scholarly journals Pseudo heparin resistance after pulmonary endarterectomy: Role of thrombus production of Factor VIII

Author(s):  
Antti I. Nykänen ◽  
Rita Selby ◽  
Karen M. McRae ◽  
Yidan Zhao ◽  
Usman M. Asghar ◽  
...  
Open Heart ◽  
2021 ◽  
Vol 8 (1) ◽  
pp. e001628
Author(s):  
Kamal Matli ◽  
Raymond Farah ◽  
Mario Maalouf ◽  
Nibal Chamoun ◽  
Christy Costanian ◽  
...  

Although primarily affecting the respiratory system, COVID-19 causes multiple organ damage. One of its grave consequences is a prothrombotic state that manifests as thrombotic, microthrombotic and thromboembolic events. Therefore, understanding the effect of antiplatelet and anticoagulation therapy in the context of COVID-19 treatment is important. The aim of this rapid review was to highlight the role of thrombosis in COVID-19 and to provide new insights on the use of antithrombotic therapy in its management. A rapid systematic review was performed using preferred reporting items for systematic reviews. Papers published in English on antithrombotic agent use and COVID-19 complications were eligible. Results showed that the use of anticoagulants increased survival and reduced thromboembolic events in patients. However, despite the use of anticoagulants, patients still suffered thrombotic events likely due to heparin resistance. Data on antiplatelet use in combination with anticoagulants in the setting of COVID-19 are quite scarce. Current side effects of anticoagulation therapy emphasise the need to update treatment guidelines. In this rapid review, we address a possible modulatory role of antiplatelet and anticoagulant combination against COVID-19 pathogenesis. This combination may be an effective form of adjuvant therapy against COVID-19 infection. However, further studies are needed to elucidate potential risks and benefits associated with this combination.


2000 ◽  
Vol 96 (Supplement) ◽  
pp. 804-806
Author(s):  
Robert A. Raschke ◽  
James R. Guidry ◽  
Michael R. Foley

2021 ◽  
Vol 41 (3) ◽  
pp. 33-41
Author(s):  
Lisa Fetters ◽  
Sue Sirianni

Introduction Heparin resistance was discovered in a patient in the surgical intensive care unit who underwent emergency endovascular coiling and later an anterior communicating artery clipping procedure to treat subarachnoid hemorrhage due to rupture of an anterior communicating artery aneurysm. Clinical Findings On intensive care unit day 17/postoperative day 3, the patient experienced shortness of breath, persistent tachycardia, and hypoxia. Bilateral pulmonary emboli, a saddle embolus, and lower-extremity and upper-extremity deep vein thrombi were diagnosed. The patient received high-dose unfractionated heparin (>35 000 U/24 h), and activated partial thromboplastin times remained subtherapeutic over the next 72 hours. Diagnosis Factor VIII activity, fibrinogen, antithrombin activity, antithrombin antigen, and platelet factor 4 were measured. The results demonstrated an increase in factor VIII activity to 342% (reference range, 50%-200%), elevated fibrinogen level of 441 mg/dL (reference range, 200-400 mg/dL), antithrombin antigen level of 92% (reference range, 80%-130%), elevated antithrombin activity of 108% (reference range, 80%-100%), and negative platelet factor 4 result, indicating that the patient did not have heparin-induced thrombocytopenia and confirming the diagnosis of heparin resistance. Conclusions Risk factors for heparin resistance include antithrombin deficiency, elevation of factor VIII or fibrinogen level, elevation in heparin-binding proteins, increased heparin clearance, sepsis, trauma, and burns. The astute critical care nurse may be the first to recognize this condition in a patient, preventing a potentially fatal complication.


F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 96 ◽  
Author(s):  
Karl C Desch

Von Willebrand factor (VWF) is a multimeric plasma glycoprotein that plays a central role in the initiation of blood coagulation. Through interactions between its specific functional domains, the vascular wall, coagulation factor VIII, and platelet receptors, VWF maintains hemostasis by binding to platelets and delivering factor VIII to the sites of vascular injury. In the healthy human population, plasma VWF levels vary widely. The important role of VWF is illustrated by individuals at the extremes of the normal distribution of plasma VWF concentrations where individuals with low VWF levels are more likely to present with mucocutaneous bleeding. Conversely, people with high VWF levels are at higher risk for venous thromboembolic disease, stroke, and coronary artery disease. This report will summarize recent advances in our understanding of environmental influences and the genetic control of VWF plasma variation in healthy and symptomatic populations and will also highlight the unanswered questions that are currently driving this field of study.


Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 17-17
Author(s):  
Dougald Monroe ◽  
Mirella Ezban ◽  
Maureane Hoffman

Background.Recently a novel bifunctional antibody (emicizumab) that binds both factor IXa (FIXa) and factor X (FX) has been used to treat hemophilia A. Emicizumab has proven remarkably effective as a prophylactic treatment for hemophilia A; however there are patients that still experience bleeding. An approach to safely and effectively treating this bleeding in hemophilia A patients with inhibitors is recombinant factor VIIa (rFVIIa). When given at therapeutic levels, rFVIIa can enhance tissue factor (TF) dependent activation of FX as well as activating FX independently of TF. At therapeutic levels rFVIIa can also activate FIX. The goal of this study was to assess the role of the FIXa activated by rFVIIa when emicizumab is added to hemophilia A plasma. Methods. Thrombin generation assays were done in plasma using 100 µM lipid and 420 µM Z-Gly-Gly-Arg-AMC with or without emicizumab at 55 µg/mL which is the clinical steady state level. The reactions were initiated with low (1 pM) tissue factor (TF). rFVIIa was added at concentrations of 25-100 nM with 25 nM corresponding to the plasma levels achieved by a single clinical dose of 90 µg/mL. To study to the role of factor IX in the absence of factor VIII, it was necessary to create a double deficient plasma (factors VIII and IX deficient). This was done by taking antigen negative hemophilia B plasma and adding a neutralizing antibody to factor VIII (Haematologic Technologies, Essex Junction, VT, USA). Now varying concentrations of factor IX could be reconstituted into the plasma to give hemophilia A plasma. Results. As expected, in the double deficient plasma with low TF there was essentially no thrombin generation. Also as expected from previous studies, addition of rFVIIa to double deficient plasma gave a dose dependent increase in thrombin generation through activation of FX. Interestingly addition of plasma levels of FIX to the rFVIIa did not increase thrombin generation. Starting from double deficient plasma, as expected emicizumab did not increase thrombin generation since no factor IX was present. Also, in double deficient plasma with rFVIIa, emicizumab did not increase thrombin generation. But in double deficient plasma with FIX and rFVIIa, emicizumab significantly increased thrombin generation. The levels of thrombin generation increased in a dose dependent fashion with higher concentrations of rFVIIa giving higher levels of thrombin generation. Conclusion. Since addition of FIX to the double deficient plasma with rFVIIa did not increase thrombin generation, it suggests that rFVIIa activation of FX is the only source of the FXa needed for thrombin generation. So in the absence of factor VIII (or emicizumab) FIX activation does not contribute to thrombin generation. However, in the presence of emicizumab, while rFVIIa can still activate FX, FIXa formed by rFVIIa can complex with emicizumab to provide an additional source of FX activation. Thus rFVIIa activation of FIX explains the synergistic effect in thrombin generation observed when combining rFVIIa with emicizumab. The generation of FIXa at a site of injury is consistent with the safety profile observed in clinical use. Disclosures Monroe: Novo Nordisk:Research Funding.Ezban:Novo Nordisk:Current Employment.Hoffman:Novo Nordisk:Research Funding.


Author(s):  
Atakan Erkilinç ◽  
Nezih Onur Ermerak ◽  
Ahmet Zengin ◽  
Şehnaz Olgun Yildizeli ◽  
Bu¨lent Mutlu ◽  
...  

2019 ◽  
pp. 089719001988523 ◽  
Author(s):  
Janelle O. Poyant ◽  
Augustus M. Gleason

Background: Argatroban, a synthetic, parenteral, nonheparin anticoagulant, is a direct thrombin inhibitor indicated for the prophylaxis or treatment of venous thromboembolism (VTE) in patients with heparin-induced thrombocytopenia with thrombosis (HITT) and for use during percutaneous coronary intervention (PCI) in patients who have or are at risk for developing HITT. Although heparin resistance occurs in approximately 0.5% to 5% of heparin-treated patients and is well documented in the literature, argatroban resistance is limited to a single case report. The objective of this case is to describe a case in which argatroban resistance was suspected in a patient with critical limb ischemia. Methods: This is a case report of a single patient. Results: A 68-year-old female admitted for critical limb ischemia requiring vascular intervention was treated for presumed HITT with argatroban. A therapeutic activated partial thromboplastin time (aPTT) was not attained (31 seconds) despite multiple uptitrations of the dose to 2.8 μg/kg/min (adjusted based on the institutional protocol and with consideration of organ dysfunction). A coagulopathy workup revealed a high level of factor VIII (265%). Conclusion: This case supports early assessment of factor VIII levels and the consideration of argatroban resistance and in patients who have a subtherapeutic aPTT, despite multiple increases in dose with an elevated factor VIII level. Early identification should prompt the use of an alternative anticoagulant to ensure efficacy.


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