Periprocedural management of abnormal coagulation parameters and thrombocytopenia in patients with cirrhosis: Guidance from the SSC of the ISTH

Prolonged prothrombin time and thrombocytopenia are common in patients with cirrhosis. These parameters do not reflect the overall hemostatic rebalance or bleeding risk in the periprocedural setting; however, attempts to correct these parameters remain frequent. We review the literature on periprocedural bleeding risk, bleeding risk factors, and the risk and benefits of hemostatic interventions in patients with cirrhosis. We provide guidance recommendations on evaluating bleeding risk in this patient group and management of hemostatic abnormalities in the periprocedural setting.     

Yersinia pseudotuberculosis disrupts intestinal barrier integrity through hematopoietic TLR-2 signaling

Intestinal barrier function requires intricate cooperation between intestinal epithelial cells and immune cells. Enteropathogens are able to invade the intestinal lymphoid tissue known as Peyer's patches (PPs) and disrupt the integrity of the intestinal barrier. However, the underlying molecular mechanisms of this process are poorly understood. In mice infected with Yersinia pseudotuberculosis, we found that PP barrier dysfunction is dependent on the Yersinia virulence plasmid and the expression of TLR-2 by hematopoietic cells, but not by intestinal epithelial cells. Upon TLR-2 stimulation, Y. pseudotuberculosis-infected monocytes activated caspase-1 and produced IL-1β. In turn, IL-1β increased NF-κB and myosin light chain kinase activation in intestinal epithelial cells, thus disrupting the intestinal barrier by opening the tight junctions. Therefore, Y. pseudotuberculosis subverts intestinal barrier function by altering the interplay between immune and epithelial cells during infection.     

Relevance of clotting tests in liver disease

Liver disease is associated with impairment of the haemostatic function due to the abnormal and decreased synthesis of the clotting factors. It is thus only logical to have considered assessment of the clotting profile (to include prothrombin time (PT) and activated partial thromboplastin time (aPTT)) to be an integral part of the comprehensive assessment of a patient who presents with liver impairment. Laboratory abnormalities of coagulation are considered to be a predictive risk factor for bleeding, but patients with liver disease do not have bleeding pattern as those who have coagulation factor deficiencies. Recent experiments have cast doubts over the use of PT and aPTT as a marker of bleeding in liver disease and the use of such tests to decide the need for plasma replacement before interventions like liver biopsy. This article reviews the relevance of the clotting profile in liver disease, the other factors involved in the haemostatic failure associated with it, and the technical problems in the interpretation of these results. Most importantly, it stresses the need for more trials to help us guide the management of bleeding in patients with liver impairment.     

The possible role of reticulocytes in sickle cell disease associated thromboembolism

Sickle cell disease (SCD) is associated with an increased incidence of deep vein thrombosis and pulmonary embolism which contributes to the morbidity and mortality associated with it. The predisposition to thrombosis has been attributed to the different blood components including platelets, the coagulation system and recently damaged red cells. This article discusses the possible role of reticulocytes in promoting thrombus formation in individuals with SCD and suggests a similar pathogenetic mechanism in thromboembolism associated with other hemolytic states.     

Modified ISTH pregnancy-specific DIC score in parturients with liver rupture: population-based case series

Objectives: Liver rupture and hematoma are rare life-threatening complications of pregnancy. The aims of the current study are to: (1) characterize in a population-based study all cases of liver hematoma and/or rupture; and (2) validate the utility of the International Society on Thrombosis and Haemostasis (ISTH) modified pregnancy specific disseminated intravascular coagulation (DIC) score in those cases.

Study design: A retrospective cohort study including all patients with liver subcapsular hematoma or rupture between the years 1996 and 2012 was conducted. Information on maternal characteristics, clinical presentation, diagnostic studies, therapeutic modalities, as well as maternal and fetal outcomes was collected. The pregnancy-specific modified ISTH DIC scores were calculated from admission to discharge, a score >26 is suggestive of DIC.

Results: Out of 175,000 births in our database, seven patients were identified with liver rupture or subcapsular hematoma, representing a prevalence of 4:100,000 deliveries. Of those, six had liver rupture and one had subcapsular liver hematoma. One patient died of hemorrhagic shock. Four patients underwent surgical liver packing and one also underwent hepatic artery ligation. Four out of seven patients were diagnosed during the immediate postpartum period with severe features of preeclampsia or with hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome. Modified ISTH pregnancy-specific DIC scores were calculated for five out of seven patients, and three (60%) had a score higher than 26. Patients with higher scores received more blood product transfusions, had longer hospitalizations, and their neonates had lower 1 and 5?minutes Apgar scores.

Conclusions: Elevated pregnancy-specific modified ISTH DIC score (>26) in patients with liver hematoma or rupture was associated with adverse maternal and neonatal outcomes and appeared to perform well in distinguishing high and low-risk cases. Postpartum preeclampsia may be associated with severe features and a more complicated disease course.     

Prognostic implications of leg ulcers from hydroxycarbamide therapy in patients with essential thrombocythaemia

Essential thrombocythemia (ET) is a clonal stem-cell disorder characterized by persistent thrombocytosis. Patients with ET and risk factors for thrombotic complications have been shown to benefit from cytoreductive therapy, the most common agent used being, hydroxycarbamide. Although this agent is usually well-tolerated, one of the recognized adverse effects is the development of leg ulcers. We undertook retrospective analysis of consecutive ET patients treated with hydroxcarbamide and identified several specific features for this complication including advanced age, female preponderance, reduced overall survival, tendency to develop future vascular events and intolerance to the second line agent, anagrelide.