Coagulation Disorders In Patients Research Articles

The risk factors for coagulation disorder of chimeric antigen receptor-T cell therapy in patients with hematological tumors: A systematic review and meta-analysis.

Currently, the frequency of coagulation dysfunction associated with chimeric antigen receptor-T cell (Car-T) therapy cannot yet be determined. We performed a systematic review and meta-analysis to examine the prevalence of abnormal laboratory tests related to coagulation disorders in patients receiving Car-T therapy and provide a reference for future risk assessment mechanisms. We searched PubMed, Embase, and Web of Science for relevant studies and evaluated their quality using the methodology index of non-random research (MINORS). 2672 quotations were retrieved via systematic searches. After screening of titles, abstracts and full-text, 45 trials involving 2541 patients were ultimately included. 41 studies reported the incidence of thrombocytopenia, 8 studies reported the rate of low fibrin, 4 trials reported the rate of APTT or PT abnormalities and only 3 trials reported the incidence of venous thromboembolism (VTE). We performed a quantitative meta-analysis to explore the incidence of thrombocytopenia following Car-T treatment. The incidence of hypofibrinogenemia, VTE, and abnormal APTT or PT was only qualitatively assessed, as fewer reports were included in this study. The overall incidence of thrombocytopenia associated with Car-T therapy was 45.8% (95%[CI], 0.384-0.533). The highest rates of thrombocytopenia occurred in patients with multiple myeloma (60.1%, 95%[CI], 0.507-0.688) and aged between 18 to 60 (50%, 95%[CI], 0.367-0.633). There was greater prevalence of thrombocytopenia in BCMA-Car-T therapy of 58.7% (95%[CI], 0.482-0.685). Thrombocytopenia occurred most frequently in Car-T patients treated with a dosage of 1 × 105-1 × 106cell/kg, at a rate of 66.2% (95%[CI], 0.561-0.749). Overall, 45.8 percent of patients receiving Car-T treatment suffered from thrombocytopenia. Multiple myeloma patients, ages between 18-60, a dose of 1 × 105-1 × 106cell/kg and BCMA-Car-T therapy are all considered high-risk factors.

Elevated levels of soluble glycoprotein V - The plasma marker of platelet activation by thrombin in patients with early stage primary biliary cholangitis (PBC)

PurposeThere is a growing body of evidence for a prothrombotic tendency in patients with primary biliary cholangitis (PBC). The aim of the study was to evaluate coagulation disorders in patients with early stage PBC compared to healthy controls and evaluation of their relationship with clinical data, with particular emphasis on minimal hepatic encephalopathy (MHE). Patients and methodsFifty-one participants (PBC group – 38 patients, all patients but one Child-Pugh A; control group – 13 healthy controls) were included in our prospective, single center study. We assessed the plasma levels of sGPV, plasma procoagulant phospholipids (PPL) and rotational thromboelastometry (ROTEM) profiles in all study participants. Porto-systemic encephalopathy syndrome test was used to assess MHE. ResultsThe sGPV levels were higher in the PBC group compared to the controls: 36.07 ​± ​11.32 ​ng/mL vs 27.04 ​± ​11.72 ​ng/mL, p ​= ​0.031. The PPL level was lower in the PBC group compared to controls resulting in increased clotting time in a factor Xa-based coagulation assay: 54.65 (47.83–58.83) sec. vs 45.90 (43.3–50.5) sec., p ​= ​0.0065. PPL levels were correlated with platelet count (rho ​= ​−0.46, p ​= ​0.001). ROTEM parameters did not differ significantly between groups. Coagulation parameters did not differ significantly between patients with and without MHE. ConclusionsWe have showed increased levels of sGPV - a plasma marker of platelet activation by thrombin in patients with early stage PBC compared to healthy controls. We found no relationship between the coagulation disorders and the occurrence of MHE. The PPL level was lower in the PBC group.

Neurological Manifestations of Hospitalized COVID-19-Infected Patients: A Single-Center Cohort Study

Background: Although COVID-19 preferentially affects the respiratory system, it has been demonstrated that coronaviruses frequently invade the nervous system. Objectives: We aimed to report the frequency and type of neurological manifestations in hospitalized patients with COVID-19. Methods: This is a retrospective, prospective observational cohort study. Data were collected from April to July 2020 at Bu-Ali Sina University Hospital, Sari, Iran. Demographic data and clinical symptoms were recorded at the onset of the disease. Neurological manifestations were recorded into 5 categories: nonspecific central nervous system (CNS) manifestations, acute cerebrovascular disease (CVD), meningitis/encephalitis, peripheral nervous system manifestations, and inflammatory disorders (myelitis and acute disseminated encephalomyelitis). Results: A total of 420 patients were admitted to the hospital with confirmed SARS-CoV-2 infection. Of the 420 patients hospitalized with COVID-19, 282 (67%) showed some form of neurological symptoms, of whom 48.33% had nonspecific neurological symptoms. Further, 35 (8.3%) patients had acute CVD, 2 patients had encephalitis (the RNA of SARS-CoV-2 was detected in cerebrospinal fluid (CSF), 1 patient had myelitis, and 83 (19.76%) patients had peripheral nervous system manifestations. Conclusions: Neurologic symptoms (from mild symptoms to life-threatening CNS disorders) are common in admitted patients with COVID-19. As a result of coagulation disorder in patients with COVID-19, some conditions (such as stroke) can be seen, even during recovery.

The correlation factors and prognostic significance of coagulation disorders after chimeric antigen receptor T cell therapy in hematological malignancies: a cohort study.

BackgroundAlong with cytokine release syndrome (CRS) and neurotoxicity, coagulation disorder is a common early complication of chimeric antigen receptor (CAR)-T cell therapy. However, the mechanisms and prognostic significance of CAR-T-related coagulation disorders are not fully known. This study explored the possible correlation factors and prognostic significance of coagulation disorders after CAR-T cell infusion in patients with relapsed/refractory hematological malignancies.MethodsThis cohort study included 56 patients with relapsed/refractory hematological malignancies who were treated with CAR-T cells between April 2017 and February 2022. The median follow-up was 26.8 months. Coagulation disorders were defined as the abnormality in at least one coagulation parameters, including prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen, and D-dimer. The correlation factors of coagulation disorders were analyzed using Wilcoxon rank-sum test, Fisher’s exact test, paired t-test and Spearman correlation coefficient. The prognostic significance of coagulation disorders was analyzed using Kaplan-Meier method and stepwise multivariate Cox regression model.ResultsThe incidence of coagulation disorders was 59% within 1 month of CAR-T cell infusion. PT prolongation, APTT prolongation, TT prolongation, and D-dimer increase peaked at a median of 6–9 days, and fibrinogen decreased to its lowest value at a median of 12 days. Coagulation disorders in patients with severe CRS were more significant (P<0.001). Abnormality of coagulation parameters was closely related to cytokines, CAR-T cells, liver function parameters, and von Willebrand Factor (VWF) in both peak level and peak time (P<0.05). Statistical analysis showed that coagulation disorders were associated with higher initial response rates (TT, P=0.006; D-dimer, P=0.010) and also longer progression‐free survival (PFS) (PT, P=0.017; APTT, P=0.018; TT, P=0.001; Fibrinogen, P=0.003; D-dimer, P<0.001) in CAR-T therapy, with TT prolongation (HR =0.279, 95% CI: 0.099–0.782, P=0.015) and D-dimer increase (HR =0.218, 95% CI: 0.087–0.548, P=0.001) independent predictors for PFS.ConclusionsThe protection of liver and endothelial cells may reduce CAR-T-related coagulation disorders. Further, coagulation disorders occurring within 1 month of CAR-T cell infusion can serve as a new predictor for prognosis in patients with hematological malignancies.

The Role of Hemostatic System and the Importance of Blood Coagulation in COVID-19: A Review Study

Background and Aim Coronavirus disease 2019 (COVID-19) is a respiratory disorder that can affect many body systems, including the hemostatic system. In this study, we aim to investigate the role of hemostatic system and the blood coagulation in COVID-19. Methods &amp; Materials In this review study, the articles were searched using the keywords COVID-19, Respiratory infection, and Coagulopathy in Google Scholar, PubMed, Google Springer and Science Direct databases. Ethical Considerations Ethical principles in writing this article were observed in accordance with the guidelines of the National Ethics Committee and the Committee on Publication Ethics (COPE). Results Many changes in the coagulation profile of infected patients were reported, including changes in the platelet count, fibrinogen/fibrin degradation product, D-Dimer, fibrinogen, prothrombin time, and activated partial thromboplastin time. With the increase in the number of patients with COVID-19, several studies found out the occurrence of thrombosis and coagulopathy in patients. Conclusion Due to the increase in the occurrence of coagulation disorders in patients with COVID-19, the administration of anticoagulants is needed for their treatment; it can play an effective role in improving the prognosis of patients.

An excerpt of AGA clinical practice guideline on the management of coagulation disorders in patients with cirrhosis (2021)

An excerpt of AGA clinical practice guideline on the management of coagulation disorders in patients with cirrhosis (2021)

Peculiarities of blood coagulation disorders in patients with COVID-19

To study the relationship of hemostatic disorders with inflammation and estimate their role in the course and outcomes of COVID-19. We examined 215 consecutive patients with moderate and severe forms of acute COVID-19. The patients were on anticoagulants and immunosuppressive drugs. Hemostasis was assessed using the thrombodynamics assay, thromboelastography, fibrinogen and D-dimer levels, prothrombin time, and soluble fibrin-monomer complexes (ethanol gelation test). The hemostatic parameters were correlated with hematological and biochemical tests, including markers of inflammation (C-reactive protein, interleukins 6 and 8), as well as with the disease severity and outcomes. Laboratory signs of coagulopathy were revealed in the vast majority of the cases. Despite the use of low-molecular-weight heparins in the prophylactic and therapeutic doses, coagulopathy in COVID-19 manifested predominantly as hypercoagulability that correlated directly with the systemic inflammation and metabolic changes due to liver and kidney dysfunction. A direct relationship was found between the grade of coagulopathy and the severity of COVID-19, including comorbidities and the mortality. The chronometric hypocoagulability observed in about 1/4 cases was associated with a high level of C-reactive protein, which may decelerate coagulation in vitro and thereby mask the true inflammatory thrombophilia. Persistent hyperfibrinogenemia and high D-dimer in the absence of consumption coagulopathy suggest the predominance of local and/or regional microthrombosis over disseminated intravascular coagulation. The results obtained substantiate the need for laboratory monitoring of hemostasis and active prophylaxis and treatment of thrombotic complications in COVID-19.

Disorders of the Blood Coagulation System in Patients with Infectious Endocarditis

Infectious endocarditis is a disease which is still hard to diagnose and treat. The success of the proposed ther-apy depends not only on the surgical correction of the heart disease, but also on effective perioperative management of this group of patients. In most cases, patients have a long history of drug treatment and compromised status of all organs and systems. Coagulation disorders in patients with infectious endocarditis are one of the main links which lead to the patient’s death, despite advances in therapeutic and surgical treatment. Since the development of infectious endocarditis is based on thrombo-inflammatory lesions of the endocardium as a result of the interaction of microorganisms and modifiers of the blood coagulation system, the appointment of effective anticoagulant therapy in the postoperative period becomes one of the important tasks in resuscitation. The need to maintain balance between the coagulation and anticoagulation systems of hemostasis requires constant monitoring of the coagulation system and careful administration of anticoagulants.&#x0D; The aim. To demonstrate an example of an alternative scheme of anticoagulant therapy in a patient with postopera-tive gastrointestinal bleeding after cardiac surgery for infectious endocarditis.&#x0D; Materials and methods. We present a clinical case of treatment of acute gastrointestinal bleeding in the early post-operative period in a patient after cardiac surgery for infectious aortic valve endocarditis. The 56-year-old patient K. was taken to the National Amosov Institute of Cardiovascular Surgery of the NAMS of Ukraine by ambulance with a diagnosis: Infectious endocarditis of the aortic and mitral valves. Combined aortic defect with a predominance of insufficiency, mitral regurgitation, tricuspid insufficiency. Pulmonary arterial hypertension. Degree II respiratory failure. Ischemic heart disease: non-Q-wave myocardial infarction (as of October 29, 2020), RCA stenting (November 2, 2020), post-infarction atheroscle-rotic cardiosclerosis. Degree III hypertension, stage 2, risk 4. Heart failure 2B, functional class III. A salvage cardiac surgery was performed: aortic valve replacement. Mitral and tricuspid valve plastics. On day 2 of the postoperative period, against the background of anticoagulant therapy prescribed according to international recommendations, gastrointestinal bleeding developed. Anticoagulant therapy regimen was adjusted. The proposed scheme of hemostasis control allowed to normalize the blood parameters and to avoid blood loss. On day 10 of the postoperative period, standard scheme of anticoagulant ther-apy could be renewed, and the patient was transferred to the therapeutic department under the supervision of cardiologist.&#x0D; Conclusions. The proposed variant of anticoagulant therapy in the postoperative period in a patient operated on for infectious endocarditis created the conditions for normalization of hemostasis. Complete withdrawal of anticoagulants and transfer of patients to a continuous infusion of heparin under the control of APTT with a target value allows not only to control the risk of bleeding, but also to prevent thrombosis.

Effects of Hyperglycemia and Diabetes Mellitus on Coagulation and Hemostasis.

In patients with diabetes, metabolic disorders disturb the physiological balance of coagulation and fibrinolysis, leading to a prothrombotic state characterized by platelet hypersensitivity, coagulation disorders and hypofibrinolysis. Hyperglycemia and insulin resistance cause changes in platelet number and activation, as well as qualitative and/or quantitative modifications of coagulatory and fibrinolytic factors, resulting in the formation of fibrinolysis-resistant clots in patients with diabetes. Other coexisting factors like hypoglycemia, obesity and dyslipidemia also contribute to coagulation disorders in patients with diabetes. Management of the prothrombotic state includes antiplatelet and anticoagulation therapies for diabetes patients with either a history of cardiovascular disease or prone to a higher risk of thrombus generation, but current guidelines lack recommendations on the optimal antithrombotic treatment for these patients. Metabolic optimizations like glucose control, lipid-lowering, and weight loss also improve coagulation disorders of diabetes patients. Intriguing, glucose-lowering drugs, especially cardiovascular beneficial agents, such as glucagon-like peptide-1 receptor agonists and sodium glucose co-transporter inhibitors, have been shown to exert direct anticoagulation effects in patients with diabetes. This review focuses on the most recent progress in the development and management of diabetes related prothrombotic state.

Platelet Receptor Activity for Predicting Survival in Patients with Intracranial Bleeding.

Blood coagulation disorders in patients with intracranial bleeding as a result of head injuries or ruptured aneurysms are a diagnostic and therapeutic problem and appropriate assessments are needed to limit CNS damage and to implement preventive measures. The aim of the study was to monitor changes in platelet aggregation and to assess the importance of platelet dysfunction for predicting survival. Platelet receptor function analysis was performed using the agonists arachidonic acid (ASPI), adenosine diphosphate (ADP), collagen (COL), thrombin receptor activating protein (TRAP), ristocetin (RISTO) upon admission to the ICU and on days 2, 3, and 5. On admission, the ASPI, ADP, COL, TRAP, and RISTO tests indicated there was reduced platelet aggregation, despite there being a normal platelet count. In ‘Non-survivors’, the platelet response to all agonists was suppressed throughout the study period, while in ‘Survivors’ it improved. Measuring platelet function in ICU patients with intracranial bleeding is a strong predictor related to outcome: patients with impaired platelet aggregation had a lower 28-day survival rate compared to patients with normal platelet aggregation (log-rank test p = 0.014). The results indicated that measuring platelet aggregation can be helpful in the early detection, diagnosis, and treatment of bleeding disorders.

Thrombin Generation in Chronic Liver Diseases-A Pilot Study.

The knowledge about coagulation disorders in patients with chronic liver disease changed in the last decade. The aim of this study was to analyze the parameters of thrombin generation in patients with chronic liver disease, as they are the most appropriate biomarkers to explore coagulation. (1) Background: The knowledge about coagulation disorders in patients with chronic liver disease changed in the last decade. The study of thrombin generation in patients with chronic liver disease provides a much more accurate assessment of the coagulation cascade; (2) Methods: This study is a prospective observational pilot study on hospitalized patients with chronic liver diseases that analyzed thrombin generation performed from their platelet-poor plasma versus that of control subjects. We analyzed a group of 59 patients with chronic liver disease and 62 control subjects; (3) Results: Thrombin generation was lower in hepatitis and cirrhosis patients compared to controls and decreases as the disease progressed. Lag time was higher in ethanolic etiology compared to the control group. Peak thrombin and endogenous thrombin potential were shorter in all etiologies when compared to the control group. The velocity index was significantly lower in HCV hepatopathies, ethanolic, and mixed etiology when compared with normal individuals; (4) Conclusions: Given the variability of thrombin generation in patients with chronic liver disease, its assay could serve to identify patients with high thrombotic and hemorrhagic risk and establish personalized conduct toward them.

Evaluation of inflammatory and coagulation markers in patients with idiopathic pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension with comorbid hypercholesterolemia

The aim of the study was to assess inflammatory and coagulation disorders in patients with idiopathic pulmonary arterial hypertension (IPAH) and chronic thromboembolic pulmonary hypertension (CTEPH) in dependence on dyslipidemia. Methods. The study involved 22 patients with IPAH and 6 patients with inoperable CTEPH complicated by hypercholesterolemia (total cholesterol (TC) level &gt; 5.8 mmol/L). Healthy volunteers with normal TC level (n = 20) were included in a control group. We measured serum cytokine concentrations, such as interleukin (IL)-2, IL-4, IL-5, IL-6, IL-10, IL-12, and interferon (INF)-γ, using a multiplex fluorescent analyzer GEN-PROBE (Luminex 200) with Bio-Plex Precision Pro set. Von Willebrand factor was measured using an immunoturbidimetric assay with STA-Liatest VWF: Ag set. D-dimer, fibrinogen, C-reactive protein, and the total blood cell count were also measured. Results. CTERH patients had lower IL-2 level and more prominent signs of chronic heart failure (CHF) compared to patients with IPAH. Serum levels of IL-10, IL-4, and IL-12 were significantly related to syncope frequency, INF-γ level and cardiac index (CI). High density lipoprotein (HDL) level was inversely related to mean pulmonary arterial pressure (mPAP) in IPAH/CTEPH patients with TC &gt; 6.5 mmol/L. Decreased thrombocyte count and decreased thrombocrit were associated with increased mPAP and mean right atrium (RA) pressure in patients with dilated right pulmonary artery. Increased D-dimer level was associated with enlarged RA area, enlarged right ventricle size, tricuspid regurgitation and decreased CI. Conclusion. Serum concentrations of the inflammatory and coagulation markers, excepting LI-2, did no differ significantly in patients with IPAH and CTEPH. Dyslipidemia was associated with activation of inflammation. Further studies are needed to estimate a predictive value of decreased HDL in patients with IPAH and CTEPH.

Value of Rotational Thromboelastometry and Impedance Aggregometry for Evaluating Coagulation Disorders in Patients With Cyanotic and Nongenetic Congenital Heart Disease

Adults with cyanotic congenital heart diseases (CCHD) have a higher risk for bleeding, but also for thrombosis. Rotational thromboelastometry (RT), using tissue factor (EXTEM), a contact activator (INTEM) or cytochalasin (FIBTEM), assesses coagulation by determining the time to initiation of clotting (CT) and clot firmness (MCF) including platelet-fibrin-interaction. The aim of this study was to evaluate RT and whole blood impedance aggregometry (IA) in CCHD compared with a control group without chronic cyanosis (NCCHD). These were used to establish normal reference ranges. We prospectively included 124 patients (76 CCHD, 48 NCCHD). Mean oxygen saturation in CCHD was 81.5%, and 98% in NCCHD (p <0.001). Fifty-five CCHD and 1 NCCHD had pulmonary hypertension. Eisenmenger syndrome was present in 39 CCHD (51.3%). Hemoglobin, hematocrit, and reticulocyte levels were significantly higher in CCHD, and they also showed more thrombocytopenia. Platelet aggregation was under normal range in 89.5% of CCHD after triggering with ADP, in 85.5% after triggering with arachidonic acid (ASPI) and in 73.7% after TRAP-6. RT showed significantly longer clotting times and reduced clot firmness in both EXTEM and INTEM tests. FIBTEM-MCF was also significantly reduced. Moderate inverse correlation was found between platelet count and erythrocytes (r = -0.608, p <0.001). Significant correlations were found between platelet number and RT-parameters as well as with all IA parameters. In conclusion, according to RT and IA, CCHD present hypocoagulable disorders. No signs of hypercoagulability were found.

Noninvasive Diagnostic Approach By per Rectal Portal Scintigraphy for Sinusoidal Obstruction Syndrome after Allogeneic Hematopoietic Cell Transplantation

BackgroundSinusoidal obstruction syndrome (SOS) is a significant, potentially life-threatening complication of allogeneic hematopoietic cell transplantation (allo-HCT). In particular, severe SOS frequently causes multiple organ failure and results in poor prognosis. Although early and accurate diagnosis of SOS is vital to intervene early and improve its prognosis, the diagnostic accuracy of clinical criteria, such as the Seattle criteria and Baltimore criteria, is unsatisfactory. Liver biopsy is a gold standard for SOS diagnosis and should be considered to confirm the diagnosis. However, this procedure confers the risk of major bleeding, potentially leading to fatal outcomes, due to low platelet counts or coagulation disorders in patients with SOS. Therefore, a novel, noninvasive diagnostic approach for SOS is needed.The hepatic venous pressure gradient (HVPG) representing portal pressure has been reported to be the most accurate for SOS diagnosis, but its measurement procedure is invasive. Per rectal portal scintigraphy (PRPS), which is a nuclear medicine examination, can estimate portal pressure safely using the portal shunt index (SI) calculated from radioactivity curves of the liver and heart. Only one case report has shown that PRPS was useful to detect portal hypertension in a patient with SOS after allo-HCT (Okamura H, et al. Acta Haematol 2013).To investigate the usefulness of PRPS for SOS diagnosis, we retrospectively analyzed patients who had hepatic disorder and/or ascites after allo-HCT and underwent transjugular liver biopsy and PRPS.MethodsWe examined consecutive patients who underwent transjugular liver biopsy with HVPG measurement and were assessed using PRPS around the same time at our institution between April 2011 and May 2017. When performing transjugular liver biopsy, we also measured the HVPG. All causes of hepatic disorder and/or ascites were pathologically determined based on liver biopsy, if applicable, with autopsy or needle necropsy findings. In PRPS, 370 MBq of Tc-99m pertechnetate was administered to the upper rectum. The SI was calculated using the ratio of liver to heart counts integrated for 24 seconds immediately after the appearance of the liver or heart time-activity curve.We assessed the diagnostic performances of the HVPG and SI for SOS using receiver-operating characteristic (ROC) curves and calculated the optimal cutoff points using the Youden index. Analyses were performed using GraphPad Prism® version 5.02 and SPSS® version 24.ResultsEleven cases were evaluable. The median onset of liver damage and/or ascites was on day 27 after allo-HCT: early-phase (within 30 days) in 7 cases and late-phase (after 30 days) in 4 cases. All patients were histologically diagnosed: 5 with SOS and 6 with non-SOS. The median interval from PRPS to transjagular liver biopsy was +4 days (range, -13 to 15 days). SI values from PRPS correlated with HVPG values in 11 pairs of the measurements (Spearman correlation coefficient 0.92, P < 0.001, Figure 1A).The areas under the ROC curves of the HVPG and SI for SOS diagnosis were 0.85 (95% confidence interval (CI), 0.61-1.0) and 0.77 (95% CI, 0.45-1.0), respectively. The best cutoff values of the HVPG and SI were calculated as 10 mmHg and 56%, respectively. Table 1 shows the sensitivity, specificity, and positive and negative predictive values for the HVPG, SI, and Seattle criteria for SOS diagnosis among all 11 cases.As a subgroup analysis, in 7 patients who developed hepatic disorder and/or ascites in the early phase after allo-HCT, both HVPG and SI were significantly higher in patients with SOS than in those without SOS (mean HVPG: 13.3 mmHg in SOS vs. 4.3 mmHg in non-SOS, P = 0.01, Figure 1B; mean SI: 58% in SOS vs. 26% in non-SOS, P = 0.03, Figure 1C). Furthermore, in these 7 patients, both the HVPG and SI made it possible to completely discriminate between SOS and non-SOS using cutoff points calculated based on the Youden index (8 mmHg for the HVPG and 44% for the SI).ConclusionWe found that the SI from PRPS represented portal pressure, even in patients after allo-HCT, and that the diagnostic accuracy of PRPS for SOS was not only superior to that of the Seattle criteria, but also comparable to that of the HVPG. In addition, especially in the early phase after allo-HCT, SI may be useful to discriminate between SOS and non-SOS. This noninvasive examination could offer a new diagnostic strategy, along with SOS clinical criteria. [Display omitted] DisclosuresHino:Otsuka Pharmaceutical Co., Ltd.: Research Funding; Novartis: Research Funding. Nakamae:Otsuka Pharmaceutical Co., Ltd.: Consultancy, Honoraria, Research Funding.

A clinical study of sepsis-related coagulation disorder.

Objective To study in the correlation of the laboratory markers of coagulation, fibrinolysis and thrombosis in patients with sepsis and SOFA score, the procalcitonin (PCT) concentration and seven-day survival rate. Methods From February 2017 to March 2018, 119 patients with sepsis admitted in ICU and another 119 patients with non-sepsis undergoing selective surgery were enrolled as control in this study. APTT (activated partial thromboplastin time), PT-INR (prothrombin time - international normalized ratio), FIB (fibrinogen), AT-Ⅲ (antithrombinⅢ), D-Dimer, FDP (fibrinogen degradation products), sTM (soluble thrombomodulin), TAT (thrombin antithrombin complex), PIC (plasmin-a2 plasminogen inhibitor complex) and t-PAI-C (tissue plasminogen activator and its inhibitor complex), were simultaneously monitored at admission. The correlation between the given laboratory markers mentioned and SOFA score, the PCT concentration and seven-day survival rate were analyzed with the Spearman correlation analysis. Results ① In the patients with sepsis, a positive correlation between SOFA score and sTM, t-PAI-C, TAT respectively was found, and a negative correlation between SOFA score and PLT (platelet count) was observed, and no correlation between SOFA score and PIC was noticed. ② A positive correlation between PCT and sTM, t-PAI-C respectively was significant, a negative correlation between PCT and PLT was marked, and no correlation between PCT and AT-Ⅲ, TAT, PIC respectively was found. ③ A negative correlation between seven-day survival rate and sTM, t-PAI-C and TAT respectively was obvious, a positive correlation between seven-day survival rate and AT-Ⅲ, PLT respectively was occurred, and no correlation between seven-day survival rate and PIC was determined. Conclusions Soluble thrombomodulin (sTM), thrombin-antithrombin (TAT) , antithrombin Ⅲ (AT-Ⅲ) and tissue plasminogen activator inhibitor complex (t-PAI-c) were good clinical monitoring indicators of coagulation disorder in patients with sepsis, which were the representative of the endothelial cell damage with highly activated coagulation, relatively insufficient anti-coagulation function and poor fibrin degradation ability. These were good adjuvants to PLT, INR and APTT for core diagnostic criteria of coagulation disorder in sepsis. Key words: Sepsis; Coagulation; Prognosis; Soluble thrombomodulin; AntithrombinⅢ; Thrombin-antithrombin

Serum ADAMTS-13 Levels as an Indicator of Portal Vein Thrombosis.

Background Coagulation disorders in patients with liver cirrhosis are a common clinical problem. Cirrhosis should be considered a state of impaired blood clotting or an imbalance of the whole coagulation system. Cirrhosis-induced coagulopathy encompasses disturbances in both the procoagulant and anticoagulant systems. This mechanism may promote the development of thrombosis with portal vein thrombosis (PVT), which is considered an obstacle to orthotopic liver transplantation (OLT). We assessed serum ADAMTS-13 levels in patients with decompensated liver cirrhosis, with and without PVT. Material and Methods Serum ADAMTS-13 levels, age, platelet count (PLT), and INR (international normalized ratio) were evaluated in (n = 64) patients with liver cirrhosis either with PVT (group 1, n = 31) or without PVT (group 2, n = 33). The results were compared with those from healthy volunteers (group 3, n = 37). Liver cirrhosis was based on Desmet's classification of chronic hepatitis in liver biopsy stage ≥ 3 or liver elastography F-score ≥ 3. Serum ADAMTS-13 levels were measured with Quantikine® ELISA Human ADAMTS13 Immunoassay, R&D Systems Inc. We used Welch's F-test, Games-Howell, one-way ANOVA, Bonferroni test, and logistic regression to determine whether ADAMTS-13 levels were a predictor that was independent of MELD and Child-Pugh scores. All results (P < 0.05) were considered statistically significant. Results The mean serum ADAMTS-13 level in patients with PVT was significantly lower than that in patients without PVT (P = 0.001) and controls (P = 0.001). The mean serum ADAMTS-13 level in patients without PVT was significantly lower than that in controls (P = 0.001). ADAMTS-13 levels were significantly associated with PVT accounting for the Child-Pugh or MELD score in the logistic regression model. Conclusions Low serum ADAMTS-13 levels can be a useful indicator of portal thrombosis in patients with decompensated liver cirrhosis irrespective of Child-Pugh or MELD scores. Further research is needed to determine whether ADAMTS-13 levels will find use in everyday clinical practice.

Vasculopathie livédoïde secondaire à une maladie cœliaque

Livedoid vasculopathy (LV) is a painful ulcerative condition involving white atrophy and livedo; a histopathologic feature seen is occlusive dermal vasculopathy. This may be associated with coagulation disorders such as hyperhomocysteinaemia (HHC). We report the case of a 52-year-old woman presenting LV in which an abnormal scan image led us to diagnose coeliac disease. This enteropathy had caused vitamin B12 and folic acid deficiency, as well as HHC. Vitamin supplementation and a gluten-free diet resulted in complete healing of the lesions. This case underlines the importance of screening for and correction of coagulation disorders in patients with LV. It also suggests that in the event of HHC, coeliac disease should be sought, even in the absence of gastrointestinal symptoms.

36th International Symposium on Intensive Care and Emergency Medicine : Brussels, Belgium. 15-18 March 2016.

36th International Symposium on Intensive Care and Emergency Medicine : Brussels, Belgium. 15-18 March 2016.

The role of coagulation disorders in patients with retinal vein occlusion.

The role of a hypercoagulable state in the pathogenesis of retinal vein occlusion (RVO) has not been conclusively established. To analyse the prevalence of thrombophilia in RVO. Prospective case-control study. All the patients diagnosed with RVO were referred to an Internal Medicine clinic and compared with sex- and age-matched individuals from a population-based cohort. Demographic, clinical and laboratory variables (including a thrombophilia panel) were analysed. One hundred and seventy patients (93 men and 77 women; 68 ± 11 years) and 170 controls (80 men and 90 women; 67 ± 10 years) were included. RVO was peripheral in 113 cases. Genetic thrombophilia was detected in 13% of patients. Acquired thrombophilia was observed in 10% of cases and 4.7 % of controls (P < 0.01). Sixty-three percent of cases and 24.6% of controls had serum hyperhomocysteinemia (odds ratio [OR] 5.2, IC 95% 2.7-10.1; P < 0.0001) : In RVO patients aged <50 years (n = 11), 36.4% had genetic thrombophilia (P = 0.04), as well as 50% of those without vascular risk factors (n = 18; P = 0.01). Forty-one (24%) patients with RVO received antiplatelet agents and 13 (7.6%) were on anticoagulants due to preexistent atrial fibrillation. We suggest that, in patients with RVO, hyperhomocysteinemia and antiphospholipid syndrome should be ruled out. Moreover, a study of genetic thrombophilia should only be considered in those aged <50 years or without cardiovascular risk factors. Antiplatelet therapy with aspirin is probably the treatment of choice of RVO, to reduce the overall vascular risk. Anticoagulation should only be considered in patients with high-risk thrombophilia.

Early Detection of Coagulation Abnormalities in Patients at Nutritional Risk: The Novel Role of Thromboelastography

It is believed that malnutrition is common among hospitalized patients and associated with increased risk of morbidity and mortality. It is unclear if it is more likely to cause coagulation disorders in patients with malnutrition. We, therefore, investigate the feasibility of using thromboelastography (TEG) in early detection of coagulation abnormalities in patients at nutritional risk. Fifty successive adult patients with gastrointestinal disease were prospectively divided into one of two groups according to nutritional risk score (less than 3 and 3 or greater). Blood samples were collected at admission for analysis of standard biochemical parameters, routine coagulation tests, and TEG parameters. A total of 62 per cent of patients (n = 31) were at nutritional risk. Serum concentrations of prealbumin, transferrin, total protein, low-density lipoprotein, high-density lipoprotein, and cholesterol were much lower in the nutritional risk group than in the no-risk group (P ≤ 0.05). There was no significant difference in routine coagulation tests, whereas most of the TEG parameters showed significant differences between the two groups. The overall coagulation function was worse in patients at nutritional risk than in patients with good nutritional status (P ≤ 0.01). TEG appears to be more sensitive for the detection of coagulation abnormalities compared with routine coagulation tests in patients at nutritional risk. The phenomenon described in this article should be useful in further studies of patients with malnutrition.