Coagulation disorders in patients with cirrhosis and severe sepsis (original) (raw)
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Coagulation parameters and major bleeding in critically ill patients with cirrhosis
Hepatology (Baltimore, Md.), 2016
Background and rationale Disturbances of coagulation and hemostasis are common in patients with liver cirrhosis. The typical laboratory pattern mimics disseminated intravascular coagulation (DIC). Aim of this study was to assess the impact of routine coagulation parameters in critically ill cirrhotic patients with regards to new onset of major bleeding and outcome. Methods A total of 1493 critically ill patients were studied prospectively. Routine coagulation parameters were assessed and the DIC score was calculated based on platelets (PLT), fibrinogen, d-dimer, and prothrombin index (PI). New onset of major bleeding during the stay at the ICU and mortality were assessed. Patients were followed for 1 year. Main results Two hundred eleven patients of the cohort had liver cirrhosis. PLT, fibrinogen, PI, activated partial thromboplastin time (aPTT) and d-dimer as well as the DIC score differed significantly between patients with and without cirrhosis (p<0.001 for all). Moreover, fib...
An Imbalance of Pro- vs Anti-Coagulation Factors in Plasma From Patients With Cirrhosis
Gastroenterology, 2009
BACKGROUND & AIMS: Patients with cirrhosis have an increased tendency to develop thromboses despite the longer coagulation times of their plasma, compared with that of healthy individuals. We investigated whether plasma from cirrhotic patients has an imbalance of provs anti-coagulation factors. METHODS: We analyzed blood samples from 134 cirrhotic patients and 131 healthy subjects (controls) for levels of pro-and anticoagulants and for thrombin generation in the presence or absence of thrombomodulin (the main physiologic activator of the protein C anticoagulant pathway). RESULTS: The median ratio of thrombin generation (with/without thrombomodulin) was higher in patients (0.80; range, 0.51-1.06) than controls (0.66; range, 0.17-0.95), indicating that cirrhotic patients are resistant to the action of thrombomodulin. This resistance resulted in greater hypercoagulability of plasma from patients of Child-Pugh class C than of class A or B. The hypercoagulability of plasma from patients of Child-Pugh class C (0.86; range, 0.70-1.06) was slightly greater than that observed under the same conditions in patients with congenital protein C deficiency (0.76; range, 0.60-0.93). Levels of factor VIII, a potent pro-coagulant involved in thrombin generation, increased progressively with Child-Pugh score (from Child-Pugh class A to C). Levels of protein C, one of the most potent naturally occurring anti-coagulants, showed the opposite trend. CONCLUSIONS: The hypercoagulability of plasma from patients with cirrhosis appears to result from increased levels of factor VIII and decreased levels of protein C-typical features of patients with cirrhosis. These findings might explain the risk for venous thromboembolism in patients with chronic liver disease.
Gastroenterology, 1995
Background & Aims: Hyperfibrinolysis may complicate the clinical course of liver cirrhosis. The aim of this study was to evaluate if, in cirrhosis, hyperfibrinolysis is primary or secondary to intravascular clotting activation and if endotoxemia is associated with activation of clotting and/or the fibrinolytic system. Methods: Clotting, fibrinolytic indexes, and endotoxemia were studied in 41 cirrhotic patients and 20 healthy subjects. Results: Twenty-seven cirrhotic patients (66%) had high plasma levels of prothrombin fragment F1+2, a marker ofthrombin generation. Nineteen patients had elevated values of D-dimer, a marker of fibrinolysis in vivo. All patients with high values of D-dimer also had high values of prothrombin fragment F1+2. Endotoxemia was elevated in patients with severe liver failure and significantly correlated to prothrombin fragment F1+2. Thirty patients were treated for 7 days either with standard therapy (n = 15) or with standard therapy plus nonabsorbable antibiotics (n --15). Although standard therapy did not significantly change laboratory indexes, a significant reduction of endotoxemia, prothrombin fragment F1+2, and D-dimer was found in those patients who received the combined treatment. Conclusions: This study shows that, in cirrhotic patients, hyperfibrinolysis is not a primary phenomenon but occurs as a consequence of clotting activation and that endotoxemia might play a pathophysiological role.
Coagulation profile in patients with chronic liver disease
International Journal of Medical Science and Public Health, 2019
Background: Chronic liver disease (CLD) is defined as a process of slow and continuous destruction and regeneration of the hepatic parenchyma giving rise to fibrosis and cirrhosis. When it has markedly progressed, it may present with clinical bleeding due to reduction in levels of procoagulant factors, barring some like factor VIII and von Willebrand factor, which are elevated. It is essential to observe that reduced levels of the procoagulants are accompanied by decrease in levels of anticoagulants such as antithrombin and protein C. Under normal conditions, the coagulation machinery is balanced, but the phenomenon of the simultaneous reduction of procoagulants as well as anticoagulants in patients with CLD has been an unsolved puzzle since long. Objective: This study was undertaken to study the relevance and significance of first-line coagulation tests (prothrombin time [PT] and activated partial thromboplastin time [aPTT]) in relation to bleeding manifestations in patients with CLD, to classify the cases of CLD enrolled on the basis of etiology, to study the platelet count, PT, and aPTT values of the cases, and to calculate the Child-Pugh (CP) and model for end-stage liver disease (MELD) scores for all the patients and stratify them accordingly. Materials and Methods: It was a prospective observational study including 40 patients known to be diagnosed with CLD. CP score and MELD were calculated for all. Values of coagulation parameters were compared in patients with and without cirrhosis, in patients belonging to different CP classes, those with low and high MELD scores, and patients with or without upper gastrointestinal (UGI) bleed. Results: Means of PT and aPTT were compared in patients with and without cirrhosis where it was found that there was no statistically significant prolongation of PT or aPTT in patients with cirrhosis compared to those without. We also studied the values of PT and aPTT through increasing grades of CP score and found statistically significant difference between values of PT between those belonging to Class A versus Class C. It was observed that the difference of the mean of PT of the two groups (with MELD <15 and above 15) is statistically significant, whereas it is not true in case of aPTT. Conclusions: The study showed no significant alterations overall in patients with CLD except those in advanced CP classes and those with high MELD scores. They were not significant in patients presenting with UGI bleed, a common manifestation in cirrhotic patients, although those constituted a very small part of the study group. These indices alone are insufficient to include as part of their prognostic and clinical work up to predict bleeding.
Evaluation of coagulation abnormalities in acute liver failure
Journal of Hepatology, 2012
Background & Aims: In acute liver failure (ALF), prothrombin time (PT) and its derivative prothrombin time ratio (PTR) are elevated, and are considered predictors of increased bleeding risk. We aimed at determining whether increased PT/PTR reflects the haemostatic potential and bleeding risk in ALF patients. Methods: Twenty consecutive ALF patients were recruited. Samples were analysed on admission for standard laboratory clotting tests (e.g. PT), thromboelastography (TEG), individual pro and anticoagulant factors and thrombin generation (TG) kinetics with and without Protac Ò , a snake venom protein C activator, and microparticle assay. TG was also measured in 20 age and sex matched healthy volunteers. Results: PT was significantly raised (50.7 s ± 7.2, p = 0.0001) but did not correlate with TEG parameters. TEG tracings were consistent with a hypocoagulable state in 20%, normal in 45%, and hypercoagulable in 35% of the patients. There was a concomitant and proportional reduction in plasma levels of both procoagulants and natural anticoagulant proteins, in conjunction with a significant elevation in plasma levels of factors-VIII (FVIII) and Von Willebrand factor, and microparticles, culminating in an overall efficient, albeit reduced, thrombin generation capacity in comparison with healthy individuals. A heparin-like effect (HLE) was also noted in most patients. No significant clinical bleeding complications occurred and no blood transfusions were required. Conclusions: In ALF, despite grossly deranged PT in all patients, estimation of bleeding risk suggests that the coagulation disturbance in ALF patients is complex and heterogeneous for which an individualised approach is required. Ó
Blood Coagulation & Fibrinolysis, 2000
Patients with liver cirrhosis and diminished prothrombin activity (PA) have decreased levels of factor (F)VII coagulation activity (FVII:C) and an increased bleeding tendency. Whether this is also true of cirrhotic patients with normal PA is unknown. This study measured FVII:C levels in such patients and investigated the correlation between altered FVII:C levels and bleeding tendency. Fifteen of 41 patients (37%) had decreased FVII:C levels. Of these, the Child-Pugh score of liver function was A (n = 9), B (n = 5) and C (n = 1), compared to A (n = 25) and B (n = 1) in patients with normal FVII:C values (χ χ χ χ χ 2 = 8.88, P = 0.012). Bleeding time was significantly prolonged in 9/15 patients (60%) with impaired FVII:C activity, compared to 3/26 (12%) patients with normal FVII:C values (relative risk: 5.2, 95% CI: 1.7-16.6; P = 0.003). In conclusion, liver cirrhosis patients may show impaired FVII:C levels despite normal PA. In those with decreased FVII:C activity, prolonged bleeding time is hypothesized to arise from an alteration in platelet activation due to FVII deficiency and diminished platelet count. Bleeding risk should be evaluated, regardless of platelet count, before these patients are subjected to invasive diagnostic or surgical procedures. Blood Coagul Fibrinolysis 11 (suppl 1):S95-S99
Coagulation abnormalities identified by thromboelastometry in patients with severe sepsis
Blood Coagulation & Fibrinolysis, 2017
The aim of this study was to monitor the development of coagulation abnormalities in patients with severe sepsis using thromboelastometry and to assess whether increased endotoxin activity was associated with a change in coagulation. Data collected on ICU admission, day 2, 3, and 4 were analysed in 61 patients. Thromboelastometry made it possible to identify patients with a normal (group 1), hypercoagulable (group 2), or hypocoagulable (group 3) pattern. The best accuracy of thromboelastometry parameters as potential indices of coagulation abnormalities was yielded by the clot formation time and maximum clot firmness. The mortality rate was low in group 1(16%) and the presence of abnormalities, indicating either a hyper or hypocoagulation pattern, was associated with significantly higher mortality (42 and 39% respectively; P U 0.05). In group 1, baseline endotoxin activity was low [0.22 endotoxin activity units (EAU), 0.15-0.43] and did not change significantly during the observation period. In group 2, baseline endotoxin activity was elevated (0.52 EAU (0.39-0.62)) and remained high on day 2, 3, and 4. In group 3, baseline endotoxin activity was elevated (0.56 EAU (0.28-0.80)) and similarly to group 2, remained high on day 2, 3, and 4. The presence of coagulation disorders indicates a high-risk subpopulation of critically ill patients as reflected in significantly higher mortality rates and increased endotoxin activity.
Advances of knowledge on coagulation disorders in liver cirrhosis and their clinical consequences
2015
Only in the last few years the medical world has ch anged views on hemoragic and thrombotic risk assessment in patients with liver cirrhosis. A more accurate understanding of the mechanisms disturbance of hemostasis, coagulation and fibrinolysis, leads to a better management of these patients, that is desirable to be reflected as a decrease in bleeding episodes and the prevention of thrombotic events. In this mi nireview we intend to present an update of knowledge on the pathophysiology of coagulation and fibrinolysis in liver cirrhosis, the ways of exploring them, their prophylactic and therapeutic consequences. We made a review based on publication in PubMed from 1995 up to now. If in the past the main concern of clinicians on the mentioned issues was the avoidance of haemorrhage, today we know that neither the procoagulant status that cirrhotic patients have, s hould not be underestimated, as they are prone to thrombosis rather than to hemorrhage and the thrombosis risk is increa...
Evidence of normal thrombin generation in cirrhosis despite abnormal conventional coagulation tests
Hepatology, 2005
The role played by coagulation defects in the occurrence of bleeding in cirrhosis is still unclear. This is partly due to the lack of tests that truly reflect the balance of procoagulant and anticoagulant factors in vivo. Conventional coagulation tests such as prothrombin time and activated partial thromboplastin time are inadequate to explore the physiological mechanism regulating thrombin, because they do not allow full activation of the main anticoagulant factor, protein C, whose levels are considerably reduced in cirrhosis. We used a thrombin generation test to investigate the coagulation function in patients with cirrhosis. Thrombin generation measured without thrombomodulin was impaired, which is consistent with the reduced levels of procoagulant factors typically found in cirrhosis. However, when the test was modified by adding thrombomodulin (i.e., the protein C activator operating in vivo), patients generated as much thrombin as controls. Hence, the reduction of procoagulant factors in patients with cirrhosis is compensated by the reduction of anticoagulant factors, thus leaving the coagulation balance unaltered. These findings help clarify the pathophysiology of hemostasis in cirrhosis, suggesting that bleeding is mainly due to the presence of hemodynamic alterations and that conventional coagulation tests are unlikely to reflect the coagulation status of these patients. In conclusion, generation of thrombin is normal in cirrhosis. For a clinical validation of these findings, a prospective clinical trial is warranted where the results of thrombin generation in the presence of thrombomodulin are related to the occurrence of bleeding. (HEPATOLOGY 2005;41:553-558.)