Laboratory hemostasis: from biology to the bench

2018 ◽  
Vol 56 (7) ◽  
pp. 1035-1045 ◽  
Author(s):  
Giuseppe Lippi ◽  
Emmanuel J. Favaloro

AbstractPhysiological hemostasis is an intricate biological system, where procoagulant and anticoagulant forces interplay and preserves blood fluidity when blood vessels are intact, or trigger clot formation to prevent excessive bleeding when blood vessels are injured. The modern model of hemostasis is divided into two principal phases. The first, defined as primary hemostasis, involves the platelet-vessel interplay, whilst the second, defined as secondary hemostasis, mainly involves coagulation factors, damaged cells and platelet surfaces, where the so-called coagulation cascade rapidly develops. The activation and amplification of the coagulation cascade is finely modulated by the activity of several physiological inhibitors. Once bleeding has been efficiently stopped by blood clot formation, dissolution of the thrombus is essential to restore vessel permeability. This process, known as fibrinolysis, also develops through coordinate action of a vast array of proteins and enzymes. An accurate diagnosis of hemostasis disturbance entails a multifaceted approach, encompassing family and personal history of hemostatic disorders, accurate collection of clinical signs and symptoms, integrated with laboratory hemostasis testing. Regarding laboratory testing, a reasonable approach entails classifying hemostasis testing according to cost, complexity and available clinical information. Laboratory workout may hence initiate with some rapid and inexpensive “screening” tests, characterized by high negative predictive value, then followed by second- or third-line analyses, specifically aimed to clarify the nature and severity of bleeding or thrombotic phenotype. This article aims to provide a general overview of the hemostatic process, and to provide some general suggestions to optimally facilitate laboratory hemostasis testing.

2020 ◽  
Vol 51 (5) ◽  
pp. 545-549
Author(s):  
Milena Njegovan ◽  
Sandra Margetić ◽  
Andrea Tešija Kuna ◽  
Lovorka Đerek ◽  
Ivana Ćelap ◽  
...  

Abstract Objective A case of interference of monoclonal protein (M-protein) on thrombin time (TT) test in a 39-year-old Caucasian male patient is presented. Methods Coagulation screening tests were performed where altered results only for TT result (>150 seconds) and activated partial thromboplastin time (aPTT) result (36 seconds) were measured. Further specific coagulation testing included measurement of individual coagulation factors FII, FV, FVII, FVIII, FIX, FX, FXI, and FXII. Diagnostic steps in detection and identification of monoclonal protein included serum protein electrophoresis and immunofixation (both serum and urine specimen). Results Monoclonal protein immunoglobulin G kappa detection and identification in serum and urine clarified the situation. Conclusion Unexpectedly altered results of screening coagulation tests without any appropriate clinical signs and symptoms in a patient without any anticoagulant therapy needs to be critically considered in the context of extended next diagnostic steps in order to clarify the cause of pathological test results.


1992 ◽  
Vol 20 (3) ◽  
pp. 390-395 ◽  
Author(s):  
Thomas Groth ◽  
Katrin Derdau ◽  
Frank Strietzel ◽  
Frank Foerster ◽  
Hartmut Wolf

Twenty years ago Imai & Nose introduced a whole-blood clotting test for the estimation of haemocompatibility of biomaterials in vitro In our paper a modification of this assay is described and the mechanism of clot formation further elucidated. It was found that neither the inhibition of platelet function nor the removal of platelets from blood significantly changed the clot formation rate on glass and polyvinyl chloride in comparison to the rate tor whole blood. Scanning electron microscopy demonstrated that platelets were not involved in clot formation near the blood/biomaterial interface. Thus, it was concluded that the system of contact activation of the coagulation cascade dominates during clot formation under static conditions. The latter conclusion was supported by the fact that preadsorption of human serum albumin or human fibrinogen onto the glass plates used, decreased the clot formation rate in the same manner.


PEDIATRICS ◽  
1992 ◽  
Vol 90 (1) ◽  
pp. 11-13
Author(s):  
Michael S. Kramer ◽  
Renée Roberts-Bräuer ◽  
Robert L. Williams

Few studies have examined the diagnostic validity of the examining physician's interpretation of chest radiographs in young febrile children, and none (to our knowledge) the extent to which the "official" (ie, the radiologist's) reading may be biased by access to the examining physician's reading and to other clinical information. The authors studied 287 consecutive chest radiographs obtained in 286 febrile children 3 to 24 months of age without chronic cardiopulmonary disease or known asthma who presented to a children's hospital emergency department between March 1989 and August 1990. The readings by treating pediatricians, official pediatric radiologists, and a "blind" pediatric radiologist were compared. Official radiologists had access to the treating pediatricians' readings and the clinical information provided on the radiography requisition. The blind radiologist knew only that each child was 3 to 24 months of age and febrile, and he was asked to judge the presence or absence of pneumonia. Using the blind radiologist's reading as the "gold standard" for judging validity of the treating physicians' and official radiologists' readings, sensitivity (.677 vs .647), specificity (.828 vs .849), positive predictive value (PPV, .537 vs .571), and kappa index (κ, .462 vs .475) were quite similar. By contrast, agreement by the treating physicians was considerably higher with the official radiologists' readings as gold standard: sensitivity = .756, specificity = .922, PPV = .795, and κ = .688. When the treating physician's reading was positive, the official radiologists' positivity rate was much higher than the blind radiologist's (74.4% vs 51.8%, P < .005), sensitivity was high (.884) but specificity was low (.436), PPV was .663, and κ was .326. When the treating physicians' reading was negative, however, the pattern was reversed: positivity = 8.5% vs 12.8% (P not significant), sensitivity = .240, specificity = .937, PPV = .353, and κ = .205. Surprisingly, none of the three sets of readings appeared to be influenced by the reporting of clinical signs and symptoms on the radiography requisition. These results indicate that official radiologists are strongly biased by the treating physician's reading. Since such a bias can lead to unnecessary antibiotic treatment and hospital admission, strategies to reduce it should receive high priority.


2021 ◽  
Vol 18 (175) ◽  
pp. 20200834
Author(s):  
Alireza Yazdani ◽  
Yixiang Deng ◽  
He Li ◽  
Elahe Javadi ◽  
Zhen Li ◽  
...  

Normal haemostasis is an important physiological mechanism that prevents excessive bleeding during trauma, whereas the pathological thrombosis especially in diabetics leads to increased incidence of heart attacks and strokes as well as peripheral vascular events. In this work, we propose a new multiscale framework that integrates seamlessly four key components of blood clotting, namely transport of coagulation factors, coagulation kinetics, blood cell mechanics and platelet adhesive dynamics, to model the development of thrombi under physiological and pathological conditions. We implement this framework to simulate platelet adhesion due to the exposure of tissue factor in a three-dimensional microchannel. Our results show that our model can simulate thrombin-mediated platelet activation in the flowing blood, resulting in platelet adhesion to the injury site of the channel wall. Furthermore, we simulate platelet adhesion in diabetic blood, and our results show that both the pathological alterations in the biomechanics of blood cells and changes in the amount of coagulation factors contribute to the excessive platelet adhesion and aggregation in diabetic blood. Taken together, this new framework can be used to probe synergistic mechanisms of thrombus formation under physiological and pathological conditions, and open new directions in modelling complex biological problems that involve several multiscale processes.


Author(s):  
Muna Noori ◽  
Catherine Nelson-Piercy

Pre-eclampsia is a multisystem disorder of pregnancy, characterized by the gestational onset of hypertension and proteinuria, which presents as part of a spectrum of disease with potentially serious consequences for both mother and foetus. Pre-eclampsia is a syndrome with multiple aetiologies, which has made it difficult to develop adequate screening tests and treatments. Pre-eclampsia is likely to develop only in vulnerable women with a mix of genetic susceptibility, vascular, metabolic, and inflammatory dysfunction. A number of prepregnancy risk factors for pre-eclampsia have been identified. However, not all women with risk factors develop pre-eclampsia, while many women without do, making it a challenging condition to predict. As pre-eclampsia cannot be prevented, its management remains supportive, with close monitoring of clinical signs and symptoms, antihypertensive therapy, seizure prophylaxis, and ultimately delivery when necessary. This chapter outlines the pathophysiology, diagnosis, and sequelae of pre-eclampsia, and provides an overview of antenatal, intrapartum, and post-natal management of women with pre-eclampsia.


2020 ◽  
Vol 6 (36) ◽  
pp. eabb4700
Author(s):  
Chunyan Wang ◽  
Shuli Wang ◽  
Hong Pan ◽  
Lingli Min ◽  
Huili Zheng ◽  
...  

Catheters are indispensable medical devices that are extensively used in daily medical treatment. However, existing catheter materials continue to encounter many problems, such as thrombosis, single functionality, and inadaptability to environmental changes. Inspired by blood vessels, we develop a self-adaptive liquid gating membrane-based catheter with anticoagulation and positionally drug release properties. Our multifunctional liquid gating membrane-based catheter significantly attenuates blood clot formation and can be used as a general catheter design strategy to offer various drugs positionally releasing applications to comprehensively enhance the safety, functionality, and performance of medical catheters’ materials.


2009 ◽  
Vol 03 (01) ◽  
pp. 19
Author(s):  
Giuseppe Lippi ◽  
Gian Cesare Guidi ◽  
◽  

The diagnosis of septic disseminated intravascular coagulation (DIC) relies on clinical signs and symptoms, identification of the underlying disease and results of laboratory testing. Since no single test result alone can definitely establish or rule out the diagnosis, the laboratory diagnostics of septic DIC encompass a combination of tests for which simple diagnostic algorithms are now available. Global tests of haemostasis provide evidence of activation of blood coagulation and, ultimately, consumption of coagulation factors, but their diagnostic efficiency is as yet questionable. Fibrinolytic markers, namely D-dimer, reflect the extent of activation of both coagulation and fibrinolysis, so a normal value can be used in a ruling-out strategy. Decreased levels of the natural inhibitors are frequently observed in patients with septic DIC, but antithrombin and protein C measurements are not incorporated in any of the widely used diagnostic algorithms. Among the inflammatory biomarkers, procalcitonin is currently regarded as the gold standard to differentiate the type of infection and guide antibiotic therapy, but its clinical usefulness in identifying and predicting the outcome of patients with septic DIC is still circumstantial.


2020 ◽  
Vol 45 ◽  
pp. 101750 ◽  
Author(s):  
Samara E. Reis ◽  
Rogeria Gabriela C. Andrade ◽  
Camila M. Accardo ◽  
Lenize F. Maia ◽  
Luiz F.C. Oliveira ◽  
...  

2020 ◽  
Vol 21 (21) ◽  
pp. 7975
Author(s):  
Anna Lichota ◽  
Eligia M. Szewczyk ◽  
Krzysztof Gwozdzinski

Venous thromboembolism (VTE) refers to deep vein thrombosis (DVT), whose consequence may be a pulmonary embolism (PE). Thrombosis is associated with significant morbidity and mortality and is the third most common cardiovascular disease after myocardial infarction and stroke. DVT is associated with the formation of a blood clot in a deep vein in the body. Thrombosis promotes slowed blood flow, hypoxia, cell activation, and the associated release of many active substances involved in blood clot formation. All thrombi which adhere to endothelium consist of fibrin, platelets, and trapped red and white blood cells. In this review, we summarise the impact of various factors affecting haemostatic disorders leading to blood clot formation. The paper discusses the causes of thrombosis, the mechanism of blood clot formation, and factors such as hypoxia, the involvement of endothelial cells (ECs), and the activation of platelets and neutrophils along with the effects of bacteria and reactive oxygen species (ROS). Mechanisms related to the action of anticoagulants affecting coagulation factors including antiplatelet drugs have also been discussed. However, many aspects related to the pathogenesis of thrombosis still need to be clarified. A review of the drugs used to treat and prevent thrombosis and natural anticoagulants that occur in the plant world and are traditionally used in Far Eastern medicine has also been carried out.


1997 ◽  
Vol 10 (02) ◽  
pp. 117-121 ◽  
Author(s):  
W. McCartney

SummaryA total of 27 dogs underwent surgery for thoracolumbar intervertebral disc prolapse. A partial pediculectomy was performed in 19 cases. In the majority of these cases the most likely position of the extruded disc material was known from clinical signs and myelography. Eight cases had partial pediculectomy performed as a first stage procedure but ended as a minihemilaminectomy of which in five the position of the extruded disc was known and in three only the disc affected was known. Disc material could be retrieved from the ventral aspect of the spinal cord through a small bony incision in the lateral pedicle without disturbing the area of the vertebral foramen. The advantages of not disturbing the vertebral foramen are avoidance of the branches of spinal artery and the nerve and vessels exiting the foramen making the surgery easier and quicker due to less bleeding.A partial pediculectomy, or modified minihemilaminecto-my was performed on 27 dogs. The location of the disc material in the vertebral canal was ascertained using lumbar myelography and clinical information. If the disc material was lying mainly over the vertebral body the vertebral foramen with its associated blood vessels was not disturbed during surgery, and the disc material was retrieved via a bony incision in the lateral pedicle via a lateral approach.


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