Variability in international normalized ratio and activated partial thromboplastin time after injury are not explained by coagulation factor deficits.
ABSTRACT: BACKGROUND:Conventional coagulation assays (CCAs), prothrombin time (PT)/international normalized ratio (INR) and activated partial thromboplastin time (aPTT), detect clotting factor (CF) deficiencies in hematologic disorders. However, there is controversy about how these CCAs should be used to diagnose, treat, and monitor trauma-induced coagulopathy. Study objectives were to determine whether CCA abnormalities are reflective of deficiencies of coagulation factor activity in the setting of severe injury. METHODS:Patients without previous CF deficiency within a prospective database at an ACS-verified Level I trauma center had CF activity levels, PT/INR, aPTT, and fibrinogen levels measured upon emergency department arrival from 2014 to 2017. Linear regression assessed how CF activity explained the aPTT and PT/INR variation. Prolonged CCA values were set as INR greater than 1.3 and aPTT greater than 34 seconds. CF deficiency was defined as less than 30% activity, except for fibrinogen, defined as less than 150 mg/dL. RESULTS:Sixty patients with a mean age of 35.8 (SD, 13.6) years and median New Injury Severity Score of 32 (interquartile range, 12-43) were included; 53.3% sustained blunt injuries, 23.3% required massive transfusion, and mortality was 11.67%. Overall, 44.6% of the PT/INR variance and 49.5% of the aPTT variance remained unexplained by CF activity. Deficiencies of CFs were: common pathway, 25%; extrinsic pathway, 1.7%; and intrinsic pathway, 6.7%. The positive predictive value for CF deficiencies were: (1) PT/INR greater than 1.3:4.4% for extrinsic pathway, 56.5% for the common pathway; (2) aPTT greater than 34 seconds:16.7% for the intrinsic pathway, 73.7% for the common pathway. CONCLUSION:Almost half of the variances of PT/INR and aPTT were unexplained by CF activity. Prolonged PT/INR and aPTT were poor predictors of deficiencies in the intrinsic or extrinsic pathways; however, they were indicators of common pathway deficiencies. LEVEL OF EVIDENCE:Prognostic, level III.
Project description:OBJECTIVE:To investigate the blood coagulation function in COVID-19 patients, and the correlation between coagulopathy and disease severity. METHODS:We retrospectively collected 147 clinically diagnosed COVID-19 patients at Wuhan Leishenshan Hospital of Hubei, China. We analyzed the coagulation function in COVID-19 patients through the data including thrombin-antithrombin complex (TAT), ?2-plasmininhibitor-plasmin Complex (PIC), thrombomodulin (TM), t-PA/PAI-1 Complex (t-PAIC), prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (APTT), fibrinogen (FIB), thrombin time (TT), D-Dimer (DD), and platelet (PLT). RESULT:The levels of TAT, PIC, TM, t-PAIC, PT, INR, FIB, and DD in COVID-19 patients were higher than health controls (p<0.05), and also higher in the patients with thrombotic disease than without thrombotic disease (p<0.05). What's more, the patients with thrombotic disease had a higher case-fatality (p<0.05). TAT, PIC, TM, t-PAIC, PT, INR, APTT, FIB, DD, and PLT were also found correlated with disease severity. Meanwhile, we found that there were significant difference in TAT, TM, t-PAIC, PT, INR, APTT, DD, and PLT in the death and survival group. Further using univariate and multivariate logistic regression analysis also found that t-PAIC and DD were independent risk factors for death in patients and are excellent predicting the mortality risk of COVID-19. CONCLUSION:Most COVID-19 patients with inordinate coagulation systems, dynamic monitoring of coagulation parameters might be a key in the control of COVID-19 death.
Project description:Coagulation tests and factors measurements have been widely applied in clinical practice. Pre-analytical conditions are very important in laboratory assessment.Here,we aim to determine the effects of storage time and temperature on activated partial thromboplastin time (APTT), fibrinogen (Fbg), prothrombin time (PT), the international normalized ratio (INR), thrombin time (TT), factor VIII activity (FVIII:C), and factor IX activity (FIX:C) in fresh plasma. Seventy-two blood samples were tested after storage for 0 (baseline), 2, 4, 6, 8, 12, and 24 h at 25°C (room temperature) and 4°C (refrigeration) in two centers. The mean percentage change of greater than 10% and the numbers of samples with greater than 10% percentage changes more than 25% were used to determine clinically relevant difference. We demonstrated that samples for Fbg, PT/INR, and TT could be safely stored for ≤24 h; FVIII:C for ≤2 h; FIX:C for ≤4 h both at 4°C and 25°C; and APTT for ≤12 h at 4°C and ≤8 h at 25°C.
Project description:Epidural anaesthesia and analgesia are indicated for oesophageal surgery. A rare but serious complication is spinal haematoma, which can occur on insertion, manipulation or withdrawal of catheters. Evidence and guidelines are vague regarding which tests are appropriate and how to interpret their results. We aimed to describe how routine coagulation test results change during oesophagectomy's perioperative course.Following ethical approval, we retrospectively identified patients who had undergone oesophagectomy between 2002 and 2012. Blood test results and details of operations, haemorrhage and complications were recorded and analysed with Excel and R. A literature search was conducted using the PubMed terms 'epidural' AND 'coagulation' AND English language. Relevant articles published in 2000 and after were included.Three hundred and seven patients received a thoracic epidural infusion with bupivacaine and morphine while 51 received an intravenous morphine infusion. Tests taken preoperatively and before the planned withdrawal of the epidural catheter demonstrated increases in all three measures: aPTT (activated partial thromboplastin time), PT-INR (prothrombin international normalised ratio) and platelet count (Plc). Postoperative thrombocytopenia was almost non-existent while aPTT or PT-INR was elevated above the reference range in 129/307 patients: aPTT was elevated in 116/307 while PT-INR was elevated in 32/307. This is too small a sample to allow meaningful estimation of risk of spinal haematoma: it may be as high as 2.3%. The literature search returned 275 articles, of which 57 were relevant. Twenty-one concerned the natural history of postoperative coagulation; 16, the incidence of and risk factors for spinal haematoma; and 5, evaluation of specific blood tests. Postoperative coagulation is characterised by thrombocytosis and transient moderately abnormal routine coagulation test results. Viscoelastic tests are not validated in the stable postoperative setting.Screening for coagulopathy before removal of epidural catheters is of unclear benefit since elevated aPTT and PT-INR are usual and may not indicate hypocoagulation. A thorough clinical assessment is important. We nevertheless recommend caution when being presented with elevated routine tests of coagulation before withdrawing an epidural catheter: viscoelastic haemostatic tests may have a role in testing before withdrawal of epidural catheters but they are so far not validated. Future research should include advanced coagulation analysis as soon as a patient is unfortunate enough to have a spinal haematoma.
Project description:BACKGROUND:Russell's viper envenoming is a major problem in South Asia and causes venom induced consumption coagulopathy. This study aimed to investigate the kinetics and dynamics of venom and clotting function in Russell's viper envenoming. METHODOLOGY/PRINCIPAL FINDINGS:In a prospective cohort of 146 patients with Russell's viper envenoming, we measured venom concentrations, international normalised ratio [INR], prothrombin time (PT), activated partial thromboplastin time (aPTT), coagulation factors I, II, V, VII, VIII, IX and X, and von Willebrand factor antigen. The median age was 39 y (16-82 y) and 111 were male. The median peak INR was 6.8 (interquartile range [IQR]: 3.7 to >13), associated with low fibrinogen [median,<0.01 g/L; IQR: <0.01-0.9 g/L), low factor V levels [median,<5%; IQR: <5-4%], low factor VIII levels [median,40%; IQR: 12-79%] and low factor X levels [median, 48%; IQR: 29-67%]. There were smaller reductions in factors II, IX and VII over time. All factors recovered over 48 h post-antivenom. The median INR remained >3 at 6 h post-antivenom but had reduced to <2, by 24 h. The aPTT had also returned to close to normal (<50 sec) at 24 h. Factor VII, VIII and IX levels were unusually high pre-antivenom, median peak concentrations of 393%, 307% and 468% respectively. Pre-antivenom venom concentrations and the INR (r = 0.20, p = 0.02) and aPTT (r = 0.19, p = 0.03) were correlated (non-parametric Spearman analysis). CONCLUSIONS:Russell's viper coagulopathy results in prolonged aPTT, INR, low fibrinogen, factors V, VIII and X which recover over 48 h. Severity of clotting abnormalities was associated with venom concentrations.
Project description:Objectives:For new analyzers or tests, analytical evaluation is required before implementation in the clinical laboratory. We evaluated the novel Roche Cobas t711 analyzer with six newly developed coagulation assays: the activated partial thromboplastin time (aPTT), prothrombin time (PT), international normalized ratio (INR), fibrinogen, d-dimer and anti-Xa. The evaluation included imprecision experiments, method comparison with the currently used Stago STA-R Evolution, monitoring of unfractionated heparin (UFH) with aPTT, a fast centrifugation protocol to improve turn-around time, and determination of sample stability in whole blood and plasma. Design and methods:Imprecision and method comparison were assessed using commercial quality control samples and patient samples, respectively. For dose monitoring of UFH with the aPTT, samples from patients treated with UFH were used. Samples from healthy volunteers were collected for evaluation of the fast centrifugation protocol (5' 2750×g) and for investigating sample stability over 6-8?h. Results:Results for between-run precision were within the desirable specification. Method comparison showed an excellent agreement for fibrinogen, d-dimer and anti-Xa. For aPTT, PT and INR, a good correlation was found, but results were significantly lower on the t711 compared to the STA-R Evolution, which is caused by different coagulation activators. Results from the fast centrifugation protocol differed not significantly from the standard protocol (15' 2500×g). Blood and plasma samples were stable at room temperature up to 6 and 8?h, respectively. Conclusions:The t711 coagulation analyzer with 6 novel tests is suitable for routine use in clinical laboratories.
Project description:Laparoscopic cholecystectomy (LC) is usually performed under general anesthesia. Recently, laparoscopic cholecystectomy under regional anesthesia has become popular, but this creates a serious risk of thromboembolism because of pneumoperitoneum, anesthesia technique, operative positioning, and patient-specific risk factors.This randomized controlled trial compares the effects of two different anesthesia techniques in laparoscopic cholecystectomy on coagulation and fibrinolysis.This randomized prospective study included 60 low-risk patients with deep vein thrombosis (DVT) who underwent elective LC without thrombo-emboli prophylaxis. The patients were randomly divided into two groups according to the anesthesia technique: the general anesthesia (group 1, n = 30) and spinal epidural anesthesia (group 2, n = 30) groups. Measurement of the prothrombin time (PT), thrombin time (TT), international normalized ratio (INR), activated partial thromboplastin time (aPTT), and blood levels of D-dimer (DD) and fibrinogen (F) were recorded preoperatively (pre), at the first hour (post 1) and 24 h (post 24) after the surgery. These results were compared both between and within the groups.The mean age was 51.5 ±16.7 years (range: 19-79 years). Pneumoperitoneum time was similar between group 1 (33.8 ±7.8) and group 2 (34.8 ±10.4). The TT levels significantly declined postoperatively in both groups. The levels of PT, aPTT, INR, D-dimer and fibrinogen dramatically increased postoperatively in both groups.While there was not any DVT, there was a significant decline in TT. There was a dramatic rise in the PT, INR, D-dimer, fibrin degradation products (FDP), and fibrinogen following LC. This may be attributed to the effects of pneumoperitoneum and anesthesia techniques on portal vein flow.
Project description:Activated partial thromboplastin time (aPTT) and prothrombin time (PT) are clinical tests commonly used to screen for coagulation-factor deficiencies. One genome-wide association study (GWAS) has been reported previously for aPTT, but no GWAS has been reported for PT. We conducted a GWAS and meta-analysis to identify genetic loci for aPTT and PT. The GWAS for aPTT was conducted in 9,240 individuals of European ancestry from the Atherosclerosis Risk in Communities (ARIC) study, and the GWAS for PT was conducted in 2,583 participants from the Genetic Study of Three Population Microisolates in South Tyrol (MICROS) and the Lothian Birth Cohorts (LBC) of 1921 and 1936. Replication was assessed in 1,041 to 3,467 individuals. For aPTT, previously reported associations with KNG1, HRG, F11, F12, and ABO were confirmed. A second independent association in ABO was identified and replicated (rs8176704, p = 4.26 × 10(-24)). Pooling the ARIC and replication data yielded two additional loci in F5 (rs6028, p = 3.22 × 10(-9)) and AGBL1 (rs2469184, p = 3.61 × 10(-8)). For PT, significant associations were identified and confirmed in F7 (rs561241, p = 3.71 × 10(-56)) and PROCR/EDEM2 (rs2295888, p = 5.25 × 10(-13)). Assessment of existing gene expression and coronary artery disease (CAD) databases identified associations of five of the GWAS loci with altered gene expression and two with CAD. In summary, eight genetic loci that account for ?29% of the variance in aPTT and two loci that account for ?14% of the variance in PT were detected and supported by functional data.
Project description:Point-of-care testing (POCT) of coagulation has been proven to be of great value in accelerating emergency treatment. Specific POCT for direct oral anticoagulants (DOAC) is not available, but the effects of DOAC on established POCT have been described. We aimed to determine the diagnostic accuracy of Hemochron® Signature coagulation POCT to qualitatively rule out relevant concentrations of apixaban, rivaroxaban, and dabigatran in real-life patients.We enrolled 68 patients receiving apixaban, rivaroxaban, or dabigatran and obtained blood samples at six pre-specified time points. Coagulation testing was performed using prothrombin time/international normalized ratio (PT/INR), activated partial thromboplastin time (aPTT), and activated clotting time (ACT+ and ACT-low range) POCT cards. For comparison, laboratory-based assays of diluted thrombin time (Hemoclot) and anti-Xa activity were conducted. DOAC concentrations were determined by liquid chromatography-tandem mass spectrometry.Four hundred and three samples were collected. POCT results of PT/INR and ACT+ correlated with both rivaroxaban and dabigatran concentrations. Insufficient correlation was found for apixaban. Rivaroxaban concentrations at <30 and <100 ng/mL were detected with >95% specificity at PT/INR POCT ?1.0 and ?1.1 and ACT+ POCT ?120 and ?130 s. Dabigatran concentrations at <30 and <50 ng/mL were detected with >95% specificity at PT/INR POCT ?1.1 and ?1.2 and ACT+ POCT ?100 s.Hemochron® Signature POCT can be a fast and reliable alternative for guiding emergency treatment during rivaroxaban and dabigatran therapy. It allows the rapid identification of a relevant fraction of patients that can be treated immediately without the need to await the results of much slower laboratory-based coagulation tests.Unique identifier, NCT02371070 . Retrospectively registered on 18 February 2015.
Project description:Extracorporeal membrane oxygenation (ECMO) is increasingly used to treat severe cases of acute respiratory or cardiac failure. Hemorrhagic complications represent one of the most common complications during ECMO, and can be life threatening. The purpose of this study was to elucidate pathophysiological mechanisms of ECMO-associated hemorrhagic complications and their impact on standard and viscoelastic coagulation tests. The study cohort included 27 patients treated with VV-ECMO or VA-ECMO. Hemostasis was evaluated using standard coagulation tests and viscoelastic parameters investigated with rotational thromboelastometry. Anticoagulation and hemorrhagic complications were analyzed for up to seven days depending on ECMO duration. Hemorrhagic complications developed in 16 (59%) patients. There were 102 discrete hemorrhagic episodes among 116 24-hour-intervals, of which 27% were considered to be clinically significant. The highest number of ECMO-associated hemorrhages occurred on the 2nd and 3rd day of treatment. Respiratory tract bleeding was the most common hemorrhagic complication, occurring in 62% of the 24-hour intervals. All 24-hours-intervals were divided into two groups: "with bleeding" and "without bleeding". The probability of hemorrhage was significantly associated with abnormalities of four parameters: increased international normalized ratio (INR, sensitivity 71%, specificity 94%), increased prothrombin time (PT, sensitivity 90%, specificity 72%), decreased intrinsic pathway maximal clot firmness (MCFin, sensitivity 76%, specificity 89%), and increased extrinsic pathway clot formation time (CFTex, sensitivity 77%, specificity 87%). In conclusions, early ECMO-associated hemorrhagic complications are related to one traditional and two novel viscoelastic coagulation abnormalities: PT/INR elevation, reduced maximum clot firmness due to intrinsic pathway dysfunction (MCFin), and prolonged clot formation time due to extrinsic pathway dysfunction (CFTex). When managing hemostasis during ECMO, derangements in PT/INR, MCFin and CFTex should be focused on.