Standard Coagulation Tests Research Articles

Cirrhosis Progression Is Not Associated with Clinically Significant Alterations in Global Hemostasis Assessed by Thromboelastography.

(1) Background: Cirrhosis is associated with frequent alterations in standard coagulation tests that do not adequately reflect hemostasis. Thromboelastography provides a global assessment of coagulation and evaluates the functional status of clotting factors, fibrinogen, platelets, and fibrinolysis. The study aimed to assess whether liver disease severity leads to progressive alterations in the thromboelastography-based assessment of coagulation. (2) Methods: Consecutive patients with cirrhosis and abnormal standard coagulation tests (at least one of International Normalized Ratio > 2, platelet count < 50 × 103/µL, fibrinogen < 200 mg/dL) were analyzed using native thromboelastography. (3) Results: A total of 106 patients were included, of whom 69 (65.1%) had a normal thromboelastography. While the standard coagulation tests were significantly worse in patients in the Child C group (n = 62, 58.5%) than in patients staged in Child A and B, no significant differences existed between any of the thromboelastography variables. Of the 50 patients (47.1%) with an International Normalized Ratio > 2, only two patients (4%) had features of hypocoagulation, while 26% had features of hypercoagulability on thromboelastography. Patients with a platelet count < 50 × 103/µL had significantly lower platelet function as assessed by thromboelastography, yet only eight patients (20%) met the criteria for platelet transfusion. A thromboelastography-based transfusion protocol might lead to a 94.6% reduction in blood product transfusion indications in a simulation where the included patients would require interventional procedures. (4) Conclusion: Standard coagulation tests showed a poor correlation with thromboelastography. Based on thromboelastography, patients with severe, decompensated liver disease have a preserved hemostasis balance despite abnormal standard coagulation tests. Therefore, standard coagulation tests should not be used to guide the administration of blood products in patients with cirrhosis.

Viscoelastic Hemostatic Testing as a Diagnostic Tool for Hypercoagulability in Liver Transplantation: A Narrative Review.

Liver transplantation is a complex surgical procedure in which various forms of coagulation dysfunction can occur, including perioperative hypercoagulability. The hemostasis balance in liver graft recipients with end-stage liver disease can shift to thrombosis or haemorrhage, depending on the associated risk factors and clinical conditions. Hypercoagulability can result in serious complications such as thromboembolism, which can affect the vessels of the newly transplanted liver graft. Standard coagulation tests (SCTs), such as prothrombin time and activated partial thromboplastin time (aPTT), have a poor ability to diagnose and monitor an early stage of hypercoagulability. Recent studies demonstrated that viscoelastic hemostatic elastic tests (VETs), such as rotational thromboelastometry (ROTEM) and thromboelastography (TEG), are promising alternative tools for diagnosing hypercoagulability disorders. VETs measure clotting and clot formation time, clot strength (maximum clot firmness), fibrin and platelet contribution to clot firmness, and fibrinolysis, which makes them more sensitive in identifying liver graft recipients at risk for thrombosis as compared with SCTs. However, developing evidence-based guidelines for the prophylaxis and treatment of hypercoagulability based on VET results is still needed.

Monitoring the efficiency of reversal on anti-Xa direct oral anticoagulants using point-of-care viscoelastic testing

Bleeding events in patients receiving direct oral anticoagulation (DOAC) can be life-threatening even at therapeutic DOAC plasma concentrations, as anticoagulation impairs hemostasis and should therefore be identified immediately after hospital admission. The anticoagulatory effects of DOAC are typically not measurable in standard coagulation tests, such as PT or aPTT. Specific calibrated anti-FXa-tests allow specific drug monitoring, but they are too time-consuming for critical bleeding events and are commonly not available for 24 h/7 days in routine care. However, recent advances in point-of-care (POC) viscoelastic testing (VET) have shown a promising approach for rapid and quantitative detection of DOAC plasma concentrations using the Russell viper venom factor V activator (RVV for FXa-inhibitors) test or the ecarin clotting time (thrombin inhibitors). In acute bleeding situations, direct FXa inhibitors can be reversed by specific antidote andexanet alfa or hemostasis can be improved by prothrombin complex factor concentrates (PCCs). After reversal, confirmation of reversal efficacy is often requested, but no routine assays are currently available. Thus, the emergency management of bleeding DOAC patients is usually “blinded” with regard to reversal efficacy. POC VET laboratory assays might therefore also be helpful for measuring DOAC effects after reversal. We present a case series demonstrating the usefulness of RVV-clotting time post-DOAC reversal with andexanet alfa.

A Deployable Viscoelastic Coagulation Monitor Enables Point-of-Care Assessment of Coagulopathy in Swine With Polytrauma.

Absence of pre-hospital coagulation tests challenges prompt management of hemostasis after trauma. The Viscoelastic Coagulation Monitor (VCM, Entegrion, Durham, NC) is a hand-held coagulation test for point-of-care. We evaluated VCM in a translational swine polytrauma model, hypothesizing that VCM correlates with a laboratory reference method, the TEG 5000 (Haemonetics, Boston, MA), and can identify coagulopathic phenotypes relevant to trauma. Our secondary hypothesis was that pre-warming of VCM disposable test cartridges using a heating plate versus pre-warming of cartridges by carrying the cartridge in the user's pocket does not significantly alter results. This study was conducted in tandem with a parent study involving anesthetized, mechanically ventilated swine (n = 20; 54 ± 5 kg) that encountered traumatic brain injury, pulmonary contusion and hemorrhage, or combination/polytrauma injury. Blood was collected at baseline, post-injury, post-shock, post-transfusion, and 6-, 24-, and 48 h post-injury to perform VCM at point-of-care. Within-group effect of time was assessed. Spearman correlation examined linear relations between VCM and standard laboratory-based coagulation tests; as well as lactate, ionized calcium, and body temperature. Logistic regression examined predictiveness of VCM to identify coagulopathic phenotypes, with receiver operator characteristic curves generated to assess diagnostic capability. At a subset of timepoints, necessity of pre-warming the VCM test cartridge using a heating plate versus pre-warming the cartridge by placement in the user's pocket was assessed by conducting simultaneous tests on two separate instruments, with results analyzed by paired t-test with crossover design. VCM revealed time-dependent changes in clotting time, clot formation time (CFT), alpha, maximum clot firmness (MCF), and lysis index (LI30). All VCM metrics correlated with the respective TEG 5000 metrics, with strongest correlation for VCM MCF with TEG MA (rhos = 0.77, P < .0001) and VCM LI30 with TEG LY30 (rhos = -0.76, P < .0001). VCM demonstrated good (area under the curve >0.70) to excellent (area under the curve >0.90) diagnostic accuracy in detection of low platelet count (MCF), low hematocrit (clotting time, clot formation time, alpha, and MCF), low fibrinogen (MCF), and high fibrinogen (alpha, MCF). There was no statistically or clinically relevant effect of cartridge warming method on results. In a trauma model, VCM detected significant changes in coagulation at point-of-care in a simplified portable form factor. VCM could enable informed hemostasis management in pre-hospital settings where coagulations tests are unavailable, pending further validation in clinical trials.

Can rotational thromboelastometry rapidly identify theragnostic targets in isolated traumatic brain injury?

Coagulation assessment in traumatic brain injury (TBI) typically relies upon laboratory-based standard coagulation tests (SCTs), including the activated partial thromboplastin time (aPTT), INR and platelet count. Rotational thromboelastometry (ROTEM) sigma is an alternative point-of-care assay; however, its role in isolated TBI is under-evaluated. The present study aims to assess the prognostic utility of ROTEM sigma in isolated TBI. ROTEM sigma analysis was performed during the initial evaluation of patients presenting to the Royal Adelaide Hospital between February 2022 and 2023 with radiographically demonstrated traumatic intracranial haemorrhage and GCS ≤14. Patients with concomitant severe extracranial injury, or who received blood products or antifibrinolytic therapy prior to sample collection were excluded. Thirty-six patients had blood samples analysed with ROTEM, 25 of these patients were also evaluated with paired SCTs. Twenty-two per cent (8/36) of patients with isolated TBI had a hypocoaguable ROTEM profile, and this was associated with an increased incidence of head injury-related death (50% [4/8] vs 11% [3/28], P = 0.03). Median diagnostic turn-around-times were shorter for ROTEM parameters compared to SCT counterparts: EXTEM clotting time (CT) versus INR (20 vs 63 min, P < 0.01), and INTEM CT versus aPTT (21 vs 63 min, P < 0.01). EXTEM CT, FIBTEM CT and INR values had similar performance in predicting head injury-related death, area under the receiver operator curves were 0.8, 0.8 and 0.7, respectively. ROTEM sigma expedites the detection of clinically significant coagulopathy in isolated TBI. EXTEM and FIBTEM CT values are more rapidly attainable than INR and comparable in predicting head injury-related death.

Comparison of Standard and Global Coagulation Tests in Hemodialysis Patients

Background Chronic kidney disease (CKD) is associated with an increased tendency of bleeding and thrombosis. There are multiple factors that interact with each other to cause either in CKD patients. Conventional or standard coagulation tests (SCT) have several limitations. Global coagulation test (GCT), such as Sonoclot, gives a real-time detailed analysis of coagulation status. Materials and Methods This is a prospective observational cross-sectional study of 50 adult CKD stage 5D (dialysis) patients conducted from January 2020 to January 2022. Clinical details were noted and blood samples were taken for conventional and global coagulation tests prior to dialysis. Correlation between SCT and GCT as well as clinical hemostatic events was analyzed. Results Fifty patients were enrolled. Bleeding and thrombosis occurred in 7 and 5 patients, respectively. There was a significant correlation between some SCT and GCT parameters. None of the SCT parameter derangement was associated with any thrombotic episodes except increased fibrinogen level which was associated with thrombotic events. On the contrary, patients with hypocoagulability according to SCT actually had thrombotic events. Parameters of GCT, such as clot rate, time to peak, and platelet function were significantly associated with thrombotic episodes. Conclusion SCT and GCT parameters do not correlate with each other. SCT is not associated with clinically significant bleeding and thrombotic events. Some GCT parameters are associated with thrombotic events. GCT are real time and are better than SCT to reflect the coagulation status in patients on dialysis.

Коагуляційні характеристики пуповинної крові при затримці росту плода

Fetal growth restriction (FGR) is a common complication of pregnancy associated with severe perinatal consequences, a significant part of which is hemorrhagic and thrombotic disorders. Fetuses with FGR have thrombocytopenia, platelet dysfunction, and distortion of standard coagulation tests. There are few studies of the coagulation system in such newborns in vivo in the literature. Аim - to assess the relationship between the Doppler criteria of FGR and the kinetic manifestations of umbilical artery blood coagulation and fibrinolysis according to rotational thromboelastometry. Materials and methods. Prenatal Doppler parameters and postpartum kinetic parameters of blood coagulation and fibrinolysis in 118 newborns from singleton births were analyzed: the Group I - 67 newborns with FGR; the Group II - 51 full-term newborns from healthy mothers. Results. A significant decrease in the uterine and umbilical arteries resistance and blood flow velocity in FGR cases has been established. Thromboelastometric tests in the umbilical cord blood of the Group I newborns showed faster than in the Group II the blood clot formation, its greater firmness and delayed fibrinolysis. Comparison using rank correlation showed a relationship of average strength between the velocity of blood flow in the umbilical cord arteries and the blood clot firmness. Correlation between blood flow velocity in the midbrain and uterine arteries and coagulation indicators are weak. Conclusions. Reduced resistance index in the middle cerebral artery of fetuses with FGR indicates reduced resistance in these vessels, which should be regarded as signs of decentralization of fetal circulation. The blood of newborns with FGR is dominated by the processes of increased coagulation and slowing down of fibrinolysis, regardless of the date of birth. An increase in the pulsation index in the umbilical cord arteries during pregnancy can be considered a prognostically favorable hemodynamic characteristic in FGR. The study was carried out in accordance with the principles of the Helsinki Declaration. The research protocol was approved by the Local Ethics Committee of the institution mentioned in the work. The authors declare that there is no conflict of interest.

Temperature effect on coagulation function in mild hypothermic patients undergoing thoracic surgeries: thromboelastography (TEG) versus standard tests

PurposeOur previous research has revealed that mild hypothermia leads to excessive bleeding in thoracic surgeries, while the underlying mechanism stayed unrevealed by the standard coagulation tests. The research question in this study was as follows: “How does mild hypothermia impair the hemostatic function in patients receiving thoracic surgeries?”. The purpose was to detect the disturbed coagulation processes by comparing the TEG parameters in patients receiving active vs. passive warming during thoracic surgeries.MethodsStandard coagulation tests and thromboelastography (TEG) were adopted to compare the hemostatic functions in patients receiving active vs. passive warming during thoracic surgeries. Furthermore, blood samples from passive warming group were retested for TEG at actual core body temperatures.ResultsSixty-four eligible patients were included in this study. TEG revealed that mild hypothermia significantly disturbed coagulation by decreasing MA (59.4 ± 4.5 mm vs. 64.2 ± 5.7 mm, p = 0.04) and α angle (70.4 ± 5.2° vs. 74.9 ± 4.4°, p = 0.05) and prolonging ACT (122.2 ± 19.3 s vs. 117.3 ± 15.2 s, p = 0.01) and K time (1.9 ± 1.0 s vs. 1.3 ± 0.4 min, p = 0.02). TEGs conducted under core body temperatures revealed more impaired coagulation than those incubated at 37 °C. Furthermore, postoperative shivering and waking time were significantly increased in mild hypothermic patients.ConclusionMild hypothermia significantly impaired coagulation function in patients receiving thoracic surgeries, which could be detected by TEGs other than the standard coagulation tests. Temperature-adjusted TEGs may provide a preferable method of hemostatic monitoring and transfusion guidance in thoracic surgeries, which warrants further clinical investigations.

Severe haemorrhages leading to a diagnosis of rare bleeding disorder occur at a very young age: A study from the FranceCoag network.

In the context of severe unexplained haemorrhage (SH), it is usual to seek haematological evaluation and investigate for an inherited rare bleeding disorder (IRBD). In such circumstances, appropriate screen can discriminate between IRBD and suspected child abuse. Yet, little information is available about the frequency of SH in the population of patients with IRBD. To collect epidemiologic data about SH and IRBD. The database of the FranceCoag network has collected information about IRBD since January 2004. Based on data gathered up to 16 March 2022, a retrospective search was conducted for of SH events having occurred before or at the time of IRBD diagnosis. Demographics and diagnosis circumstances were retrieved, as well as information about SH, defined as any life-threatening bleeding or intracranial haemorrhage. Among the 13,433 patients of the database, 109 (0.8%) fulfilled inclusion criteria including a known date of IRBD diagnosis, haemophilia A or B (HA/HB) being the most frequent (82.5%). IRBD was discovered as a consequence of an SH event in 82.6% of the cases while CNS was involved in 55%. Severe and moderate HA/HB and other severe IRBD presented significantly more intracranial haemorrhage (p<.02) and a lower age at diagnosis (p=.03). These data support that any unusual SH should raise a suspicion of IRBD. Particularly before 1-year of age, it is suggested to first confirm moderate or severe haemophilia and severe IRBD by standard coagulation tests (APTT, PT and fibrinogen), combined with a clotting FXIII assay as first-line investigation. Subsequent assays of coagulation factors should be performed in the case of abnormal values, in second-line investigation.

Effect of Splenectomy on Coagulation and Platelet Function in Adult Liver Transplant Recipients Assessed With Rotational Thromboelastometry and Standard Coagulation Tests.

Splenectomy during liver transplant can affect platelet function. In this study, our primary aim was to assess the perioperative platelet function by rotational thromboelastometry and the effects of splenectomy on platelet function. We studied 40 consecutive liver transplant recipients with end-stage liver disease (50% as a result of hepatitis C). Patients with splenectomy were compared with patients without splenectomy (n = 20/group). Three platelet function parameters by rotational thromboelastometry were studied: platelet activation with arachidonic acid, platelet activation with adenosine diphosphate, and platelet activation with thrombin receptor-activating peptide 6. Patients were monitored perioperatively and until postoperative day 21. Heparin was infused for 2 days postoperatively (60-180 U/kg/day), followed by administration of subcutaneous low-molecular-weight heparin (40 mg/24 h) on postoperative days 2 and 3 and oral acetylsalicylic acid when platelet count was >50 × 103/μL. Liver disease contributed to low perioperative platelet count and function. Patients showed significant improvement by postoperative day 14 and day 21, particularly after splenectomy. Platelet count was significantly correlated with the 3 platelet function parameters by rotational thromboelastometry (P < .001). Acetyl salicylic acid was required earlier (postoperative day 3) for patients with splenectomy (8/20) but only affected the platelet function represented by platelet activation with arachidonic acid, whereas other platelet activation pathways were less affected. Patients received no transfusions of platelet units. End-stage liver disease significantly contributed to low platelet function and counts before transplant. Two weeks were required for recovery of patients posttransplant, with further enhancement by splenectomy. Some recipients showed recovery that exceeded the normal reference range, which warranted monitoring. Acetyl salicylic acid only affected 1 platelet activation receptor.

Coagulological disorders during liver resections in patients with malignant tumors

The purpose of the study. To study the coagulation profile of patients undergoing liver resections using laboratory tests and thromboelastography. Materials and methods. The results of observation of coagulological changes in 45 patients were studied: with colorectal liver metastases - 24 (53.3%) cases, with hepatocellular cancer - 14 (31.1%), with cholangiocellular cancer - 7 (15.6%). Right-sided hemihepatectomy was performed in 22 (48.9%) patients, right-sided extended hemihepatectomy - in 7 (15.6%), left-sided hemihepatectomy - in 8 (17.8%), resection of the left sector - in 8 (17.8%). Laboratory diagnostics included standard conventional coagulation tests and thromboelastography. Results. The concentrations of total bilirubin and alkaline phosphatase significantly increased up to 3 days of the postoperative period inclusive. The international normalized ratio increased significantly after liver resection immediately after surgery, as well as after 1, 3 and 5 days of observation. The level of fibrinogen in the first day after surgery decreases, and then increased to the initial value. Thromboelastometric parameters indicated a stable and normal coagulation function with a short ability to hypercoagulate immediately after liver resection. Conclusion. Although standard routine laboratory tests such as activated partial thromboplastin time and international normalized ratio may remain within normal limits or indicate hypocoagulation, the patient may be at risk for thrombosis. Thromboelastography measures the rate of formation, stabilization, and lysis of a clot using whole blood, which gives a more complete picture of coagulation status. Thus, routine laboratory parameters alone should not be used to decide whether to delay thromboembolic prophylaxis after liver resection.

The coagulation changes associated with acute variceal bleeding in patients with HCV-induced cirrhosis as assessed by rotational thromboelastometry

Background and objectivesAlterations of hemostasis in patients with decompensated cirrhosis are complex. Accordingly, standard coagulation tests are not feasible to evaluate bleeding risk in these patients. The aim of this study was to assess the coagulation kinetics in cirrhotic patients with variceal bleeding using rotational thromboelastometry (ROTEM). ROTEM including EXTEM, INTEM, and FIBTEM which represent extrinsic, intrinsic pathways, and fibrinogen activity, respectively, was measured in 60 cirrhotic patients with variceal bleeding who were compared to 60 patients with stable cirrhosis. APTEM was optionally performed to evaluate fibrinolysis.ResultsOverall, cirrhosis patients displayed features of hypofibrinolysis, whereas the state of hypocoagulability was significantly higher in cirrhotic patients with variceal bleeding (61.7% versus 30%, p = 0.001). Values of clot formation time (CFT) by EXTEM and INTEM correlated positively with those of model for end-stage liver disease score (r = 0.529, p = 0.001, and r = 0.595, p < 0.001, respectively). Furthermore, in a multivariate analysis, values of CFT in both assays were significantly associated with increased risk of 1.9 (95% CI = 1.04–2.45, p = 0.02) and of 1.78 (95% CI = 1.02–2.14, p = 0.01), respectively, for occurrence of variceal bleeding.ConclusionCirrhotic patients with variceal bleeding frequently showed a hypocoagulable state that is triggered by thrombocytopenia and/or hypofibrinogenemia. CFT by EXTEM and INTEM seemed to be an extra marker for disease severity and prognosis in cirrhosis patients, in addition to its valuable role in prediction of variceal bleeding in these patients. However, large multicenter studies have yet been required.

Gingival bleeding is a useful clinical feature in the diagnosis of hereditary bleeding disorders in children.

The search for hereditary bleeding disorders (HBD) prior to invasive procedures in children is primarily based on personal and family bleeding history. Although several scores are available, they have only been evaluated in specific situations or in adults. Our monocentric retrospective study aimed to analyze the association between clinical history and four scores (HEMSTOP, PBQ, ISTH-BAT, TOSETTO) and the diagnosis of MHC in children referred to the University Hospital of Montpellier for hemostasis investigations. A total of 117 children were retrospectively included in the study. Of these, 57 (49%) were diagnosed with HBD, with 30 having primary bleeding disorders and 27 having coagulation disorders. The diagnosis of HBD was significantly associated with gingival bleeding, which was present in 30% of HBD patients. In our population, only the HEMSTOP score showed an association with the diagnosis of HBD, but it was positive in only 48% of patients. By including gingival bleeding as a factor, we modified the HEMSTOP score, which increased its sensitivity from 0.45 to 0.53. When examining primary bleeding disorders, the modified HEMSTOP score, with the inclusion of gingival bleeding, enables us to diagnose 63% of patients (see Fig.1). Conclusion: Therefore, gingival bleeding should be considered a useful factor in bleeding history for HBD diagnosis. Adding this symptom to a screening score such as HEMSTOP improves its sensitivity. To confirm our findings, a prospective study is required. Trial registration: Study registration number: NCT05214300. What is Known: • Screening for hereditary bleeding disorder diseases is a necessity and a challenge in children. • Minor disorders of primary hemostasis are the most common, but often escape standard coagulation tests. What is New: • Gingival bleeding is a frequent symptom that is easy to investigate and may point to a primary hemostasis disorder. • Adding the gingival bleeding item to a routine screening score such as HEMSTOP improves sensitivity.

Results of Preclinical Studies of 4-(2-(4-nitrophenyl)-2-oxoethyl)-1-(thietane-3-yl)-1H-1,2,4-triazole-4-th Bromide in Relation to the Hemostasis System &lt;i&gt;in vivo&lt;/i&gt;

Introduction. A characteristic manifestation of vascular brain damage is depressive disorders that accompany both acute and chronic disorders of cerebral circulation. Depression not only reduces the patient's quality of life, but also complicates the treatment of basic vascular disease, increases the risk of stroke and death. Therefore, complex therapy of vascular depression includes not only antidepressants, but also basic means to correct the consequences of disorders of cerebral blood flow, including with antiplatelet activity. In this regard, the development of a new molecule based on thietane-containing heterocycles, combining the properties of an antidepressant and an antiplatelet agent.Aim. To conduct a preclinical evaluation of 4-(2-(4-nitrophenyl)-2-oxoethyl)-1-(thietane-3-yl)-1H-1,2,4-triazol-4 bromide when administered to rats.Materials and methods. A study was conducted of the effect of 4-(2-(4-nitrophenyl)-2-oxoethyl)-1-(thietan-3-yl)-1H-1,2,4-triazol-4-bromide on the hemostasis system during intravenous and intragastric administration to healthy white non-linear sexually mature male rats (n = 160). Thromboelastography was performed on a TEG 5000 device, activated with a 0.2 M solution of calcium chloride, Born aggregometry and standard clotting tests to assess the coagulation component of hemostasis.Result and discussion. The findings show that 4-(2-(4-nitrophenyl)-2-oxoethyl)-1-(thietane-3-yl)-1H-1,2,4-triazole-4-th bromide with peroral administration exceeded acetylsalicylic acid by 2.8 times in terms of ED50, and by 1.8 times with intravenous way of administration accordingly. A similar effect of pentoxifylline in the intravenous route of administration was recorded at a concentration of 27.8 mg/kg versus 12.4 mg/kg of compound I. The results of a complex method to assess the state of the hemostasis system indicate a more pronounced antiaggregational effect of compound I compared with pentoxifylline and acetylsalicylic acid.Conclusion. Preclinical studies of 4-(2-(4-nitrophenyl)-2-oxoethyl)-1-(thietane-3-yl)-1H-1,2,4-triazole-4 bromide, was demonstrated that a combination of antidepressant and antiplatelet activity, which can serve as a basis for further drug development.

Hemostatic Profile of Intrauterine Growth-Restricted Neonates: Assessment with the Use of NATEM Assay in Cord Blood Samples.

Intrauterine growth restriction (IUGR) is associated with hemorrhagic and thrombotic complications during the perinatal period. Thrombocytopenia, platelet dysfunction, and prolonged standard coagulation tests are observed in this population. The aim of this study is to examine the hemostatic profile of IUGR neonates with the use of a non-activated assay (NATEM) in cord blood samples. During an 18 month period, a NATEM ROTEM assay was performed on cord blood samples of 101 IUGR neonates. A total of 189 appropriate for gestational age (AGA) neonates were used as a control group. The NATEM variables recorded include the following: clotting time (CT); clot formation time (CFT); clot amplitude at 5, 10, and 20 min (A5, A10, A20); α-angle (a°); maximum clot firmness (MCF); lysis index at 30 and 60 min (LI30, LI60); and maximum clot elasticity (MCE). IUGR neonates demonstrate a hypocoagulable state, with lower A5, A10, A2, MCF, and MCE values when compared to AGA. Using multiple linear regression, we determined IUGR as an independent factor influencing all NATEM parameters (except CT and LI30) exhibiting a hypocoagulable and hypofibrinolytic profile. Platelet count was positively correlated with A5, A10, A20, MCF, alpha angle, and MCE, and negatively correlated with CFT. IUGR neonates appear with lower clot strength and elasticity and prolonged clot kinetics, as illustrated by ROTEM variables.

Assessment of haemostasis in pregnant women

BACKGROUND Contemporary guidelines pertaining to the evaluation of bleeding risk recommend conducting a comprehensive examination of both personal and family histories concerning haemorrhagic diatheses. OBJECTIVES We employed the standardised HEMSTOP (Hematoma, hEmorrhage, Menorrhagia, Surgery, Tooth extraction, Obstetrics, Parents) questionnaire in pregnant women to evaluate its efficacy in detecting a haemostatic disorder and predicting the risk of haemorrhage associated with delivery. DESIGN A single-centre retrospective observational cohort study. SETTING Brugmann Hospital, a tertiary university institution. PATIENTS All full-term parturients who underwent vaginal or caesarean delivery in our hospital between January 2020 and December 2021 were included in the study. A total of 3588 patients were enrolled. MAIN OUTCOME MEASURES The primary aim of this study was to assess the sensitivity and specificity of the HEMSTOP questionnaire in identifying individuals with an abnormal primary haemostatic profile. The secondary objective was to evaluate the sensitivity and specificity of the HEMSTOP questionnaire in predicting postpartum haemorrhage (PPH; defined as blood loss &gt;1000 ml). Additionally, positive-predictive values and negative-predictive values (NPVs) were calculated. RESULTS The specificity and sensitivity of the HEMSTOP questionnaire to predict an abnormal standard coagulation test in pregnant women are respectively 96% [95% confidence interval (CI), 0.95 to 0.97] and 39% (95% CI, 0.20 to 0.61). Its NPV is 100%. The specificity and sensitivity of the HEMSTOP questionnaire to predict postpartum bleeding risk are respectively 96% (95% CI, 0.95 to 0.97) and 8% (95% CI, 0.06 to 0.11). CONCLUSION In the conditions of our study, the HEMSTOP questionnaire enables the prediction of a primary haemostatic anomaly with a specificity and sensitivity comparable to routine haemostatic assessments. These findings concur with the recommendation against the routine prescription of laboratory tests for patients lacking a history of bleeding diathesis. TRIAL REGISTRATION Clinical Trial NCT 05191251.

Evaluation of Clotting Parameters in Pregnant Women with Placental Blood Clots: Impact of Patient Characteristics and Assessment of Clexane Efficacy

Background: Clexane is used in pregnant women (PW) to minimize placental blood clotting (PBC) and fetal danger. Standard coagulation tests such as prothrombin time (PT), activated partial thromboplastin time (APTT), and international normalized ratio (INR) are critical for anticoagulant medication optimization. As a result, the study's goal was to evaluate the efficacy of clexane as well as adherence to the American Heart Association's recommended limits for routine coagulation tests. Methods: The study included forty normal PW as controls and forty PW with PBC as patients from Al-Mafraq Hospital in Jordan. Patients were administered daily subcutaneous injections of 40 mg of clexane as an anticoagulant, in conjunction with a daily 75 mg aspirin regimen. During the first trimester, 5 ml of venous blood were drawn from each participant. The PT, INR and APTT were measured. This assessment also considered variables including plasma fibrinogen concentration (PFC), age, body mass index (BMI), blood type, and fetal gender. Results: The mean age \(\pm\) SD were 29.6 \(\pm\) 6.2 for the patient group and 28.3 \(\pm\) 5.9 years for the control group. The changes in PT, INR, APTT and PFC between the control and patient groups were statistically significant independent of mother's age, BMI, baby gender, or blood type. Patients displayed inadequate anticoagulation with an INR of 0.8, falling below the recommended therapeutic range of 2-3 for anticoagulant treatment. Surprisingly, by the end of the clinical study, all patients under investigation had safely delivered their babies without difficulties. Conclusion: The observed rise in fibrinogen levels among patients may contribute to PBC formation, necessitating further investigation. Evaluation of the safety and efficacy of a combined 40 mg Clexane and 75 mg aspirin regimen in PW from the Al-Mafraq region, Jordan, is warranted.

Validation of the time to attain maximal clot amplitude after reaching maximal clot formation velocity parameter as a measure of fibrinolysis using rotational thromboelastometry and its application in the assessment of fibrinolytic resistance in septic patients: a prospective observational study: communication from the ISTH SSC Subcommittee on Fibrinolysis

BackgroundIn sepsis, fibrinolysis resistance correlates with worse outcomes. Practically, rotational thromboelastometry (ROTEM) is used to report residual clot amplitude relative to maximum amplitude at specified times after clot formation clot lysis indices (CLIs). However, healthy individuals can exhibit similar CLIs, thus making it challenging to solely diagnose the low fibrinolytic state. Furthermore, CLI does not include the kinetics of clot formation, which can affect overall fibrinolysis. Therefore, a more nuanced analysis, such as time to attain maximal clot amplitude after reaching maximal clot formation velocity (t-AUCi), is needed to better identify fibrinolysis resistance in sepsis. ObjectivesTo evaluate the correlation between the degree of fibrinolytic activation and t-AUCi in healthy or septic individuals. MethodsWhole blood (n = 60) from septic or healthy donors was analyzed using tissue factor–activated (EXTEM) and nonactivated (NATEM) ROTEM assays. Lysis was initiated with tissue-type plasminogen activator, and CLI and t-AUCi were calculated. Standard coagulation tests and plasma fibrinolysis markers (D-dimer, plasmin-α2-antiplasmin complex, plasminogen activator inhibitor type 1, and plasminogen) were also measured. Resultst-AUCi values decreased with increasing fibrinolytic activity and correlated positively with CLI for different degrees of clot lysis both in EXTEM and NATEM. t-AUCi cutoff value of 1962.0 seconds in EXTEM predicted low fibrinolytic activity with 81.8% sensitivity and 83.7% specificity. In addition, t-AUCi is not influenced by clot retraction. ConclusionWhole-blood point-of-care ROTEM analyses with t-AUCi offers a more rapid and parametric evaluation of fibrinolytic potential compared with CLI, which can be used for a more rapid and accurate diagnosis of fibrinolysis resistance in sepsis.

Detection of glycocalyx degradation in real time: A conceptual model of thromboelastography

BackgroundThe endothelial glycocalyx is a critical component of the vascular barrier; its disruption after shock states may contribute to coagulopathy in a variety of conditions. Measurement of glycocalyx components in plasma have been used to index glycocalyx degradation but are not available as a point of care test. Heparanoids, such as heparan sulfate, may affect coagulation which may be detected by either thromboelastography or activated clotting time. MethodsEndothelial glycocalyx components syndecan-1 and heparan sulfate were added to blood samples at clinically relevant concentrations. Thromboelastography values included clot reaction time, clot amplification and fibrinogen values, and maximum clot strength (maximum amplitude, platelets). The heparinase thromboelastography cartridge was used to detect a heparin-like effect. The activated clotting time test was performed subsequently using the heparan sulfate blood samples to compare a standard coagulation test with thromboelastography clot reaction times. ResultsBoth thromboelastography clot reaction time (with comparison to heparinase) and activated clotting time were useful to detect effects of coagulation. Thromboelastography also detected platelet and fibrinogen abnormalities at higher heparan sulfate concentrations. Studies using thromboelastography or even activated clotting time may be useful to detect glycocalyx degradation after shock states and may guide clinical decision making. ConclusionThromboelastography and or activated clotting time may be useful to detect glycocalyx degradation as a point of care test in patients in the acute setting. Additionally, these assays may detect previous undisclosed coagulopathy due to glycocalyx degradation.

Point-of-care, goal-directed management of bleeding in trauma patients.

The purpose of this review is to consider the clinical value of point-of-care (POC) testing in coagulopathic trauma patients with traumatic brain injury (TBI) and trauma-induced coagulopathy (TIC). Patients suffering from severe TBI or TIC are at risk of developing pronounced haemostatic disorders. Standard coagulation tests (SCTs) are insufficient to reflect the complexity of these coagulopathies. Recent evidence has shown that viscoelastic tests (VETs) identify haemostatic disorders more rapidly and in more detail than SCTs. Moreover, VET results can guide coagulation therapy, allowing individualised treatment, which decreases transfusion requirements. However, the impact of VET on mortality remains uncertain. In contrast to VETs, the clinical impact of POC platelet function testing is still unproven. POC SCTs are not able to characterise the complexity of trauma-associated coagulopathy. VETs provide a rapid estimation of underlying haemostatic disorders, thereby providing guidance for haemostatic therapy, which impacts allogenic blood transfusion requirements. The value of POC platelet function testing to identify platelet dysfunction and guide platelet transfusion is still uncertain.