Management of patients with acute hemorrhage requires addressing the source of bleeding, replenishing blood volume, and addressing any coagulopathy that may be present. Assessing coagulopathy and predicting blood requirements in real-time in patients experiencing ongoing bleeding can pose substantial challenges. In these patients, transfusion concepts based on ratios do not effectively address coagulopathy or reduce mortality. Moreover, ratio-based concepts do not stop bleeding; instead, they just give physicians more time to identify the bleeding source and plan management strategies. In clinical practice, standard laboratory coagulation tests (SLCT) are frequently used to assess various aspects of blood clotting. However, these tests may not always offer a comprehensive understanding of clinically significant coagulopathy and the severity of blood loss. Furthermore, the SLCT have a considerable turnaround time, which may not be ideal for making prompt clinical decisions. In recent years, there has been a growing interest in point-of-care viscoelastic assays like rotational thromboelastometry, which provide real-time, dynamic information about clot formation and dissolution.

Congenital cardiac surgery with cardiopulmonary bypass (CPB) alters patients' hemostasis. Viscoelastic testing is a modern technology identifying coagulation abnormalities. A new device, the Quantra-QPlus System (HemoSonics LLC, Charlottesville, VA) has not yet been investigated during congenital cardiac surgery.

This prospective observational pilot study investigated the correlation of Quantra and TEG-5000 in children undergoing cardiac surgery at Stanford Medicine Children's Health (SMCH).

Patients (0-8 years) undergoing cardiac surgery with CPB were included after parental consent. Per standard of care at SMCH, a TEG-5000 and Clauss Fibrinogen were measured on CPB during rewarming (T1) as well as after administration of blood components and coagulation factors (T2). For the study purpose, Quantra measurements were performed simultaneously at T1 and T2. Quantra results were correlated with TEG-5000 results and Clauss Fibrinogen. In addition, the agreement for normal and abnormal results was calculated, and a post hoc simulated transfusion algorithm using TEG-5000 and Quantra thresholds was compared to patients' clinical management.

From October 2022 to May 2023, 289 congenital cardiac surgeries were performed, 97 met inclusion criteria, 63 patients were consented, and 40 patients (12 females [30%] 28 males [70%]) included in the analysis. Median age and weight were 0.5 years and 6.33 kg, respectively. Correlation of Quantra/Clauss Fibrinogen was "moderate" and correlation of Quantra/TEG-5000 parameters ranged from "weak" to "very strong" Levels of agreement ranged from 15% to 97%. The post hoc simulated transfusion algorithm for TEG-5000 showed an agreement of 56% for FFP, 56% for Fibrinogen, and 95% for platelets and for Quantra, it was 40% for FFP, 87.5% for Fibrinogen, and 98% for platelets.

Despite weaknesses in correlation and agreement both VET devices suggested appropriate coagulation management based on the simulated transfusion algorithms. Quantra and TEG-5000 are not interchangeable and none of them can be considered as "the gold standard".

NTC 05295693.

Thrombophilia, a blood coagulation disorder, poses risks of venous thromboembolism (VTE). Coagulation assays may not be sufficient to assess VTE risk and global assays such as Rotational Thromboelastometry (ROTEM) may add valuable information. We investigated ROTEM's capacity to detect hypercoagulability in patients undergoing thrombophilia screening, its potential impact on patient outcomes, and limitations.

Comprehensive clinical, laboratory, genetic tests, and ROTEM (EXTEM and INTEM) were conducted for 356 patients referred for thrombophilia screening at an academic hospital outpatient unit. Hypercoagulability was identified as a shorter clot formation time (CFT), larger alpha angle (AA), and greater maximum clot firmness (MCF), and was compared in patients with and without VTE. Statistically this was analyzed using Mann-Whitney U and Chi-square tests with p < 0.05 considered significant.

Among 356 patients, 64.6% had previous VTE, with 76.9% experiencing one event, 14.3% recurrent (35.6% unprovoked, 64.4% provoked). 22.5% of patients were on anticoagulation. Those with VTE history exhibited significant alterations in EXTEM and INTEM parameters compared to those without (p < 0.001), showing decreased CFT and increased AA and MCF. However, receiver operating characteristic curves for these variables indicated that none were able to discriminate between those individuals with and without thromboembolic complications.

ROTEM does not appear to be a strong discriminatory test. However, it can detect hypercoagulopathy in patients referred for thrombophilia screening. Abnormal ROTEM may indicate a higher risk for recurrence. However, this can only be determined in prospective cohort studies.

Haemostasis in Chronic Kidney Disease (CKD) is complex, with patients experiencing both thrombotic and haemorrhagic risks. Current therapies, such as dialysis and blood transfusions, often rely on clinical judgment, which may not fully address these haemostatic abnormalities. This systematic review and meta-analysis aimed to determine whether Thromboelastography (TEG) offers a better ability to assess coagulation abnormalities in CKD compared to standard coagulation tests like activated partial thromboplastin time (aPTT), and prothrombin time (PT). A search across five databases identified 10 studies comparing TEG parameters in CKD patients versus healthy controls. TEG detected hypercoagulability in CKD, with significant reductions in Kinetics Time (P = 0.04), increases in Alpha angles (P = 0.02), and elevated Maximum Amplitude values (P = 0.0006). However, Reaction Time (P = 0.43) and Lysis 30 (P = 0.28) showed no significant differences. Standard coagulation tests, including aPTT and PT, also showed no significant differences between groups (P = 0.30 and P = 1.00), suggesting their limitations in detecting the complex haemostatic changes in CKD. Platelet counts were lower in CKD patients (P = 0.0009) but remained within normal ranges. Elevated fibrinogen levels (P = 0.003), linked to chronic inflammation, indicated a prothrombotic profile. Despite high heterogeneity in some parameters due to variability in CKD stages and treatment types, TEG demonstrates a more detailed assessment of haemostatic changes in CKD, suggesting its potential as a predictive tool for managing coagulation abnormalities.

Thrombotic diseases remain the major cause of death and disability worldwide, and the contribution of inflammation is increasingly recognized. Thromboinflammation has been identified as a key pathomechanism, but an unsupervised map of immune-cell states, trajectories, and intercommunication at a single-cell level has been lacking. Here, we reveal innate leukocyte substates with prominent thrombolytic properties by employing single-cell omics measures on human stroke thrombi. Using in vivo and in vitro thrombosis models, we propose a pro-resolving monocyte-neutrophil axis, combining two properties: (1) NR4A1hi non-classical monocytes acquire a thrombolytic and neutrophil-chemoattractive phenotype, and (2) blood neutrophils are thereby continuously recruited to established thrombi through CXCL8-CXCR1 and CXCR2 and adopt a hypoxia-induced thrombus-resolving urokinase receptor (PLAUR)+ phenotype. This immunothrombolytic axis results in thrombus resolution. Together, with this immune landscape of thrombosis, we provide a valuable resource and introduce the concept of "immunothrombolysis" with broad mechanistic and translational implications at the crossroad of inflammation and thrombosis.

Traumatic haemorrhage often requires initiation of a massive haemorrhage protocol (MHP). The primary aim of this exploratory Emergency Department (ED) study was to examine the utility of point of care Viscoelastic Haemostatic Assays (VHA) in terms of accuracy. The primary outcome was prediction of the need for massive transfusion (MT) at 24-hours.

Prospective observational study of consecutive trauma patients investigated with reported using STARD guidelines. Patients in an Australian ED setting < 1-hour from triage enrolled in a three-year window. The point-of-care device used was a TEG6s™ (Haemonetics, Braintree, MA, USA). The primary outcome was accuracy VHA testing for predicting MT delivery at 24-hours (an internationally recognised of massive transfusion was used). Other trauma outcomes such as product transfusion, injury severity score (ISS) and demographics were recorded. For analysis of accuracy the cohort was divided into VHA-normal (n = 44) and VHA-abnormal (n = 70) binary groups. Secondary outcomes included utility of TEG6s™ individual components and accuracy of VHA when combined with validated MHP decision scores.

Among eligible cases (n = 114) in-patient mortality was 7.0% with 91.2% receiving transfusion. Presence of (any) abnormal VHA result provided a 73.6% (95%CI 59.7-84.7) sensitivity and 49.3% (95%CI 36.1-62.3) specificity for predicting MT. Citrated Functional Fibrinogen (CFF) component had a higher performance for MT "rule-in" specificity (86.9%). When VHA was combined with validated MHP decision scores performance was increased. For example, normal VHA with Trauma Associated Severe Haemorrhage score < 8.5 was observed to yield a sensitivity of 96.2% for MT requirement rule-out. Further studies should examine if VHA test parameters can be added or (replace INR) in the existing clinical scores used to make decisions about transfusion in ED patients.

The standalone performance of early VHA testing in the ED setting was insufficient to reliably for predict a need for massive transfusion.

Rotational thromboelastometry (ROTEM®) is used widely in cardiac surgery. Reference ranges are derived from healthy volunteers but may not be interchangeable with those from patients undergoing cardiac surgery. Furthermore, sex and age seem to influence rotational thromboelastometry profiles. We performed a secondary analysis of two prospective observational study cohorts from a single centre in the Netherlands, which establishes pre-operative ROTEM® sigma reference ranges for adult patients undergoing cardiac surgery and examines sex- and age-specific variations.

Reference ranges (2.5-97.5th percentiles) were compared with those reported by the manufacturer by calculating 95%CIs around the percentiles. Sex- and age-specific variations were evaluated similarly by creating subgroups (comparing males with females and different age groups) and calculating the 95%CIs for the ranges in each subgroup. Non-overlapping CIs indicated statistically significant different ranges.

We included 381 patients in the analysis. Differences were found in ROTEM sigma reference ranges compared with those stated by the manufacturer: EXTEM and FIBTEM clot firmness upper limits were higher, and clotting time ranges in EXTEM and INTEM were wider. The lower limit of LI60 EXTEM was lower. When comparing males (n = 260) and females (n = 121), female patients had shorter CT EXTEM and higher A5, A10 and MCF in EXTEM and FIBTEM, but the reference ranges were not significantly different. No differences in medians or reference bounds were found across four age categories, divided by quartiles.

Reference ranges for patients undergoing cardiac surgery differed from the manufacturer reference ranges. Pre-operatively, female patients exhibited a slightly more hypercoagulable ROTEM profile than males when comparing medians, though the reference ranges were similar. No differences were found across age categories. Cardiovascular-specific, but not sex- or age-specific ROTEM sigma reference ranges might be needed.

IntroductionBleeding and thrombotic complications are common in extracorporeal membrane oxygenation (ECMO) patients and are associated with increased mortality and morbidity. The optimal anticoagulation monitoring protocol in these patients is unknown. This study aims to compare the incidence of thrombotic and hemorrhagic complications before and after a protocol change. In addition, the association between hemostatic complications, coagulation tests and risk factors is evaluated.MethodsThis is a retrospective single center cohort study of adult ECMO patients. We collected demographics, ECMO parameters and coagulation test results. Outcomes of the aPTT guided and multimodal protocol, including aPTT, anti-Xa assay and rotational thromboelastometry were compared and the association between coagulation tests, risk factors and hemostatic complications was determined using a logistic regression analysis for repeated measurements.ResultsIn total, 250 patients were included, 138 in the aPTT protocol and 112 in the multimodal protocol. The incidence of thrombosis (aPTT: 14%; multimodal: 12%) and bleeding (aPTT: 36%; multimodal: 40%), did not significantly differ between protocols. In the aPTT guided protocol, the aPTT was associated with thrombosis (Odds Ratio [OR] 1.015; 95% confidence interval [CI] 1.004-1.027). In both protocols, surgical interventions were risk factors for bleeding and thrombotic complications (aPTT: OR 93.2, CI 39.9-217.6; multimodal OR 17.5, CI 6.5-46.9).DiscussionThe incidence of hemostatic complications was similar between both protocols and surgical interventions were a risk factor for hemostatic complications. Results from this study help to elucidate the role of coagulation tests and risk factors in predicting hemostatic complications in patients undergoing ECMO support.

Extracorporeal Membrane Oxygenation (ECMO) is a technology that offers organ support for critically ill patients with respiratory and/or cardiac failure. Despite improvements in recent years in technology and the biocompatibility of circuits, patients on ECMO remain at high risk of hematologic complications, such as bleeding or thrombosis. Anticoagulation is required in most cases to limit the risk of clotting, but questions persist regarding the optimal anticoagulation strategy. More precisely, there is still debate around the best anticoagulation agent and monitoring tools as well as on the transfusion thresholds and appropriate corrective measures when faced with complications. This narrative review provides an overview of hemostasis on ECMO and the impact of circuit size and coating. The benefits and downsides of unfractionated heparin (UHF) and Direct Thrombin Inhibitors (DTIs) as anticoagulation agents are reviewed. Finally, commonly available coagulation tests (activated clotting time, activated partial thrombin time, anti-Xa, and viscoelastic tests) and their limitations are addressed. In conclusion, future research is needed to determine the best anticoagulation strategy for patients on ECMO.

Trauma-induced coagulopathy (TIC) carries significant risks, including increased mortality. Traditional TIC definitions rely on laboratories that result slowly and do not highlight therapeutic targets. We hypothesized that a TIC score, based on thromboelastography (TEG) and rotational thromboelastometry (ROTEM), collectively termed viscoelastic hemostatic assays, is associated with in-hospital mortality and packed red blood cell (pRBC) transfusion.

This retrospective cohort study used a database of adult patients undergoing institutional massive transfusion at seven level 1 trauma centers (2013-2018). A "TIC score" was developed, with 1 point assigned for abnormal TEG R-time (≥ 9 min) or ROTEM clot time (≥ 80 sec), ɑ-angle (< 65o), or maximum amplitude (< 55 mm). TIC+ patients (TIC score 1-3) were compared with TIC- patients (TIC score 0). TIC Score composition and abnormal cutoff values were adjusted to investigate optimal weighting and thresholds. Multiple logistic and negative binomial regression was used to control confounders while evaluating the association between abnormal TIC values, in-hospital mortality, and 24-hour pRBC transfusion.

Of 1499 patients in the final analysis, 591 (39.4%) were TIC+. Each 1-point increase in TIC score was associated with a 53% increase in the odds of mortality (odds ratio [OR], 1.53, 95% CI, 1.33-1.76, P < .001) and a 25% increase in pRBC transfusion volumes (incidence rate ratio, 1.25, 95% CI, 1.16-1.34, P < .001). Abnormal maximum amplitude was associated with both mortality (OR 1.50, 95% CI, 1.03-2.19, P = .034) and pRBC transfusion volumes (P < .001), whereas abnormal ɑ-angle was associated with mortality (OR, 1.59, 95% CI, 1.09-2.32, P = .015). The unequal weighting of TIC score components and adjustments to normal/abnormal cutoff thresholds were maintained but did not improve the model's predictive power.

A viscoelastic hemostatic assay-based TIC score is independently associated with mortality and pRBC transfusion volumes. This association persists with unequal weighting and adjustment of normal/abnormal cutoff thresholds of TEG components.

Viscoelastic hemostatic assays (VHAs) have become a valuable tool in guiding transfusion therapy, particularly in trauma care. While various forms of VHA exist, all provide a quantitative assessment of clot kinetics, strength, and dissolution. Studies have demonstrated that VHA can reduce both mortality and utilization of blood products in the general population. Interpreting VHA results requires consideration of specific patient factors, such as age and altered physiological properties as in pregnancy and the process of aging. Further research is needed to establish accurate reference ranges for these specific populations. This review article provides a comprehensive overview of the technical aspects of VHA as well as their clinical uses in trauma resuscitation.

Traumatic brain injury (TBI) patients on antiplatelet therapy face higher mortality because of impaired platelet function, which may be treated by platelet transfusion. The value of testing platelet function in this cohort remains controversial. We aimed to evaluate the relationship between platelet function assays and outcomes in TBI patients on antiplatelet therapy receiving platelet transfusions. We hypothesized that the magnitude of change in platelet assay performance following a transfusion would predict meaningful clinical outcomes.

A cohort of patients, aged 18 to 89 years, with a history of preinjury antiplatelet therapy or who required platelet transfusion, and who were deemed at risk for neurosurgical intervention, was selected from a prospective randomized controlled trial of platelet transfusion for TBI. Pre- and posttransfusion blood samples were drawn. Platelet hemostatic function assays (PHFAs) included thromboelastography with platelet mapping (TEG-PM) and VerifyNow. Logistic regression models assessed the association of temporal assay results with 30-day all-cause mortality, need for craniotomy, and initial and follow-up Rotterdam scores.

Data from 94 TBI patients (43% female) with a median age of 76 years were analyzed. The 30-day mortality rate was 14%. VerifyNow aspirin assay was able to capture increases in platelet function following a platelet transfusion in patients on aspirin (significant positive Δ = 65 aspirin response units, p < 0.001). Thromboelastography with platelet mapping parameters detected improved platelet function following transfusion, although the absolute value of changes was minimal. Thromboelastography with platelet mapping parameters predicted important clinical outcomes on logistic regression, although no significant associations with clinical outcomes were identified by the change in PHFA after transfusion or after adjusting for multiple comparisons.

Higher absolute pre- and posttransfusion values of TEG-PM were associated with decreased mortality, decreased need for neurosurgical intervention, and decreased risk of progression of hemorrhage in TBI patients taking antiplatelet agents, although neither the change in TEG-PM after transfusion nor any other PHFA value predicted outcomes.

Prognostic and Epidemiological; Level II.

Umbilical cord blood is used for the testing of various parameters in newborns. However, data on its applicability for hemostasis assays is insufficient.

To evaluate whether umbilical cord blood can be used for standard tests, thromboelastometry and thrombodynamics for preterm and term newborns.

187 newborns were included in the study. Blood was taken from the umbilical cord and by venipuncture of the newborn. Clotting times, fibrinogen, D-dimer, thromboelastometry and thrombodynamics were measured.

Clotting times and fibrinogen indicated a hypocoagulable shift, while thromboelastometry and thrombodynamics showed a hypercoagulable shift in hemostasis in umbilical cord blood compared to newborn blood. D-dimer indicated an enhanced process of thrombus lysis in newborn blood compared to cord blood. Collecting blood into a tube with the addition of a contact pathway inhibitor did not significantly change the global assay parameters in either umbilical cord blood or newborn blood. In the thrombodynamics assay, spontaneous clotting was detected but suppressed by the addition of a tissue factor inhibitor.

Hemostasis in cord and newborn blood differs for both global and standard tests. Hypercoagulability in newborns registered with the global assay thrombodynamics is associated with the presence of tissue factor in the blood.

1. We found a hypercoagulation shift in newborns compared with the adult references, possibly due to the presence of tissue factor in blood. 2. Blood coagulation is enhanced in cord blood compared with blood sampled from the vein of a newborn according to thromboelastometry and thrombodynamics assays. 3. Clotting times and fibrinogen concentrations in cord blood differ from these parameters in newborn blood. 4. Studying of the (patho)physiological features of hemostasis in newborns should consider differences in cord blood and vein sampled blood.

Objective: This prospective, descriptive, cross-sectional study aimed to establish kaolin-based thromboelastography reference values for previously known healthy third-trimester pregnancy patients. Methods: The study included 280 patients aged 18-38 years who were admitted to labor or scheduled for elective c-sections. Blood specimens collected via IV catheters were immediately mixed with reagents, placed in coagulation cups, and subjected to 60 min of testing at 37°C using a Haemonetics TEG 5000 system. The Hoffman regression method calculated the reference values; furthermore, effect size determination was done using Cohen's δ for comparison of data from other sources. Results: Patients had a median age of 26 (IQR 22-31), and their thromboelastography profile exhibited reference values for: R time (1-7 min), clot kinetics (1-2), angle (59°-82°), maximum amplitude (60-86 mm), and clot lysis at both 30 min (0%-6%) and 60 min (0%-8%). Results revealed significant differences in various thromboelastography parameters when comparing local patient cohorts against published reports, mainly European and North American counterparts. Shorter reaction times, enhanced clot kinetics, larger angles, and higher maximum amplitude, curve amplitude at 30 min, and amplitude at 60 min indicated distinct coagulation profiles and behaviors in the northeastern region of Mexico. Conclusion: Reference values for the Northern region of Mexico have been calculated and are characterized by a shorter clot reaction time, faster clot dynamics, higher angle values, overall greater curve amplitude, and no differences in enzymatic lysis activity compared to samples from other geographic regions.

Systemic heparinization during cardiopulmonary bypass (CPB) can significantly affect thromboelastography (TEG). This study investigated the feasibility of adding protamine in vitro to allow assessment of coagulation status using the TEG 6s system during CPB.

In this prospective observational study, 21 patients undergoing elective cardiac valve surgery were evaluated. During CPB, protamine was added in vitro to the heparinized blood of these patients at a concentration of 0.05 mg/mL and analyzed with the TEG 6s (Pre). The TEG parameters were compared to those analyzed after CPB withdrawal and systemic protamine administration (Post).

The citrated kaolin maximal amplitude (CK-MA) and the citrated functional fibrinogen maximal amplitude (CFF-MA) exhibited strong correlations between Pre and Post measurements (r = 0.790 and 0.974, respectively, P < 0.001 for both), despite significant mean differences (-2.23 mm for CK-MA and -0.68 mm for CFF-MA). Bland-Altman analysis showed a clinically acceptable agreement between Pre and Post measurement of CK-MA and CFF-MA (the percentage error was 10.6% and 12.2%, respectively). In contrast, the citrated kaolin reaction time (CK-R) showed no significant correlation between Pre and Post measurements (r = 0.328, P = 0.146), with a mean difference of 1.42 min (95% CI: -0.45 to 3.29).

In vitro protamine addition allows assessment of coagulation status during CPB using the TEG 6s system. CK-MA and CFF-MA measured during CPB using this method revealed a strong correlation and agreement with post-CPB measurements, suggesting that our method potentially facilitates early prediction of post-CPB coagulation status and decision-making on transfusion strategies.

The study was registered in the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR, registration number: UMIN000041097, date of registration: July 13, 2020, https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000046925 ) before the recruitment of participants.

Deep vein arterialization (DVA) is an innovative surgical technique aimed at enhancing blood flow in compromised limbs facing amputation. Maintenance of flow postrevascularization is crucial to limb salvage. As this is a new technique, no standardized thromboprophylaxis regime is currently established, and postprocedure thromboprophylaxis is at the discretion of the proceduralist. This study aims to evaluate coagulation profiles using viscoelastic studies in peripheral artery disease patients who underwent DVA, assessing the impact of various postprocedure thromboprophylaxis regimens.

Patients (aged > 60 years) undergoing DVA were prospectively evaluated using thromboelastography at baseline, 1, 3, and 6 months (2020-2024). Postprocedure thromboprophylaxis included mono antiplatelet therapy (MAPT), MAPT + direct oral anticoagulant (DOAC), dual antiplatelet therapy (DAPT), or DAPT + DOAC. Coagulation profiles were analyzed using descriptive statistics.

Among 16 patients (mean age 66.6 years, 75% male/Caucasian), hypertension and hyperlipidemia were present in 91%, and diabetes in 88%. The DAPT + DOAC group showed consistently superior platelet inhibition with the lowest adenosine diphosphate maximum amplitude values throughout baseline (35.65 mm vs. 42.2-65.03 mm in other groups), 1 month (26.7 mm vs. 32.14-69.4 mm), 3 months (27.36 mm vs. 32.2-39.97 mm), and 6 months (43.7 mm vs. 50.2-50.5 mm). MAPT demonstrated the slowest clot strengthening (citrated kaolin angle 65.25° vs. 68.7-71.55°).

Thromboelastography with platelet mapping demonstrated enhanced platelet inhibition and reduced clot formation in the DAPT + DOAC group, suggesting the importance of coagulation monitoring.

Peripheral artery disease (PAD) is prevalent among the elderly population, with Black Americans facing a higher incidence and complications than White Americans. Antiplatelet therapy is crucial for PAD. This observational study aims to discern racial variability in platelet function using viscoelastic assays in patients' postrevascularization for PAD.

Patients with PAD who underwent revascularization between December 2020 and October 2023 were prospectively enrolled. The cohort was divided by race and antiplatelet therapy regimen. Serial perioperative Thromboelastography with Platelet Mapping assays were performed, and the platelet function was evaluated.

A total of 42 patients met the study criteria, and 99 samples were analyzed. In the Thromboelastography with Platelet Mapping assay, the White-Americans cohort showed a significantly lower maximum amplitude (clot strength), lower percentage of platelet aggregation (platelet reactivity), and a significantly higher percentage of platelet inhibition than Black, Asian, and Hispanic Americans on the same antiplatelet regimen.

These findings suggest potential racial disparities in platelet response to standard medications, highlighting the critical need for personalized pharmacological approaches that account for genetic and physiological variations across different ethnic populations. Further research is essential to elucidate the underlying mechanisms of these differential platelet responses, which could have significant implications for precision medicine and targeted therapeutic strategies.

Viscoelastic testing at point-of-care is associated with reduced blood loss and blood product transfusions. The ROTEM (Werfen) sigma is a cartridge-based system that may facilitate point-of-care use, but limited studies exist comparing the sigma with the predicated ROTEM delta.

We compared the performance of the ROTEM delta with that of the sigma.

Citrated blood was collected from 20 healthy donors and patients during liver transplants (n = 17), obstetrics (n = 15), cardiovascular (n = 9), and trauma surgeries (n = 10). A method comparison was performed using the delta as the predicate. Imprecision was assessed at 2 levels for each assay. Manufacturer reference intervals were verified using 20 healthy donors. An algorithm used for cardiovascular surgery with the delta was compared with the sigma.

The coefficient of variation was <10% for all assays/parameters except for the thromboelastometry with extrinsic activation (EXTEM) clotting time (10.3%) and EXTEM amplitude (A)5 (10.2%). Reference intervals for the delta and sigma were comparable to manufacturer claims. The Pearson r comparing the delta and sigma exceeded .85 for all parameters/assays except for thromboelastometry with cytochalasin D-mediated platelet inhibition (FIBTEM) A10 (.77; 95% CI, .66-.86), FIBTEM A20 (.78; 95% CI, .65-.87), and thromboelastometry with heparinase clotting time (.77; 95% CI, .61-.87). No difference was observed in extrapolated thresholds from the delta-guided algorithm. However, extrapolated sigma A5 parameters for EXTEM were 5 mm lower, and for FIBTEM were 1 mm lower than delta A10 parameters.

The ROTEM delta and sigma devices had comparable performance. A negative bias was observed in the FIBTEM assay with lower extrapolated clinical decision points for a delta-guided treatment algorithm for the FIBTEM and EXTEM A5.

Fibrinolysis is initiated by the activation of plasminogen to plasmin via tissue-plasminogen activator (tPA) and urokinase-plasminogen activator (uPA); plasmin then converts fibrin to fibrin degradation products (FDPs). The antifibrinolytics counterbalancing this system include plasminogen activator inhibitor-1 (PAI-1), which inhibits tPA and uPA, α-2 antiplasmin (α2AP), which inhibits plasmin, and thrombin activatable fibrinolysis inhibitor, which inhibits the conversion of fibrin to FDP. Inherited disorders of the fibrinolytic pathway are rare and primarily have hemorrhagic phenotypes in humans: PAI-1 deficiency, α2AP deficiency, and Quebec platelet disorder. Patients with these disorders are usually treated for bleeds or receive prophylaxis to prevent bleeds in the surgical setting, with pharmacological antifibrinolytics such as aminocaproic acid and tranexamic acid. Disorders of the fibrinolytic pathway with fibrin deposition are extremely rare, mostly noted in patients with plasminogen deficiency, who have more recently benefited from advances in human plasma-derived plasminogen concentrates administered intravenously or locally. These disorders can be very difficult to diagnose using conventional or even specialized coagulation testing, as testing can be nonspecific or have low sensitivity. Testing of the corresponding protein's activity and antigen (where applicable) can be obtained in specialized centres, and routine laboratory measures are not diagnostic. Genetic testing of the pathogenic mutations is recommended in patients with a high suspicion of an inherited disorder of the fibrinolytic pathway.

To assess whether the Quantra-Qplus can provide the cutoff values for predicting transfusion thresholds after cardiopulmonary bypass.

Prospective observational study.

Single-center university hospital.

Adult patients undergoing cardiac surgery.

The Quantra-Qplus and conventional laboratory coagulation test were performed.

We enrolled 50 adult patients, and collected blood samples at 4 times (preoperative, during cardiopulmonary bypass, after protamine administration, and at the end of surgery). We obtained the values of the Quantra-Qplus (fibrinogen contribution to clot stiffness [FCS] and platelet contribution to clot stiffness [PCS]) and the values of conventional laboratory coagulation test (fibrinogen concentration and platelet count). To determine the cutoff values for FCS and PCS predicting blood transfusion thresholds at after protamine, receiver operating characteristic curve, area under the curve (AUC) with 95% confidence intervals (95% CIs), and Youden index were used. The cutoff value of FCS for predicting a fibrinogen concentration of less than 150 mg/dL was 0.95 hPa (AUC = 0.94; 95% CI, 0.86-1.00), and PCS for predicting a platelet count of less than 50,000/mm3 was 7.05 hPa (AUC = 0.97; 95% CI, 0.92-1.00) at after protamine administration. The cutoff values of FCS and PC varied during cardiac surgery.

Our study provides potential cutoff values of FCS and PCS to guide fibrinogen administration or platelet transfusion in cardiac surgery patients after protamine administration. These cutoff values might vary during surgery, and different cutoff values for predicting transfusion thresholds during cardiac surgery might apply.

Hemostatic derangements are common in critically ill and premature neonates. Nevertheless, hemostasis assessment in neonates is still challenging. The hemostatic system undergoes age-related physiological changes during its maturation and exhibits quantitative and qualitative differences between infants and adults. Conventional coagulation tests are mainly responsive to procoagulant factors, regardless of the contribution of cellular elements, anticoagulants and fibrinolytic contributors and, therefore, their role in predicting bleeding in neonatal acquired coagulopathy is somewhat limited. Viscoelastic coagulation tests offer a promising alternative, enabling a bedside and real-time assessment of the entire hemostatic process in short turn-around times with a limited amount of blood. These tests allow a targeted hemostatic monitoring and a tailored management of blood products and anticoagulation. The routine use of VCTs in the NICU remains limited, especially for premature infants, due to the lack of established normative ranges. In this review we will provide an overview of the main evidence related to the clinical application of viscoelastic monitoring in the neonatal setting.

Rotational thromboelastometry (ROTEM) is widely used for point-of-care coagulation testing to reduce blood transfusions. Accurate interpretation of ROTEM data is crucial and requires substantial training. This study investigates the inter- and intrarater reliability of ROTEM interpretation among experts and compares their interpretations with a ROTEM-guided algorithm.

This study was conducted at Amsterdam University Medical Center and included 90 cardiac surgery patients. ROTEM data were collected at 4 surgical stages: before induction, after aortic declamping, postcoagulation correction, and within 2 hours of intensive care unit (ICU) admission. An international panel of 7 cardiovascular anesthesiologists and one intensivist interpreted the data. Interrater reliability was assessed using Fleiss' kappa for binary decisions and the simple matching coefficient (SMC) for multiple-choice questions. Intrarater reliability with the ROTEM-guided algorithm was also evaluated.

Three hundred forty-three ROTEM measurements were analyzed. The interrater reliability for binary decisions was substantial to almost perfect, except after declamping (Fleiss' kappa = 0.34). The SMC for determining type of abnormality and interventions ranged from good to excellent across all ROTEM measuring moments (SMC ≥0.75). Intrarater reliability was almost perfect for binary questions (intraclass correlation coefficient [ICC] ≥0.81) and showed excellent agreement for multiple-choice questions. Comparing expert recommendations with the algorithm resulted in an average SMC of 0.70 indicating differences in intervention recommendations, with experts frequently recommending fibrinogen and protamine over the algorithm's suggestions of plasma and PCC.

This study demonstrates high inter- and intrarater reliability in ROTEM interpretation among trained professionals in cardiac surgery, with almost perfect agreement on abnormalities and interventions. However, differences between expert evaluations and the ROTEM-guided algorithm underscore the need for advanced clinical decision-making tools. Future efforts should focus on developing personalized, data-driven algorithms without predefined cutoff values to improve accuracy and patient outcomes.

Bleeding is a well-known and severe complication of cardiac surgery. Cardiopulmonary bypass, along with heparinization and hemodilution, is thought to affect all pathways of the hemostatic process, leading to excessive bleeding and worsened morbidity and mortality. The traditionally used standard laboratory tests (SLTs) were not designed for the surgical setting, have long turnaround times, and are poor predictors of bleeding. This review aims to give an overview of viscoelastic assays (VEAs), compare VEAs to conventional testing methods, and summarize the evidence for VEAs in cardiac surgery. A search of Medline via Pubmed, Scopus, and Embase yielded 2,868 papers, which we reviewed and summarized the key findings. VEAs such as rotational thromboelastometry and thromboelastography provide a quick turnaround, graphical, global impression of hemostasis in whole blood. VEAs allow for the analysis of specific contributors to the coagulation process and may facilitate cause-oriented hemostatic treatment and the development of treatment algorithms. VEAs have been found to have a high specificity and high negative predictive value for coagulopathic bleeding. Patients treated with VEA-based algorithms have been shown to have lower rates of bleeding, transfusion requirements, and exposure to allogeneic blood products. However, VEA-based algorithms have not demonstrated a mortality benefit and evidence for outcomes such as surgical re-exploration and hospital length of stay remains equivocal. In conclusion, VEAs have been shown to be comparable if not superior to SLTs in cardiac surgery. Further large-scale studies are needed to better evaluate the impact of VEAs on clinical outcomes.

Coagulation disorders are a primary symptom of envenomation caused by snakes belonging to the genus Bothrops. In the Northeast region of Brazil, the species Bothrops erythromelas and Bothrops leucurus are the main responsible for snakebite accidents. Due to the specific action of Bothrops venoms on several components of the coagulation cascade, the objective of this work was to characterize the coagulotoxic profile of B. erythromelas and B. leucurus venoms and the neutralizing potential of bothropic antivenom, considering that their venom are not used in the production of antivenom. Regarding the clotting components targeted by the venom of these species, B. leucurus samples had higher thrombin-like activity and ability to activate prothrombin, while the activation of Factor X was comparable between these two species. B.erythromelas and B. leucurus venom displayed α- and β-fibrinogenolytic activities, with the former presenting higher overall fibrinogenolytic activity. In contrast, B. erythromelas venom showed greater procoagulant activity on human plasma, assessed through the coagulation time induced by the venom samples and thromboelastometry. Bothropic antivenom inhibited the procoagulant potential of B. leucurus venom better than B. erythromelas. However, the ability of the antivenom to neutralize this activity is lower compared to that determined for the venom of B. jararaca, which is used for antivenom production. The results shown herein describe the procoagulant activity of B. leucurus and B. erythromelas venoms and highlight the differences regarding their procoagulant capacity on human plasma, contributing to a deeper understanding of the pathophysiology of the envenomation caused by these species.

Haemorrhage is a leading cause of morbidity and mortality in trauma, and prehospital transfusion of blood products is often necessary. Whole blood has been proposed to be the best alternative, but it is unclear whether, and how, storage and transport of the blood in a helicopter affects the blood units. We investigated the coagulation capacity and platelet function in whole blood at different time points during helicopter missions.

Twenty units of low-titre group O RhD negative whole blood were collected from healthy volunteers and analysed before, during and after transport in a helicopter. Coagulation and platelet function, as measured by thromboelastography, and blood samples for pH, electrolytes, glucose and lactate were assessed at baseline and 24, 72 and 168 h after storage in the helicopter. Plasma concentrations of coagulation factors and haemoglobin and blood counts were measured at baseline and after 168 h.

Plasma concentrations of coagulation factors and haemoglobin did not change during storage and transport. Platelet counts decreased from a baseline mean of 172 ± 29 × 109/L to a mean of 120 ± 28 × 109/L after 168 h, and platelet function worsened slightly but significantly by 8%-9% during storage and transport. pH and glucose decreased while potassium and lactate levels increased after 168 h compared with baseline.

Storage and transport of whole-blood units in a rescue helicopter, for up to 168 h, had a slight impact on the blood quality. Storage of whole blood on board of the helicopter holds up to European standard, measured as temperature and haemolysis.

Access to blood components in pre-hospital bleeding resuscitation is challenging. Dried plasma is a logistically superior alternative, and new products are emerging. Therefore, we aimed to evaluate laboratory and practical differences in three differently produced dried plasma products.

Single-donor lyophilized LyoPlas®, pooled-donor, lyophilized and pathogen-reduced OctaplasLG Powder®, and single-donor sprayed-dried FrontlineODP™ along with fresh plasma (in-house, pre-FrontlineODP and OctaplasLG) as controls were analysed (n = 8). Laboratory tests included measurements of various coagulation factors and thromboelastography. The practical evaluation of the dried plasma products included preparation time, time to dissolve the dried plasma and total time, together with subjective opinions from eight clinical users.

The coagulation factor content was within human reference ranges for all dried plasma, with approximately 10%-20% loss compared with fresh plasma. More variations were observed in the single-donor products compared with the pooled products. Clot formation analysed by thromboelastography showed normal graphs. Reconstitution time was similar, ranging from on average 7-9 min. In the user evaluation, the reconstitution time and the possibility of using a plastic bag for the transfusion were emphasized as important, the latter fulfilled by two of the products.

The study supports that dried plasma may be produced with lyophilization or spray-drying technique, as well as with the addition of pathogen reduction, with preserved coagulation capability. The products were reconstituted in acceptable time and deemed feasible for pre-hospital use by eighth test users.

Arterial and venous thromboembolism are leading causes of morbidity and death worldwide. Despite significant advances in the diagnosis, prognostication, and treatment of thrombotic diseases over the past 3 decades, the adoption of findings stemming from translational biomarker research in clinical practice remains limited. Biomarkers provide an opportunity to enhance our understanding of pathophysiological processes and optimize treatment strategies. They hold the promise of revolutionizing patient care. Still, this potential remains untapped, and several factors impede their use for near-patient applications. We sought to provide an overview of biomarker research in arterial and venous thromboembolic disease. We then aimed to discuss key barriers to the broader clinical implementation of biomarker research and highlight promising strategies to overcome them. We emphasize the merits of translational and implementation science to bridge the gaps from bench to bedside. Innovative trial design, data sharing, and collaborative efforts between academia and industry will be essential. Purposeful regression methodology using rational conceptual framework design, causal mediation analysis, and artificial intelligence might better leverage the use of observational data. Dedicated translational science training programs geared toward educating physicians on the appropriate measurement, interpretation, and integration of biomarker data in clinical practice should foster endorsement by frontline physicians. Finally, we make the case in support of a paradigm shift in cardiovascular medicine. Improved recognition of biomarker research and a greater emphasis on mechanistic evidence can better equip clinicians to deal with the uncertainty that defines the practice of thrombosis medicine.

Vaginal bleeding in early pregnancy is a common presentation in the Emergency Department (ED), often resulting in pregnancy loss. Hypercoagulability exceeding normal physiological changes may be associated with miscarriage, but conventional clotting tests do not reliably detect this effect. Rotational thromboelastometry (ROTEM), which performs a more comprehensive clotting evaluation, may demonstrate coagulopathic abnormalities contributing to vaginal bleeding and miscarriage in early pregnancy that are not present in normal gestation.

This study aimed to evaluate the relationship between coagulation results from ROTEM testing in patients undergoing active evaluation for possible miscarriage compared to samples taken from asymptomatic patients with healthy pregnancies.

This was a prospective case control study from a single center. Patients with chief complaint of vaginal bleeding in early pregnancy (less than 20 weeks) were recruited from the ED for ROTEM testing. These results were compared to healthy pregnant women presenting for routine prenatal care at our hospital's obstetrical clinic. Crude results were analyzed using t-test for ROTEM measures, and differences were then compared using multiple linear regression, controlling for patient age, race, ethnicity, number of prior pregnancies, and estimated gestational age (EGA) in weeks. ROTEM measurements of interest were the clot formation kinetics using EXTEM, INTEM, and NATEM tracings.

Over the study, 46 patients were recruited from the ED and 51 from the obstetric clinic. Both groups had similar mean ages, and racial and ethnic distribution. ED patients had earlier EGA than OB clinic patients, 7.6 weeks vs. 10.7 weeks, but higher patient age and higher number of prior pregnancies. ROTEM results were not significantly different between groups on univariate analysis except for INTEM CFT and INTEM MCF. After controlling for the patient age and estimated gestational age, no ROTEM result differed between groups.

In pregnant patients presenting to the ED with vaginal bleeding before 20 weeks, ROTEM differences were not different in comparison to healthy pregnant patients at the same gestation stage. This suggests that ROTEM clotting profiles may not be useful in the evaluation of vaginal bleeding within this population.

Enhanced fibrinolysis or hyperfibrinolysis may lead to life-threatening blood loss, while reduced activity may contribute to thrombosis. Euglobulin clot lysis time (ECLT) is a manual method that measures plasma fibrinolytic activity and is considered the gold standard. However, the data on reference interval is scarce and outdated. We have employed one-sided reference interval (>3 h) since the implementation of ECLT in our laboratory; therefore, we aimed to establish reliable ECLT reference interval and to explore the possible preanalytical influence of different blood collection tubes on the established ECLT reference interval. Establishing a reference interval for fibrinolysis was performed according to CLSI EP28-A3c guidelines by employing a posteriori direct sampling technique. The predefined exclusion criteria included a history of malignant or hepatobiliary disease, a history of deep vein thrombosis/pulmonary embolism (DVT/PE), an acute inflammatory state at the time of the venipuncture. We collected vein blood samples in Vacutest plastic coagulation tubes (Kima, Italy) and Vacutainer glass coagulation tubes (Beckton Dickinson, USA) containing 0.109 mol/l buffered trisodium citrate as an anticoagulant at a blood-to-anticoagulant ratio 9 : 1. We calculated two-sided reference interval and presented as 2.5th and 97.5th percentiles. ECLT values did not differ between sexes or the types of tubes enrolled in the study ( P  = 0.8979). The established reference interval ranged from 130 to 297 min for the KIMA Vacutest tube and from 120 to 292 min for the BD Vacutainer tube. The established ECLT reference interval differed significantly from the currently used cut-off value in our laboratory, thus enabling the assessment of hyperfibrinolysis by employing double-sided reference interval.

Echis ocellatus envenomings are a public health problem in West Africa, leading to bleeding and hypocoagulability. The aim of this study was to assess the hemostasis disorders associated with E. ocellatus envenoming. Envenomed patients with an abnormal whole blood clotting test (WBCT) were prospectively included at Tanguiéta, Benin. A WBCT with a sequential reading (i.e., at 20, 30, and 60 min), viscoelastic analysis (VA) using the Quantra analyzer, and blood count were performed on admission. VA and the WBCT were also assessed at 4, 8, 12, 24, 48, and 72 h after antivenom administration. Nineteen patients were included. On admission, the main results were an absence of a clot on VA and a slight decrease in platelets. Clot time gradually decreased over time while clot stiffness, fibrinogen, and platelet contributions to stiffness increased. Sequential reading improved the sensitivity of the WBCT. At H48, all patients with recurrence bleeding after antivenom administration had an abnormal WBCT while patients with a normal WBCT never had bleeding during their follow-up. VA allows the identification of various hemostasis disorders. Hypofibrinogenemia was the main disorder that persisted for several days after treatment. A WBCT with a sequential reading is an effective alternative for monitoring hypocoagulability in the absence of a laboratory.

Background: Blunt thoracic trauma possesses unique physiopathological traits due to the complex interaction of immune and coagulation systems in the lung tissue. Hemogram-based ratios such as neutrophil-to-lymphocyte (NLR), platelet-to-lymphocyte (PLR), neutrophil-to-lymphocyte × platelet (NLPR) ratios have been studied as proxies for immune dysregulation and survival in trauma. We hypothesized that blunt thoracic trauma patients exhibit distinct patterns of coagulation and inflammation abnormalities identifiable by the use of readily available hemogram-derived markers. Methods: The present study represents a retrospective observational analysis that included 86 patients with blunt thoracic trauma from a single high-volume level one trauma center. The primary outcome was mortality prediction in blunt thoracic trauma patients using these derived biomarkers. Secondary outcomes included phenotypes of the immune response and coagulopathy and the prediction of non-fatal adverse events. Results: A U-shaped distribution of mortality was found, with high rates of early deaths in patients with an NLPR value of <3.1 and high rates of late deaths in patients with NLPR > 9.5. A subgroup of blunt thoracic trauma patients expressing moderate inflammation and inflammation-induced hypercoagulation objectified as NLPR between 3.1 and 9.5 may have a survival benefit (p < 0.0001). The NLPR cut-off for predicting early deaths and the need for massive transfusion was 3.1 (sensitivity = 80.00% and specificity = 71.05%). Conclusions: These findings suggest that blunt thoracic trauma patients exhibit distinct phenotypes of the immune response and coagulopathy from the early stages. A controlled, balanced interaction of immune, coagulation, and fibrinolytic systems might effectively achieve tissue repair and increase survival in thoracic trauma patients and should be subject to further research.

Hemorrhagic shock remains a leading cause of preventable death worldwide, with mortality patterns varying significantly based on injury mechanisms and severity. This comprehensive review examines the complex pathophysiology of hemorrhagic shock, focusing on the temporal evolution of inflammatory responses, biomarker utility, and evidence-based therapeutic interventions. The inflammatory cascade progresses through distinct phases, beginning with tissue injury and endothelial activation, followed by a systemic inflammatory response that can transition to devastating immunosuppression. Recent advances have revealed pattern-specific responses between penetrating and blunt trauma, necessitating tailored therapeutic approaches. While damage control resuscitation principles and balanced blood product administration have improved outcomes, many molecular targeted therapies remain investigational. Current evidence supports early hemorrhage control, appropriate blood product ratios, and time-sensitive interventions like tranexamic acid administration. However, challenges persist in biomarker validation, therapeutic timing, and implementation of personalized treatment strategies. Future directions include developing precision medicine approaches, real-time monitoring systems, and novel therapeutic modalities while addressing practical implementation barriers across different healthcare settings. Success in hemorrhagic shock management increasingly depends on integrating multiple interventions across different time points while maintaining focus on patient-centered outcomes.

The potential use of TEG/ROTEM® in evaluating the bleeding risk for rare coagulation disorders needs to be assessed, considering the common mismatch among laboratory tests and the clinical manifestations. As a result, there is currently no published data on the use of viscoelastic tests to assess coagulation in FVII deficient patients undergoing elective neurosurgery. We describe the case of a patient affected by severe FVII deficiency who underwent microvascular decompression (MVD) craniotomy for hemifacial spasm (HFS). The ROTEM® did not show a significant coagulopathy according to the normal ranges, before and after the preoperative administration of the recombinant activated FVII, but a substantial reduction in EXTEM and FIBTEM Clotting Times was noted. The values of coagulation in standard tests, on the contrary, were indicative of a coagulopathy, which was corrected by the administration of replacement therapy. Whether this difference between ROTEM® and standard tests is due to the inadequacy of thromboelastographic normal ranges in this setting, or to the absence of clinically significant coagulopathy, has yet to be clarified. Neurosurgery is a typical high bleeding risk surgery; additional data is required to clarify the potential role for thromboelastographic tests in the perioperative evaluation of the FVII deficient neurosurgical patients.

Extracorporeal membrane oxygenation (ECMO) is mainly used for support of patients with cardiopulmonary collapse. The increasing use of ECMO has shown promising outcomes; however, it still carries the risk of significant complications. Inferior vena cava (IVC) thrombosis is an underestimated complication.

We described a series of 5 ECMO patients diagnosed with IVC thrombosis in our institution. An electronic literature search of the PubMed, Cochrane Library and Web of Science databases. A total of 12 cases were identified.

The occurrence of IVC thrombosis in ECMO patients is not uncommon. In our case series, elevated CRP and PCT levels and activated partial thromboplastin times (aPTT) of less than 50 s during ECMO operation were observed. In the literature review, a higher proportion of veno-arterial (VA) ECMO application (67%; 8/12) was presented in patients with IVC thrombosis. Eight patients (73%; 8/11) were monitored for anticoagulation using either aPTT or a combination of aPTT and ACT, with all aPTT measurements achieving the target range for anticoagulation. The mainstay of treatment for IVC thrombosis was anticoagulation alone (75%; 9/12). After the treatment, IVC thrombosis disappeared in the majority of patients (75%; 9/12) and there was no thrombosis-related mortality.

Factors such as elevated CRP and PCT levels, low aPTT levels, and the use of VA ECMO may contribute to the development of ECMO-related IVC thrombosis. Monitoring of anticoagulation with aPTT alone or in combination with ACT during ECMO may have inherent limitations. Anticoagulation alone may be an effective treatment for IVC thrombosis.

Despite medical interventions, COVID-19 continues to persist at pandemic proportions. A hypercoagulation state was rapidly observed in the severely ill, and the incidence of thromboembolic events remains elevated. Interleukin inhibitors have demonstrated positive effects on the hyperactivation of the immune system in COVID-19, with the interleukin-6 inhibitor tocilizumab showing promising results in reducing mortality. Nevertheless, the impact of interleukin inhibitors on the coagulation system remains incompletely understood.

In this clinical trial conducted in Stockholm, Sweden, interleukin inhibitors, namely anakinra (ANA) or tocilizumab (TOCI), were randomly administered in addition to standard care (SC) to hospitalized patients with COVID-19. A control group received only SC. The primary outcome sought to measure effects on global hemostasis, as indicated by changes in functional coagulation tests, specifically Rotational Thromboelastometry (ROTEM) or Overall Hemostatic Potential (OHP), visualized through scanning electron microscopy images. Secondary outcomes included effects on conventional coagulation laboratory tests.

The study enrolled 74 patients who were randomized to receive either ANA or TOCI in addition to SC, or SC alone. In the TOCI group, ROTEM variables exhibited less hypercoagulation after 29 days compared with ANA or SC treatment groups, characterized by prolonged clot formation time and decreased clot firmness. OHP decreased, but there were no significant differences among the three treatment groups. Plasma fibrinogen levels, initially elevated, decreased significantly in TOCI recipients over time.

Tocilizumab treatment demonstrated a significant reduction of hypercoagulation in hospitalized COVID-19 patients, by improvements in both global coagulation tests and conventional laboratory tests, in comparison with anakinra or SC alone. This finding underscores the significance of tocilizumab as a viable treatment option in severe COVID-19 cases, with the potential to decrease thrombosis incidence.

Factor XIII (FXIII), a plasma transglutaminase, is a coagulation factor that plays a crucial role in blood clotting and patient blood management. The studies have demonstrated that FXIII targets a wide range of additional substrates that have an important role in hemostasis, especially in posttraumatic patients, patients undergoing surgery or obstetrics, being involved in wound healing and tissue repair. Morover, FXIII deficiency has also been described and an extensive research has shown that FXIII deficiency is a rare coagulopathy that leads to longer bleeding time, perioperative and postoperative complications and slower wound healing. Present article aims to overview the diverse functions of FXIII and to highlight its role in patient blood management.

Hematological abnormalities are common in cirrhosis and are associated with various pathophysiological mechanisms. Studies have documented a prevalence of thrombocytopenia, leukopenia, and anemia in patients with compensated cirrhosis of 77.9%, 23.5%, and 21.1%, respectively. These abnormalities carry significant clinical implications, including considerations for invasive procedures, infection risk, bleeding risk, and prognosis. Previously, cirrhosis was believed to predispose patients to bleeding due to alterations observed in classical coagulation tests such as prothrombin time, partial thromboplastin time, international normalized ratio, and thrombocytopenia. However, this understanding has evolved, and cirrhosis patients are now also acknowledged as being at a high risk for thrombotic events. Hemostasis in cirrhosis patients presents a complex phenotype, with procoagulant and anticoagulant abnormalities offsetting each other. This multifactorial phenomenon is inadequately reflected by routine laboratory tests. Thrombotic complications are more prevalent in decompensated cirrhosis and may correlate with disease severity. Bleeding is primarily associated with portal hypertension, endothelial dysfunction, mechanical vessel injury, disseminated intravascular coagulation, endotoxemia, and renal injury. This review comprehensively outlines hematologic index abnormalities, mechanisms of hemostasis, coagulation, and fibrinolysis abnormalities, limitations of laboratory testing, and clinical manifestations of bleeding and thrombosis in patients with liver cirrhosis.

Abdominal paracentesis is a common procedure performed for both diagnostic and therapeutic purposes in patients with chronic liver disease and ascites. This review aims to provide an overview of the current evidence on the risk of bleeding associated with abdominal paracentesis. Electronic search was performed using PubMed, MEDLINE, and Ovid EMBASE from inception to 29 October 2023. Studies were included if they examined the risk of bleeding post-abdominal paracentesis or the efficacy of interventions to reduce bleeding in patients with chronic liver disease. Random-effects model was used to calculate the pooled proportions of bleeding events following abdominal paracentesis. Heterogeneity was determined by I 2, τ2 statistics, and P-value. Eight studies were included for review. Six studies reported incident events of post-abdominal paracentesis bleeding. Pooled proportion of bleeding events following abdominal paracentesis was 0.32% (95% CI: 0.15-0.69%). The mean values for pre-procedural INR and platelet count of patients in these studies ranged between 1.4 and 2.0, and 50 and 153 × 109/L, respectively. The highest recorded INR was 8.7, and the lowest platelet count was 19 × 109/L. Major bleeding after abdominal paracentesis occurred in 0-0.97% of the study cohorts. Two studies demonstrated that the use of thromboelastography (TEG) before paracentesis in patients with chronic liver disease identified those at risk of procedure-related bleeding and reduced transfusion requirements. The overall risk of major bleeding after abdominal paracentesis is low in patients with chronic liver disease and coagulopathy. TEG may be used to predict bleeding risk and guide transfusion requirements.