Paul D. Mintz

Hypercoagulation and thrombophilia in liver disease

Summary.  A complex balance exists between endogenous procoagulants and the anticoagulant system in liver disease patients. Hypercoagulable events occur in cirrhosis patients despite the well‐known bleeding diathesis of liver disease. These events may be clinically evident, such as in portal vein thrombosis or pulmonary embolism, but these conditions may also be a silent contributor to certain disease states, such as portopulmonary hypertension or parenchymal extinction with liver atrophy as well as thrombosis of extracorporeal circuits in dialysis or liver assist devices. Moreover, liver disease‐related hypercoagulability may contribute to vascular disease in the increasingly common condition of non‐alcoholic fatty liver disease. Despite the incidence of these problems, there are few widely accessible and practical laboratory tests to evaluate the risk of a hypercoagulable event in cirrhosis patients. Furthermore, there is little research on the use of commonly accepted anticoagulants in patients with liver disease. This article is a result of an international symposium on coagulation disorders in liver disease and addresses several areas of specific interest in hypercoagulation in liver disease. Critical areas lacking clinical information are highlighted and future areas of research interest are defined with an aim to foster clinical research in this field.

Hyperleukocytosis, leukostasis and leukapheresis: practice management.

Hyperleukocytosis, arbitrarily defined in acute leukemia as a white blood cell count greater than 100,000/mL, often is associated with increased morbidity and mortality in patients with leukemic processes. It can induce leukostasis, tumor lysis syndrome and disseminated intravascular coagulopathy and has significant prognostic implications with or without one of these clinical complications. The main sites that tend to be injured from the obstructions are the central nerve system and lungs. Despite characteristic clinical presentations, the diagnosis of leukostasis is rarely made with high confidence. The main goal of the management of hyperleukocytosis and/or leukostasis is to reduce the white blood cell count before starting induction chemotherapy. The cytoreduction can be achieved by either leukapheresis and/or hyroxyurea. The technical aspects, complications and efficacy of leukapheresis are discussed in the current article.

A randomized, controlled Phase III trial of therapeutic plasma exchange with fresh-frozen plasma (FFP) prepared with amotosalen and ultraviolet A light compared to untreated FFP in thrombotic thrombocytopenic purpura

BACKGROUND: Photochemical treatment of fresh‐frozen plasma (FFP) with amotosalen and ultraviolet (UV) A light (PCT FFP) results in inactivation of a broad spectrum of pathogens while retaining coagulation factor activity, antithrombotic proteins, and von Willebrand factor–cleaving protease (VWF‐CP) activity.

Therapeutic efficacy and safety of red blood cells treated with a chemical process (S-303) for pathogen inactivation: a Phase III clinical trial in cardiac surgery patients

BACKGROUND: A randomized, double‐blind trial is reported of the clinical efficacy of red blood cells (RBCs) treated for pathogen inactivation with S‐303, a synthetic labile alkylating agent.

Novel oral anticoagulants and reversal agents: Considerations for clinical development

This white paper provides a summary of presentations and discussions that were held at an Anticoagulant-Induced Bleeding and Reversal Agents Think Tank co-sponsored by the Cardiac Safety Research Consortium and the US Food and Drug Administration (FDA) at the FDAs White Oak Headquarters on April 22, 2014. Attention focused on a development pathway for reversal agents for the novel oral anticoagulants (NOACs). This is important because anticoagulation is still widely underused for stroke prevention in patients with atrial fibrillation. Undertreatment persists, although NOACs, in general, overcome some of the difficulties associated with anticoagulation provided by vitamin K antagonists. One reason for the lack of a wider uptake is the absence of NOAC reversal agents. As there are neither widely accepted academic and industry standards nor a definitive regulatory policy on the development of such reversal agents, this meeting provided a forum for leaders in the fields of cardiovascular clinical trials and cardiovascular safety to discuss the issues and develop recommendations. Attendees included representatives from pharmaceutical companies; regulatory agencies; end point adjudication specialist groups; contract research organizations; and active, academically based physicians. There was wide and solid consensus that NOACs overall offer improvements in convenience, efficacy, and safety compared with warfarin, even without reversal agents. Still, it was broadly accepted that it would be helpful to have reversal agents available for clinicians to use. Because it is not feasible to do definitive outcomes studies demonstrating a reversal agents clinical benefits, it was felt that these agents could be approved for use in life-threatening bleeding situations if the molecules were well characterized preclinically, their pharmacodynamic and pharmacokinetic profiles were well understood, and showed no harmful adverse events in early human testing. There was also consensus that after such approval, efforts should be made to augment the available clinical information until such time as there is a body of evidence to demonstrate real-world clinical outcomes with the reversal agents. No recommendations were made for more generalized use of these agents in the setting of non-life-threatening situations. This article reflects the views of the authors and should not be construed to represent FDAs views or policies.

Instituting a thawed plasma procedure: it just makes sense and saves cents.

BACKGROUND: The objectives of this time‐series study were to elucidate the impact of a thawed plasma standard operating procedure (TP SOP) on plasma wastage and on cost savings.

Independent roles for platelet crossmatching and HLA in the selection of platelets for alloimmunized patients.

Background: Although HLA‐matched platelets are frequently requested for alloimmunized patients, recent evidence has indicated that 1‐hour posttransfusion platelet increments in these patients are specifically sensitive to crossmatch compatibility.

Transfusion therapy in emergency medicine

Volume replacement is critical to the resuscitation of the hemorrhaging patient, but this usually can be accomplished quickly and safely with crystalloid and/or colloid solutions. Red cells should be used in addition to asanguinous fluids in the treatment of tissue hypoxia due to anemia. The need for whole blood as opposed to packed red blood cells is controversial. However, plasma should not be used as a volume expander, and its use to supplement coagulation factors during the massive transfusion of red cells should be guided by laboratory tests that document a coagulopathy. Similarly, platelet transfusions are indicated to correct documented thrombocytopenia or platelet dysfunction, and routine prophylaxis after fixed volumes of red cells results is unwarranted. Many anticipated complications of massive transfusions, including hemostatic abnormalities, acid-base imbalances, hyperkalemia, and hypocalcemia, are uncommon or of limited clinical significance. The risks of immune hemolysis and transfusion-transmitted diseases, on the other hand, are significant, and argue for judicious use of blood components. In emergencies in which blood is required immediately before compatibility testing can be completed, O-negative uncrossmatched blood can be requested. Careful blood specimen collection and patient identification prior to transfusion are critical. Practices that emphasize blood conservation, including the use of autologous salvaged blood, are always to the patients advantage.

Plasmapheresis in Thyroxine Overdose: A Case Report

Thyrotoxicosis from an overdose of medicinal thyroid is a condition which may be associated with a significant delay in onset of toxicity. We report a case treated with plasmapheresis, and conclude that the amount of thyroid hormone removed was insignificant compared to the total ingestion. We also note that the plasma half-life of thyroxine is apparently reduced in an acute massive ingestion.

Rapid Preparation of Small-Volume Autologous Fibrinogen Concentrate and Its Same Day Use in Bleb Leaks After Glaucoma Filtration Surgery

The authors evaluated small-volume preparation of autologous fibrin glue (AFG) and same day use in postglaucoma filtration surgery patients with Seidel positive bleb leaks and determined fibrinogen concentrations in autologous fibrinogen concentrates (AFCs) from 10 volunteers. Thirty milliliters of blood was centrifuged (5 min, 2400 x g); plasma was frozen (5 min-ethanol and ice), thawed (1-6 C, 30-60 min), and centrifuged (10 min, 5 C, 2800 x g); and the precipitate was transferred to a 1.0-ml tuberculosis syringe. Thrombin (1000 U) was dissolved (0.8 sterile water, 0.2 ml aminocaproic acid) and warmed (37 C). Average preparation time was 90 minutes. Alternating drops of AFC and thrombin were applied to bleb leaks until AFC clotted. Seidel testing with fluorescein determined success. AFC was prepared from 10 volunteers and fibrinogen was measured. AFG was initially successful with two (Seidel negative) eyes; one eye remained negative. AFG was unsuccessful in one briskly Seidel-positive leak. Mean +/- SD fibrinogen concentration in AFCs from the 10 volunteers was 2314 +/- 643 mg/dl (range 1608-3431 mg/dl). AFG may successfully close bleb leaks in outpatient settings. Brisk aqueous flow may impair effectiveness of AFG. Fibrinogen concentrations were comparable with previous reports.