Performance of the microINR Point-of-Care System: A Multicenter Clinical Trial

INTRODUCTION: There are limited publications about the microINR point-of-care (POC) system (iLine Microsystems). The current microINR POC system was compared with the ACL TOP 500 laboratory analyzer (Instrumentation Laboratory) and with the CoaguChek XS POC system (Roche Diagnostics). METHODS: This study was performed at three United States medical centers. Sixty-eight nonanticoagulated normal donors and 245 warfarin anticoagulated patients were included. Testing was performed in duplicate using capillary blood samples for the POC systems and venous blood samples for the laboratory testing. Accuracy and imprecision were assessed. RESULTS: Comparing microINR to ACL revealed a correlation coefficient (r) of 0.973, a slope of 1.00 (95% confidence interval [CI], 0.97-1.03), and an intercept of 0.08 (95% CI, 0.04-0.15). When compared with the CoaguChek XS, r was 0.977 with a slope of 0.92 (95% CI, 0.89-0.94) and an intercept of 0.15 (95% CI, 0.08-0.19). Predicted bias values at international normalized ratio (INR) 2.0, 3.5, and 4.5 were /= 4.5 +/- 25%, respectively. Agreement for the combined INR ranges was 96% against ACL and \u3e 96% against the CoaguChek XS. The coefficient of variation of the microINR was 5.03% for INR \u3c 2.0 and 4.68% for the therapeutic INR range 2.0 to 3.5. CONCLUSION: The microINR results demonstrate adequate imprecision and accuracy to both ACL and CoaguChek XS. This indicates that monitoring INR by this microINR POC system is reliable and acceptable for the management of warfarin therapy

Updates in Anticoagulation Therapy Monitoring

In the past six decades, heparin and warfarin were the primary anticoagulants prescribed for treatment and prophylaxis of venous thromboembolism worldwide. This has been accompanied by extensive clinical knowledge regarding dosing, monitoring, and reversal of these anticoagulants, and the resources required to do so have largely been readily available at small and large centers alike. However, with the advent of newer oral and parenteral anticoagulants such as low molecular weight heparins, factor Xa inhibitors, and direct thrombin inhibitors in recent years, new corresponding practice guidelines have also emerged. A notable shift in the need for monitoring and reversal agents has evolved as well. While this has perhaps streamlined the process for physicians and is often desirable for patients, it has also left a knowledge and resource gap in clinical scenarios for which urgent reversal and monitoring is necessary. An overview of the currently available anticoagulants with a focus on the guidelines and available tests for anticoagulant monitoring will be discussed in this article

Updates in Anticoagulation Therapy Monitoring

In the past six decades, heparin and warfarin were the primary anticoagulants prescribed for treatment and prophylaxis of venous thromboembolism worldwide. This has been accompanied by extensive clinical knowledge regarding dosing, monitoring, and reversal of these anticoagulants, and the resources required to do so have largely been readily available at small and large centers alike. However, with the advent of newer oral and parenteral anticoagulants such as low molecular weight heparins, factor Xa inhibitors, and direct thrombin inhibitors in recent years, new corresponding practice guidelines have also emerged. A notable shift in the need for monitoring and reversal agents has evolved as well. While this has perhaps streamlined the process for physicians and is often desirable for patients, it has also left a knowledge and resource gap in clinical scenarios for which urgent reversal and monitoring is necessary. An overview of the currently available anticoagulants with a focus on the guidelines and available tests for anticoagulant monitoring will be discussed in this article

Acquired bleeding disorders secondary to immune checkpoint inhibitors: a case report and systematic literature review

Acquired bleeding disorders because of an autoimmune phenomenon are rare events. Acquired von Willebrand disease (aVWD) has been estimated as having a prevalence of 400 per million in the general population. Acquired hemophilia A (AHA), the most common of the acquired hemophilias, has an estimated incidence of 1.3-1.5 cases per million per year. Immune checkpoint inhibitors (ICI) targeting PD-1, PD-L1, and CTLA-4 are being used with increasing frequency for hematologic and oncologic disorders. Acquired hemophilias and aVWD have been reported with the use of ICI therapy. We performed a systematic review of the literature to identify cases of acquired bleeding disorders with ICI therapy and contribute our own institution\u27s experience with a case of AHA after pembrolizumab therapy. Six cases of AHA, one case of aVWD, and one case of factor V inhibitor were identified in the literature. Inhibitors were successfully eradicated in five of the eight cases identified. We propose that a centralized registry, possibly through the Scientific and Standardization Subcommittee on Plasma Coagulation Inhibitors through the International Society on Thrombosis and Hemostasis (ISTH), be developed to record treatment and outcomes of this rare ICI complication in order to prognosticate risk and better understand optimal treatment strategies

Essential Role of Rho-Associated Kinase in ABO Immune Complex-Mediated Endothelial Barrier Disruption

ABO immune complexes (ABO-IC) formed by ABO-incompatible antigen-antibody interaction are associated with hemolysis and platelet destruction in patients transfused with ABO-nonidentical blood products. However, the effects of ABO-IC on endothelial cells (EC) are unclear. ABO-IC were formed in vitro from normal donor-derived plasma and serum. Human pulmonary artery EC (HPAEC) were cultured and treated with media, ABO-identical and –non-identical plasma, and ABO-IC. EC barrier integrity was evaluated using transendothelial electrical resistance (TEER), scanning electron microscopy (SEM), vascular endothelial (VE)-cadherin and phalloidin staining, and Rho-associated Kinase (ROCK) inhibitor treatment. TEER revealed significant/irreversible barrier disruption within 1–2 h of exposure to ABO non-identical plasma and ABO-IC; this occurred independently of EC ABO type. Treatment with ABO-IC resulted in decreased VE-cadherin staining and increased phalloidin staining in a time-dependent manner, suggesting that the resultant increased EC barrier permeability is secondary to actin stress fiber formation and loss of cell surface VE-cadherin. Inhibition of ROCK was effective in protecting against IC-induced barrier disruption even two hours after ABO-IC exposure. ABO-IC causes increased EC barrier permeability by decreasing cell surface VE-cadherin and promoting stress fiber formation, which is preventable by inhibiting ROCK activation to protect against EC contraction and gap formation

In Vitro and In Vivo Comparison of Hemoglobin and Electrolytes Following the Collection of Cell Saver Blood Washed with Either Normal Saline or Plasma-Lyte A

Cell saver blood is typically washed with normal saline (NS); however, recent studies have reported decreased red blood cell hemolysis and increased platelet function when a more physiologic washing solution, such as Plasma-Lyte A (PL-A) is used. We evaluated the in vitro and in vivo effects of NS compared to PL-A as washing solutions for cell saver blood in pediatric cardiac surgery. Cell saver blood was re-infused for up to 24 hours post-collection. Laboratory and clinical data were collected from infants receiving cell saver washed with either NS (n = 20) or PL-A (n = 21). Compositions of the cell saver blood were compared between groups at 5 in vitro time points and in vivo patient blood at 24 hours post-bypass. Although there were differences in in vitro laboratory values between groups; 24 hours post-bypass, in vivo results were similar. Our data supports 24-hour reinfusion of cell saver washed with either NS versus PL-A in pediatric cardiac surgery patients, and provides data on the differences in cell saver composition to guide future studies

Platelet transfusion—the new immunology of an old therapy

Platelet transfusion has been a vital therapeutic approach in patients with hematologic malignancies for close to half a century. Randomized trials show that prophylactic platelet transfusions mitigate bleeding in patients with acute myeloid leukemia. However, even with prophylactic transfusions, as many as 75% of patients experience hemorrhage. While platelet transfusion efficacy is modest, questions and concerns have arisen about the risks of platelet transfusion therapy. The acknowledged serious risks of platelet transfusion include viral transmission, bacterial sepsis, and acute lung injury. Less serious adverse effects include allergic and non-hemolytic febrile reactions. Rare hemolytic reactions have occurred due to a common policy of transfusing without regard to ABO type. In the last decade or so, new concerns have arisen; platelet derived lipids are implicated in transfusion related acute lung injury after transfusion. With the recognition that platelets are immune cells came the discoveries that supernatant IL-6, IL-27 sCD40L, and OX40L are closely linked to febrile reactions and sCD40L with acute lung injury. Platelet transfusions are pro-inflammatory, and may be pro-thrombotic. Anti-A and anti-B can bind to incompatible recipient or donor platelets and soluble antigens, impair hemostasis and thus increase bleeding. Finally, stored platelet supernatants contain biological mediators such as VEGF and TGF-β1 that may compromise the host versus tumor response. This is particularly of concern in patients receiving many platelet transfusions, as for acute leukemia. New evidence suggests that removing stored supernatant will improve clinical outcomes.This new view of platelets as pro-inflammatory and immunomodulatory agents suggests that innovative approaches to improving platelet storage and pre-transfusion manipulations to reduce toxicity could substantially improve the efficacy and safety of this long employed therapy