Standard Coagulation Parameters Research Articles

Bleeding patients on extracorporeal membrane oxygenation have reduced platelet aggregation and plasma fibrinogen: a longitudinal observational study

This study investigated changes in coagulation and associations with occurrence of bleeding and thrombosis during extracorporeal membrane oxygenation (ECMO) therapy. The study included 100 adult ECMO-patients. Standard coagulation parameters, platelet aggregation and thromboelastometry (ROTEM®) were compared with healthy controls. Data on bleeding and thrombosis were collected until recovery or death. Mortality data were collected 30 days after weaning from ECMO. During ECMO therapy, 53 patients experienced at least one moderate or major bleed. Among these, 42 (79%) patients experienced the first bleeding on day 1 or 2. Platelet aggregation and ROTEM® revealed a hypocoagulable state in ECMO patients when compared with healthy controls. Patients bleeding on day 1 or 2, had lower platelet count (p = 0.04), poorer platelet aggregation and lower levels of fibrinogen (p < 0.01) than patients not bleeding on day 1 or 2. Further, ROTEM® clot propagation was reduced in bleeding patients (p < 0.001). Mortality was higher among bleeding patients than patients not bleeding on day 1 or 2 (67% versus 34%, p < 0.01). Congruity existed between ROTEM® measurements and standard coagulation assays, but plasma fibrinogen had a stronger association with bleeding than ROTEM® measurements. The present study does not support ROTEM® analysis as a routine part of coagulation monitoring during ECMO therapy.

Indicators of endothelial dysfunction and the rate of thrombotic complications in patients with type 2 diabetes mellitus at different periods after COVID-19

Introduction. Damage to the vascular endothelium and hypercoagulation are two of the main causes of post-­COVID-19 complications. The aim of our study was to evaluate endothelial dysfunction and thrombotic complications at different periods after COVID-19 in patients with type 2 diabetes mellitus. Patients and methods. We conducted a cross-­sectional study of 135 patients with type 2 diabetes mellitus who applied for inpatient treatment at the RSSPMCE clinic (Tashkent, Uzbekistan) in the period from 3 to 24 months after the acute period of COVID-19. The following laboratory parameters were assessed: fibrinogen, INR, APTT, D-dimer, von Willebrand factor, and cell adhesion molecules (VCAM-1, ICAM-1). Results. Despite normal or near-normal INR, APTT and fibrinogen levels, many patients had elevated levels of D-dimer (41.4 % of cases), von Willebrand factor (27.6 % of cases) and vascular cell molecules up to 24 months after infection. The concentrations of ICAM-1 and VCAM-1 did not have statistically significant correlations with the degree of compensation of diabetes mellitus (HbA1c level). At various times after COVID-19, cases of ischemic forms of diabetic foot syndrome and thrombosis affecting the cavernous sinus and upper extremities were recorded. Conclusion. Taking into account the results obtained, patients with type 2 diabetes mellitus after SARS-CoV-2 infection require careful monitoring, and, in addition to assessing standard coagulation parameters, determining the level of cell adhesion molecules may have diagnostic value.

Inter-α-inhibitor heavy chain H4 and sepsis-related coagulation disturbances: Another link between innate immunity and coagulation

BackgroundThe protease inhibitor inter-α-inhibitor heavy chain H4 (ITIH4) has been described as an acute-phase reactant and could potentially aid in sepsis monitoring and prognostication. ObjectivesTo investigate ITIH4 plasma levels in sepsis patients compared with healthy controls and to examine the association between ITIH4 and acute-phase response markers, blood coagulation, and organ dysfunction in sepsis. MethodsWe performed a post hoc study to a prospective cohort study. Patients with septic shock (n = 39) were enrolled upon intensive care unit admission. ITIH4 was analyzed using an in-house immunoassay. Standard coagulation parameters, thrombin generation, fibrin formation and lysis, C-reactive protein, organ dysfunction markers, Sequential Organ Failure Assessment score, and disseminated intravascular coagulation (DIC) score were registered. ITIH4 levels were also investigated in a murine Escherichia coli sepsis model. ResultsITIH4 did not display acute-phase behavior as mean ITIH4 levels were not increased in patients with septic shock or in E. coli-infected mice. However, ITIH4 exhibited large interindividual variation in patients with septic shock compared with healthy controls. Low ITIH4 was associated with sepsis-related coagulopathy, including a high DIC score (mean ITIH4: DIC, 203 μg/mL vs non-DIC, 267 μg/mL, P = .01), low antithrombin (r = 0.70, P < .0001) and decreased thrombin generation (mean ITIH4: first peak thrombin tertile, 210 μg/mL vs third peak thrombin tertile, 303 μg/mL, P = .01). ITIH4 showed moderate correlation with arterial blood lactate (ρ = -0.50, P < .001) but only weak correlations with C-reactive protein, alanine transaminase, bilirubin, and Sequential Organ Failure Assessment score (all, ρ < 0.26, P > .05). ConclusionITIH4 is associated with sepsis-related coagulopathy but is not an acute-phase reactant during septic shock.

Coagulation Abnormalities in Dogs with Parvoviral Enteritis.

Hemostatic alterations have been documented in dogs with canine parvoviral enteritis. This study's aims were to measure the standard coagulation parameters, and to assess the relationship between them and the clinical variables in dogs with canine parvoviral enteritis. Nine client-owned dogs with a canine parvoviral infection were included in a prospective, observational clinical study. Clinical score and coagulation status were assessed at admission. All nine dogs showed alterations of three or more standard coagulation variables. A correlation analysis evidenced a significantly high positive correlation between the activated partial thromboplastin time and clinical score. The present study concurs that dogs with canine parvoviral enteritis have coagulation disorders that are detectable by measuring the standard coagulation parameters.

Thromboelastography versus Standard Coagulation Assays in Patients with Postpartum Hemorrhage.

Thromboelastography (TEG), a point-of-care test that measures blood's dynamic viscoelastic properties, is routinely used to guide resuscitation in surgical specialties with high hemorrhage risk. Patients with ongoing postpartum hemorrhage (PPH) often develop coagulopathy and hypofibrinogenemia. Timely assessment of fibrinogen is crucial because cryoprecipitate for repletion requires thawing time prior to administration. TEG may provide rapid assessment of coagulopathy in ongoing hemorrhage but this has not been thoroughly studied. Our objective was to determine if TEG accurately reflects coagulopathy in ongoing PPH when compared with standard assays. This was a retrospective cohort study of people with ongoing PPH (quantified blood loss >1,000 mL), from January 1, 2016, to December 31, 2019. TEG variables and standard coagulation parameters were compared in patients who had both assays drawn simultaneously. As a secondary analysis, patients who had TEG were compared with those who did not. The Mann-Whitney, Fisher's exact, Kruskal-Wallis, Spearman's rho, and logistic regression tests were used for analysis. Significance was set at p < 0.05. A total of 680 patients were included, 69 of whom had TEG and coagulation parameters drawn simultaneously and were included in the primary analysis. The remainder were included in the secondary analysis. TEG variables and coagulation assays correlated significantly-prolonged R with increased PTT (rho 0.25, p = 0.04), prolonged K and decreased α angle with decreased fibrinogen (rho -0.61, p < 0.001; rho 0.24, p < 0.001), and decreased maximum amplitude with decreased platelets (rho 0.62, p < 0.001). Those who had thromboelastographic assays had higher blood loss and need for interventions to manage hemorrhage than those who did not. TEG correlated significantly with standard laboratory assays in ongoing PPH, including for patients with hypofibrinogenemia. Given the point-of-care nature and rapid turnaround time, TEG should be considered for timely hemorrhage evaluation and directed resuscitation of coagulopathy. · TEG significantly correlates with standard laboratory measures of coagulopathy in postpartum hemorrhage, including in patients with hybofibrinogemia (fibrinogen <200).. · TEG is routinely used in nonobstetric hemorrhage, and should be considered in PPH.. · Due to the point-of-care nature, TEG may allow for rapid guided resuscitation, including fibrinogen..

Only Subclinical Alterations in the Haemostatic System of People with Diabetes after COVID-19 Vaccination.

People with diabetes have an increased risk of experiencing adverse COVID-19 outcomes. COVID-19 vaccination is, therefore, highly recommended. However, people with diabetes have an inherently elevated risk of thrombotic events and the impact of the vaccination on the coagulation system in this patient population remains to be elucidated. The aim of this study was to investigate the impact of COVID-19 vaccination on the haemostatic system in people with type 1 or type 2 diabetes. We evaluated the effects of COVID-19 vaccination (BioNTech Pfizer, Moderna, AstraZeneca) on standard coagulation parameters, whole blood coagulation (Thrombelastometry), platelet function (impedance aggregation), and thrombin generation (calibrated automated thrombography) in people with type 1 diabetes mellitus (n = 41) and type 2 diabetes mellitus (n = 37). Blood sampling points were prior to vaccination and two weeks after the respective vaccination. Thrombelastometry measurements indicated moderately increased clot formation post-vaccination in people with type 1, as well as with type 2, diabetes: "Clot formation times" were significantly shorter, and both "maximum clot firmness" and "alpha angles" were significantly higher, as compared to the respective pre-vaccination values. Therefore, TEM parameters were not altered after vaccination in patients receiving ASA. Moreover, platelet aggregation was enhanced in people with type 1 diabetes, and plasma levels of D-Dimer were increased in people with type 2 diabetes, following COVID-19 vaccination. All other standard coagulation parameters, as well as thrombin generation, were not affected by the vaccination. The coagulation responses of people with diabetes to COVID-19 vaccination were only subclinical and comparable to those observed in healthy individuals. Our findings suggest that people with diabetes do not face an increased activation of the coagulation post-vaccination.

Plasmatic coagulation profile after major traumatic injury: a prospective observational study

PurposeUncontrolled hemorrhage is still the major cause of preventable death after trauma and is aggravated by trauma-induced coagulopathy (TIC). The underlying pathophysiology of TIC is still elusive, but several key effectors such as the thrombin-generation capacity, the protein C (PC) pathway, and the fibrinolytic activity could be identified. The aim of this prospective observational study was to investigate plasma coagulation markers attributed to reflect the course of TIC and to identify the mechanisms being responsible for the coagulopathy after major trauma.MethodsSeventy-three consecutive patients after major trauma and admission to a level-1-trauma unit were included to the study. During early trauma management, extended coagulation testing including the measurement of circulating thrombin markers and activated PC (APC) was performed and correlated with standard shock parameters and the patients’ clinical course and outcome.ResultsIn contrast to standard coagulation parameters, thrombin markers and APC were found to be increased in correlation with injury severity. Even in patients with lower impact mechanisms, early endogenous accumulation of thrombin markers and APC (ISS < 16: 0.5 ng/ml; ISS ≥ 16–26: 1.5 ng/ml; ISS > 26: 4.1 ng/ml) were observed. Furthermore, APC showed ISS- and injury-dependent patterns while ROC curve analysis revealed that especially APC plasma levels were predictive for coagulopathy and general patient outcome.ConclusionIncreased levels of APC and thrombin markers in patients after major trauma were positively correlated with injury severity. APC showed an ISS- and injury-dependent kinetic and might serve as candidate biomarker to identify patients at risk for developing TIC.

Platelet activation state in early stages of COVID-19.

Platelet activation at the early stage of COVID-19 is poorly described. The need for antiplatelet therapy in patients with COVID-19 remains controversial. We characterized the platelet activation profile in hospitalized patients at the early stage of COVID-19 using the modified prothrombinase Platelet Activation State (PAS) Assay. Sixteen patients admitted to the emergency department of the IRCCS San Raffaele Hospital (Milan, Italy) between February 8 and April 2021 were enrolled. All patients presented with respiratory symptoms and tested positive for severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2). Platelet activation was measured via the PAS Assay within 24 hours from patients' hospital admission. Data were compared with those measured in N.=24 healthy subjects (controls). Platelet activation was significantly higher in COVID-19 patients with respect to controls (PAS=0.63 [0.58-0.98%] vs. 0.46 [0.40-0.65%], respectively; P=0.03). Of note, highest PAS values were measured in the two patients with the worst clinical outcome, i.e., death because of respiratory failure (PAS=2.09% and 1.20%, respectively). No differences in standard coagulation parameters were noted between these two patients and those who were later discharged home. This study provides evidence of significant platelet activation state at the early stage of COVID-19 and suggests that the patient-specific platelet activation profile is a reliable clinical marker to stratify COVID-19 patients at high risk of poor clinical outcome who might potentially benefit from antiplatelet therapy.

EFFECT OF ANTICOAGULANT TREATMENT OF DABIGATRAN AND WARFARIN ON HEMOSTASIS IN PATIENTS WITH LIVER CIRRHOSIS AND ATRIAL FIBRILATION.

The aim of this work. To evaluate and compare standard coagulation parameters and parameters of the low-frequency piezothromboelastography (LPTEG), global test of hemostasis assessment in patients with liver cirrhosis and atrial fibrillation before and after treatment with warfarin and dabigatran, as well as to determine the differences in parameters between patients of both groups.&#x0D; Material and methods. Stage I of the study was prospective, cross-sectional, II stage - randomized experimental study involving 70 patients (46 men and 22 women aged 42 to 83 years), who were divided at second stage into groups IA and received dabigatran at a dose of 110 mg 2g /d, and the IB group, who received warfarin at an initial dose of 5 mg for 3 months. Standard coagulation parameters and low-frequency piezothromboelastography data were assessed in comparison with treatment initiation and between groups. Statistical analysis was performed using the Excel for Windows software package and IBM SPSS Statistics.&#x0D; Results. After treatment with anticoagulant drugs, a statistically significant increase in the INR was revealed by 48.5% (p = 0.035), PT prolongation by 5.4% (p = 0.027) and thrombin time by 19.7% (p˂0.001) compared with initiation of treatment. Group IA showed a significant prolongation of APTT and TT parameters as compared to group IB (p˂0.01), while group IB had prolonged INR, PTI, PT and decreased fibrinogen levels (p˂0.05). According to the LPTEG data, in all patients, the t1 time was prolonged by 33.3%, the ICC index was decreased by 8% (p˂0.05), the CTA was decreased by 46% (p˂0.001), the coagulation time t3 was prolonged (p˂0.001) , parameters ICD, ICP, ITC, MA were significantly reduced by 26.7%, t5 was prolonged (p˂0.001), ICLR was reduced (p˂0.001) and CTAA was decreased by 10.3% (p˂0.001) compared with the beginning of treatment. Comparative analysis of IА and IB group of patients showed a statistically significant difference in all parameters of the LPTEG at the level of p˂0.001.&#x0D; Conclusions. Treatment with anticoagulant drugs had a greater effect on the laboratory values ​​of external and general coagulation pathways parameters and almost did not affect the platelet-vascular hemostasis initial stage, internal coagulation pathway and fibrinolysis system. According to the LPTEG data, the hemostatic potential (HP) of patients in group IB was characterized by a statistically significant shift towards hypocogulation after the treatment. A detailed analysis of the LPTEG parameters of group IA patients showed a decrease in the aggregation activity of blood cells and normocoagulative HP.

Correlations between rotational thromboelastometry (ROTEM) and standard coagulation tests following viper snakebites.

BackgroundA high prevalence of venom-induced consumption coagulopathy has been reported in individuals with viper snakebites. Rotational thromboelastometry (ROTEM) is a rapid technique that could be advantageous in assessing and monitoring coagulation disorders.PurposeTo explore correlations between ROTEM and standard coagulation tests.Patients and methodsThis prospective observational study was performed among 41 patients with viper envenomation admitted to the Vietnam Poison Control Center from April 2016 to October 2017. Standard coagulation measurements [platelet count, prothrombin time (PT), activated partial thromboplastin time (aPTT), and fibrinogen level] and ROTEM indicators [clotting time (CT), amplitude (at set time: 5 and 10 minutes), clot information time (CFT) and maximum clot firmness (MCF) for extrinsic (EXTEM), intrinsic (INTEM), and fibrin based (FIBTEM) ROTEM] were obtained.ResultsFor INTEM, EXTEM, the FIBTEM, proportions of patients with prolonged CT were 34.1%, 63.4%, and 61.0% respectively and the proportions of patients with decreased MCF were 62.2%, 62.2%, and 35.5%, respectively. Moderate correlations were observed between PT and EXTEM CT (r = 0.627), aPTT and INTEM CT (r = 0.626), fibrinogen and FIBTEM MCF (r = 0.723), and platelet count and EXTEM MCF (0.60).ConclusionROTEM indicated a hypocoagulation state in patients with viper snakebite and was moderately correlated with standard coagulation parameters.

Liver fibrosis indices associated with substantial hematoma expansion in Chinese patients with primary intracerebral hemorrhage

BackgroundWhether liver fibrosis is associated with increased risk for substantial hematoma expansion (HE) after intracerebral hemorrhage (ICH) is still uncertain. We evaluated the association between various liver fibrosis indices and substantial HE in a Chinese population with primary ICH.MethodsPrimary ICH patients admitted to West China Hospital within 24 h of onset between January 2015 and June 2018 were consecutively enrolled. Six liver fibrosis indices were calculated, including aspartate aminotransferase (AST)-platelet ratio index (APRI), AST/alanine aminotransferase ratio-platelet ratio index (AARPRI), fibrosis-4 (FIB-4), modified fibrosis-4 (mFIB-4), fibrosis quotient (FibroQ) and Forns index. Substantial HE was defined as an increase of more than 33% or 6 mL from baseline ICH volume. The association of each fibrosis index with substantial HE was analyzed using binary logistic regression.ResultsOf 436 patients enrolled, about 85% showed largely normal results on standard hepatic assays and coagulation parameters. Substantial HE occurred in 115 (26.4%) patients. After adjustment, AARPRI (OR 1.26, 95% CI 1.00-1.57) and FIB-4 (OR 1.15, 95% CI 1.02-1.30) were independently associated with substantial HE in ICH patients within 24 h of onset, respectively. In ICH patients within 6 h of onset, each of the following indices was independently associated with substantial HE: APRI (OR 2.64, 95% CI 1.30-5,36), AARPRI (OR 1.55, 95% CI 1.09-2.21), FIB-4 (OR 1.35, 95% CI 1.08-1.68), mFIB-4 (OR 1.09, 95% CI 1.01-1.18), FibroQ (OR 1.08, 95% CI 1.00-1.16) and Forns index (OR 1.37, 95% CI 1.10-1.69).ConclusionsLiver fibrosis indices are independently associated with higher risk of substantial HE in Chinese patients with primary ICH, which suggesting that subclinical liver fibrosis could be routinely assessed in such patients to identify those at high risk of substantial HE.

Plasmatic hemostasis at very high altitude — a thrombelas-tometric approach

Introduction: Changes in blood coagulation during exposure to high altitude are not well understood and studies of activation and consumption of specific coagula-tion factors in hypoxic humans have yielded conflicting results. In this study we used thrombelastometry (TEM) which allows a global evaluation of clot formation and lysis process to study blood coagulation profiles in volunteers exposed to pro-longed hypobaric hypoxia at extreme altitudes. Material and methods: We conducted a prospective, observational study in 39 healthy volunteers during a research expedition up to an altitude of 7050 m. Plasma based thrombelastometric measurements and standard coagulation parameters were performed at different altitudes. Results: TEM measurements showed an increase in clotting time (CT) and maxi-mum clot firmness (MCF) at high altitudes, paralleled by an increase in international normalized ratio (INR) and activated partial thromboplastin time (aPTT). Fibrinogen concentration increased until 6022 m. D-Dimer and Thrombin-Antithrombin complex (TAT) increased with time exposed to severe hypoxia. For both measurements highest levels were found at 4844 m after acclimatization; in contrast, lower values were observed again at 7050m in the group of summiteers. Activated protein C resistance (APC-R) was slightly lowered at all altitudes. Conclusion: Our results suggest that activation of the coagulation and fibrinolytic system occurs with increasing hypobaric hypoxia with concurrent use of coagula-tion factors indicating the occurrence of a consumption-coagulopathy phenotype.

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ASSESSMENT OF COAGULATION PROFILE IN PATIENTS WITH LIVER CIRRHOSIS AND ATRIAL FIBRILLATION

&#x0D; &#x0D; &#x0D; The comorbid course of liver cirrhosis and atrial fibrillation causes higher levels of hospitalizations, mortality and ischemic stroke. According to current data, hemostasis in patients with liver cirrhosis is in a rebalanced dynamic state, but there are no data on the effect of atrial fibrillation on the hemostasis in patients with liver cirrhosis. Aims of the study. To assess abnormalities in primary, secondary haemostasis and fibrinolytic system in patients with liver cirrhosis and atrial fibrillation by using standard laboratory coagulation parameters and to investigate their changes depending on the stage of liver cirrhosis A, B, C according to Child-Pugh score. Materials and methods. A cross-sectional prospective study was conducted with the inclusion of 106 patients aged 42 to 83 years: group I (n = 70) - with liver cirrhosis and atrial fibrillation, II (n = 36) - with liver cirrhosis, which were distributed depending on the Child- Pugh score stages of cirrhosis and 20 healthy individuals. The levels of platelets, activated partial thromboplastin time, international normalized ratio, prothrombin time, thrombin time, fibrinogen, D-dimer were assessed on a Steellex M200 coagulometer. Statistical analysis (IBM SPSS Statistics) was performed. Results. The level of platelets in patients of group I was reduced by 37.4% (200 ± 8.33 vs. 274.7 ± 3.4; p,000.001), an activated partial thromboplastin time was prolonged by 38.6% (44.35 ± 1.39 vs. 32.01 ± 0.63, p˂0.001), prothrombin time was prolonged by 73.5% (19.4 ± 0.87 vs. 11.18 ± 0.53, p˂0.001), thrombin time was prolonged by 2.07 (25,7 ± 1.31 vs. 12.4 ± 0.66, p˂0.001), the international normalized ratio was increased by 24.3% (1.38 ± 0.04 vs.1.11 ± 0.01, p˂0.001) compared to control. The fibrinogen level was 20.9% higher (4.17 ± 0.17 vs. 3.45 ± 0.11, p˂0.001)&#x0D; &#x0D; &#x0D; &#x0D; than in control group and was 83.7% higher (4.17 ± 0.17 vs. 2.27 ± 0.13, p˂0.001) than in group II. The D-dimer level was 83% higher than in control (675 ± 22.3 vs. 368.8 ± 21.85, p˂0.001) and 44% higher (675 ± 22.3 vs. 469 ± 37.18, p ˂0.001) compared with group II. Conclusions. In patients with liver cirrhosis and atrial fibrillation abnormalities of primary hemostasis are detected due to decrease of platelets on the background of portal hypertension. At the secondary stage of hemostasis indicators of external and internal coagulation mechanisms are prolonged due to the reduced synthesis of coagulation factors by the liver. Increased level of fibrinogen is determined at the stage of compensated and subcompensated cirrhosis with a gradual decrease at the stage of decompensation. The high activity of the fibrinolytic system is observed due to increase in the D-dimer levels, which may indicate a prothrombotic state in these patients.&#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D;

A Matter of Caution: Coagulation Parameters in COVID-19 Do Not Differ from Patients with Ruled-Out SARS-CoV-2 Infection in the Emergency Department.

COVID-19 (coronavirus disease 2019) patients often show excessive activation of coagulation, associated with increased risk of thrombosis. However, the diagnostic value of coagulation at initial clinical evaluation is not clear. We present an in-depth analysis of coagulation in patients presenting to the emergency department (ED) with suspected COVID-19. N = 58 patients with clinically suspected COVID-19 in the ED were enrolled. N = 17 subsequently tested positive using SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) polymerase chain reaction (PCR) swabs, while in n = 41 COVID-19 was ruled-out. We analyzed both standard and extended coagulation parameters, including thromboplastin time (INR), activated partial thromboplastin time (aPTT), antithrombin, plasminogen, plasminogen activator inhibitor-1 (PAI-1), D-dimers, and fibrinogen at admission, as well as α2-antiplasmin, activated protein C -resistance, factor V, lupus anticoagulant, protein C, protein S, and von Willebrand diagnostics. These data, as well as mortality and further laboratory parameters, were compared across groups based on COVID-19 diagnosis and severity of disease. In patients with COVID-19, we detected frequent clotting abnormalities, including D-dimers. The comparison cohort in the ED, however, showed similarly altered coagulation. Furthermore, parameters previously shown to distinguish between severe and moderate COVID-19 courses, such as platelets, plasminogen, fibrinogen, aPTT, INR, and antithrombin, as well as multiple nonroutine coagulation analytes showed no significant differences between patients with and without COVID-19 when presenting to the ED. At admission to the ED the prevalence of coagulopathy in patients with COVID-19 is high, yet comparable to the non-COVID-19 cohort presenting with respiratory symptoms. Nevertheless, coagulopathy might worsen during disease progression with the need of subsequent risk stratification.

Hemostasis assessment with standard coagulation tests and rotational thromboelastometry (ROTEM) during therapeutic plasma exchange treatment.

In therapeutic plasma exchange (TPE), large amounts of plasma with all components, including antibodies, albumin, coagulation factors and inhibitors, are removed and usually replaced with replacement fluid without coagulation factors. Hemostatic parameters should be closely monitored in patients at risk of bleeding or with large volume exchanges with a short recovery interval. In this prospective study, we compared standard coagulation parameters and the rotational thromboelastometry (ROTEM) point-of-care test to identify hemostatically severely compromised patients treated with TPE. 22 patients without recent or planned invasive procedures received 63 TPE treatments with regional citrate anticoagulation. One plasma volume was exchanged with replacement fluid containing albumin and electrolytes. Standard coagulation tests, fibrinogen concentration, and rotational thromboelastometry (ROTEM, including EXTEM test, INTEM test, and FIBTEM test) were performed before and after each TPE treatment. Fibrinogen concentration decreased significantly and international normalized ratio increased slightly after TPE. Activated partial thromboplastin time, EXTEM, INTEM, and FIBTEM clotting times as well as clot formation times were prolonged, and maximum clot firmness decreased after TPE procedures. No serious adverse events occurred during TPE treatment. Our study showed that ROTEM parameters changed significantly after TPE performed with replacement fluid without coagulation factors. Among all parameters, FIBTEM clotting time showed the highest percentual change after TPE. According to this data, the ROTEM point-of-care test may have a potential to guide TPE therapy, particularly in patients at high risk for bleeding.

Thromboelastography clot strength profiles and effect of systemic anticoagulation in COVID-19 acute respiratory distress syndrome: a prospective, observational study.

Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) infection may yield a hypercoagulable state with fibrinolysis impairment. We conducted a single-center observational study with the aim of analyzing the coagulation patterns of intensive care unit (ICU) COVID-19 patients with both standard laboratory and viscoelastic tests. The presence of coagulopathy at the onset of the infection and after seven days of systemic anticoagulant therapy was investigated. Forty consecutive SARS-CoV-2 patients, admitted to the ICU of a University hospital in Italy between 29th February and 30th March 2020 were enrolled in the study, providing they fulfilled the acute respiratory distress syndrome criteria. They received full-dose anticoagulation, including Enoxaparin 0.5 mg·kg-1 subcutaneously twice a day, unfractionated Heparin 7500 units subcutaneously three times daily, or low-intensity Heparin infusion. Thromboelastographic (TEG) and laboratory parameters were measured at admission and after seven days. At baseline, patients showed elevated fibrinogen activity [rTEG-Ang 80.5° (78.7 to 81.5); TEG-ACT 78.5 sec (69.2 to 87.9)] and an increase in the maximum amplitude of clot strength [FF-MA 42.2 mm (30.9 to 49.2)]. No alterations in time of the enzymatic phase of coagulation [CKH-K and CKH-R, 1.1 min (0.85 to 1.3) and 6.6 min (5.2 to 7.5), respectively] were observed. Absent lysis of the clot at 30 minutes (LY30) was observed in all the studied population. Standard coagulation parameters were within the physiological range: [INR 1.09 (1.01 to 1.20), aPTT 34.5 sec (29.7 to 42.2), antithrombin 97.5% (89.5 to 115)]. However, plasma fibrinogen [512.5 mg·dl-1 (303.5 to 605)], and D-dimer levels [1752.5 ng·ml-1 (698.5 to 4434.5)], were persistently increased above the reference range. After seven days of full-dose anticoagulation, average TEG parameters were not different from baseline (rTEG-Ang p = 0.13, TEG-ACT p = 0.58, FF-MA p = 0.24, CK-R p = 0.19, CKH-R p = 0.35), and a persistent increase in white blood cell count, platelet count and D-dimer was observed (white blood cell count p < 0.01, neutrophil count p = 0.02, lymphocyte count p < 0.01, platelet count p = 0.13 < 0.01, D-dimer levels p= 0.02). SARS-CoV-2 patients with acute respiratory distress syndrome show elevated fibrinogen activity, high D-dimer levels and maximum amplitude of clot strength. Platelet count, fibrinogen, and standard coagulation tests do not indicate a disseminated intravascular coagulation. At seven days, thromboelastographic abnormalities persist despite full-dose anticoagulation.

Prevention of postoperative bleeding after complex pediatric cardiac surgery by early administration of fibrinogen, prothrombin complex and platelets: a prospective observational study

BackgroundPostoperative bleeding is a major problem in children undergoing complex pediatric cardiac surgery. The primary aim of this prospective observational study was to evaluate the effect of an institutional approach consisting of early preventive fibrinogen, prothrombin complex and platelets administration on coagulation parameters and postoperative bleeding in children. The secondary aim was to study the rate of re-intervention and postoperative transfusion, the occurrence of thrombosis, length of mechanical ventilation, ICU stay and mortality.MethodsIn fifty children (age 0–6 years) with one or more predefined risk factors for bleeding after cardiopulmonary bypass (CPB), thrombelastography (TEG) and standard coagulation parameters were measured at baseline (T1), after CPB and reversal of heparin (T2), at sternal closure (T3) and after 12 h in the ICU (T4). Clinical bleeding was evaluated by the surgeon at T2 and T3 using a numeric rating scale (NRS, 0–10).ResultsAfter CPB and early administration of fibrinogen, prothrombin complex and platelets, the clinical bleeding evaluation score decreased from a mean value of 6.2 ± 1.9 (NRS) at T2 to a mean value of 2.1 ± 0.8 at T3 (NRS; P < 0.001). Reaction time (R), kinetic time (K), maximum amplitude (MA) and maximum amplitude of fibrinogen (MA-fib) improved significantly (P < 0.001 for all), and MA-fib correlated significantly with the clinical bleeding evaluation (r = 0.70, P < 0.001). The administered total amount of fibrinogen (mg kg− 1) correlated significantly with weight (r = − 0.42, P = 0.002), priming volume as percentage of estimated blood volume (r = 0.30, P = 0.034), minimum CPB temperature (r = − 0.30, P = 0.033) and the change in clinical bleeding evaluation from T2 to T3 (r = 0.71, P < 0.001). The incidence of postoperative bleeding (> 10% of estimated blood volume) was 8%. No child required a surgical re-intervention, and no cases of thrombosis were observed. Hospital mortality was 0%.ConclusionIn this observational study of children with an increased risk of bleeding after CPB, an early preventive therapy with fibrinogen, prothrombin complex and platelets guided by clinical bleeding evaluation and TEG reduced bleeding and improved TEG and standard coagulation parameters significantly, with no occurrence of thrombosis or need for re-operation.Trial registrationGerman Clinical Trials Register DRKS00018109 (retrospectively registered 27th August 2019).

Blood Loss and Transfusion in Pediatric Craniofacial Surgery in the Antifibrinolytic Era

Background : Children undergoing complex cranial vault reconstruction (CCVR) for craniosynostosis experience high rates of bleeding and blood product transfusion, increasing the risk of perioperative complications. The most severe issues relate to the rate and extent of blood loss, which can be up to several times the patient's total blood volume and is often equated to controlled massive hemorrhage. ε-Aminocaproic acid (EACA) and tranexamic acid (TXA) are antifibrinolytic agents that have been shown to reduce intraoperative hemorrhage and transfusion requirements during CCVR. However, the relative efficacy of EACA vs. TXA in CCVR has not yet been evaluated. The aim of this study was to compare perioperative blood loss and need for transfusion in children receiving EACA and TXA. We hypothesized that TXA is associated with a greater decrease in blood loss and transfusion requirements when compared to EACA. Methods: All patients who underwent CCVR from September 2015 to December 2019 at our institution were retrospectively evaluated. The primary outcome measures included intraoperative estimated blood loss (EBL), red blood cell (RBC) transfusion volume (mL/kg), and calculated blood loss (CBL) (Kearney et al., Can J Anaesth 1989). Secondary outcome measures included hematologic and coagulation parameters. Study cohort demographic and outcome data were analyzed; Fisher's exact test was used for categorical data, student's t-test was used for continuous data. A p-value of &amp;lt; 0.05 was considered statistically significant. Results: 104 patients were included in the study with 48 patients in the EACA cohort and 56 patients in the TXA cohort. There were slightly more patients with syndromic craniosynostosis in the EACA group, but overall no significant differences in cohort characteristics (Table 1). Mean EBL (mL/kg) was slightly higher in the EACA group vs. the TXA group (21 ± 13 vs. 17 ± 10), but not statistically significant. Intraoperative mean CBL (34 ± 21mL/kg) and intraoperative percent blood volume lost (43 ± 26%) for the cohort were high, but these were equal between groups. Likewise, postoperative DO, CBL and percent blood volume lost were similar between groups. Overall, intraoperative RBC transfusion was required in 66 (64%) of patients and was similar between groups (69% of EACA patients vs. 59% of TXA patients). Intraoperative transfusion of other products was equal between groups. Postoperatively, 23 (22%) of patients required RBC transfusion. Postoperative blood product transfusions were equal between groups (Table 2). We compared routine hematologic and coagulation parameters peri-operatively and did not find any differences between the EACA and TXA group (Table 3). In the EACA group, there were 6 reported perioperative complications, including 2 suspected seizure events, as compared to 7 complications in the TXA group, which included 2 thromboembolic events. Discussion: Pediatric CCVR is a high blood loss surgery and this can lead to a consumptive coagulopathy for which intraoperative antifibrinolytic agents have been demonstrated to improve outcomes. We found no significant difference in blood loss, transfusion requirements, or hematologic parameters between patients who received EACA and TXA in our retrospective pediatric CCVR cohort. Overall there were 4 postoperative outcomes that could have been related to antifibrinolytic use (seizure, thromboembolism), but this was equal between groups and causality was not confirmed. Further research is needed to define optimal antifibrinolytic dosing and duration of therapy. While standard hematologic and coagulation parameters were similar between groups, the mechanisms of surgically induced coagulopathy in CCVR still need to be explored. Future studies investigating coagulation-based and inflammatory assays may be useful in defining surgical-induced coagulopathy. Disclosures No relevant conflicts of interest to declare.

Procedural bleeding risk, rather than conventional coagulation tests, predicts procedure related bleeding in cirrhosis.

Standard coagulation parameters are used to guide prophylactic blood product transfusion prior to invasive procedures in cirrhotic patients despite limited high-quality evidence. We aimed to describe coagulation parameters and prophylactic blood product use in cirrhotic patients having invasive procedures, and the influence of both on periprocedural bleeding. We conducted a cohort study of cirrhotic patients undergoing invasive procedures at a referral hospital. Procedures were classified into low or moderate-high bleeding risk. Prophylactic blood component was defined as fresh frozen plasma, cryoprecipitate or platelet transfusion prior to procedures. Univariate and multivariate logistic regression was performed to identify factors associated with procedure-related bleeding. We identified 566 procedures in 233 cirrhotic patients. Prophylactic blood product was given before 16% of high-risk and 11% of low-risk procedures (P = 0.18). Eight (8.3%) high-risk procedures were complicated by postprocedural bleeding, six of which occurred in patients without significant coagulopathy. The bleeding rate for low-risk procedures was 0.4%. For patients with international normalized ratio >1.5, platelet count <50 x 109/L, or both, the rate of bleeding was comparable between those given and not given prophylactic blood products (3.1 vs. 1.9%; P = 0.63). After adjusting for age, sex, platelet count, international normalized ratio, acute kidney injury, sepsis and model of end-stage liver disease, the only factor significantly predicting procedure-related bleeding was the procedural bleeding risk category (P < 0.01). Procedure-related bleeding in cirrhotic patients cannot be accurately predicted by INR or platelet count, nor prevented by blood component prophylaxis using these parameters. Procedure-related bleeding is best predicted by the bleeding risk status of procedures.