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The Journal of Emergency Medicine May 2020
Topics: Blood Coagulation Factors; Humans; International Normalized Ratio; Prothrombin; Warfarin
PubMed: 32546335
DOI: 10.1016/j.jemermed.2019.07.024 -
Journal of Pediatric Surgery Nov 2022After liver transplantation (LT), synthesis of coagulation factors by the graft recovers faster for pro thrombotic than anti thrombotic factors, resulting in a potential... (Observational Study)
Observational Study
AIMS
After liver transplantation (LT), synthesis of coagulation factors by the graft recovers faster for pro thrombotic than anti thrombotic factors, resulting in a potential pro thrombotic imbalance. We studied the thrombotic and hemorrhagic complications in our pediatric LT series, providing supplementation of fresh frozen plasma (FFP) and/or antithrombin (AT) in the prophylactic antithrombotic regimen.
METHODS
This was a retrospective observational single center study. All isolated pediatric LTs performed between 1/11/2009 and 31/12/2019 (n = 181) were included. Postoperatively, in addition to low molecular weight heparin, 22 patients (12%) received FFP (10 ml/kg twice daily for 10 days), 27 patients (15%) were given FFP (reduced duration) and AT (50-100 IU/kg/day if AT activity remained <70%), and 132 (73%) received AT only. Complications, outcome, and coagulation profiles in postoperative days 0-10 were analyzed.
RESULTS
In all three treatment groups, AT activity normalized by day 4 while prothrombin remained <70% of normal until day 9. Hepatic artery thrombosis (HAT), portal vein thrombosis (PVT), and hemorrhagic complications occurred in 2.8%, 3.3%, and 3.9% of LTs. One- and 5-year patient and graft survival were 88% (±2.4% Standard Error) and 84% (±2.5%), and 86% (±2.6%) and 84% (±2.7%), respectively, without difference between groups. HAT were associated with low AT on days 0 and 1, and PVT with low AT on day 0.
CONCLUSIONS
Low antithrombin activity after LT was associated with postoperative thromboses. FFP and/or AT supplementation allowed early normalization of AT activity, while thrombotic or hemorrhagic complications were rare, suggesting efficient and safe management of post-LT coagulopathy.
Topics: Anticoagulants; Antithrombin III; Antithrombins; Child; Dietary Supplements; Fibrinolytic Agents; Heparin, Low-Molecular-Weight; Humans; Liver Transplantation; Portal Vein; Prothrombin; Retrospective Studies; Risk Factors; Thrombosis; Venous Thrombosis
PubMed: 35871859
DOI: 10.1016/j.jpedsurg.2022.06.008 -
PloS One 2021There is limited data on the markers of coagulation and hemostatic activation (MOCHA) profile in Coronavirus disease 2019 (COVID-19) and its ability to identify COVID-19...
BACKGROUND
There is limited data on the markers of coagulation and hemostatic activation (MOCHA) profile in Coronavirus disease 2019 (COVID-19) and its ability to identify COVID-19 patients at risk for thrombotic events and other complications.
METHODS
Hospitalized patients with confirmed SARS-COV-2 from four Atlanta hospitals were included in this observational cohort study and underwent admission testing of MOCHA parameters (plasma d-dimer, prothrombin fragment 1.2, thrombin-antithrombin complex, fibrin monomer). Clinical outcomes included deep vein thrombosis, pulmonary embolism, myocardial infarction, ischemic stroke, access line thrombosis, ICU admission, intubation and mortality.
MAIN RESULTS
Of 276 patients (mean age 59 ± 6.4 years, 47% female, 62% African American), 45 (16%) had a thrombotic endpoint. Each MOCHA parameter was independently associated with a thrombotic event (p<0.05) and ≥ 2 abnormalities was associated with thrombotic endpoints (OR 3.3, 95% CI 1.2-8.8) as were admission D-dimer ≥ 2000 ng/mL (OR 3.1, 95% CI 1.5-6.6) and ≥ 3000 ng/mL (OR 3.6, 95% CI 1.6-7.9). However, only ≥ 2 MOCHA abnormalities were associated with ICU admission (OR 3.0, 95% CI 1.7-5.2) and intubation (OR 3.2, 95% CI 1.6-6.4). MOCHA and D-dimer cutoffs were not associated with mortality. MOCHA with <2 abnormalities (26% of the cohort) had 89% sensitivity and 93% negative predictive value for a thrombotic endpoint.
CONCLUSIONS
An admission MOCHA profile is useful to risk-stratify COVID-19 patients for thrombotic complications and more effective than isolated d-dimer for predicting risk of ICU admission and intubation.
Topics: Aged; Antithrombin III; Area Under Curve; COVID-19; Cohort Studies; Female; Fibrin Fibrinogen Degradation Products; Humans; Intensive Care Units; Male; Middle Aged; Odds Ratio; Patient Admission; Peptide Fragments; Peptide Hydrolases; Prothrombin; ROC Curve; Risk Factors; SARS-CoV-2; Survival Rate; Thrombosis
PubMed: 33740793
DOI: 10.1371/journal.pone.0248230 -
International Journal of Molecular... Jan 2023Diabetic encephalopathy (DE) is an inflammation-associated diabetes mellitus (DM) complication. Inflammation and coagulation are linked and are both potentially...
Diabetic encephalopathy (DE) is an inflammation-associated diabetes mellitus (DM) complication. Inflammation and coagulation are linked and are both potentially modulated by inhibiting the thrombin cellular protease-activated receptor 1 (PAR1). Our aim was to study whether coagulation pathway modulation affects DE. Diabetic C57BL/6 mice were treated with PARIN5, a novel PAR1 modulator. Behavioral changes in the open field and novel object recognition tests, serum neurofilament (NfL) levels and thrombin activity in central and peripheral nervous system tissue (CNS and PNS, respectively), brain mRNA expression of tumor necrosis factor α (TNF-α), Factor X (FX), prothrombin, and PAR1 were assessed. Subtle behavioral changes were detected in diabetic mice. These were accompanied by an increase in serum NfL, an increase in central and peripheral neural tissue thrombin activity, and TNF-α, FX, and prothrombin brain intrinsic mRNA expression. Systemic treatment with PARIN5 prevented the appearance of behavioral changes, normalized serum NfL and prevented the increase in peripheral but not central thrombin activity. PARIN5 treatment prevented the elevation of both TNF-α and FX but significantly elevated prothrombin expression. PARIN5 treatment prevents behavioral and neural damage in the DE model, suggesting it for future clinical research.
Topics: Animals; Mice; Diabetes Mellitus, Experimental; Disease Models, Animal; Inflammation; Mice, Inbred C57BL; Prothrombin; Receptor, PAR-1; Receptors, Thrombin; RNA, Messenger; Streptozocin; Thrombin; Tumor Necrosis Factor-alpha
PubMed: 36768341
DOI: 10.3390/ijms24032021 -
Rehabilitacion 2020Multifocal osteonecrosis is defined as the presence of osteonecrosis in three or more osseous sites. It is an infrequent entity representing less than 3% of cases among... (Review)
Review
Multifocal osteonecrosis is defined as the presence of osteonecrosis in three or more osseous sites. It is an infrequent entity representing less than 3% of cases among osteonecrosis patients. Multifocal osteonecrosis has been associated with systemic diseases, with patients at highest risk being those with lupus erythematosus, transplant recipients and those with haematological disorders or prolonged high-dose glucocorticoid treatment. The area most prone to disturbances is the femoral head. The pathogenesis of this particular disorder has not been fully defined, although several risk factors have been identified. We report the case of a young woman with abnormal hemostatic factors and a history of glucocorticoid and oral contraceptive therapy who developed bilateral hip osteonecrosis, followed by shoulder ON. The present article also provides an extensive literature review of the aetiology and treatment of multifocal ON.
Topics: Adult; Contraceptives, Oral, Hormonal; Cyproterone Acetate; Ethinyl Estradiol; Female; Femur Head Necrosis; Glucocorticoids; Humans; Humeral Head; Mutation; Osteonecrosis; Prothrombin; Shoulder Joint
PubMed: 32007184
DOI: 10.1016/j.rh.2019.07.006 -
Zhonghua Gan Zang Bing Za Zhi =... Nov 2022To investigate the related risk factors in patients with decompensated cirrhosis complicated with sepsis. 1 098 cases with decompensated cirrhosis were collected from...
To investigate the related risk factors in patients with decompensated cirrhosis complicated with sepsis. 1 098 cases with decompensated cirrhosis were collected from January 2018 to December 2020. A total of 492 cases with complete data meeting the inclusion criteria were included. Among them, the sepsis group (240 cases) was complicated with sepsis and the non-sepsis group (252 cases) was not complicated with sepsis. Albumin, cholinesterase, total bilirubin, prothrombin activity, urea, creatinine, international normalized ratio and other indicators of the two groups of patients were collected. Child-Pugh classification and MELD score were performed on two groups of patients. Mann-Whitney U test was used for non-normally distributed measurement data, and rank sum test for grade data. Logistic regression analysis was performed on sepsis-related factors that may affect patients with decompensated cirrhosis complicated with sepsis. 162 cases of gram negative bacteria, 76 cases of gram positive bacteria and 2 cases of Candida were detected. Child-Pugh grade C was mainly in the sepsis group, and Child- Pugh grade A and B was mainly in the non-sepsis group (=-13.01, <0.05). MELD score was significantly higher in patients with sepsis than that of patients without sepsis (=-12.30, <0.05). Neutrophils percentage, C-reactive protein, procalcitonin, and total bilirubin in patients with decompensated cirrhosis complicated with sepsis were 86.90% (79.00%, 91.05%), 48.48 (17.63, 97.55) mg/l,1.34 (0.40, 4.52) ng/l, and 78.50 (32.75149.80) μmol/L, which were significantly higher than that of patients without sepsis [69.55% (58.58%, 75.90%), 5.34 (5.00, 14.94) mg/l, 0.11(0.06,0.24) ng/l, 22.50(15.10,37.55) respectively] μmol/L, <0.05], while the albumin level, prothrombin activity level, and the cholinesterase level in sepsis patients were 27.30 (24.45, 30.60) g/L, 46.00% (33.50%, 59.00%), and 1.87 (1.29, 2.66) kU/L, respectively, which was significantly lower than the non-sepsis group [32.65 (28.95, 37.23) g/l, 73.00(59.75~84.85)%, 3.13(2.23~4.59) kU/L, <0.05]. Logistic regression analysis showed that serum total bilirubin, albumin, prothrombin activity level and diabetes mellitus were the independent risk factors for complicated sepsis. Patients with decompensated cirrhosis with poor liver function and higher MELD scores are more likely to be complicated with sepsis. Therefore, during the clinical diagnosis and treatment course, patients with decompensated cirrhosis with poor liver reserve function should be actively and dynamically monitored for infection-related indicators such as neutrophil percentage, procalcitonin, C-reactive protein, in an attempt to detect possible potential infections and sepsis, and improve early treatment and prognosis.
Topics: Humans; Liver Cirrhosis; Procalcitonin; C-Reactive Protein; Prothrombin; Risk Factors; Prognosis; Bilirubin
PubMed: 36891692
DOI: 10.3760/cma.j.cn501113-20210913-00469 -
Arteriosclerosis, Thrombosis, and... Jul 2023
Topics: Protein C; Protein S; Prothrombin; Blood Coagulation
PubMed: 37199157
DOI: 10.1161/ATVBAHA.123.319442 -
Journal of Thrombosis and Haemostasis :... Nov 2023Most of the carriers/patients triple-positive for antiphospholipid antibodies (lupus anticoagulant [LAC], immunoglobulin G [IgG]/immunoglobulin M [IgM] anticardiolipin,...
Close link between antiphosphatidylserine/prothrombin antibodies, lupus anticoagulant, and activated protein C resistance in tetra antiphospholipid antibody-positive subjects.
BACKGROUND
Most of the carriers/patients triple-positive for antiphospholipid antibodies (lupus anticoagulant [LAC], immunoglobulin G [IgG]/immunoglobulin M [IgM] anticardiolipin, and anti-β2-glycoprotein I antibodies) are tetra-positive, being positive for antiphosphatidylserine/prothrombin (aPS/PT) antibodies. The relationship between aPS/PT titer, LAC potency, and resistance to activated protein C (aPC-R) has not been investigated.
OBJECTIVES
The aim of this study was to clarify the mutual interdependence of these parameters in tetra-positive subjects.
METHODS
Twenty-three carriers and 30 patients with antiphospholipid syndrome, none of whom were being treated with anticoagulants, and 30 age- and sex-matched controls were studied. Detection of aPS/PT, LAC, and aPC-R in each individual was performed with established methods in our laboratory. Carriers and patients were positive for IgG or IgM aPS/PT or for both isotypes without significant difference. Since both IgG and IgM aPS/PT have anticoagulant activity, we used the sum of their titers (total aPS/PT) for the correlation studies.
RESULTS
Total aPS/PT in all individuals studied exceeded that in controls. There was no difference in total aPS/PT titers (P = .72), LAC potency (P = .56), and aPC-R (P = .82) between antiphospholipid antibody-carriers and patients with antiphospholipid syndrome. There was a significant correlation between total aPS/PT and LAC potency (r = 0.78; P < .0001) and between total aPS/PT titers and aPC-R (r = 0.80; P < .0001). LAC potency also was correlated significantly with aPC-R (r = 0.72; P < .0001).
CONCLUSION
This study shows that there is interdependence between aPS/PT, LAC potency, and aPC-R.
Topics: Humans; Antiphospholipid Syndrome; Lupus Coagulation Inhibitor; Prothrombin; Activated Protein C Resistance; Phosphatidylserines; Antibodies, Antiphospholipid; Immunoglobulin G; Immunoglobulin M
PubMed: 37422199
DOI: 10.1016/j.jtha.2023.06.033 -
Journal of Thrombosis and Haemostasis :... Jul 2023Current assays that monitor thrombin generation in plasma rely on fluorogenic substrates to follow the kinetics of zymogen activation, which may be complicated by...
BACKGROUND
Current assays that monitor thrombin generation in plasma rely on fluorogenic substrates to follow the kinetics of zymogen activation, which may be complicated by substrate cleavage from other proteases. In addition, these assays depend on activation following cleavage at the prothrombin R320 site and fail to report the cleavage at the alternative R271 site, leading to the shedding of the auxiliary Gla and kringle domains of prothrombin.
OBJECTIVES
To develop a plasma assay that directly monitors prothrombin activation independent of fluorogenic substrate hydrolysis.
METHODS
Cleavage at the R271 site of prothrombin is monitored through loss of Förster resonance energy transfer in plasma coagulated along the extrinsic or intrinsic pathway.
RESULTS
The availability of factor (F)V in plasma strongly influences the rate of prothrombin activation. The rate of thrombin formation is equally perturbed in FV or prothrombin-depleted plasma, implicating that the thrombin-catalyzed feedback reactions that amplify the coagulation response play an important role in generating sufficient amounts of FVa required for the assembly of prothrombinase. Congenital deficiencies in FVIII and FIX significantly slow down cleavage at R271 in plasma coagulated along the extrinsic and intrinsic pathways. Prothrombin activation in FXI-deficient plasma is only perturbed when coagulation is triggered along the intrinsic pathway.
CONCLUSION
The Förster resonance energy transfer assay enables direct monitoring of prothrombin activation through cleavage at R271 without the need for fluorogenic substrates. The assay is sensitive enough to assess how deficiencies in coagulation factors affect thrombin formation.
Topics: Humans; Prothrombin; Thrombin; Fluorescence Resonance Energy Transfer; Fluorescent Dyes; Blood Coagulation Factors; Factor Xa
PubMed: 36931601
DOI: 10.1016/j.jtha.2023.03.008 -
Cancer Medicine Sep 2023Prothrombin induced by vitamin K absence-II (PIVKA-II) and Alpha-fetoprotein (AFP) have been widely used as diagnostic markers in hepatocellular carcinoma (HCC), but the...
BACKGROUND
Prothrombin induced by vitamin K absence-II (PIVKA-II) and Alpha-fetoprotein (AFP) have been widely used as diagnostic markers in hepatocellular carcinoma (HCC), but the prognostic values of the two serum markers and their clinical usefulness in patient selection for different surgical approaches remain largely unclear.
METHODS
HCC patients received surgical treatment between 2015 and 2019 were included. Patients were divided into four statuses according to the serum PIVKA-II and AFP secretion status: PIVKA-II (-) AFP (-) (status 1); PIVKA-II (+) AFP (-) (status 2); PIVKA-II (-) AFP (+) (status 3); PIVKA-II (+) AFP (+) (status 4). Kaplan-Meier analyses were conducted to compare the survivals of the four groups and the HCC patients received different surgical interventions; time-dependent AUC curves were introduced to evaluate the prognostic value of the PIV-AFP status; Cox regression model was used to identify prognostic indexes for overall survival (OS) and recurrence-free survival (RFS).
RESULTS
A total of 518 patients were included. Patients with PIVKA-II (+) and APF (+) presented significantly decreased OS and RFS comparing to the other statuses. The areas under ROC curves of PIV-AFP status in predicting OS and RFS were superior to the PIVKA-II or the AFP alone. The HCC patients in early stages with PIVKA-II (+) and APF (+) had worse RFS when received laparoscopic hepatectomy than those who received open hepatectomy, whereas there was no difference in other secretion statuses. The PIVKA-II (+) and AFP (+) secretion status was an independent risk factor for OS, RFS.
CONCLUSIONS
The PIV-AFP secretion status is of favorable clinical utility in predicting the OS and RFS of the HCC patients; extra caution is needed when applicated the laparoscopic approach in the HCC patients with PIVKA-II (+) and AFP (+).
Topics: Humans; Carcinoma, Hepatocellular; alpha-Fetoproteins; Prothrombin; Liver Neoplasms; Vitamin K; Biomarkers; Laparoscopy; Biomarkers, Tumor
PubMed: 37596739
DOI: 10.1002/cam4.6422