Coagulation Studies Research Articles

Tachypnea and Epistaxis in a Full-term Infant.

1. Daniela Titchiner, MD* 2. Priya Dukes, MD* 3. Rebecca Speier, MD* 4. Sharla Rent, MD* 1. *Duke University Hospital, Durham, NC 1. Address correspondence to Daniela Titchiner, MD, Department of Neonatology, Duke University Hospital, 2301 Erwin Rd, Durham, NC 27710. E-mail: daniela.titchiner{at}duke.edu A 3.8-kg male infant is born at 40 weeks’ gestation to a 30-year-old primigravida woman via normal spontaneous vaginal delivery. The pregnancy is uncomplicated, with appropriate prenatal care. Delivery is uneventful; the patient receives routine delivery care with Apgar scores of 7 at 1 minute and 9 at 5 minutes. The infant is transferred to newborn nursery with no complications. At 19 postnatal hours, he develops persistent tachypnea and stertor. The patient’s nares are suctioned bilaterally, followed by frank epistaxis and 2 episodes of bloody emesis. As a result, he is admitted to the NICU due to concern for respiratory distress and evaluation of bloody emesis. Initial examination in the NICU reveals an appropriate for gestational age term infant with mild tachypnea with RR 80, no increased work of breathing, saturating > 97% on room air. Chest radiograph demonstrates no abnormalities. The results of a complete blood cell count and coagulation studies are within normal limits. The examining NICU physician notes a soft-tissue mass in the left nasal meatus, without facial asymmetry or visible oropharynx abnormality noted. Pediatric otolaryngology (ENT) department is consulted and via flexible fiberoptic laryngoscopy visualizes a “soft, pink, mass in the …

Investigating the antimicrobial and coagulation properties of Chrysophyllum albidum seeds

In the present study, plant-based coagulant namely the seed of the Chrysophyllum albidum was investigated for its coagulation and antimicrobial efficacy. The coagulation study was conducted on a turbid surface water sample obtained at the Ezu River in Anambra State, Nigeria. The highest coag-flocculation activity was recorded at dosage of 0.4 g/400 mL, pH of 3, coagulation rate constant K = 7.4733 × 10−4m3/kg.s, and coagulation period τ = 2.29 secs. The observed turbidity removal efficiency of over 75% proved that the natural coagulant improved the quality of the water sample. On disinfection, the results indicated that the C. albidum seed extracts showed varying degrees of growth inhibitions on both gram positive and gram negative organisms. The antimicrobial activity observed ranged from 0 to 10 mm at different concentrations. The study shows that the C. albidum seed extracts are therefore a potential bio-coagulant and disinfectant that requires further studies and development.

Investigating the antimicrobial and coagulation properties of <i>Chrysophyllum albidum</i> seeds

In the present study, plant-based coagulant namely the seed of the Chrysophyllum albidum was investigated for its coagulation and antimicrobial efficacy. The coagulation study was conducted on a turbid surface water sample obtained at the Ezu River in Anambra State, Nigeria. The highest coag-flocculation activity was recorded at dosage of 0.4 g/400 mL, pH of 3, coagulation rate constant K = 7.4733 × 10−4m3/kg.s, and coagulation period τ = 2.29 secs. The observed turbidity removal efficiency of over 75% proved that the natural coagulant improved the quality of the water sample. On disinfection, the results indicated that the C. albidum seed extracts showed varying degrees of growth inhibitions on both gram positive and gram negative organisms. The antimicrobial activity observed ranged from 0 to 10 mm at different concentrations. The study shows that the C. albidum seed extracts are therefore a potential bio-coagulant and disinfectant that requires further studies and development.

Unexpected upper limb compartment syndrome due to venous thrombosis in frontal glioma surgery: A case report

Although it is well known that 49% cases of upper limb deep-vein thrombosis are due to malignancies and the likelihood of venous thromboembolism is increased in patients with high grade gliomas due to the heightened prothrombotic milieu, requisite preoperative laboratory coagulation studies are not performed routinely in these patients to decide whether appropriate antithrombotic medications are required preoperatively. In addition, it is controversial whether antithrombotic therapy should be initiated before neurosurgery in view of the risk of intraoperative bleeding. Here, we have described the case of a 29-year-old female with high grade frontal malignant astrocytoma who developed the extremely rare complication of upper limb compartment syndrome postoperatively. The patient had no history of thrombotic events, and her basic laboratory parameters were not deranged in the pre-operative period. This rare case, supported with a literature review, suggested that the risk of thrombosis is increased in high grade and large gliomas, making us rethink the overall battery of investigations and perioperative medical management of such cases. We strongly recommend peri-operative coagulation studies and appropriate antithrombotic measures along with vigilant perioperative monitoring to avoid thrombotic complication in this subset of patients.

Use of Fibrinogen Determination Methods in Differential Diagnosis of Hypofibrinogenemia and Dysfibrinogenemia.

Fibrinogen plays an important role in hemostasis. The normal concentration of fibrinogen in blood plasma is between 1.8 - 4.2 g/L. Decreased fibrinogen levels are observed in congenital afibrinogenemia, hypofibrinogenemia, dysfibrinogenemia, disseminated intravascular coagulation, fibrinolytic therapy, some more severe hepatic parenchymal disorders, and increased blood loss. Elevated fibrinogen levels occur in inflammatory diseases and neoplastic diseases, in pregnancy, and postoperative conditions. Functional fibrinogen measurement is also one of the basic coagulation screening tests. The fibrinogen antigen assay is used to distinguish between qualitative and quantitative fibrinogen disorders. The aim of the study was the use of fibrinogen determination methods in differential diagnosis of hypofibrinogenemia and dysfibrinogenemia, statistical evaluation and determine the relationship of fibrinogen Clauss assay, prothrombin time (PT) derived fibrinogen assay, and fibrinogen antigen in the group of 60 patients with congenital fibrinogen disorders (n = 40 dysfibrinogenemia; n = 20 hypofibrinogenemia). The results measured by the PT-derived fibrinogen assay were approximately four times higher compared to the fibrinogen Clauss assay in the group of patients with dysfibrinogenemia. In patients with hypofibrinogenemia, there is a correlation (r = 0.9016) between the fibrinogen Clauss assay and PT-derived fibrinogen assay with a statistical significance of p < 0.0001. Using a linear or quadratic interpolation function, we were able to determine the fibrinogen Clauss assay and the fibrinogen antigen assay before analysis. The higher level of the PT-derived fibrinogen assay compared to the fibrinogen Clauss assay in the group of patients with dysfibrinogenemia may pose a greater risk to asymptomatic patients who require diagnosis and treatment in case of bleeding. The fibrinogen value using the PT-derived fibrinogen assay could erroneously give a normal level. The use of the interpolation function is important to estimate the value of fibrinogen activity and antigen before the analysis itself by the Clauss assay or analysis by the fibrinogen antigen assay.

Investigation of attributes of bourbon oil and cobalt nitrate constituted electrospun nanoscaffolds for blood compatibility and in vitro bone formation.

This work aims to fabricate scaffold using polyurethane (PU) integrated with bourbon oil (BB) and cobalt nitrate (CoNO3) using the electrospinning technique. Morphological investigation signified a fall in fibre diameter for the PU/BB and PU/BB/CoNO3 nanocomposite than the PU. Spectral analysis indicated that BB and CoNO3 were added within the PU matrix. Wettability analysis insinuated an increase in the hydrophobic nature of the PU/BB than the PU. PU/BB/CoNO3 turned to be hydrophilic due to the integration of CoNO3 in the polymer matrix. Mechanical testing of PU/BB and PU/BB/CoNO3 indicated an increase in the tensile strength of the fabricated composites. Atomic force microscopy (AFM) portrayed the reduction in the roughness of the PU/BB and PU/BB/CoNO3 compared to the PU. The coagulation studies invariably documented the improved anticoagulant behaviour and less toxic nature of the PU/BB and PU/BB/CoNO3 in comparison with the PU. Further, bone mineralization testing revealed the enhanced apatite formation of the nanocomposite. Nanocomposite scaffolds with the fore-mentioned properties hold good potential for bone tissue engineering.

Evaluation of markers of thrombosis and fibrinolysis in malaria patients in tertiary care hospital in Central India

Background: Cases of malaria are known to be associated with variable degrees of coagulopathy asevident from abnormalities of screening coagulation assays in a large number of patients during theillness. However, attempts to use laboratory parameters as indicators of the severity of theunderlying coagulopathy and for monitoring disease progression have met with only partial success.Methods: This prospective study was conducted in the department of Pathology in RuxmanibenDeepchand Gardi Medical College, Ujjain. Blood samples of all the patients diagnosed positive withmalaria were collected in vials containing ethylene tetra-acetic acid tri potassium salt forhematological parameters and in trisodium citrate tubes for coagulation assays. Result: Out of thetotal positive cases, PT was prolonged in 65% of total cases, Percentage positivity for prolonged PTfor falciparum and vivax is 60% and 68.5% respectively. APTT has raised 47% of malaria positivecases with percentage positivity for falciparum and vivax 48% and 45.7% respectively. 55% of totalcases showed raised levels of fibrin degradation products, which included 48% of falciparum casesand 60% of vivax cases. Out of 120 positive cases of malaria, D- Dimer was raised 41.7% cases.Conclusion: As blood is the chief component affected by malaria, not only proper examination ofperipheral smears is required for detection and species identification, but a careful evaluation ofother laboratory parameters should be done irrespective of the malarial species for the earlydiagnosis of compensatory and non-compensatory consumptive coagulopathy.

Trilayer Interlinked Graphene Oxide Membrane for Wearable Hemodialyzer.

2D nanomaterials have long been considered for development of high permeability membranes. However, current processes have yet to yield a viable membrane for practical use due to the lack of scalability and substantial performance improvements over existing membranes. Herein, an ultrathin graphene oxide (GO) membrane with a permeability of 1562 mL h-1 mmHg-1 m-2, two orders of magnitude higher than the existing nanofiltration membranes, and a tight molecular weight cut-off is presented. To build such a membrane, a new process involving self-assembly and optimization of GO nanoplatelet physicochemical properties is developed. The process produces a highly organized mosaic of nanoplatelets enabling ultra-high permeability and selectivity. An adjustable molecular interlinker between the layers enables absolute nanometer-scale size cut-offs. These characteristics promise significant improvements to many nanoparticle and biological separation applications. In this work, the performance of the membrane in blood dialysis scenarios is evaluated. Urea and cytochrome-c sieving coefficients of 0.5 and 0.4 are achieved while retaining 99% of albumin. Hemolysis, complement activation, and coagulation studies exhibit a performance on par or superior to the existing dialysis membrane materials.

New approaches to the diagnosis and treatment of coagulation disorders

With the advent of new approaches in coagulation studies capable of identifying regulatory mechanisms involved in transport processes, the spatial localization of processes and interaction between the coagulation system and the immune system, the complement system, and fibrinolysis, the existing diagnostic and treatment approaches used in clinical and laboratory practice are changing as well. This review describes modern diagnostic methods for hemostasis disorders that are based on an integrative approach and are used to assess many aspects of the coagulation system at once. The reviewed methods are sensitive not only to bleeding but also to prothrombotic states, and enable monitoring of treatment with various medications including both oral anticoagulants and antihemophilic agents. We will also cover new approaches to the treatment of hemostasis disorders made possible by the understanding of the involved control mechanisms, such as the use of bispecific antibodies as an alternative to coagulation cofactors, the inhibition of inhibitors and the development of new drug delivery techniques.

Pathophysiology of coagulation during bleeding

Background. Analysis of 99 studies found that the predictor properties of various tests to determine the blood coagulation condition, including the newest ones (thromboelastography, rotational thromboelastometry), regarding the risk of intra- and postoperative bleeding are low. The results of prothrombin time or activated partial thromboplastin time measurements can be very variable depending on the concentration of reagents and the characteristics of the analysis. That is why standard methods of screening to assess the condition of the coagulation system in all patients in the preoperative period are not recommended.&#x0D; Objective. To describe the features of perioperative blood clotting and management of patients.&#x0D; Materials and methods. Analysis of literature data on this topic.&#x0D; Results and discussion. Before performing invasive procedures, a careful history should be taken to determine the presence and severity of previous bleeding and to ask about antithrombotic medications. If the general hemorrhagic history is favorable, further determination of coagulographic parameters is not required. If the history is unfavorable or there is evidence of potential risk factors for bleeding (e. g., liver disease), a comprehensive coagulation study should be performed. Bleeding coagulopathy is a component of the so-called lethal triad, which also includes hypothermia and acidosis. Active administration of infusion solutions can deepen or provoke coagulopathy due to hemodilution. The use of balanced infusion solutions reduces the risk of this complication. According to some authors, the fibrinogen level &lt;2 g/L is the predictor of bleeding probability. The causes of this condition include hyperfibrinolysis, dysfunctional fibrinogen in case of the administration of colloid solutions, increased decomposition of fibrinogen due to acidosis. Colloidal solutions (hydroxyethyl starch) increase the risk of reoperation and the need for transfusions, so their routine use is not currently recommended. Hyperfibrinolysis is a condition in which the rate of blood clot breakdown exceeds the rate of blood clot formation. As a result, hemorrhagic shock worsens and coagulopathy develops. Hyperfibrinolysis develops due to fibrinolytic agents and hypoperfusion. Tranexamic acid is used for heavy bleeding, in particular, postpartum. The WOMAN study involved 20,600 women with postpartum haemorrhage who received 1 g of tranexamic acid or placebo. Mortality due to bleeding in the tranexamic acid group was 1.2 %, and in the placebo group – 1.7 % (p=0.008).&#x0D; Conclusions. 1. Routine use of colloid solutions should be avoided during bleeding. 2. It is necessary to detect and eliminate anemia, hypothermia and acidosis. 3. Detection and elimination of deficiency or dysfunction of coagulation factors, hyperfibrinolysis, thrombocytopenia is an important component of bleeding prevention. 4. Reducing bleeding and improving blood clotting leads to the less need for transfusions and better outcomes for the patient.

A retrospective study of coagulation parametres in patients of pregnancy induced hypertension

Introduction: Human pregnancy also known as gestation, is the time between fertilization of ovum to delivery of a baby. It is approcximately a process of 9 months during which new baby develops inside a womb. Physiologically, pregnancy is a hypercoagulative state. Hypercoagulable state in pregnancy is a naturally occuring preventive response to prevent excess loss of blood during delivery. It is essential to know the range of variations of the coagulation factors during normal pregnancy, if any specific component has to be incriminated as a causative agent for the vascular disorder. Preeclampsia is a serious and life threatening complication in pregnant women. It is a pregnancy specific disorder which rates among one of the major causes of maternal and foetal morbidity and mortality. Aims and Objectives: To evaluate severity of eclampsia by estimating coagulation profile tests in pregnancy induced hypertensive patients. To compare these biochemical parameters between the test group and control group. To correlate the outcome of pregnancy with these biochemical parameters. Materials and Methods: This retrospective study includes 120 females of uncomplicated pregnancy of age group 16-35 years as a control group and 120 females of same age group with pregnancy with hypertension (PIH) attending obstetric outdoor patient department (OPD) of the institute in the year of 2015. Blood samples are withdrawn from all participants for biochemical markers of coagulation study that includes total platelet count (PC), prothrombin time (PT) and activated partial thromboplastin time (APTT). Results: Among total 120 PIH participants, 44 (36.67%) cases were having mild gestational hypertension, 11 (9.17%) cases were having severe gestational hypertension, 34 (28.33%) cases were having mild preeclampsia and 31 (25.83%) cases were having severe preeclampsia. The mean value of PT and APTT is found to be high in PIH cases as compared to control group participants. Conclusion: Parameters

A Novel Nonsense Mutation in FGB (c.1421G>A; p.Trp474Ter) in the Beta Chain of Fibrinogen Causing Hypofibrinogenemia with Bleeding Phenotype.

Congenital hypofibrinogenemia is a rare bleeding disorder characterized by a proportional decrease of functional and antigenic fibrinogen levels. Hypofibrinogenemia can be considered the phenotypic expression of heterozygous loss of function mutations occurring within one of the three fibrinogen genes (FGA, FGB, and FGG). Clinical manifestations are highly variable; most patients are usually asymptomatic, but may appear with mild to severe bleeding or thrombotic complications. We have sequenced all exons of the FGA, FGB, and FGG genes using the DNA isolated from the peripheral blood in two unrelated probands with mild hypofibrinogenemia. Coagulation screening, global hemostasis, and functional analysis tests were performed. Molecular modeling was used to predict the defect of synthesis and structural changes of the identified mutation. DNA sequencing revealed a novel heterozygous variant c.1421G>A in exon 8 of the FGB gene encoding a Bβ chain (p.Trp474Ter) in both patients. Clinical data from patients showed bleeding episodes. Protein modelling confirmed changes in the secondary structure of the molecule, with the loss of three β sheet arrangements. As expected by the low fibrinogen levels, turbidity analyses showed a reduced fibrin polymerisation and imaging difference in thickness fibrin fibers. We have to emphasize that our patients have a quantitative fibrinogen disorder; therefore, the reduced function is due to the reduced concentration of fibrinogen, since the Bβ chains carrying the mutation predicted to be retained inside the cell. The study of fibrinogen molecules using protein modelling may help us to understand causality and effect of novel genetic mutations.

Сравнительное изучение кинетики свертывания крови и тромбообразования реологическими и электрореологическими методами.

Цель исследования: изучить механизмы формирования и тромбодинамические свойства кровяного сгустка при тромбообразовании in vitro и представить сравнительное исследование кинетики тромбообразования с помощью реологических и электрореологических методов в условиях постоянного и осциллирующего сдвигового вискозиметрического течения; оценить свертывание цельной и консервированной крови, ее вязкоупругие свой ства и влияние фибриногена и декстранов на формирование сгустка. Материалы и методы. Вязкость и удельную электропроводимость нормальной и консервированной с CPD-A1-адениновым раствором крови измеряли ротационным вискозиметром Low Shear 30 Contraves (LS30) с коаксиальными цилиндрами и копией измерительной системы MS1/1 со встроенными электродами (разработана на базе LS30) в условиях постоянного сдвигового потока и в электрическом поле. Вязкоупругие свойства нормальной цельной крови исследовали с помощью реометра Physica MCR 301 (Anton Paar, Austria) в условиях осциллирующего синусоидального потока. Результаты. Представлены результаты кинетики динамической вязкости и удельной электропроводимости консервированной крови в процессе коагуляции в условиях постоянного сдвигового потока и в электрическом поле. Исследованы вязкоупругие свойства цельной крови в условиях синусоидального осциллирующего вискозиметрического течения и представлены зависимости упругого модуля G' (storage modulus) и модуля потерь G'' (loss modulus), а также нормальных сил как функция времени при свертывании. Приводятся данные эффекта фибриногена и декстрана на упругий модуль G' и на модуль потерь G'' цельной крови в процессе коагуляции. Заключение. В условиях вискозиметрического течения при низких скоростях сдвига кинетика тромбообразования характеризуется начальным этапом постепенного увеличения кажущейся вязкости и уменьшения удельной электропроводимости крови и периодом интенсивной коагуляции, характеризирующимся экспоненциальным ростом вязкости и параллельным уменьшением удельной электропроводимости исследуемого образца. Установлено, что коагулирующая цельная кровь обладает нелинейными вязкоупругими свойствами. Кинетика образования сгустка в условиях осциллирующего вискозиметрического течения крови характеризуется увеличением упругого модуля G' и модуля потерь G'' со временем. Одновременно зарегистрирована и отрицательная нормальная сила исследуемого образца в зазоре между пластинами при постоянной толщине зазора. Повышение содержание фибриногена ускоряет коагуляцию и увеличивает значения упругого модуля G' и модуля потерь G'', а также и нормальной силы коагулирующей цельной крови. Objectives: to study the mechanisms of thrombus formation and thrombodynamic properties of a blood clot during coagulation in vitro and to present a comparative study of clot kinetics formation under conditions of steady and oscillating shear viscometric flow and at electric field by rheological and electrorheological methods; to evaluate the coagulation of whole and preserved blood, its viscoelastic properties and the effect of fi brinogen and dextrans on clot formation. Materials/ Methods. The viscosity and electrical conductivity of normal blood and blood preserved with CPD-A1-adenine solution were measured with a Low Shear 30 Contraves (LS30) rotational viscometer with coaxial cylinders and with a copy of the measuring system MS1 / 1 with builtin electrodes at a steady viscometric shear flow and in an electric field too. The viscoelastic properties of normal whole blood were investigated using a Physica MCR 301 rheometer (Anton Paar, Austria) at an oscillating sinusoidal flow. Results. Kinetics of the dynamic viscosity and electrical conductivity of preserved blood during coagulation at a steady shear flow and at electric field were obtained. The viscoelastic properties of whole blood were investigated under conditions of sinusoidal oscillating viscometric flow. The dependences of the elastic (storage) modulus G' and the loss modulus G'', as well as the normal coagulation forces as a function of time are presented. The effect of fibrinogen and dextran on the elastic modulus G' and the loss modulus G'' of whole blood during coagulation are presented. Conclusions. The kinetics of blood coagulation at low shear rates is characterized by a gradual increase of the apparent viscosity and a decrease in blood conductivity at the initial stage and an exponential increase in viscosity during intensive coagulation and a parallel decrease of conductivity too. It was established that coagulating whole blood exhibit nonlinear viscoelastic properties under conditions of sinusoidal blood flow. The kinetics of thrombus formation is characterized by increasing the elastic modulus G' (storage modulus) and the loss modulus G'' with time. The negative normal force in the gap between the plates is also registered at a constant thickness of the gap. An increase in fibrinogen content accelerates coagulation and increases the values of elastic modulus G' and loss modulus G', as well as of the normal force of coagulating whole blood.

LGG-24. CARBOPLATIN-INDUCED HEMATURIA IN A PEDIATRIC PATIENT WITH LOW-GRADE GLIOMA AND REVIEW OF LITERATURE

OBJECTIVEIn this case report, we present a pediatric patient with gross hematuria and hydroureteronephrosis associated with high dose carboplatin. Given the paucity of literature on the subject, we also conduct and present a review of cases. CASE PRESENTATION: A 6-year-old Caucasian female with history of Type 1 neurofibromatosis was undergoing treatment for a low-grade glioma with monthly high dose carboplatin (560 mg/m2). After 8th dose out of 13, the patient developed severe nausea and vomiting and was admitted for dehydration. She was noted to have microscopic hematuria. After 9th dose, the patient again developed severe nausea, vomiting and gross hematuria with clots. She was admitted and treated with IV hydration. Renal ultrasound showed newly developed bilateral hydroureteronephrosis. Coagulation studies were normal. Multiple cultures and viral studies were negative. Hematuria cleared spontaneously after 4 days of aggressive hydration.RESULTSSubsequent carboplatin was given with aggressive hydration and minimized nausea/vomiting and no hematuria was observed. Literature review revealed only 4 reported cases of carboplatin-induced hematuria, including only one pediatric case that occurred in a patient with concurrent thrombocytopenia. Carboplatin may exhibit toxicity to the transitional epithelial cells of the urogenital tract causing hemorrhage from the renal pelvis and ureters. If untreated, this may lead to urinary outflow obstruction and subsequent obstructive nephropathy.CONCLUSIONWe present a rare toxicity, gross hematuria caused by high-dose carboplatin treatment. Providers should be aware of this rare toxicity and provide timely hydration and supportive care to prevent development of obstructive kidney injury and/or renal failure.

Technological properties of cow’s milk depending on the season of the year

Provision of the population with a sufficient amount of domestically produced food, including milk and dairy products, is directly related to advances in breeding of dairy cattle as the main supplier of raw materials for dairy processing enterprises. Along with increased requirements for the quality of milk – raw material in production of dairy products – the focus is placed on its technological properties, namely the possibility of its effective use for processing into certain products: fermented milk, cheese, butter, etc. It is known that milk is affected by many factors, including the season of the year, which impacts not only supply of raw materials to the dairy industry but also its quality. The study aimed to investigate the impact of the season of the year on raw milk intended for processing into various dairy products. The study revealed that sensory properties of milk met the requirements of the regulatory documents. The milk color changed depending on the season of the year. A more intense yellowish hue could be observed in summer and autumn milk, which is related to the carotene content in feed. The highest content of dry solids, milk solids-not-fat, fat and protein in milk was found in winter, while in summer these indicators were lowest. In spring, mechanical contamination of milk increased up to group 2. In general, the bulk of the milk was of the highest grade. The study of rennet coagulation of milk showed the superiority of milk produced in spring, as evidenced by a phase of coagulation of milk, which was shorter by 0’05“–2’35” (P <0.001). A clot formed faster in the presence of rennet in summer milk. Thermal stability of milk was high throughout the year.

Plasma exchange for COVID-19 thrombo-inflammatory disease.

Severe COVID‐19 disease is a hyperinflammatory, pro‐thrombotic state. We undertook plasma exchange (PEX) to determine its effects on organ function and thrombo‐inflammatory markers.Seven critically ill adults with severe COVID‐19 respiratory failure (PaO2:FiO2 ratio < 200 mm Hg) requiring invasive or noninvasive ventilatory support and elevated thrombo‐inflammatory markers (LDH >800 IU/L and D‐dimer >1000 μg/L (or doubling from baseline) received PEX, daily, for a minimum of 5 days. No other immunomodulatory medications were initiated during this period. Seven patients matched for age and baseline biochemistry were a comparator group.Coagulation screening revealed no evidence of coagulopathy. However, von Willebrand Factor (VWF) activity, antigen and VWF antigen: ADAMTS13 ratio, Factor VIII and D‐dimers were all elevated. Following 5 days of PEX, plasma levels of all the above, and ferritin levels, were significantly reduced (P < .05) while lymphocyte counts normalized (P < .05). The PaO2:FiO2 ratio increased from a median interquartile range (IQR) of 11.6 (10.8‐19.7) kPa to 18.1 (16.0‐25.9) kPa (P < .05). Similar improvements were not observed in controls. Acute kidney injury (AKI) occurred among five patients in the control arm but not in patients receiving PEX.PEX improved oxygenation, decreased the incidence of AKI, normalized lymphocyte counts and reduced circulating thrombo‐inflammatory markers including D‐Dimer and VWF Ag:ADAMTS13 ratio.

International Council for Standardization in Haematology (ICSH) laboratory guidance for the evaluation of haemostasis analyser-reagent test systems. Part 1: Instrument-specific issues and commonly used coagulation screening tests.

Before a new method is used for clinical testing, it is essential that it is evaluated for suitability for its intended purpose. This document gives guidance for the performance of verification, validation and implementation processes required by regulatory and accreditation bodies. It covers the planning and execution of an evaluation of the commonly performed screening tests (prothrombin time, activated partial thromboplastin time, thrombin time and fibrinogen assay), and instrument-specific issues. Advice on selecting an appropriate haemostasis analyser, planning the evaluation, and assessing the reference, interval, precision, accuracy, and comparability of a haemostasis test system are also given. A second companion document will cover specialist haemostasis testing.

Protein repellent anti-coagulative mixed-charged cellulose derivative coatings

This study describes the formation of cellulose based polyelectrolyte charge complexes on the surface of biodegradable polycaprolactone (PCL) thin films. Anionic sulphated cellulose (CS) and protonated cationic amino cellulose (AC) were used to form these complexes with a layer-by-layer coating technique. Both polyelectrolytes were analyzed by charge titration methods to elucidate their pH-value dependent protonation behavior. A quartz crystal microbalance with dissipation (QCM-D) in combination with X-ray photoelectron spectroscopy (XPS) and atomic force microscopy (AFM) were used to follow the growth, stability and water content of up to three AC/CS bi-layers in aqueous environment. This was combined with coagulation studies on one, two and three bilayers of AC/CS, measuring the thrombin formation rate and the total coagulation time of citrated blood plasma with QCM-D. Stable mixed charged bilayers could be prepared on PCL and significantly higher masses of AC than of CS were present in these complexes. Strong hydration due to the presence of ammonium and sulphate substituents on the backbone of cellulose led to a significant BSA repellent character of three bilayers of AC/CS coatings. The total plasma coagulation time was increased in comparison to neat PCL, indicating an anticoagulative nature of the coatings. Surprisingly, a coating solely composed of an AC layer significantly prolonged the total coagulation time on the surfaces although it did not prevent fibrinogen deposition. It is suggested that these cellulose derivative-based coatings can therefore be used to prevent unwanted BSA deposition and fibrin clot formation on PCL to foster its biomedical application.

Analyzing coagulation dynamics during treatment of vascular malformations with thromboelastography.

Slow-flow vascular malformations are abnormal vessels that can lead to activation and consumption of coagulation factors and thrombosis, known as localized intravascular coagulopathy (LIC). Most clinical and research evidence of vascular malformation hemostasis relies on conventional coagulation studies, which may not provide a complete picture. Thromboelastograpy (TEG) is a tool that can provide real-time assessment of a patient's coagulation dynamics, and may allow for a more individualized treatment approach. We hypothesized that patients with slow-flow vascular malformations will have changes in TEG parameters peri-procedure that will help predict blood product or medication administration. Institutional Review Board approved prospective study of patients with slow-flow vascular malformations undergoing a sedated, minor procedure. TEG and conventional coagulation studies were obtained preprocedure, 15min, and when possible, at 30min after the start of the procedure. Twenty-five patients were enrolled. Median age was 15years (range 3-47years). Procedures included laser and/or sclerotherapy. There were no changes in TEG parameters from baseline to 15min or 30min. The following decreased from baseline to 15min: fibrinogen 313 to 287mg/dL (P=.001), D-dimer 1.3 to 1.1mg/L (P=.02), hemoglobin 12.8 to 11.8g/dL (P=.001), and platelet count 272000 to 256000 (P=.006). No patient had a bleeding/thrombotic complication during or within 1week postprocedure. We saw no change in TEG parameters or bleeding or clotting complications despite significant numerical changes in conventional coagulation profiles, suggesting that conventional studies may not be as useful in determining risks of bleeding or thrombotic complications peri-procedure for minor procedures.

Pulmonary Embolism in Children with Asymptomatic Proximal Deep Vein Thromboembolism: Single-Center Experience from Sweden

Introduction: Pulmonary embolism (PE) is rare in childhood but a potentially fatal condition in the venous thromboembolism spectrum. However, the incidence of PE in children has been steadily increasing, which can be multifactorial. Adults data suggested that the finding of asymptomatic proximal DVT on routine ultrasonography is associated with increased mortality. Data on pulmonary embolism in children are scarce. Objective: To evaluate the relationship between asymptomatic proximal deep vein thrombosis detected in children presented with Pulmonary embolism. Methods: We conducted a retrospective chart review of all consecutive ICD 9 codes of Pulmonary Embolism (PE) in children over 10 years (January 1, 2000, to December 31, 2010) in Skåne university hospital in Sweden, using an electronic diagnosis hospital database. Eligible subjects were children aged 1-18 years presenting with PE diagnosed with imaging, and having undergone complete lower extremities radiological screening workup for DVT and lacking symptoms of acute lower extremity DVT. Data regarding subject demographics and medical history, risk stratification, low risk, massive or submissive PE, location of the proximal DVT, imaging method, presence of congenital vascular anomaly, time from symptom onset to diagnosis of the pulmonary embolism. Coagulation studies at primary investigation including at least plasma concentrations of protein C, protein S, antithrombin, resistance to activated protein C, and the genotypes FVG1691A and FIIG20210A. Also, plasma values for coagulation factors, VIII, cardiolipin antibodies, management, duration of anticoagulant, and the outcome were analyzed. Results: A total of 20 children enrolled. Age range 10-18 years (mean 15.8), 18 (90%) were female. Time from symptom onset to diagnosis of the PE: mean 4.8 days (range 1-28). All were low risk, and 6 (30%) associated with asymptomatic proximal DVT. The most common acquired risk factor was OCP/hormonal therapy was in 11 (55%). Minor thrombophilia in 5 (25%) of the cohort. All received anticoagulation therapy for 6 months, non-received pharmacologic thrombolysis. No bleeding, recurrence, nor thrombosis related mortality in 4 years follow uptime. Conclusion: PE is rare in children, and it is associated with asymptomatic proximal DVT is not uncommon. Our finding demonstrated the prevalence of PE associated with asymptomatic proximal DVT is 30%. This finding highlighted the importance of anticoagulant therapy for all patients with incidental proximal DVT. Figure Disclosures No relevant conflicts of interest to declare.