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Editor-in-chief
Maria Stella Graziani

Deputy Director
Martina Zaninotto

Associate Editors
Ferruccio Ceriotti
Davide Giavarina
Bruna Lo Sasso
Giampaolo Merlini
Martina Montagnana
Andrea Mosca
Paola Pezzati
Rossella Tomaiuolo
Matteo Vidali

EIC Assistant
Francesco Busardò

International Advisory Board Khosrow Adeli Canada
Sergio Bernardini Italy
Marcello Ciaccio Italy
Eleftherios Diamandis Canada
Philippe Gillery France
Kjell Grankvist Sweden
Hans Jacobs The Netherlands
Eric Kilpatrick UK
Magdalena Krintus Poland
Giuseppe Lippi Italy
Mario Plebani Italy
Sverre Sandberg Norway
Ana-Maria Simundic Croatia
Tommaso Trenti Italy
Cas Weykamp The Netherlands
Maria Willrich USA
Paul Yip Canada


Publisher
Biomedia srl
Via L. Temolo 4, 20126 Milano

Responsible Editor
Giuseppe Agosta

Editorial Secretary
Chiara Riva
Biomedia srl
Via L. Temolo 4, 20126 Milano
Tel. 0245498282
email: biochimica.clinica@sibioc.it

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ISSN print: 0393 – 0564
ISSN digital: 0392- 7091



BC: Articoli scritti da B. Montaruli

Il D-dimero nell’esclusione del tromboembolismo venoso nella donna in gravidanza: stato dell’arte
D-dimer in the exclusion of venous thromboembolism in pregnant women: state of the art
<p>The diagnosis of pulmonary embolism (PE) in non-pregnant patients with suspected PE, relies on diagnostic strategies based on sequential assessment of clinical pre-test probability (PTP), determination of plasma D-dimer (DD) levels and diagnostic management: computed tomographic pulmonary angiography (CTPA), pulmonary ventilation/perfusion (V/Q SCAN) and compression ultrasonography (CUS). In pregnant women the use of conventional algorithms for PE is limited by several factors: pregnant women were not included in the studies that derived models assessing PPT of PE, normal pregnancy causes a progressive increase in circulating DD and finally DD levels often exceed non pregnant<!--[if !supportFootnotes]--><span style="font-family:calibri,sans-serif; font-size:11.0pt">[1]</span><!--[endif]-->validated cut-off points, being likely to produce more false positive results. Therefore, guidelines advice against the use of DD determination in pregnancy and recommend to proceed directly to diagnostic imaging. Nevertheless, the clinical presentation of PE can be confused with features of a healthy pregnancy and the prevalence of PE is lower than in non-pregnant population. This leads to a high proportion of negative diagnostic imaging findings. The most recent European Society of Cardiology guidelines, on the basis of two important studies (CT-PE-Pregnancy, ARTEMIS), recognize a possible role of the DD to rule out PE during pregnancy with stratification according PTP and a negative DD result. In the two studies, however, different clinical algorithms and different cut-offs for the DD are used. DD may be a useful diagnostic tool in the management of pregnant women with suspected PE, but further trials are needed to derive and validate models assessing PTP and to identify the optimal DD cut offs during pregnancy.</p>
Biochimica Clinica ; 46(3) S069-S075
Opinioni - Opinions
 
Interpretazione degli esami relativi all’emostasi in corso di gravidanza
Interpretation of hemostasis tests during physiological pregnancy
<p>Pregnancy is associated with significant modifications of the hemostatic system (endothelium, platelets, coagulation and fibrinolysis) resulting in a prothrombotic state. This is mainly due to an increase in the activity of some procoagulant factors and to the decrease of some physiological inhibitors. The plasma concentrations of these hemostatic system components therefore show important modifications during the three trimesters of pregnancy; as a consequence, the clinical laboratory should report specific reference intervals for the three trimesters of pregnancy or at least add a comment to the laboratory report. The screening tests (although very differently) are also influenced by this hypercoagulability condition and therefore also for PT, APTT, fibrinogen, antithrombin and D-dimer, different reference intervals for the three trimesters of pregnancy should be considered. Global tests have been used (viscoelastometric techniques and thrombin generation test) for monitoring the hemostatic imbalance that occurs during pregnancy; these techniques are very promising but, except for the use of viscoelastometry in monitoring post-partum hemorrhagic risk, they are still far from clinical practice.</p>
Biochimica Clinica ; 46(3) S055-S068
Rassegne - Reviews
 
Alterazioni dei meccanismi dell’emostasi in corso di infezione da SARS-CoV-2 (COVID-19)
Alterations of hemostasis during SARS-CoV-2 infection (COVID-19)
<p>The corona virus infection (named COVID-19), first identified in December 2019 in Wuhan, China, has contributed to significant mortality in several countries with the number of infected cases increasing exponentially worldwide, in particular in Italy and in the USA. The majority of the most severely ill patients initially presents with single organ failure (i.e. severe respiratory syndrome), but some of them progress to more systemic disease and multiple organ failure (MOF). One of the most significant poor prognostic features in these patients is the development of coagulopathy, similarly to patients who develop sepsis from various infectious agents. Coagulopathy in patients with COVID-19 may be asymptomatic but, in some cases, the septic state may evolve into Sepsis-Induced Coagulopathy (SIC) and overt Disseminated Intravascular Coagulopathy (DIC). In patients with severe clinical manifestations, a cytokine storm occurs that contributes to triggering a greater imbalance of the hemostatic mechanisms by promoting the development of microthrombosis at the level of the pulmonary endothelium. The effectiveness of anticoagulant therapies, performed primarily with low-molecular weight heparin, is greater the earlier the diagnosis is made. This is possible through the adoption of diagnostic protocols that include laboratory tests and clinical scores. The laboratory tests suggested for this purpose by the available Guidelines are prothrombin time, platelet count, D-dimer and fibrinogen. D-dimer appears to be the parameter with the greatest prognostic significance since it also allows a stratification of the thrombotic risk.</p>
Biochimica Clinica ; 44(4) 015-016
COVID-19 - COVID-19
 
Il ruolo del laboratorio di coagulazione nel monitoraggio del trattamento eparinico dei pazienti con COVID-19
The role of laboratory monitoring in heparin treatment of COVID-19 patients
<p>Coronavirus disease 2019 (COVID-19) can be associated with serious clinical complications such as acute respiratory distress syndrome (ARDS), sepsis and multiple organ failure (MOF). A key event in the pathophysiology of ARDS is immunothrombosis, a process initiated by the innate immune system that provides a first line of defense for local control of infection. In its physiological form, immunothrombosis is intended to facilitate the recognition, containment and destruction of pathogens, thus protecting the integrity of the host without inducing significant collateral damage. The cytokine storm that occurs during COVID-19 induces often venous and arterial thrombotic events affecting different organs, not limited to the respiratory system. It is therefore necessary to introduce an anticoagulant treatment in patients with COVID-19 to prevent the onset and the extension of thrombotic events. The low molecular weight heparin (LMWH) is the first-choice drug recommended by the main international scientific societies; alternatively, unfractionated heparin (UFH) or fondaparinux can be used. The dosage of these drugs in patients with COVID-19 is still under discussion. The coagulation testing plays an important role in monitoring the efficacy and safety of UFH treatment; in the case of LMWHs, these usually do not require monitoring but, if alterations of renal function occur, it is important to perform the chromogenic determinations of the anti-Xa activity, paying a particular attention to the timing of sampling, the pre-analytical variables, calibration of the test and reference ranges.</p>
Biochimica Clinica ; 44(4) 017-018
COVID-19 - COVID-19
 
La variabilità preanalitica in coagulazione
Pre-analytical issues in coagulation testing
<p>Poor standardization of preanalytic variables influences greatly thereliability of coagulation testing, consuming health care resources and compromising patient outcomes. Thesevariables include patient preparation, sample collection, handling, transportation, processing, and storage until timeof analysis: lack of standardized procedures for sample collection accounts for most of the errors encountered withinthe total testing process. Most pre-analytical problems may arise from system faults and insufficient audit of theoperators involved in specimen collection and handling, leading to unsuitable specimens due to misidentification,hemolysis, clotting, inappropriate volume, wrong container, contamination from the infusive route. Detection,acknowledgement and management of pre-analytical variables, is mandatory for delivering accurate laboratoryresults. The present document, issued by the Study Group on Haemostasis of the Italian Society of LaboratoryMedicine, is a summary of the recommendations for standardisation of the pre-analytical phase of the coagulationtesting, related to sample collection, transportation, and storage and provides guidance to reduce the effects of pre-analytical issues that can have a significant impact on patient care.</p>
Biochimica Clinica ; 43(3) 313-326
Documenti SIBioC - SIBioC Documents
 
Durata della fibrinolisi post-operatoria e rischio trombotico dopo somministrazione di acido tranexamico negli interventi di protesi d’anca e ginocchio
Duration of post-operative fibrinolysis and thrombotic risk after tranexamic acid administration in hip and knee prosthesis interventions
<p>Strong evidence indicates that TXA reduces blood loss and blood transfusion requirement in orthopedic surgery. However, drug safety and side effects are still a controversial issue, because TXA may increase thromboembolic risk. Aim of our study was to quantify the duration of postoperative fibrinolysis and to assess the impact of TXA administration after total hip (THR) and total knee replacement (TKR). Fifteen patients undergoing THR and 10 undergoing TKR were included in the study. Among these patients, 14 THR and 8 TKR received TXA, while 3 (one THR and 2 TKR) were employed as controls (i.e., no TXA administration). D-dimer and thrombin generation time were measured prior to surgery as well as 3, 6, 24 and 72 h after. No statistically significant difference in D-dimer was observed between patients treated and not treated with TXA, even if D-dimer increased postoperatively (6 h) more in patients not treated with TXA than in patients receiving TXA. Thrombin peak was lower in patients treated with TXA than in patients not receiving it. Our study shown that TXA limits postoperative fibrinolysis after THR and TKR, as evidenced by a lesser increase in D-dimer in patients receiving TXA, with no increase in prothrombotic risk.</p>
Biochimica Clinica ; 41(3) 235-238
Contributi scientifici - Scientific papers
 
Presenza concomitante di anticorpi tipo Lupus e malattia di von Willebrand: una condizione reale?
Combined von Willebrand factor and lupus anticoagulant abnormalities: a true finding?
<p>We present a case of a 74-year-old woman with myelofibrosis, hypothyroidism and negative bleeding history, showing a prolonged APTT performed within a pre-intervention screening. The laboratory tests showed a positivity for the presence of lupus anticoagulant antibodies (LA). Further investigations revealed normal intrinsic factor and von Willebrand factor (VWF) antigen concentrations, and normal to only slightly reduced VWF Ristocetin Cofactor (VWF:RCo) by chemiluminescent assay and by platelet agglutination. The VWF:RCo by a latex- immunoturbidimetric method was strongly reduced and the platelet function test was found to be abnormal. The negative bleeding history, the myeloproliferative chronic disease, the LA positivity and the other laboratory findings were consistent with the presence of acquired VWF disease. However, the disproportionate values of VWF:RCo measurements obtained by the latex method and all the other assays, made us to conclude for the presence of an interference (possibly due to autoantibodies) on latex VWF:RCo immunoassay and the patient went successfully to surgery without anti-haemorrhagic prophylaxis.</p>
Biochimica Clinica ; 41(1) e4-e8
Casi Clinici - Case Report
 
Test di generazione della trombina nella coagulopatia da COVID-19
Thrombin generation test in COVID-19 related coagulopathy
<p>Introduction: critically ill COVID-19 patients are known to have a coagulopathy characterized by increased levels of&nbsp; D-dimer (DD) associated to a thrombotic risk and a significant increase in mortality. However, it is not known whether the associated COVID-19 coagulopathy is due to a prothrombotic state or is caused by endothelial dysfunction and inflammation. Aim of our study, was to better characterize the hypercoagulability&nbsp; state of COVID-19 patients using Thrombin Generation analyser (ST Genesia&Acirc;&reg;, Diagnostica Stago, Asni&Atilde;&uml;res, France).<br />Methods: a total of 46 non-critically ill hospitalized COVID-19 patients were compared to 19 critically ill COVID-19 patients utilizing calibrated automated thrombography and other biochemical, hematological and coagulation parameters.<br />Results: critically ill patients had a significant increase in C reactive protein (CRP), interleukin-6 (IL-6), prothrombin time (PT), DD and a significant decrease in lymphocytes count. No significant differences in Thrombin Generation Test (TGT) parameters were&nbsp; observed between&nbsp; the two groups of patients with the only exception of the &acirc;&euro;&oelig;Lag Time&acirc;&euro; parameter.<br />Discussion: the obtained results confirmed increased levels of DD and PT in critically ill COVID-19 patients. Of note, disease severity did not cause an increase in Thrombin Generation when compared to non-critically COVID-19 patients. The significantly prolonged Lag Time in critically ill COVID-19 patients without decreased endogenous thrombin potential suggests an hypocoagulability state in these patients. The relevance of this finding is uncertain and may appear counterintuitive since these patients are expected to have a hypercoagulability status, and requires further research.</p>
Biochimica Clinica ; 17(1)
Contributi Scientifici - Scientific Papers