F. Iannuzzi

Detection of the Imbalance of Procoagulant Versus Anticoagulant Factors in Cirrhosis by a Simple Laboratory Method

Patients with cirrhosis possess an imbalance in procoagulant versus anticoagulant activity due to increased factor VIII and decreased protein C. This imbalance can be detected by thrombin‐generation assays performed in the presence/absence of thrombomodulin (predicate assay) that are not readily available in clinical laboratories. We sought to assess this hypercoagulability with a simpler thrombin‐generation assay performed in the presence/absence of Protac, a snake venom that activates protein C in a manner similar to thrombomodulin (new assay). We analyzed blood from 105 patients with cirrhosis and 105 healthy subjects (controls). Results for the predicate‐assay or the new‐assay were expressed as ratio (with:without thrombomodulin) or as Protac‐induced coagulation inhibition (PICI%). By definition, high ratios or low PICI% translate into hypercoagulability. The median(range) PICI% was lower in patients (74% [31%‐97%]) than controls (93% [72%‐99%]; P < 0.001), indicating that patients with cirrhosis are resistant to the action of Protac. This resistance resulted in greater plasma hypercoagulability in patients who were Child class C than those who were A or B. The hypercoagulability of Child C cirrhosis (63% [31%‐92%]) was similar to that observed for patients with factor V Leiden (69% [15%‐80%]; P = 0.59). The PICI% values were correlated with the levels of protein C (rho = 0.728, P < 0.001) or factor VIII (rho = −0.517, P < 0.001). Finally, the PICI% values were correlated with the predicate assay (rho = −0.580, P < 0.001). Conclusion: The hypercoagulability of plasma from patients with cirrhosis can be detected with the new assay, which compares favorably with the other markers of hypercoagulability (i.e., high factor VIII and low protein C) and with the predicate‐assay based on thrombin‐generation with/without thrombomodulin. Advantages of the new assay over the predicate assay are easy performance and standardized results. Prospective trials are needed to ascertain whether it is useful to predict thrombosis in patients with cirrhosis. HEPATOLOGY 2010

Point-of-care coagulation monitors calibrated for the international normalized ratio for cirrhosis (INRliver) can help to implement the INRliver for the calculation of the MELD score

BACKGROUND/AIMS The MELD defines a score used to prioritize patients awaiting liver transplantation and includes results for bilirubin, creatinine and PT expressed as INR. It is assumed that the MELD for individual patients is the same regardless of the laboratory method used for testing, thus ensuring parity of organ allocation. Previous studies showed that the INR calibrated for patients on vitamin K antagonists (INR(vka)) does not normalize results across thromboplastins, whereas an alternative calibration called INR(liver) does. However, implementation of INR(liver) calibration for thromboplastins is difficult in practice. This study aimed to assess whether easy-to-run whole-blood coagulation monitors (widely used for patients on VKA) can be calibrated to measure efficiently the INR(liver) and minimize the interlaboratory variability. METHODS PT values for 61 cirrhotic patients were measured on native-blood with 2 monitors calibrated in terms of INR(vka). PTs for these subjects were also measured with a WHO-standard for thromboplastin. Paired-PTs with the monitors and the standard were subsequently used to calibrate the monitors in terms of INR(liver). INR(vka) and INR(liver) were then compared to assess for statistical significance. RESULTS The mean INR(vka) obtained with the monitors and the standard were significantly different (p<0.001). Conversely, the corresponding INR(liver) were not. CONCLUSIONS The INR(liver) calibration as previously described for thromboplastins works also for the easy-to-run whole-blood coagulation monitors. Once the monitors are calibrated by the manufacturer in terms of INR(liver) they could be used as near-patient-testing devices directly by the personnel of liver units making the determination of the INR for patients awaiting liver transplantation much easier and standardized.

Primary prophylaxis of variceal bleeding in cirrhotic patients: A cohort study

BACKGROUND Current guidelines recommend beta-blockers for primary prevention of variceal haemorrhage in cirrhotic patients, and band ligation for patients with contraindications or intolerance to beta-blockers. However, it has been suggested that these patients may respond poorly to band ligation. AIM We evaluated the usefulness of a strategy in which band ligation was used to treat patients with contraindications or intolerance and patients not responding to beta-blockers identified by hepatic vein pressure gradient measurement. Haemodynamic responders and patients refusing hepatic vein pressure gradient measurement were given long-term beta-blockers. METHODS One hundred and thirty-five consecutive patients with high-risk oesophageal varices and no prior bleeding were enrolled. Twenty-five patients with contraindications (group A), 26 with intolerance to beta-blockers (group B) and 25 showing a poor haemodynamic response (Group C) underwent band ligation. Twenty-two haemodynamic responders (Group D) and 37 refusing hepatic vein pressure gradient measurement (Group E) were treated with beta-blockers. RESULTS Median follow-up was 32 months. 12/135 patients (8.9%) bled: 3/25 (12%) in group A, 1/26 (3.8%) in group B, 0/25 (0%) in group C, 0/22 (0%) in group D and 8/37 (22.2%) in group E. Mortality was 8/135 (5.9%). CONCLUSIONS Patients with contraindications, intolerance or not responding to beta-blockers treated with band ligation achieve protection from variceal bleeding comparable to that of good responders to beta-blockers.

Acute variceal bleeding: Pharmacological treatment and primary/secondary prophylaxis

Variceal bleeding is one of the most severe complications of portal hypertension related to liver cirrhosis. Primary prophylaxis is considered mandatory in patients with cirrhosis and high-risk oesophageal varices, and once varices have bled, every effort should be made to arrest the haemorrhage and prevent further bleeding episodes. In acute variceal bleeding, vasoactive drugs that lower portal pressure should be started even before endoscopy, and should be maintained for up to 5 days. The choice of vasoactive drug should be made according to local resources. Terlipressin, somatostatin and octreotide can be used; vasopressin plus transdermal nitroglycerin may be used if no other drug is available. In variceal bleeding, antibiotic therapy is also mandatory. In primary and secondary prophylaxis, beta-blockers are the mainstay of therapy. In secondary prophylaxis (but not in primary prophylaxis) these drugs can be combined with organic nitrates.

Impact of portal vein thrombosis on the efficacy of endoscopic variceal band ligation

BACKGROUND Influence of portal vein thrombosis on efficacy of endoscopic variceal banding in patients with cirrhosis or extrahepatic portal vein obstruction has never been evaluated. Aim of the study was to assess influence of thrombosis on rate and time to eradication in cirrhosis and extrahepatic portal vein obstruction undergoing banding, compared to cirrhotic patients without thrombosis. METHODS Retrospective analysis of 235 consecutive patients (192 with cirrhosis without thrombosis, 22 cirrhosis and thrombosis and 21 extrahepatic portal vein obstruction) who underwent banding. Banding was performed every 2-3 weeks until eradication; endoscopic follow-up was performed at 1, 3, 6 months, then annually. RESULTS Eradication was achieved in 233 patients. Median time to eradication in cirrhotic patients with portal vein thrombosis vs. cirrhotic patients without thrombosis was 50.9 days (12-440) vs. 43.4 days (13-489.4); log-rank: 0.04; patients with extrahepatic portal vein obstruction vs. cirrhotic patients without thrombosis 63.9 days (31-321.6) vs. 43.4 days (13.0-489.4); log-rank: 0.008. Thrombosis was shown to be the only risk factor for longer time to eradication. CONCLUSIONS Portal vein thrombosis per se appears to be the cause of a longer time to achieve eradication of varices but, once eradication is achieved, it does not influence their recurrence.

Schwann cell hamartoma: case report

BackgroundColorectal polyps of mesenchymal origin represent a small percentage of gastrointestinal (GI) lesions. Nevertheless, they are encountered with increasing frequency since the widespread adoption of colonoscopy screening.Case presentationWe report a case of a small colonic polyp that presented as intramucosal diffuse spindle cell proliferation with a benign cytological appearance, strong and diffuse immunoreactivity for S-100 protein, and pure Schwann cell phenotype. Careful morphological, immunohistochemical and clinical evaluation emphasize the differences from other stromal colonic lesions and distinguish it from schwannoma, a circumscribed benign nerve sheath tumor that rarely arises in the GI tract.ConclusionAs recently proposed, this lesion was finally described as mucosal Schwann cell hamartoma.

Procedure for Small Bowel Video Capsule Endoscopy

The standard equipment necessary to perform a small bowel video capsule endoscopy (SBCE) procedure is summarized in Table 4.1. A video capsule designed for small bowel evaluation is required. Measuring 26 mm × 11 mm, current models operate at either a fixed frame rate of 4 frames per second (Fig. 4.1) or an adaptive frame rate of 2–6 frames per second. Each capsule is sealed in a small box and marked with an identifiable number and expiration date. The capsule is activated upon opening the box and has a minimum battery life of 12 h. Specific technological detail was discussed further in Chap. 3.

HVPG-Guided Prophylaxis

Portal hypertension is defined as an increase of the pressure in the portal vein system. Nowadays portal hypertension is generally assessed using HVPG measurement. 10 mmHg is the threshold for clinically significant portal hypertension when complications of portal hypertension (i.e., esophageal variceal bleeding, ascites) can arise. HVPG measurement, if performed properly, can give important prognostic information and guide the treatment of patients in primary and secondary prophylaxis and in case of acute variceal bleeding. Several studies have shown that the decrease of HVPG to ≤12 mmHg by chronic treatment, in primary and secondary prophylaxis completely prevents variceal bleeding. In case of a reduction ≥20 % from baseline, even though not below 12 mmHg, there is still a protection from variceal bleeding. About 30–40 % of patients in primary prophylaxis and 40–50 % in secondary prophylaxis achieve a reduction in HVPG to ≤12 mmHg or ≥20 % during chronic medical treatment for portal hypertension and can be considered good hemodynamic responders. Those patients who do not achieve an hemodynamic response are considered nonresponders and their risk of bleeding is about 30–40 % at 2–3 years in primary prophylaxis and 46–65 % in secondary prophylaxis. In the setting of acute variceal bleeding, the finding of HVPG values ≥20 mmHg was a predictor of high risk of treatment failure; these “high risk” patients may benefit from treatment with “early TIPS” placement.