Thrombin Generation Increasing with Age and Decreasing with Use of Heparin Indicated by Calibrated Automated Thrombogram Conducted in Chinese

Objective Calibrated Automated Thrombogram（CAT） is a test to monitor the generation of thrombin. It can be described by four parameters： lag time, peak thrombin, endogenous thrombin potential （ETP） and time to peak （ttPeak）. This study aims to determine the normal ranges of CAT parameters in Chinese, and evaluate whether thrombin generation is correlated with the concentration of heparin/Iow molecular weight heparin. Methods Plasma from 120 healthy subjects were collected to determine the normal rangea of CAT parameters in Chinese. Normal plasma pool （NPP, n=25） spiked with different concentrations of heparin or enoxaparin were used to detecte CAT parameters. The overall and age specific normal ranges of CAT parameters were calculated using descriptive statistics method with mean＋-2SD. The correlation between CAT parameters and age or concentrations of heparin, enoxaparin were analyzed with linear regression model. Results The normal ranges for lag time, peak thrombin, ETP, ttPeak in the subjects were 3.648＋2.465 min, 367.39＋151.93 nmol/L, 2277＋_1030 nmol/L.min and 6.372＋_4.280 min respectively. Age was linearly correlated with lag time （r=-0.6583, P〈0.0002）, peak thrombin （r=0.4863, P〈0.0002）, ETP （r=0.3608, P〈0.0014） and ttPeak （r=-0.6323, P〈0.0002）. The values of ETP/peak ratio were linearly correlated with concentrations of heparin. Conclusion The normal ranges of four CAT parameters for Chinese were determined. CAT parameters are associated with age. ETP/peak ratio could be used to monitor the process of anticoagulation therapy.

Hemostasis testing in patients with liver dysfunction: Advantages and caveats

Due to concomitant changes in pro-and anti-coagulant mechanisms,patients with liver dysfunction have a“rebalanced hemostasis”,which can easily be tipped toward either a hypo-or a hypercoagulable phenotype.Clinicians are often faced with the question whether patients with chronic liver disease undergoing invasive procedures or surgery and those having active bleeding require correction of the hemostasis abnormalities.Conventional coagulation screening tests,such as the prothrombin time/international normalized ratio and the activated partial thromboplastin time have been demonstrated to have numerous limitations in these patients and do not predict the risk of bleeding prior to high-risk procedures.The introduction of global coagulation assays,such as viscoelastic testing(VET),has been an important step forward in the assessment of the overall hemostasis profile.A growing body of evidence now suggests that the use of VET might be of significant clinical utility to prevent unnecessary infusion of blood products and to improve outcomes in numerous settings.The present review discusses the advantages and caveats of both conventional and global coagulation assays to assess the risk of bleeding in patients with chronic liver disease as well as the current role of transfusion and hemostatic agents to prevent or manage bleeding.

Clinical Considerations of Coagulopathy in Acute Liver Failure

Acute liver failure (ALF) is the rapid onset of severe liver dysfunction, defined by the presence of hepatic encephalop-athy and impaired synthetic function (international normal-ized ratio of≥1.5) in the absence of underlying liver disease. The elevated international normalized ratio value in ALF is often misinterpreted as an increased hemorrhagic tendency, which can lead to inappropriate, prophylactic transfusions of blood products. However, global assessments of coagulop-athy via viscoelastic tests or thrombin generation assay suggest a reestablished hemostatic, or even hypercoagu-lable, status in patients with ALF. Although the current versions of global assays are not perfect, they can provide more nuanced insights into the hemostatic system in ALF than the conventional measures of coagulopathy.

Potential mechanisms of resistance to current antithrombotic strategies in Multiple Myeloma

Multiple Myeloma(MM)is a common haematological malignancy that is associated with a high rate of venous thromboembolism(VTE)with almost 10% of patients suffering thrombosis during their disease course.Recent studies have shown that,despite current thromboprophylaxis strategies,VTE rates in MM remain disappointingly high.The pathophysiology behind this consistently high rate of VTE is likely multifactorial.A number of factors such as anti-thrombin deficiency or raised coagulation Factor VIII levels may confer resistance to heparin in these patients,however,the optimal method of clinically evaluating this is unclear at present,though some groups have attempted its characterisation with thrombin generation testing(TGT).In addition to testing for heparin resistance,TGT in patients with MM has shown markedly varied abnormalities in both endogenous thrombin potential and serum thrombomodulin levels.Apart from these thrombin-mediated processes,other mechanisms potentially contributing to thromboprophylaxis failure include activated protein C resistance,endothelial toxicity secondary to chemotherapy agents,tissue factor abnormalities and the effect of immunoglobulins/“M-proteins”on both the endothelium and on fibrin fibre polymerisation.It thus appears clear that there are a multitude of factors contributing to the prothrombotic milieu seen in MM and further work is necessitated to elucidate which factors may directly affect and inhibit response to anticoagulation and which factors are contributing in a broader fashion to the hypercoagulability phenotype observed in these patients so that effective thromboprophylaxis strategies can be employed.