Thrombocytopenia and Hemostatic Changes in Acute and Chronic Liver Disease: Pathophysiology, Clinical and Laboratory Features, and Management

Thrombocytopenia, defined as a platelet count <150,000/μL, is the most common complication of advanced liver disease or cirrhosis with an incidence of up to 75%. A decrease in platelet count can be the first presenting sign and tends to be proportionally related to the severity of hepatic failure. The pathophysiology of thrombocytopenia in liver disease is multifactorial, including (i) splenomegaly and subsequently increased splenic sequestration of circulating platelets, (ii) reduced hepatic synthesis of thrombopoietin with missing stimulation both of megakaryocytopoiesis and thrombocytopoiesis, resulting in diminished platelet production and release from the bone marrow, and (iii) increased platelet destruction or consumption. Among these pathologies, the decrease in thrombopoietin synthesis has been identified as a central mechanism. Two newly licensed oral thrombopoietin mimetics/receptor agonists, avatrombopag and lusutrombopag, are now available for targeted treatment of thrombocytopenia in patients with advanced liver disease, who are undergoing invasive procedures. This review summarizes recent advances in the understanding of defective but at low level rebalanced hemostasis in stable cirrhosis, discusses clinical consequences and persistent controversial issues related to the inherent bleeding risk, and is focused on a risk-adapted management of thrombocytopenia in patients with chronic liver disease, including a restrictive transfusion regimen.

Effect of Citrofortunella microcarpa (Calamansi) Peelings on Whole Blood Coagulation Using Blood Samples from Albino Mice

Citrofortunella microcarpa, locally known as calamansi in the Philippines, is an intergeneric hybrid between Citrus reticulata and Fortunella japonica. This fruit is widely cultivated in the Philippines for its fruit juice as an abundant source of vitamin C and as a condiment in many local foods in the country. Sadly, only the pulp is needed for squeezing while the peels are thrown after extracting the juice. Previous studies revealed that the peels of Citrus, as member of the Rutaceae family, can synthesize both coumarins and furanocoumarins wherein their derivates are used as oral anticoagulants which can inhibit vitamin K from functioning as a cofactor in the hepatic synthesis of the vitamin K-dependent coagulation factors II, VII, IX, and X. In this study, the extract of calamansi peelings were proven to have an anticoagulant property on blood samples from albino mice. This study will pave the way for scientists to allot time in studying calamansi peelings for it may be another source of medicine to help patients who are prone to have stroke, myocardial infarction, and other blood clotting diseases.

Decreased antithrombin activity and inflammation in cats

Objectives The objective of this study was to determine if inflammatory markers are associated with antithrombin activity in cats. Methods For a retrospective population of 231 cats admitted to a referral hospital, antithrombin activity was classified as decreased (n = 77), intermediate (n = 97) or in the upper quartile (n = 57). Odds ratios (ORs) were calculated for an association between decreased or upper quartile activity and hypoalbuminemia, hyperfibrinogenemia, band neutrophilia and toxic change. Multiple logistic regression was performed to determine if an association between band neutrophilia and decreased antithrombin activity was independent of decreased hepatic synthesis, consumptive coagulopathy or protein loss. Results Cats with decreased antithrombin activity were more likely than cats with intermediate-to-upper quartile activity to have band neutrophilia (OR 2.85; P = 0.0050), hypoalbuminemia (OR 12.1, P <0.0001) or toxic neutrophils (OR 4.47, P <0.0001). Cats with antithrombin activity in the upper quartile were less likely than those with intermediate-to-low activity to have hypoalbuminemia (OR 0.31, P = 0.0023) or toxic neutrophils (OR 0.44, P = 0.033). In a regression model that included other mechanisms for decreased antithrombin, band neutrophilia remained associated with decreased antithrombin activity (adjusted OR 2.62, P = 0.013). Conclusions and relevance Contrary to previous studies suggesting antithrombin is a feline positive acute phase protein, this study demonstrates an association between decreased antithrombin activity and inflammation. Further studies are needed to determine the mechanistic basis of this association.

A Critical Role of Hepatic GABA in The Metabolic Dysfunction and Hyperphagia of Obesity

Hepatic lipid accumulation is a hallmark of type II diabetes (T2D) and associated with hyperinsulinemia, insulin resistance, and hyperphagia. Hepatic synthesis of GABA, catalyzed by GABA-transaminase (GABA-T), is upregulated in obese mice. To assess the role of hepatic GABA production in obesity-induced metabolic and energy dysregulation, we treated mice with two pharmacologic GABA-T inhibitors and knocked down hepatic GABA-T expression using an antisense oligonucleotide. Hepatic GABA-T inhibition and knockdown decreased basal hyperinsulinemia and hyperglycemia, and improved glucose intolerance. GABA-T knockdown improved insulin sensitivity assessed by hyperinsulinemic-euglycemic clamps in obese mice. Hepatic GABA-T knockdown also decreased food intake and induced weight loss without altering energy expenditure in obese mice. Data from people with obesity support the notion that hepatic GABA production and transport are associated with serum insulin, HOMA-IR, T2D, and BMI. These results support a key role for hepatocyte GABA production in the dysfunctional glucoregulation and feeding behavior associated with obesity.

The Role of Cholesterol in Assessing the Condition of the Surgical Patients

Summary Cholesterol is a white, waxy substance that always takes part in building each cell in the human body. The role of cholesterol in the normal functioning of the human body has been known for a long time, however, it is mainly due to its elevated levels and the health risk of it. It is less well known that low serum cholesterol levels are associated with serious health problems. When it comes to intensive care unit (ICU) patients, hypocholesterolemia may indicate infectious complications, impaired hepatic synthesis, significant bodily injury. Surgical patients are judged for operative trauma and perioperative stress, as well as for the resuscitation process.

Prolonged Hypercupremia after Laparoscopic Vertical Sleeve Gastrectomy Successfully Treated with Oral Zinc

A 30-year-old female underwent vertical sleeve gastrectomy. Postoperatively, hypercupremia and elevated ceruloplasmin were identified. Further testing revealed normal blood levels of transaminases, alkaline phosphatase, and albumin. She stopped ingestion of multivitamins, began a copper-free multivitamin, and then began a low copper diet, but with no improvement in hypercupremia. Protein electrophoresis was normal with no M-spike. Urinary copper excretion was normal at 0.24 micromol/24 hours (normal: < 0.55), and there were no Kayser-Fleischer rings on slit lamp examination. Two years postoperatively, she lost 44% of excess preoperative weight and she began zinc sulfate before meals twice daily (115 mg elemental Zinc/day). At 2 months and 8 months later, plasma copper and ceruloplasmin had essentially normalized. Increased production of ceruloplasmin could have been a response to significant weight loss or the presence of nonalcoholic steatohepatitis. The mechanism of zinc’s beneficial effect is uncertain but may be related to suppressing hepatic synthesis of or secretion of ceruloplasmin.