Fibrinogen contribution to clot strength in patients with sepsis and hematologic malignancies and thrombocytopenia-a prospective, single-center, analytical, cross-sectional study.

Background: Patients with hematological malignancies (HM) frequently present thrombocytopenia and higher risk of bleeding. Although transfusion is associated with higher risk of adverse events and poor outcomes, prophylactic transfusion of platelets is a common practice to prevent hemorrhagic complications. Thromboelastometry has been considered a better predictor for bleeding than isolated platelet counts in different settings. In early stages of sepsis, hypercoagulability may occur due to higher fibrinogen levels. Objectives: To evaluate the behavior of coagulation in patients with HM who develop sepsis and to verify whether a higher concentration of fibrinogen is associated with a proportional increase in maximum clot firmness (MCF) even in the presence of severe thrombocytopenia. Methods: We performed a unicentric analytical cross-sectional study with 60 adult patients with HM and severe thrombocytopenia, of whom 30 had sepsis (sepsis group) and 30 had no infections (control group). Coagulation conventional tests and specific coagulation tests, including thromboelastometry, were performed. The main outcome evaluated was MCF. Results: Higher levels of fibrinogen and MCF were found in sepsis group. Both fibrinogen and platelets contributed to MCF. The relative contribution of fibrin was significantly higher (60.5 ± 12.8% vs 43.6 ± 9.7%; P < .001) and that of platelets was significantly lower (39.5 ± 12.8% vs 56.4 ± 9.7%; P < .001) in the sepsis group compared with the control group. Conclusion: Patients with sepsis and HM presented higher concentrations of fibrinogen than uninfected patients, resulting in greater MCF amplitudes even in the presence of thrombocytopenia.

Communication from the Scientific Standardization Committees of the International Society on Thrombosis and Haemostasis on vascular endothelium-related biomarkers in disseminated intravascular coagulation.

Disseminated intravascular coagulation (DIC) is not a disease criterion but a pathomechanistic process that accompanies various underlying diseases. According to the International Society on Thrombosis and Haemostasis definition, endothelial injury is an essential component in addition to systemic coagulation activation. Despite this definition, current diagnostic criteria for DIC do not include biomarkers for vascular endothelial injury. Endothelial cells are critical for hemostatic regulation because they produce various antithrombotic substances and express anticoagulant factors at the same time as facilitating coagulation, inflammatory reactions, platelet aggregation, and fibrinolysis with acute injury. Endothelial cells also exhibit various receptors, adhesion molecules, and the critical role of glycocalyx that regulates cellular interactions in thromboinflammation. For clinicians, biomarkers suitable for assessing endothelial injury are not readily available. Although we still do not have ideal biomarkers, antithrombin activity and von Willebrand factor can be candidates for the endothelium-related markers because those reflect the severity and are available in most clinical settings. Further, the dysfunction of endothelial cell in DIC arising from various underlying diseases is likely highly variable. For example, the involvement of endothelial dysfunction is significant in sepsis-induced coagulopathy, while moderate in trauma-induced coagulopathy, and variable in hematologic malignancy-associated coagulopathy. Because of the complexity of disease status associated with DIC, further research searching clinically available endothelium-related biomarkers is expected to establish individualized diagnostic criteria and potential therapeutic approaches.

Cirrhotic Cardiomyopathy-A Veiled Threat.

Cirrhotic cardiomyopathy (CCM) is defined as cardiac dysfunction in patients with liver cirrhosis without preexisting cardiac disease. According to the definition established by the World Congress of Gasteroenterology in 2005, the diagnosis of CCM includes criteria reflecting systolic dysfunction, impaired diastolic relaxation, and electrophysiological disturbances. Because of minimal or even absent clinical symptoms and echocardiographic signs at rest according to the 2005 criteria, CCM diagnosis is often missed or delayed in most clinically stable cirrhotic patients. However, cardiac dysfunction progresses in time and contributes to the pathogenesis of hepatorenal syndrome and increased morbidity and mortality after liver transplantation, surgery, or other invasive procedures in cirrhotic patients. Therefore, a comprehensive cardiovascular assessment using newer techniques for echocardiographic evaluation of systolic and diastolic function, allowing the diagnosis of CCM in the early stage of subclinical cardiovascular dysfunction, should be included in the screening process of liver transplant candidates and patients with cirrhosis in general. The present review aims to summarize the most important pathophysiological aspects of CCM, the usefulness of contemporary cardiovascular imaging techniques and parameters in the diagnosis of CCM, the current therapeutic options, and the importance of early diagnosis of cardiovascular impairment in cirrhotic patients.

Continuous renal replacement therapy in cytokine release syndrome following immunotherapy or cellular therapies?

Recently, an increasing number of novel drugs were approved in oncology and hematology. Nevertheless, pharmacology progress comes with a variety of side effects, of which cytokine release syndrome (CRS) is a potential complication of some immunotherapies that can lead to multiorgan failure if not diagnosed and treated accordingly. CRS generally occurs with therapies that lead to highly activated T cells, like chimeric antigen receptor T cells or in the case of bispecific T-cell engaging antibodies. This, in turn, leads to a proinflammatory state with subsequent organ damage. To better manage CRS there is a need for specific therapies or to repurpose strategies that are already known to be useful in similar situations. Current management strategies for CRS are represented by anticytokine directed therapies and corticosteroids. Based on its pathophysiology and the resemblance of CRS to sepsis and septic shock, as well as based on the principles of initiation of continuous renal replacement therapy (CRRT) in sepsis, we propose the rationale of using CRRT therapy as an adjunct treatment in CRS where all the other approaches have failed in controlling the clinically significant manifestations.

Can goal-directed fluid therapy decrease the use of blood and hemoderivates in surgical patients?

The purpose of goal-directed therapy (GDT) is to improve patient outcome by the optimization of hemodynamic status, as it is considered that many perioperative complications are related to microcirculatory disturbance due to an imbalance between oxygen delivery and consumption. The application of GDT protocols incorporating the assessment and optimization of patients' intravascular status should theoretically lead to a reduction in perioperative bleeding and transfusion requirements, as both hypervolemia and hypovolemia and their consequences such as dilutional coagulopathy, anemia and inadequate oxygen delivery to the tissues are avoided. However, the research reporting decreased usage of blood products in patients which received targeted fluid management is sparse; decreased blood loss and transfusion requirements were reported in spine surgery using GDT, while studies in abdominal or cardiac surgery did not consistently report significant decreases in blood products transfusion when GDT were applied. These heterogenous results reported can be explained by the differences between the GDT protocols used, as the differences in therapeutic goals can impact on blood transfusion requirements. In the future, the GDT protocols should include not only the prediction of fluid responsiveness and optimization of hemodynamic status, but also the assessment of microcirculation and measures to improve tissue oxygenation, parameters which can also guide the decision for blood product transfusion. A better standardization of GDT algorithms is also required in order to perform a more accurate assessment of the effects of applying GDT on the consumption of blood products.

Gastric Cancer, Hemophilia A and Angiodysplasia - An Unreported Association with Clinical Implications in a Patient with Digestive Hemorrhage.

Introduction: Gastric cancer is a rare cause of upper digestive hemorrhage. Associated co-morbidities may have a detrimental effect on both early and long-term outcomes after surgery for gastric cancer. Association of gastric adenocarcinoma with hemophilia A and angiodysplasia was not previously reported, and the impact on postoperative outcome is not known. Case Report: A 49-year-old male with inherited hemophilia A presented with upper digestive hemorrhage and severe anemia, and was diagnosed with gastric carcinoma. The patient underwent total gastrectomy with splenectomy and D2 lymph nodes dissection. The postoperative outcome was complicated by digestive hemorrhage due to the presence of lesions of angiodysplasia of the cecum and jejunum that were successfully treated with coils mounted by the interventional radiologic approach. During the pre and postoperative periods, the patient received human coagulation factor VIII and developed auto-antibodies against factor VIII. Thus, human coagulation factor VIII administration was stopped and replaced with factor eight inhibitor bypassing activity (FEIBA). The patient was discharged at home on postoperative day 41, without any signs of bleeding. Conclusion: To the best of our knowledge, this is the first reported association of gastric adenocarcinoma, hemophilia A and angiodysplasia. All these lesions may lead to digestive hemorrhage and can pose very difficult problems of decision for diagnosis and therapy. A multidisciplinary approach including hematologist, surgeon, anesthesiologist, endoscopist and the interventional radiologist is mandatory to have a proper diagnosis and management for these patients.

Effects of malignancy on blood coagulation in septic intensive care patients.

: The objectives of the study are to examine the effect of sepsis on the coagulation profile of patients having solid cancer and to test the hypothesis that septic patients with cancer have normal or increased hemostatic capacity despite prolonged standard coagulation tests (SCTs) compared with noninfected cancer patients. Patients with solid cancer were included in the study forming two groups: study group included patients with sepsis with minimum two organ dysfunctions and control group formed by noninfected cancer patients. SCTs, platelet count, plasma levels of coagulation factors and rotation thromboelastometry (TEM International GmbH, Munich, Germany) were determined in both groups. Study group patients (n = 35) showed prolonged SCTs, thrombocytopenia, decreased coagulation factor levels and increased D-dimer compared with control group (n = 35). However, fibrinogen levels and clot firmness assessed by rotation thromboelastometry were not different between groups and clot lysis indexes at 45 and 60 min were increased in study group compared with control group. The first derivative of the clot firmness curve revealed an increased time to the maximum velocity of clot formation for study group, without differences in the maximum velocity of clot formation, or in total thrombus formation. Sepsis with organ dysfunction in cancer patients is associated with delayed initiation of coagulation and reduced fibrinolysis compared with control patients, but overall clot formation and stabilization is not different. For septic cancer patients, SCTs and plasmatic indicators of fibrinolysis do not translate well to whole blood clot formation and may be misleading indicators of thrombotic or bleeding risk.