Standard Coagulation Tests Research Articles

A prospective randomized open-label trial on the comparative effects of 6% hydroxyethyl starch 130/0.4 versus polyionic isotonic crystalloids on coagulation parameters in dogs with spontaneous hemoperitoneum.

To evaluate the effects of 6% hydroxyethyl starch 130/0.4 (HES) and a polyionic isotonic crystalloid (CRYS) on standard coagulation tests and rotational thromboelastometry (ROTEM) in dogs with spontaneous hemoperitoneum (SHP). Prospective randomized open-label clinical study. University teaching hospital. Forty-two client-owned dogs presented with SHP. Dogs diagnosed with SHP and hypovolemic shock were randomly allocated to receive HES (10mL/kg, n=22) or CRYS (30mL/kg, n=20) intravenously over 20 minutes for hemodynamic stabilization. Parameters measured before (T0 ) and after (T1 ) treatment were HCT, platelet counts, prothrombin time, activated partial thromboplastin time, fibrinogen concentrations, and extrinsic activated (EXTEM), intrinsic activated (INTEM), and extrinsic activated with platelet inhibition ROTEM assays. Data were analyzed as absolute values and as the percentage change from T0 to T1 . No significant differences between groups were detected in any variable at T0 , and for HCT, platelet counts, prothrombin time, activated thromboplastin time, and fibrinogen concentrations at T1 . Clot formation time in EXTEM was significantly prolonged (P= 0.037), and maximum clot firmness was significantly decreased (P= 0.038) in the HES group compared to the CRYS group at T1 . The percentage change in EXTEM clotting time (P= 0.012) and INTEM clot formation time (P= 0.031) was greater after HES than CRYS. Lysis indices remained at 100% for all ROTEM assays in both groups. Compared to a 3-fold volume of CRYS, administration of HES was associated with impairment in ROTEM parameters in dogs with SHP, but no evidence of hyperfibrinolysis was detected.

Coagulation Changes during Central Hypovolemia across Seasons.

Lower body negative pressure (LBNP) application simulates hemorrhage. We investigated how seasons affect coagulation values at rest and during LBNP. Healthy participants were tested in cold (November–April) and warm (May–October) months. Following a 30-min supine period, LBNP was started at −10 mmHg and increased by −10 mmHg every five minutes until a maximum of −40 mmHg. Recovery was for 10 min. Blood was collected at baseline, end of LBNP, and end of recovery. Hemostatic profiling included standard coagulation tests, calibrated automated thrombogram, thrombelastometry, impedance aggregometry, and thrombin formation markers. Seven men (25.0 ± 3.6 years, 79.7 ± 7.8 kg weight, 182.4 ± 3.3 cm height, and 23.8 ± 2.3 kg/m2 BMI) and six women (25.0 ± 2.4 years, 61.0 ± 8.4 kg weight, 167 ± 4.7 cm height, and 21.8 ± 2.4 kg/m2 BMI) participated. Baseline levels of prothrombin (FII), tissue factor (TF) and markers for thrombin generation F1+2 and the thrombin/antithrombin complex (TAT) were higher during summer. Factor VIII, prothrombin fragment 1+2 (F1+2), TAT and the coagulation time showed significant increases during LBNP in both seasons. Some calibrated automated thrombography variables (Calibrated automated thrombography (CAT): lag, time to peak (ttPeak), peak) shifted in a procoagulant direction during LBNP in summer. Red blood cell counts (RBC), hemoglobin and white blood cell counts (WBC) decreased during LBNP. LBNP application reduced prothrombin time in winter and activated partial thromboplastin time in summer. Greater levels of FII, TF, F1+2, and TAT—a more pronounced LBNP-induced procoagulative effect, especially in CAT parameters (lag time (LT), Peak, ttPeak, Velindex)—were seen in summer. These results could have substantial medical implications.

Clinical and pathophysiologic aspects of ECMO-associated hemorrhagic complications.

Extracorporeal membrane oxygenation (ECMO) is increasingly used to treat severe cases of acute respiratory or cardiac failure. Hemorrhagic complications represent one of the most common complications during ECMO, and can be life threatening. The purpose of this study was to elucidate pathophysiological mechanisms of ECMO-associated hemorrhagic complications and their impact on standard and viscoelastic coagulation tests. The study cohort included 27 patients treated with VV-ECMO or VA-ECMO. Hemostasis was evaluated using standard coagulation tests and viscoelastic parameters investigated with rotational thromboelastometry. Anticoagulation and hemorrhagic complications were analyzed for up to seven days depending on ECMO duration. Hemorrhagic complications developed in 16 (59%) patients. There were 102 discrete hemorrhagic episodes among 116 24-hour-intervals, of which 27% were considered to be clinically significant. The highest number of ECMO-associated hemorrhages occurred on the 2nd and 3rd day of treatment. Respiratory tract bleeding was the most common hemorrhagic complication, occurring in 62% of the 24-hour intervals. All 24-hours-intervals were divided into two groups: “with bleeding” and “without bleeding”. The probability of hemorrhage was significantly associated with abnormalities of four parameters: increased international normalized ratio (INR, sensitivity 71%, specificity 94%), increased prothrombin time (PT, sensitivity 90%, specificity 72%), decreased intrinsic pathway maximal clot firmness (MCFin, sensitivity 76%, specificity 89%), and increased extrinsic pathway clot formation time (CFTex, sensitivity 77%, specificity 87%). In conclusions, early ECMO-associated hemorrhagic complications are related to one traditional and two novel viscoelastic coagulation abnormalities: PT/INR elevation, reduced maximum clot firmness due to intrinsic pathway dysfunction (MCFin), and prolonged clot formation time due to extrinsic pathway dysfunction (CFTex). When managing hemostasis during ECMO, derangements in PT/INR, MCFin and CFTex should be focused on.

Relationship of Edoxaban Plasma Concentration and Blood Coagulation in Healthy Volunteers Using Standard Laboratory Tests and Viscoelastic Analysis.

The capability of viscoelastic measurement parameters to screen anticoagulation activity of edoxaban in relation to its plasma concentrations was evaluated in 15 healthy male volunteers. Blood samples were drawn before the oral administration of edoxaban 60 mg and 2, 4, 6, 8, and 24 hours after administration. At each time, standard coagulation tests were performed, blood viscoelastic properties were measured with a thromboelastometry device ROTEM delta analyzer (Instrumentation Laboratory, Werfen, Barcelona, Spain), and edoxaban plasma concentrations were measured. Our primary interest was the possible correlation between edoxaban plasma concentrations and values for ROTEM ExTEM, and FibTEM. We also studied the correlation of edoxaban plasma concentrations with the results of standard coagulation tests. We saw the effect of a single dose of edoxaban most clearly in clotting time (CT) of ROTEM ExTEM and FibTEM. Changes in these parameters correlated significantly with edoxaban plasma concentrations up to 6 hours from the ingestion of the drug. Activated partial thromboplastin time, prothrombin time, and anti-factor Xa were also affected. Peak changes were observed 2 and 4 hours after administration of edoxaban. The changes were mostly reversed after 8 hours. In conclusion, ROTEM CT correlates significantly with edoxaban plasma concentrations and can be used to estimate the effect of edoxaban. ROTEM should be considered as part of the assessment of coagulation, with the big advantage of being readily available on site.

Menstrual Phase Affects Coagulation and Hematological Parameters during Central Hypovolemia.

Background: It has been reported that women have a higher number of heart attacks in the “follicular phase” of the menstrual cycle. We, therefore, tested the hypothesis that women in the follicular phase exhibit higher coagulability. As lower body negative pressure (LBNP) has been used previously to assess coagulation changes in whole blood (WB) samples in men and women, effects of menstrual phase on coagulation was assessed during LBNP. Methods: Seven women, all healthy young participants, with no histories of thrombotic disorders and not on medications, were tested in two phases of the menstrual cycle (early follicular (EF) and mid-luteal (ML)). LBNP was commenced at −10 mmHg and increased by −10 mmHg every 5 min until a maximum of −40 mmHg. Recovery up to 10 min was also monitored. Blood samples were collected at baseline, at end of LBNP, and at end of recovery. Hemostatic profiling included comparing the effects of LBNP on coagulation values in both phases of the menstrual cycle using standard coagulation tests, calibrated automated thrombogram, thrombelastometry, impedance aggregometry, and markers of thrombin formation. Results: LBNP led to coagulation activation determined in both plasma and WB samples. During both phases, coagulation was affected during LBNP, as reflected in their decreased partial thromboplastin time (PTT) and elevated coagulation factor VIII FVIII, F1 + 2, and thrombin-antithrombin (TAT) levels. Additionally, during the ML phase, greater PT [%] and shorter time to peak (ttPeak) values (implying faster maximum thrombin formation) suggest that women in the ML phase are relatively hypercoagulable compared to the early follicular phase. Conclusions: These results suggest that thrombosis occurs more during the midluteal phase, a finding with substantial medical implications.

Early thromboelastography in acute traumatic coagulopathy: an observational study focusing on pre-hospital trauma care

BackgroundMajor brain injury and uncontrolled blood loss remain the primary causes of early trauma-related mortality. One-quarter to one-third of trauma patients exhibit trauma-induced coagulopathy (TIC). Thromboelastometry (ROTEM) and thrombelastography (TEG) are valuable alternatives to standard coagulation testing, providing a more comprehensive overview of the coagulation process.PurposeEvaluating thromboelastographic profile, the incidence of fibrinolysis (defined as Ly30 > 3%) in severe trauma patients, and factors influencing pathological coagulation pattern.MethodsProspective observational 2 years cohort study on severe trauma patients assisted by Helicopter Emergency Medical System (HEMS) and Level 1 Trauma Center, in a tertiary referral University Hospital.ResultsEighty three patients were enrolled, mean NISS (new injury severity score) 36 (± 13). Mean R value decreased from 7.25 (± 2.6) to 6.19 (± 2.5) min (p < 0.03); 48 (60%) patients had a reduction in R from T0 to T1. In NISS 25–40 and NISS > 40 groups, changes in R value increased their significance (p = 0.04 and p < 0.03, respectively). Pathological TEG was found in 71 (88.8%) patients at T0 and 74 (92.5%) at T1. Hypercoagulation was present in 57 (71.3%) patients at T0, and in 66(82.5%) at T1. 9 (11.3%) patients had hyperfibrinolysis at T0, 7 (8.8%) patients at T1. Prevalence of StO2 < 75% at T0 was greater in patients whose TEG worsened (7 patients, 46.7%) against whose TEG remained stable or improved (8 patients, 17.4%) from T0 to T1 (p = 0.02). 48 (57.8%) patients received < 1000 mL of fluids, while 35 (42.2%) received ≥ 1000 mL. The first group had fewer patients with hypercoagulation (20, 41.6%) than the second (6, 17.6%) at T1 (p < 0.03). No differences were found for same TEG pattern at T0, nor other TEG pattern.ConclusionOur population is representative of a non-hemorrhagic severe injury subgroup. Almost all of our trauma population had coagulation abnormalities immediately after the trauma; pro-coagulant changes were the most represented regardless of the severity of injury. NISS appears to affect only R parameter on TEG. Hyperfibrinolysis has been found in a low percentage of patients. Hypoperfusion parameters do not help to identify patients with ongoing coagulation impairment. Small volume resuscitation and mild hypotermia does not affect coagulation, at least in the early post-traumatic phase.

Trauma-Induced Coagulopathy and Massive Bleeding: Current Hemostatic Concepts and Treatment Strategies.

Hemorrhage after trauma remains a significant cause of preventable death. Trauma-induced coagulopathy (TIC) at the time of hospital admission is associated with an impaired outcome. Rather than a universal phenotype, TIC represents a complex hemostatic disorder, and standard coagulation tests are not designed to adequately reflect the complexity of TIC. Viscoelastic testing (VET) has gained increasing interest for the characterization of TIC because it provides a more comprehensive depiction of the coagulation process. Thus, VET has been established as a point-of-care-available hemostatic monitoring tool in many trauma centers. Damage-control resuscitation and early administration of tranexamic acid provide the basis for treating TIC. To improve survival, ratio-driven massive transfusion protocols favoring early and high-dose plasma transfusion have been implemented in many trauma centers around the world. Although plasma contains all coagulation factors and inhibitors, only high-volume plasma transfusion allows for adequate substitution of lacking coagulation proteins. However, high-volume plasma transfusion has been associated with several relevant risks. In some European trauma facilities, a more individualized hemostatic therapy concept has been implemented. The hemostatic profile of the bleeding patient is evaluated by VET. Subsequently, goal-directed hemostatic therapy is primarily based on coagulation factor concentrates such as fibrinogen concentrate or prothrombin complex concentrate. However, a clear difference in survival benefit between these two treatment strategies has not yet been shown. This concise review aims to summarize current evidence for different diagnostic and therapeutic strategies in patients with TIC.

Thromboelastography to Assess Coagulopathy in Traumatic Brain Injury Patients Undergoing Therapeutic Hypothermia.

Therapeutic hypothermia has been a treatment option for patients with severe traumatic brain injury (TBI) for many years. There has, however, been uncertainty whether hypothermia in this context also increased clinical bleeding risk, perhaps due to platelet dysfunction. Standard coagulation tests do not allow accurate assessment of in vivo coagulation. We studied specific coagulation abnormalities in patients undergoing therapeutic hypothermia for severe TBI using bedside thromboelastography (TEG).We studied 20 patients with severe blunt TBI from a single tertiary ICU who were enrolled in the prophylactic hypothermia to lessen traumatic brain injury (POLAR) trial. Ten patients had been randomized to hypothermia, and 10 were controls receiving normothermic standard care. TEG was undertaken during and after therapeutic hypothermia, and at the same time points in controls. Coagulation profiles were then compared between the hypothermic and control patients, and also between hypothermia and later normothermia in the study patients. Patients were primarily young (mean age 34 years) and male (85%). Measures of injury severity, including Glasgow coma score and injury severity scale, were not different between groups. Using TEG, the median alpha angle was reduced in hypothermic patients compared with controls (69.2° vs. 72.0°, p = 0.02), although both were within the normal range. LY30 was also reduced (0.0% vs. 0.5%, p < 0.01). Both differences persisted when hypothermic patients were compared with themselves during later normothermia. Therapeutic hypothermia during severe TBI causes a small decrease in the rate of clot formation. However, this decrease is within the normal range, and is unlikely to be clinically significant.

Fibrin monomers and association with significant hemorrhage or mortality in severely injured trauma patients

BackgroundPost-traumatic hemorrhage is still the leading cause of potentially preventable death in patients with severe trauma. Traumatic-induced coagulopathy has been described as a risk factor for significant hemorrhage and mortality in this population. Fibrin monomers (FMs) are a direct marker of thrombin action, and thus reflect coagulation activation. This study sought to determine the association of FMs levels at admission with significant hemorrhage and 28-day mortality after a severe trauma. MethodsWe conducted a retrospective, observational study including all severe trauma patients admitted in a level-1 trauma center between January 2012 and December 2017. Patients with severe traumatic brain injury or previous anticoagulant / antiaggregant therapies were excluded. FMs measurements and standard coagulation test were taken at admission. Significant hemorrhage was defined as a hemorrhage requiring the transfusion of ≥ 4 Red Blood Cells units during the first 6 h. Multivariable analysis was applied to identify predictors of significant hemorrhage and a simple logistic regression analysis was applied to identify an association between FMs and 28-day mortality. ResultsOverall, 299 patients were included. A total of 47 (16%) experienced a significant hemorrhage. The ROC curve demonstrated that FMs had a poor accuracy to predict the occurrence of significant hemorrhage with an AUC of 0.65 (0.57–0.74). The best threshold at 92.45 µg/ml had excellent sensitivity (87%) and negative predictive value (95%), but was not independently associated with significant hemorrhage (OR = 1.5; 95%CI (0.5–4.2)). The 28-day mortality rate was 5%. In simple logistic regression analysis, FMs values ≥109.5 µg/ml were significantly associated with 28-day mortality (unadjusted OR = 13.2; 95%CI (1.7–102)). ConclusionsFMs levels at admission are not associated with the occurrence of a significant hemorrhage in patients with severe trauma. However, the excellent sensitivity and NPV of FMs could help to identify patients with a low risk of severe bleeding during hospital care. In addition, FMs levels ≥109.5 µg/ml might be predictive of 28-day mortality.

Site-Of-Care Viscoelastic Assay in Major Trauma Improves Outcomes and Is Cost Neutral Compared with Standard Coagulation Tests.

Major hemorrhage is often associated with trauma-induced coagulopathy. Targeted blood product replacement could achieve faster hemostasis and reduce mortality. This study aimed to investigate whether thromboelastography (TEG®) goal-directed transfusion improved blood utilization, reduced mortality, and was cost effective. Data were prospectively collected in a U.K. level 1 trauma center, in patients with major hemorrhage one year pre- and post-implementation of TEG® 6s Hemostasis Analyzers. Mortality, units of blood products transfused, and costs were compared between groups. Patient demographics in pre-TEG (n = 126) and post-TEG (n = 175) groups were similar. Mortality was significantly lower in the post-TEG group at 24 h (13% vs. 5%; p = 0.006) and at 30 days (25% vs. 11%; p = 0.002), with no difference in the number or ratio of blood products transfused. Cost of blood products transfused was comparable, with the exception of platelets (average £38 higher post-TEG). Blood product wastage was significantly lower in the post-TEG group (1.8 ± 2.1 vs. 1.1 ± 2.0; p = 0.002). No statistically significant difference in cost was observed between the two groups (£753 ± 651 pre-TEG; £830 ± 847 post-TEG; p = 0.41). These results demonstrate TEG 6s-driven resuscitation algorithms are associated with reduced mortality, reduced blood product wastage, and are cost neutral compared to standard coagulation tests.

Thromboelastography maximum amplitude predicts short-term mortality in patients with hepatitis B virus-related acute-on-chronic liver failure.

Patients with hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF) exhibit complex hemostatic defects. Thromboelastography (TEG) can be used to reveal global hemostasis in patients with liver disease; however, little is known about the association between TEG and the outcome of patients with HBV-related ACLF. The present study aimed to investigate the value of TEG for predicting 90 day mortality in patients with HBV-related ACLF. A total of 51 patients with HBV-related ACLF, 26 patients with chronic hepatitis B (CHB) and 26 healthy controls (HC) were enrolled in the present study. TEG, standard coagulation tests, routine blood tests, biochemical markers and demographic variables were recorded and assessed for prognostic value. The results indicated that a prolonged reaction and kinetics (K) time, a shortened α angle and a decreased maximum amplitude (MA) and coagulation index (CI) were observed in patients with HBV-related ACLF, compared with CHB and HC subjects. Patients with HBV-related ACLF in the mortality group exhibited a decrease in α angle, MA, lysis at 30 min, CI, fibrinogen and platelet count, and an increase in K time, international normalized ratio (INR) and the model for end-stage liver disease (MELD) score in comparison with the survival group. MA and INR were two independent predictors of 90 day mortality in patients with HBV-related ACLF, with hazard ratios of 0.918 (95% CI, 0.867-0.971; P=0.003) and 3.141 (95% CI, 1.843-5.354; P<0.001) respectively. When predicting 90 day mortality, MA + INR exhibited the highest area under the receiver operating characteristic curve, followed by INR, MELD score and MA. Patients with ACLF and MA ≤51.5 mm exhibited a poorer outcome than those with MA >51.5 mm, as revealed via the Kaplan-Meier analysis. In summary, the findings of the present study suggested that TEG MA was associated with 90 day mortality in patients with HBV-related ACLF, and a combination of MA and INR was superior to MA, INR and MELD score in terms of prognostic value.

Assessment and monitoring of liver graft viability and initial function using interstitial microdialysis

Assessing the viability and monitoring the function of liver graft in the early postoperative period are critical clinical tasks. One possible solution is to determine the changes in concentration of blood glucose, its metabolites and glycerol in the graft using interstitial microdialysis. Objective: to study the dynamics of interstitial glucose, lactate, pyruvate and glycerol in the early post-liver transplant period – depending on the initial graft function (IGF) – and to compare with the results of standard laboratory blood tests. Materials and methods. Four selected clinical observations of deceased donor liver transplantation are presented. Two of the observations showed normal IGF, one observation – early allograft dysfunction (EAD), complicated by hepatic artery thrombosis (HAT), while one observation demonstrated primary non-function (PNF). Collection of microdialysis samples began after arterial reperfusion of the liver graft and continued continuously for 7 days or until death. Standard blood biochemistry and coagulation tests were performed at least once a day. Results. With normal IGF and a smooth postoperative period, interstitial concentrations of glucose, lactate, pyruvate and glycerol remained stable throughout the observation period, ranging from 5 to 20 mmol/L, 1.1 to 7.5 mmol/L, 90 to 380 μmol/L, and 10–100 μmol/L, respectively. EAD was associated with initially higher levels of glucose, lactate, and pyruvate. With HAT development, there was a rapid (within 2–4 hours) five-fold increase in interstitial concentration of lactate with simultaneous decrease in glucose and pyruvate levels to 0.1 mmol/L and 11 μmol/L, respectively. In the case of PNF, there was an initially high concentration of interstitial lactate – 16.4 mmol/L, which increased further to 35.5 mmol/L. Glucose concentration was close to 0. Changes in interstitial glucose, its metabolites and glycerol concentrations chronologically preceded the corresponding changes in peripheral blood composition by 3–5 hours. Conclusion. Microdialysis measurement of interstitial glucose, lactate, pyruvate and glycerol concentrations facilitates real-time monitoring of liver graft viability and function. The high sensitivity of the method could help in accelerating diagnosis of vascular complications (HAT in particular), as well as graft dysfunction with other causes. Therefore, the method is feasible in clinical practice.

Implementation of Thromboelastometry for Coagulation Management in Isolated Traumatic Brain Injury Patients Undergoing Craniotomy.

BackgroundCoagulopathy (CP) is a modifiable factor linked with secondary brain damage and poor outcome of traumatic brain injury (TBI). A shift towards goal-directed coagulation management has been observed recently. We investigated whether rotational thromboelastometry (ROTEM) based management could be successfully implemented in TBI patients and improve outcomes.Material/MethodsA prospective, case-control study was performed. Adult patients with isolated TBI requiring craniotomy were included in this study. All patients underwent standard coagulation tests (SCT). Patients were identified as either in control group or in case group. Patients in the case group were additionally tested with ROTEM to specify their coagulation status. Management of the patients in the control group was based on SCT, whereas management of patients in the case group was guided by ROTEM. Outcome measures were as follows: CP rate, protocol adhesion, blood loss, transfusions, progressive hemorrhagic injury (PHI), re-intervention, Glasgow coma score (GCS) and Glasgow outcome score (GOS) at discharge, and in-hospital mortality.ResultsThere were 134 patients enrolled (65 patients in the control group and 69 patients in the case group). Twenty-six patients in the control group (40%) were found to be coagulopathic (control-CP subgroup) and 34 patients in the case group (49.3%) were found to be coagulopathic (case-CP subgroup). Twenty-five case-CP patients had ROTEM abnormalities triggering protocolized intervention, and 24 of them were treated. Overall ROTEM-based protocol adhesion rate was 85.3%. Postoperative ROTEM parameters of case-CP patients significantly improved, and the number of coagulopathic patients decreased. The incidence of PHI (control versus case group) and neurosurgical re-intervention (control-CP versus case-CP subgroup) was in favor of ROTEM guidance (P<0.05). Mortality and GCS and GOS at discharge did not differ significantly between groups.ConclusionsROTEM led to consistent coagulation management, improved clot quality, and decreased incidence of PHI and neurosurgical re-intervention. Further studies are needed to confirm benefits of ROTEM in cases of TBI.

Thromboinflammation and the hypercoagulability of COVID‐19

Thromboinflammation and the hypercoagulability of COVID‐19

The procoagulant pattern of patients with COVID‐19 acute respiratory distress syndrome

BackgroundFew observations exist with respect to the pro‐coagulant profile of patients with COVID‐19 acute respiratory distress syndrome (ARDS). Reports of thromboembolic complications are scarce but suggestive for a clinical relevance of the problem. ObjectivesProspective observational study aimed to characterize the coagulation profile of COVID‐19 ARDS patients with standard and viscoelastic coagulation tests and to evaluate their changes after establishment of an aggressive thromboprophylaxis. MethodsSixteen patients with COVID‐19 ARDS received a complete coagulation profile at the admission in the intensive care unit. Ten patients were followed in the subsequent 7 days, after increasing the dose of low molecular weight heparin, antithrombin levels correction, and clopidogrel in selected cases. ResultsAt baseline, the patients showed a pro‐coagulant profile characterized by an increased clot strength (CS, median 55 hPa, 95% interquartile range 35‐63), platelet contribution to CS (PCS, 43 hPa; interquartile range 24‐45), fibrinogen contribution to CS (FCS, 12 hPa; interquartile range 6‐13.5) elevated D‐dimer levels (5.5 μg/mL, interquartile range 2.5‐6.5), and hyperfibrinogenemia (794 mg/dL, interquartile range 583‐933). Fibrinogen levels were associated (R2 = .506, P = .003) with interleukin‐6 values. After increasing the thromboprophylaxis, there was a significant (P = .001) time‐related decrease of fibrinogen levels, D‐dimers (P = .017), CS (P = .013), PCS (P = .035), and FCS (P = .038). ConclusionThe pro‐coagulant pattern of these patients may justify the clinical reports of thromboembolic complications (pulmonary embolism) during the course of the disease. Further studies are needed to assess the best prophylaxis and treatment of this condition.

The Thromboelastographic Profile at Birth in Very Preterm Newborns with Patent Ductus Arteriosus

Background: The role of hemostasis in the closure of patent ductus arteriosus (PDA) in preterm infants is controversial. Objective: To assess thromboelastography (TEG) at birth in very-low-birth-weight (VLBW) infants affected by PDA. Methods: This was an ancillary study of a prospective observational study aimed at defining the TEG profile in healthy VLBW infants in the first month of life. In this analysis, we included neonates of <33 weeks’ gestational age (GA) with PDA and compared TEG traces based on (1) spontaneous closure versus the need for pharmacological treatment and (2) treatment response. We collected blood samples in the 1st day of life to perform recalcified native-blood TEG (reaction time, maximum amplitude, and lysis at 30 min [Ly30)]), standard coagulation tests, and a full blood count. Results: We enrolled 151 infants with a PDA at the first echocardiogram; 111 experienced spontaneous PDA closure while 40 required treatment. Mean GA was 29.7 ± 1.7 and 27.6 ± 2.1 weeks, and birth weight was 1,158 ± 256 and 933 ± 263 g in the 2 groups, respectively (p < 0.001). The hemostatic profile was similar between groups. Median hematocrit (44.6 and 48.7%; p = 0.01) and platelet count (187 and 216 × 10³/μL; p = 0.04) were lower in the treated group, although differences lost significance after controlling for GA and illness severity in the multivariate analysis. Responders to PDA treatment (n = 20) had a significantly lower median Ly30 than nonresponders (0 and 0.7%; p = 0.02). Conclusion: TEG at birth does not predict spontaneous PDA closure in preterm newborns. Fibrinolysis is enhanced in nonresponders to PDA treatment; this observation warrants further investigation.

Whole-Blood Capillary Tube Clotting Time as a Possible Predictor of Hypertensive Disorders in Pregnancy

Background: Hypertensive disorders in pregnancy (HDP) are associated with coagulation abnormalities. However, results of standard coagulation tests in patients with HDP have been inconsistent. Aim: The aim of this study was to determine mean clotting time (CT) in subjects with HDP attending antenatal clinic at Murtala Muhammad specialist Hospital Kano, Nigeria and to assess CT as a possible predictor of HDP. Materials and Methods: Eighty-four HDP subjects and equal number of normotensive pregnant women were recruited for the study. Blood pressure was measured according to standard protocol. Urinalysis was performed using urine test strips (Medi-Test Combi 9®). Whole-blood CT was determined using capillary tube method. Hypertensive disorders in pregnancy were defined according to the report of National high blood pressure education program working group on high blood pressure in pregnancy. Data were analyzed using IBM SPSS version 23.0. Chi-square test of association and independent t test were used to determine association and difference between categorical and quantitative variables respectively. Pearson’s correlation was used to determine relationship between quantitative variables.

Considerations for Pediatric Heart Programs During COVID-19: Recommendations From the Congenital Cardiac Anesthesia Society.

Considerations for Pediatric Heart Programs During COVID-19: Recommendations From the Congenital Cardiac Anesthesia Society.

Global Coagulation Assays in Transgender Women on Oral and Transdermal Estradiol Therapy.

The thrombotic effects of estradiol therapy in transgender women are unclear. Global coagulation assays (GCA) may be better measures of hemostatic function compared with standard coagulation tests. To assess the GCA profiles of transgender women in comparison to cisgender controls and to compare how GCA differ between routes of estradiol therapy in transgender women. Cross-sectional case-control study. General community. Transgender women, cisgender male and cisgender female controls. Citrated blood samples were analyzed for (i) whole blood thromboelastography (TEG®5000), (ii) platelet-poor plasma thrombin generation (calibrated automated thrombogram); and (iii) platelet-poor plasma fibrin generation (overall hemostatic potential assay). Mean difference (95% confidence intervals) between groups are presented. Twenty-six transgender women (16 oral estradiol, 10 transdermal estradiol) were compared with 98 cisgender women and 55 cisgender men. There were no differences in serum estradiol concentration (P = 0.929) and duration of therapy (P = 0.496) between formulations. Transgender women demonstrated hypercoagulable parameters on both thromboelastography (maximum amplitude + 6.94 mm (3.55, 10.33); P < 0.001) and thrombin generation (endogenous thrombin potential + 192.62 nM.min (38.33, 326.91); P = 0.009; peak thrombin + 38.10 nM (2.27, 73.94); P = 0.034) but had increased overall fibrinolytic potential (+4.89% (0.52, 9.25); P = 0.024) compared with cisgender men. No significant changes were observed relative to cisgender women. Route of estradiol delivery or duration of use did not influence the GCA parameters. Transgender women on estradiol therapy demonstrated hypercoagulable GCA parameters compared with cisgender men with a shift towards cisgender female parameters. Route of estradiol delivery did not influence the GCA parameters.

Is placental blood a reliable source for the evaluation of neonatal hemostasis at birth?

Phlebotomy is among the main determinants of anemia of prematurity. Blood sparing policies endorsed umbilical cord blood (here called placental) as an alternative source for laboratory testing. Little is known on the suitability of placental blood to evaluate neonatal hemostasis of newborn infants. We aimed to compare the hemostatic profile of paired placental and infant venous blood, by means of prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen, antithrombin, protein C, thromboelastography (TEG) and thrombin generation assay (TGA). This was an observational single-center study. We collected at birth venous citrated blood from both placental and infant venous source and performed PT, APTT, fibrinogen, antithrombin, protein C, TEG (reaction time-R; kinetics-K alpha angle-α, maximum amplitude-MA and lysis at 30 minutes-LY30), and TGA (endogenous thrombin potential-ETP). We enrolled 60 neonates with a median gestational age (range) of 37 weeks (28+1 -41) and birth-weight 2417 g (950-4170). Based on TEG and TGA, placental blood showed a procoagulant imbalance as indicated by lower median R (4.0 vs. 6.1 min; p < 0.001) and K (1.3 vs. 2.2 min; p < 0.001); higher α-angle (69.7 vs. 57.4°; p < 0.001) and ETP (1260 vs. 1078; p = 0.002) than those observed for infant venous blood. PT and APTT did not differ significantly between the two groups. While placental and neonatal blood samples are equally suitable to measure the standard coagulation tests PT and APTT, placental blood leads to a procoagulant imbalance when testing is performed with TEG or TGA. These effects should be considered when interpreting results stemming from investigation of neonatal hemostasis.