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PubMed2002

Prothrombin time quality assessment scheme in the Basque Country.

The Basque Country Quality Assessment Scheme on Oral Anticoagulant Treatment (PEEC-CAV) was first launched in 1984. This project combined prothrombin time (PT) quality controls and a new in-house standard reagent called Thromboplastin Bilbao (TBi). Originally, this reagent was of human origin, but in 1994, it was replaced by one derived from rabbit brain following WHO recommendations. Nine hospitals in the area collaborated in carrying out quality controls (a) to assess different systems of PT test performance in the Basque Country and (b) to evaluate TBi response in these controls. Evaluation over the period 1994-1999 yielded an INR coefficient of variation (CV) for the plasmas used in these controls of 8.29+/-4.18% using the laboratories' routine system (reagent and coagulometer), and 9.7+/-2.70% using TBi and the manual technique. These results were similar to those obtained in the CV of PT ratio with human brain thromboplastin from 1984 to 1988 (9.26+/-2.84%).

Animals↗
PubMed2002

A peptide derived from human prothrombin fragment 2 inhibits prothrombinase and angiogenesis.

We constructed the synthetic peptide library representing human prothrombin fragment 2 (F2) sequence and explored the inhibitory sequence for prothrombinase, which was reconstituted in vitro by adding factor Xa, factor Va, and calcium into phospholipids. The nonapeptide NSAVLQVEN (NSA9) suppressed prothrombinase reconstituted not only on phospholipid vesicles but also on the bovine capillary endothelial (BCE) cell surface. Kinetic analyses demonstrated that NSA9 is a mixed-type inhibitor of Xa. Furthermore, the nonapeptide inhibited the proliferation of BCE cells and also suppressed angiogenesis in chicken embryos. The inhibitory activities of NSA9 were abrogated by pre-incubation with anti-F2 monoclonal antibody, 4E7. These data demonstrate that anti-angiogenic activity of F2 may be related to its ability to inhibit prothrombinase.

Amino Acid Sequence↗
PubMed1997

Prothrombin activation fragment (F1.2) is increased in pregnant patients with antiphospholipid antibodies.

Recurrent fetal wastage has been attributed to thrombosis in the antiphospholipid antibody syndrome (APAS); however, this has not been proven. Assays of coagulation activation fragments which may provide evidence for a role for thrombosis, have not been previously reported in this setting. We therefore investigated whether F1.2 levels are altered in APAS pregnancies. F1.2 levels were performed on plasmas obtained from fifty-four APA patients with a history of persistent elevation of antiphospholipid antibodies and recurrent abortion who were studied during eighty-three consecutive visits. Results from these patients were compared to a control group of thirty-two healthy pregnant females. F1.2 levels were significantly higher in APAS patients than controls in the second trimester (6.5 nM +/- 4.3 nM vs. 1.2 nM +/- 0.9 nM, p < 0.0001), and in the third trimester of pregnancy (8.6 nM +/- 2.5 nM vs. 3.7 nM +/- 2.0 nM, p < 0.0001). The F1.2 levels in the APA group returned to baseline soon after delivery. No correlation was observed between F1.2 and APA values. This study shows that pregnant patients with a history of recurrent abortions and APA have significantly increased activation of prothrombin compared to healthy pregnant females. These data indicate that the potential value of activations peptide assays such as F1.2 in this setting should be tested in prospective clinical trials.

Adult↗
PubMed1997

Effect of bezafibrate on hypercoagulability assessed by fluorogenic prothrombin time in hyperlipidemic patients with non-insulin-dependent diabetes mellitus.

We investigated the usefulness of the fluorogenic prothrombin time (FPT) for detection of hypercoagulability and its association with hyperlipidemia in 19 patients with non-insulin-dependent diabetes mellitus (NIDDM) and 10 healthy control subjects, compared with plasma levels of fibrinogen, plasminogen activator inhibitor-1 (PAI-1) and D-dimer. We also evaluated the effect of bezafibrate on hypercoagulability in 10 hyperlipidemic NIDDM patients. The plasma levels of FPT and fibrinogen were significantly higher in hyperlipidemic NIDDM patients than in normolipidemic NIDDM patients and controls. Plasma levels of PAI-1 and D-dimer were significantly higher in normolipidemic and hyperlipidemic NIDDM patients compared with controls. The FPT was correlated with the HbA1c, the body mass index, and levels of total cholesterol, fibrinogen and PAI-1. Six-months therapy with bezafibrate reduced the levels of FPT, triglycerides and basal insulin, but did not alter levels of fibrinogen, PAI-1 and D-dimer. Our results showed that the FPT was useful for detection of hypercoagulability and evaluation of the effect of drugs. The increased FPT in patients with NIDDM suggested that hypercoagulability was present in association with hyperlipidemia.

Aged↗
PubMed1997

Measurement of factor VII and of activated factor VII in healthy individuals and in prothrombin complex concentrates.

We established reference ranges for factor VII clotting activity (FVII:C), factor VII amidolytic activity (FVII:AM), and activated factor VII (FVIIa) in 102 healthy individuals. The reference ranges were 65-160 U/100 ml, 70-165 U/100 ml, and 30-170 mU/ml, respectively (2.5 and 97.5 percentiles). Freezing and thawing of the plasma samples had no influence on the assay results. Due to the small sample size, the results were not influenced by gender, age, smoking habits, and oral contraceptive use. The plasma levels of FVII:C, FVII:AM, and FVIIa were significantly correlated with each other. The significant correlation between FVIIa and FVII:AM indicates that FVIIa is not completely independent of circulating FVII mass. There was also a significant, though weak, correlation between FVIIa and FVII:C/FVII:AM ratios. Sixteen batches of prothrombin complex concentrates (PCC) from 3 manufacturers were also analysed. FVIIa could be detected in all preparations, with considerable variations from batch to batch. In contrast to the results obtained in plasma from normal individuals, there was a close correlation between FVIIa and FVII:C/FVII:AM ratios. The preparations could be characterized by their FVII and FVIIa potencies and by their FVII:C/FVII:AM ratios. In PCC, FVII:C was very strongly correlated with FVIIa, whereas no significant correlation was observed between FVII:AM and FVII:C and between FVII:AM and FVIIa, respectively. These results demonstrate that the FVII:C assay used is sensitive for detecting FVIIa. Thus, we cannot confirm that FVIIa sensitivity of one-stage clotting assays for FVII:C is low when a rabbit thromboplastin and a non-adsorbed FVII-deficient plasma is used.

Adolescent↗
PubMed1997

Evaluation of bedside prothrombin time and activated partial thromboplastin time measurement by coagulation analyzer CoaguCheck Plus in various clinical settings.

In the present study CoaguCheck Plus (CCP), a coagulation test system using whole blood, was evaluated with respect to its comparability with widely distributed conventional routine coagulation assays. A correlation of r = 0.997 (p < 0.0001) was found between INR of CCP-prothrombin time (CCP-PT) and Thrombotest (KC-1 analyzer) in patients on oral anticoagulant therapy. A correlation of r = 0.899 (p < 0.001) between CCP-aPTT and Actin ES aPTT (STA analyzer) was found in heparinized patients. Impaired hepatic hepatic coagulation factor synthesis in liver cirrhosis patients was detected by CCP-PT with a sensitivity of 0.75 and by Normotest (STA analyzer) with a sensitivity of 0.92. Those patients with normal CCP-PT values and liver disease had, only mild reductions (> 30% of normals) in coagulation factors II, V, VII or X. CCP-aPTT was also performed in patients with a deficiency in the so called endogenous coagulation factors VIII, IX, XI and XII. CCP-aPTT showed a sensitivity similar to that of Actin FS aPTT in the detection even of mild deficiencies in factors VIII, IX and XII; factor XI deficiency was however detected only in patients with severe (< 12% of normals) disease; lupus anticoagulants were detected with a high sensitivity.

Blood Coagulation Tests↗
PubMed1998

Prothrombin fragment 1 + 2 measures treatment effect in patients with antiphospholipid syndrome.

Antiphospholipid syndrome (APS) is characterized by recurrent thrombosis. The anticoagulant management of APS thrombosis remains controversial. Few reports on markers of in vivo activation of coagulation have been reported. To determine whether plasma levels of prothrombin fragment 1 + 2 (F1 +2) correlate with thrombotic risk and treatment effect in patients with APS, plasma F1 + 2 levels were followed in 57 patients with this syndrome for more than 2 years. Clinical findings were also observed in these patients. Plasma levels of F1 + 2 in patients with APS were significantly higher when compared with control subjects (p<.05). These results suggest patients with APS are in a hypercoagulable state. Plasma levels of F1 + 2 significantly decreased following treatment with either aspirin, or aspirin plus warfarin (p<.05 and p<.01, respectively). Recurrent thromboses or spontaneous abortions occurred in all eight patients whose plasma levels of F1 + 2 remained higher than 1 nmol/l after treatment with either aspirin alone or no anticoagulants. These patients were subsequently treated with warfarin as well as aspirin, and plasma levels of F1 + 2 decreased to less than 1 nmol/l, with no additional thrombotic events over the remainder of the 2-year follow-up. No fatal bleeding was observed in treated patients. Our results suggest plasma levels of F1 + 2 are useful indicators of successful treatment. It is also suggested that warfarin plus mini-dose aspirin therapy is effective for patients with APS to protect from recurrent thromboses without harmful side effects. Further, prospective cohort studies are needed to substantiate these associations.

Antiphospholipid Syndrome↗
PubMed1999

Two multiplex PCR-based DNA assays for the thrombosis risk factors prothrombin G20210A and coagulation factor V G1691A polymorphisms.

Two coagulation factor polymorphisms, G1691A in the factor V gene and G20210A in the prothrombin gene, are currently the most common known genetic risk factors for venous thrombosis in caucasian populations. Experimental conditions that permit simultaneous determination of these two polymorphisms using PCR-based DNA assays with the restriction enzyme, Hind III, were developed. Moreover, novel PCR-based DNA assays were established using primers that introduce specific cleavage sequences which then permit the simultaneous determination of these polymorphisms using Sac I restriction digestion analysis. Multiplex PCR-based DNA assays were used to analyze a family with a history of venous thrombosis in which these polymorphisms were both present and the results confirm the interesting variability of these genetic risk factors among family members who are symptomatic.

Biological Assay↗
PubMed1999

Thrombogenicity of prothrombin complex concentrates.

Thrombogenicity of factor IX complex or prothrombin complex concentrates (PCC) is a well-acknowledged problem. The exact incidence is unknown but has decreased with the improvement of the quality of coagulation factor concentrates and a more judicious use of these products. The clinical spectrum of thrombogenicity ranges from superficial thrombophlebitis, deep-vein thrombosis and pulmonary embolism, and arterial thrombosis to disseminated intravascular coagulation. Several risk factors have been identified: (a) predisposing clinical factors (underlying disease and clinical condition), (b) therapy factors (dosing, concomitant therapy and drug interactions), and (c) quality of the PCC used. It is generally assumed that the risk of thromboembolic adverse effects is greater in patients with acquired disorders of hemostasis than in patients with inherited coagulation factor deficiencies. In hemophilia B, clinical conditions with an increased risk include large muscle hematomas, immobilization, surgery (especially orthopedic surgery), and liver disease. In acquired disorders of hemostasis, a prethrombotic state can be assumed in all patients where an indication for PCC concentrates is considered. Liver disease and/ or antithrombin deficiency are considered as major risk factors. Therapy factors with an increased risk include large, repetitive doses of PCC. It is assumed that heparin and, in the case of antithrombin deficiency, antithrombin substitution decrease the incidence of thromboembolic adverse effects. Heparin neutralisation with protamine and aprotinin therapy may be additional risk factors. The declining incidence and the recent cluster of fatal thromboembolic adverse events in Germany with one brand of PCC is strong evidence for the crucial role of the quality of PCC in the occurrence of thromboembolic adverse effects.

Blood Coagulation Factors↗
PubMed1999

Indications for prothrombin complex concentrates in massive transfusions.

A major hemorrhagic insult may require massive transfusions to maintain oxygen transport and hemostasis. Thus an adequate transfusion budget must consider losses, patient's blood volume, critical levels of laboratory parameters, replacement rates of coagulation factors from the extravascular space, and the efficacy of blood products. The substitution of large quantities of blood or red cell concentrates can induce and aggravate a complex haemostatic disorder. Some patients develop generalized microvascular bleeding. A transfusion regimen is described, which in our hands can reduce complications of massive transfusion. For hemostatic support, platelet concentrates and fresh frozen plasma are the treatment of choice. Localization and persistence of bleeding, hepatic disease, and vitamin K deficiency due to medication or intestinal malabsorption may require the supplementary use of prothrombin complex concentrates. Furthermore, antithrombin and fibrinogen concentrates may be indispensable.

Adult↗
PubMed2001

The need for routine pre-operative coagulation screening tests (prothrombin time PT/partial thromboplastin time PTT) for healthy children undergoing elective tonsillectomy and/or adenoidectomy.

In some medical centers, the routine pre-operative evaluation of healthy children undergoing elective tonsillectomy and/or adenoidectomy (T and A) includes coagulation screening tests (PT, prothrombin Time; PTT, partial thromboplastin time; and INR, international normalized ratio). In this retrospective study, we determined whether there is a positive correlation between prolonged PT/PTT/INR tests in healthy children, with no prior medical history of coagulation problems, and bleeding during surgery and/or bleeding in the month following surgery. We reviewed the records of 416 elective T and A surgeries performed at the Soroka University Medical Center in Beer-Sheva, Israel, over the course of 1999. One hundred and twenty-one (29.1%) patients had preoperative prolonged PT values but only four (3.3%) of these patients experienced light bleeding during surgery. Seven (5.8%) of the 121 patients with prolonged PT tests experienced bleeding episodes during the 1st month subsequent to the surgery. Of the 65 (15.6%) patients who had prolonged pre-operative INR values, only three (4.6%) experienced light bleeding during surgery. Two (3.1%) patients with prolonged INR values experienced light bleeding during the 1st month subsequent to surgery. Sixty-one (14.7%) patients had prolonged first preoperative PTT values, only five of whom (8.2%) experienced light bleeding during surgery. Two (3.3%) of the 61 with prolonged PTT values experienced light bleeding during the 1st month subsequent to surgery. We therefore concluded that pre-operative coagulation screening tests provide low sensitivity and low bleeding predictive value. As such, routine coagulation tests before T &A are not indicated unless a medical history of bleeding tendency is suspected.

Adenoidectomy↗
PubMed1998

Picosecond tryptophan fluorescence of membrane-bound prothrombin fragment 1.

The wavelength-dependent tryptophan (Trp) fluorescence decays of Ca-prothrombin fragment 1 (Ca-BF1), which contains three tryptophan residues, in the presence of pure phosphatidylcholine (PC) small unilamellar vesicles (SUV) and PC-SUV containing either 25% phosphatidyl-l-serine (PS), and 25% or 40% phosphatidylglycerol (PG) are characterized, using fluorescence lifetime distribution, conventional multiexponential, and global analysis. In analogy to previous investigations on apo- and Ca-BF1 (M. Hof, G.R. Fleming, V. Fidler, Proteins Struct. Func. Genet. 24 (1996) 485-494), the analysis resulted in a five exponential decay model in all investigated systems, where the five fluorescence lifetimes (e.g. 0. 04+/-0.02 ns (component A), 0.24+/-0.02 ns (B), 0.66+/-0.03 ns (C), 2.4+/-0.3 ns (D), and 5.4+/-0.4 ns (E) for Ca-BF1 in the presence of PC-SUV) are wavelength-independent. The fluorescence lifetimes and the corresponding amplitudes of the 'Gla-Trp' (components D and E) and of the two 'kringle-Trp' (components B, C, and D) remain unchanged when bound to the PS-containing vesicles. Saturation binding to PG-containing membranes leads to a prolongation of the Gla component E from 5.3 in solution to 7.5 ns, indicating a change in the Gla-domain conformation. The results represent the first experimental evidence of a lipid-specific conformational change in the N-terminal 'Gla domain' of a vitamin K-dependent protein.

Animals↗
PubMed1999

Correction of both prothrombin time and primary haemostasis by recombinant factor VII during therapeutic alcohol injection of hepatocellular cancer in liver cirrhosis.

We evaluated the efficacy of recombinant factor VII to correct impaired haemostasis in a patient with liver cirrhosis requiring an invasive procedure. A test intravenous bolus of 80 microg/kg of recombinant factor VII was given to a Jehovah's Witness, with a solitary 4.4-cm hepatocellular carcinoma and underlying hepatitis C virus cirrhosis, in an attempt to correct his haemostatic disorders and safely inject the tumour with alcohol. An extensive portal block had precluded consideration of liver transplantation. Haemostasis was evaluated by clotting assays, bleeding time and thromboelastography 10 min before and 10 min and 1, 2, 4, 8 and 24 h after factor VII infusion. Parameters of both coagulation (prothrombin time) and platelet function (bleeding time and the alpha and ma parameters of thrombelastography) were improved 10 min after factor VII infusion; improvements lasted 4 to 8 h or more. Platelet count did not change and there was no evidence of disseminated intravascular coagulation. The improvements in haemostatic parameters correlated significantly with the increases in factor VII plasma concentrations (p<0.04). Factor VII clearance was 25.1 U/h/kg and its half-life was 5.8 h. The same dose of recombinant factor VII was given to the patient 1 week later, just before the alcohol injections. The patient had no subsequent bleeding or other complication, with no change in haemoglobin levels over 24 h. Thus, recombinant factor VII represents a therapeutic advance, as it can correct fully both coagulation and platelet function defects in cirrhosis and allow invasive procedures to be performed safely.

Carcinoma, Hepatocellular↗
PubMed1997

Value of preoperative prothrombin time/partial thromboplastin time as a predictor of postoperative hemorrhage in pediatric patients undergoing tonsillectomy.

OBJECTIVE: Hemorrhage after tonsillectomy is a potentially lethal complication. Preoperative assessment consisting of prothrombin time (PT) and activated partial thromboplastin time (PTT) has been used to identify patients at risk for hemorrhage after tonsillectomy and adenoidectomy. We sought to assess the value of PT/PTT screening as a predictor of posttonsillectomy hemorrhage. DESIGN: A retrospective chart review was carried out with a minimum of 1 month follow-up. SETTING: Tertiary academic referral center. PATIENTS: Between January 1992 and June 1995, 382 patients undergoing tonsillectomy were examined; 339 patients with a minimum of 1 month follow-up were reviewed for this study. MAIN OUTCOME MEASURE: Normal and prolonged PT/PTT values were examined. Bleeding in the intraoperative, immediate postoperative, and delayed phases of healing was examined. RESULTS: Two-hundred and twenty-two patients had normal PT/PTT, 39 had prolonged PT/PTT, and 78 had no preoperative studies performed. Bleeding occurred in 2.7%, 2.6%, and 3.3%, respectively, of patients. Eight patients had positive family histories of bleeding tendencies. One patient (12.5%) with a normal PT/PTT experienced a delayed posttonsillectomy bleed. Of 39 patients with abnormal coagulation studies, 30 were borderline elevations with no repeat studies done; one patient experienced postoperative hemorrhage. Nine abnormal results were repeated; three returned to normal, three remained prolonged but underwent tonsillectomy with no intervention, and three received hematology consultations. One patient had lupus anticoagulant, one had Hageman Factor deficiency, and one was cleared for surgery with no diagnosis. All patients underwent tonsillectomy with no episodes of postoperative bleeding. CONCLUSIONS: Preoperative PT/PTT provides no additional information than does a bleeding history for the general pediatric population undergoing tonsillectomy. This should only be done in selective cases where warranted by history.

Child↗
PubMed1993

Are baseline prothrombin time/partial thromboplastin time values necessary before instituting anticoagulation?

STUDY OBJECTIVES: To determine whether baseline prothrombin time (PT) or partial thromboplastin time (PTT) values provide information that is useful to the clinician before initiating anticoagulation and whether emergency physicians elicit historical information about bleeding disorders before beginning anticoagulant therapy. DESIGN: A three-year retrospective review of the records of 199 patients admitted through the ED with an ICD-9-CM diagnosis of deep-vein thrombosis or pulmonary embolus using a predesigned study sheet that included historical questions, baseline PT and PTT values, treatment given, timing of treatment, and underlying medical problems. SETTING: University-affiliated tertiary-care hospital. MEASUREMENTS AND MAIN RESULTS: Deep-vein thrombosis was the primary diagnosis in 75% of patients. Pertinent historical items were not documented in 92% to 100% of patients. Baseline PT and PTT values were obtained in 94% of patients. An elevated baseline PT was found in 26 patients, all of whom were taking warfarin. An elevated baseline PTT was found in 21 patients. These results were attributed to laboratory error (one), warfarin use (nine), heparin therapy before baseline tests (five), anticardiolipin antibodies (five, one of whom was on warfarin therapy), and unknown causes (three). Heparin therapy was not altered for any patient. CONCLUSION: Emergency physicians rarely document pertinent questions about bleeding disorders before initiating anticoagulation therapy. Baseline PT and PTT values are almost routinely obtained despite the fact that they do not alter therapy or serve as sensitive or specific screening tests. Routine baseline PT and PTT values are rarely needed before initiating anticoagulation. Eliminating such routine testing would result in significant cost savings.

Adolescent↗
PubMed2000

[G20210A transition in the prothrombin gene and venous thromboembolic disease].

INTRODUCTION: Genetic predisposition to venous thrombosis can be due to coagulation inhibitor deficiencies (antithrombin, protein C or protein S) or to activated protein C resistance resulting from factor V Leiden mutation (FV Leiden). Poort et al. recently identified a new polymorphism in the 3'-untranslated region of the prothrombin gene, the G20210A transition (FII G20210A), which was found to be associated with an increased risk of venous thrombosis. EXEGESIS: The prevalence of the A allele is approximately 1 to 4% in the general population, and 5 to 7% in patients with venous thrombosis. Heterozygous carriers have a three to five times increased risk of thrombosis. The diagnosis is based on a polymerase chain reaction technique and restriction enzyme digestion from genomic DNA. Recent studies aim to determine the relative risk of thrombosis and the clinical features which are associated with the mutation (age of first thrombosis, recurrence). The thrombotic risk seems to be higher when FII G20210A transition is associated with the FV Leiden mutation. CONCLUSION: The presence of heterozygous FII G20210A transition does not modify the management of acute thrombotic events but can lead to an increase in the duration of the anticoagulant treatment. When such a genetic abnormality is identified, thorough information of the patient is needed, including on the prophylactic heparin in high-risk situations and caution on the prescription of oral contraceptives containing estrogens.

Factor V↗
PubMed2002

Elevated prothrombin is a risk factor for cerebral arterial ischemia in young adults.

The prevalence of elevated prothrombin (PT) in the absence of the G20210A mutation has not been studied in patients with cerebral ischemia. We carried out a case-control study of PT G20210A and PT activity in 49 adult patients aged 45 years or less, with TIA or ischemic stroke without cardiac embolism or large vessel disease, and 87 controls from a group of blood donors. Five patients were heterozygous for PT 20210A (OR=2.3, 95% CI: 0.6-8.0). Even after exclusion of individuals with the PT gene variant, the PT activity was significantly higher in patients than in controls (1.11 vs. 0.97, P=0.0003). The relative risk of cerebral ischemia in patients within the fourth quartile of PT activity (1.10 U/ml or higher), was 3.2 fold (95% CI: 1.03-9.96), than in patients whose level of PT activity was in the second or third quartile. We conclude that, although PT 20210A may be a weak risk factor for TIA and ischemic stroke in young patients, increased PT activity, which is more frequent than the mutation, appears to be more strongly related to cerebral ischemia.

Adolescent↗
PubMed2000

The role of des-gamma-carboxy prothrombin levels in hepatocellular carcinoma and liver tissues.

We aimed to clarify the clinical significance of des-gamma-carboxy prothrombin (DCP) levels in both hepatocellular carcinoma (HCC) and liver tissues with a special reference to the relationship between DCP level in non-cancerous parts of the liver and the multicentric occurrence of HCC. Twenty-eight patients with HCC, who underwent hepatectomy, were studied. Surgical specimens were obtained from both HCC and non-cancerous liver of each patient. After the preparation of the liver tissues, including tissues with HCC, the DCP levels both in HCC and non-cancerous liver tissue were measured using an electro-chemiluminescence immunoassay. The correlation was investigated between DCP levels and other clinicopathological factors. The DCP level of HCC ranged from 55 to 77735 U/0.1 g tissue weight, with a median of 2801, while the DCP level of non-cancerous parts of the liver ranged from 24 to 721 U/0.1 g tissue weight, with a median of 86. The DCP level in the liver tissue in patients having a multicentric occurrence of HCC was significantly higher than that in patients without multicentric occurrence of HCC. The logarithm of the plasma DCP level correlated with that of the DCP level in HCC (correlation coefficient =0.46; P<0.05). No significant correlation was found between the DCP level in HCC and other clinicopathological parameters. The DCP level in non-cancerous parts of the liver with simultaneous multicentric occurrence of HCC was significantly higher than that in the liver without multicentric HCC. Furthermore, the DCP level in non-cancerous parts of the liver was one of the most important predictable factors of the multicentric occurrence of HCCs among various clinicopathological factors. Therefore, the DCP level may have an important role in hepatocarcinogenesis.

Aged↗