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This review focuses on significant advances in the field of pediatric hemostasis and thrombosis, with a focus on published studies within the past decade. The evaluation and management of patients with excessive bleeding remain cornerstones of consultative hematology. We will describe the development of validated bleeding assessment tools relevant to pediatric practice, laboratory advances in the evaluation of von Willebrand disease, and a shift in clinical practice regarding the interpretation of normal coagulation studies in patients with significant bleeding phenotypes. There have also been critical advances in the management of hemostatic disorders. This review highlights new treatment paradigms in hemophilia and the rise of multidisciplinary medical homes for women living with bleeding disorders. Given the continued increase in the incidence of thrombosis, particularly in the hospital setting, a full call to arms against pediatric venous thromboembolism is now essential. We will describe recently completed clinical trials of direct oral anticoagulants in children and adolescents and ongoing work to elucidate the appropriate duration of therapy for children with provoked thrombosis. Recent work regarding the prevention of pediatric venous thromboembolism is highlighted, including studies of thromboprophylaxis and the development of risk prediction models for hospital-acquired thrombosis. Finally, we review advances in our understanding of thrombotic sequelae and the need for continued refinement of our evaluation tools. Despite the significant advances in pediatric hemostasis and thrombosis over the past decade, many unanswered questions remain for the next generation of investigators.

Background and Aims Standard coagulation tests such as prothrombin time, activated partial thromboplastin time, and international normalized ratio are determined by liver-synthesized coagulation factors. Despite an increased international normalized ratio, patients with cirrhosis are in a “rebalanced” state of hemostasis as the concomitant effect of reduced protein C, protein S, and thrombomodulin is not evaluated in standard coagulation tests. The cell-based model of hemostasis indicates additional mechanisms such as systemic inflammation, sepsis, and organ failures tip the delicate coagulation balance to an anticoagulant type in acute-on-chronic liver failure. In acute liver failure, thrombin generation and platelet function remain intact despite a marked prolongation in prothrombin time. We aimed to explain the principles, application, and utility of viscoelastic tests such as thromboelastography, rotational thromboelastometry, and Sonoclot. Methods We reviewed the available literature from MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trial with the search terms 'coagulation', 'cirrhosis', 'acute-on-chronic liver failure', 'thromboelastography', 'thromboelastometry' and 'sonoclot' for cross sectional studies, cohort studies and randomized trials Results The point-of-care viscoelastic tests provide actionable targets for correcting the coagulation defect in a patient with bleeding and provide evidence-based algorithms for use in liver disease. A limitation of these tests is the inability to assess vessel injury and endothelial elements. Conclusion Global coagulation tests provide a comprehensive estimate of coagulation in vitro; however, their use has only been validated in the setting of liver transplantation. Newer guidelines for hemostatic resuscitation are now accepting these POC tests, but additional data are required to validate their use as standard of care.

Factor X deficiency ranks among the rarest coagulopathies and has a variable presentation spectrum. We intend to present a proposal for anesthesia protocol for individuals with the coagulopathy. The excision of an ovarian neoplasm was proposed for a 26-year-old, female, ASA II patient, with congenital Factor X deficiency. Physical examination and lab tests were normal, except for Prothrombin Time (PT) 22.1s (VR: 8-14s), International Normalized Ratio (INR) 1.99 (VR: 0.8-1.2) and Activated Partial Thromboplastin Time (aPTT) 41.4s (VR: 25-37s). We concluded that a history of bleeding should always be investigated, along with a pre-anesthetic coagulation study.

The objective of this study was to quantify intraoperative bleeding in patients with cirrhosis and correlate it with clinical characteristics and laboratory coagulation tests.A case-control study was carried out with 74 patients with cirrhosis who were submitted to preoperative coagulation tests (complete blood count, platelet count, prothrombin time/international normalized ratio, thrombin time, activated partial thrombin time, platelet aggregation, fibrinogen, protein C, protein S, antithrombin, and von Willebrand factor level and activity). The levels of nitrogen compounds that can affect the platelet function were determined in saliva and blood by using automated enzymatic-colorimetric assays.Patients with cirrhosis had changes in almost all coagulation tests. The average volumes of intraoperative bleeding and blood lost per minute in the study group (5.36 mL/min and 0.19 mL/min, respectively) were greater than those in the control group (3.05 mL/min and 0.11 mL/min, respectively; P.05). In the control group, ascites (P = .012) and presence of periapical lesion (0.034) were positively correlated with bleeding (mL/min). With regard to coagulation tests and nitrogen compounds, only a positively moderate correlation with the platelet aggregation test was observed.No patients had hemorrhagic events and it was not possible to correlate a greater amount of bleeding with coagulation tests or nitrogen compounds in the study group.

Bleeding caused by coagulopathy is common in children undergoing cardiac surgery and causes adverse outcomes. Coagulation testing assists selection of treatments to stop bleeding but has an uncertain role for predicting bleeding. We aimed to evaluate how well prospective coagulation testing predicted excessive bleeding during and after cardiac surgery compared to prediction using clinical characteristics alone. The study was a single-center, prospective cohort study in children having a range of cardiac surgery procedures with coagulation testing at anesthetic induction and immediately after cardiopulmonary bypass. The primary outcome was clinical concern about bleeding (CCB), a composite of either administration of prohemostatic treatments in response to bleeding or a high chest drain volume after surgery. In 225 children, CCB occurred in 26 (12%) during surgery and in 68 (30%) after surgery. Multivariable fractional polynomial models using the clinical characteristics of the children alone predicted CCB during surgery (c-statistic 0.64; 95% confidence interval 0.53, 0.76) and after surgery (0.74; 0.67, 0.82). Incorporating coagulation test results into these models improved prediction (c-statistics 0.79; 0.70, 0.87, and 0.80; 0.74, 0.87, respectively). However, this increased the overall proportion of children classified correctly as CCB or not CCB during surgery by only 0.9% and after surgery by only 0.4%. Incorporating coagulation test results into predictive models had no effect on prediction of blood transfusion or postoperative complications. Prospective coagulation testing marginally improves prediction of CCB during and after cardiac surgery but the clinical impact of this is small when compared to prediction using clinical characteristics.

Quantra® Hemostasis Analyzer is a Point of the care device that uses ultrasound technology to assess clot formation. In this study, we establish how Quantra® system performs compared to conventional coagulation tests at low levels of fibrinogen in the blood obtained from pregnant women. 24 mL blood was obtained from each healthy parturient. Blood was analyzed for Quantra® variables (Q): Clot time (CT), Clot stiffness (CS), platelet contribution to CS (PCS), fibrinogen contribution to CS (FCS), and conventional coagulation (CL) tests: PT, aPTT, INR, Factor VIII and fibrinogen. 6 ml blood were centrifuged to obtain pregnant plasma. 30 mL of saline was added to 10 mL of blood to simulate crystalloid resuscitation (DB) and was evaluated for Q and CL. Fractions of pregnant plasma, or nonpregnant plasma (Blood Bank) was added to DB to obtain 15% and 30% clotting factor enriched samples. 4 ml of DB was added to 4 ml of original blood (1:1) to obtain the final sample (resus). Each of the samples were analyzed for Q and CL parameters. Regression analysis and Receiving Characteristics Curves were used to study the relationship between Quantra variables and CL tests. There were remarkably high linear correlations between Fibrinogen and CS (R = 0.93, P

Thrombin is the pivotal enzyme in the biochemistry of secondary hemostasis crucial to maintaining homeostasis of hemostasis. In contrast to routine coagulation tests (PT or aPTT) or procoagulant or anticoagulant factor assays (e.g. fibrinogen, factor VIII, antithrombin or protein C), the thrombin generation assay (TGA), also named thrombin generation test (TGT) is a so-called "global assay" that provides a picture of the hemostasis balance though a continuous and simultaneous measurement of thrombin formation and inhibition. First described in the early 1950s, as a manual assay, efforts have been made in order to standardize and automate the assay to offer researchers, clinical laboratories and the pharmaceutical industry a versatile tool covering a wide range of clinical and non-clinical applications. This review describes technical options offered to properly run TGA, including a review of preanalytical and analytical items, performance, interpretation, and applications in physiology research and pharmacy.

Objective Posttonsillectomy bleeding is a dreadful complication that may be life-threatening. Preoperative coagulation tests have not been shown to be effective in predicting this complication. The Pediatric Bleeding Questionnaire (PBQ) is a validated and sensitive tool in diagnosing children with abnormal hemostatic functions, and the objective of our study was to assess its utility as a preoperative screening tool for predicting posttonsillectomy bleeding. Study design Prospective single-blinded cohort study. Setting Tertiary care hospital system. Methods All children scheduled for tonsil surgery between 2017 and 2019 in the Galilee Medical Center were included. The PBQ was completed by the caregivers prior to surgery, and all children underwent coagulation tests. Each PBQ item is scored on a scale of -1 to 4, and the total score per candidate is based on summation of all items. Results An overall 272 patients were included in the study with a mean age of 5.2 years; 57.7% were boys. The main finding was that in a multivariable model adjusted to age, a PBQ score of 2 is correlated with increased postoperative bleeding risk (odds ratio, 10.018 [95% CI, 1.20-82.74]; P = .046). The results of the PBQ demonstrated better predictive ability when compared with abnormal coagulation test results (odds ratio, 1.76 [95% CI, 0.63-4.80]; P = .279). Sex was not found to be significant (odds ratio, 1.45 [95% CI, 0.70-3.18]; P = .343). Conclusions This study demonstrated that a PBQ score ≥2 has a higher yield for detecting children at risk for posttonsil surgery bleeding as compared with coagulation studies.

Background Proprotein convertase subtilisin/kexin type 9 (PCSK9) is considered to have multiple roles in the development of atherosclerosis, which is recently reported to participate in the thrombotic process. We aimed to examine the relationship between PCSK9 concentration, coagulation indexes and cardiovascular events. Methods A total of 2293 consecutive patients with angina-like chest pain and without lipid-lowering drugs treatment were enrolled and followed up for major adverse cardiovascular events (MACEs). Circulating PCSK9 concentration was determined by ELISA. The routine coagulation tests including activated partial thromboplastin time (APTT), prothrombin time (PT) and thrombin time were performed. The associations between PCSK9 concentration, routine coagulation indicators and MACEs were analyzed. Results Patients with high PCSK9 levels had lower PT and APTT levels (all p p Conclusions Our study firstly suggested that PCSK9 concentration was negatively correlated with plasma levels of PT. Furthermore, high PCSK9 and low PT were associated with MACEs and the combination of PCSK9 with PT had an addictive effect on predicting cardiovascular outcomes in patients with chest pain, which was useful for further subdivision of cardiovascular risks.

Background Few studies detail the evolution of COVID-19 associated coagulopathy. We performed serial thromboelastography (TEG) and laboratory coagulation studies in 40 critically-ill, mechanically ventilated COVID-19 patients over a 14-day period and analysed differences between 30-day survivors and non-survivors. Methods Single-center prospective, observational study including 40 patients with severe COVID-19 pneumonia admitted to the intensive care unit (ICU) for mechanical ventilation. TEG analysis was performed on days 1, 7 and 14 of ICU admission and laboratory coagulation studies were performed on days 1 and 14. Coagulation variables were evaluated for change over the 14-day observation period. Differences between survivors and non-survivors at 30-days were analysed and compared. Results On admission, TEG maximum amplitude (MA) with heparinase correction was above the upper limit of the reference range in 32 (80%) patients while 33 (82.5%) presented with absent clot lysis at 30 min. The functional fibrinogen MA was also elevated above the upper limit of the reference range in 37 (92.5%) patients. All patients had elevated D-dimer and fibrinogen levels, mildly prolonged prothrombin times (PT), normal platelet counts and normal activated partial thromboplastin times (aPTT). The heparinase MA decreased significantly with time and normalised after 14 days (p = p = 0.113). No significant differences in TEG analysis were noted between 30-day survivors and non-survivors at all time points. No patients developed disseminated intravascular coagulopathy (DIC) after 14-days, however thrombosis and bleeding were each reported in 3 (7.5%) patients. Conclusion Critically-ill patients with COVID-19 present in a hypercoagulable state characterised by an increased clot strength. This state normalises after 14 days despite a persistently increased fibrin contribution to clot strength. We were unable to demonstrate any significant differences in TEG parameters between 30-day survivors and non-survivors at all time points.

Background We aim to determine the clinical utility of reflex coagulation investigations (RCI) for prolonged lupus insensitive activated partial thromboplastin time (aPTT) at our institution. Methods We retrospectively reviewed all potential RCI (lupus insensitive aPTT of ≥32s) from April 2014 to June 2019. Our diagnostic algorithm requires completion of RCI only if samples had no interfering medications to explain a prolonged aPTT and were either from a preoperative sample or from a patient presenting with unexplained bleeding. Appropriate RCI samples undergo further investigations with one-stage factor activity testing for factors 8(FVIII), 9(FIX), and 11(FXI) reflexively. Data were obtained through electronic medical records to capture clinical characteristics, laboratory findings, prophylactic hemostatic replacement, and bleeding outcomes. Results Three thousand and three hundreds seventeen samples from 2940 distinct patients were considered as potential RCI during the study period. 263/3317 (8%) samples had RCI completed. Of those, 55/263 (21%) had abnormal factor testing, with the majority from preoperative setting (43/55; 78%). 5/43 (12%) patients were referred to hematology for preoperative evaluation. 5/43 patients received preoperative hemostatic support. A total of 5 patients (5/43) developed postop bleeding. Six patients (6/55) had RCI for unexplained bleeding, and five patients (83%) had a newly identified clinically significant bleeding disorder. Conclusion Reflex coagulation investigations benefited patients presenting with unexplained bleeding as this expedited the diagnosis and management of clinically significant bleeding disorders. RCI for preoperative evaluation infrequently led to additional hemostatic support/referral to hematology. The lack of additional workup for an abnormal factor activity level suggests laboratory alert fatigue as a potential contributory factor.

Introduction The use of direct oral anticoagulants (DOAC) is increasing. Specific concentrations are available and have been proven to be reliable and reproducible in optimising patient care. This retrospective, monocentric study aimed to describe the indications and consequences of monitoring DOAC plasma levels on patient care. Materials and methods We collected data of patients hospitalised at the Bordeaux University Hospital between January 2017 and December 2018. These included demographics, indications, type, dose of DOAC, standard coagulation tests, creatinine clearance and DOAC plasma concentration using specifically calibrated rivaroxaban and apixaban anti-Xa and dabigatran anti-IIa assays. The date of last DOAC intake, the time between intake and plasma level measurement were also collected and analysed. Results A total of 2197 DOAC assays in 1488 patients were obtained in various clinical situations: urgent or elective procedures, context of acute renal failure, suspicion or occurrence of ischemic strokes, intra-cranial and other bleeding sites. Interpretation of these assays led physicians to maintain, postpone or cancel invasive and high haemorrhagic risk procedures in 757, 261 and 56 cases respectively. The remaining 1123 assays were associated with no significant modification of patient care. DOAC plasma concentration was ≤30 ng ml-1 (sensitivity 85.4%, specificity 73.6%, positive predictive value 71.1%, negative predictive value 86.7%, AUC 0.81) after a last intake of at least 2 days. Conclusions Our study is, to date, the largest report of real-life measurement of specific DOAC plasma level at a single institution. Patient care was not modified in more than half of the assays.

Factor XII (FXII) is a serine protease zymogen produced by hepatocytes and secreted into plasma. The highly glycosylated coagulation protein consists of six domains and a proline-rich region that regulate activation and function. Activation of FXII results from a conformational change induced by binding ("contact") with negatively charged surfaces. The activated serine protease FXIIa drives both the proinflammatory kallikrein-kinin pathway and the procoagulant intrinsic coagulation cascade, respectively. Deficiency in FXII is associated with a prolonged activated partial thromboplastin time (aPTT) but not with an increased bleeding tendency. However, genetic or pharmacological deficiency impairs both arterial and venous thrombosis in experimental models. This review summarizes current knowledge of FXII structure, mechanisms of FXII contact activation, and the importance of FXII for diagnostic coagulation testing and thrombosis.Faktor XII (FXII) ist das Zymogen der Serinprotease FXIIa, wird von Hepatozyten produziert und ins Plasma sekretiert. Das Plasmaprotein besteht aus sechs Domänen sowie einer Prolin-reichen Region und ist stark glykosyliert. Die Aktivierung von FXII erfolgt durch eine Konformationsänderung, die durch die Bindung (den „Kontakt“) mit negativ geladenen Oberflächen hervorgerufen wird. In der Folge aktiviert FXIIa sowohl das proinflammatorische Kallikrein-Kinin-System, welches Bradykinin produziert, als auch die intrinsische Gerinnungskaskade. Eine FXII-Defizienz oder Dysfunktionalität ist mit einer verzögerten aktivierten partiellen Thromboplastinzeit (aPTT) assoziiert, nicht aber mit einer erhöhten Blutungsneigung. Dennoch zeigen experimentelle Modelle, dass FXII essentiell für die Bildung arterieller und venöser, Gefäß-verschließender Thrombosen ist. Diese Übersichtsarbeit fasst das aktuelle Wissen über die Struktur von FXII, den Mechanismus der FXII-Kontaktaktivierung und die Bedeutung von FXII für diagnostische Gerinnungstests zusammen.

BACKGROUND Essential thrombocythemia (ET) is associated with increased risk of bleeding secondary to acquired von Willebrand syndrome (AVWS). Bleeding in ET requires urgent platelet reduction by cytoreductive therapy such as hydroxyurea or thrombocytapheresis. We report on the efficacy and safety of thrombocytapheresis in managing AVWS in a patient with ET and multivisceral transplantation. CASE REPORT The patient was a 51-year-old female who underwent multivisceral transplantation. Her postoperative course was complicated by bleeding from oral cavity, IV lines, gastrointestinal and upper respiratory tracts as well as vaginal bleeding, which coincided with ET flare with a platelet count of 1512 × 109 /L. Coagulation studies including von Willebrand factor (vWF) antigen and activity, vWF propeptide antigen, and vWF multimer analysis were consistent with AVWS. Hydroxyurea was initiated. However, due to major bleeding, rapidly increasing platelet count, and uncertainty of response to hydroxyurea being given through the enteral tube, thrombocytapheresis was initiated for rapid platelet reduction. The patient tolerated the procedure well. Platelet count was reduced from 1636 × 109 /L to 275 × 109 /L with rapid cessation of bleeding. The patient's condition stabilized over the next few days; however, bleeding recurred with increasing platelet count, which required a second thrombocytapheresis 8 days after the first one. The patient was maintained on hydroxyurea 500 mg twice/day. At 11-month follow-up, she had a normal platelet count and no recurrence of bleeding. DISCUSSION Thrombocytapheresis is safe and efficient in managing postoperative bleeding due to ET/AVWS in solid organ transplant patients. The procedure can be an adjunct to bridging therapy before response to hydroxyurea is achieved.

From preoperative medications to intraoperative needs to postoperative thromboprophylaxis, anticoagulants are encountered throughout the perioperative period. This review focuses on coagulation testing clinicians utilize to monitor the effects of these medications.

Višestruka uloga von Willebrandova faktora (VWF) u hemostazi, složenost njegove strukture i veliki broj mutacija u različitim dijelovima gena za VWF čine von Willebrandovu bolest (VWB) klinički izrazito heterogenim poremećajem, a njegovu pravilnu dijagnostiku i razlikovanje od blage hemofilije A otežanima. Cilj ovog istraživanja bio je primijeniti cjeloviti pristup dijagnostici VWB-a u Republici Hrvatskoj koji uključuje globalne i visokodiferentne koagulacijske pretrage kojima su ispitana funkcionalna i strukturna svojstva VWF-a te molekularnu analizu svih sljednih varijanti u genima za VWF i faktor zgrušavanja VIII (FVIII) sekvenciranjem sljedeće generacije (NGS) i dodatnim pretraživanjem velikih delecija i duplikacija metodom višestrukog umnažanja vezanih sondi. Istraživanje je obuhvatilo 83 ispitanika, a mutacije u genu za VWF nađene su kod njih 48. Na temelju rezultata koagulacijskih pretraga i genetičke analize, 19 ispitanika klasificirano je kao tip 1 VWB-a, šest kao tip 3, dok je među 23 ispitanika s tipom 2 VWB-a 15 imalo tip 2A, sedam tip 2B, a tip 2N potvrđen je u jednom slučaju. Heterozigotni genotip utvrđen je kod 38 ispitanika, sedam su bili složeni heterozigoti i tri homozigoti. Ukupno je utvrđeno 36 različitih mutacija u genu za VWF, od kojih su 13 novootkrivene. Mutacije u genu za FVIII nađene su kod petero ispitanika, pri čemu je u dva muška homozigota postavljena dijagnoza blage hemofilije A, dok su tri ženske ispitanice heterozigoti i smatraju se nositeljicama hemofilije A. Kod jedne je ispitanice uz mutaciju u genu za FVIII nađena i mutacija u genu za VWF. Dvije su mutacije u genu za FVIII novootkrivene. Kod 30 (36 %) ispitanika nisu nađene mutacije u genima za VWF i FVIII, pri čemu je devet ispitanika zbog aktivnosti VWF-a ispod 50 % svrstano u kategoriju tzv. ꓹꓹniskog VWF-a“. Ovo istraživanje upozorilo je na znatnu heterogenost genetičke osnove VWB-a u hrvatskoj populaciji, a istodobno sekvenciranje gena za VWF i FVIII tehnologijom NGS omogućilo je jednoznačno postavljanje dijagnoze VWB-a te diferencijalno dijagnostičko razlučivanje od blage hemofilije A. Time je osigurana osnova za pravilno liječenje i skrb za bolesnike te su razjašnjeni molekulsko-patofizološki mehanizmi koji su u podlozi poremećaja krvarenja kod obrađenih bolesnika. Multiple functions of von Willebrand factor (VWF), its structural complexity and numerous mutations throughout the whole VWF gene impact the clinical heterogeneity of von Willebrand disease (VWD) and make its accurate diagnosis and distinction from mild haemophilia A challenging. The aim of the present study was to introduce a comprehensive laboratory diagnostic approach that included screening and specific coagulation assays, as well as molecular analysis of VWF and coagulation factor VIII (FVIII) genes by means of next-generation sequencing (NGS) and additional targeted screening for deletions and duplications using the multiplex ligation-dependent probe amplification method. Of the 83 study participants, 48 were identified with disease-associated mutations in the VWF gene, of whom 19 were classified as type 1 VWD, six as type 3 VWD, while among the 23 patients with type 2 VWD, 15 were assigned as type 2A, seven as type 2B, and in one case type 2N VWD was confirmed. Heterozygous genotype was present in 38 patients, compound heterozygosity in seven patients while three patients were homozygous for mutations within the VWF gene. In total, 36 distinct disease-associated mutations were found within the VWF gene, of which 13 were novel. Four study participants were identified with mutations within the FVIII gene only, while one female participant had mutations both in VWF and FVIII genes. The two siblings who were homozygous for a mutation in the FVIII gene were diagnosed with mild haemophilia A, while the three heterozygous females were classified as carriers of mild haemophilia A. Two mutations within the FVIII gene were novel. Of the remaining 30 (36 %) study participants without mutations within the VWF and FVIII genes, nine had VWF activity below 50 % and were classified as “low VWF“. The present study revealed considerable genetic heterogeneity among patients with VWD in Croatia. The application of simultaneous sequencing of whole VWF and FVIII genes by means of NGS was proven as a valid approach for differential diagnosis of VWD subtypes, as well as for unambiguous distinction of VWD from mild haemophilia A. This study provided basis for appropriate patient treatment and care, as well as enhanced the understanding of the underlying molecular pathophysiology of the bleeding phenotype in the evaluated patients.

Background: Rejection of hemolysed samples for coagulation test is the standard practice.However, when clinicians deal with extremely sick patients where repeat sampling is difficult toobtain, rejection of the sample is a lost opportunity for the lab physician to assist inpatient care.Proceeding with the test and providing a clinically helpful interpretation of the results will ensure theactive participation of the laboratory physician. Different principles of coagulation testing handle thehemolysed samples differently. It is essential to know the best principle to proceed with thehemolysed sample if need be. This study set out to estimate the predictive values of post-hemolyticsample coagulation test results with various coagulation test principles. Methods: This is aprospective experimental study where the non-hemolysed samples were processed for coagulationtests. Part of the sample was deliberately hemolysed, and the coagulation tests were repeated.Results: Two hundred and forty-eight samples were studied. A median of 11% hemolysis wasachieved experimentally. The mean difference in prothrombin time between pre and post hemolyticsamples with normal PT was 0.9 and with abnormal PT, it was 1.1 seconds. The same for APTT was4.9 and 1.1 seconds, respectively. The majority of the samples showed prolonged coagulation posthemolysis. Positive (PPV) and negative (NPV) predictive values for prothrombin time are 97.3 and73.4%, respectively. Similarly, PPV and NPV for APTT are 97.4 and 47.1%, respectively.Conclusions: Samples with normal values after hemolysis are more likely to be normal.

BACKGROUND: Hypercoagulability plays an important role in predisposing patients to venous thromboembolism (VTE) after total hip arthroplasty (THA). We used thromboelastography (TEG) to examine the coagulation status of patients undergoing THA. AIM: To examine coagulation as measured by TEG in patients undergoing THA who received standard VTE chemoprophylaxis with enoxaparin. METHODS: After ethical approval, we performed a retrospective analysis of data collected in patients undergoing primary elective THA. We analyzed TEG data on samples performed before skin incision, intraoperatively and for 5 d postoperatively. Conventional coagulation tests were performed preoperatively and on postoperative day 5. RESULTS: Twenty patients undergoing general anesthesia and 32 patients undergoing spinal anesthesia (SA) were included. TEG demonstrated a progressively hypercoagulable state postoperatively, characterized by elevated maximum amplitude. TEG also demonstrated transient intraoperative hypercoagulability in patients receiving SA. In contrast, conventional coagulation tests were normal in all patients, pre- and postoperatively, except for an increase in plasma fibrinogen day 5 postoperatively. CONCLUSION: Despite VTE prophylaxis, patients following total hip replacement remain in a hypercoagulable state as measured by both TEG and conventional tests. This group may benefit from more optimal anticoagulation and/or additional perioperative hemostatic monitoring, via TEG or otherwise.

We carried out a literature search in MEDLINE (PubMed) and EMBASE literature databases to provide a concise review of the role of viscoelastic testing in assessing peri-interventional platelet function and coagulation. The search identified 130 articles that were relevant for the review, covering the basic science of VHA and VHA in clinical settings including cardiac surgery, cardiology, neurology, trauma, non-cardiac surgery, obstetrics, liver disease, and COVID-19. Evidence from these articles is used to describe the important role of VHAs and platelet function testing in various peri-interventional setups. VHAs can help us to comprehensively assess the contribution of platelets and coagulation dynamics to clotting at the site-of-care much faster than standard laboratory measures. In addition to standard coagulation tests, VHAs are beneficial in reducing allogeneic transfusion requirements and bleeding, in predicting ischemic events, and improving outcomes in several peri-interventional care settings. Further focused studies are needed to confirm their utility in the peri-interventional case.

Background Patients with acquired hemophilia A (AHA) who require open heart surgery have a life-threatening risk of hemorrhage. Limited data exist to guide perioperative management of these patients. Case presentation A 53-year-old female with rheumatoid arthritis, concomitant aortic valve endocarditis, and severe aortic regurgitation presented to our hospital. Bleeding and abnormal coagulation tests were noted during the initial workup, and she was diagnosed with AHA. The perioperative management plan included the use of pharmaceuticals, porcine recombinant factor VIII, and blood products. Extensive preoperative coagulation data were obtained, and factor VIII levels were continuously monitored to mitigate bleeding complications. The aortic valve replacement and root repair were uneventful. Conclusion Cardiac surgery in patients with AHA is possible as long as complex perioperative hemostatic and hematology management is used.

To investigate the current experience and expertise for haemophilia inhibitor patient management in haemophilia treatment centres (HTCs) in mainland China. Questionnaires were distributed to 'tertiary tier A' hospital HTCs across China to collect information on treatment preferences for bleeding control, prophylaxis and inhibitor eradication, as well as their regimens in real-world clinical practice. Of 40 questionnaires distributed, 39 were returned. In all, 38 were analysable for treatment preferences and 34 for actual clinical practice. For haemostatic treatment, 76·3% (29/38) HTCs preferred activated recombinant human Factor VII (rFVIIa). In clinical practice, the most widely used by-pass agent was prothrombin complex concentrate (26 HTCs). Although 65·8% (25/38) of HTCs believed prophylaxis treatment was necessary, it was prescribed in only 12. Similarly, 65·8% (25/38) of HTCs believed immune tolerance induction (ITI) therapy was necessary but only 14·8% (92/622) of patients in 19 HTCs received low-dose ITI treatment. HTCs in relatively economically developed cities (with higher-than-average per-capita gross domestic product) had better access to haemostatic treatment, coagulation testing and were more likely to provide prophylaxis and ITI in practice. The present survey showed there were gaps in haemophilia inhibitor care between the HTC physicians' preferences and their actual clinical practice. More specific care guidelines, education and clinical decision support tools are needed to guide clinical practice.

Intraperitoneal administration of BromAc (bromelain + acetylcysteine) is currently undergoing a phase 1 clinical trial for pseudomyxoma peritonei at our institution. This study reports on analysis of routine blood parameters before and after treatment for a series of 25 patients in this trial. Blood parameters assessed included full blood count, electrolytes, urea, and creatinine, liver function tests, coagulation studies, as well as inflammatory markers (CRP). Certain parameters such as CRP, and white cell count, were significantly elevated after treatment whilst serum albumin level was reduced indicating an inflammatory reaction. However, liver enzymes, coagulation studies, and other parameters were not affected. Therefore, there are no additional safety signals evident upon analysis of routine blood parameter testing.

Objectives: To determine the influence of prolonged exposure to radiation based on dosimeter readings on hematological parameters among radiologic technologists (RTs) in Saudi Arabia. Methods: The study was specifically conducted on selected RTs with experience of more than 10 years and the highest thermoluminescent dosimeter (TLD) readings among all RTs in the Radiological Department, Sabya General Hospital, Ministry of Health, Saudi Arabia from August to October 2020. The RTs group was compared with a control group of non-irradiated participants. Blood samples were collected for hematological and coagulation profile evaluation. Results: The acquired radiation dose analysis revealed that the average accumulated dose in 10 years is 7.6 mSv. The medians of prothrombin time (PT) and activated partial thromboplastin time (APTT) of the RTs group were significantly lower when compared to the control group. In addition, RTs group exhibited a significant reduction in neutrophil count and an elevation in lymphocyte count. Conclusion: Chronic exposure to radiation revealed a significant change in blood tests and may reflect an effect on RTs tissues, leading to serious health problems. However, further investigation in a large cohort to study the association between alteration in hematological parameters and chronic radiation exposure is required.

Beta thalassemia major is associated with a subclinical hypercoagulable state. Endothelial activation markers like soluble Intercellular adhesion molecule (sICAM-1) and E-selectin have been implicated in the pathogenesis of endothelial dysfunction and hemostatic alterations. In this study we aimed to study serum levels of sICAM-1 and E-selectin in polytransfused children with β thalassemia major and their association with serum ferritin and D-dimer levels. Sixty-two polytransfused β-thalassemia major children aged between 5 and 17 years and 26 age and gender matched healthy controls were enrolled in the study. Complete blood count with peripheral smear, liver function tests, serum ferritin, coagulation tests [PT, APTT, D-dimer] and endothelial activation marker tests [ICAM-1 and E-selectin] were performed. PT, APTT and D-dimer levels were significantly higher in beta-thalassemia major patients than in control group (p = 0.003, p

Early descriptions of COVID-19 associated coagulopathy identified it as a disseminated intravascular coagulation (DIC). However, recent studies have highlighted the potential role of endothelial cell injury in its pathogenesis, and other possible underlying mechanisms are being explored. This study aimed to analyse the coagulation parameters of critically and noncritically ill patients with COVID-19 bilateral pneumonia, determine if coagulation factors consumption occurs and explore other potential mechanisms of COVID-19 coagulopathy. Critically and noncritically ill patients with a diagnosis of COVID-19 bilateral pneumonia were recruited. For each patient, we performed basic coagulation tests, quantification of coagulation factors and physiological inhibitor proteins, an evaluation of the fibrinolytic system and determination of von Willebrand Factor (vWF) and ADAMTS13. Laboratory data were compared with clinical data and outcomes. The study involved 62 patients (31 ICU, 31 non-ICU). The coagulation parameters assessment demonstrated normal median prothrombin time (PT), international normalized ratio (INR) and activated partial thromboplastin time (APTT) in our cohort and all coagulation factors were within normal range. PAI-1 median levels were elevated (median 52.6 ng/ml; IQR 37.2-85.7), as well as vWF activity (median 216%; IQR 196-439) and antigen (median 174%; IQR 153.5-174.1). A mild reduction of ADAMTS13 was observed in critically ill patients and nonsurvivors. We demonstrated an inverse correlation between ADAMTS13 levels and inflammatory markers, D-dimer and SOFA score in our cohort. Elevated vWF and PAI-1 levels, and a mild reduction of ADAMTS13 in the most severe patients, suggest that COVID-19 coagulopathy is an endotheliopathy that has shared features with thrombotic microangiopathy.

Premature infants are at high risk of haemorrhage and thrombosis. Our understanding of the differences between the neonatal and adult haemostatic system is evolving. There are several limitations to the standard coagulation tests used in clinical practice, and there is currently a lack of evidence to support many of the transfusion practices in neonatal medicine. The evaluation of haemostasis is particularly challenging in neonates due to their limited blood volume. The calibrated automated thrombogram (CAT) is a global coagulation assay, first described in 2002, which evaluates both pro- and anti-coagulant pathways in platelet-rich or platelet-poor plasma. In this review, the current applications and limitations of CAT in the neonatal population are discussed.Conclusion: CAT has successfully elucidated several differences between haemostatic mechanisms in premature and term neonates compared with adults. Moreover, it has been used to evaluate the effect of a number of haemostatic drugs in a pre-clinical model. However, the lack of evidence of CAT as an accurate predictor of neonatal bleeding, blood volume required and the absence of an evidence-based treatment algorithm for abnormal CAT results limit its current application as a bedside clinical tool for the evaluation of sick neonates. What is Known:• The Calibrated automated thrombogram (CAT) is a global coagulation assay which evaluates pro- and anti-coagulant pathways.• CAT provides greater information than standard clotting tests and has been used in adults to evaluate bleeding risk. What is New:• This review summarises the physiological differences in haemostasis between neonates and adults described using CAT.• The haemostatic effect of several drugs has been evaluated in neonatal plasma using CAT.

BACKGROUND The Sysmex CN-6500 is a new haemostasis analyser with an integrated immunoassay module that performs chemiluminescence enzyme assay (CLEIA) in addition to coagulation, turbidimetric, chromogenic and platelet aggregation tests. AIMS To evaluate the analytical performance of the CN-6500 against the predicate device (Sysmex HISCL-800) for soluble thrombomodulin (TM), thrombin-antithrombin (TAT), tissue plasminogen activator/plasminogen activator inhibitor 1 complex (tPAI-C) and plasmin α2 plasmin inhibitor complex (PIC) assays. METHODS Imprecision was assessed by testing two levels of quality control plasmas 10 times on 5 separate days. Comparability was studied in 230 plasmas from normal donors (n = 30), patients with suspected disseminated intravascular coagulation (DIC, n = 100), sepsis (n = 20) or liver disease (n = 20), lipaemic (n = 20), haemolysed (n = 20) and icteric samples (n = 20). Limit of detection, limit of quantitation and linearity were determined by testing serial dilutions of normal plasma. Sample carryover was assessed by testing samples with high and low normal levels of the analytes concerned. RESULTS The CN-6500 performed 21 CLEIA tests per hour, while simultaneously performing coagulation tests. Acceptable between-run imprecision was obtained using commercial controls with normal and high activity for each analyte (%CV 0.99) across the measurement range. The lower limits of detection and quantitation were as follows: TM 0.1/

Algorithms for treatment of diffuse bleeding in cardiac surgery are based on intervention thresholds of coagulation tests, such as rotational thromboelastometry (ROTEM) or conventional laboratory tests. The relationship between these two approaches is unclear in patients with increased risk of coagulation abnormalities. We retrospectively analyzed the data of 248 patients undergoing major cardiac and/or aortic surgery. ROTEM and conventional laboratory tests were performed simultaneously after termination of cardiopulmonary bypass and protamine administration to investigate the extrinsic and intrinsic system, and to determine deficiencies in platelets and fibrinogen. We evaluated the association between ROTEM and conventional tests by linear regression analysis and compared the frequency of exceeding established thresholds for clinical intervention. Significant linear associations between ROTEM 10 min after the start of coagulation, and plasma fibrinogen concentration or platelet count (FIBTEM A10, R2 = 0.67, p 2 = 0.47, p 3–122 × 103/µL platelets at the intervention threshold of EXTEM A10 = 40 mm). The association between EXTEM and INR (R2 = 0.23), and INTEM and aPTT (R2 = 0.095) was poor. The frequency of exceeding intervention thresholds and, consequently, of triggering treatment, varied markedly between ROTEM and conventional tests (p

Background: Patients with chronic liver disease (CLD) planned for liver transplantation (LT) often show severe thrombocytopenia, but there is a lack of evidence in deciding the threshold for prophylactic platelet transfusion.Case: A 47-year-old women with acute liver failure was referred for LT. Despite daily transfusion of platelets, platelet counts remained under 10,000/µl. During LT, 2 units of single donor platelets (SDP) were transfused. Although platelet counts remained extremely low (3,000–4,000/µl) no diffuse oozing was observed and the blood loss was 860 ml. Postoperatively, there was no sign of active bleeding or oozing, and the patient received only 1 unit SDP transfusion.Conclusions: CLD patients may have severe thrombocytopenia. However, primary hemostasis may not be significantly hindered due to the existence of rebalanced hemostasis. Prophylactic platelet transfusion in these patients should not be decided based on platelet counts only, but also take other coagulation tests and clinical signs into consideration.

Prospective study. The main purpose of this study was to investigate whether the use of a tourniquet changes the blood coagulation state following primary total knee arthroplasty (TKA) by means of conventional coagulation tests and thromboelastography (TEG) analyses. A total of 154 patients who underwent primary unilateral TKA from January 2018 to October 2020 were enrolled. Seventy-nine patients were randomized into a tourniquet group, and 75 were randomized into a no-tourniquet group. Demographic data, surgical time, intra-operative blood loss, transfusion rate, and wound complications were collected. Complete blood count, conventional coagulation tests, and TEG were performed the day before surgery, one day after surgery, three days after surgery, and seven days after surgery. Lower extremity Doppler ultrasound was performed the day before surgery and seven days after surgery. The baseline characteristics of the patients were similar between the two groups. Hidden blood loss, transfusion rate, and wound complications were similar between the two groups, but the intra-operative blood loss of the tourniquet group was lower than that of the no-tourniquet group. The calculated total blood loss of the tourniquet group was higher than that of the no-tourniquet group. In terms of conventional coagulation tests and TEG, the tourniquet group had higher values of fibrin degradation products, D-dimer, maximum amplitude, and coagulation index (p

Background Gallbladder mucocele (GBM) is a common biliary disorder in dogs. Limited information is available on the coagulation status of dogs with GBM. Hypothesis/objectives To determine patterns of coagulation alterations in dogs with GBM and correlate them with clinicopathologic abnormalities and ultrasonographic findings of disease severity. Animals Twenty-three dogs with GBM identified on ultrasound examination were prospectively enrolled. Methods At the time of GBM identification, blood and urine were collected for CBC, serum biochemical panel, urinalysis, prothrombin time, activated partial thromboplastin time (aPTT), factor VIII, protein C (PC), von Willebrand's factor (vWF), antithrombin activity, fibrinogen, D-dimers, and thromboelastrography (TEG). Gallbladder mucoceles were classified into ultrasound types 1 to 5. Medical records were reviewed for clinical presentation, underlying conditions and to determine if systemic inflammatory response syndrome (SIRS) was present. Results Based on TEG parameters, maximal amplitude, and G, 19/23 (83%) of dogs with GBM had evaluations consistent with hypercoagulability. On plasma-based coagulation testing, dogs with GBM had increased total PC activity (20/23, 87%), fibrinogen (9/23, 39%), platelet count (9/23, 39%), and D-dimers (6/15, 40%) as well as prolongations in aPTT (9/22, 41%) and low vWF activity (5/21, 24%). No correlation was found between TEG G value and any coagulation or clinical pathology variables, ultrasound stage of GBM or disease severity as assessed by the presence of SIRS. Conclusions and clinical importance Dogs with ultrasonographically identified GBM have changes in whole blood kaolin-activated TEG supporting a hypercoagulable state although traditional plasma-based coagulation testing suggests that a complex state of hemostasis exists.

Background Coagulopathy is the major cause of mortality and morbidity throughout the world. Globally, about 26–45% of healthy people have a history of bleeding symptoms, which may be a result of thrombocytopenia, factor deficiency, or pathological inhibitory. Objective To assess coagulopathy and its associated factors among patients with bleeding diathesis at the University of Gondar Specialized Referral Hospital from January to May 2020. Method A cross-sectional study was conducted on 384 study participants with bleeding diathesis recruited by using a convenient sampling technique. Socio-demographic and clinical characteristics were collected by using questioners. Then 6 ml venous blood was collected with a needle and syringe method. About 3 ml blood was transferred to EDTA test tube for platelet count and 2.7 ml blood was transferred to a test tube containing 0.3 ml of 3.2% sodium citrated anticoagulant for coagulation test. For those study participants with prolonged coagulation tests, a mixing test was done. Blood film and stool examination were also done for malaria and intestinal parasite identification, respectively. The data were entered into EPI-Info version 3.5.3 and then transferred to SPSS version-20 for analysis. Descriptive statistics were summarized as percentages, means, and standard deviations. Bivariate and multivariate logistic regression was used to identify the associated factors, and a P-value less than 0.05 was considered statistically significant. Results In this study, the prevalence of coagulopathy was 253/384 (65.9%; 95% CI: 61.16, 70.64). From them, 21.3% (54/253), 51.4% (130/253), and 27.3% (69/253) had only thrombocytopenia, only prolonged coagulation test, and mixed abnormality, respectively. Among participants with prolonged coagulation time, the prevalence of factor deficiency was 21.1% (42/199). Cardiac disease (AOR = 4.80; 95% CI: 2.65, 23.1), and other chronic diseases (AOR = 8.1; 95% CI: 1.84, 35.58) were significantly associated with coagulopathy. Conclusion In this study, coagulopathy due to inhibitory was a public health problem. The participants with cardiac and other chronic diseases were at high risk for coagulopathy. Therefore, mixing tests could be done for all prolonged coagulation tests and it could be considered as a routine laboratory test.

Hemostasis is a complex physiological process based on the balance between pro-coagulant and anticoagulant systems to avoid pathological bleeding or thrombosis. The changes in standard coagulation tests in liver disease were assumed to reflect an acquired bleeding disorder, and cirrhotic patients were considered naturally anticoagulated. In the light of the new evidence, the theory of rebalanced hemostasis replaced the old concept. According to this model, the hemostatic alteration leads to a unique balance between pro-coagulant, anticoagulant, and fibrinolytic systems. But the balance is fragile and may prone to bleeding or thrombosis depending on various risk factors. The standard coagulation tests [INR (international normalized ratio), platelet count and fibrinogen] only explore parts of the hemostasis, not offering an entire image of the process. Rotational thromboelastometry (ROTEM) and thromboelastography (TEG) are both point of care viscoelastic tests (VET) that provide real-time and dynamic information about the entire hemostasis process, including clot initiation (thrombin generation), clot kinetics, clot strength, and clot stability (lysis). Despite prolonged PT/INR (international normalized ratio of prothrombin time) and low platelet counts, VET is within the normal range in many patients with both acute and chronic liver disease. However, bleeding remains the dominant clinical issue in patients with liver diseases, especially when invasive interventions are required. VET has been shown to asses more appropriately the risk of bleeding than conventional laboratory tests, leading to decrial use of blood products transfusion. Inappropriate clotting is common but often subtle and may be challenging to predict even with the help of VET. Although VET has shown its benefit, more studies are needed to establish cut-off values for TEG and ROTEM in these populations and standardization of transfusion guidelines before invasive interventions in cirrhotic patients/orthotopic liver transplantation.

Background: Intracerebral Hemorrhage (ICH) is one of the most feared complications after brain tumor surgery. Postoperative hemorrhage has been described in presence of a reduction of Factor XIII (FXIII) with normal routine coagulation tests in different fields. The primary objetive was to evaluate the influence of perioperative FXIII levels on ICH after brain surgery. Methods: A prospective, observational, 18-month study was conducted at a third-level hospital in Spain. It included all consecutive adults (18 years of age or alder) operated on elective brain tumor surgery with postoperative stay in the Neurointensive Care Unit (N-ICU). Informed consent from all participants and ethical approval were obtained. Younger than 18 years of age, informed refusal, death in the OR, incomplete blood sample or non-tumoral tissue were exclusion criteria. Three blood samples evaluated FXIII levels (A-presurgical, B-postsurgical and C-24 hours after surgery). ICH, as a primary outcome variable, was defined as bleeding that generates radiological signs of intracranial hypertension either by volume or by mass effect on the routine CT scan 24 hours after surgery. The influence of tumoral data and standard coagulation were also analized. Chi-square (χ2) and Fisher’s exact tests, Mann-Whitney U and T-Tests and multiple regression were used for inferential analysis. Results: The study included 109 patients. ICH was finally confirmed in 39 of them (35,78%). Inferential analisys determined statistical association between lenght of stay in ICU (p

Postoperative coagulopathic bleeding is common in cardiac surgery and is associated with increased morbidity and mortality. Ideally, real-time information on in-vivo coagulation should be available. However, up to now it is unclear which perioperative coagulation parameters can be used best to accurately identify patients at increased risk of bleeding. The present study analyzed the associations of perioperative fibrinogen concentrations and whole blood viscoelastic tests with postoperative bleeding in 89 patients undergoing combined cardiac surgery procedures. Postoperative bleeding was recorded until 24 hours after surgery. Regression analyses were performed to establish associations between blood loss and coagulation parameters after cardiopulmonary bypass including a prediction model with known confounding factors for bleeding. Coagulation tests show large changes over the perioperative course with the strongest coagulopathic deviations from baseline after cardiopulmonary bypass. After adjustment for multiple confounders, viscoelastic clot strength instead of fibrinogen concentration showed a similar performance for 24 hour blood loss and a better performance for 6 hour blood loss. This makes intraoperative viscoelastic testing a useful tool to strengthen early clinical decision-making with the potential to reduce perioperative blood transfusions.

OBJECTIVES Fibrinolytic shutdown is associated with poor prognosis in adult sepsis, but data in the pediatric population are sparse. This study aimed to identify the association between impaired fibrinolysis and mortality in pediatric septic shock. DESIGN A prospective, observational study conducted between August 2019 and August 2020. SETTING PICU at a pediatric tertiary hospital in Hanoi, Vietnam. PATIENTS Fifty-six pediatric patients who met septic shock criteria were enrolled. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Conventional coagulation tests and rotational thromboelastometry were performed at diagnosis. The fibrinolytic activity on extrinsic pathway thromboelastometry was negatively correlated with the Vasoactive-Inotropic Score at 24 hours post-PICU admission, peak lactate level during the first 24 hours, Pediatric Logistic Organ Dysfunction-2 score, and Pediatric Risk of Mortality-III score (all p < 0.05). Compared with patients with nonovert disseminated intravascular coagulation, dysfunction of less than two organs, and who survived, patients with overt disseminated intravascular coagulation, dysfunction of greater than two organs, and who died showed significantly lower fibrinolytic activity, represented by significantly higher lysis indexes (%) and lower maximum lysis (%) (all p < 0.05). The threshold values for prediction of mortality were lysis index 60 minutes greater than 97.5 (area under the curve = 0.86; sensitivity = 73%; specificity = 90%), maximum lysis less than 6.5 (area under the curve = 0.83; sensitivity = 73%; specificity = 87%), and lysis index 45 minutes greater than 99.5 (area under the curve = 0.83; sensitivity = 73%; specificity = 85%). Hypofibrinolysis was associated with prolonged PICU length of stay in survivors and with early mortality in nonsurvivors. CONCLUSIONS Fibrinolytic shutdown in pediatric septic shock is associated with an increase in disease severity and mortality. This highlights the need for further investigations regarding whether fibrinolytic therapy improved the outcome of pediatric septic shock.

The pathogenesis of hypercoagulability in HIV infection is multifactorial and usually more than one factor is responsible for a thromboembolic episode. The present study was conducted to evaluate the effect of HIV infection and antiretroviral therapy on various coagulation parameters in paediatric patients. Forty two newly diagnosed paediatric patients with HIV infection who were enrolled at the Anti-Retro viral Therapy (ART) centre of Kalawati Saran Children’s Hospital were included in the study. The patients were grouped into 4 clinical stages according to the WHO clinical staging of HIV disease. Coagulation tests [PT, aPTT, fibrinogen, D-Dimer and coagulation inhibitors i.e. Protein C (PC), Protein S (PS) and antithrombin III (AT III), Lupus anticoagulant (LA) and Anti phospholipid antibody (APLA)] were performed in all the patients at the time of diagnosis and repeated after 6 months. All the patients were started on antiretroviral therapy within 2 months of their diagnosis. At the time of diagnosis, prolonged PT and aPTT were observed in 30.9% and 23% of the cases respectively. Hyperfibinogenemia was seen in 11.9% of patients. D-Dimer was raised in 83.3% of patients. PS, PC & AT activities were reduced in 90.4%, 42.8% & 11.9% of cases respectively. A reduction in the PC and AT activity was seen from clinical stage 1 to 4, but the change was not statistically significant. On follow up after 6 months, a statistically significant reduction in the level of fibrinogen and D-Dimer was seen. Even though there was improvement in the activity of all the coagulation inhibitor after 6 months, statistically significant improvement was seen only for PS. The current study shows that HIV produces a hypercoagulable state in children. Raised d-dimer level and deficiency of natural anticoagulants contribute to the thrombophilic state.

Objectives To verify a single platform of hemostasis instrumentation, the ACL TOP 50 Family, comprising 350, 550, and 750 instruments, across a large network of 60 laboratories. Methods Comparative evaluations of instrument classes (350 vs 550 and 750) were performed using a large battery of test samples for routine coagulation tests, comprising prothrombin time/international normalized ratio, activated partial thromboplastin time (APTT), thrombin time, fibrinogen and D-dimer, and using HemosIL reagents. Comparisons were also made against existing equipment (Diagnostica Stago Satellite, Compact, and STA-R Evolution) and existing reagents to satisfy national accreditation standards. Verification of manufacturer normal reference ranges (NRRs) and generation of an APTT heparin therapeutic range were undertaken. Results The three instrument types were verified as a single instrument class, which will permit standardization of methods and NRRs across all instruments (n = 75) to be deployed in 60 laboratories. In particular, ACL TOP 350 test result data were similar to ACL TOP 550 and 750 and showed no to limited bias. All manufacturer NRRs were verified with occasional minor variance. Conclusions This ACL TOP 50 Family (350, 550, and 750) verification will enable harmonization of routine coagulation across all laboratories in the largest public pathology network in Australia.

Coagulopathy in traumatic brain injury (TBI) is associated with increased risk of poor outcomes, but accurate prediction of clinically significant progressive hemorrhagic injury (PHI) in patients with severe TBI remains a challenge. Thromboelastography (TEG) is a real-time test of whole blood coagulation that provides dynamic information about global hemostasis. This study aimed to identify differences in TEG values between patients with severe TBI who did or did not experience clinically significant PHI. This was a single-center retrospective cohort study of adult patients with severe TBI. Patients were eligible for inclusion if initial Glasgow coma scale (GCS) was ≤ 8 and baseline head computed tomography (CT) imaging and TEG were available. Exclusion criteria included receipt of hemostatic agents prior to TEG. PHI was defined as bleeding expansion on CT within 24 h associated with 2-point drop in GCS, neurosurgical intervention, or mortality within 24 h. The primary endpoint was TEG value differences between patients with and without PHI. Secondary endpoints included differences in conventional coagulation tests (CCTs) between groups. Of the 526 patients evaluated, 141 met inclusion criteria. The most common reason for exclusion was lack of baseline TEG and receipt of reversal product prior to TEG. Sixty-four patients experienced PHI in the first 24 h after presentation. K time (2.03 min vs. 1.33 min, P = 0.035) and alpha angle (65° vs. 69°, P = 0.015) were found to be significantly different in patients experiencing PHI. R time (5.25 min vs. 4.71 min), maximum amplitude (61 mm vs. 63 mm), and clot lysis at 30 min after maximum clot strength (3.5% vs. 1.7%) were not significantly different between groups. Of the CCTs, only activated partial thromboplastin time (30.3 s vs. 27.6 s, P = 0.014) was found to be different in patients with PHI. Prolonged K time and narrower alpha angle were found to be associated with developing clinically significant PHI in patients with severe TBI. Despite differences detected in alpha angle, median values in both groups were within normal reference ranges. These abnormalities may reflect pathologic hypoactivity of fibrinogen, and further study is warranted to evaluate TEG-guided cryoprecipitate administration in this patient population.

Background: Plasma transfusions are commonly used in adult and paediatric intensive care units. Latest data showed a correlation in adult trauma patients between plasma transfusions and worse clinical results. Plasma transfusions are frequently prescribed worldwide; the indications for their use remain unclear. Objective: To identify signs of plasma transfusions and evaluation of the impact of plasma transfusions on coagulation studies. Patients and Methods: This prospective cohort study was conducted at the Pediatric Intensive Care unit, Zagazig University Hospital between July 2019 and January 2020. Participants in the study had a full background of socio-demographic characteristics. Total clinical examination and the seriousness of the disease was measured at admission using the Sequential Organ Failure Assessment (SOFA) score as per Ferreira 2001. Patients have been checked for critical parameters. Results: Our analysis found that 50 percent of plasma transfusions were attributed to bleeding, 40.7 percent to hypoalbuminemia, and 9.3 percent of plasma transfusions were due to surgical conceptions. The mortality rate in our study was 25.9 percent. Conclusion: Plasma transfusion does not have a statistical effect on mortality, but there has been little improvement in mortality over predictive SOFA mortality. Approximately ten times, no bleeding or proposed bleeding-risk operations earned plasma, based on the physician's views and conceptions. Plasma transfusion was insufficient to correct minor coagulation irregularities. Major research evaluating effective plasma transfusion techniques are desperately needed.

Extracorporeal membrane oxygenation (ECMO) support has a high incidence of both bleeding and thrombotic complications. Despite clear differences in patient characteristics and pathologies between veno-venous (VV) and veno-arterial (VA) ECMO support, anticoagulation practices are often the same across modalities. Moreover, there is very little data on their respective coagulation profiles and comparisons of thrombin generation in these patients. This study compares the coagulation profile and thrombin generation between patients supported with either VV and VA ECMO. A prospective cohort study of patients undergoing VA and VV ECMO at an Intensive care department of a university hospital and ECMO referral centre. In addition to routine coagulation testing and heparin monitoring per unit protocol, thromboelastography (TEG), multiplate aggregometry (MEA), calibrated automated thrombinography (CAT) and von-Willebrand’s activity (antigen and activity ratio) were sampled second-daily for 1 week, then weekly thereafter. VA patients had significantly lower platelets counts, fibrinogen, anti-thrombin and clot strength with higher d-dimer levels than VV patients, consistent with a more pronounced consumptive coagulopathy. Thrombin generation was higher in VA than VV patients, and the heparin dose required to suppress thrombin generation was lower in VA patients. There were no significant differences in total bleeding or thrombotic event rates between VV and VA patients when adjusted for days on extracorporeal support. VA patients received a lower median daily heparin dose 8500 IU [IQR 2500–24000] versus VV 28,800 IU [IQR 17,300–40,800.00]

Inherited bleeding disorders (IBDs) encompass a large number of different but rare conditions that can lead to increased risk of bleeding. The most common IBDs are von Willebrand disease, haemophilia A and haemophilia B. The diagnosis of IBDs requires a detailed history of the bleeding and specialized coagulation testing. The management of bleeding episodes in patients with IBDs can include the use of coagulation factor concentrate, desmopressin and antifibrinolytics such as tranexamic acid. This brief review focuses on the more common IBDs.

Objectives Use of viscoelastic testing, such as thromboelastography (TEG), is recommended in cardiac surgery to monitor coagulation and to guide the transfusion of blood products. The Quantra QPlus System is a novel point-of-care platform that uses ultrasonic pulses to characterize dynamic changes in viscoelastic properties of a blood sample during coagulation. Despite the ability to assess similar aspects of clot formation, limited studies addressing the interchangeability of viscoelastic testing parameters exist. The primary aim of the present study was to assess the correlation and agreement between Quantra and TEG5000 results using blood samples from cardiac surgery patients. Design Tertiary care, academic medical center. Setting Prospective observational study. Participants Twenty-eight patients undergoing elective cardiac surgery undergoing cardiopulmonary bypass were evaluated. Measurements and Main Results Perioperative blood samples were collected and assessed using Quantra, and results were compared with TEG and conventional coagulation testing. Method comparison analysis demonstrated that Quantra parameters (Quantra clot time, clot stiffness, and fibrinogen contribution to clot stiffness) significantly correlated with TEG R and TEG G after induction of anesthesia, during cardiopulmonary bypass, and after rewarming (rs = 0.83, rs = 0.84, and rs = 0.73, respectively). However, Quantra parameters demonstrated poor agreement compared with equivalent TEG5000 parameters. Conclusions The Quantra QPlus System significantly correlated with TEG5000, suggesting that this test may be used in a similar clinical context. Despite the strength of correlation between Quantra and TEG parameters, measurements are not interchangeable.

Graphical abstract Many patients develop coagulation abnormalities due to chronic and hereditary disorders, infectious disease, blood loss, extracorporeal circulation, and oral anticoagulant misuse. These abnormalities lead to bleeding or thrombotic complications, the risk of which is assessed by coagulation analysis. Current coagulation tests pose safety concerns for neonates and small children due to large sample volume requirement and may be unreliable for patients with coagulopathy. This study introduces a containerless drop-of-blood method for coagulation analysis, termed “integrated quasi-static acoustic tweezing thromboelastometry” (i-QATT™), that addresses these needs. In i-QATT™, a single drop of blood is forced to levitate and deform by the acoustic radiation force. Coagulation-induced changes in drop turbidity and firmness are measured simultaneously at different instants. The parameters describing early, intermediate, and late stages of the coagulation process are evaluated from the resulting graphical outputs. i-QATT™ rapidly ( 0.9) was established between fibrinogen concentration and two i-QATT™ parameters: maximum clot firmness and maximum fibrin level. Factor XIII activity was uniquely measured by the fibrin network formation time (r2 = 0.9). Reaction time, fibrin formation rate, and time to firm clot formation were linearly correlated with heparin concentration (r2 > 0.7). tPA-induced hyperfibrinolysis was detected in the clot firmness output at 10 min. i-QATT™ provides comprehensive coagulation analysis in point-of-care or laboratory settings, well suited to the needs of neonatal and pediatric patients and adult patients with anemia or blood collection issues. Supplementary Information The online version contains supplementary material available at 10.1007/s00216-021-03278-8.

The diagnosis of coagulopathy or thrombophilia in pediatric patients can be challenging. Congenital coagulopathies often present in the pediatric period and require appropriate work-up for diagnosis and ongoing management. Acquired coagulopathies of childhood are frequently encountered in hospitalized children and warrant appropriate coagulation testing for goal-directed therapy. The incidence of thrombosis is increasing in pediatric patients. After identifying the presence of thrombus, acute management includes initiating therapeutic anticoagulation. Choice of anticoagulant depends on patient's clinical status, along with availability of the anticoagulant. Thrombophilia evaluation is performed when children present with spontaneous thrombosis. Thrombophilia tests are inaccurate during acute illness.

Background The objective of the current study was to summarize and evaluate all published evidence regarding viscoelastic testing in the field of liver surgery. Methods A systematic search of the literature was performed using Medline/PubMed, Scopus, Cochrane Library Central, Google Scholar, and clinicaltrials.gov databases. The following keywords were used:“Thromboelastography”, “Thromboelastometry”, “Viscoelastic tests OR testing”, “Sonoclot Devices”, “Point-of-care tests OR testing”, “Coagulation OR Haemostasis OR Hemostasis”, “Liver OR Hepatic Surgery”, “Cirrhosis.” Results A total of 12 studies analyzing 348 patients who underwent viscoelastic testing of coagulation during liver surgery for benign or malignant diseases were included; 7 (58.3%) studies reported on the use of thromboelastography (TEG), and 5 (41.7%) reported on rotational thromboelastometry (ROTEM). Viscoelastic testing (TEG and ROTEM) identified normo-, hyper- and hypo-coagulable status in 77% (n = 268/348), 18.4% (n = 64/348), and 4.6% (n = 16/348) of patients, respectively. In contrast, conventional coagulation tests indicated normo-coagulability in 111 patients (34.2% out of 325) and hypo-coagulability in 214 (65.8% out of 325) patients following liver resection. No patient (0% out of 291) experienced postoperative hemorrhage, whereas 5.8% (n = 17/291) experienced postoperative thromboembolic events. Conclusions Global viscoelastic testing may be a reasonable adjunct to conventional coagulation testing to provide a more robust assessment of the coagulation status of patients undergoing liver surgery.

Trauma-induced coagulopathy is associated with very high mortality, and hemorrhage remains the leading preventable cause of death after injury. Directed methods to combat coagulopathy and attain hemostasis are needed. The available literature regarding viscoelastic testing, including thrombelastography (TEG) and rotational thromboelastometry (ROTEM), was reviewed to provide clinically relevant guidance for emergency resuscitation. These tests predict massive transfusion and developing coagulopathy earlier than conventional coagulation testing, within 15 min using rapid testing. They can guide resuscitation after trauma, as well. TEG and ROTEM direct early transfusion of fresh frozen plasma when clinical gestalt has not activated a massive transfusion protocol. Reaction time and clotting time via these tests can also detect clinically significant levels of direct oral anticoagulants. Slowed clot kinetics suggest the need for transfusion of fibrinogen via concentrates or cryoprecipitate. Lowered clot strength can be corrected with platelets and fibrinogen. Finally, viscoelastic tests identify fibrinolysis, a finding associated with significantly increased mortality yet one that no conventional coagulation test can reliably detect. Using these parameters, guided resuscitation begins within minutes of a patient's arrival. A growing body of evidence suggests this approach may improve survival while reducing volumes of blood products transfused.

As patients with COVID-19 pneumonia admitted to intensive care unit (ICU) have high rates of thrombosis, high doses of thromboprophylaxis have been proposed. The associated bleeding risk remains unknown. We investigated major bleeding complications in ICU COVID-19 patients and we examined their relationship with inflammation and thromboprophylaxis. Retrospective monocentric study of consecutive adult patients admitted in ICU for COVID-19 pneumonia requiring mechanical ventilation. Data collected included demographics, anticoagulation status, coagulation tests and outcomes including major bleeding and thrombotic events. Among 56 ICU COVID-19 patients, 10 (18%) patients had major bleeding and 16 (29%) thrombotic events. Major bleeding occurred later than thrombosis after ICU admission [17(14-23) days versus 9(3-11) days respectively (p = 0.005)]. Fibrinogen concentration always decreased several days [4(3-5) days] before bleeding; D-dimers followed the same trend. All bleeding patients were treated with anticoagulants and anticoagulation was overdosed for 6 (60%) patients on the day of bleeding or the day before. In the whole cohort, overdose was measured in 22 and 78% of patients receiving therapeutic anticoagulation during fibrinogen increase and decrease respectively (p < 0.05). Coagulation disorders had biphasic evolution during COVID-19: first thrombotic events during initial hyperinflammation, then bleeding events once inflammation reduced, as confirmed by fibrinogen and D-dimers decrease. Most bleeding events complicated heparin overdose, promoted by inflammation decrease, suggesting to carefully monitor heparin during COVID-19. Thromboprophylaxis may be adapted to this biphasic evolution, with initial high doses reduced to standard doses once the high thrombotic risk period ends and fibrinogen decreases, to prevent bleeding events.

Background Accumulating evidence indicates toward an association between severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and procoagulatory state in blood. Thromboelastographic investigations are useful point-of-care devices to assess coagulation and fibrinolysis.Objectives We investigated the hypothesis that the procoagulatory state in COVID-19 patients is associated with impaired fibrinolysis system.Methods Altogether, 29 COVID-19 patients admitted to normal wards or to the intensive care unit (ICU) were included in this descriptive study. Whole blood samples were investigated by thromboelastography to assess coagulation and fibrinolysis. Additionally, standard routine coagulation testing and immunoassays for factors of fibrinolysis as plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (tPA), plasminogen activity and α2-antiplasmin (A2AP) were performed.Results A significantly increased lysis resistance and a significantly longer time of lysis after adding tissue plasminogen activator were observed in blood samples from ICU COVID-19 patients compared with healthy controls (maximal lysis: 3.25 ± 0.56 vs. 6.20 ± 0.89%, p = 0.0127; lysis time: 365.7 ± 44.6 vs. 193.2 ± 16.3 seconds, p = 0.0014). PAI-1 activity was significantly higher in plasma samples of ICU COVID-19 patients (PAI-1: 4.92 ± 0.91 vs. 1.28 ± 0.33 U/mL, p = 0.001). A positive correlation between the activity of PAI-1 and lysis time of the formed clot (r = 0.70, p = 0.0006) was observed.Conclusion Our data suggest that severe SARS-CoV-2 infection is associated with impaired fibrinolytic activity in blood, where fibrinolytic inhibitors are elevated leading to an increased resistance to clot lysis. Thromboelastography could offer a tool to investigate the contribution of the fibrinolytic status to the procoagulatory condition in COVID-19.