cangrelor and Thrombocytopenia

Anticoagulation management for cardiopulmonary bypass (CPB) is challenging in patients with acute heparin-induced thrombocytopenia (HIT). The strategy of combining cangrelor intraoperatively with heparin for CPB anticoagulation is of increasing interest but exposes to specific unresolved problems. We report the case of a patient requiring surgical pulmonary embolectomy for pulmonary embolism at the very acute phase of HIT, with a high titre of anti-PF4/heparin antibodies and severe thrombocytopenia. For CPB management, cangrelor was administered in combination with heparin prescribed and monitored as usual. Surgery was successfully performed, but postoperatively, the patient developed a new thrombotic event. We discussed the specific problems associated with such strategy, including the dose of cangrelor and its monitoring, the management of the cell-saver, the risk of heparin rebound and the risk of platelet transfusion. These issues must be addressed before considering the combination of cangrelor and unfractionated heparin as a standard of care for CBP.

Topics: Anticoagulants; Cardiopulmonary Bypass; Heparin; Humans; Thrombocytopenia

Perioperative anticoagulation management for patients with heparin-induced thrombocytopenia requiring cardiopulmonary bypass and deep hypothermic circulatory arrest presents a clinical challenge. Alternative anticoagulants have been used but can cause significant postoperative bleeding. We report the successful use of cangrelor and heparin in a 30-year-old patient with severe heparin-induced thrombocytopenia undergoing urgent pulmonary thromboendarterectomy.

Topics: Adenosine Monophosphate; Adult; Endarterectomy; Fibrinolytic Agents; Heparin; Humans; Male; Platelet Aggregation Inhibitors; Pulmonary Embolism; Thrombocytopenia

Topics: Adenosine Monophosphate; Cardiopulmonary Bypass; Heparin; Humans; Thrombocytopenia

A 66-YEAR-OLD female requiring cardiac surgery had persisting anti-platelet factor 4 (PF4)/heparin antibodies (HIT-abs) 8 years after heparin-induced thrombocytopenia (HIT). In 2010, she developed thrombotic thrombocytopenic purpura (TTP) (ADAMTS-13 <5%, inhibitor at 1.0 BU/mL), which was treated successfully with corticotherapy, plasmapheresis, and intravenous heparin. While taking heparin, she developed HIT, as evidenced by a positive functional test. Her platelet count fully resolved without thrombotic complications with danaparoid treatment. In 2018, the preoperative titer of HIT-abs was still 0.38 U/mL by chemoluminescent immunoassay (CLIA), and positive by particle-gel agglutination immunoassay (PaGIA) with a titer of 2 and was strongly positive on an enzyme-linked immunosorbent assay (ELISA). The authors of the case report chose to use cangrelor combined with heparin during cardiopulmonary bypass (CPB). Cangrelor was used without increased postoperative bleeding or thrombotic complications. Postoperatively she exhibited a huge rise in HIT-abs (14.22 U/mL on postoperative day 11) with a positive functional assay. There was no recurrence of HIT, however. This case illustrates the importance of excluding the presence of persisting HIT-abs before CPB and ensuring close medical follow-up after even a single exposure to heparin.

Topics: Adenosine Monophosphate; Anticoagulants; Cardiac Surgical Procedures; Female; Follow-Up Studies; Forecasting; Heparin; Humans; Middle Aged; Platelet Aggregation Inhibitors; Platelet Factor 4; Postoperative Complications; Thrombocytopenia

Topics: Adenosine Monophosphate; Cardiopulmonary Bypass; Heparin; Humans; Kidney Failure, Chronic; Thrombocytopenia

Topics: Adenosine Monophosphate; Cardiopulmonary Bypass; Heparin; Humans; Kidney Failure, Chronic; Thrombocytopenia

The management of heparin-induced thrombocytopenia (HIT) in the perioperative period for patients undergoing cardiac surgery requiring cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA) can be a challenging clinical scenario. Once a diagnosis of HIT has been established, heparin products typically are avoided and alternative therapies for anticoagulation are started. Alternative anticoagulation strategies for CPB are limited and often have various pharmacokinetic profiles that may lead to increased perioperative bleeding. Historically the use of a GPIIb/IIIa inhibitor, such as tirofiban, followed by unfractionated heparin (UFH) is the typical alternative for surgeries requiring DHCA in patients with HIT at the authors' institution. This article presents a case in which cangrelor followed by UFH was used in a 20-year-old patient with suspected HIT and chronic thromboembolic pulmonary hypertension undergoing pulmonary thromboendarterectomy surgery requiring CPB and DHCA. Due to the frequency of significant postoperative bleeding encountered when using tirofiban and UFH, it was decided to attempt to block platelet aggregation with significantly shorter-acting cangrelor. The authors hypothesized that cangrelor would reduce the risk of significant bleeding compared with tirofiban because of its favorable pharmacokinetics. Specifically, cangrelor has a short elimination half-life of 3 to 6 minutes, and its elimination is not altered by renal and hepatic impairment. This case report discusses the pathophysiology of HIT, the alternative anticoagulants used for HIT type II in pulmonary thromboendarterectomy, and the potential of cangrelor in conjunction with UFH to be a favorable option for patients in similar clinical scenarios.

Topics: Adenosine Monophosphate; Anticoagulants; Blood Coagulation; Drug Therapy, Combination; Endarterectomy; Heparin; Humans; Male; Platelet Aggregation Inhibitors; Thrombocytopenia; Young Adult

Current guidelines emphasize the need for at least 6-12 months of oral dual antiplatelet therapy consisting of aspirin and a P2Y12 inhibitor following drug-eluting coronary artery stent implantation. In patients with recently implanted coronary artery stents who require urgent cardiac or noncardiac surgery, the benefits of maintaining oral dual antiplatelet therapy must be carefully weighed against the risks of excessive bleeding, and current practice is largely guided by individual surgeon preferences. When the effects of a second oral antiplatelet agent are undesirable during the perioperative period, the use of a short-acting intravenous antiplatelet agent as "bridge" therapy that can be discontinued shortly before surgery is associated with a reduced occurrence of adverse clinical events in patients with recently implanted coronary stents requiring urgent coronary artery bypass graft surgery. Cangrelor is an intravenous adenosine triphosphate analog P2Y12 receptor antagonist with a short plasma half-life that has been used off label in patients with recent coronary stents as a bridge to invasive procedures with excessive bleeding risk. To our knowledge, this is the first case report to demonstrate the safe and effective use of cangrelor as a bridge to left ventricular assist device implantation in a patient with a recently implanted drug-eluting coronary artery stent who developed acute thrombocytopenia following reexposure to tirofiban, a glycoprotein IIb/IIIa inhibitor.

Topics: Adenosine Monophosphate; Angioplasty, Balloon, Coronary; Dose-Response Relationship, Drug; Drug-Eluting Stents; Heart-Assist Devices; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Thrombocytopenia; Tirofiban; Treatment Outcome; Ventricular Dysfunction, Left

Heparin is the only well-established anticoagulant medication for cardiopulmonary bypass making selecting an alternative anticoagulant challenging in patients with heparin-induced thrombocytopenia. Other anticoagulant medications can cause significant postoperative bleeding, especially in patients with end-stage renal disease. We present a case of a 63-year-old woman requiring aortic valve replacement with a history of heparin-induced thrombocytopenia and end-stage renal disease. Cangrelor and heparin were successfully used during cardiopulmonary bypass, offering an option for anticoagulation management for a uniquely challenging patient population.

Topics: Adenosine Monophosphate; Cardiopulmonary Bypass; Female; Heart Valve Prosthesis Implantation; Heparin; Humans; Intraoperative Care; Kidney Failure, Chronic; Middle Aged; Thrombocytopenia; Treatment Outcome

Topics: Adenosine Monophosphate; Anticoagulants; Cardiac Surgical Procedures; Heparin; Humans; Thrombocytopenia

The influence of cangrelor on the incidence and outcomes of post-percutaneous coronary intervention (PCI) thrombocytopenia is not defined. We aimed to explore the incidence, predictors, and clinical impact of thrombocytopenia after PCI in cangrelor-treated patients.. This was a pooled, patient-level analysis of the CHAMPION trials (Cangrelor Versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition), which compared cangrelor with clopidogrel for prevention of thrombotic complications during and after PCI. Acquired thrombocytopenia was defined as either a drop in platelet count to <100 000 after PCI or a drop of >50% between baseline and a follow-up. The main efficacy outcome was major adverse cardiac events. The primary safety outcome was noncoronary artery bypass grafting-related Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries-defined severe bleeding at 48 hours. Patients (23 783) were enrolled, and 3009 (12.7%) received a GPI (glycoprotein IIb/IIIa inhibitor). Acquired thrombocytopenia occurred in 200 patients (0.8%). The adjusted rate of major adverse cardiovascular events at 48 hours was significantly higher in patients who developed thrombocytopenia compared with those who did not (odds ratio, 3.00; 95% confidence interval, 1.89-4.69;. Acquired thrombocytopenia after PCI is strongly associated with substantial early morbidity and mortality, as well as major bleeding. GPI use is a significant predictor of thrombocytopenia. Cangrelor is not associated with acquired thrombocytopenia, and its clinical efficacy and safety is consistent irrespective of thrombocytopenia occurrence.. URL: https://www.clinicaltrials.gov. Unique identifiers: NCT00305162, NCT00385138, and NCT01156571.

Topics: Adenosine Monophosphate; Aged; Clopidogrel; Female; Hemorrhage; Humans; Incidence; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Platelet Count; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Thrombocytopenia; Time Factors; Treatment Outcome

Topics: Adenosine Monophosphate; Blood Platelets; Humans; Incidence; Percutaneous Coronary Intervention; Thrombocytopenia

Optimal anticoagulation strategy for cardiopulmonary bypass (CPB) in end-stage heart failure patients with heparin-induced thrombocytopenia (HIT) requiring left ventricular assist device (LVAD) implantation remains uncertain. Presently, there are no large-scale randomized studies comparing outcomes of alternative anticoagulation strategies for CPB in this patient population. A novel antiplatelet agent - cangrelor, which is a potent P2Y12 inhibitor with robust antiplatelet efficacy, rapid reversibility, and measurable drug effect, has become available since 2015. Intraoperative anticoagulation for CPB using cangrelor with heparin has not been reported before.. We report the case of a 47-year-old male with ischemic cardiomyopathy and acute HIT, who underwent an urgent LVAD implantation using cangrelor with heparin for anticoagulation on CPB. This novel strategy resulted in satisfactory anticoagulation for CPB without perioperative thromboembolic events or major bleeding requiring reoperation.. Cangrelor with heparin was an effective anticoagulation strategy for CPB in this critically ill patient with acute HIT requiring an urgent LVAD implantation. Further studies are warranted to evaluate its efficacy and replicability in other patients with acute or subacute HIT who require urgent cardiac surgery.

Topics: Acute Disease; Adenosine Monophosphate; Anticoagulants; Blood Coagulation Disorders; Cardiopulmonary Bypass; Drug Therapy, Combination; Heart-Assist Devices; Heparin; Humans; Intraoperative Complications; Male; Middle Aged; Platelet Aggregation Inhibitors; Prosthesis Implantation; Thrombocytopenia

The paper describes an alternative method for quantification of in vivo ADP-induced thromboembolism. The aim of the studies was to develop a method of quantification which would not require either extravasation or labelling of platelets. Our proposed approach is based on the monitoring of changes of blood flow with the use of laser Doppler flowmetry.. Mice of C57Bl strain were used in the study. ADP was injected to the vena cava and blood flow was monitored with the use of a laser Doppler flowmeter in the mesentery. Measurements in platelet-depleted mice, mice pretreated with cangrelor, an ADP receptor antagonist, and eptifibatide, a blocker of fibrinogen binding to GPIIbIIIa, were conducted as the proof-of-concept in the performed experiments. Intravital microscopy and ex vivo imaging of organs was performed to identify the sites of aggregate formation resulting from ADP injection.. The injection of ADP resulted in a dose-dependent reduction of the blood flow in the mesentery. These responses were fully attributable to blood platelet aggregation, as shown by the lack of the effect in platelet-depleted mice, and significantly reduced responses in mice pretreated with cangrelor and eptifibatide. No platelet aggregate formation in mesenteric vessels was revealed by intravital microscopy, while ex vivo imaging showed accumulation of fluorescent labelled platelets in the lung.. Injection of ADP to the venous system results in the formation of platelet aggregates predominantly in the lung. This results in reversible blood flow cessation in peripheral blood vessels. The measurement of this blood flow cessation in the mesentery allows indirect measurement of ADP-induced pulmonary thromboembolism. We suggest that this approach can be useful for in vivo screening for antiplatelet drug candidates.

Topics: Adenosine Diphosphate; Adenosine Monophosphate; Animals; Area Under Curve; Blood Platelets; Eptifibatide; Intravital Microscopy; Laser-Doppler Flowmetry; Lung; Male; Mesentery; Mice; Mice, Inbred C57BL; Microscopy, Fluorescence; Peptides; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Pulmonary Embolism; Thrombocytopenia