thromboplastin and Liver-Failure

We aimed at evaluating the performance of a new prothrombin time (PT) reagent (STA-NeoPTimal) with two other PT reagents (STA-Neoplastine R and STA-Neoplastine CI Plus) and the reference PT reagent used in our laboratory (ReadiPlasTin).. Evaluation consisted in intra- and interassay precision assessment, determination of sensitivity to unfractionated heparin (UFH) or enoxaparin in spiked samples and to direct oral anticoagulants (DOACs) in patients (n = 43). Method comparison of the 4 PT reagents, factor II, V, VII and X assays was tested on normal (n = 20) and abnormal samples: VKA (n = 47), preoperative (n = 23), liver failure (n = 12) and burned patients (n = 37).. Analytical performance met manufacturers' criteria for all reagents. All PT reagents gave correlation coefficients >0.8 and even >0.9 in many situations. In some VKA samples, differences ≥ 0.5 INR units were found in samples within and above therapeutic ranges. For burned patients, PT correlations were good but with some minimal bias (<5.0%) while factor assays gave very consistent results (R > .8 and mainly >0.9). As expected, poor responsiveness of the PT to DOAC concentrations was observed with all four assays.. The STA-NeoPTimal showed comparable performance to ReadiPlasTin, making it suitable for VKA control, detection of factors II, V, VII, X deficiency and assessment of liver disease coagulopathy. However, for patients receiving VKA, some significant differences were observed. We confirmed the inability of the PT assay to detect residual DOAC concentrations. Finally, burned patients results showed that recombinant thromboplastins were less sensitive to factor deficiencies in comparison to extraction thromboplastins.

Topics: Blood Coagulation; Blood Coagulation Tests; Humans; International Normalized Ratio; Liver Failure; Preoperative Period; Prothrombin Time; Reproducibility of Results; Sensitivity and Specificity; Thromboplastin; Vitamin K

The coagulation "cascade" model accurately represents the mechanisms of the prothrombin time and activated partial thromboplastin time tests. However, these tests and the "cascade" model do not accurately reflect the risk of hemorrhage or thrombosis in vivo. In hepatic insufficiency, a balanced reduction in the levels of most of pro- and anticoagulant proteins produced in the liver does not impair thrombin generation until levels are quite low. However, the ability of the coagulation system to tolerate or recover from an insult is markedly impaired in liver disease. This allows the coagulation system to be more easily tipped into a state favoring either hemorrhage or thrombosis.

Topics: Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Platelets; Hemorrhage; Hemostasis; Humans; Liver Cirrhosis; Liver Failure; Models, Biological; Prothrombin Time; Thrombin; Thromboplastin; Thrombosis

International Normalized Ratio (INR), which standardizes prothrombin time (PT) during oral anticoagulation, has been extended to standardize PT in liver diseases and is included in prognostic models such as the Model for End stage Liver Disease (MELD). However, mechanisms of PT prolongation in liver diseases differ from those involved in oral anticoagulation, and the thromboplastin reagents differ in their sensitivities to these 2 mechanisms. Our aim was to determine whether, in the calibration model for thromboplastins proposed by the World Health Organization, the use of plasmas from patients with liver diseases instead of plasmas from patients on oral anticoagulation could lead to a new INR specific for liver diseases (INR "LD"), achieving a real standardization of PT. First, 5 thromboplastins were calibrated against an international reference using 60 plasmas of patients with liver failure and, in a second step, the variation of PT reported as seconds, the ratio of patient PT to normal PT, INR, and INR"LD" was assessed in 34 other patients. MELD scores were calculated with the INR values obtained with the 5 thromboplastins. Only INR"LD" eliminated variability in PT results observed with the different thromboplastins. The discrepancy between MELD scores were up to 4 and 7 points in 52% and 17% of the patients, respectively.. INR "LD" may provide a common international scale of PT reporting in hepatology. Its adoption would be an important step because of the significant impact on MELD score induced by interlaboratory variability in INR determination.

Topics: Adult; Aged; Calibration; Female; Humans; International Normalized Ratio; Liver Failure; Male; Middle Aged; Prothrombin Time; Severity of Illness Index; Thromboplastin; Vitamin K

The use of porcine extracorporeal liver perfusion (PECLP) to provide temporary hepatic support for patients in fulminant hepatic failure has been limited by the fact that individual perfusions can be sustained for only a few hours. Inadequate liver function and/or hemodynamic instability are the major contributing factors for early interruption of PECLP. Recent reports suggest that the choice of single (portal vein only) vs dual (portal vein and hepatic artery) vessel perfusion may influence the duration of perfusion. We hypothesize that PECLP with single vessel perfusion (SVP) is associated with worse liver function and greater hemodynamic instability than PECLP with dual vessel perfusion (DVP).. To eliminate the potentially confounding influences of liver failure and xenograft rejection, liver isografts procured from White-Landrace pig donors were perfused by either SVP or DVP via an extracorporeal circuit established with normal White-Landrace pig recipients. The function of perfused livers was evaluated by measuring production of bile and Factors V and VIII, clearance of ammonia and lactate, and extraction of O(2) at baseline and at 0, 1, 3, 6, 12, and 24 h after initiation of PECLP. The impact of PECLP on recipient hemodynamic status was assessed by monitoring BP, heart rate, urine output, O(2) saturation, etc. Among other parameters evaluated were serum albumin and total protein and hepatic release of IL-1beta and nitric oxide to assess their possible contributions to hemodynamic instability.. DVP and SVP livers cleared ammonia and lactate similarly. Both approaches were associated with progressive hypoalbuminemia and hypoproteinemia. DVP livers produced more bile and Factor V and were associated with less recipient hypotension and IL-1beta and NO release than SVP livers.. Livers with DVP function better than livers with SVP. The duration of PECLP can be limited by recipient hypotension, although this complication is less severe with DVP than with SVP.

Topics: Ammonia; Animals; Bile; Blood Pressure; Diuresis; Extracorporeal Circulation; Factor V; Female; Heart Rate; Hemodynamics; Hepatic Artery; Hypotension; Lactic Acid; Liver; Liver Failure; Oxygen; Oxygen Consumption; Portal Vein; Swine; Thromboplastin

Prothrombin time (PT) is a universal indicator of liver disease severity. However, variability in thromboplastin reagents leads to large interlaboratory differences in PT results. The aim of this study was to determine whether the use of the international normalized ratio (INR) or other modes of expression might achieve PT standardization in patients with liver failure. PT was measured with seven thromboplastin reagents with different sensitivities in plasmas from 27 patients with miscellaneous chronic and acute liver failure and, as a control population, 29 patients on oral anticoagulation therapy. PT was expressed in seconds, ratio, activity percentage, and INR. In patients with liver failure, only activity percentage expression eliminated variability in PT results obtained with the seven thromboplastins while INR, seconds, and ratio values remained significantly different (P < .01). In patients on oral anticoagulant therapy, only INR normalized PT results. We conclude that, in patients with liver failure, INR fails to yield a PT expression independent of the thromboplastin used and only activity percentage expression may provide a common international scale of PT reporting.

Topics: Analysis of Variance; Anticoagulants; Humans; Liver Failure; Liver Failure, Acute; Prothrombin Time; Recombinant Proteins; Reference Values; Reproducibility of Results; Sensitivity and Specificity; Thromboplastin