Hepaplastin Test Research Articles

Decreased urinary excretion of thiamine propyl disulfide metabolites in patients with liver disease.

The urinary excretion of 2-hydroxypropyl methyl sulfone (2HPMS) and methyl propyl sulfone (MPS) after oral administration of thiamine propyl disulfide (TPD) was examined in the patients with various liver diseases, in order to investigate the relationship between the liver function and the ability of drug disposition including metabolism. The patients were divided into six groups as follows ; acute hepatitis in convalescent stage (AHconv), acute hepatitis in active stage (AHact), chronic inactive hepatitis (CIH), chronic active hepatitis (CAH), liver cirrhosis in compensated stage (LCcom) and decompensated stage (LCdec). The results obtained from these groups were compared with those of normal subjects. For MPS, only LCdec showed either lesser or delayed excretion in the 0-48 h urine compared to normal subjects. In other liver diseases the excretion pattern of MPS was similar with that of normal subjects, and the amount excreted in the 0-48 h urine was not significantly different. In urinary excretion of 2HPMS, the amount excreted in the 0-48 h urine decreased in the order CIH > AHconv > AHact > CAH > LCcom > LCdec, and the decrease in the amount correlated roughly to the severity of liver disease. This amount in liver disease, except CIH, was significantly less than that in normal subjects. Differences between CIH and CAH, and LCcom and LCdec were also significant. Delayed excretion of 2HPMS was observed in chronic liver diseases, especially in LCdec. Excretion of 2HPMS in the 0-48 h urine was correlated with the alterations of liver functions such as serum albumin concentration, serum choline esterase activity, hepaplastin test and indocyanine green tolerance test. From the results, measurement of the amount of 2HPMS excreted in the 0-48 h urine after oral dose of TPD is suggested to be useful for evaluation of the liver function.

Effect of splenectomy on blood coagulation and fibrinolysis in liver cirrhosis

The analysis of the blood coagulation and fibrinolysis system was performed to evaluate the effect of splenectomy for the patient of hepatic cirrhosis and the degree of recovery of hepatic function after surgical procedures.Seventeen patients with known hepatic cirrhosis were selected for study. All patients were performed splenectomy, devascularization, and esophageal transection, and were investigated about blood examination, biochemical test, blood coagulation and fibrinolysis test.1) Preoperative platelet count was 9.8×104±1.0 (SE). After splenectomy it was increased to 22.5×104±2.1 significantly. As platelet function, it showed high activity preoperatively but after operation normalized. On the other hand, there was a high statistical correlation between platelet count and weight of removed spleen. (r=-0.57, p<0.001).2) The preoperative fibrinogen (Fbg.) level was lower than normal and this thend was not changed after operation. In the prothrombin time (PT) and the hepaplastin test (HPT), the vitamin K dependent factors were decreased in cirrhotic patients and it's values were not recovered by the operation. The Fbg. and PT level of preoperative cirrhotic patients were well correlated with their serum albumin level.3) In cases of which the fibrinogen and fibrin degradation product (FDP) value showed more than 10μg/ml, the disappearance of FDP was not observed until about 4 weeks after the operation. There is a high statistical correlation between the Fbg. and FDP in cirrhotic patients (r=-0.67, p<0.001).4) The patients having continous fever after splenectomy showed low platelet count and low level of Fbg. postoperatively.

Studies on the variation in Factor X activity in patients given warfarin according to the assay methods

Measurements of Factor X clotting activity by using tissue thromboplastin (T. T.) and Russell's viper venom (R. V. V.) showed the correlated result for normal rabbit plasma and human plasmas from healthy persons and patients with liver disease. However the clotting activity of Factor X in plasmas from the rabbits and patients given warfarin become variable according to the assay methods, the activity assayed by T. T. was decreased, whereas it was not so by using R. V. V.Plasma samples are tested in a series of dilutions (D) and the coagulation time (t) measured with assay system using T. T., R. V. V. and hepaplastin test (H. T.).When t is plotted against D, a straight line was obtained. Extrapolation to infinite substrate concentration gives the minima coagulation time (tmin). Normal or liver disease plasma display the same value for tmin, when using any assay systems. Plasma from persons or rabbits given warfarin display the same value for tmin when using R. V. V. or H. T., but not by T. T.These results show that clotting activity of Factor X assayed by T. T. is disturbed with competitive inhibitors probably Protein Induced by Vitamin K Absence or Antagonists (PIVKA) but assayed by R. V. V. or H. T. is not inhibited, as suggested by HEMKER.The value of amidolytic activity of Factor X is higher than that of its clotting activity assayed by R. V. V. for plasma from the persons or rabbits given warfarin.It is likely that there might be some substances which have no clotting activity but amidolytic activity associated with Factor X.Further studies might be necessary to clarify the relationship between the clotting activity and the amidolytic activity of Factor X.

Changes in plasma complement system in relation to the coagulation and fibrinolysis systems in obstructive jaundice

In addition to the coagulation and fibrinolytic activities, changes in plasma C3, C4 and C1INH levels were investigated in 52 patients with obstructive jaundice. Increase of fibrinogen levels and prolongation of euglobulin lysis time (ELT) were the common features in patients without cholangitis. Whereas, patients with cholangitis showed more prominent prolongation of activated partial thromboplastin time and ELT, and reduction of thrombotest values, hepaplastintest (HPT) values, antithrombin III levels and plasminogen levels than those without cholangitis. These abormalities improved favorably after the appropriate biliary drainage. A marked reduction of plasminogen levels associated with prolonged ELT was considered to be an unfavorable sign suggesting a significant risk of major complications especially acute gastrointestinal hemorrhage and shock after the biliary drainage. The postoperative rise of HPT values and plasminogen levels, which occurred generally in the control group, was not proved in the patients who had the postoperative complications especially gastrointestinal hemorrhage and liver failure.Among the complement system, levels of C3, C4 and C1INH showed a significant increase in obstructive jaundice. Increased levels of C3 and C1INH improvedd significantly after the biliary drainage. There was a significant correlation between the levels of C1INH and ELT. This result suggested that the increase of plasma C1INH levels should play a certain role in decrease of fibrinolytic activity in obstructive jaundice.

Correlations between Hemostatic Functions and and Liver Functions in the Neonatal Period

Hemostatic tests such as; thrombotest, hepaplastin test, prothrombin time, activated-partial thromboplastin time, factor VIII and IX, fibrinogen and platelet counts were studied in 91 full-term appropriate-for-date (AFD) newborn infants, who were considered to be mature healthy newborn, and 39 preterm AFD newborn infants, who were born with short gestational period and immature functions, and 37 fullterm small-for-date (SFD) newborn infants, who were considered with disturbed fetal growth. At the same time, some liver function tests such as; total bilirubin, TTT and ZTT, alkaline phosphatase, LAP, LDH, GOT and GPT, choline esterase and total protein were examined.Hemostatic tests revealed moderate disturbances in full-term AFD and severe hypofunction in preterm AFD during 1 to 3 days of age. Then, they increased their levels gradually. In full-term SFD, hemostatic abilities were a little different from other two groups; they did not show a gradual increase with days of age.Functions of liver were not reflected in routine liver tests; they had high bilirubin level due to physiological hemolysis and elevated LDH and GOT originated in RBC. But, decreased choline esterase activity indicates poor protein synthesis in the liver.The correlation between hemostatic and liver function tests were not so definite in newborn infants.To evaluate liver functions in the neonatal period, correctly, it would be proper to examine these hemostatic tests, such as thrombotest, hepaplastintest and prothrombin time, before and after the administration of vitamin K.

A Study on Hepaplastintest in Liver diseases

The liver has close relation with blood coagulation. All the factors of blood coagulation except factor VIII are synthesized by the liver. Hepaplastintest (HPT) is a method to assay the activity of three coagulation factors (II, VII, X) which are synthesized by the hepatocyte. As the level of coagulation factors depends both on hepatic synthesis and on the effect of inhibitors, it is suspected that HPT (an inhibitor-insensitive method) might be available for liver function test.HPT was compared with other biochemical tests to asess its diagnostic and prognostic value in hepatocellar disease. Fourty five patients with acute hepatitis, chronic hepatitis, liver cirrhosis and primary liver carcinoma were studied. Still, HPT in rabbits with acute liver injury induced by carbon tetrachloride is assayed, and our results are summarized below.1) The value of HPT decreased in the early stage of acute hepatitis, but increased following the recovery. HPT often became restored to normal before the transaminase.2) In the patients with chronic inactive hepatitis, HPT values varied within normal range, but in most cases with chronic active hepatitis and especially with liver cirrhosis ramained decreased for long. However, in the cases with primary hepatoma the values of HPT deviated almost only within the normal range or decreased slightly.3) We found highly significant correlation of HPT with serum albumin, cholinesterase, ICG and prothrombin time.4) In rabbits with acute liver cell damage induced by CCl4, HPT values most decreased one day after CCl4 administration, while SGOT and SGPT most elevated one day and three days respectively after the administration of CCl4. HPT values were improved and became normal during seven days, however SGPT remained at a high level.In the clinical and experimental study we observed that HPT often normalized earlier than the SGPT activity of serum in acute liver injury, but it was not clear whether transaminases became elevated before the HPT values became reduced.HPT, which reflects the synthesis of three clotting factors in the hepatocyte, is usef ull as diagnostic and prognostic tools. HPT also has advantage of easy technical practicability.

Studies on Hepaplastintest in hepato-blliary diseases

Hepaplastintest (HPT) was studied on 96 patients with hepato-biliary discorders at Hirosaki University Hospital and its affiliated hospitals for recent four months.As healthy controls HPT were carried out in 50 males and 50 females of healthy hospital employee. HPT was determined on 3.8% citrated venous blood. Coagulation activity was reported in per cent derived from correlation curve of batch number 163.The mean HPT value±SD for healthy controls was 77±12.0 (male 78.5±13.2, female 75.7±10.7).There was no significant difference in mean value between male and female. The mean HPT value±SD showed 34.7±16.8 in 9 cases with extreme stage of acute hepatitis. In 6 of these 9 cases the author observed precipitous fall of the HPT value to bellow 30%. And severe 4 out of these 6 cases were complicated with disturbed consiousness.The mean HPT values±SD for other various hepatobiliary diseases were as follows: 13 cases on recovery stage of acute hepatitis, 60±16.1; 17 cases with chronic hepatitis, 64.4±13.1; decompensated hepatic cirrhosis, 43.5±8.7; 9 cases with compensated hepatic cirrhosis, 55.3±11.7; 4 cases with primary hepatoma, 55.3±12.0; 11 cases with metastatic tumor of the liver, 65±12.8; and 5 cases with constitutional hyperbilirubinemia including 4 Gilbert diseases, 88±13.1. The mean HPT value for each disease mentioned above, except constitutional hyperbilirubinemia, was significantly lower than that of the control group.HPT was reflected slightly on total protein, S-GOT, S-GPT, fibrinogen, cholesterol and partial thromboplastin time. HPT was correlative apparently with γ-globulin, platelet, prothrombin time with Quick's method (sec), Thrombotest (%) and ICG.Further more HPT was correlative with factor II, VII and X but not with fator IX.If HPT was remarkably impoved in cases with acute hepatitis in spite of the very low initial value less than 30% in the beginning stage of the disease they showed clinical improvement followed by desirable prognosis. It could be suggested the HPT well reflected the synthesis of coagulation factors or the protein synthesis in liver cells.So we could conclude that HPT reflected well the degree of hepatic cellular disfunction and was enable one to suspect the degree in severity and prognosis of the hepatobiliary disorders, especially of acute hepatitis.

Check of hypercoagulable state in pregnancy and during oral contraception using Hepaplastintest

The many coagulation factors increase during pregnancy, accordingly pregnant women often complicate thromboembolic episodes. The side effect of oral contraceptives such as thromboembolism and disorders of liver function have long been called attention, but the suitable and simple test to predict these side effects has not been known.Prothrombin time (PT) and Thrombotest (TT) are sensitive only at low coagulation activities. On the other hand, Hepaplastintest (HT) gives reliable results in the assay of hypercoagulable state, still more HT can be used as a liver function test.It is the purpose of this paper to clarify wether HT is available to assay the hypercoagulability during pregnancy and to check the side effects during the use of oral contraceptives.HT was studied in 41 non-pregnant, 40 pregnant (pregnancy VII th-X th month), and 90 sex-hormones administrated women. TT, PT, GOT and GPT were also examined. The results were following.1) HT mean value in normal non-pregnant women was 101.26±16.08%.2) HT mean value in pregnancy VII th month women was 131.40±14.8%, in VIIIth 142.50±13.87%, in IXth 143.66±7.10%, in Xth 158.07±4.15%. These high values could be measured by using non-diluted samples. None of these pregnant women complicated thromboembolic disease. Therefore the relation between these high values and an increasing tendency to thrombosis was not determined.3) HT, GOT and GPT was studied in 3 groups taking sex-hormones.: 7 women taking Mestranol (60γ/day×11 days), 41 women taking Norethisterone (15mg/day×5 days) and 42 women taking oral contraceptives (Anovlar 1 Tab/day×21 days). HT values elevated moderately during the use of sex-hormones and reduced after the ceasing. 10% women in each groups had high HT values above the normal non-pregnant women. None of them had thromboembolic disease.No correlation between the HT values and the GOT and GPT values could be seen. The GOT value elevated above 40 units in 4 cases and GPT in 8 cases, whose HT values were in normal range. HT could not be available to check the slight liver disorders during oral contraceptives.4) It was concluded that HT was useful for the assay of hypercoagulable state. The possible correlation between high HT values and an increased risk of thrombosis should be further investigated.

Utilization of hepaplastintest for diagnosis and prognosis of liver diseases

In four groups of liver diseases, Hepaplastin test and other coagulation tests were studied and compared with various liver function tests.The value of Hepaplastin test in liver cirrhosis revealed 49.1%±16.8 S. D., in acute hepatitis 69.7%±17.5 and in chronic hepatitis 71.5%±16.8.In 5 cases of 7 cholestasis, in which the value of Hepaplastin test remained normal, obstructive Lipoprotein (Lp-X) were positive. But in all cases of 6 cholestasis, in which the value of Hepaplastin test were reduced, Lp-X were negative.The value of Hepaplastin test revealed good correlation with Choline esterase, α-Lipoprotein and Lecithin-cholesterol acyl transferase activity which reflect the reduction of synthesis in liver cells, and also revealed good correlation with ICG-R15.It is already known that the osmotic fragility of RBC decreases in liver diseases. We found that the value of Hepaplastin test correlated with the end osmotic pressure of hemolysis of RBC measured by Coil planet centrifuge system.We judged the prognosis of hepatitis by considering the combination of Hepaplestintest and α-Lipoprotein value. The patients that the value of Hepaplastin test and α-Lipoprotein remained normal in spite of the remarkable elevation of S-GOT, made rapid recovery. In the value of Hepaplastintest and α-Lipoprotein recovered after normalization of S-GOT, the elevation of S-GOT recurred after a few monthes.Hepaplastintest, test for extrinsic clotting system which measures factors II, VII and X is said to reflect the liver function. In our study, Hepaplastin test seems to be usefull for the judgement of prognosis of liver diseases except cholestasis.

Coagulation and fibrinolysis in hepatic cirrhosis

In order to clarify coagulation and fibrinolysis in hepatic cirrhosis following items were examined.1) Counts of megakaryocyte and its classification. 2) Lifespan of 5Cr-labeled platelet. 3) Platelet volume and its distribution (Coulter Counter ZB). 4) Platelet spreading test (Breddin's method). 5) Platelet aggregation (Evans Aggregometer). 6) Platelet Factor-3 (Kaolin). 7) Serum phospholipids and its fractionation. 8) Hepaplastin test (Eisai pharmaceutical Co, test for II, Vll, X factors) 9) Plasma fibrinogen (Tyrosine). 10) FDP (HIT). 11) Protamine sulfate test (Lipinski's). 12) Total plasmin (fibrin plate). 13) Plasminogen and antiplasmin (lysine sepharose affinity chromatography) 14) Factor XIII (Urayama's). from these examinations following facts were clarified.1) Reduction of platelet counts is due to disturbance of platelet formation and enhanced breakdown of platelets and may either due to pooling in the spleen.The remarkable reduction and its characteristic asthenic pattern of platelet aggregation may suggest hypofunction of the platelet cell. It may be supported with the facts of the large spreading tendency of the platelet and reduction of PF-3 availability.2) Hepaplastin test clearly shows reduction of extrinsic factor in cirrhosis of the liver.3) In regard to f ibrinolysis, in case of the hepatic cirrhosis, plasma fibrinogen tends to decrease, on the other hand protamind sulfate test tend to show higher value.Total plasma plasmin increased remarkably, on the other hand, plasminogen and antiplasmin slightly decreased. Factor XIII decreased either in case of cirrhosis.Whether the enhanced fibrinolysis may occur primary or secondary must be examined more in detail.

A study on the correalation between hemostatic function and liver diseases

Nowadays There is no donbt that coagulation studies of hepatic damages give information for the severity, but the clear relationship in this diagnostic value is not established yet.Present studies indicated that hemostatic tests have some pathophysiogical significance for disturbed liver functions.Coagulation and fibrinolytic tests, such as bleeding time (BT), clotting time (CT), recalcification time (RT), prothrombin time (PT), thrombotest (TT) hepaplastintest (HPT), activated partial thromboplastin time (APTT), T E G, concentration of factor V, VIII, IX and fibrinogen (Fbg.), platelet counts (Plt. C), F D P, plasminogen (Plg.), antithrombin III (A T III), α2-macroglobulin (α2-Mac.), and α1-antitrypsin (α1-A T) were made on 6 cases with acute hepatitis (A H), 14 with inactive chronic hepatitis (inact. C H), 4 with active chronic hepatitis (act. C H), 12 with liver cirrhosis without ascites (L C ascites(-)), 3 with liver cirrhosiswith ascites (L C ascites(+)), and 7 other liver disorders such as Banti's syndrome, acute cholestasis and hypercitrullinemia.BT, RT and CT were almost in normal range. Prolonged PT and decreased TT and HPT value were shown in CH and L C groups, but in A H, PT TT and HPT were all in normal range. APTT was prolonged in many cases of each group. In L C with or without ascites, T E G ma was shortened and Plt. C decreased. Low concentration of F V and IX was revealed in many cases with C H and L C. Fbg. level elevated in some cases with A H and other liver disoders, but in most cases with C H and L C showed its decrease. In each group. F D P was almost in normal and Plg. was not elevated.Fibrinolytic inhibitors showed variable changes in same group. In A H, three inhibitors were all in normal range. In C H, A T III was in normal range and α2-Mac. and α1-A T were slightly increased. In L C ascites(-), A T III decreased and α2-Mac. and α1-A T increased. In L C ascites(+), A T III decreased, α2-Mac. increased and α1-A T was in normal.There were 19 cases out of 46, with normal values in screening liver function tests in the present study. They had abnormal values with high frequency in TT, APTT, TEGma, α2-Mac., Plt. C, PT and so on. Thirty-three percent of them showed decreased HPT value. So that these coagulation and fibrinolytic tests may be utilized in the diagnostic procedure for liver functions.Abnormal hemostatic results were reffered with TTT, ZTT, Ch-E and serum albumin level in the presnt studies which were performed mainly on chronic liver diseases, and thues these Suggested disturbed protein metabolism, especially in live cells.

Diagnostic value of coagulation tests in liver disease

The diagnostic value of five differerent clotting tests were evaluated on 109 patients with acute and chronic liver disease. The tests were performed Hepaplastintest (Normotest), Thrombotest, prothrombin time, active partial thromboplastin time and fibrinogen determination. More than 90% of the patients gave abnormal values in some of the tests.1. Most of the patients with acute hepatitis gave slightly abnormal values and their changes were well correlated to clinical condition. The prognosis of a few patients with markedly decreased levels of hepaplastin test was always poor.2. Most of the patients with chronic hepatitis showed abnormal values. No significant discrepancy was observed between active type and inactive type of the disease.3. The majority of the patients of liver cirrhosis showed marked abnormality. Among the tests, the hepaplastin test seemed to the useful to differentiate the compensative phase from incompensative phase, giving moderately decrease in the former, markedly decrease in the latter.4. The results of hepaplastin test and BSP tolerance test were usually parallel with each other.

The indices determing the severity of the liver disease and evaluating the total functioning hepatic cell mass

It has been well known that levels of blood coagulation factors decrease in various liver diseases and this decrease relates to the development of disseminate intravascular coagualtion (DIC). In the present study, serial dilution protamin sulfate (SDPS) test and hepaplastin (Hp) test were performed to evaluate the clinical role of the changes in blood coagulation factors in various liver diseases.Out of 65 cases of various liver disease, 5 cases including 3 of subacute hepatitis, 1 of hepatic cirrhosis and hepatic cancer, were positive for SDPS test. These five cases died shortly after the development of positive SDPS test, suggesting that development of DIC is the terminal event of severe liver diseases. PIVKA index, which is an index of circulating anticoagulant level, was not rel ated to the development of DIC in this study.Hp test, which represnts the total activity of factor II, VII and X, were decreased markedly in subacute hepatitis, moderately in liver cirrhosis, and slightly in classical acute hepatitis and chronic hepatitis, respectively. In intrahepatic cholestasis, values of Hp test were normal, despite of marked jaundice and elevation of serum transaminase activity. In acute hepatitis, values of Hp test were clossely related to the extent of hepatic cell necrosis. The levels of serum prealbumin, which is mainly produced in the liver and has rapidly turnover rate, showed similar change to that of Hp test and correlation between Hp test and serum prealbumin levels was significant statistically. In the hepatectomized rats, values of Hp test and the residual liver weigt were significantly correlated. These results suggested that Hp test or serum prealbumin level is an excellent index to evaluate the total functioning hepatic cell mass.At present time, there is no specific test to evaluate the total functioning hepatic cell mass, which is one of the most important factors to decide prognosis of liver disease. Determination of Hp test values and serum prealbumin level are essential for the treatment various liver diseases.