Laboratory Coagulation Tests Research Articles

Thrombin Generation and D-Dimer Significantly Predict for Early Disease Progression and Mortality in Patients with Gastrointestinal Cancer

Background: Abnormalities of laboratory coagulation tests are common in cancer patients, underlying a subclinical hypercoagulable state. Due to the reciprocal interaction between coagulation and cancer, the biomarkers of hemostatic system activation are under evaluation as a tool for predicting cancer outcomes, disease progression, and mortality. Aim: In this analysis of a prospective cohort of patients with newly diagnosed metastatic gastro-intestinal (GI) cancer, we wanted to evaluate whether the pre-chemotherapy abnormalities of hemostatic biomarkers may predict for early-disease progression (E-DP), i.e. within 6 months from cancer diagnosis, and for 1-year overall survival (1-year OS). Methods: The study cohort included 304 newly diagnosed metastatic GI cancer patients, candidate to chemotherapy associated or not with immunotherapy, enrolled from March 2012 to March 2019 in the HYPERCAN study (ClinicalTrials.gov, ID# NCT02622815), an ongoing Italian prospective, multicenter, observational study; 191 healthy subjects acted as a control group. At diagnosis, before starting any curative chemotherapy, plasma samples were collected and tested for the following hypercoagulation biomarkers: D-dimer and fibrinogen by an automated coagulometer analyzer (ACL TOP500, Werfen Group), and prothrombin fragment 1+2 (F1+2) by ELISA (Siemens). In addition, thrombin generation (TG) potential was evaluated by Calibrated Automated Thrombogram (CAT) assay at 5 pM tissue factor and endogenous thrombin potential (TG ETP) and TG peak were analyzed. Clinical data [i.e. age, sex, BMI, ECOG Performance Status (ECOG-PS), relevant comorbidies] and the hemochromocytometric parameters were recorded at enrollment, whereas E-DP was clinically monitored every 3 chemotherapy cycles and during follow-up. Results: A cohort of 304 (205M/99F) metastatic GI cancer patients (206 colorectal and 98 gastric cancers) with a median age of 66 years (min-max: 29-85) was available for analysis. At enrollment, patients presented with a hypercoagulable state, as shown by significantly higher (p<0.001) plasma levels of D-dimer, fibrinogen and F1+2, and significantly higher (p<0.01) TG peak and TG ETP values than controls. After 6 months from the start of chemotherapy, E-DP had occurred in 80 patients, providing a cumulative incidence of 29.6% (CI 95% 24.1-35.1). E-DP subjects had significantly (p<0.05) higher baseline D-dimer levels and TG ETP value than non-E-DP patients. Correlation analyses showed that pre-chemotherapy fibrinogen (β = -0.127; p=0.048), D-dimer (β = -0.198; p=0.002) and TG ETP (β = -0.133; p=0.034) levels were significantly and inversely associated with time to E-DP. By Multivariate Cox regression analysis, gastric cancer diagnosis (HR=1.546), pre-chemotherapy D-dimer (HR=1.001) and TG ETP values (HR=1.001) were identified as independent risk factors for E-DP. After 1 year from the start of chemotherapy, 228 patients were dead and the OS was 66.6% (CI 95% 61.3-71.9). Patients who died within 1 year showed higher baseline D-dimer, F1+2, fibrinogen, TG peak and TG ETP values compared to the remaining subjects. Multivariate Cox regression identified independent risk factors for 1-year OS the followings: gastric cancer diagnosis (HR=2.237), D-Dimer (HR=1.001) and TG ETP (HR=1.001) levels, white blood cell count (HR=1.094), ECOG-PS>1 (HR=3.858), and chemotherapy plus immunotherapy treatment (HR=2.274). Conclusion: Our results show that, in newly diagnosed metastatic gastrointestinal cancer patients, before the start of antitumor treatment, a procoagulant state exists. Among the different hemostatic parameters evaluated, D-dimer and TG ETP appear as candidate biomarkers to predict for 6-month DP and 1-year OS. In particular, in this setting, the role of TG as a prognostic biomarker emerges for the first time in a large prospective cohort of GI cancer patients. Project funded by "5xMILLE" n. 12237 grant from the "Italian Association for Cancer Research (AIRC)" Disclosures Santoro: Bristol-Myers Squibb, SERVIER, Gilead Sciences, Pfizer, Eisai, Bayer, MSD, Sanofi, ArQule: Consultancy; Arqule, Sanofi: Consultancy; Takeda, Roche, Abbvie, Amgen, Celgene, AstraZeneca, ArQule, Lilly, Sandoz, Novartis, Bristol-Myers Squibb, Servier, Gilead Sciences, Pfizer, Eisai, Bayer, MSD: Speakers Bureau; Takeda, Roche, Abbvie, Amgen, Celgene, AstraZeneca, ArQule, Lilly, Sandoz, Novartis, Bristol-Myers Squibb, Servier, Gilead Sciences, Pfizer, Eisai, Bayer, MSD: Speakers Bureau; Bristol Myers Squibb, Servier, Gilead, Pfizer, Eisai, Bayer, MSD: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb, SERVIER, Gilead Sciences, Pfizer, Eisai, Bayer, MSD, Sanofi, ArQule: Consultancy, Speakers Bureau; Bristol-Myers Squibb, SERVIER, Gilead Sciences, Pfizer, Eisai, Bayer, MSD, Sanofi, ArQule: Consultancy.

Референсные интервалы параметров ротационной тромбоэластометрии у беременных и родильниц: одноцентровое рандомизированное исследование

Введение: В последнее время стали востребованы интегральные тесты оценки системы гемостаза у женщин во время беременности, а также во время акушерских операций, связанных с кровотечением. В нашей стране отсутствуют работы по определению популяционных норм ротационной тромбоэластометрии (РОТЕМ) у беременных, рожениц и родильниц. Цель исследования: определить пределы референсных интервалов показателей РОТЕМ во время физиологически протекающей беременности и в раннем послеродовом периоде и провести корреляционный анализ со стандартными показателями коагулограммы. Материалы и методы: Обследовано 229 женщин Красноярского края, которые были поделены на 5 групп: небеременные (контроль), беременные II и III триместров, женщины раннего послеродового периода после операции кесарева сечения и естественных родов. Все женщины были сопоставимы по возрасту, индексу массы тела, сопутствующей патологии. Референсные интервалы рассчитывали либо через среднее и стандартное отклонение (для нормального распределения), либо через медиану и 2,5 и 97,5% перцентили (для ненормального распределения). Результаты: В процессе исследования подтвердилось, что во время беременности и в раннем послеродовом периоде происходят изменения в системе гемостаза в сторону гиперкоагуляции. Показатели ROTЕM у женщин в III триместре беременности и раннем послеродовом периоде существенно отличаются от показателей небеременных в популяции. У женщин после родов вне зависимости от способа родоразрешения различий между параметрами ROTЕM не установлено. Корреляция между параметрами ROTЕM и традиционными лабораторными тестами коагуляции выявила взаимосвязь между амплитудой плотности сгустка в тесте FIBTEM и уровнем фибриногена по Клаусу. Заключение: Представлены референсные интервалы параметров РОТЕМ у женщин Красноярского края. Найдена корреляция между параметрами РОТЭМ и уровнем фибриногена. Background: Recently, integral tests for hemostasis assessment in pregnant women as well as during obstetric surgery associated with bleeding have become popular. In our country, there are no studies of population norms for rotational thromboelastometry (ROTEM) in pregnant women, parturients and puerperants. Objectives: to identify reference intervals limits for ROTEM parameters during physiological pregnancy and in early postpartum period and to carry out correlation analysis with standard coagulogram parameters. Patients/Methods: We examined 229 women in Krasnoyarsk region; they were divided into 5 groups: nonpregnant (control), pregnant women in II and III trimesters, women in early postpartum period after cesarean section and after vaginal delivery. All women were comparable in age, body mass index, and concomitant pathology. Reference intervals were calculated either as the mean and standard deviation (for normal distribution), or as the median and 2.5 and 97.5% percentiles (for abnormal distribution). Results: The study confirmed hemostasis hypercoagulation changes during pregnancy and in early postpartum period. ROTEM parameters in women in III trimester of pregnancy and in early postpartum period differ significantly from those in non-pregnant women. Differences between ROTEM parameters in puerperants, regardless of the delivery method, not found. The correlation between ROTEM parameters and traditional laboratory coagulation tests revealed a relationship between clot density amplitude in FIBTEM test and Klaus fi brinogen level. Conclusions: Reference intervals of ROTEM parameters in women of Krasnoyarsk region are presented. A correlation was found between ROTEM parameters and fibrinogen level

Assessment of the effects of sugammadex on coagulation profiles using thromboelastographic parameters

This study evaluated the effects of sugammadex at conventional doses of 2 and 4 mg/kg on the coagulation profile by analyzing thromboelastographic parameters and performing a traditional laboratory coagulation analysis. A total of 100 patients undergoing arthroscopic shoulder surgery were enrolled. The patients were randomly divided into the 2 mg and 4 mg groups. The laboratory coagulation test and thromboelastographic analysis were performed before and 15 min after administering sugammadex. Prothrombin time (PT) was significantly prolonged after sugammadex administration than before it in intragroup comparisons of the 2 mg group (12.8 ± 0.6 s vs. 13.6 ± 0.7 s, p < 0.001) and the 4 mg group (13.0 ± 0.5 s vs. 13.7 ± 0.5 s, p < 0.001). R time, derived from thromboelastography, was also significantly prolonged after sugammadex administration (4.7 ± 1.8 min vs. 5.8 ± 2.1 min, p = 0.005). In conclusion, the conventional doses of 2 or 4 mg/kg sugammadex prolonged PT. Sugammadex 4 mg/kg also prolonged R time, although the value was within the normal range. Therefore, physicians should be cautious with the higher sugammadex dose, particularly in patients with a high risk of bleeding because the higher dose was associated with less coagulation.Trial registration: KCT0002133 (https://cris.nih.go.kr).

Methylene tetrahydrofolate reductase C677T polymorphism in Korean livedoid vasculopathy patients

Methylene tetrahydrofolate reductase C677T polymorphism in Korean livedoid vasculopathy patients

Thromboelastometry and a hemostasis management system are most beneficial for guiding hemostatic therapy in cardiac surgery patients with a EuroSCORE II of ≥1.83%: a randomized controlled two-step trial.

We evaluated the efficacy of hemostatic therapy based on point-of-care (POC) testing in patients undergoing cardiac surgery. This was a single-institution, prospective, randomized, double-blinded study. In step 1, 90 patients scheduled for elective cardiac surgery underwent complete blood count and fibrinogen measurements at baseline, after cardiopulmonary bypass (CPB) initiation (CPB start), just after CPB end, and in the intensive care unit (ICU). In step 2, 72 patients scheduled for elective cardiac surgery underwent conventional laboratory coagulation tests (control group) or POC coagulation tests (POC group). Transfusions were prepared using the fibrinogen and platelet values at mainly "CPB start" for the control group, and using the ROTEM values at mainly "CPB end" for the POC group. Consequently, the step 2 patients were divided into high- and low-risk subgroups based on the EuroSCORE II by logistic regression analysis; transfusion data and bleeding volumes were compared between the control and POC groups within the high- and low-risk subgroups. In step 1, all blood components were significantly decreased at CPB start compared with baseline, and platelet and fibrinogen levels remained almost constant from CPB start to end. In step 2, the transfusion rates and perioperative bleeding volumes did not significantly differ between the control and POC groups. Subgroup analysis suggested that only the high-risk subgroup significantly differed regarding perioperative red blood cell transfusion and total bleeding volume in the ICU. POC testing is beneficial for cardiac surgery patients with a EuroSCORE II of ≥1.83%.

Author response: Low hemoglobin and hematoma expansion after intracerebral hemorrhage.

The comments posited by Yu et al.1 appropriately highlight limitations of single-center observational data and the importance of external replication for our findings. While adjusting for laboratory coagulation testing is important to consider, it is worth noting that we excluded patients with laboratory evidence of coagulopathy because of systemic medical disease. In addition, we adjusted for anticoagulation use, which should account for prothrombin time/international normalized ratio elevations due to a medication effect. Subsequently, it would be unlikely that the addition of laboratory coagulation markers in a multivariable model would affect the conclusions seen in our cohort.

Guidelines on the use of liver biopsy in clinical practice from the British Society of Gastroenterology, the Royal College of Radiologists and the Royal College of Pathology

Liver biopsy is required when clinically important information about the diagnosis, prognosis or management of a patient cannot be obtained by safer means, or for research purposes. There are several...

Characterization of hereditary factor XI deficiency in Taiwanese patients: identification of three novel and two common mutations.

Hereditary coagulation factor XI (FXI) deficiency is a rare bleeding disorder, but information on FXI deficiency in Taiwanese patients remains scarce. We evaluated clinical and genetic features of severe FXI deficiency patients in Taiwan. We collected clinical information and performed coagulation laboratory tests and genetic studies in ten unrelated Taiwanese families with severe FXI deficiency. FXI coagulation activity was assayed using a one-stage method. FXI antigen was determined using enzyme-linked immunosorbent assay. Underlying genetic mutations were evaluated using direct sequencing methods. Ten unrelated Taiwanese patients with hereditary FXI deficiency and variable bleeding tendencies were analyzed. Half of the patients were male. The most common bleeding manifestations were easy bruising (40%), bleeding after dental procedures (40%), and postoperative bleeding (33%). Two patients (20%) were asymptomatic. No correlation was found between bleeding manifestations and baseline FXI levels. Three novel mutations were identified: c.1322delT p.Lys442Cysfs*8, c.599G > C p.Cys200Ser, and IVS4 c.325 + 2del124. Two common mutations, c.1107C > T p.Tyr369* (40%) and c.841C > T p.Gln281* (30%), were also found. No correlation existed between bleeding and FXI activity, highlighting the difficulty in predicting FXI deficiency-related bleeding. Three novel FXI genetic mutations and two common mutations were identified, contributing to the known spectrum of FXI deficiency-related mutations.

Influence of saliva on the results of global laboratory coagulation tests.

Oral wounds inevitably come into contact with saliva which can affect thetime needed for bleeding to stop. The influence of saliva can be non-specific, related to dilution of blood, and/or mediated by salivary factors that affect haemostasis directly. The aim of this study was to assess if mixing blood with anindividual's saliva would affect the rate of its coagulation measured by global coagulation tests, prothrombin time (PT) and activated partial thromboplastin time (APTT). The study included 30 healthy non-smoking volunteers. Paired blood and unstimulated saliva samples were obtained from each participant and PT and APTT were determined in blood, blood+saliva and blood+water mixtures. Coagulation tests were performed using the mechanical clot detection method. PT was significantly longer in both blood+saliva and blood+water mixtures compared to blood alone. APTT was significantly longer only in blood+water mixture compared to blood. Similarly prolonged PT in both mixtures suggests that both saliva and water prolong coagulation evenly due to their non-specific effect of blood dilution. The finding that APTT was significantly prolonged only when blood was mixed with water could indicate presence of tissue factor in saliva, however, in a concentration too low to influence the results of PT.

Isolated prolongation of activated partial thromboplastin time in intensive care unit patients: a practical diagnostic algorithm and management options.

Abnormal values for standard laboratory tests of coagulation are frequently reported in critically ill patients. Sepsis-associated coagulopathy with prolonged prothrombin time and thrombocytopenia is common among patients hospitalized in the intensive care unit (ICU). Isolated prolongation of activated partial thromboplastin time (aPTT) occurs less frequently in the ICU setting and has numerous causes. Moreover, there are several preanalytical factors that may impact on results obtained. Isolated prolongation of aPTT in the absence of clinically relevant bleeding is a common finding in patients in the ICU. The first step in the diagnostic process is exclusion of preanalytical error. Next, based on the clinical picture (normal haemostasis vs. bleeding tendency), the appropriate tests should be ordered, taking into account acquired and congenital causes. To establish a diagnosis in a timely fashion, the proposed practical diagnostic algorithm can be followed.

Laboratory coagulation tests and emicizumab treatment A United Kingdom Haemophilia Centre Doctors' Organisation guideline.

The factor VIII mimetic emicizumab (Hemlibra, Hoffman-la Roche, Basel, Switzerland) has a novel mode of action that affects the laboratory monitoring of patients receiving this treatment. This guideline from the United Kingdom Haemophilia Centre Doctors Organisation (UKHCDO) aims to provide advice for clinical and laboratory staff on appropriate use of laboratory assays in patients with Haemophilia A treated with emicizumab. The guideline was prepared by a review of the available literature and discussion and revision by the authors. The guideline describes the effect of emicizumab on commonly used coagulations tests and provides recommendations on the use of assays for measurement of factor VIII and factor VIII inhibitor in the presence of emicizumab. The guideline also provides recommendations on measurement of emicizumab. Knowledge of the effect of emicizumab on coagulation tests and factor assays is required to ensure appropriate testing and monitoring of therapy in patients receiving this drug.

A prospective study on the correlation between thromboelastometry and standard laboratory tests – influence of type of surgery and perioperative sampling times

This prospective study aimed at investigating the influence of surgery type and perioperative sampling times on the correlations between rotational thromboelastometry (ROTEM) parameters and standard laboratory coagulation tests assessing comparable coagulation phases. Patients undergoing glioblastoma multiforme resection (GBR group, n = 60) or laparoscopic colon cancer resection (CCR group, n = 40) were prospectively included. Blood samples for ROTEM and laboratory assessments were consecutively drawn within 24-hours prior to surgery (baseline), and at 2, 24 and 48-hours after surgery. Correlations between perioperative ExTEM clotting-time (CT-exTEM) and prothrombin time (PT), and between FibTEM maximum clot firmness (MCF-fibTEM) with and plasma fibrinogen (pFB) concentration (Clauss method), were evaluated using the Spearman’s rho test. The efficiency of recommended cut-offs of CT-exTEM (>75 s) and MCF-fibTEM (<10 mm) for predicting a prolonged PT (>15 s) or a low pFB (<2 g/L), respectively, was assessed using Receiver-Operator Characteristic curves. Correlations between CT-exTEM and PT were weak in GBR (rho = 0.25 [0.12–0.38], p < .01), and very weak in CCR (rho = 0.06 [−0.12–0.27]). Those between MCF-fibTEM and pFB, were strong in both GBR (rho = 0.69 [0.61–0.76], p < .01) and CCR (rho = 0.70 [0.60–0.78], p < .01). These correlations remained largely unchanged over the studied perioperative period in both groups. Recommended CT-exTEM and MCF-fibTEM cut-offs had poor sensitivity for predicting a prolonged PT (17% [8–31]) or a low pFB (46% [32–62]), without group-related differences. Neither the type of surgery nor the perioperative sampling times had a significant influence on the correlations between ROTEM parameters and standard laboratory tests. ClinicalTrials.gov ID: NCT02652897

Prophylactic plasma transfusion for patients without inherited bleeding disorders or anticoagulant use undergoing non-cardiac surgery or invasive procedures.

Prophylactic plasma transfusion for patients without inherited bleeding disorders or anticoagulant use undergoing non-cardiac surgery or invasive procedures.

Utility of Perioperative Laboratory Tests in Pediatric Patients Undergoing Spinal Fusion for Scoliosis

Study DesignRetrospective comparative study. ObjectivesWe aimed to characterize the frequency of perioperative laboratory tests for posterior spinal fusion (PSF) for adolescent idiopathic scoliosis (AIS) and to assess whether test results affected clinical management. Summary of Background DataPerioperative laboratory tests for PSF including complete blood count, coagulation laboratory tests, basic metabolic panels (BMPs), and type and screen, are commonly ordered based on providers' discretion or existing order sets. Studies have shown unnecessary laboratory tests as financially and physically costly in adults; however, no studies have examined the necessity of common perioperative laboratory tests in pediatric spinal deformity surgery. MethodsRetrospective review of patients aged 10–18 years who underwent PSF for AIS at our center in the past three years. The clinical utility of perioperative laboratory tests was assessed based on detected incidence of anemia, blood transfusions, hematology/endocrinology/nephrology consultations, insulin administration, and postponed/canceled surgeries. ResultsA total of 234 patients were included (mean age 14.4 ± 1.8 years, 75% female). Of 105 (44.9%) patients with preoperative coagulation laboratory tests, 21 (20%) had abnormal results; however, none had subsequent hematology consultations or canceled/postponed surgeries. Postoperatively, only 5 (2.1%) patients and 30 (12.8%) patients had hemoglobin values less than 8 g/dL on postoperative day (POD) 1 and 2, respectively. Multivariate analysis identified POD1 hemoglobin ≤9.35 g/dL as the only predictor of hemoglobin <8 g/dL on POD2. Overall, there were 8 (3.4%) indicated blood transfusions postoperatively. Costs of unnecessary laboratory tests averaged $95.27 (range $49.72 to $240.27) per patient. ConclusionsMany perioperative laboratory orders may be unnecessary in pediatric spinal deformity surgery, subjecting patients to extraneous costs and needlesticks. In particular, preoperative coagulation laboratory tests, perioperative BMPs, and additional postoperative CBCs for those with hemoglobin >9.35 on POD1 may not be warranted. Level of EvidenceLevel III, retrospective cohort study.

Clotting factors: Clinical biochemistry and their roles as plasma enzymes.

The purpose of this review is to describe structure and function of the multiple proteins of the coagulation system and their subcomponent domains. Coagulation is the process by which flowing liquid blood plasma is converted to a soft, viscous gel entrapping the cellular components of blood including red cells and platelets and thereby preventing extravasation of blood. This process is triggered by the minimal proteolysis of plasma fibrinogen. This transforms the latter to sticky fibrin monomers which polymerize into a network. The proteolysis of fibrinogen is a function of the trypsin-like enzyme termed thrombin. Thrombin in turn is activated by a cascade of trypsin-like enzymes that we term coagulation factors. In this review we examine the mechanics of the coagulation cascade with a view to the structure-function relationships of the proteins. We also note that two of the factors have no trypsin like protease domain but are essential cofactors or catalysts for the proteases. This review does not discuss the major role of platelets except to highlight their membrane function with respect to the factors. Coagulation testing is a major part of routine diagnostic clinical pathology. Testing is performed on specimens from individuals either with bleeding or with thrombotic disorders and those on anticoagulant medications. We examine the basic in-vitro laboratory coagulation tests and review the literature comparing the in vitro and in vivo processes. In vitro clinical testing typically utilizes plasma specimens and non-physiological or supraphysiological activators. Because the review focuses on coagulation factor structure, a brief overview of the evolutionary origins of the coagulation system is included.

Breakfast can Affect Routine Hematology and Coagulation Laboratory Testing: An Evaluation on Behalf of COLABIOCLI WG-PRE-LATAM.

Laboratories worldwide perform both hematological and coagulation testing on patients avoiding fasting time. In 2017, the Latin America Confederation of Clinical Biochemistry (COLABIOCLI) commissioned the Latin American Working Group for Preanalytical Phase (WG-PRE-LATAM) to study preanalytical variability and establish guidelines for preanalytical procedures to be applied by clinical laboratories and health care professionals. This study, on behalf of COLABIOCLI WG-PRE-LATAM, aims to evaluate the effect of the breakfast on routine hematology and coagulation laboratory testing. We studied 20 healthy volunteers who consumed a breakfast containing a standardized amount of carbohydrates, proteins, and lipids. We collected blood specimens for routine hematology and coagulation laboratory testing before breakfast and 1, 2, and 4 hours thereafter. Significant differences between samples were assessed by the Wilcoxon ranked-pairs test. Statistically significant differences ( p < 0.05) between basal and 4 hours after the breakfast were observed for red blood cells, hemoglobin, hematocrit, mean corpuscular volume, white blood cells, neutrophils, lymphocytes, monocytes, mean platelet volume, and activated partial thromboplastin time. In conclusion, the significant variations observed in several hematological parameters, and activated partial thromboplastin time due to breakfast feeding demonstrate that the fasting time needs to be carefully considered prior to performing routine hematological and coagulation testing to avoid interpretive mistakes of test results, and to guarantee patient safety. Therefore, COLABIOCLI WG-PRE-LATAM encourages laboratory quality managers to standardize the fasting requirements in their laboratory, i.e., 12 hours.

P4744Patients with atrial fibrillation exhibit a systemic prothrombotic state attributable to impaired endogenous fibrinolysis

Abstract Background The association of atrial fibrillation (AF) with thromboembolic stroke due to stasis in the left atrium and left atrial appendage is well described. Whether AF is associated with a systemic prothrombotic state, detectable in peripheral blood, unclear. Previous studies have been inconsistent, with some very small previous studies (&lt;30 patients each) variably indicating that patients with AF may have raised platelet reactivity and levels of antithrombin III, d-dimer, PAI-1 and t-PA-PAI complexes. These cumbersome laboratory tests of coagulation and fibrinolysis are not readily available in the clinical setting. Purpose It was our aim to compare, in peripheral venous blood, thrombotic and endogenous fibrinolytic profile of healthy volunteers and patients with newly diagnosed nonvalvular atrial fibrillation (NVAF), using a point-of-care technique. Methods In a prospective observational study, venous blood samples were taken from 98 healthy volunteers and 100 patients with newly diagnosed NVAF in the out-patient setting. Patients with newly diagnosed NVAF had venous blood tested before any treatment was initiated with aspirin or oral anticoagulation. Thrombotic status was assessed using the Global Thrombosis Test (GTT), a point-of-care test using native non-coagulated blood, assessed within 15 sec of blood withdrawal. The time to form an occlusive venous thrombus in native (non-citrated) blood, a measure of platelet reactivity (occlusion time, OT) and the time taken to spontaneous endogenous fibrinolysis to restore flow (lysis time, LT) were assessed. Results Basic blood tests (full blood count, renal and liver function, inflammatory markers) were normal in all subjects. The groups were matched for sex and race. Mean age of the healthy cohort was 34±8 years and patients 65±10 years. Endogenous fibrinolysis was markedly impaired in patients with NVAF compared to healthy individuals as shown by markedly prolonged LT (median 2015s [interquartile range IQR 1555–2507] vs. 1124s [IQR 919–1554], p&lt;0.ehz745.11201). There was no difference in platelet reactivity between patients and normal volunteers (369s [IQR 308–445]vs 368s [IQR 309–441], p=0.704). Sensitivity analysis was performed on a subgroup matched for age, sex and race. LT remained significantly longer in patients with NVAF compared to controls (1569s [IQR 1499–2244] vs. 1219s [IQR 943–1560], p=0.03), with no difference in platelet reactivity (p=NS). Conclusion In the largest study to date and using a clinically-friendly automated point-of-care technique, we show that patients with NVAF exhibit a systemic prothrombotic state, attributable to significantly impaired endogenous fibrinolysis compared with healthy volunteers. Further studies are needed to see if this could become a screening test for the prothrombotic state in patients with NVAF. Acknowledgement/Funding None

The association between abnormal coagulation testing in preeclampsia, adverse pregnancy outcomes, and placental histopathology

ABSTRACTObjective: We aimed to determine whether abnormal coagulation laboratory testing results in preeclampsia, are associated with adverse pregnancy outcomes and placental histopathology lesions.Methods: Demographic, labor, laboratory-testing, and placental histopathology reports of pregnancies complicated by preeclampsia were compared between those with and without abnormal coagulation profile (ACP).Results: Of 348 cases of preeclampsia 16.1% had ACP. There were no differences between the groups in GA at delivery, severe features, placental-abruption, SGA, composite adverse neonatal outcome and placental histopathology lesions.Conclusion: ACP in pregnancies complicated by preeclampsia was not associated with any of the studied outcomes. Our data question the usefulness of routine coagulation tests in the initial assessment of women presenting with preeclampsia.

Perioperative effects of desflurane versus propofol on hemostasis guided by thromboelastometry in splenectomy with liver cirrhosis

ABSTRACTBackground: Cirrhotic patients have impaired hemostasis with variable incidence of hypersplenism necessitating splenectomy. Rotation thromboelastometery (ROTEM) facilitates diagnosis and guides management. This study evaluates perioperative effects of desflurane versus propofol on hemostasis in cirrhotic patients undergoing splenectomy guided by ROTEM and laboratory hemostatic tests.Methods: Thirty hepatic Child A patients, ASA II- III, of either sex, aged 25–55 years, undergoing splenectomy were randomly allocated into two equal groups: Group D; anesthetized with desflurane 1 MAC (6%) and Group P; with propofol Target Controlled Infusion 2–5 µg/ml. Six blood samples were collected; preoperatively, after splenic artery ligation, immediately, first, third postoperative day then one month later. The samples were handled to measure complete blood picture, liver and kidney functions, screening coagulation tests (INR, PT and PTT), specific hemostatic factors (P-Selectin/CD62P, fibrinogen and D-dimer) as well as ROTEM criteria; clotting time (CT), clot formation time (CFT) and maximum clot firmness (MCF) via EX-TEM, IN-TEM and FIB-TEM commercial kits.Results: This study displayed postoperative hemoglobin reduction; however, platelet and WBCs as well as CT, CFT and MCF increased versus baseline. Screening and specific hemostatic factors as all other changes were within reference range and comparable between both groups.Conclusions: The current study concluded comparable effects of desflurane and propofol anesthesia on coagulation parameters within acceptable range as monitored by ROTEM and laboratory coagulation tests in cirrhotic patients with hypersplenism. Thus both anesthetics are considered safe in such patients who have high incidence of coagulopathy.

Coagulation in Brain Tumors: Biological Basis and Clinical Implications.

Cancer patients commonly show abnormal laboratory coagulation tests, indicating a subclinical hypercoagulable condition that contribute to morbidity and mortality. The hypercoagulation status not only increases the risk of thromboembolic events but also influences the tumor biology promoting its growth and progression by stimulating intracellular signaling pathways. Recent molecular studies characterized the role of oncogene and suppressor gene in activating clotting pathways, as an integral feature of the neoplastic transformation. It is now clear how haemostatic processes, activated by cancer cells harboring oncogenic mutations, rely on the molecular profile of a particular malignancy, an aspect particularly evident in the differential coagulome profiles showed by different molecular subtypes of brain tumors, such as glioblastoma and medulloblastoma. This review focuses on the biological and clinical aspects of haemostasis in cancer with particular regard on brain tumors.