Partial Thromboplastin Time Levels Research Articles

Thrombosis of the aortic root and ascending aorta during extracorporeal membrane oxygenation

Emergent coronary artery bypass grafting was performed in a 73-year-old male patient due to an interventional left main stem coronary artery dissection. Following the operation the patient had to be put on femoral extracorporeal membrane oxygenation (ECMO) due to postcardiotomy cardiogenic shock. ECMO flow was adjusted according to measurements of the mixed venous or central venous saturation of oxygen (target 70 %; 4–4.5 l/min ECMO flow). Anticoagulation with intravenous heparin was guided by the activated clotting time (ACT), which was kept strictly above 140 s throughout the whole period of treatment resulting in partial thromboplastin time levels of between 44 and 65 s. Additionally, the thrombocyte count was between 35 and 75 Gyl throughout the whole period of treatment. A heparin-induced thrombocytopenia was ruled out by testing for platelet factor 4–heparin complexes. Three days later, after failed weaning from ECMO, echocardiography showed severe biventricular failure and thrombosis of the entire aortic root and the proximal part of the ascending aorta (Fig. 1). The patient died as a consequence of long-lasting myocardial ischemia and secondary multiple organ failure. If left ventricular output is not

Association of activated partial thromboplastin time and fibrinogen level in patients with type II diabetes mellitus

BackgroundPatients with diabetes mellitus have a high risk of atherothrombotic events. Diabetes contributes for initiation and progression of microvascular and macrovascular complications. Shortened activated partial thromboplastin time (aPTT) values may reflect hypercoaguable state, which is associated with increased thrombotic risk and adverse cardiovascular events. Increased level of fibrinogen is common in type II diabetes. The present study was conducted to study the aPTT and fibrinogen levels in diabetics in a tertiary care Teaching Hospital of Nepal.MethodsObservational study was performed at out-patients visiting Pathology Department at Tribhuvan University Teaching Hospital from August 5 to September 7, 2012. Research protocol was approved by Institutional Review Board at Tribhuvan University Institute of Medicine. Altogether 90 people who came to the hospital during study period and who met inclusion criteria were selected, out of which 72 were diabetics and 18 were normal controls. Diabetic cases were identified via verbal interview with patients themselves and review of laboratory findings and diagnosis performed by their physicians. Diabetics with a diabetic history of more than one year and stabilized with antidiabetic medicines such as insulin, metformin, glibenclamide, and gliclazide and diabetics with controlled diabetes as revealed by HbA1c in the range 6.2-7% were taken for the study purpose. Data were analyzed with chi square test and Fischer’s exact test (when each cell frequency was less than 5) using Statistical Package for Social Sciences 17.ResultsMaximum (53; 73.6%) diabetics and all non-diabetics had aPTT in the range 26–40 seconds. Maximum (51; 70.8%) patients had fibrinogen beyond 351 whereas all non-diabetics had fibrinogen in the range 151–350. Mean aPTT values of the diabetic patients and non-diabetic persons were 29.88 ± 4.89 seconds and 32.44 ± 2.25 seconds respectively. Mean fibrinogen values of the diabetic patients and non-diabetic persons were 388.57 ± 60.90 mg/dL and 320.89 ± 10.20 mg/dL respectively. Test data identified in results were statistically significant for aPTT (p value 0.000) and fibrinogen (p value 0.000) between the diabetics and non-diabetics.ConclusionsDiabetics have an increased level of fibrinogen and relatively shortened aPTT as compared to the non-diabetic patients.

International survey on plasma transfusion practices in critically ill children

Studies have shown heterogeneity in red blood cell transfusion practices. Although plasma transfusion is common in intensive care, there are no data on plasma transfusion practices in pediatric critical care units. A scenario-based survey was sent to 718 pediatric critical care physicians working in Europe, North America, Australia, and New Zealand. Respondents were asked to report their decisions regarding plasma transfusion practice with respect to four scenarios: pneumonia, septic shock, traumatic brain injury (TBI), and postoperative care after a Tetralogy of Fallot correction. The response rate was 187 of 718 (26%); half of the responders worked in North America. The proportion of physicians who transfused plasma to nonbleeding patients, solely based on abnormal international normalized ratio (INR), varied from 66% for pneumonia to 84% for TBI (p < 0.001). In such nonbleeding patients, the median INR threshold that would trigger plasma transfusion was 2.5 for pneumonia and septic shock patients and 2.0 for TBI and the cardiac postoperative patients (p < 0.001). Minor bleeding, minor surgery, insertion of a femoral line, hypotension, abnormal activated partial thromboplastin time, thrombocytopenia, and anemia levels were important determinants of plasma transfusion, whereas none of the respondents' demographic characteristics were important. More than two-thirds of responding pediatric critical care physicians prescribe plasma transfusions for nonbleeding critically ill children. Additionally, there is a significant variation in transfusion practice patterns with respect to plasma transfusion thresholds.

Therapeutic Anticoagulation After Craniotomies: Is the Risk for Secondary Hemorrhage Overestimated?

Deep venous thrombosis (DVT) and pulmonary embolism (PE) are major causes of postoperative morbidity and mortality in surgery. However, there is neither a standardized protocol for perioperative prevention of DVT or PE in neurosurgery nor a consensus concerning the management of postoperative DVT or PE after craniotomy in the early postoperative course. We retrospectively analyzed management and complications in a group of patients with postoperative DVT or PE after craniotomy between 2006 and 2011 to estimate the risk of secondary hemorrhage under therapeutic anticoagulation. The interval between time of craniotomy and diagnosis of PE or DVT, administered anticoagulation, and the appearance of a clinically relevant secondary hemorrhage were analyzed. Forty-two patients met the given criteria. Indications for surgery were intracranial tumors (n = 33), aneurysms (n = 5), and hematomas (n = 4). PE or DVT was observed between the first and the 28th postoperative day (median, fifth postoperative day). Therapeutic anticoagulation was performed with enoxaparin or heparin (according to partial thromboplastin time levels). Full heparinization was applied in 30 patients between the second and the 30th postoperative day (median, 12th postoperative day). None of these patients developed a secondary hemorrhage. The documented differences in the anticoagulative drug used, the drug's dosage, and the start of medication reflect the lack of a standardized protocol concerning the treatment of postoperative PE or DVT after craniotomy. A more aggressive management regarding the application of anticoagulative drugs after craniotomy may be justified considering the absence of clinically relevant hemorrhages in this study and the life-threatening potential of perioperative DVT or PE.

Leptin and plasminogen activator inhibitor-1 levels in children on chronic dialysis

Purpose: In this study, it is aimed to compare the serum leptin and PAI-1 levels and evaluate their relationship in children on hemodialysis (HD) and peritoneal dialysis (PD). Method: Thirty-six patients on HD (mean age: 15.0 ± 2.8 years), 19 patients on PD (mean age: 13.0 ± 3.5 years) and 15 healthy subjects (mean age: 14.5 ± 2.7 years) were included in the study. Laboratory investigations included blood count, biochemical parameters, serum iron, iron binding capacity, parathormone, erythrocyte sedimentation rate, C-reactive protein (CRP), prothrombin time (PT), partial thromboplastin time (PTT), fibrinogen, serum leptin and PAI-1 levels. Results: Serum leptin levels were significantly higher in HD group than in control group when the effects of BMI and sex were controlled, while PD and control groups had similar leptin levels. PAI-1 levels were also significantly higher in HD group than in control group, while there was no statistically significant difference in PAI-1 levels of PD and control group. PAI-1 levels and leptin levels were significantly correlated, which was independent of the effect of BMI in both HD and PD groups when they are evaluated separately. Conclusion: Results of our study showed that HD patients had higher leptin and PAI-1 levels and leptin and PAI-1 levels were correlated significantly in both patient groups. The effect of elevated serum leptin and PAI-1 levels on the cardiovascular complications remains to be established.

Fondaparinux

AIM OF THE STUDY To review the best evidence-based knowledge about the clinical pharmacology and use of fondaparinux. DESIGN OF THE STUDY Narrative review. RESULTS Fondaparinux is a synthetic pentasaccharide anticoagulant that binds selectively with high affinity to antithrombin and catalyses the inactivation of factor Xa, which results in a dose-dependent inhibition of thrombin generation. Fondaparinux does not bind to platelets or inhibit platelet aggregation, does not cross-react with antibodies to heparin-PF4 complexes (HIT antibodies) and has no effects on the activated partial thromboplastin time, prothrombin time and antithrombin levels. Fondaparinux shows a linear and highly predictable pharmacokinetic profile in humans, with very limited intraindividual and interindividual variability, which makes routine monitoring and dose adjustments unnecessary for the majority of the population. After subcutaneous iniection fondaparinux undergoes complete and dose-independent absorption; it is not significantly metabolized by the liver and does not interfere with cytochrome P450-mediated transformation of other drugs. Fondaparinux is almost entirely excreted unchanged in the urine with a half-life of approximately 17 hours, allowing for once-daily dosing. Its plasma clearance is reduced in patients with moderate or severe renal insufficiency. In the clinical trials and post-marketing surveillance fondaparinux shows an excellent tolerability profile, with a low incidence of major bleeding across a wide dose range and no cases of severe thrombocytopenia or heparin-induced thrombocytopenia (HIT). CONCLUSIONS Fondaparinux has been approved in many countries for use in thromboprophylaxis after major orthopedic surgery and in medical patients, and for the treatment of sintomatic venous thromboembolism (deep venous thrombosis and hemodynamically stable pulmonary embolism) and acute coronary syndromes (unstable angina, and acute miocardial infartion, with or without ST elevation). In these clinical settings fondaparinux is at least as effective and safe as unfractionated heparin or low molecular weight heparins, and may be easier to use.

Activation of coagulation and fibrinolysis during coronary artery bypass grafting: a comparison between on-pump and off-pump techniques.

Coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB) is associated with intense activation of hemostatic mechanisms. But the precise knowledge of the effects of eliminating CPB in patients undergoing off-pump coronary artery bypass grafting (CABG) are not well established. The present study was carried out to compare and document the changes in selected coagulation and fibrinolysis variables in patients undergoing on-pump and off-pump CABG (OPCAB). A total of 42 patients of on-pump and 31 patients of off-pump CABG were selected for the study. Platelet count, prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), Fibrinogen and D-dimer levels were measured immediately, 24h and 7days after operation and compared with the baseline preoperative values. Statistical analysis was done by mixed ANOVA for repeated measures and Post-hoc tests using the Bonferroni correction, Chi square and unpaired t test. All the parameters were significantly changed (P<0.05) with the time. Platelet counts, fibrinogen and D-dimer levels were significantly different between on-pump and off-pump CABG patients on immediate and 24h postoperative period and attained almost same level after 7days of operation. Fibrinogen level and platelet counts were increased after a sharp fall in the immediate post-operative period whereas D-dimer levels were persistently increased with a sharp peak of rise in the immediate post-operative period in on-pump group. On-pump surgery was associated with excessive fibrinolytic activity immediately after operation. The off-pump group demonstrated less activation of coagulation and fibrinolysis and delayed postoperative response that became almost equal to the on-pump group in the later postoperative period.

Intracranial Hemorrhages Related with Warfarin Use and Comparison of Warfarin and Acetylsalicylic Acid

Acetylsalicylic acid (ASA) and warfarin are used to prevent ischemic cerebrovascular events. They have serious complications including intracranial hemorrhages (ICHs). Warfarin-related intracerebral hemorrhage (ich) incidence is .2%-5% in population that accounts for 10%-12% of all ichs. In this article, we investigated the profile of ASA and warfarin-related spontaneous ICHs in comparison with ICHs without any drug use (WADU) with their clinical, radiological, and biochemical properties. In all, 486 patients aged 18-101 years with spontaneous ICHs were included. Patients constituted 4 separate groups: users of warfarin, ASA, ASA + warfarin, and WADU. Clinical, neurological, etiological, and radiological data of these patients were compared. There were 32 patients in warfarin, 58 patients in ASA, and 7 in warfarin + ASA group. Most of the patients were in no drug group (389 patients). The most frequent type of hemorrhage was supratentorial intraparenchymal hemorrhage. The most common accompanying disease was hypertension. The number of female patients was statistically significant in the warfarin group. Glasgow Coma Scale (GCS), accompanying diseases, opening of the hematoma to the ventricle, localization of the hemorrhage, age of the patient, and activated partial thromboplastin time level are all related to the outcome of patients. Warfarin users had worst mortality rate. Use of warfarin, low GCS score, opening to ventricle, older age, accompanying diabetes, and/or hypertension were worse prognostic factors. It is possible that patients with these unfavorable prognostic factors cannot survive.

The Relationship Between Inflammatory Reagents and Mortality in Patients Over the Age of 55 Hospitalised in the Internal Medicine Intensive Care Unit from the Emergency Service

Objective: In this study, we tried to determine the relationship between inflammatory reagents, acute phase reactants, GCS, APACHE-II, SAPS-II scores and mortality of the patients over the age of 55 hospitalised inthe internal medicine intensive care unit. Material and Methods: This study was planned as a prospective, randomized study and the patients hospitalized in the intensive care unit from the emergency medicine department were enrolled in this study following the ethics committee approval. A standard data collection form was prpeared to collect the data in a standard way. 48 (%65.8) male, 25 (%34.2) women and a total of 73 patients were included in our study. Blood samples were taken from each patient and white blood cell (WBC), hemoglobin, c-reactive protein (CRP), interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-alpha), prothrombin time (PTZ), activated partial thromboplastin time (aPTT), albumin and ferritin levels were studied in our laboratory. Glasgow Coma Scale, SAPS-II and APACHE-II scores were calculated for each patient. “SPSS for Windows version 18” package program was used for statistical analysis of the data. Chi square test was used to compare categorical measures between the groups. Mann-Whitney U test and T-test were used to compare quantitative measurements between the groups. Results: There was no statistically significant difference in mean age among patients who died and survived . Mean duration of hospitalization inthe patient group who died was less than for the survived patients group but there was no statistically significant difference between groups. A significant relationship was found between mortality and the high levels of ferritin, aPTT, SAPS-II and the low levels of albumin, GCS. No significant relationship was found between mortality and leukocyte count, haemoglobin, PTZ, CRP, TNFalpha, IL-1, IL-6, IL-10 and APACHE-II score. Conclusion: SAPS-II, GCS, ferritin, albumin, aPTT measurements were determined to be used in the mortality estimation of the patients hospitalised in the intensive care unit. (JAEM 2013; 12: 13-8)

Use of thromboelastography to assess the combined role of pregnancy and obesity on coagulation: a prospective study

BackgroundThromboelastography (TEG®) is a point of care monitor of whole blood coagulation and has previously demonstrated hypercoagulability in both pregnant and obese populations. However, the individual and combined contribution of pregnancy and obesity on coagulation status has not been defined. We carried out a study to assess the effect of both pregnancy and body mass index (BMI) on blood coagulation using laboratory tests of coagulation and thromboelastography. MethodsThis was a prospective study of 96 women divided into four equal groups; non-pregnant lean (NPL) BMI <25kg/m2, pregnant lean (PL) BMI <25kg/m2, non-pregnant obese (NPO) BMI >35kg/m2 and pregnant obese (PO) BMI >35kg/m2. Women were of either >36weeks of gestation presenting for elective caesarean delivery; non-pregnant women with BMI >35kg/m2 presenting for bariatric surgery; or non-pregnant volunteers with BMI <25kg/m2. Eligible women were then allocated to a group based on BMI and pregnancy status. TEG® analysis, full blood count and coagulation profiles were performed on all patients. The main outcome measures were TEG® profile (including r time, k time, α angle, maximum amplitude and coagulation index), platelet count, activated partial thromboplastin time, prothrombin time, and fibrinogen levels. ResultsThe coagulation index was significantly higher in the obese patient groups compared with the lean groups (NPL −4.5 vs. NPO 1.9, P<0.001; PL −4.3 vs. PO 2.5, P<0.001). However, comparisons between the pregnant and non-pregnant groups when matched for BMI demonstrated no significant difference in coagulation. ConclusionsThe combined effect of pregnancy and obesity on coagulation has not previously been investigated. Thromboelastographic comparison of pregnant and non-pregnant females separated into low or high BMI cohorts in the current study suggests that obesity correlates more with a hypercoagulable state than with pregnancy, particularly in pregnant patients at the extremes of low and high body weight.

Analysis of risk factors for spontaneous rupture of hepatocellular carcinoma

To assess the risk factors for spontaneous rupture of hepatocellular carcinoma (SRHC). A retrospective analysis of 34 consecutive patients with SRHC treated by emergency interventional embolization in our hospital from July 2003 to July 2011 was conducted. General condition, laboratory examination and imaging data were analyzed, and compared with the data of 34 patients with primary hepatocellular carcinoma but without rupture, randomly selected from 215 concurrent patients. The patients with SRHC were selected for risk factor analysis, and the non-SRHC patients were taken as control group. No significant difference between the SRHC group and control group was found in age, sex, Child-Turcotte-Pugh (CTP) grade, Barcelona clinic liver cancer (BCLC) stage, HBsAg, HBsAb, HBeAg, HBeAb, HBcAb, prothrombin time (PT), thrombin time (TT), international normalized ratio (INR), glucose (GLU), cirrhosis, portal tumor thrombus, the maximum diameter of tumor, location, and cholecystitis or cholelithiasis. The univariate analysis showed that activated partial thromboplastin time (APTT), lower or normal plasma fibrinogen (FIB) level, alpha fetoprotein (AFP), tumor protrusion > 1 cm above the liver surface were all associated with increased risk of SRHC (P < 0.05). Multivariate analysis only showed that lower or normal level of FIB (P = 0.033) and tumor protrusion > 1 cm above the liver surface (P = 0.041) were significant independent risk factors for SRHC. Lower or normal level of FIB and tumor protrusion > 1 cm above the liver surface are significant independent risk factors for spontaneous rupture of hepatocellular carcinoma.

Evaluation of Weight-Based Dosing of Unfractionated Heparin in Obese Children

To determine whether pediatric patients with obesity receiving weight-based dosages of unfractionated heparin (UFH) exhibit an enhanced response when dosed by actual body weight compared with nonobese patients as assessed primarily by the frequency of supratherapeutic anticoagulation. Secondary measures included UFH doses associated with therapeutic anticoagulation. This single-institution retrospective case-matched study included children with and without obesity, matched on a 1:1 basis, who received a weight-based continuous infusion of UFH. Therapeutic monitoring values were defined for activated partial thromboplastin time (aPTT) level (70-101 seconds) and anti-activated factor X (Xa) level (0.35-0.7 U/mL). The study included 50 children. The percentage of patients with supratherapeutic anticoagulation at any point in the study, as measured by either aPTT or anti-Xa level, was similar in the obese and nonobese groups (76% vs 72%; P = 1.0). However, compared with patients without obesity, those with obesity received a lower mean starting dose (17.4 vs 20.2 U/kg/hour; P = .013) and a lower mean maintenance dose (19.1 vs 24.3 U/kg/hour; P = .033) to achieve stable therapeutic monitoring test values. There was no difference in mean initial post-UFH aPTT between the 2 groups, but the mean initial anti-Xa level was higher in the obese group (0.45 vs 0.29 U/mL; P = .045). Compared with children without obesity, those with obesity who received actual body weight-based continuous UFH infusions did not exhibit a higher frequency of supratherapeutic anticoagulation, but did require lower dosages to achieve comparable anticoagulation. Our results highlight recognized discrepancies between aPTT and anti-Xa monitoring assays.

Diagnosis and Management of Common Acquired Bleeding Disorders

Acquired bleeding disorders (ABD) are commonly encountered in both inpatient and outpatient settings. ABD can occur due to consumption, decreased synthesis, or inhibition of coagulation factors and platelets. Clinical presentation may vary, ranging from mild bruising to life-threatening hemorrhage. The location, frequency, severity, and provocation of bleeding provide insight into the cause of ABD. Obtaining a good medical, surgical, family, social, and medication history is a crucial step in determining the underlying etiology. Basic laboratory parameters, such as prothrombin time, partial thromboplastin time, thrombin time, fibrinogen, platelet count, and D-dimer levels, aid in further elucidating the reason for bleeding. Optimal management depends on accurate interpretation of the history and laboratory values. Treatment options include administration of vitamin K; blood component transfusion, consisting of plasma, cryoprecipitate, and/or platelets; and blood derivatives, including single and multiple factor concentrates. These products should be used judiciously, due to potential infectious and noninfectious complications, including transfusion-related acute lung injury and transfusion-associated circulatory overload. This article discusses the management of the more common causes of ABD.

Preoperative Low Dose Recombinant Activated Factor VII Effect during Liver Transplantation

Background: End stage liver disease patients are prone to coagulopathy and frequently require blood transfusion during transplantation. Methods: Prospective study (2008-2011) to investigate the effect of prophylactic intravenous administration of low dose recombinant activated factor VII (rFVIIa) (20 μ/kg) 30 min prior to surgery and repeated one hour later on Standard Coagulation Tests (SCTs), Rotational Thromboelastomery (ROTEM) and Blood Transfusion (BT) requirements during Living Donor Liver Transplantation (LDLT). SCT include Prothrombin Time (PT), International Normalized Ratio (INR) of prothrombin time, Activated Partial Thromboplastin Time (aPPT), fibrinogen and platelets blood levels. ROTEM include EXTEM and INTEM representing coagulation extrinsic and intrinsic pathways respectively, and FIBTEM for fibrinogen activity. Blood transfusion was guided by ROTEM parameters. Control group(C), n=25 and rFVII group, n=25 Results: Both groups preoperative MELD scores, ROTEM and SCTs were comparable (P>0.05). After initial dose to end of dissection, a reduction in INR and aPTTin rFVII group versus control were observed, associated with a reduction in clotting time (CT) and increased alpha angle in ROTEM (P 0.05). BT correlated positively with dissection time (r=0.7, p<0.01), but weakly with preoperative HB (r=-0.3, p<0.05). Conclusion: Low dose rFVII monitored by ROTEM improved coagulation and reduced BT requirements with no evidence of thromboembolic events. Dissection time was another important contributing factor.

Coronary embolism in a patient with massive left atrial thrombus and mechanical valve thrombus: hybrid treatment with surgery and percutaneous intervention

A 67-year-old female was admitted to the emergency department with chest pain for the last 24 hours. She had a history of rheumatic mitral stenosis and had received a mechanical mitral valve (24-mm bi-leaflet St. Jude valve) three years ago. She had been inadequately anti-coagulated for the last two months. At the time of presentation, her international normalized ratio (INR) was 1.02. The electrocardiogram (ECG) revealed atrial fibrillation with a heart rate of 130 beats per minute, right bundle brunch block, and precordial ST segment elevation (Fig. A). Transthoracic echocardiography (TTE) revealed hypokinesis of the apex, apical and mid septal walls, with an ejection fraction of 40%, in normal range of mitral valve area of 2.3 cm2; the peak and mean transmitral gradients were 15 mmHg and 7 mmHg, respectively. Transesophageal echocardiography (TEE) showed up to 1.4 cm fibrillar thrombi on the mitral prosthetic valve and a huge thrombus completely filling the left atrial walls except for the mitral prosthetic valve line and extending to the right and left pulmonary vein ostia on the posterior wall and into the appendix (Fig. B, Video file 1*). Based on the symptom of chest pain and ECG findings, she was diagnosed as subacute anterior myocardial infarction and underwent coronary angiography, which revealed total occlusion of the proximal segment of the left anterior descending artery. The patient was anticoagulated with unfractionated heparin. Lesion wiring and predilatation were done using 2.0x12 and 2.5x20 mm balloons. A 2.75x32 mm bare metal stent was implanted (Fig. C). Heparin was infused for 10 days with adjustment of activated partial thromboplastin time (aPTT) level to 50-70 seconds. Because the follow-up TEE showed no regression of the thrombus on the mechanical valve or of the left atrial thrombus, surgical thrombectomy was planned. Median sternotomy was performed and huge left atrial thrombus fragments (7.5x3 cm, 6x4 cm, 6.5x5 cm, 1.7x0.7 cm, and 1.5x0.7 cm) were excised without mechanical valve replacement (Fig. D). The patient was discharged with optimal anticoagulation. She was asymptomatic and had normal mechanical valve functions on TTE examination at the twomonth follow-up. 784

Fatal pulmonary thromboembolism during total hip replacement under spinal anesthesia

Fatal pulmonary thromboembolism during total hip replacement under spinal anesthesia

Multiple Choice Questions

1.Regarding drug induced liver injury (DILI) the following are TRUE EXCEPT:1.Most common cause of drug induced acute liver failure in India is paracetamol.2.Most common cause of drug induced liver injury in India is antitubercular drugs.3.Degree of liver enzyme elevation correlates with severity of liver disease.4.Clinical jaundice is a predictor of mortality.5.Cholestatic pattern of DILI can be prolonged even on stopping the offending drug.2.Regarding surgery in patients with liver disease the following are TRUE:1.Child-Turcotte-Pugh (CTP) and model for end-stage liver disease (MELD) scores can reliably predict operative mortality in chronic liver disease.2.Acute viral hepatitis is not a contraindication for surgery.3.Laparoscopic cholecystectomy can be safely performed in compensated cirrhotics.4.Umbilical hernias have low risk of complications in cirrhotics and elective repair should not be attempted.5.Preferred anaesthetic agents include sevoflurane, desflurane and isoflurane.3.Regarding peri-operative monitoring after liver transplantation the following are TRUE:1.Cardiovascular events are the most common cause of readmission to intensive care and non-graft related deaths after liver transplantation.2.Conventional tests of coagulation like prothrombin time, activated partial thromboplastin time, platelet count and plasma fibrinogen levels are sufficient measure of coagulation intra-operatively.3.Hyperglycemia is an ominous sign of poor graft function.4.Serum potassium levels are independent predictors of death after liver transplantation.5.Commonest acid-base disorder in the immediate post-operative period is metabolic acidosis.4.Regarding tuberculosis (TB) in chronic liver disease the following are TRUE EXCEPT:1.Cirrhotic patients have a higher chance of developing extra-pulmonary tuberculosis than those without cirrhosis.2.Adenosine deaminase for diagnosis of TB in cirrhosis with ascites has high sensitivity.3.Tuberculin skin testing is sensitive for the diagnosis of TB in cirrhotic patients.4.Likelihood of anti-tubercular drug induced hepatotoxicity is higher in pre-existing liver disease patients.5.Isoniazid induced hepatotoxicity is more common in slow acetylators.5.Regarding hepatotoxicity of anti-tubercular therapy (ATT) the following are TRUE:1.Rechallenge with isoniazid is contraindicated if patient has history of isoniazid induced hepatotoxicity.2.Isoniazid induced transaminitis is self limited and asymptomatic in majority of patients.3.Isolated conjugated hyperbilirubinemia is seen with rifampicin.4.Pyrazinamide mainly causes idiosyncratic hepatotoxicity.5.Inactive carriers of hepatitis B do not have increased risk of ATT induced hepatotoxicity.6.Regarding Budd-Chiari syndrome (BCS) the following are TRUE EXCEPT:1.Most common cause of BCS in India is membranous obstruction of inferior vena cava.2.Ascites with high protein and high serum ascitic albumin gradient is suggestive of BCS.3.Initial imaging modality of choice to diagnose BCS is magnetic resonance venogram.4.Failure to visualize the hepatic veins on Doppler is diagnostic of BCS.5.Direct intrahepatic portosystemic shunt can be done even if all hepatic vein ostia are blocked.7.Regarding the role of gut microbiota in hepatic encephalopathy (HE) the following are TRUE:1.Markers of systemic inflammation are better correlated with HE than the severity of liver disease.2.Pathogen associated molecular patterns (PAMPs) are microbial components that initiate inflammatory cascade.3.Gut microbiota of patients with cirrhosis and normal controls is similar.4.Lactulose exerts its actions in HE predominantly by altering the composition of gut microbiota.5.Stool microbiota is an accurate estimate of intestinal microbiota.8.Regarding primary sclerosing cholangitis (PSC) the following are TRUE:1.Majority of patients with PSC have isolated extrahepatic disease.2.Magnetic resonance cholangiography is the diagnostic modality of choice.3.Dominant stricture is a stenosis with a diameter of <1.5 mm in the hepatic duct or of <1 mm in the common bile duct.4.Inflammatory bowel disease is usually diagnosed after diagnosis of PSC.5.Cholecystectomy is recommended in a patient with PSC with a gallbladder mass lesion, irrespective of its size.9.Regarding primary biliary cirrhosis (PBC) the following are TRUE EXCEPT:1.Antimitochondrial antibodies (AMA) are highly sensitive and specific for the diagnosis of PBC.2.AMA negative cases of PBC have less aggressive disease and better prognosis.3.Ursodeoxycholic acid improves symptoms but does not alter natural course of PBC.4.Modafinil may improve fatigue in patients with PBC.5.Sjogren's syndrome occurs more frequently in PBC than matched controls.10.Regarding overlap syndromes the following are TRUE:1.Overlap of autoimmune hepatitis (AIH) and PBC is the most common variant.2.Overlap of PSC and PBC is common.3.Autoimmune sclerosing cholangitis refers to features of PSC in children with AIH.4.The components of the overlap syndrome may develop sequentially with one appearing years after the first.5.UDCA does not have a beneficial role in overlap syndromes.

Comparison of Thromboelastometry (ROTEM®) With Standard Plasmatic Coagulation Testing in Paediatric Surgery

Background Thromboelastometry (ROTEM®) might be useful to detect intraoperative coagulation disorders early in major paediatric surgery. This observational trial compares this technique to standard coagulation tests. Methods Intraoperative blood sampling was obtained in children undergoing elective major surgery. At each time point, standard coagulation tests [activated partial thromboplastin time (aPTT), prothrombin time (PT), and fibrinogen level] and ROTEM® analyses (InTEM, ExTEM, and FibTEM) were performed simultaneously by trained hospital laboratory staff. Results A total of 288 blood samples from 50 subjects were analysed. While there was a poor correlation between PT and aPTT to ExTEM clotting time (CT) and InTEM CT, respectively, a good correlation was detected between PT and aPTT to clot formation time, and a very good correlation between fibrinogen level and FibTEM assay (r=0.882, P Conclusions PT and aPTT cannot be interchangeably used with ROTEM® CT. Based on the results of ROTEM®, recommended thresholds for PT and aPTT might overestimate the need for coagulation therapy. A good correlation was found between the fibrinogen level and the FibTEM assay. In addition, ROTEM® offered faster turnaround times.

Prognostic significance of D-dimer, natural anticoagulants and routine coagulation parameters in acute pancreatitis

This study was conducted to assess the predictive value of coagulation abnormalities in determining disease severity and prognosis of acute pancreatitis (AP). Patients of AP and 25 healthy volunteers were included in this prospective observational study. The final outcomes were disease severity assessed by Computed Tomography Severity Index, Acute Physiological Assessment and Chronic Health Evaluation--II, presence of organ failure and mortality. Prothrombin time (PT), partial thromboplastin time (PTT), thrombin time (TT), fibrinogen, antithrombin-III (AT-III), protein-C, and protein-S levels were assessed on day 0, 3 and 7 of admission. Of the 38 patients included, 13 died. Mean PT and TT were similar between patients and controls on any given day. PTT showed elevation on day 3 and 7 (p = 0.001) compared to controls, although fibrinogen and D-dimer were significantly higher in patients on all days. Protein C and AT-III were significantly lower in patients and more so in non survivors ( (p = 0.001)) than controls. Multiple logistic regression analysis revealed D-dimer levels > or = 400 - 800 ng/ml and AT- III level of < 71% at admission were associated with high mortality (OR 11.2, AUROC 0.70 and OR 16.6, AUROC 0.82 respectively) as well as predicted organ failure. Serum D-dimer and antithrombin-III levels can be used to assess disease severity and predict outcome of patients with acute pancreatitis.

The Effects of MDCO-2010, a Serine Protease Inhibitor, on Activated Clotting Time in Blood Obtained from Volunteers and Cardiac Surgical Patients

The activated clotting time (ACT) is widely used for monitoring heparin anticoagulation during cardiac surgery. Celite-based ACT values are prolonged when aprotinin is administered. MDCO-2010, a novel serine protease inhibitor, is currently being evaluated as a possible alternative to aprotinin. Therefore, we evaluated the in vitro effects of this novel agent on ACT values using 3 different point-of-care instruments with kaolin or celite as an activator. The study was performed in 2 parts. In the first part, blood samples were obtained from 15 healthy volunteers. Samples were pipetted into small Eppendorf tubes and 2 concentrations of the MDCO-2010 (100 and 500 nM, final concentration) alone or with heparin (1.2 or 2.4 U/mL) were added. ACTs were measured using Helena (celite), Hemochron (kaolin), and Medtronic (kaolin) devices. In the second part of the study, blood samples were obtained intraoperatively, at 5 time points, from 15 patients undergoing cardiopulmonary bypass. MDCO-2010 at a final concentration of 100 or 500 nM was added and ACT testing was performed as before. Additional coagulation tests included prothrombin time, activated partial thromboplastin time, fibrinogen, antithrombin, prothrombin, and anti-Xa levels. Addition of MDCO-2010 concentration-dependently prolonged ACTs in volunteers' and patients' blood samples regardless of the ACT activator or device used. In volunteer samples (no heparin) and in patient samples (baseline and intensive care unit) percent changes in ACTs due to MDCO-2010 were on average 3.1 ± 1.8 times higher (95% confidence interval 2.6-3.6; P < 0.001) for the celite-based Helena device compared with either Hemochron or Medtronic devices. MDCO-2010 causes less ACT prolongation with kaolin than with celite activation.