Hemostatic and fibrinolytic effects of systemic prostaglandin E1 therapy in patients with peripheral arterial disease

BACKGROUND: The study was designed to evaluate if there is any evidence of a hyperfibrinolytic bleeding-risk under systemic treatment with prostaglandin E1 (PGE1) of patients with peripheral arterial disease (PAD). PATIENTS AND METHODS: The in vivo effect of PGE1 on the fibrinolytic and hemostatic process was tested on 15 patients before and after treatment with Alprostadil for 21 days using D-dimers (DD), fibrinogen, prothrombin time (PT), partial thromboplastin time (PTT), antithrombin (AT), ProC-Global, plasminogen, plasminogen activator inhibitor activity (PAI), alpha 2-antiplasmin, coagulation factor XII, basal and activated fibrinolytic capacity (fib. cap.). RESULTS: There was no significant difference in DD, fibrinogen, PT, PTT, AT, ProC-Global, plasminogen, PAI, alpha 2-antiplasmin, coagulation factor XII, basal and activated fibrinolytic capacity observed after the treatment. CONCLUSION: Summarizing this study there is no hyperfibrinolytic bleeding-risk after the systemic therapy with Alprostadil to be expected.     

Elevated urokinase-type plasminogen activator level and bleeding in amyloidosis: case report and literature review

Hyperfibrinolytic states are reported to be a cause of bleeding in patients with amyloidosis. We reviewed the literature on excessive fibrinolysis in association with amyloidosis and report our findings from a patient with idiopathic amyloidosis who developed a bleeding diathesis. Coagulation laboratory studies indicated elevated plasminogen activator levels associated with a reduction of plasminogen and alpha 2-plasmin inhibitor (alpha 2-PI) levels. The level of tissue-type plasminogen activator (t-PA) inhibitor and t-PA antigen were normal. However, the patient did have a five- to sevenfold increase in amidolytic activity for the urokinase substrate pyro-Glu-Gly-Arg-pNA (S-2444). This case therefore represents a novel example of a hyperfibrinolytic state associated with amyloidosis caused by elevated urokinase-type plasminogen activator (u-PA). Epsilon-amino caproic acid (EACA) therapy resulted in an increase in alpha 2-PI and plasminogen levels and effectively reduced the blood loss. Hyperfibrinolytic states in amyloidosis have now been reported to be due to elevated t-PA and u-PA and depleted t-PA inhibitor.     

Thrombin activation and increased fibrinolysis in patients with chronic liver disease

The respective roles of intravascular coagulation (DIC) and fibrinolysis were assessed in severe chronic liver disease by measuring thrombin-antithrombin (TAT) complexes, tissue-type plasminogen activator antigen (tPA Ag) and fibrinogen and fibrin degradation products (FgDP and FbDP respectively) in 66 patients with liver disease caused by cirrhosis (n = 34) or chronic hepatitis (n = 32) as compared to findings in a control group (n = 30). There was a significant increase of TAT complexes (P less than 0.01), tPA Ag (P less than 0.002), FDP and FbDP (P less than 0.001) in patients as compared to controls. FbDP increase was more evident in patients with cirrhosis than in those with hepatitis (P less than 0.01). Significant correlations between these parameters with some liver function tests were also demonstrated. Thus, in patients with severe liver disease, an increased thrombin activity, as demonstrated by high TAT levels; followed by hyperfibrinolysis suggest that a low grade DIC may occur.     

Hemostatic abnormalities in chronic aggressive hepatitis and liver cirrhosis.

Hemostatic defects of chronic aggressive hepatitis (CAH), 25 cases, and of liver cirrhosis, 20 cases, were investigated. The following assays were performed: liver function tests, thromboelastogram, prothrombin time (PT), partial thromboplastin time (PTT), factors I, II, V, X, XIII, euglobulin lysis time, fibrinogen degradation products (FDP), platelet count, morphology and agglutinability. High incidence of hemostatic defects was present in both groups. Thromboelastogram, PTT, prothrombin and qualitative platelet abnormalities were most common. On the whole, severity of hemostatic alterations in cirrhosis was more pronounced than that found in CAH, FDPs were increased in more than 50% of the CAH cases and only in a few cirrhotic patients. Bleeding occurred more frequently in cirrhosis (55%) than in CAH (4%) and, within the cirrhotic patients' group, it was associated with a more severe thrombocytopenia.     

Clinical evaluation of tissue plasminogen activator (t-PA) levels in patients with liver diseases.

Tissue plasminogen activator (t-PA) levels in plasma or serum were studied in 416 patients with liver diseases: acute hepatitis (AH, n = 30); fulminant hepatitis (FH, n = 36); chronic inactive hepatitis (CIH, n = 57); chronic active hepatitis (CAH, n = 39); compensated liver cirrhosis (cLC, n = 78); decompensated liver cirrhosis (dLC, n = 84); hepatocellular carcinoma (HCC, n = 64); advanced hepatocellular carcinoma (aHCC, n = 28); and compared with that of a control group (n = 106) of healthy subjects. The t-PA levels showed significant increase in patients with AH, FH, CAH, cLC, dLC and HCC, compared with normal controls. The abnormal rates in t-PA levels (higher than 8.3 ng/ml) for each type of liver diseases were 86.1% in FH, 46.2% in CAH, 50% in cLC, 85.7% in dLC, 67.2% in HCC, and 89.3% in aHCC. t-PA levels tended to be higher in more advanced liver diseases. t-PA levels significantly correlated positively with plasminogen activator inhibitor (PAI-1) in AH, cLC, dLC, HCC and aHCC, and negatively with plasmin alpha 1-plasmin inhibitor complex (PIC), plasminogen (Plg), FDP, AT III and alpha 2-plasmin inhibitor (alpha 2-PI) in dLC, prothrombin time (PT) and fibrinogen (Fbg) in HCC. t-PA levels in patients with FH, CAH and dLC were significantly higher than those in patients with AH, CIH and cLC, respectively. Moreover, the changes of t-PA levels in the clinical courses of various liver diseases revealed that t-PA levels increased sensitively with progression of liver diseases or in advanced liver diseases.(ABSTRACT TRUNCATED AT 250 WORDS)     

Behaviour of 125I-fibrinogen and 131I-albumin in experimental galactosamine-induced hepatitis.

The turnover of 125I-labelled fibrinogen and 131I-labelled albumin was studied in the course of galactosamine-induced hepatitis in rabbits. In addition to galactosamine, some animals were treated with epsilon-aminocaproic acid (EACA) to inhibit the activation of the fibrinolytic system. The infusion of galactosamine and EACA caused generation of fibrin-rich microclots in the renal glomerular capillaries in seven out of 12 rabbits. Correspondingly, the incorporation of 125I-radioactivity into liver, spleen, and kidneys was pronounced in galactosamine- and EACA-treated rabbits compared with control animals treated with EACA. An acceleration of the 125I-fibrinogen elimination from the plasma was observed between eight and 12 hours after the start of the galactosamine infusion. The administration of heparin in addition to galactosamine and EACA prevented the occurrence of intravascular coagulation, but shortened the survival times of the animals because of bleeding into visceral organs. The elimination of 131I-albumin in plasma as well as the distribution of 131I-radioactivity in organs were similar in all the rabbits independent of the treatment with galactosamine, EACA, or heparin. The experiments indicate that, in addition to diminished synthesis of coagulation factors, disseminated intravascular coagulation is involved in galactosamine-induced hepatitis and contributes to the haemostatic disorder.     

The role of protein metabolism in 204 liver cirrhotics with and without hepatic encephalopathy. I. Clinical and general biochemical findings

Alcohol, hepatitis B, and Non A Non B hepatitis were the main aetiologies of 124 patients with hepatic encephalopathy (HE) due to histologically proven liver cirrhosis. All had severe portal hypertension (PH) and usually increased inflammatory activity of the liver. In stage I (n = 27) 7.4% died, in stage II (n = 28) 14.3%, in stage III (n = 32) 50% and in stage IV (n = 37) 94.6%. Even in cirrhotics without PH, serum albumin, cholinesterase activity and prothrombin time (PT) were significantly decreased. But only in the case of PT did the magnitude of the decrease parallel the stage of HE. Hyperammonaemia and serum creatinine were increased in parallel with the stage of HE. Therefore, in liver cirrhosis a quotient derived from decreased PT and increased serum creatinine has a good prognostic value. Early diagnosis of HE is possible on the basis of writing tests and the determination of free or toxic ammonia.     

Reducing the use of coagulation test panels

Use of a coagulation panel [prothrombin time (PT), partial thromboplastin time (PTT), thrombin time (TT) and fibrinogen], intended for evaluation of bleeding, tripled over 6 years, out of proportion to admissions, surgery, or transfusions. To determine whether the panels were ordered appropriately, we classified 28,737 sets of panel results into groups followed by chart reviews to determine typical patient histories. In 39% of panels, PT/PTT was normal. Prolonged PT occurred in 33% of results, due to liver failure (8%), warfarin (23%), and presumed vitamin K deficiency (69%). Prolonged PTT occurred in 34% of results and was primarily associated with long PT or lupus inhibitors. Prolonged PTT and TT (15% of panels) indicated heparin therapy. Fibrinogen was normal in 98% and low in 1.4%. Critical fibrinogen (below 100 mg/dl, 0.6% of panels) was associated with bleeding in 90% of patients. Only 8% of panel orders were clinically indicated based on patient history. Clinician interviews indicated many were unaware the panel included fibrinogen and TT. Interventions included an education program and an order form change. The education program had no effect on overall order volume or test selection. A later order form change made TT and fibrinogen a separate order. This reduced TT and fibrinogen testing by 90% without complaints or changes in blood transfusion statistics. We conclude that many coagulation test panel orders were not clinically indicated, that PT more often diagnosed vitamin K deficiency than bleeding risk, and that order-based restriction of testing was more effective than educational programs at introducing change in clinical test utilization.     

Fibrinolysis and hemorrhage after streptokinase in acute myocardial infarct

The purpose of this study is to analyze the relationship between occurrence of hemorrhagic complications, kinetic of fibrinogen degradation-regeneration and the changes of prothrombin time (PT), partial thromboplastin time (PTT), after intravenous administration of Streptokinase (SK), 1.500.000 U., in acute myocardial infarction. 45 selected patients with acute myocardial infarction had pretreatment analysis and serial post-SK measurement of fibrinogen levels, PT, PTT (for 48 hours). Basal fibrinogen levels were 3.2 g/l and displayed significant depression for 18 hours (0.30-0.46 g/l) and normalization after 30 hours from SK infusion. Similar behaviour showed PT and PTT. Minor bleeding was identified in 25 patients. In bleeders mean fibrinogen levels, PT, PTT before and maximum changes after SK were not significantly different compared with non bleeders. We conclude that SK infusion produces important and prolonged changes of fibrinogen levels, PT, PTT; hemorrhagic risk is not related, however, to the extent of lytic state, but probably to pre-existent vascular derangement, predisposing to bleeding complications during fibrinolytic therapy. Therefore we believe to be prudent to delay the infusion of heparin for 12-18 hours after SK administration, when fibrinogen levels are beginning to increase.     

替比夫定治疗乙型肝炎肝硬化患者48周临床观察

目的观察替比夫定治疗乙型肝炎肝硬化患者48周疗效。方法采用随机、对照队列研究方法,将93例乙型肝炎肝硬化患者分成三组,替比夫定（LDT）组32例,拉米夫定（LAM）组31例,对照组30例,采用常规保肝对症治疗,疗程均为48周。观察治疗不同时间点患者的病毒学、生化学、凝血酶原时间（PT）、肝纤维化指标及Child—Pugh计分等变化情况。结果LDT组患者HBVDNA水平显著下降,HBVDNA转阴率优于LAM组和对照组,差异均有统计学意义（P〈0．05）。在24和48周LDT组患者血清HBeAg阴转率及HBeAg／抗-HBe血清学转换率与对照组比较,差异有统计学意义（P〈0．05）。AⅡ、AST、TBil明显下降,肝纤维化指标改善,Child—Pugh计分下降,在24和48周,LDT组和LAM组较治疗前比较差异有统计学意义（P〈0．05）。结论LDT治疗乙型肝炎肝硬化患者能有效、快速抑制病毒复制,改善肝功能、肝纤维化指标及Child—Pugh计分等。     

Protein C and antithrombin III in polytransfused thalassemic patients

Seventy-four patients with beta-thalassemia major were studied to test the hypothesis that a deficiency of protein C (PC) and antithrombin III (AT III), both antithrombotic proteins, could contribute to the pathogenesis of CNS thromboembolic lesions. In 70 patients, PC levels were found to be significantly lower than normal, whereas AT III activity was found to be lower only in 41 patients. The lowest values of PC and AT III were found in older splenectomized patients, a low PC value only was found in chronic hepatitis patients. Prothrombin time and fibrinogen were found to be particularly abnormal in patients with chronic hepatitis and without spleen. A relatively poor correlation was observed between PC and AT III (p less than 0.02). PC correlated with age (p less than 0.001), transfusional iron (p less than 0.001) and ferritin (p less than 0.001). It also correlated with serum albumin (p less than 0.001), prothrombin time (p less than 0.001) and fibrinogen (p less than 0.02) and with serum transaminases (GPT) (p less than 0.001). The same indexes correlated less significantly with AT III activity. Nevertheless, only 2 of our patients had CNS thromboembolic complications. It is probable that low clotting factors, hyperfibrinolysis and thrombocytopenia (which are common in chronic liver disease) could have the opposite effect on hemostasis from that of low levels of anticoagulant proteins such as PC and AT III.     

The hemostatic defect of chronic liver disease. Kinetic studies using 75Se-selenomethionine.

With the use of cohort labeling with 75Se-selenomethionine, simultaneous platelet, fibrinogen, and plasminogen survival studies were carried out in 8 patients with chronic alcoholic liver disease and in 5 normal subjects. Clinical features, liver function tests, coagulation and fibrinolytic system activities, and platelet function were also assessed. On the basis of platelet survival, the patients could be divided into two groups. Three patients had shortened platelet survival; they were all thrombocytopenic and had greater prolongation of the prothrombin time (PT) and activated partial thromboplastin time (PTT) than the other 5 patients. However, platelet turnover was decreased in all the patients, and there was no difference between the two groups with regard to fibrinogen or plasminogen survival nor in the in vitro evidence of disseminated intravascular coagulation (DIC). Fibrinogen survival was increased in 5 of the 8 patients. Plasminogen survival was normal in 6 patients and prolonged in 2 patients with very low plasminogen levels. The absence of increased fibrinogen turnover in the patients studied indicates that the abnormalities in coagulation tests were not due to consumption coagulopathy. The authors' studies suggest that, at least for patients with chronic stable alcoholic liver disease, the concept that the coagulopathy of liver disease is due to increased utilization of clotting factors should be revised with caution.     

2级高血压患者血栓前状态分子标志物的变化

目的 探讨2级高血压患者血栓前状态相关指标的改变及其临床意义.方法 采用流式细胞仪、酶联免疫吸附双抗体夹心法(ELISA)、全自动血凝分析仪等检测2级高血压血小板表面P-选择素(P-selectin,CD62P)、血浆组织型纤溶酶原激活剂(t-PA)、抑制剂(PAI-1)和凝血四项即血浆纤维蛋白原(FIB)水平、活化部分凝血活酶时间(APTT)、凝血酶原时间(PT)、凝血酶时间(TT).结果 2级高血压组CD62P的表达、血浆PAI-1、FIB三项指标均较正常组增高(P＜0.05),而t-PA水平较正常组降低(P＜0.05);2级高血压APTT和PT时间明显缩短(P＜0.05);正常组与2级高血压组TT时间比较无统计学意义(P＞0.05).结论 2级高血压患者血小板活化、凝血功能增强、纤溶功能减退,存在明显的血栓前状态;测定血小板表面CD62P的表达、血浆t-PA和PAI-1和凝血四项有助于早期发现2级高血压患者血栓前状态并有助于导临床早期干预治疗.     

Photochemically treated fresh frozen plasma for transfusion of patients with acquired coagulopathy of liver disease

An ex vivo photochemical treatment (PCT) process was developed to inactivate pathogens in fresh frozen plasma (PCT-FFP). A prospective, controlled, double-blinded, randomized study was conducted to evaluate the efficacy and safety of PCT-FFP compared with conventional FFP (C-FFP). Patients (n = 121) with acquired coagulopathy, largely due to liver disease, including hepatic transplantation, were transfused with either PCT-FFP or C-FFP for up to 7 days. Primary end points were changes in the prothrombin time (PT) and the partial thromboplastin time (PTT) in response to the first FFP transfusion. Secondary analyses compared changes in the PT and the PTT, factor VII levels, clinical hemostasis, blood component usage, and safety following FFP transfusions for up to 7 days. Following the first transfusion, correction in the PT and PTT adjusted for FFP dose and patient weight was not different. Changes in the PT were equivalent between treatment groups (P = .002 by noninferiority). Equivalence was not demonstrated for changes in the PTT. Following multiple transfusions, correction of the PT and the PTT was similar between groups. No differences were observed in use of blood components, clinical hemostasis, or safety. These results suggest PCT-FFP supported hemostasis in the treatment of acquired coagulopathy similarly to conventional FFP.     

Early treatment with N-acetylcysteine in children with acute liver failure secondary to hepatitis A

Introduction. Hepatitis A virus can evolve to acute liver failure with a fatal outcome if it is not reversed.Objective. We describe the clinical course of 12 children who presented with hepatitis A acute liver failure and received treatment with oral N-acetylcysteine (NAC).Materials and methods. Of the seventy-two patients with viral hepatitis A, 12 patients who had acute hepatic failure were included. The variables evaluated were age, sex, duration of clinical features prior to hospitalization, signs and symptoms, laboratory parameters [alanine aminotransferase (ALT), aspartate aminotransferase (AST), prothrombin time (PT), partial thromboplastin time (PTT), internal normalization ratio and ammonia], treatment (oral NAC 100 mg/kg/day, lactulose, neomycin and general measures) and clinical course during hospitalization.Results. Six males and six females were included. School-aged and adolescent children predominated. All presented with jaundice, nausea, vomiting and hepatomegaly. Two had stage 2 neurological signs as per the West-Haven scale. All had altered laboratory parameters. All received NAC, six patients for a week and the remaining six for 9-36 days. Treatment was not ceased until patients showed clinical and laboratory improvement. All data were analyzed using both student’s t test and Wilcoxon signed rank with alpha = 0.05, the ALT with P = 0.0003 and 0.005, AST with P = 0.0001 and 0.0005, PT with P = 0.0237 and 0.0005, PTT with P = 0.0515 and 0.0039, ammonia with P = 0.0197 and 0.0015 and direct bilirubin with P = 0.0190 and 0.068. There was good tolerance to medications and a satisfactory clinical course.Discussion. The use of oral NAC appears to be an effective therapeutic alternative for hepatitis A-induced liver failure if it is offered appropriately. It can modify the clinical course to a favorable one and prevent the fatal outcome of hepatic encephalopathy.     

Modifications of coagulation and fibrinolysis mechanism in laparoscopic vs. open cholecystectomy

BACKGROUND/AIMS: The incidence of thromboembolic complications following laparoscopic cholecystectomy as well as the indication for prophylactic thrombophylaxis is still controversially discussed. The aim of this study is to evaluate the alterations of the coagulation and fibrinolytic mechanism after laparoscopic vs. open cholecystectomy. METHODOLOGY: Forty-five patients, who were submitted to laparoscopic (LC-group, n=30) or open cholecystectomy (OC-group, n=15) were included in the study. The following parameters were measured preoperatively and 24h and 48h postoperatively: platelet count (PLT), prothrombin time (PT), partial thromboplastin time (PTT), fibrinogen (FG), d-dimers (DD) and antithrombin III (AT-III). RESULTS: The preoperative values were within the normal range and did not differ between the two groups. No significant alterations were noted concerning PT and PTT. FG and PLT were significantly increased in both groups at 24h and 48h compared to the baseline values, with no statistical significant difference between them at all time points. D-dimers were significantly elevated at 24h and 48h postoperatively in both groups. The LC-group showed significantly higher AT-III levels at 24h, and significantly lower DD levels at 24h and 48h compared to the OC-group (p < 0.05). CONCLUSIONS: Laparoscopic cholecystectomy seems to induce a lower activation of the hemostatic mechanism compared to open cholecystectomy.     

Effects of solvent/detergent-treated plasma and fresh-frozen plasma on haemostasis and fibrinolysis in complex coagulopathy following open-heart surgery

BACKGROUND AND OBJECTIVES: Solvent/detergent-treated plasma (SDP) contains markedly lower protein S (PS) and plasmin inhibitor (PI) activity than standard fresh-frozen plasma (FFP). It has also been reported that SDP contains no alpha(1)-antitrypsin. Despite the lack of clinical data, it is suspected that SDP may be less effective than FFP in the treatment of complex coagulopathies. We therefore conducted a prospective trial to study the impact of SDP and FFP on haemostasis and fibrinolysis in complex coagulopathy after open-heart surgery. MATERIALS AND METHODS: Patients received either 600 ml of SDP (n = 36) or 600 ml of FFP (n = 31) at an infusion rate of 30 ml/min. The following parameters were measured before treatment and 60 min after termination of plasma infusion: prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen, factor VIII, antithrombin, protein C (PC), free PS and PS activity, prothrombin fragments F1+2 (F1+2), D-dimers (DD), fibrinogen degradation products (FDP), plasmin-plasmin inhibitor complexes (PPI), plasminogen, PI and alpha(1)-antitrypsin. RESULTS: The rise in fibrinogen, factor VIII, antithrombin, PC, free PS, alpha(1)-antitrypsin and plasminogen, and the decrease in PT and APTT, did not significantly differ between the two study arms. However, PS activity did not increase after SDP infusion but did show a significant elevation after infusion with FFP. PI declined significantly after SDP and remained uninfluenced by FFP. Neither SDP nor FFP had any significant influence on F1+2, DD or FDP. However, a significant decrease in PPI levels caused by both types of plasma indicated a reduction in hyperfibrinolysis. Clinical haemostasis evaluation revealed no significant difference between the two treatment regimens. No adverse reactions were observed. CONCLUSION: With the exception of PS and PI, SDP and FFP improved haemostasis and fibrinolysis to a similar degree. The clinical significance of these findings has to be determined in patients with severe acquired PS and PI deficiency requiring plasma transfusions.     

The clinical significance of slightly to moderately increased liver transaminase values in asymptomatic patients

BACKGROUND: Our aim was to study liver disorders in asymptomatic patients with slightly to moderately increased liver transaminase values in a population living in an area with a low prevalence of viral and hereditary liver diseases. METHODS: One hundred and fifty consecutive patients with slightly to moderately increased liver transaminases for at least 6 months without symptoms or signs of liver disease were included. Median (range) was 0.75 microkat/l (0.24-2.9) for aspartate aminotransferase (ASAT) and 1.18 microkat/l (0.28-4.5) for alanine aminotransferase (ALAT). A percutaneous liver biopsy was performed, and blood was sampled for a detailed biochemical and serologic profile. RESULTS: Chronic viral hepatitis C was found in 15.3% of the patients, autoimmune hepatitis in 1.3%, primary biliary cirrhosis in 1.3%, and heterozygotic alpha-1-antitrypsin deficiency in 0.7%. Presumed alcoholic liver disease was diagnosed in 8%, and non-alcoholic steatohepatitis in 2%. Chronic hepatitis with no obvious etiology was diagnosed in 24%, of whom 39% had interface hepatitis (piecemeal activity). Seventy-one per cent of these 39% had measurable levels of autoantibodies, but IgG levels within normal limits prevented the 'clinical' diagnosis of autoimmune hepatitis. Liver steatosis was the diagnosis in 40%. Most were overweight and had increased serum triglyceride levels. However, in 13.3% the fatty infiltration was considered 'essential', as both body mass index (BMI) and triglyceride levels were normal. Other diagnoses were liver fibrosis with no obvious inflammatory activity (3.3%), cirrhosis of unknown etiology (0.7%), and for the remaining (3.3%) patients histopathologic findings were considered 'normal'. Cirrhosis was found in five biopsy specimens: hepatitis C (n = 2), autoimmune hepatitis (n = 1), primary biliary cirrhosis (n = 1), and cryptogenic cirrhosis (n = 1). No concomitant disease was of importance for the diagnosis and/or histopathologic findings. No obvious drug-related increased liver test results were found with any single drug. However, patients with chronic hepatitis of unknown etiology, especially with interface hepatitis, significantly more often than the rest of the population were receiving drug treatment. CONCLUSION: Most transaminitis patients had steatosis, and some had defined diseases including chronic hepatitis C. Chronic hepatitis of unknown etiology was found in a substantial proportion (24%) of a population living in an area with a low burden of hepatic viruses and genetic disorders.     

Hyperbilirubinemia and cholestatic liver injury in hepatitis C-infected liver transplant recipients

OBJECTIVE: A cholestatic pattern of liver injury has been observed in liver transplant recipients with rapidly progressive hepatitis C. We assessed the frequency and causes of cholestasis in hepatitis C-infected liver transplant patients, and evaluated the clinical and pathological course of those with cholestatic hepatitis C. METHODS: Sixty-nine sequential liver transplant recipients who had detectable hepatitis C viremia were studied retrospectively. Records and diagnostic tests were examined from patients who developed hyperbilirubinemia. RESULTS: Hyperbilirubinemia occurred in 33 of 69 (48%) hepatitis C-infected liver transplant patients. A thorough evaluation including review of clinical and laboratory data, ultrasound with Doppler, cholangiogram, and liver biopsy identified causes of hyperbilirubinemia other than hepatitis C in 26 of 33 patients. Seven patients developed cholestatic hepatitis C characterized by histological features of recurrent hepatitis C and cholestatic liver injury with ballooning of centrilobular hepatocytes, bile ductular proliferation, and canalicular cholestasis, in the absence of other causes of cholestasis. Five progressed rapidly to bridging fibrosis and two died of complications related to liver failure. Four patients with cholestatic hepatitis C showed extended survival after the onset of hyperbilirubinemia. CONCLUSIONS: 1) Hepatitis C is a relatively infrequent cause of cholestasis in liver transplant recipients. 2) The diagnosis of cholestatic hepatitis C requires a multimodality approach to exclude other causes of cholestasis. 3) Cholestatic hepatitis C ranges in severity and is not always associated with rapid development of graft failure, although significant histological abnormalities are frequent.     

Does glycemic regulation affect hypercoagulable states in diabetic patients?

Diabetes is a common disorder, and many studies have shown that patients with diabetes mellitus have increased thrombotic complications including arterial and venous thromboses. Poorly controlled diabetes increases the risk of thrombosis. Recent reports have shown that a shortened activated partial thromboplastin time (APTT) and increased fibrinogen levels indicate a procoagulant condition. In this study, we evaluated the differences in global coagulation test values such as APTT, prothrombin time (PT), or fibrinogen levels, between well and poorly controlled diabetes. Three hundred forty-nine patients with type 2 diabetes mellitus were included. APTT, PT, fibrinogen, fasting plasma glucose (FPG), postprandial plasma glucose (PPG), complete blood count (CBC), serum lipids, and HbA1c have been measured. Those with APTT <22 s and PT <10.5 s were identified. Furthermore, patients were divided into two groups based on HbA1c levels as follows: regulated diabetic group (HbA1c ≤7.0 %) and dysregulated diabetic group (HbA1c >7.0 %). No significant differences were found between the two groups in terms of shortened APTT (<22 s), PT (<10.5 s), or fibrinogen levels. Although inexpensive and widely available, global coagulation assays such as APTT, PT, and fibrinogen levels did not prove useful for evaluating hypercoagulable states in patients with diabetes.