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JACC. Asia Aug 2023Little is known about the relationship between coagulation biomarkers and clinical outcomes in patients with atrial fibrillation (AF) treated with anticoagulants,...
BACKGROUND
Little is known about the relationship between coagulation biomarkers and clinical outcomes in patients with atrial fibrillation (AF) treated with anticoagulants, especially direct oral anticoagulants (DOACs) and warfarin.
OBJECTIVES
This subcohort study evaluated the association between coagulation biomarkers and clinical outcomes in elderly Japanese patients with nonvalvular AF using the ANAFIE (All Nippon AF In the Elderly) Registry.
METHODS
Patients with a definitive diagnosis of nonvalvular AF and aged ≥75 years at enrollment were included. At enrollment, biomarker levels for D-dimer, thrombin-antithrombin complex (TAT), prothrombin fragment 1+2 (F1+2), and soluble fibrin monomer complex (SFMC), along with data on anticoagulant use, were recorded.
RESULTS
Of the 3,194 patients, 95.1% were using oral anticoagulants (OACs) (71.7% DOACs, 23.4% warfarin). D-dimer, TAT, and F1+2 levels, as well as the proportion of patients with a positive SFMC, were lower among those receiving OACs compared with those not receiving OACs. In the DOAC group, higher levels of D-dimer (≥1.0 μg/mL) and TAT (>3 ng/mL) were significantly associated with increased incidences of cardiovascular (CV) events (stroke, myocardial infarction, cardiac intervention, heart failure, and CV death), all-cause death, and CV death. In the warfarin group, higher levels of D-dimer were significantly associated with increased rates of all-cause death, higher levels of TAT with increased major bleeding, and positive SFMC with increased major bleeding and CV events.
CONCLUSIONS
Higher levels of coagulation biomarkers were associated with a higher risk of worse clinical outcomes, and the relationships between the coagulation biomarkers and outcomes differed between the DOAC and warfarin groups. (Prospective Observational Study in Late-Stage Elderly Patients with Non-Valvular Atrial Fibrillation All Nippon AF In Elderly Registry-ANAFIE Registry; UMIN000024006).
PubMed: 37614535
DOI: 10.1016/j.jacasi.2023.06.004 -
Journal of Clinical Medicine Jul 2023The measurement and identification of plasma biomarkers can support the estimation of risk and diagnosis of deep vein thrombosis (DVT) associated with the use of a... (Review)
Review
BACKGROUND
The measurement and identification of plasma biomarkers can support the estimation of risk and diagnosis of deep vein thrombosis (DVT) associated with the use of a peripherally inserted central catheter (PICC).
OBJECTIVES
This systematic review and meta-analysis aimed to identify the association between the levels of potential biomarkers that reflect the activation of the blood system, long-term vascular complications, inflammatory system, and the occurrence of PICC-related DVT.
METHODS
Seven electronic databases (Embase, Web of Science, Medline, Scopus, Cinahl, Cochrane Central Register of Controlled Trials, and ERIC) were searched to identify literature published until December 2022. Studies were required to report: (I) adult and pediatric patients, outpatient or admitted to clinical, surgical, or ICU with PICC; (II) patients with PICC-related DVT and patients without PICC-related DVT as a comparator; and (III) at least one biomarker available. The Newcastle-Ottawa Scale was used to evaluate the quality of the studies. Study precision was evaluated by using a funnel plot for platelets level. We provided a narrative synthesis and meta-analysis of the findings on the biomarkers' outcomes of the studies. We pooled the results using random effects meta-analysis. The meta-analysis was conducted using Review Manager software v5.4. This systematic review is registered in PROSPERO (CRD42018108871).
RESULTS
Of the 3564 studies identified (after duplication removal), 28 were included. PICC-related DVT was associated with higher D-dimers (0.37 μg/mL, 95% CI 0.02, 0.72; = 0.04, I = 92%; for heterogeneity < 0.00001) and with higher platelets (8.76 × 10/L, 95% CI 1.62, 15.91; = 0.02, I = 41%; for heterogeneity = 0.06).
CONCLUSIONS
High levels of D-dimer and platelet were associated with DVT in patients with PICC. However, biomarkers such as APTT, fibrinogen, FDP, glucose, hemoglobin, glycated hemoglobin, INR, prothrombin time, prothrombin fragment 1.2, the thrombin-antithrombin complex, and WBC were not related to the development of DVT associated with PICC.
PubMed: 37445515
DOI: 10.3390/jcm12134480 -
JAMA Network Open Feb 2024Intracerebral hemorrhage (ICH) associated with direct oral anticoagulant (DOAC) use carries extremely high morbidity and mortality. The clinical effectiveness of...
IMPORTANCE
Intracerebral hemorrhage (ICH) associated with direct oral anticoagulant (DOAC) use carries extremely high morbidity and mortality. The clinical effectiveness of hemostatic therapy is unclear.
OBJECTIVE
To compare the clinical and radiological outcomes of DOAC-associated ICH treated with prothrombin complex concentrate (PCC) vs conservative management.
DESIGN, SETTING, AND PARTICIPANTS
In this population-based, propensity score-weighted retrospective cohort study, patients who developed DOAC-associated ICH from January 1, 2016, to December 31, 2021, in Hong Kong were identified. The outcomes of patients who received 25 to 50 IU/kg PCC with those who received no hemostatic agents were compared. Data were analyzed from May 1, 2022, to June 30, 2023.
MAIN OUTCOMES AND MEASURES
The primary outcome was modified Rankin scale of 0 to 3 or returning to baseline functional status at 3 months. Secondary outcomes were mortality at 90 days, in-hospital mortality, and hematoma expansion. Weighted logistic regression was performed to evaluate the association of PCC with study outcomes. In unweighted logistic regression models, factors associated with good neurological outcome and hematoma expansion in DOAC-associated ICH were identified.
RESULTS
A total of 232 patients with DOAC-associated ICH, with a mean (SD) age of 77.2 (9.3) years and 101 (44%) female patients, were included. Among these, 116 (50%) received conservative treatment and 102 (44%) received PCC. Overall, 74 patients (31%) patients had good neurological recovery and 92 (39%) died within 90 days. Median (IQR) baseline hematoma volume was 21.7 mL (3.6-66.1 mL). Compared with conservative management, PCC was not associated with improved neurological recovery (adjusted odds ratio [aOR], 0.62; 95% CI, 0.33-1.16; P = .14), mortality at 90 days (aOR, 1.03; 95% CI, 0.70-1.53; P = .88), in-hospital mortality (aOR, 1.11; 95% CI, 0.69-1.79; P = .66), or reduced hematoma expansion (aOR, 0.94; 95% CI, 0.38-2.31; P = .90). Higher baseline hematoma volume, lower Glasgow coma scale, and intraventricular hemorrhage were associated with lower odds of good neurological outcome but not hematoma expansion.
CONCLUSIONS AND RELEVANCE
In this cohort study, Chinese patients with DOAC-associated ICH had large baseline hematoma volumes and high rates of mortality and functional disability. PCC treatment was not associated with improved functional outcome, hematoma expansion, or mortality. Further studies on novel hemostatic agents as well as neurosurgical and adjunctive medical therapies are needed to identify the best management algorithm for DOAC-associated ICH.
Topics: Humans; Female; Aged; Male; Conservative Treatment; Cohort Studies; Retrospective Studies; Factor IX; Hemostatics; Cerebral Hemorrhage; Hematoma; Anticoagulants; Blood Coagulation Factors
PubMed: 38319661
DOI: 10.1001/jamanetworkopen.2023.54916 -
EJHaem Feb 2024Lumbar puncture (LP) is rarely complicated by cerebral vein thrombosis (CVT), especially if other risk factors coexist. We describe the case of a 28-year-old woman who...
Lumbar puncture (LP) is rarely complicated by cerebral vein thrombosis (CVT), especially if other risk factors coexist. We describe the case of a 28-year-old woman who developed CVT after corticosteroid treatment and LP performed for suspected multiple sclerosis. The day after LP, she developed intense headache and on Day 8 generalized tonic-clonic seizures. A brain computed tomography scan showed thrombosis of the superior sagittal sinus and cortical veins. Thrombophilia screening showed heterozygous G20210A prothrombin mutation. Anticoagulant therapy with low molecular weight heparin and then warfarin was administered until Day 16 after LP, when a brain magnetic resonance imaging showed a subdural hematoma. Warfarin was interrupted and dabigatran was started. The patient recovered completely, both from the initial thrombotic event and the hemorrhagic complication. This case highlights the importance to keep in mind CVT in the differential diagnosis of post-LP headache not responsive to standard therapy, and suggests that dabigatran can be considered an effective and safe treatment of CVT.
PubMed: 38406529
DOI: 10.1002/jha2.803 -
Journal of Pediatric Intensive Care Sep 2023Prothrombin complex concentrates (PCCs) are used to manage bleeding in critically ill children. We performed a repeat cross-sectional study using the Pediatric Health...
Prothrombin complex concentrates (PCCs) are used to manage bleeding in critically ill children. We performed a repeat cross-sectional study using the Pediatric Health Information System registry to describe PCC utilization in the U.S. children's hospitals over time and determine the relationship between PCC use and specific risk factors for bleeding. We included children < 18 years who received three-factor or four-factor PCC during hospital admission between January 2015 and December 2020 to describe the association between PCC therapy, anticoagulation therapies, and inherited or acquired bleeding diatheses. PCC use steadily increased over the 6-year study period (from 1.3 to 4.6 per 10,000 encounters). Patients exhibited a high degree of critical illness, with 85.0% requiring intensive care unit admission and a mortality rate of 25.8%. PCCs were used in a primarily emergent or urgent fashion (32.6 and 39.3%, respectively) and more frequently in surgical cases (79.0% surgical vs. 21.0% medical). Coding analysis suggested a low rate of chronic anticoagulant use which was supported by review of concomitant anticoagulant medications. PCC use is increasing in critically ill children and does not correlate with specific anticoagulant therapy use or other bleeding risk factors. These findings suggest PCC use is not limited to vitamin K antagonist reversal. Indications, efficacy, and safety of PCC therapy in children require further study.
PubMed: 37565019
DOI: 10.1055/s-0041-1731686 -
American Journal of Obstetrics and... Mar 2024More than 150 million women worldwide use oral contraceptives. Women with inherited thrombophilia and carriers of certain thrombophilia gene variants, such as factor V...
BACKGROUND
More than 150 million women worldwide use oral contraceptives. Women with inherited thrombophilia and carriers of certain thrombophilia gene variants, such as factor V Leiden and the prothrombin, are at an increased risk for venous thromboembolism, especially when combined with oral contraceptive use. Venous thromboembolism is a complex disorder involving many genetic risk factors, and recently, polygenic risk scores have been proposed to capture a significant proportion of the genetic risk of venous thromboembolism.
OBJECTIVE
The aim of this study was to estimate the risk for developing venous thromboembolism when initiating oral contraceptive use (first 2 years) and during continued use among women with a high genetic liability.
STUDY DESIGN
We used a prospective study design in which 244,420 participants from the UK Biobank were followed from birth. The effect of oral contraceptive use during the first 2 years and in the remaining years of oral contraceptive use on the risk of developing venous thromboembolism was estimated using a Cox regression with a time-dependent exposure variable. Women were stratified according to their polygenic risk scores and whether they were carriers of factor V Leiden and/or prothrombin variants.
RESULTS
When genetic risk was not considered, an increased risk for venous thromboembolism was observed during the first 2 years of oral contraceptive use (hazard ratio, 3.09; 95% confidence interval, 3.00-3.20) but not during continued use (hazard ratio, 0.92; 95% confidence interval, 0.80-1.05). However, when genetic risk was considered, women in the highest polygenic risk score category had a more pronounced risk of developing a venous thromboembolism during the first 2 years of oral contraceptive use (hazard ratio, 6.35; 95% confidence interval, 4.98-8.09), and a high risk was also observed among factor V Leiden (hazard ratio, 5.73; 95% confidence interval, 5.31-6.17) and prothrombin variant carriers (hazard ratio, 5.23; 95% confidence interval, 4.67 - 5.87). A high polygenic risk score in combination with being a factor V Leiden and prothrombin variant carrier conferred the highest risk for developing a venous thromboembolism during the first 2 years of oral contraceptive use (hazard ratio, 14.8; 95% confidence interval, 9.28-23.6). Women with a high genetic liability also had an increased risk during continued use but it was less pronounced, and the highest risk was conferred to carriers of both factor V Leiden and the prothrombin variant (hazard ratio, 4.93; 95% confidence interval, 3.16-7.7).
CONCLUSION
Evaluating polygenic risk can identify additional venous thromboembolism risk that is not captured in the commonly investigated genes for inherited thrombophilia. Our results indicate that oral contraceptive use is associated with an increased risk for developing a venous thromboembolism, particularly among women with a high genetic predisposition, and that oral contraceptive use dramatically increases the risk thereof short after initiation of use, which decreases with continued use. This suggests that the polygenic risk score could be used to identify women who are at high risk for developing a venous thromboembolism and advise them on alternative methods of contraception.
Topics: Humans; Female; Venous Thromboembolism; Contraceptives, Oral; Prospective Studies; Prothrombin; UK Biobank; Biological Specimen Banks; Thrombophilia; Risk Factors; Contraception; Factor V
PubMed: 37734636
DOI: 10.1016/j.ajog.2023.09.012 -
Beijing Da Xue Xue Bao. Yi Xue Ban =... Dec 2023To investigate whether anti-phosphatidylserine/prothrombin antibodies and its IgG or IgM subtypes were correlated with unexplained recurrent miscarriages.
OBJECTIVE
To investigate whether anti-phosphatidylserine/prothrombin antibodies and its IgG or IgM subtypes were correlated with unexplained recurrent miscarriages.
METHODS
In our a single-center retrospective study, 283 patients with at least one unexplained miscarriage who visited the Third Hospital of Peking University between January 2021 and August 2023, aged between 18-40 years, and tested for anti-phosphatidylserine/prothrombin antibodies IgG or IgM subtypes, were included. The patients with either positive IgG or IgM anti-phosphatidylserine/prothrombin antibody were regarded as positive for anti-phosphatidylserine/prothrombin antibody. SPSS 26.0 software was used for statistical analysis. Chi-square test and Logistic regression analysis were used to study the correlation of anti-phosphatidylserine/prothrombin antibodies and its IgG or IgM subtypes with unexplained recurrent miscarriages. And the diagnostic sensitivity, specificity, the positive predictive value, the negative predictive value of anti-phosphatidylserine/prothrombin antibodies and its IgG or IgM subtypes in unexplained miscarriages was calculated with four-fold table.
RESULTS
Chi-square analysis showed that anti-phosphatidylserine/prothrombin antibodies and its IgM subtypes were correlated with recurrent miscarriages (both < 0.05), while the IgG subtype was not correlated with recurrent miscarriages (>0.05). After adjusting with anticardiolipin antibodies, anti-β glycoprotein antibodies, lupus anticoagulants, antinuclear antibodies, and age by Logistic regression analysis, anti-phosphatidylserine/prothrombin antibodies were correlated with unexplained recurrent miscarriages (=2.084, 95% 1.045-4.155, < 0.05), and anti-phosphatidylserine/prothrombin antibody IgM subtypes were correlated with unexplained recurrent miscarriages (=2.368, 95% 1.187-4.722, < 0.05).The sensitivity of anti-phosphatidylserine/prothrombin antibody in recurrent miscarriage was 65.43%, the specificity was 48.51%, the positive predictive value was 33.76%, and the negative predictive value was 77.78%. In the patients with recurrent miscarriages with negative classical antiphospholipid antibodies, the sensitivity of anti-phosphatidylserine/prothrombin antibody was 59.09%, the specificity was 63.23%, the positive predictive value was 40.63%, and the negative predictive value was 78.40%. The sensitivity of the anti-phosphatidylserine/prothrombin antibody IgM subtype for the diagnosis of recurrent miscarriage was 65.43%, the specificity was 50.99%, the positive predictive value was 34.87%, and the negative predictive value was 78.63%.
CONCLUSION
Anti-phosphatidylserine/prothrombin antibody and IgM subtype antibody are correlated with unexplained recurrent miscarriages in patients with at least one unexplained miscarriage. Whether positive anti-phosphatidylserine/prothrombin antibody or IgM subtype could predict future unexplained recurrent miscarriages warrants a prospective study.
Topics: Pregnancy; Female; Humans; Adolescent; Young Adult; Adult; Prothrombin; Retrospective Studies; Phosphatidylserines; Prospective Studies; beta 2-Glycoprotein I; Antibodies, Antiphospholipid; Antiphospholipid Syndrome; Antibodies, Anticardiolipin; Abortion, Habitual; Immunoglobulin G; Immunoglobulin M
PubMed: 38101789
DOI: 10.19723/j.issn.1671-167X.2023.06.016 -
Liver Transplantation : Official... Oct 2023In patients with HCC awaiting liver transplantation (LT), there is a need to identify biomarkers that are superior to AFP in predicting prognosis. AFP-L3 and...
In patients with HCC awaiting liver transplantation (LT), there is a need to identify biomarkers that are superior to AFP in predicting prognosis. AFP-L3 and des-gamma-carboxyprothrombin (DCP) play a role in HCC detection, but their ability to predict waitlist dropout is unknown. In this prospective single-center study commenced in July 2017, 267 HCC patients had all 3 biomarkers obtained at LT listing. Among them, 96.2% received local-regional therapy, and 18.8% had an initial tumor stage beyond Milan criteria requiring tumor downstaging. At listing, median AFP was 7.0 ng/mL (IQR 3.4-21.5), median AFP-L3 was 7.1% (IQR 0.5-12.5), and median DCP was 1.0 ng/mL (IQR 0.2-3.8). After a median follow-up of 19.3 months, 63 (23.6%) experienced waitlist dropout, while 145 (54.3%) received LT, and 59 (22.1%) were still awaiting LT. Using Cox proportional hazards analysis, AFP-L3≥35% and DCP≥7.5 ng/mL were associated with increased waitlist dropout, whereas AFP at all tested cutoffs, including ≥20,≥ 100, and≥250 ng/mL was not. In a multivariable model, AFP-L3≥35% (HR 2.25, p =0.04) and DCP≥7.5 ng/mL (HR 2.20, p =0.02) remained associated with waitlist dropout as did time from HCC diagnosis to listing ≥ 1 year and increasing MELD-Na score. Kaplan-Meier probability of waitlist dropout within 2 years was 21.8% in those with AFP-L3<35% and DCP<7.5 ng/mL, 59.9% with either AFP-L3 or DCP elevated, and 100% for those with both elevated ( p <0.001). In this prospective study, listing AFP-L3% and DCP were superior to AFP in predicting waitlist dropout with the combination of AFP-L3≥35% and DCP≥7.5 ng/mL associated with a 100% risk of waitlist dropout, thus clearly adding prognostic value to AFP alone.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Biomarkers, Tumor; Prospective Studies; alpha-Fetoproteins; Liver Transplantation; Biomarkers; Prothrombin
PubMed: 37159217
DOI: 10.1097/LVT.0000000000000149 -
Expert Review of Hematology 2024Thrombophilia testing (TT) is a laboratory procedure designed to detect the risk factors involved in the pathogenesis of vascular occlusions. The role of TT is also... (Review)
Review
INTRODUCTION
Thrombophilia testing (TT) is a laboratory procedure designed to detect the risk factors involved in the pathogenesis of vascular occlusions. The role of TT is also controversial because it has a limited impact on the choice and duration of antithrombotic treatments.
AREAS COVERED
We reviewed, by examining MEDLINE up to October 2023. Accepted and not accepted thrombophilia markers are discussed along with the appropriateness or not of prescribing TT in several conditions such as: provoked and unprovoked venous thromboembolism (VTE), women who are planning a pregnancy whose relatives had VTE or have a hereditary thrombophilia, before assumption of estro-progestins, after multiple pregnant loss, arterial thrombosis, retinal vein occlusion, and splanchnic vein thrombosis.
EXPERT OPINION
TT is not essential in the management of VTE, but it may be useful for limiting adverse events in case of thrombophilia. We expose our criticism of items afforded by other guidelines by presenting our opinion based on both the scientific evidence and clinical practice. We also deal with common mistakes in prescribing and interpretations of TT hoping to purpose an educational approach on this topic. Finally, we emphasize the creation of the expert in hemostasis and thrombosis who should be present in every hospital.
Topics: Pregnancy; Humans; Female; Venous Thromboembolism; Thrombophilia; Venous Thrombosis; Risk Factors
PubMed: 38228491
DOI: 10.1080/17474086.2024.2306821 -
F1000Research 2022Background In COVID-19, the release of pro-inflammatory mediators in the cytokine storm, primarily interleukin-6 (IL-6), has been hypothesized to induce pulmonary...
Background In COVID-19, the release of pro-inflammatory mediators in the cytokine storm, primarily interleukin-6 (IL-6), has been hypothesized to induce pulmonary intravascular coagulation. However, the relationship between IL-6 and coagulopathy remains unclear in COVID-19 progression. We aimed to investigate the correlation of IL-6 with D-dimer, fibrinogen, prothrombin time (PT), and ferritin. Furthermore, we also analyzed the effect of those parameters on the worsening of COVID-19 patients. Methods A prospective cohort study was conducted in moderate and severe COVID-19 patients from June 2020 to January 2021. A serial evaluation of IL-6, D-dimer, fibrinogen, ferritin, and PT was performed and correlated with the patient's condition at admission and on the 14th day. The outcomes (improvement, worsening, or discharged patients) were recorded during the study. Results Of 374 patients, 73 study subjects (61 severe and 12 moderate COVID-19) were included in this study. A total of 35 out of 61 severe and one out of 12 moderate illness subjects had experienced worsening. Spearman-rank correlation of IL-6 with with ferritin, D-dimer, fibrinogen, and PT was 0.08 ( =0.5), -0.13 ( =0.27), 0.01 ( =0.91), and 0.03 ( =0.77), respectively. In ROC analysis, D-dimer (74,77%) and IL-6 (71,32%) were the highest among other variables (>60%). Conclusions In COVID-19 patients, there was a correlation between elevated IL-6 and D-dimer levels with disease deterioration. There was no correlation between elevated IL-6 levels with ferritin, D-dimer, fibrinogen, and PT levels. Therefore, changes in IL-6 and D-dimer can predict worsening in moderate and severe COVID-19 patients.
Topics: Humans; Blood Coagulation Disorders; COVID-19; Disease Progression; Ferritins; Fibrinogen; Interleukin-6; Prospective Studies; SARS-CoV-2
PubMed: 37841828
DOI: 10.12688/f1000research.125115.2