Levels Of Coagulation Parameters Research Articles

The Impact of SARS-CoV-2 on the Coagulation Profile of Pregnant Women

A prospective study was conducted in the Clinic Hospital of Obstetrics and Gynecology "Dr. I.A. Sbârcea" Brașov, which included hospitalized pregnant women diagnosed with COVID-19 from January 1, 2020, to March 8, 2022. The study aimed to evaluate the influence of SARS-CoV-2 on the coagulation status, the blood levels of coagulation parameters, and the presence of disseminated intravascular coagulation in pregnant women with COVID-19. To analyze the coagulation status of the pregnant women we used the following parameters: Fibrinogen level, INR, D-dimer test, and the presence of disseminated intravascular coagulation. Following the study, we concluded that the occurrence of coagulation disorders in pregnant women is related to the severity of the SARS-CoV 2. LMWH administration generally improved the prognosis of pregnancy-associated COVID-19 and mostly prevented the occurrence of severe thromboembolic complications such as disseminated intravascular coagulation or deep venous thrombosis.

Peripheral Coagulation Parameters and Prostate Cancer Association: A Retrospective Study and Mendelian Randomization.

The limitations of prostate-specific antigen (PSA) in diagnosing prostate cancer (PCa) necessitate the exploration of novel biomarkers. Recent studies suggest a potential link between coagulation markers, particularly fibrinogen and D-dimer, and PCa. A retrospective single-center analysis on 466 biopsy-undergone patients was conducted, categorized into PCa and benign prostatic hyperplasia (BPH) groups. Baseline and coagulation parameter levels were analyzed. Utilizing a Mendelian randomization (MR) approach, we investigated the causative relationship between D-dimer and PCa risk. Individuals with PCa, compared with those with BPH, exhibited significantly higher D-dimer levels (P < .001), total PSA (P < .001), and PSA density (P < .001). Fibrinogen levels did not exhibit significant differences (P = .505). The MR analysis suggested a probable causal link between elevated D-dimer levels and an increased risk of PCa (odds ratio: 1.81, 95% confidence interval: 1.48-2.21, P = 7.4 × 10-9). This research highlights D-dimer as a potential biomarker for diagnosing PCa, supported by clinical and MR analyses. The study paves the way for future large-scale, multi-center research to corroborate these findings and further explore the relationship between coagulation markers and PCa mechanisms.

A First-in-Human Phase 1 Study of Abbv-319, an Antibody-Drug Conjugate Composed of a CD19 Antibody Linked to a Potent Proprietary Glucocorticoid Receptor Modulator, in Patients with Relapsed or Refractory B-Cell Malignancies

Background Systemic glucocorticosteroids (ie, glucocorticoid receptor modulators [GRMs]) show robust monotherapy activity against B-cell malignancies at high doses; however, they may be accompanied by steroid-associated toxicities that limit dosing. CD19 is a marker essential for B-cell proliferation and has high expression across B-cell malignancies including diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and chronic lymphocytic leukemia (CLL). ABBV-319 is a CD19-GRM antibody-drug conjugate (ADC) composed of an optimized high-affinity immunoglobulin G1 antibody conjugated to a potent proprietary glucocorticosteroid payload. ABBV-319 takes advantage of both enhanced antibody-dependent cellular cytotoxicity (via afucosylation) and targeted GRM payload delivery to maximize anticancer activity while lowering the risk of systemic steroid toxicities. Preclinically, ABBV-319 demonstrates sustained antitumor efficacy in models of human B-cell malignancies that compares favorably with approved therapeutics. This phase 1 study evaluates safety and clinical activity of ABBV-319 monotherapy in patients with relapsed or refractory (R/R) B-cell malignancies. Methods This is a phase 1, first-in-human, open-label, dose-escalation, dose-expansion, biomarker/pharmacodynamic (PD) study in patients aged ≥18 years with R/R B-cell malignancies. Key eligibility criteria include measurable disease and Eastern Cooperative Oncology Group performance status of 0 or 1. In addition, patients must meet predefined criteria for adrenal, bone marrow, kidney, and liver function, coagulation parameter levels, and hemoglobin A1c levels (dose escalation only) during screening. The primary objectives are to evaluate safety, tolerability, pharmacokinetics (PK), and immunogenicity of ABBV-319 and identify a recommended phase 2 dose (RP2D). The secondary objective is to evaluate the efficacy of ABBV-319 in patients with R/R DLBCL, FL, and CLL. Exploratory objectives include evaluating the effect of ABBV-319 on QT prolongation and evaluating PD and predictive biomarkers. This study will be conducted in 2 parts - dose escalation (Part 1) and dose expansion (Part 2). Part 1 aims to determine the RP2D for ABBV-319 following a Bayesian optimal interval design, with a maximum of 2-fold increments that reduce as the dose increases. RP2D will be determined on the basis of all the data collected in Part 1 including safety, tolerability, PK, PD, and efficacy, if available. Part 2 will further evaluate ABBV-319 at the RP2D in 3 separate subtypes of B-cell malignancies - DLBCL, FL, and CLL. A total of 114 patients are planned to be enrolled - 54 patients with various R/R B-cell malignancies in Part 1, and 60 patients in Part 2 (20 patients included for each R/R B-cell malignancy subtype: DLBCL, FL, and CLL). ABBV-319 will be administered intravenously until disease progression, intolerable toxicity, or other study discontinuation criteria are met, for a maximum of ~24 months from the last patient enrolled. Safety assessments include adverse event monitoring (per National Cancer Institute Common Terminology Criteria for Adverse Events v5.0), physical examinations, vital sign measurements, and clinical laboratory testing. Dose-limiting toxicities will be assessed. PK parameters including maximum observed serum/plasma concentration (Cmax), time to Cmax, terminal plasma elimination half-life, and area under the serum/plasma concentration-time curve will be analyzed using noncompartmental methods for ABBV-319 total antibody, ADC, and unconjugated GRM payload. Antidrug antibodies (ADAs) and neutralizing ADAs may also be determined, as appropriate. Efficacy will be evaluated in terms of response per disease-specific criteria (including International Workshop on Chronic Lymphocytic Leukemia, International Workshop on Waldenstrom's Macroglobulinemia, and Lugano classification). Duration of response, time to response, progression-free survival, and overall survival will be evaluated per Kaplan-Meier analysis. QT prolongation, PD, and biomarker data will be assessed as changes from baseline and may be summarized for each scheduled postbaseline visit.

Lower-leg injury and knee arthroscopy have distinct effects on coagulation

AbstractIt is unknown how lower-leg injury and knee arthroscopy, both associated with venous thromboembolism (VTE), affect coagulation. To study the effect of (1) lower-leg trauma and (2) knee arthroscopy on coagulation, plasma samples of the Prevention of Thrombosis following CAST immobilization (POT-CAST, #NCT01542762) and Prevention of Thrombosis following Knee Arthroscopy (POT-KAST, #NCT01542723) trials were used, which were collected shortly after lower-leg trauma and before/after (<4 hours) knee arthroscopy. For aim 1, 1204 lower-leg injury patients were compared with preoperative samples of 1001 controls. Mean differences/ratios (if ln-retransformed because of skewedness) were adjusted for sex, age, body mass index, comorbidity, malignancy, and oral contraceptives using linear regression. For aim 2, perioperative mean changes of 715 arthroscopy patients were calculated. Plasma levels of fibrinogen, factor (F)VIII, FIX, FXI, von Willebrand Factor (VWF), and D-dimer were measured in all individuals. Parameters of underlying mechanisms (tissue factor, interleukin-6 [IL-6], myeloperoxidase DNA, cell-free DNA) were measured in random subsets. In lower-leg injury patients, coagulation parameter levels increased, especially FVIII, VWF, and D-dimer, that is, adjusted mean differences: FVIII 26.8% (95% confidence interval [CI], 23.7-29.9), FIX 13.8% (95% CI, 11.9-15.6), FXI 5.1% (95% CI, 3.3-7.0), VWF 29.8% (95% CI, 26.0-33.6), fibrinogen 32.5 mg/dL (95% CI, 25.8-39.2), and D-dimer (mean ratio) 3.3 (95% CI, 3.1-3.6). Remaining parameters were unchanged, except for increased IL-6 levels. After arthroscopy, all parameters decreased. Lower-leg trauma is associated with increased procoagulant factor levels in contrast to knee arthroscopy. This suggests that, in both situations, different pathways are involved in development of VTE.

Clinical Efficacy and Safety Comparison of Rivaroxaban and Dabigatran for Nonvalvular Atrial Fibrillation Patients Undergoing Percutaneous Left Atrial Appendage Closure Operation.

Objective: Due to the clinical complexity of warfarin, novel oral anticoagulation (NOAC) has been a feasible and safe alternative anticoagulant approach during left atrial appendage closure (LAAC). This study was designed to compare the efficacy and safety of rivaroxaban and dabigatran for nonvalvular atrial fibrillation patients undergoing percutaneous LAAC. Methods: One single and prospective cohort study was performed among patients who received anticoagulation with dabigatran or rivaroxaban. All patients were medicated with a 3-month course of NOAC to facilitate device endothelialization, followed by dual antiplatelet therapy until 6 months, then lifelong aspirin after discharge. Repeated transesophageal echocardiography was scheduled to evaluate thrombosis formation on occluders and thrombus dissolution ability. Results: A total of 262 consecutive patients were initially enrolled. A final number of 250 patients were analyzed; two patients were excluded due to procedure failure and 10 patients had a loss of follow-up; 97 were from the dabigatran group and 153 from the rivaroxaban group. Three patients (1.9%) in the rivaroxaban group and eight (8.2%) in the dabigatran group were experiencing device-related thrombosis (DRT) events during follow-ups. Cumulative Kaplan–Meier estimates showed that the incidence of DRT was lower under rivaroxaban medication during the 6-month follow-ups (p = 0.038*, OR = 3.843, 95%CI: 0.991–14.836). The transesophageal echocardiography (TEE) results showed that the average length and width of DRT in the rivaroxaban group was significantly lower compared with that in the dabigatran group (2.16 vs. 1.60 mm, p = 0.017*, and 1.71 vs. 1.30 mm, p = 0.003*, respectively). The thrombosis dissolved after the switch from dabigatran or rivaroxaban to warfarin within the target range, represented by the average length and width of thrombus with the cooperation of secondary TEE for the dabigatran and rivaroxaban groups (0.64 vs. 0.40 mm, p = 0.206, and 0.43 vs. 0.27 mm, p = 0.082, respectively). No significant difference was found between the two groups with respect to the levels of coagulation parameters, cardiac function, and bleeding events. Conclusion: Compared to dabigatran, post-procedural rivaroxaban anticoagulation might be advantageous in preventing DRT complications expected after LAAC, without increasing the risk of hemorrhage.

D-Dimer Levels and Disease Prognosis in COVID-19 Patients

Elevated or abnormal levels of coagulation parameters indicate thrombotic disorders that need to be managed at the earliest to prevent complications and reduce mortality in coronavirus disease (COVID-19) patients. D-dimer is a product that is a part of fibrin abasement, which can be used as a test for the diagnosis of thrombotic disorders. Higher D-dimer levels are a strong indicator of mortality in patients with active COVID-19. This study aimed to determine the relationship between D-dimer levels and the clinical prognosis of COVID-19 patients. This observational, prospective study was conducted between April 2020 and September 2020. All patients with COVID-19 infection were considered for this study, along with their D-dimer values. Patients with higher D-dimer levels and pre-existing morbidities experienced a longer hospital stay and increased complications when compared to patients without pre-existing morbidities. Abnormally elevated D-dimer levels were frequently observed upon admission due to COVID-19 and are analogous to the increased occurrence of critical illness, thrombotic events, acute kidney injury, and death. Therefore, D-dimer levels could be a valuable clinical biomarker and an important indicator of prognosis for patients with COVID-19 with pre-existing morbidities.

Changes in levels of coagulation parameters in different trimesters among Chinese pregnant women.

BackgroundThis article is to explore changes in levels of coagulation parameters in different trimesters among healthy pregnant women in China.MethodsA total of 760 eligible women were enrolled (first‐trimester group: n = 183, second‐trimester group: n = 183, third‐trimester group: n = 263, non‐pregnant group: n = 131). Seven parameters including prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen (FIB), D‐dimer (DD), fibrinogen degradation products (FDP), and antithrombin III (ATIII), of all participants were collected. The non‐parametric 2.5th–97.5th percentiles reference intervals were calculated for each parameter.ResultsThe reference intervals for FIB, PT, APTT, TT, FDP, DD, and ATIII at first trimester were 2.11–4.32 g/L, 10.90–13.85 s, 24.60–39.28 s, 12.95–15.88 s, 0.04–2.55 μg/mL, 0.03–1.15 μg/mL, and 75.57%‐125.31%, respectively. The reference intervals at second trimester were 2.31–4.77 g/L, 9.70–12.64 s, 24.16–35.43 s, 12.95–15.88 s, 0.15–7.40 μg/mL, 0.08–2.13 μg/mL, and 74.35%‐119.28%, respectively. For the third‐trimester, the intervals were 2.39–4.96 g/L, 9.20–11.95 s, 23.90–35.51 s, 13.41–18.00 s, 0.55–13.43 μg/mL, 0.15–3.60 μg/mL, and 71.61%‐118.29%, respectively. The third‐trimester group showed decreased PT, APTT, and ATIII and increased FIB, TT, DD and FDP as compared with the other groups.ConclusionIn this study, level changes of coagulation parameters in different trimesters were observed. And the ranges for coagulation parameters were presented, which may provide some reference for clinicians to more accurately monitor the coagulation and fibrinolytic system in pregnant women.

Comparison of factor XII levels in gestational diabetes, fetal macrosomia, and healthy pregnancies

BackgroundIf not detected and treated, gestational diabetes mellitus (GDM) can cause serious pregnancy complications such as macrosomia, preeclampsia, and fetal/neonatal mortality. Many studies have examined underlying contributing factors for GDM, including hypercoagulation. Factor XII (FXII) is a coagulation factor that increases throughout normal pregnancies, and we evaluated the relationship of GDM with FXII, FXIIa (activated FXII), and other coagulation parameter levels. GDM and macrosomia are closely related, but it is not known whether FXII could be an independent causal factor for macrosomia.MethodsIn this prospective study, blood samples were taken from 69 pregnant women at the time of term delivery to determine levels of FXII, FXIIa, and other coagulation parameters. Based on the results, pregnancies fell into GDM, non-diabetic with macrosomia (M), or healthy (C [control]).ResultsFXII concentration levels were significantly higher in GDM patients compared with the M and C groups. There were no significant differences when comparing FXIIa, activated partial thromboplastin time, prothrombin time (PT), and international normalized ratio. The GDM group saw a significant negative correlation between FXII concentrations and maternal pregestational body mass index (BMI) and BMI before delivery. In the M group, a positive correlation was observed between FXII concentrations and newborn weight and newborn weight percentile.ConclusionsAn increase in FXII levels was observed in patients with gestational diabetes. Associations between coagulation parameters and GDM should be further analyzed to define the mechanisms of GDM and possible treatment modalities.Trial registrationOur study has been registered at clinicaltrials.gov (NCT03583216). Registered on July 11, 2018,

Association between fluid management and dilutional coagulopathy in severe postpartum haemorrhage: a nationwide retrospective cohort study

BackgroundThe view that 2 l of crystalloid and 1.5 l of colloid can be infused while awaiting compatible blood for patients with major postpartum haemorrhage is based on expert opinion documents. We describe real-world changes in levels of coagulation parameters after the administration of different volumes of clear fluids to women suffering from major postpartum haemorrhage.MethodsWe performed a nationwide retrospective cohort study in the Netherlands among 1038 women experiencing severe postpartum haemorrhage who had received at least four units of red cells or fresh frozen plasma or platelets in addition to red cells. The volume of clear fluids administered before the time of blood sampling was classified into three fluid administration strategies, based on the RCOG guideline: < 2 L, 2–3.5 L and > 3.5 L. Outcomes included haemoglobin, haematocrit, platelet count, fibrinogen, aPTT and PT levels.ResultsHaemoglobin, haematocrit, platelet count, fibrinogen and aPTT were associated with volumes of clear fluids, which was most pronounced early during the course of postpartum haemorrhage. During the earliest phases of postpartum haemorrhage median haemoglobin level was 10.1 g/dl (IQR 8.5–11.6) among the women who received < 2 L clear fluids and 8.1 g/dl (IQR 7.1–8.4) among women who received > 3.5 L of clear fluids; similarly median platelet counts were 181 × 109/litre (IQR 131–239) and 89 × 109/litre (IQR 84–135), aPTT 29 s (IQR 27–33) and 38 s (IQR 35–55) and fibrinogen 3.9 g/L (IQR 2.5–5.2) and 1.6 g/L (IQR 1.3–2.1).ConclusionsIn this large cohort of women with severe postpartum haemorrhage, administration of larger volumes of clear fluids was associated with more severe deterioration of coagulation parameters corresponding to dilution. Our findings provide thus far the best available evidence to support expert opinion-based guidelines recommending restrictive fluid resuscitation in women experiencing postpartum haemorrhage.Trial registrationNetherlands Trial Register (NTR4079), registration date July 17, 2013.

Safety and Efficacy of Enoxaparin Prophylaxis in Adults Receiving Peg-Asparaginase Containing Induction Regimens for Acute Lymphoblastic Leukemia (ALL)

Background:Peg-asparaginasecan cause dysregulationof pro-coagulant and anti-coagulant proteins, resulting in a significant risk of venous thromboembolism(VTE) in ALL, particularly in adults undergoing induction chemotherapy. In late 2014, we adopted a policy at our institution to use prophylactic dose ofenoxaparin 40 mg daily for up to 3 weeks following the administration of peg-asparaginase. Patients are also to undergo monitoring of complete blood count, and coagulation parameters including fibrinogen and anti-thrombin. Enoxaparin may be held if patients develop severe thrombocytopenia (platelet count <30,000/µL). Cryoprecipitate is given if fibrinogen drops below 100 mg/dl. In the present study, we aim to analyze primarily the safety, and secondarily the efficacy ofenoxaparin prophylaxis in this setting and highlight the changes in coagulation parameters following peg-asparaginase use during induction therapy.Methods:This is a single-center study of17 consecutive adult patients (>18 years old) treated for ALL with peg-asparaginasecontaining induction regimen before and after the establishment of institutional policy to useenoxaparinprophylaxis. Patients were identified from hospital research database. The diagnoses were verified. Medical records were reviewed for the occurrence of any clinically relevant bleeding and VTE within 3 months of receiving peg-asparaginase. Levels of coagulation parameters, whenever available, were collected at baseline and at weekly intervals for up to 4 weeks after receiving peg-asparaginase. The risk of bleeding and VTE among patients receivingenoxaparinwas compared to those who did not receiveenoxaparin. Fisher exact test was used for testing the association of categorical variable, and binomial exact test was used for computing confidence intervals. T-test or nonparametric test was used for comparing the continuous variables depending on whether or not the data were normally distributed.Results:The patient population consisted of 59% females. Mean age was 35 years. Histology consisted of Pre-B ALL in 76%, pre-T ALL in 18% and mixed lineage leukemia in 6%. 88% percent received pediatric-type chemoregimenand intramuscular peg-asparaginase; the most common doses of peg-asparaginaseincluded 2000 mg/m2 (41%) and 2500 mg/m2 (35%). Duration ofenoxaparin prophylaxis was 21 days in 66.7% and 7 days in 33.3%. Average changes in coagulation parameters at baseline and at weekly intervals following the use of peg-asparaginase therapy are highlighted in figures 1 and 2. The drop inantithrombin and fibrinogen levels was the highest during the first two weeks after the administration of peg-asparaginase. 41% of patients required cryoprecipitate (median 15 units, range 5-35 units over 4 weeks). No patients, including theenoxaparin group, had any clinically relevant bleeding event. The risk of VTE was 18% (95% confidence 4-43%); 2 out of 3 VTE events were cerebral venous thrombosis. No VTE occurred in theenoxaparin prophylaxis group (n=9), whereas 37% of patients (3 out of 8 patients), who did not receiveenoxaparin, developed VTE.Enoxaparin prophylaxis was associated with a trend towards a lower risk of VTE, however, the difference was not statistically significant (p=0.08).Conclusion:Within the limits of this study, in adult ALL patients receiving peg-asparaginase, the use of daily prophylactic dose ofenoxaparinmay not be associated with an increased risk of clinically relevant bleeding, and may have a potential to lower the risk of VTE. Patients receivingenoxaparin, however, should be carefully monitored for the need of platelet transfusion and cryoprecipitate supplementation. The difference in the risk of VTE was not statistically significant, which may be, in part, due to a small sample size.Antithrombindepletion may also contribute to a reduction in the efficacy ofenoxaparin. Larger prospective studies should be performed to validate the preliminary findings. [Display omitted] [Display omitted] DisclosuresArmitage:Spectrum Pharmaceuticals: Consultancy; Roche: Consultancy; Conatus - IDMC: Consultancy; GlaxoSmithKline IDMC: Consultancy; ZiopharmOncology: Consultancy; Tesaro bio Inc: Membership on an entity's Board of Directors or advisory committees. Lunning:Genentech: Consultancy; AbbVie: Consultancy; Bristol-Myer-Squibb: Consultancy; Juno: Consultancy; Spectrum: Consultancy; Pharmacyclics: Consultancy; Celgene: Consultancy; Gilead: Consultancy; TG Therapeutics: Consultancy.

Plasma ADAMTS13 Activity Associates with Injury Severity in Pediatric Trauma Patients

Background: Acute traumatic coagulopathy occurs in both pediatric and adult trauma patients and is associated with an increased risk of mortality. Trauma patients not only have increased risk for hemorrhagic complications, but also are at increased risk for thrombosis due to multiple factors including local tissue injury, inflammation, and immobility. The complex underlying pathophysiology of coagulation abnormalities associated with traumatic injury have yet to be fully elucidated. Additionally, there are significant differences in the hemostatic system of pediatric patients compared to adults.Objectives: The purpose of this study was to determine the levels of coagulation parameters including von Willebrand factor (VWF) antigen and ADAMTS13 activity in pediatric trauma patients and evaluate for possible association with injury severity and/or mortality.Methods: This study utilized plasma specimens collected from pediatric trauma patients that presented to our institution over a 2-year time period. The specimens were collected at initial presentation and 24 hours later. The injury severity was estimated using both the Glasgow Coma Scale (GCS) and Injury Severity Score (ISS). A cohort of control samples was obtained from pediatric patients for elective surgical procedures over the same time period. Plasma VWF antigen was determined by a sandwich ELISA; plasma ADAMTS13 activity was determined by FRETS-VWF73. The results were determined by nonparametric tests for the differences in median values.Results: A total of 106 trauma patient samples at initial time point, 78 trauma samples at 24 hour time point, and 54 control samples were obtained and utilized for study. There were statistically significant differences (p<0.05) in the plasma levels of VWF antigen, ADAMTS13 activity, and the ratio of ADAMTS13 activity to VWF antigen for the trauma patient samples at initial presentation when compared to controls (Table 1). At 24 hours, there were still statistically significant differences between ADAMTS13 activity and the ratio of ADAMTS13 activity to VWF antigen in trauma patients compared to controls, but there was no significant difference in VWF antigen between the two cohorts (Table 2). There was a significant difference between the decrease in ADAMTS13 activity and injury severity as estimated by ISS ³ 15 or GCS < 8 at both time points; however, ADAMTS13 activity was not statistically different in survivors vs. non-survivors. A higher VWF antigen level at initial presentation was the only factor found to be significantly different in non-survivors.Conclusions: This study demonstrates significant differences in plasma ADAMTS13 activity and VWF antigen in pediatric trauma patients compared to controls. In patients with more severe injuries as estimated by GCS and ISS, there was also a significant association with decreased levels of ADAMTS13 activity. These finding may underlie part of the prothrombotic propensity in microcirculation that occurs in patients post-trauma. Further investigation is warranted to better understand the mechanisms of acute traumatic coagulopathy and potential prognostic factors, and to determine the most effective interventions for acute traumatic coagulopathy in the pediatric population. [Display omitted] DisclosuresZheng:Ablynx: Consultancy; Alexion: Research Funding.

Norepinephrine infusion without but not with alpha-adrenergic blockade by phentolamine increases coagulation parameter levels in healthy men

Norepinephrine infusion without but not with alpha-adrenergic blockade by phentolamine increases coagulation parameter levels in healthy men

Time course of soluble P-selectin and von Willebrand factor levels in trauma patients: a prospective observational study

BackgroundCoagulopathy often develops in patients with serious trauma and is correlated with the clinical outcome. The contribution of platelet activity and endothelial dysfunction to trauma-induced coagulopathy remain to be defined. The purpose of this study was to investigate the time courses of soluble P-selectin (sPsel, an index of platelet activation) and von Willebrand factor (VWF, an index of endothelial dysfunction) in trauma patients and elucidate their relationship to coagulation parameter levels, the presence of coagulopathy, and patient outcome.MethodsThis prospective observational study, which took place in a university hospital intensive care unit (ICU), included 82 severely injured trauma patients. The sPsel, VWF antigen, protein C, and factor VII levels were measured and routine coagulation tests were performed upon admission to ICU and daily within the first week. The 30-day mortality rate was also determined.ResultsThirty-seven (45.1%) patients developed coagulopathy upon admission to the ICU, and the 30-day mortality rate was 20.7% (n = 17). Both the admission sPsel and VWF levels were lower in patients with coagulopathy than in those without (p < 0.05) and were significantly correlated with the protein C and factor VII levels, respectively (all p < 0.05). The VWF levels were lower during the first 3 days and higher on day 7 after admission in nonsurvivors than in survivors (all p < 0.05). No significant differences in sPsel levels were found between nonsurvivors and survivors on each day during the first week.ConclusionIn severely injured trauma patients in the ICU, lower levels of sPsel and VWF on admission were associated with the presence of coagulopathy and might not predict a better outcome. An increase in the VWF level at the end of the first week after admission to ICU was associated with increased 30-day mortality.

Comparison of four different treatment regimens on coagulation parameters, hormonal and metabolic changes in women with polycystic ovary syndrome

To determine the effects of different treatment regimens on the hormonal features, metabolic parameters, and hematologic variables in women with polycystic ovary syndrome (PCOS). Forty-eight women with PCOS were randomized into four treatment protocols: ethinyl estradiol/cyproterone acetate (EE/CA; n =12), EE/CA-metformin (n = 12), metformin alone (n =12) and EE/CA-spironolactone (n =12). These treatment protocols were given for 3 months and pre- and post-treatment variables were compared. Activated partial thromboplastin time (APTT) and prothrombin time (PT) levels, D-dimer, HOMA-IR, insulin, WBC, MPV as well as androgen levels decreased in all treatment groups. EE/CA-metformin and metformin alone groups resulted in a higher proportional reduction of D-dimer levels than the other protocols, while no significant different proportional reduction was observed in all the four groups for MPV, WBC, APTT, PT values. EE/CA-metformin group showed higher proportional reduction fasting insulin concentrations, HOMA-IR and free testosterone levels than metformin alone and EE/CA-spironolactone groups. DHEAs levels significantly decreased in group EE/CA-metformin than EE/CA alone and EE/CA-spironolactone groups. In multiple stepwise regression analyses, reduction in proportional insulin levels was independently and positively associated with decrease of MPV, D-dimer, free testosterone levels. In all treatment groups, we observed reduced levels of coagulation parameters, improvement of hormonal, hematological and metabolical variables by most probably reducing insulin levels. Among the treatment groups, EE/CA-metformin may be a more effective therapeutic option than the other protocols and this may be due to the beneficial effect of EE/CA-metformin on insulin resistance.

PREOPERATIVE METHYLPREDNISOLONE ADMINISTRATION MAINTAINS COAGULATION HOMEOSTASIS IN PATIENTS UNDERGOING LIVER RESECTION

Alterations in hemostatic parameters are a common finding after major hepatic resection. There is growing evidence that inflammation has a significant role in inducing coagulation disarrangement that follows major surgery. To determine whether preoperative methylprednisolone administration has a protective effect against the development of coagulation disorders, we evaluated the effect of preoperative steroids administration on changes in hemostatic parameters and plasma levels of inflammatory cytokines in patients undergoing liver surgery. Seventy-three patients undergoing liver resection were randomized to a steroid group or to a control group. Patients in the steroid group received 500 mg of methylprednisolone preoperatively. Serum levels of coagulation parameters (prothrombin time, platelets, fibrinogen, plasma fibrin degradation products [D-dimer], antithrombin III) and inflammatory mediators (IL-6 and TNF-alpha) were measured before and immediately after the operation and on postoperative days 1, 2, and 5. Multivariate analysis was performed to identify factors related to the characteristics of the patients and surgery affecting coagulation parameters between the two groups. Decreases in antithrombin III, platelet count and fibrinogen levels, prolongation of prothrombin time, and increases in the plasma fibrin degradation products were significantly suppressed by the administration of methylprednisolone. Cytokines production was also significantly suppressed by the administration of methylprednisolone, and there was significant correlation between plasma levels of cytokines and coagulation alterations. These findings suggest that preoperative methylprednisolone administration inhibits the development of coagulation disarrangements in patients undergoing liver resection, possibly through suppressing the production of inflammatory cytokines.

Alterations in the Coagulation Profile in Renal Pig-to-Monkey Xenotransplantation

Five monkey recipients of a porcine renal xenograft were studied to determine the relationship between fibrin formation in acute humoral xenograft rejection (AHXR) and procoagulant and anticoagulant factor levels to establish whether changes in coagulation parameters could be used to predict AHXR and determine whether AHXR is associated with overt disseminated intravascular coagulopathy (DIC) in this model.Variable degrees of compensated consumptive coagulopathy were observed in each primate. Elevated thrombin-antithrombin (TAT), F1+2 and D-dimer levels consistent with thrombin generation and fibrin formation were recorded. There was no consumption of the main clotting inhibitors (including antithrombin) or a progressive, severe drop in fibrinogen levels and platelet counts, although grafts were left in situ. After transplantation, D-dimer levels remained persistently high, so they were of limited value in defining this coagulopathy. At post mortem, no cases of multiorgan involvement typical of overt DIC were observed. The lack of a rapid postoperative recovery of clotting inhibitor levels after transplantation was invariably associated with early poor outcome.This study shows that AHXR is associated with various degrees of compensated consumptive coagulopathy in our pig-to-primate model. No clear relationship was found between coagulation parameter levels and graft outcome.

Blood chemistry of rats pretreated with Mucuna pruriens seed aqueous extract MP101UJ after Echis carinatus venom challenge.

The effect of a lethal Echis carinatus venom on serum enzyme levels and blood plasma coagulation parameters in rats pretreated with Mucuna pruriens seed aqueous extract MP101UJ (21 mg/kg body wt) 24 h and 3 wk before i.p venom injection (0.50 mg/kg rat) and rats injected with venom alone (0.50 mg/kg body wt) was investigated. The enzyme levels and coagulation parameter levels were measured 4 h after venom administration. The results showed that the increased enzymes lactate dehydrogenase (LDH), glutamic pyruvic transaminase (SGPT), creatinine kinase (CK) and changed coagulation parameters D-Dimer and Quick levels due to the venom effect were inhibited by M. pruriens seed aqueous extract MP101UJ in pretreated rats. Rats pretreated with a single dose (21 mg/kg and multiple doses 21 mg/kg rat) of extract MP101UJ maintained the normal enzyme levels and showed an anticoagulant effect as evidenced by the high PTT level which was also observed in venom treated animals. D-Dimer and Quick values were normal. However, the extract MP101UJ appeared to significantly inhibit the lethal venom induced myotoxic, cytotoxic and coagulation activities in experimental animals.

Development of a Membrane Oxygenator for Long-Term Respiratory Support and Its Experimental Evaluation in Prolonged ECMO

The authors developed a new membrane oxygenator (MO) for long-term respiratory support and evaluated its performance in animal experiments for as long as 336 hr. The MO, with a membrane area of 1.2 m2 and priming volume of 140 ml, is compact and designed to be interposed in a ventricular assist system (VAS) conduit. It is made with a novel hollow fiber membrane, in which micropores are blind-ended so that serum leakage can be prevented during prolonged use. The blood contacting surface of the MO is heparinized with a newly developed covalent bonding technique that ensures good thrombus resistance. In vivo evaluation with five adult goats was performed by installing the MO into a venoarterial or venovenous bypass circuit. No systemic anticoagulant therapy was used, except for a heparin-added fluid infusion to keep the pressure monitoring lines open (2-3 U/kg/hr). Throughout the experiments, no plasma leakage was observed, and gas transfer rates were maintained in a satisfactory range. Platelet counts did not decrease to less than 60% of levels before bypass, and hemolysis was negligible. The levels of coagulation parameters including fibrinogen, fibrin degradation products (FDP), antithrombin III (AT III), antiplasmin, prothrombin time (PT) and activated partial thromboplastic time (APTT) remained within physiologic ranges and relatively constant. At the end of the evaluation, no thrombus formation was noted in three of five MOs. These results suggest that this MO is a promising device for long-term respiratory support.

Effect of low-dose oral triphasic contraceptives on blood viscosity, coagulation and lipid metabolism

The purpose of the study was to determine the relationship between hemorheological profile, i.e. blood viscosity, and other risk factors for cardiovascular and thrombotic diseases in women taking oral contraceptives and if blood viscosity may be considered a marker of cardiovascular risk in OC users. Plasma levels of coagulation parameters, serum lipids, blood viscosity and RBC deformability were determined in a group of 10 women taking OC vs. 10 controls. The blood parameters were evaluated before OC use and thereafter at 3 and 6 months. A significant change in the partial thromboplastin time, fibrinogen, HDL and apolipoprotein A-I was observed, while the other parameters remained unchanged. Plasma viscosity was significantly increased during OC treatment; whole blood viscosity and RBC deformability remained unchanged. However, although some parameters were significantly modified during OC treatment, all alterations remained within the normal range of laboratory values. The data confirm that low-dose triphasic OC therapy does not affect significantly the coagulation system, serum lipid metabolism and blood viscosity. Plasma viscosity measurement may be considered as a marker for monitoring women using OC because it is apparently the most sensitive parameter.