Antithrombin Levels Research Articles

PO-0538 Deep Venous Thrombosis And Streptococcus Pyogenes Infection In A Healthy Newborn – A Rare Association

<h3>Introduction</h3> Despite its rare ocurrence, thromboembolic events are more frequent in newborns than in any other paediatric age group, and can results of diverse congenital or acquired prothrombotic factors. We report a case of deep venous thrombosis (DVT) in a previously healthy newborn admitted with <i>Streptococcus pyogenes </i>infection. <h3>Case Report</h3> 7-day old term female infant, born by vacuum delivery (birth weight 3780 g, Apgar 9/10), referred to our NICU with a 24 h history of grunting, anorexia and painful, swollen and purple discoloration of left lower limb. Laboratory findings showed leucopenia (1750/uL), neutrophilia (88%), C Reactive Protein 4.5 mg/dL, normal haematocrit and platelet count. Remaining lab values, including electrolytes and coagulation tests were normal. Soft tissue infection was suspected and antibiotics started. Lower limb ultrasound and Doppler showed extensive DVT in the left side. Subcutaneous enoxaparin was started and dosage was adjusted according with anti-Xa factor levels. Homocisteyne, protein S, protein C and antithrombin levels were normal. Factor V Leiden, G2021A prothrombin and antiphospholipid antibodies were absent. <i>Streptococcus pyogenes</i> was isolated in blood and cerebrospinal fluid cultures confirming the diagnosis of sepsis and meningitis. <h3>Discussion</h3> Thrombosis in neonatal period can cause significant morbidity and be life threatening. Early diagnosis and optimal treatment strategies are important to avoid complications. <i>Streptococcus pyogenes</i> has been associated with thromboembolic events in adults and older children. Despite being an uncommon cause of infection in neonates, this agent should be considered as the possible aetiology of DVT in previously healthy newborns.

Changes in haemostatic parameters during the menstrual cycle and subsequent use of drospirenone-containing oral contraceptives

IntroductionOral contraceptives (OC) increase the risk of venous thromboembolism that depends on the OC formulation and could at least partially be explained by impaired function of the protein C-system (APC resistance) and the tissue factor pathway inhibitor (TFPI)-system. There is limited information available on the effects of OC, containing a newer progestogen- drospirenone (DRSP-OC) on these two major anticoagulant pathways, thrombin generation, reflecting the overall state of coagulation, and other coagulation parameters. MethodsIn a study population consisting of 14 healthy women (age 21–33years) we investigated the effect of the menstrual cycle and subsequent use of DRSP-OC on APC resistance, the function of the TFPI-system, thrombin generation and on their major determinants, i.e. prothrombin, antithrombin, FV, FX, FVIII, protein C, protein S(total and free) and TFPI(full-length and free). ResultsAll studied parameters remained unchanged during the menstrual cycle. During DRSP-OC use we observed a significant increase in APC resistance (~2.4-fold), thrombin generation measured at low (~2.2-fold) and high tissue factor concentrations (~1.4-fold), plasma concentrations of prothrombin (19%), FX (31%), FVIII (17%) and protein C (43%). DRSP-OC use impaired the function of the TFPI-system and decreased plasma levels of antithrombin (−6%), FV (−22%), protein Stotal (−21%), protein Sfree (−20%), TFPIfull-length (−36%) and TFPIfree (−46%). ConclusionsDRSP-OC caused procoagulant changes in all studied haemostatic parameters. The impairment of the protein C- and TFPI-systems was more pronounced than the impairment of the coagulation pathways and can at least partially account for the increased risk of venous thromboembolism in users of DRSP-OC.

Administration of antithrombin concentrate in infants and children on extracorporeal life support improves anticoagulation efficacy.

Unfractionated heparin (UFH) is required in children on extracorporeal life support (ECLS) to maintain circuit patency. When high-dose UFH is inadequate to maintain an anticoagulant effect, the addition of antithrombin concentrate (ATC) is considered. The objective of this study was to review clinical experience giving 1,000 units (U) of ATC to patients on ECLS and UFH anticoagulation. Specifically, antithrombin (AT) levels pre- and post-administration of high-dose ATC, estimation of the efficacy of high-dose ATC administration as measured by the level of anticoagulation, and the incidence of adverse effects were determined. A retrospective chart review of all infants and children on ECLS who received ATC between June 2008 and May 2011 at Stollery Children's Hospital, Edmonton, Canada, was performed. A total of 78 doses of ATC were administered to 36 patients with a median age of 2.9 months (interquartile range, 0.6-12.6) on ECLS. Mean dose of ATC was 241 U/kg (95% confidence interval, 199-283). Mean AT level pre- and post-administration was 0.40 and 0.93 U/ml, respectively. Mean anti-Xa level pre- and post-AT administration was 0.23 and 0.41 U/ml, respectively. There were no associated acute adverse events. The administration of high-dose ATC decreases UFH dose requirements.

Antithrombin: Could It be a Diagnostic and Prognostic Marker in Septic Neonatal Foals?

Antithrombin (AT) levels are lower in human neonates affected by sepsis and in nonsurvivors compared with survivors. The aims of this study were to evaluate AT profile in healthy newborn foals and its diagnostic and prognostic role in septic foals during the first week of life. Fifteen healthy foals and 35 septic foals were enrolled. Blood samples were collected from each healthy foal at 30 minutes, 3 and 12 hours from birth, daily from days 1–7, and at days 10 and 14. Blood was collected from each septic foal twice a day from admission to discharge or death. The AT analysis was performed by chromogenic method. Healthy foals showed decreasing levels of AT between 3 hours and 2 days, followed by an increasing trend. Septic foals did not show any difference during the period of observation, and no differences were found between healthy and septic age-matched foals. The analysis of AT activity on the day of admission in septic foals showed higher levels compared with healthy foals, in animals hospitalized at 12 and 24 hours of age (P < .01). No differences were found at admission between foals affected by sepsis and that with septic shock. Nonsurviving foals showed significantly lower levels at 3 and 4 days of age compared with surviving foals; when surviving and nonsurviving foals were compared independently by the age, nonsurviving foals showed significant (P < .05) lower levels 12 hours after admission. In conclusion, AT seems to show neither a diagnostic nor a prognostic role in septic neonatal foals.

Abnormal hemostatic function one year after orthotopic liver transplantation can be fully attributed to endothelial cell activation

The long-term risk of thrombotic and vascular complications is elevated in liver transplant recipients compared to the general population. Patients with cirrhosis are in a hypercoagulable status during and directly after orthotopic liver transplantation, but it is unclear whether this hypercoagulability persists over time. We aimed to investigate the hemostatic status of liver transplant recipients one year after transplantation. We prospectively collected blood samples of 15 patients with a functioning graft one year after orthotopic liver transplantation and compared the hemostatic status of these patients with that of 30 healthy individuals. Patients one year after liver transplantation had significantly elevated plasma levels of von Willebrand factor (VWF). Thrombin generation, as assessed by the endogenous thrombin potential, was decreased in patients, which was associated with increased plasma levels of the natural anticoagulants antithrombin and tissue factor pathway inhibitor. Plasma fibrinolytic potential was significantly decreased in patients and correlated inversely with levels of plasminogen activator inhibitor-1. One year after liver transplantation, liver graft recipients have a dysregulated hemostatic system characterised by elevation of plasma levels of endothelial-derived proteins. Increased levels of von Willebrand factor and decreased fibrinolytic potential may (in part) be responsible for the increased risk for vascular disease seen in liver transplant recipients.

Characterization of antithrombin levels in pregnancy

ObjectiveTo characterize antithrombin (AT) levels in normal pregnancy. MethodsWe performed secondary analyses with data from 3 studies. Using a single measurement from each subject in the first analysis (cross-sectional), we correlated AT levels with gestational age from the middle of the second trimester throughout the third trimester of pregnancy. Using serial measurements in a second analysis (cohort), we compared AT levels between the late first and second trimesters of pregnancy and baseline (the level at 6weeks postpartum). Using serial measurements in a third analysis (cohort), we analyzed the pattern of change in AT levels in the immediate postpartum period. Assays of AT activity were performed using the Dade Behring (Siemens) Berichrom Antithrombin III Chromogenic Assay. AT levels were correlated with gestational age using the Pearson correlation coefficient and compared between the different time points using one-way ANOVA. ResultsOverall, AT levels were 20% lower than baseline during pregnancy (p<0.01). There was no significant difference between AT levels obtained between late first trimester and late second trimester. From midtrimester to term, however, AT levels were negatively correlated with gestational age with a 13% drop during this period of time (r=−0.26 [−0.39, −0.11]; p<0.01). Immediately after childbirth, AT levels fell precipitously to 30% below baseline (p<0.05) and reached a nadir 12hours postpartum before rising and returning to baseline by 72hours postpartum. ConclusionIt appears that antithrombin (AT) is consumed at the time of delivery. Our findings have implications for AT replacement or even anticoagulation at the time of delivery.

Abnormal hemostatic function one year after orthotopic liver transplantation can be fully attributed to endothelial cell activation

Background: The long-term risk of thrombotic and vascular complications is elevated in liver transplant recipients compared to the general population. Patients with cirrhosis are in a hypercoagulable status during and directly after orthotopic liver transplantation, but it is unclear whether this hypercoagulability persists over time. Aim: We aimed to investigate the hemostatic status of liver transplant recipients one year after transplantation. Methods: We prospectively collected blood samples of 15 patients with a functioning graft one year after orthotopic liver transplantation and compared the hemostatic status of these patients with that of 30 healthy individuals. Results: Patients one year after liver transplantation had significantly elevated plasma levels of von Willebrand factor (VWF). Thrombin generation, as assessed by the endogenous thrombin potential, was decreased in patients, which was associated with increased plasma levels of the natural anticoagulants antithrombin and tissue factor pathway inhibitor. Plasma fibrinolytic potential was significantly decreased in patients and correlated inversely with levels of plasminogen activator inhibitor-1. Conclusion: One year after liver transplantation, liver graft recipients have a dysregulated hemostatic system characterised by elevation of plasma levels of endothelial-derived proteins. Increased levels of von Willebrand factor and decreased fibrinolytic potential may (in part) be responsible for the increased risk for vascular disease seen in liver transplant recipients.

Antithrombin levels are unaffected by warfarin use.

The results of studies among patients with antithrombin deficiency have suggested that the use of warfarin will increase the level of antithrombin. To reevaluate the effect of warfarin on antithrombin levels using an automated amidolytic method in current use. Antithrombin levels were measured in patients who were receiving warfarin for atrial fibrillation and were compared with antithrombin levels in preoperative patients who had not received warfarin. Patients receiving warfarin had a mean antithrombin level of 100.40% (range, 81%-153%). Patients not receiving warfarin had a mean antithrombin level of 99.97% (range, 79%-120%). The Student t test was not significant for a difference between the mean antithrombin levels of the 2 populations. The use of warfarin does not increase the level of antithrombin in patients receiving the drug.

SEPCR Levels in Chronic Myeloproliferative Diseases and Their Association with Thromboembolic Events: A Case-Control Study.

Objective: Venous, arterial, and microcirculatory events are frequently encountered in the clinical course of essential thrombocytosis and polycythemia vera. We aimed to investigate the levels of soluble endothelial protein C receptor (sEPCR) in myeloproliferative diseases to see whether there was a difference between the patients with and without history of thromboembolism. Materials and Methods: The study included patients with polycythemia vera (n=12), patients with essential thrombocytosis (n=13), and controls (n=29). In all groups, we measured proteins C and S, antithrombin and sEPCR levels, and plasma concentrations of thrombin-antithrombin complex, prothrombin fragments 1+2, and D-dimer. Results: Comparing the patients with and without history of thromboembolic attack, statistically significant differences were not observed in terms of sEPCR, D-dimer, thrombin-antithrombin complex, prothrombin fragments 1+2, and hematocrit levels (p=0.318, 0.722, 0.743, 0.324, and 0.065, respectively). Conclusion: Significant increase in the parameters that reflect activation of coagulation, such as sEPCR, thrombin-antithrombin complex, prothrombin fragments 1+2, and D-dimer, reflects the presence of a basal condition that leads to a tendency toward thrombosis development in ET and PV when compared to healthy controls.

Differential associations of oral estradiol and conjugated equine estrogen with hemostatic biomarkers

The risk of venous thrombosis (VT) associated with oral hormone therapy (HT) may differ by type of estrogen compound. To compare the thrombotic profile of women using oral conjugated equine estrogens (CEE) with that of women using oral estradiol (E2). In postmenopausal, female, health maintenance organization (HMO) members with no history of VT, we measured thrombin generation, levels of factor VII activity, antithrombin activity and total protein S antigen. Mean levels of hemostasis biomarkers were cross-sectionally compared by use and type of estrogen using multiple linear regressions. The type of estrogen used was determined primarily by the HMO formulary, which changed its preferred estrogen from CEE to E2 during the study period. The sample included 92 E2 users and 48 CEE users, with a mean age of 64.1 years and mean BMI of 29.1 kg m(-2) . Twenty-seven per cent of HT contained medroxyprogesterone acetate. Compared with E2 users, CEE users had greater thrombin generation peak values and endogenous thrombin potential, and lower total protein S (multivariate adjusted differences of 49.8 nm (95% CI, 21.0, 78.6), 175.0 nm × Min (95% CI, 54.4, 295.7) and -13.4% (95% CI, -19.8, -6.9), respectively). Factor VII and antithrombin levels were not different between E2 and CEE users. Results were similar in subgroups of users of unopposed HT, opposed HT, low-dose estrogen and standard dose estrogen. The hemostatic profile of women using CEE is more prothrombotic than that of women using E2. These findings provide further evidence for a different thrombotic risk for oral CEE and oral E2.

Elevated Tissue Plasminogen Activator and Reduced Plasminogen Activator Inhibitor Promote Hyperfibrinolysis in Trauma Patients

Severe hyperfibrinolysis after trauma is a poorly understood phenomenon associated with profound shock, serious anatomic injuries, increased transfusions, and high mortality rates. Molecular mechanisms driving hyperfibrinolysis in trauma have not been completely delineated. The authors aimed to determine the relationship between severe hyperfibrinolysis and outcomes in trauma patients and characterize the role of the plasminogen activator (PA) system in this condition. A prospective observational study was performed in 163 adult level I trauma patients admitted between April and August 2012. Blood was collected on admission, and fibrinolysis was determined by plasmin-α2 antiplasmin (PAP) levels. Tissue-derived and urokinase PA (tPA and uPA, respectively), PA inhibitor (PAI-1), fibrinogen, and antithrombin levels were also measured. Patient demographics, vital signs, laboratory values, mechanisms and severity of injuries, transfusions, and outcomes were collected at admission or from patient records. Moderate fibrinolysis was defined as PAP level 1,500 to 20,000 μg/L and severe hyperfibrinolysis as PAP level more than 20,000 μg/L. Severe hyperfibrinolysis was observed in 10% of patients and associated with increased injury severity, greater transfusions, fewer ventilator and hospital-free days, and higher mortality. Plasmin-α2 antiplasmin level was directly correlated with tPA level and inversely correlated with PAI-1 level. Patients with both elevated tPA and reduced PAI-1 were more severely injured, received more transfusions, and experienced fewer ventilator and hospital-free days. In conclusion, Severe hyperfibrinolysis is observed in a small percentage of trauma patients and is associated with severe injuries, greater transfusions, and worse outcomes. This condition is mediated, in part, by excessive upregulation of profibrinolytic tPA in the absence of concomitant increases in antifibrinolytic PAI-1.

Abnormal hemostatic function one year after orthotopic liver transplantation can be fully attributed to endothelial cell activation

Background: The long-term risk of thrombotic and vascular complications is elevated in liver transplant recipients compared to the general population. Patients with cirrhosis are in a hypercoagulable status during and directly after orthotopic liver transplantation, but it is unclear whether this hypercoagulability persists over time. Aim: We aimed to investigate the hemostatic status of liver transplant recipients one year after transplantation. Methods: We prospectively collected blood samples of 15 patients with a functioning graft one year after orthotopic liver transplantation and compared the hemostatic status of these patients with that of 30 healthy individuals. Results: Patients one year after liver transplantation had significantly elevated plasma levels of von Willebrand factor (VWF). Thrombin generation, as assessed by the endogenous thrombin potential, was decreased in patients, which was associated with increased plasma levels of the natural anticoagulants antithrombin and tissue factor pathway inhibitor. &nbsp;Plasma fibrinolytic potential was significantly decreased in patients and correlated inversely with levels of plasminogen activator inhibitor-1. Conclusion: One year after liver transplantation, liver graft recipients have a dysregulated hemostatic system characterised by elevation of plasma levels of endothelial-derived proteins. Increased levels of von Willebrand factor and decreased fibrinolytic potential may (in part) be responsible for the increased risk for vascular disease seen in liver transplant recipients.

Abnormal hemostatic function one year after orthotopic liver transplantation can be fully attributed to endothelial cell activation

Background: The long-term risk of thrombotic and vascular complications is elevated in liver transplant recipients compared to the general population. Patients with cirrhosis are in a hypercoagulable status during and directly after orthotopic liver transplantation, but it is unclear whether this hypercoagulability persists over time.Aim: We aimed to investigate the hemostatic status of liver transplant recipients one year after transplantation.Methods: We prospectively collected blood samples of 15 patients with a functioning graft one year after orthotopic liver transplantation and compared the hemostatic status of these patients with that of 30 healthy individuals.Results: Patients one year after liver transplantation had significantly elevated plasma levels of von Willebrand factor (VWF). Thrombin generation, as assessed by the endogenous thrombin potential, was decreased in patients, which was associated with increased plasma levels of the natural anticoagulants antithrombin and tissue factor pathway inhibitor. Plasma fibrinolytic potential was significantly decreased in patients and correlated inversely with levels of plasminogen activator inhibitor-1.Conclusion: One year after liver transplantation, liver graft recipients have a dysregulated hemostatic system characterised by elevation of plasma levels of endothelial-derived proteins. Increased levels of von Willebrand factor and decreased fibrinolytic potential may (in part) be responsible for the increased risk for vascular disease seen in liver transplant recipients.

Characteristics of AIDS patients in Dutch intensive care units

Background: Infection with HIV enhances the risk to develop invasive bacterial infection, often resulting in sepsis. Both HIV infection and sepsis are associated with activation of the coagulation system. The influence of HIV infection on the sepsis-induced disturbance of the hemostatic balance is unknown. We aimed to determine the impact of HIV infection on coagulation activation during sepsis. Methods & Materials: We performed a prospective observational study in Lambarene, Gabon, and included all patients that were hospitalized with either fever or hypothermia and at least one other SIRS (Systemic Inflammatory Response Syndrome) criterion. Blood cultures, HIV testing and malaria diagnostics were performed. Patients with evidence of infection (based on adapted Centers for Disease Control and Prevention, and International Sepsis Forum Consensus Conference definitions) were classified as sepsis cases. Citrated plasma was obtained on admission, as well as in asymptomatic controls with or without HIV infection from the same region. Statistical analyses were done using the KruskalWallis test followed by a post-hoc Mann-Whitney U test. Results: We included113 sepsis patients (34 HIV positive), and 95 asymptomatic controls (60 HIV positive). Both asymptomatic HIV infection and sepsis were associated with activation of coagulation, as reflected by elevated levels of D-dimer and fibrinogen, and endothelial cell activation, as evidenced by elevated levels of Von Willebrand factor. Sepsis was associated with similar changes albeit to a greater extent; in addition, sepsiswas accompaniedwith downregulation of anticoagulant pathways, as reflected by reduced antithrombin and protein S levels. In asymptomatic HIV infection protein S was downregulated, whereas antithrombin levels were increased. Sepsis, but not HIV infection, resulted in prolonged prothrombin time and activated partial thromboplastin time. Coinfection with HIV did not impact on activation of coagulation during sepsis. Importantly, however, HIV co-infection did aggravate perturbations in VonWillebrand and protein S levels in sepsis patients. Conclusion: Both HIV infection and sepsis cause a net procoagulant state. HIV co-infection augments impairment of the anticoagulant system and activation of endothelium during sepsis. These mechanisms may play a role in enhanced sepsis related morbidity of HIV patients.

The influence of HIV infection on coagulation activation during sepsis

Background: Infection with HIV enhances the risk to develop invasive bacterial infection, often resulting in sepsis. Both HIV infection and sepsis are associated with activation of the coagulation system. The influence of HIV infection on the sepsis-induced disturbance of the hemostatic balance is unknown. We aimed to determine the impact of HIV infection on coagulation activation during sepsis. Methods & Materials: We performed a prospective observational study in Lambarene, Gabon, and included all patients that were hospitalized with either fever or hypothermia and at least one other SIRS (Systemic Inflammatory Response Syndrome) criterion. Blood cultures, HIV testing and malaria diagnostics were performed. Patients with evidence of infection (based on adapted Centers for Disease Control and Prevention, and International Sepsis Forum Consensus Conference definitions) were classified as sepsis cases. Citrated plasma was obtained on admission, as well as in asymptomatic controls with or without HIV infection from the same region. Statistical analyses were done using the KruskalWallis test followed by a post-hoc Mann-Whitney U test. Results: We included113 sepsis patients (34 HIV positive), and 95 asymptomatic controls (60 HIV positive). Both asymptomatic HIV infection and sepsis were associated with activation of coagulation, as reflected by elevated levels of D-dimer and fibrinogen, and endothelial cell activation, as evidenced by elevated levels of Von Willebrand factor. Sepsis was associated with similar changes albeit to a greater extent; in addition, sepsiswas accompaniedwith downregulation of anticoagulant pathways, as reflected by reduced antithrombin and protein S levels. In asymptomatic HIV infection protein S was downregulated, whereas antithrombin levels were increased. Sepsis, but not HIV infection, resulted in prolonged prothrombin time and activated partial thromboplastin time. Coinfection with HIV did not impact on activation of coagulation during sepsis. Importantly, however, HIV co-infection did aggravate perturbations in VonWillebrand and protein S levels in sepsis patients. Conclusion: Both HIV infection and sepsis cause a net procoagulant state. HIV co-infection augments impairment of the anticoagulant system and activation of endothelium during sepsis. These mechanisms may play a role in enhanced sepsis related morbidity of HIV patients.

Hepatic Ischemia/Reperfusion Injury Is Diminished by Atorvastatin in Wistar Rats

Temporal occlusion of the hepatoduodenal ligament (HDL) is often used during liver surgeries in order to reduce blood loss, resulting in ischemia/reperfusion injury (I/R). The aim of the study was to investigate the effects of atorvastatin (ATOR) on hepatic I/R injury and on serum levels of tumor necrosis factor-alpha (TNF-α), endothelin-1 (ET-1), antithrombin III (ATIII) and intracellular adhesion molecule-1 (ICAM-1). Liver ischemia was induced in Wistar rats by clamping the HDL for 60 min, followed by either 60 or 180 min reperfusion. Rats received either vehicle or 10 mg/kg ATOR before hepatic I/R. Control group received sham surgery. Livers were examined for histological damage and serum AST, ALT, TNF-α, ET-1, ATIII and ICAM-1 concentrations were measured. After I/R, AST and ALT were significantly elevated, ATIII levels were significantly depleted, both TNF-α and ICAM-1 levels increased and ET-1 was significantly elevated (at 180 min). ATOR pretreatment attenuated these alterations and diminished histological injury scores. Our results show that ATOR protects the liver from I/R injury.

Poor prognosis of hypocoagulability assessed by thrombin generation assay in disseminated intravascular coagulation

Overall assessment of the hemostatic system including procoagulant and anticoagulant changes may help assess the clinical status and prognosis of disseminated intravascular coagulation (DIC). The thrombin generation assay provides useful information about the global hemostatic status. Therefore, we measured several parameters of global hemostatic potential by the thrombin generation assay in patients suspected of having DIC. A total of 114 patients with suspected DIC were included. The thrombin generation assay was performed on the calibrated automated thrombogram using tissue factor with or without the addition of thrombomodulin, showing three parameters: lag time, endogenous thrombin potential (ETP), and peak thrombin. Both 1 and 5 pmol/l tissue factor-stimulated ETP and peak thrombin were well correlated with DIC severity. Interestingly, antithrombin level greatly affected ETP, whereas protein C influenced lag time. Prognostic analysis revealed that the area under the curve of peak thrombin stimulated by 1 pmol/l tissue factor was superior to that of D-dimer. Moreover, multivariate Cox analysis showed that the lag time and time to peak with both 1 and 5 pmol/l tissue factor were independent prognostic markers. ETP and peak thrombin well reflect DIC severity. Hypocoagulability manifesting as prolonged lag time and time to peak is expected to be an independent prognostic marker in DIC.

Plasma antithrombin levels correlate with albumin and total protein in gestational hypertension and preeclampsia.

To analyze the antithrombin-III (AT-III) activity in the plasma in relation to the serum albumin and total protein in preeclampsia and gestational hypertension. The medical records of 139 patients who were diagnosed with gestational hypertension (n=33) and preeclampsia (n=106) were reviewed, and the relationships between the activity of AT-III and serum albumin or total protein were evaluated. The plasma AT-III activity in gestational hypertension and preeclampsia was correlated with the serum albumin and TP levels. There were significant correlations between AT-III activity and albumin in gestational hypertension (r=0.504, p=0.003) and preeclampsia (r=0.343, p=0.003). There were also significant correlations between AT-III activity and TP in gestational hypertension (r=0.619, p=0.001) and preeclampsia (r=0.366, p=0.001). Regression coefficients between AT-III and albumin and between AT-III and TP in gestational hypertension (23.7 and 14.0, respectively) were significantly steeper than those in preeclampsia (14.6 and 9.6, respectively). The plasma AT-III activity in gestational hypertension and preeclampsia was correlated with the serum albumin and TP levels. This suggests that AT-III activity is more likely to decrease in gestational hypertension than in preeclampsia.

Changes in Plasma Levels of Natural Anticoagulants in Disseminated Intravascular Coagulation: High Prognostic Value of Antithrombin and Protein C in Patients with Underlying Sepsis or Severe Infection

BackgroundDysfunctional natural anticoagulant systems enhance intravascular fibrin for mation in disseminated intravascular coagulation (DIC), and plasma levels of natural anti coagulants can be used in the diagnosis and prognosis of DIC. Herein, the diagnostic value of 4 natural anticoagulants was assessed, and the prognostic value of antithrombin and protein C were validated in a large population.MethodsPart 1 study included 126 patients with clinically suspected DIC and estimated plasma levels of 4 candidate anticoagulant proteins: antithrombin, protein C, protein S, and protein Z. Part 2 comprised 1,846 patients, in whom plasma antithrombin and protein C levels were compared with other well-known DIC markers according to the underlying dis eases. The 28-day mortality rate was used to assess prognostic outcome.ResultsAntithrombin and protein C showed higher areas under the ROC curve than pro tein S and protein Z. In part 2 of the study, antithrombin and protein C levels significantly correlated with DIC score, suggesting that these factors are good indicators of DIC severity. Antithrombin and protein C showed significant prognostic power in Kaplan-Meier analyses. In patients with sepsis/severe infection, antithrombin and protein C showed higher hazard ratios than D-dimer. Platelet count showed the highest hazard ratio in patients with hemato logic malignancy. In patients with liver disease, the hazard ratio for antithrombin levels was significantly high.ConclusionsDecreased plasma anticoagulant levels reflect florid consumption of the phys iologic defense system against DIC-induced hypercoagulation. Plasma antithrombin and protein C levels are powerful prognostic markers of DIC, especially in patients with sepsis/severe infection.

Low plasma levels of antithrombin III in the early post‐operative period following pediatric liver transplantation: Should they be replaced? A single‐center pilot study

eHAT after LT remains a life-threatening complication. In the majority of anticoagulation protocols, heparin is used to prevent thromboses. Our study aimed to monitor AT-III levels in the early post-LT period to assess the need for the administration of AT-III concentrate to ensure the effectiveness of heparin. We monitored coagulation daily by measuring INR, APTT, fibrinogen, platelets, and AT-III. Anticoagulation therapy consisted of LMWH, AT-III, and dipyridamole. AT-III concentrate was administered when AT-III activity was ≤60%. DUS was performed daily for the first five post-operative days or whenever vascular thrombosis was suspected. Between October 2007 and October 2011, 39 LT were performed in our center. The median age was 26 months (6-196) with a median weight of 9 kg (5.5-49). AT-III activity was ≤60% in 27 patients. Lower levels were particularly observed in partial grafts and recipients weighing less than 10 kg. Patent arterial flow was present in all 39 LT during the first five post-operative days. AT-III levels were low in 70% of pediatric patients following LT, thereby risking heparin ineffectiveness. These results may implicate low AT-III levels in the etiology of eHAT post-LT. However, this is a small single-center pilot study and further larger prospective trials are required to confirm these results.