The patient with cirrhosis: poised to bleed or poised to clot?

It turns out to be a little of both. A number of reviews have addressed this. [1] [2] [3]  Here are some of the key points:

The old maxim that cirrhotic patients are auto-anticoagulated is a myth. Severe liver disease is associated with a delicate balance between bleeding and clotting. In general, cirrhosis tends to be a hypercoagulable state. The relative risk for VTE in such patients has been estimated at around 2.

 

What are the mechanisms for the hypercoagulability of liver disease?

In primary hemostasis, while platelet numbers are often decreased these platelets tend to be hyper-functional. This is due to low levels of ADAM TS 13, correspondingly increased levels of VW factor and multifactorial endothelial dysfunction.

In secondary hemostasis, reasons for hypercoagulability include decreased levels of liver dependent natural anticoagulants such as protein C, protein S, and antithrombin. Factor VIII (not synthesized in the liver) tends to be increased.

There is also impaired fibrinolysis with increased levels of PAI-1 and decreased levels of plasminogen.

What are the clinical implications?

Traditional hemostatic tests are generally used but are of limited reliability. There's been increasing interest in global hemostatic tests such as viscoelastic assays which are conceptually more valid but are not yet ready for translation into clinical practice.

For low risk procedures, prophylactic hemostatic products peri-procedure are generally not indicated.

Antithrombotic treatments should be given in accordance with standard clinical indications recognizing a potentially increased risk of bleeding.

DOACs can be used in many patients but certain published restrictions apply.

Update on management of the acute abdomen in critically ill patients

 

From a recent review in Current Opinion in Critical Care Medicine:

Purpose of review

The aim of this study was to describe important features of clinical examination for the surgical abdomen, relevant investigations, and acute management of common surgical problems in the critically ill.

Recent findings

Lactate remains a relatively nonspecific marker of gut ischemia. Dual energy computed tomography (DECT) scan can improve diagnosis of bowel ischemia. Further evidence supports intravenous contrast during CT scan in critically ill patients with acute kidney injury. Outcomes for acute mesenteric ischemia have failed to improve over time; however, increasing use of endovascular approaches, including catheter-directed thrombolysis, may decrease need for laparotomy in the appropriate patient. Nonocclusive mesenteric ischemia remains a challenging diagnostic and management dilemma. Acalculous cholecystitis is managed with a percutaneous cholecystostomy and is unlikely to require interval cholecystectomy. Surgeon comfort with intervention based on point-of-care ultrasound for biliary disease is variable. Mortality for toxic megacolon is decreasing.

Summary

Physical examination remains an integral part of the evaluation of the surgical abdomen. Interpreting laboratory investigations in context and appropriate imaging improves diagnostic ability; intravenous contrast should not be withheld for critically ill patients with acute kidney injury. Surgical intervention should not be delayed for the patient in extremis. The intensivist and surgeon should remain in close communication to optimize care.

Check point inhibitor induced colitis

An emerging entity.

Should docusate be removed from your hospital’s formulary?

According to this article it should.

Hepatic encephalopathy update

From a recent review:

Hepatic encephalopathy is a state of brain dysfunction resulting from decompensation of cirrhosis. The mortality and morbidity associated with the overt form of hepatic encephalopathy are high, and even the covert form associates with poor outcomes and poor quality of life. We know that the dysfunction is not just an acute insult to the brain but rather results in long-standing cognitive issues that get worse with each episode of HE. Hence, there is an urgency to accurately diagnose these conditions, start appropriate therapy, and to maintain remission. Currently, we have two mainstay pharmacological treatment options (lactulose and rifaximin), but the narrative is evolving with new therapies under trial. Microbiome manipulation resulting in a favorable change to the gut microbiota seems to be a promising new area of therapy.

The strong ion difference in predicting the severity of acute pancreatitis

From a recent paper:

Conclusions

In a cohort of patients with AP, SIG was a strong independent predictor of severity and mortality. Besides, SIG might also be an early marker for acute kidney injury in AP patients. Additional research is needed to identify the nature of the unmeasured anions responsible for such findings.

PPI use may be associated with better heart failure outcomes

From a recently published study:

Abstract

Background It has been recently reported that histamine H2 receptor antagonists (H2RAs) are associated with impairment of ventricular remodeling and incident heart failure. In addition, favorable pleiotropic effects and adverse effects of proton pump inhibitors (PPIs) on cardiovascular disease have also been reported. We examined the associations of acid suppressive therapy using H2RAs or PPIs with cardiac mortality in patients with heart failure.

Methods and Results In total, 1191 consecutive heart failure patients were divided into 3 groups: a non–acid suppressive therapy group (n=363), an H2RA group (n=164), and a PPI group (n=664). In the follow‐up period (mean 995 days), 169 cardiac deaths occurred. In the Kaplan–Meier analysis, cardiac mortality was significantly lower in the PPI group than in the H2RA and non–acid suppressive therapy groups (11.0% versus 21.3% and 16.8%, respectively; log‐rank P=0.004). In the multivariable Cox proportional hazards analysis, use of PPIs, but not H2RAs, was found to be an independent predictor of cardiac mortality (PPIs: hazard ratio 0.488, P=0.002; H2RAs: hazard ratio 0.855, P=0.579). The propensity‐matched 1:1 cohort was assessed based on propensity score (H2RAs, n=164; PPIs, n=164). Cardiac mortality was significantly lower in the PPI group than in the H2RA group in the postmatched cohort (log‐rank P=0.025). In the Cox proportional hazards analysis, the use of PPIs was a predictor of cardiac mortality in the postmatched cohort (hazard ratio 0.528, P=0.028).

Conclusions PPIs may be associated with better outcome in patients with heart failure.

Secondary sclerosing cholangitis in critically ill patients (SSC-CIP)

From a review of this increasingly recognized entity:

Conclusion

SSC-CIP is a rather newly recognized condition that has been gaining more attention in recent years due to rise in ICU treatment-related diseases with improved ICU treatment. SSC-CIP is usually a progressive disease with an aggressive nature leading to liver cirrhosis and hepatic failure without LT.42 During the initial stages of the disease, the clinical symptoms and biochemical profile are not specific and do not differentiate much from endotoxin-associated jaundice, which is a common condition in critically ill patients. Thus, increased awareness and early detection of SSC-CIP and its complications are believed to be crucial to improve the poor prognosis. Biliary casts formation may be considered pathognomonic for SSC-CIP since most patients have them in early stages of the disease and these casts have not been described in the literature in either PSC or IgG4 cholangiopathy.18

Spontaneous bacterial peritonitis

Reviewed in Cureus.

Stool PCR panels

The stool PCR panel can detect a wide variety of pathogens. Here is some info from Mayo Clinic Labs with algorithms for appropriate use.

Fighting C diff: the case for gastric acid suppressant stewardship

A meta-analysis of observational studies suggests it might decrease the risk of Cdiff recurrence.  This includes PPIs and H2 blockers.

Pulmonary manifestations of inflammatory bowel disease

Here is a free full text review.

These can take the form of extraintestinal manifestations of the IBD itself or disease associations due to shared risk factors.

They can occur in both ulcerative colitis and Crohn disease.

Direct extraintestinal manifestations include bronchiolitis, obliterative bronchiolitis and bronchiectasis.

Associated diseases include asthma and sarcoidosis.

Treating portal vein thrombosis in patients with cirrhosis

From a recently published study:

Highlights

•LMWH is effective in about 60% of LC with PVT patients.

•The resolution of thrombus associated with LMWH use is accompanied by improvement in liver function.

•It is more effective for PVT treatment to start LMWH early and to maintain it for a long time.

•LMWH treatment of usual dose and schedule is tolerable for LC patients.

Abstract

Introduction

Portal vein thrombosis (PVT) is a well-known complication in patients with liver cirrhosis (LC). The aim of this study is to investigate the outcomes of cirrhotic patients with PVT treated with low-molecular-weight heparin (LMWH).

Method

Ninety-one LC patients with PVT were treated with dalteparin or enoxaparin for six months. Patients with major bleeding during the last three months, severe thrombocytopenia, or impaired renal function were excluded.

Results

The median age was 62.9 years, and 59 patients had hepatocellular carcinoma. The overall recanalization rate was 61.5%. Patients with a favorable Child-Pugh class and those recently diagnosed as having a thrombus showed significantly better responses. In those who responded to the anticoagulation therapy, the post-treatment bilirubin and platelet levels were improved compared to those in the pre-treatment state. The relapse rate for PVT was 56.6%, and the median time to relapse was 4.0 months. Bleeding was reported in 13 patients (14.4%), and two patients died due to fatal bleeding. A history of variceal bleeding and low serum albumin were risk factors for bleeding.

Conclusion

LMWH therapy for PVT in LC is effective. Advanced LC and a delayed start of anticoagulation treatment decrease the effect of LMWH. Despite its effectiveness, there is a risk of hemorrhage, hence anticoagulation should be carefully considered, especially in patients with advanced LC and a history of variceal bleeding.

Inflammatory bowel disease and primary sclerosing cholangitis

Here’s a nice free full text review.

Pioglitazone use improves NASH and associated fibrosis

JAMA Internal Medicine:

Question What is the association of thiazolidinedione therapy with advanced liver fibrosis in nonalcoholic steatohepatitis?

Findings In this meta-analysis of 8 randomized clinical trials enrolling 516 patients with biopsy-proven nonalcoholic steatohepatitis, thiazolidinedione therapy was associated with reversed advanced fibrosis, improved overall fibrosis stages, and resolution of nonalcoholic steatohepatitis. Pioglitazone hydrochloride use accounted for all of the effects of thiazolidinedione therapy in nonalcoholic steatohepatitis, and these benefits were observed in patients without diabetes as well.

Meaning Pioglitazone use improves advanced fibrosis in nonalcoholic steatohepatitis, even in patients without diabetes, and may thus halt disease progression to end-stage liver disease in this patient population.

Percutaneous gallbladder aspiration in acute cholecystitis

Here’s a free full text systematic review.

Obesity related digestive diseases

From a free full text review:

Obesity is a growing medical and public health problem worldwide. Many digestive diseases are related to obesity. In this article, the current state of our knowledge of obesity-related digestive diseases, their pathogenesis, and the medical and metabolic consequences of weight reduction are discussed. Obesity-related digestive diseases include gastroesophageal reflux disease, Barrett’s esophagus, esophageal cancer, colon polyp and cancer, nonalcoholic fatty liver disease, hepatitis C-related disease, hepatocellular carcinoma, gallstone, cholangiocarcinoma, and pancreatic cancer. Although obesity-related esophageal diseases are associated with altered mechanical and humoral factors, other obesity-related digestive diseases seem to be associated with obesity-induced altered circulating levels of adipocytokines and insulin resistance. The relationship between functional gastrointestinal disease and obesity has been debated. This review provides a comprehensive evaluation of the obesity-related digestive diseases, including pathophysiology, obesity-related risk, and medical and metabolic effects of weight reduction in obese subjects.

The pancreatitis activity scoring system (PASS)

Pancreatitis is both vexing and fascinating. The spectrum of severity and complications is wide. Unfortunately, all too often it is not apparent on day one. Complications typically unfold, one organ system at a time, over several days. When admitting a patient with pancreatitis from the ER it is all but impossible to answer the question “Where will this patient be in four days?” Home? Or in the ICU on mechanical ventilation? The Ranson score, for example, requires assessment out to 48 hours in order to predict mortality. Since Ranson there have been many attempts to develop easier to use tools to assess severity and predict complications. One of the latest is the PASS. The PASS can predict severity on day one according to this report. This free full text article explains the score in more detail. My concern is that it is difficult to use and incorporates subjective components (numeric pain scale).

Non-gastrointestinal presentations of celiac disease

From a recent paper in the American Journal of Medicine:

Abstract

Purpose

The purpose of our study is to investigate the delay in diagnosis of patients with biopsy-proven celiac disease in those who present with gastrointestinal complaints vs nongastrointestinal complaints at our tertiary care center. Celiac disease is an autoimmune disorder that affects approximately 1% of the population worldwide. Celiac disease can have variable clinical presentations; it can be characterized by predominately gastrointestinal symptoms, or it may present without any gastrointestinal symptoms.

Methods

We retrospectively reviewed the charts of 687 adult patients who carried the diagnosis of celiac disease. Patients included had biopsy-proven celiac disease and were categorized based on presence or absence of gastrointestinal symptoms prior to their diagnosis.

Results

There were 101 patients with biopsy-proven celiac disease that met inclusion criteria. Fifty-two patients presented with gastrointestinal symptoms and 49 had nongastrointestinal complaints. Results from Mann-Whitney statistical analysis showed a median delay in diagnosis of 2.3 months for the gastrointestinal symptoms group and 42 months for the nongastrointestinal group (P less than .001); 43.2% of patients with nongastrointestinal symptoms had abnormal thyroid-stimulating hormone, as opposed to 15.5% in the gastrointestinal symptom group (P = .004). Of patients with nongastrointestinal symptoms, 69.4% had anemia, compared with 11.5% of the gastrointestinal symptom group (P less than .001). The majority of patients in the nongastrointestinal symptom group, 68%, were noted to have abnormal bone density scans, compared with 41% in the gastrointestinal symptom group. No sex differences were noted on chi-squared analysis between the 2 groups (P = .997).

Conclusions

Although there is growing awareness of celiac disease, the delay in diagnosis for patients without gastrointestinal symptoms remains prolonged, with an average delay of 3.5 years.

Clinical Significance

There is a mean delay in the diagnosis of celiac disease of 3.5 years in patients who present with nongastrointestinal symptoms.

Specifically, patients with thyroid abnormalities, anemia, or bone mineral density loss should be screened for celiac disease.

Celiac disease is an autoimmune disorder that affects approximately 1% of the population worldwide.1 As many as 6 of 7 cases of celiac disease remain undiagnosed.2 This discrepancy falls in line with the widely accepted “celiac iceberg” concept and may be due to the fact that patients have variable presentations of celiac disease. Manifestations of celiac disease range from typical gastrointestinal complaints characterized by malabsorption and diarrhea, to more silent forms in patients without overt gastrointestinal complaints. Nongastrointestinal presentations may include anemia, thyroid dysfunction, osteoporosis, liver function test abnormalities, and skin manifestations such as dermatitis herpetiformis. The variable presentations create a clinical challenge to physicians in reaching an early diagnosis. As a result, delay in diagnosis is not uncommon and does not go without consequence. Undiagnosed celiac disease can lead to osteoporotic fractures, infertility, unnecessary surgical procedures including bowel resection, and malignancy.1 As the majority of cases of celiac disease can be treated with a strict gluten-free diet alone, adherence to this diet can reverse the risk for adverse clinical outcomes.

Another review on acute pancreatitis

Form the paper:

Purpose of review

Acute pancreatitis is a common condition that affects patients with varying degrees of severity and may lead to significant morbidity and mortality. The present article will review the current paradigm in acute pancreatitis management within the first 72 h of diagnosis.

Recent findings

Patients presenting with acute pancreatitis should be evaluated clinically for signs and symptoms of organ failure in order to appropriately triage. Initial management should focus on fluid resuscitation, with some data to support Ringer's lactate over physiological saline. Routine use of prophylactic antibiotics in acute pancreatitis is not recommended, nor is urgent endoscopic retrograde cholangiopancreatography in the absence of concomitant acute cholangitis. Early oral feeding should be encouraged, not avoided, and use of parenteral nutrition is discouraged. Cholecystectomy during the same admission of biliary pancreatitis should be performed in order to prevent future acute pancreatitis episodes. Patients with acute pancreatitis secondary to alcohol should receive alcohol counseling. Finally, there is ongoing interest in the development of prognostic laboratory tests in acute pancreatitis and pharmacological therapies to reduce the inflammation that occurs in acute pancreatitis.

Summary

Acute pancreatitis is a common and heterogeneous condition with the potential for significant morbidity. Best practices in acute pancreatitis management focus on triage, hydration and enteral feeding.