clinical outcomes with warfarin therapy. The present review provides a critical overview of the role of warfarin therapy in the current OAC arsenal and strategies for improving therapeutic control and patient adherence. : Nair T. Critical Appraisal on the Role of Warfarin in the Current Era. J Assoc Physicians India 2023;71(10):31-36.
Topics: Humans; Warfarin; Anticoagulants; International Normalized Ratio; Drug Monitoring
PubMed: 38716521
DOI: 10.59556/japi.71.0378 -
BioRxiv : the Preprint Server For... Aug 2023Antibodies to β2-glycoprotein I (β2GPI) cause thrombosis in antiphospholipid syndrome, however the role of β2GPI itself in regulation of coagulation pathways is not...
BACKGROUND
Antibodies to β2-glycoprotein I (β2GPI) cause thrombosis in antiphospholipid syndrome, however the role of β2GPI itself in regulation of coagulation pathways is not well understood.
METHODS
We developed β2GPI-deficient mice by deleting exon 2 and 3 of using CRISPR/Cas9 and compared the propensity of wild-type (WT) and mice to develop thrombosis using rose bengal and FeCl -induced carotid thrombosis, laser-induced cremaster arteriolar injury, and inferior vena cava (IVC) stasis models. We also compared tail bleeding times and assessed platelet activation in WT and mice in the absence and presence of exogenous β2GPI.
RESULTS
Compared to WT littermates, mice demonstrated a prolonged time to occlusion of the carotid artery after exposure to rose bengal or FeCl , and reduced platelet and fibrin accumulation in cremasteric arterioles after laser injury. Similarly, significantly smaller thrombi were retrieved from the IVC of mice 48 hours after IVC occlusion. The activated partial thromboplastin time (aPTT) and prothrombin time, as well as aPTT reagent- and tissue factor-induced thrombin generation times using plasma from and WT mice revealed no differences. However, we observed significant prolongation of tail bleeding in mice, and reduced P-selectin expression and binding of fibrinogen to the activated α2bβ3 integrin on platelets from these mice after stimulation with low thrombin concentrations; these changes were reversed by exogenous β2GPI. An antibody to PAR3 blocked thrombin-induced activation of WT, but not platelets, as well as the ability of β2GPI to restore the activation response of platelets to thrombin. β2GPI deficiency did not affect platelet activation by a PAR4-activator peptide, or ADP.
CONCLUSIONS
In mice, β2GPI may mediate procoagulant activity by enhancing the ability of PAR3 to present thrombin to PAR4, promoting platelet activation at low thrombin concentrations.
KEY POINTS
β2GPI deficient mice are protected from experimental arterial, venous, and microvascular thrombosis.β2GPI deficient mice display prolonged tail bleeding times and reduced PAR3-facilitated platelet activation by low concentrations of thrombin.
PubMed: 37662286
DOI: 10.1101/2023.08.23.554547 -
The International Journal of Lower... Oct 2023We aim to identify the factors associated with the failure of amputation of one to three toes (index toe amputation) in patients with diabetes and foot infection. We... (Review)
Review
We aim to identify the factors associated with the failure of amputation of one to three toes (index toe amputation) in patients with diabetes and foot infection. We conducted a retrospective cohort of 175 patients with diabetes who were hospitalized for moderate to severe foot infection and underwent amputation of one to three toes. A Poisson regression model was used to determine the prevalence ratio (PR) as a measure of association. The mean age was 63.3 ± 11.4 years. Fifty-three patients presented failure after undergoing toe amputation (30.3%). Multivariate analysis, adjusted for age and sex, showed the following significant variables: severe infection (PR: 1.78; 95% confidence interval [CI]: 1.14-2.78; 0.011), infection by (PR: 2.21; 95% CI: 1.42-3.43; < 0.001), infection by (PR: 2.11; 95% CI: 1.29-3.43; 0.003) and prothrombin time (PR: 1.13; 95% CI: 1.05-1.21; 0.001), obesity (PR: 0.58; 95% CI: 0.37-0.93; 0.024), and haemoglobin value (PR: 0.92; 95% CI: 0.86-0.99; 0.023). About one-third of patients who underwent amputation of one to three toes for diabetic foot infection presented a failure and required a more proximal surgery. Severe infections, isolation of and , and prolonged prothrombin time were associated with a higher prevalence of failure. However, obesity and an elevated haemoglobin level were associated with a lower prevalence of failure.
PubMed: 37885211
DOI: 10.1177/15347346231207679 -
Thrombosis Research Nov 2023Heat-related illness is becoming more problematic due to ongoing global warming. Heat-related injury causes systemic inflammation and coagulopathy, due to leukocyte,... (Review)
Review
Heat-related illness is becoming more problematic due to ongoing global warming. Heat-related injury causes systemic inflammation and coagulopathy, due to leukocyte, platelet, and vascular endothelial cell activation and injury. Hyperthermia directly modulates platelet function and can induce cellular damage. Meanwhile, heat also affects platelet function via activated coagulation, excess inflammation, production of cytokines, and heat shock proteins. Aberrant hyperthermia-induced interactions between leukocytes and endothelial cells are also involved in platelet regulation. Heat-induced coagulopathy commonly progresses to disseminated intravascular coagulation (DIC), leading to multiple organ failure and in some cases enhanced bleeding. Consequently, platelet count, prothrombin time, and DIC score are useful for evaluating the severity of heat-related illness in addition to other organ damage markers such as Glasgow Coma Scale, creatinine, and bilirubin. Despite the increasing risk, therapeutic modalities targeting platelets are limited and no established therapy exists. In this review, we summarize the current knowledge about the role of platelets in the pathogenesis, diagnosis, and management of heat-related illness.
Topics: Humans; Disseminated Intravascular Coagulation; Endothelial Cells; Blood Coagulation Disorders; Hemostasis; Inflammation
PubMed: 35989192
DOI: 10.1016/j.thromres.2022.08.009 -
International Journal of Molecular... Sep 2023Lenalidomide, a well-established drug for the treatment of multiple myeloma, significantly enhances patients' survival. Previous clinical studies have demonstrated that...
Lenalidomide, a well-established drug for the treatment of multiple myeloma, significantly enhances patients' survival. Previous clinical studies have demonstrated that its main side effect is an increased risk of thrombotic events. However, the underlying mechanism remains unexplored. Therefore, this study aims to elucidate the mechanism and offer insights into the selection of clinical thrombotic prophylaxis drugs. Firstly, we conducted a retrospective analysis of clinical data from 169 newly diagnosed multiple myeloma patients who received lenalidomide. To confirm the impact of lenalidomide on thrombosis formation, FeCl-induced thrombosis and deep venous thrombosis models in mice were established. To investigate the effects of lenalidomide on platelet function, both in vivo and in vitro experiments were designed. During the follow-up period, 8 patients developed thrombotic events, including 8 venous and 1 arterial. Further investigation using mice models demonstrated that lenalidomide significantly promoted the formation of venous thrombosis, consistent with clinical findings. To elucidate the underlying mechanism, assays were conducted to assess platelet function and coagulation. We observed that lenalidomide did not have any noticeable impact on platelet function, both in vitro and in vivo, while administration of lenalidomide resulted in significant decreases in prothrombin time, thrombin time, and prothrombin time ratio in patients, as well as a remarkable reduction in tail-bleeding time in mice. The administration of lenalidomide had no significant impact on platelet function, which may affect venous thrombus formation by affecting coagulation. Therefore, anticoagulant drugs may be superior to antiplatelet drugs in the selection of clinical thrombus prophylaxis.
PubMed: 37762399
DOI: 10.3390/ijms241814097