Time to Adjust the Knowledge Doubling Curve in Hepatology

In his book, Critical path, Buckminster Fuller (Fuller 1981), American architect, systems theorist, author, designer, inventor, and futurist, created the ‘knowledge doubling curve’. He noticed that until 1900 human knowledge doubled approximately every century and by the end of World War II knowledge was doubling every 25 years (Knowledge is not everything, Paul Chamberlain). Now the doubling of knowledge, in the age of the internet and social media, has become even shorter, perhaps less than a year.

I was thinking about this knowledge doubling curve after reading two practice guidances in a recent issue of Hepatology:

The first guidance is mainly for reference as pediatric gastroenterologists do not focus on reproductive health. The authors do provide guidance on contraceptive options which is an important topic for adolescents. The main guidance is disease-specific information for pregnancy in the setting of underlying liver conditions including liver transplantation, cirrhosis, viral hepatitis, autoimmune hepatitis, PSC, PBC, Wilson’s disease, hepatitis C, nonalcoholic fatty liver disease, HELLP, acute fatty liver disease of pregnancy, Budd-Chiari, FNH, hepatocellular adenoma, and others. The guidance also provides recommendations for how to evaluate abnormal liver tests in pregnancy and reviews liver medications during pregnancy (Table 4).

The second guidance reviews the following:

  • An overview of the current understanding of bleeding and thrombosis in cirrhosis.
  • An evidence‐based justification for bleeding risk assessment in patients with cirrhosis before invasive procedures, including current concepts in preprocedural testing and laboratory analysis and their role in predicting bleeding complications.
  • An outline of established and recently identified risk factors for venous thrombosis in the portal and hepatic venous systems in both patients with and without cirrhosis along with thrombophilia testing recommendations.
  • A review of the strengths and weaknesses of the various classification systems for portal vein thrombosis and a proposal for standard nomenclature regarding characterization of portal vein thrombosis location, time course, and progression.

Useful points:

  • In patients with cirrhosis, there are “complex hemostatic changes that are not adequately captured by traditional laboratory measures of hemostasis, such as PT, aPTT, and platelet count.”
  • “Because of conflicting data in the literature, there is no data-driven specific INR or platelet cut-off in which procedural bleeding risk is reliable increased.” In some studies, the authors conclude that “that the low platelet count may have been merely a reflection of advanced portal hypertension and not a causative risk factor for bleeding.”
  • For Platelets in the setting of cirrhosis: “Given the low risk of bleeding of many common procedures, potential risks of platelet transfusion, lack of evidence that elevating the platelet count reduces bleeding risk, and ability to use effective interventions, including transfusion and hemostasis if bleeding occurs, it is reasonable to perform both low‐ and high‐risk procedures without prophylactically correcting the platelet count...An individualized approach to patients with severe thrombocytopenia before procedures is recommended because of the lack of definitive evidence for safety and efficacy of interventions intended to increase platelet counts in patients with cirrhosis.” The authors note in Table 4, that the AASLD does not have a specific threshold for platelets, whereas other societies have used values of >30 or >50.
  • For INR in setting of cirrhosis: “The INR should not be used to gauge procedural bleeding risk in patients with cirrhosis who are not taking vitamin K antagonists (VKAs)…Measures aimed at reducing the INR are not recommended before procedures in patients with cirrhosis who are not taking VKAs…FFP transfusion before procedures is associated with risks and no proven benefits.”
  • The guidance lists a step‐by‐step treatment and surveillance algorithm for portal vein thrombosis in patients with cirrhosis (and without cirrhosis).
  • The guidance provides updated diagnostic, treatment, and management recommendations for sinusoidal obstruction syndrome (formerly known as hepatic-veno-occlusive disease), hereditary hemorrhagic telangiectasia, and hepatic vein thrombosis (aka Budd-Chiari).
  • Classification and management recommendations for idiopathic noncirrhotic portal hypertension and the portosinusoidal vascular disorders.
  • Surveillance and evaluation recommendations for hepatic and splenic artery aneurysms.
  • A review of the management issues in vascular liver disorders specific to children and guidance on early intervention in extrahepatic portal vein obstruction in children.

My take: In essence, these two articles are condensed textbooks. The first on Liver Disease, Pregnancy and Reproductive Health. And the second on Bleeding in the Setting of Chronic Liver Disease and Vascular Liver Diseases.

Parenteral Omega-3 Lipid Emulsions and Risk of Bleeding

A recent study indicates that patient’s placed on omega-3 lipid emulsions (eg. Omegaven) may be at risk for bleeding due to platelet dysfunction (J Pediatr 2014; 164: 652-4).

While omega-3 lipid emulsions have received a lot of attention due to improvements in intestinal failure associated liver disease (IFALD) (see previous links to prior posts below), the amount of data supporting their usage and potential advantages compared with standard lipids at similar dosing remains limited.

This case report describes a 9-month old who developed life-threatening hemorrhage following a standard central line placement.  Due to difficulty stopping the bleeding, the patient’s omegaven was discontinued.  Standard workup for bleeding disorders were negative.  Subsequently, the authors investigated clot formation and platelet function in a neonatal animal model.

Key Result: Piglets treated with omegaven had a doubling of time to clot formation and marked platelet agonist inhibition.

The discussion notes that “there is an acknowledged risk of high dose O3FA lipids [omegaven] increasing bleeding time because of competitive inhibition of AA [arachidonic acid] production, hence decreased TxA2 [thromboxane A2].  In addition, platelet-derived growth factor-like protein and endothelial platelet activation factor are decreased.”

Take home points (from the authors):

  • “the case report and piglet studies together demonstrate that there is potential for a significant antiplatelet effect and inhibition of the coagulation cascade with O3FA therapy…”
  • “We would suggest discontinuation of Omegaven therapy 72 hours preoperatively in high-risk cases where bleeding may be difficult to directly control.”
  • “Institutionally, we have abandoned the sole use of Omegaven therapy.”

Related blog posts: