Increased metallopeptidase activity, compromised endothelial integrity and impaired pathogen recognition revealed by transcriptomics in Angiostrongylus vasorum-infected dogs with hypocoagulability and vascular dysfunction

Bleeding during disseminated intravascular coagulation

: Waiting for lab tests results for the calculation of disseminated intravascular coagulation (DIC) scores leads to unwanted delays in diagnosis. The use of rotational thromboelastometry (ROTEM) for this purpose would allow for a more rapid DIC diagnosis at the bedside. The aim of this study was to assess the ability of standard ROTEM parameters and calculated parameters from the ROTEM velocity curve to predict DIC. The retrospective observational study included 97 septic patients. Japanese Association for Acute Medicine score was used for DIC diagnosis and whole-blood ROTEM was performed at study inclusion. Univariate analysis revealed delayed coagulation initiation and propagation and reduced clot firmness and maximum elasticity in DIC patients compared with patients without DIC. To adjust for confounders, multivariable logistic regression models were created and fibrinogen levels, prothrombin time and ROTEM parameters such as maximum clot firmness, maximum clot elasticity (MCE) and total thrombus formation [area under the curve (AUC)] were identified as significant predictors of DIC. According to receiver operating characteristics analysis, MCE and total thrombus formation (AUC) were the most useful ROTEM parameters for DIC prediction. MCE less than 158 (73% sensitive, 80% specific) and AUC less than 6175 mm × 100 (73% sensitive, 76% specific) predicted DIC in septic patients. Both standard and derived ROTEM parameters are useful for rapid DIC prediction in septic patients, allowing the timely identification of patients with higher mortality risk which might benefit from additional therapies. Further studies are needed to assess the clinical relevance of these findings.

Consensus Guidelines for Periprocedural Management of Coagulation Status and Hemostasis Risk in Percutaneous Image-guided Interventions

BackgroundHantaan virus (HTNV), Seoul virus (SEOV) and Puumala virus (PUUV) are major serotypes of the Hantavirus, which can cause hemorrhagic fever with renal syndrome (HFRS). The pathophysiology of HFRS in humans is complex and the determinants associated with mortality, especially the coagulation and fibrinolysis disorders, are still not been fully elucidated. Severe patients usually manifest multiple complications except for acute kidney injury (AKI). The aim of this study was to observe the levels of peripheral blood routine, biochemical and coagulation parameters during the early stage, so as to find independent risk factors closely related to the prognosis, which may provide theoretical basis for targeted treatment and evaluation.MethodsA total of 395 HFRS patients from December 2015 to December 2018 were retrospectively enrolled. According to prognosis, they were divided into a survival group (n = 368) and a death group (n = 27). The peripheral blood routine, biochemical and coagulation parameters were compared between the two groups on admission. The relationship between the parameters mentioned above and prognosis was analyzed, and the dynamic changes of the coagulation and fibrinolysis parameters during the first week after admission were further observed.ResultsIn addition to AKI, liver injury was also common among the enrolled patients. Patients in the death group manifested higher levels of white blood cell counts (WBC) on admission. 27.30% (107/392) of the patients enrolled presented with disseminated intravascular coagulation (DIC) on admission and DIC is more common in the death group; The death patients manifested longer prothrombin time (PT) and activated partial thromboplastin time (APTT), higher D-dimer and fibrinogen degradation product (FDP), and lower levels of platelets (PLT) and fibrinogen (Fib) compared with those of the survival patients. The proportion of D-dimer and FDP abnormalities are higher than PT, APTT and Fib. Prolonged PT, low level of Fib and elevated total bilirubin (TBIL) on admission were considered as independent risk factors for prognosis (death).ConclusionsDetection of PT, Fib and TBIL on admission is necessary, which might be benefit to early predicting prognosis. It is also important to pay attention to the dynamic coagulation disorders and hyperfibrinolysis during the early stage in the severe HFRS patients.

Clotting abnormalities in critically ill COVID-19 patients are inconsistent with overt disseminated intravascular coagulation

Trauma‐induced coagulopathy: The past, present, and future: A comment

A Normal Prothrombin Time, Activated Partial Thromboplastin Time and Fibrinogen Level Do Not Eliminate Disseminated Intravascular Coagulation (DIC) and Bleeding Risk in Patients with Acute Promyelocytic Leukemia

Objective Coagulation dysfunction plays a critical role in the pathogenesis and prognosis of secondary haemophagocytic lymphohistiocytosis (sHLH) in children. This study aims to systematically analyze the coagulation profiles in paediatric sHLH patients, evaluate their prognostic value and provide an effective basis for reducing mortality in children with HLH. Methods A total of 209 paediatric patients with sHLH were enrolled in this study. Coagulation parameters at admission were collected and compared across groups stratified by aetiology, prognosis and presence of disseminated intravascular coagulation (DIC). The dynamic evolution of coagulation parameters was analyzed using LOWESS curve fitting. LASSO regression was applied to screen for potential risk factors for DIC in sHLH patients, followed by univariate and multivariate logistic regression to identify independent risk factors. Similarly, Kaplan–Meier survival analysis along with univariate and multivariate logistic regression models were used to determine independent risk factors associated with prognosis in sHLH patients. Results Paediatric patients with secondary haemophagocytic lymphohistiocytosis (sHLH) presented with significant coagulation abnormalities upon hospital admission, as evidenced by markedly elevated prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (APTT), thrombin time (TT) and D-dimer (DD) levels (all p < 0.01). Those with infection-associated HLH demonstrated significantly prolonged PT (p = 0.009), APTT (p < 0.001) and TT (p = 0.0028), along with significantly lower fibrinogen (FIB) levels (p < 0.001), compared to patients with autoimmune-associated HLH. Compared to survivors, deceased HLH patients had significantly higher PT and INR (p < 0.01), as well as significantly elevated DD (p = 0.014). Significant differences were observed in coagulation parameters – PT, INR, APTT, TT, DD, FIB, thrombin-antithrombin complex (TAT) and tissue-type plasminogen activator-inhibitor complex (t-PAIC) – between HLH patients with and without disseminated intravascular coagulation (DIC) (all p < 0.05), and the dynamic changes in these parameters (particularly PT, FIB and DD) also differed notably between the two groups. Neurological involvement, hyper­ferritinaemia and elevated INR were identified as independent risk factors for DIC, while neurological involvement and the presence of DIC itself were independent predictors of mortality in paediatric patients. Conclusion Coagulation dysfunction serves as a core pathological driver in paediatric sHLH, being especially severe in infection-associated cases. Dynamic monitoring of key coagulation parameters and ferritin levels is crucial for early risk warning and timely intervention. Targeted management of coagulation abnormalities, together with proactive prevention and control of neurological complications, may improve outcomes in paediatric patients.

Fibrinogen concentrate for management of bleeding

Background: Coagulopathy after cardiopulmonary bypass (CPB) may lead to increased morbidity and mortality. Routine conventional coagulation tests are not always suitable to detect rapid changes in patient’s coagulation status. A point-of-care instrument such as ROTEM (rotational thromboelastometry) is a timely and comprehensive method to evaluate hemostasis during cardiac surgery may reduce the need for blood transfusion. Objectives: In this study, ROTEMwas compared to coagulation tests routinely performed during cardiac surgery for postoperative bleeding volume and consumption of blood products. Patients and Methods: Fifty patients undergoing cardiac surgical procedures were enrolled. Blood was obtained before the operation and after CPB weaning. Twenty-five of patients were checked only by traditional blood coagulation test and 25 other patients were checked by ROTEM in addition to routine coagulation tests. The results of these two groups of patients were compared. Results: There was a significant correlation between platelet count (PLT) and fibrinogen level with EXTEM-MCF (r = 0.79, P value: 0.008, r = 0.55, P value: 0.04 respectively). EXTEM-CT was correlated with prothrombin time (PT) (r = 0.56, P value: 0.01) and International normalized Ratio (INR) (r = 0.57, P value: 0.01). There was a significant correlation between PLT count and fibrinogen level with INTEM-MCF (r = 0.69, P value: 0.02, r = 0.71, P value: 0.01, respectively). INTEM-CT was correlated with partial thromboplastin time (PTT) (r = 0.57, P value: 0.02). There was a significant correlation between FIBTEM-MCF and fibrinogen level (r = 0.80, P value: 0.001). HEPTEM was not correlated with any of the coagulation variables. Postoperative consumption of packed blood cell (BPC) was increased in non-ROTEM group in comparison with ROTEM group (645.17 ± 279.16 in Non-ROTEM vs. 387.50 ± 262.88 in ROTEM, P: 0.03) Conclusions: ROTEM can be used to detect postoperative hemostatic changes following cardiac surgery appropriately and can be useful to choose suitable blood products that may reduce the need for blood transfusion, contributing to better patient blood management.

Traitement substitutif symptomatique des CIVD (à lˈexclusion des antithrombine et protéine C)

: Coagulopathy has a high incidence in critically ill patients and is often caused by disseminated intravascular coagulation (DIC). Although the clinical picture of DIC ranges from a prothrombotic state to severe consumption coagulopathy with an increased bleeding tendency, there are no clinical tests that reflect of in-vivo hemostatic profile. Rotational thromboelastometry (ROTEM) may be able to indicate whether a patient has a hypocoagulable or hypercoagulable profile and possibly be able to discriminate patients with and without DIC. The aim of this article was to study the diagnostic ability of thromboelastometry to detect DIC. A predefined subgroup analysis of a clinical trial in critically ill patients with a coagulopathy was done. ROTEM and markers of coagulation and levels of natural anticoagulants were measured in patients with and without DIC. Twenty-three patients were included, 13 fulfilled criteria for overt DIC. Patients with DIC had lower platelet count, lower levels of fibrinogen, factors II, VII and VIII compared with those without DIC. Antithrombin, protein C and S were also reduced in DIC patients. Receiver operator characteristic analyses showed that EXTEM CFT, alpha angle and MCF were capable of discriminating patients with and without DIC. Combination of ROTEM values with protein C or antithrombin further improved discriminatory ability. In patients with DIC, thromboelastometry profiles were more hypocoagulable compared with those without DIC. ROTEM correlates well with ISTH DIC score, diagnostic strength improves when ROTEM values are combined with antithrombin or protein C levels. Thereby, ROTEM may be a useful tool in diagnosing DIC in the critically ill.

We examined 395 patients with disseminated intravascular coagulation (DIC) divided into two groups: non-leukemic and leukemic. In 58% of the patients as a whole, treatment of DIC resulted in complete or partial remission, while exacerbation and death occurred in 31%. The efficacy of DIC treatment in the non-leukemic group was less than that in the leukemic group, indicating that the outcome of DIC depended, in part, on the underlying disease. We examined hemostatic indicators in relation to DIC score: prothrombin time (PT) ratio, FDP, platelet count, and fibrinogen levels were found to be important indicators for the diagnosis of DIC, but not for Pre-DIC. Plasma levels of fibrin-D-dimer, thrombin-antithrombin complex (TAT), and plasmin-plasmin inhibitor complex (PPIC) were significantly increased in pre-DIC. The efficacy of treatment in relation to the DIC score when the treatment was begun showed that greater efficacy was achieved in pre-DIC than in DIC patients. The outcome was poorer with increasing DIC score, suggesting that early diagnosis and early treatment are important. On examining the relationship between outcome and hemostatic indicators, we found that the PT ratio and the levels of antithrombin, plasminogen, PPIC, the PPIC/TAT ratio, and thrombomodulin were related to outcome, suggesting that very high consumption of blood coagulation factors, liver dysfunction, hypofibrinolysis, or organ failure caused a poor outcome. Although the outcome in DIC patients may not depend substantially on plasma levels of TAT and fibrin-D-dimer, we can use these indicators to treat DIC patients at an early stage.

Bleeding is the leading cause of death for patients with acute promyelocytic leukemia (APL). Blood component transfusion to correct coagulopathy is the keystone in reducing bleeding. The benefit of fresh frozen plasma transfusion is unproven. Using laboratory profiles to predict bleeding is important guidance for the determination of transfusion policies in the treatment of APL. For 116 patients of APL, bleeding events were collected and correlated with various hematologic and coagulation parameters, including leukemic cell percentages, white blood cell (WBC) and platelet counts, prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen levels, and disseminated intravascular coagulation (DIC) scores. Overt DIC occurred in 77.6% of patients. Severity of DIC was associated with bone marrow leukemic cell percentages but unrelated to bleeding. Patients with bleeding had significantly higher WBC counts (26.73 ± 6.18 vs. 13.03 ± 3.03 per μL, P = 0.026) and more prolonged PT (4.85 ± 0.70 vs. 2.59 ± 0.28 s, P = 0.002) and APTT (3.98 ± 1.68 vs. 0.96 ± 0.93 s, P = 0.017). Fibrinogen levels, platelet counts, and leukemia cell percentages were not significantly different between bleeding and non-bleeding patients. PT is valuable in prediction of bleeding. Patients with PT ≧ 5 s had a relative risk of 6.14 for bleeding. Seven patients had severe bleeding before initiation of all-trans retinoic acid (ATRA). Patients with APL are susceptible to DIC and subsequent bleeding events. Prompt ATRA administration is crucial in preventing hemorrhagic events. High WBC counts, prolonged PT, and APTT are associated with clinical bleeding in our series. PT is the most accurate parameter in predicting bleeding. Based on these findings, supportive care should be directed toward correction of coagulopathy to prevent bleeding complications and fresh frozen plasma appears to be indicated for coagulopathy associated with APL.

Rotational thromboelastometry (ROTEM), known as point-of-care testing, has been incorporated into various kinds of postsurgical management. However, the utility of ROTEM for rapid diagnosis of sepsis-induced disseminated intravascular coagulation (DIC) has not been investigated. This retrospective study includes 13 sepsis patients who underwent ROTEM in our emergency department in 2013. All patients were divided into two groups on the basis of the presence of DIC diagnosed by the Japanese Association for Acute Medicine (JAAM) DIC score. We evaluated the demographics, clinical characteristics, laboratory data, ROTEM test and outcomes for each patient. The correlations between JAAM DIC score and significantly different parameters by univariate analysis and receiver operating characteristic (ROC) analysis were performed to assess the accuracy of the variables. There were seven and six patients in the DIC group and non-DIC group, respectively. The DIC group showed significantly longer prothrombin times, international normalized ratio of prothrombin time and clotting times (CTs) in the EXTEM test, and higher fibrinogen and fibrin degradation products and D-dimer. The CT in EXTEM test was correlated more with JAAM DIC score (r = 0.798), than the standard coagulation test. These parameters were accurate predictors in the diagnosis of septic DIC, with an AUC of 0.952, and a cut-off value of more than 46.0 s, resulting in a sensitivity of 100.0% and a specificity of 83.3%. CT in the EXTEM test was a single reliable indicator of sepsis-induced DIC diagnosed by the JAAM DIC score, and strongly associated with severity of DIC.