Continuous venovenous haemofiltration using polyacrylonitrile filters does not activate contact system and intrinsic coagulation pathways

Salmon, J.; Cardigan, Rebecca; Mackie, Ian; Cohen, S.; Machin, SJ; Singer, Mervyn

doi:10.1007/s001340050288

Cited by 54 publications

(55 citation statements)

References 23 publications

(18 reference statements)

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“…Standard laboratory tests of coagulation were normal and did not change with haemodialysis, which is in keeping with previous studies [17]. Thrombin times were marginally elevated pre-dialysis, but did not increase further.…”

Section: Discussionsupporting

confidence: 73%

Dialyzers Designed to Increase Internal Filtration Do Not Result in Significantly Increased Platelet Activation and Thrombin Generation

et al. 2010

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Introduction: To increase middle molecule clearances, high-flux dialyzers with increased internal filtration have been developed. However, dialyzer design and structure may affect thrombin generation and platelet activation, thereby risking increased clotting and reduced dialyzer clearances. Methods: Coagulation parameters, platelet, white cell and endothelial activation markers were measured prior to and following dialysis sessions in 12 patients using two different dialyzers designed for increased internal filtration. Results: Prior to dialysis, patients had evidence of activation of coagulation with increased factor VIII:C, thrombin-antithrombin complexes and prothrombin fragment 1+2, increased platelet activation, with raised platelet factor 4, β-thromboglobulin levels and increased fibrinolysis (raised D-dimers). Dialysis was associated with the release of soluble platelet integrin, sP selectin, increased endothelial activation with increased levels of von Willebrand factor (vWF) antigen (vWF:Ag) and vWF propeptide (vWF:pp) and sE selectin. There was no difference in tinzaparin levels at the end of the dialysis session using either dialyzer, as shown by anti-Xa activity – 0.145 ± 0.027 versus 0.11 ± 0.017 IU/ml, respectively. Conclusion: Haemodialysis patients have an inflammatory phenoytype, characterized by increased activation of coagulation, platelets and also fibrinolysis. However, dialyzers designed to increase internal filtration did not significantly increase platelet activation or thrombin generation.

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Section: Discussionsupporting

confidence: 73%

Dialyzers Designed to Increase Internal Filtration Do Not Result in Significantly Increased Platelet Activation and Thrombin Generation

et al. 2010

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“…In a study of critically ill hemofiltered patients [5], we found that premature clotting of the filter circuit occurring within the first 24 h was associated with low baseline levels of AT-III and heparin cofactor II. Only in these patients did thrombin-antithrombin complex antibodies rise significantly, representing evidence of thrombin generation.…”

Section: Introductionmentioning

confidence: 99%

Keeping the Circuit Open: Lessons from the Lab

2002

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Background: Hemofiltration circuits generally require anticoagulation to prevent the membrane from clotting. Understanding the mechanisms involved in premature clotting of the filtration circuit is useful to optimize anticoagulation and maintain filter patency. Aims: To discuss research performed at our institution which throws light on the causes of premature clotting of the hemofilter, and to highlight our approach to anticoagulation. Discussion: Premature clotting of the circuit is related to low baseline levels of antithrombin III (AT-III), heparin co-factor II and tissue factor pathway inhibitor. Clotting is preceded by a precipitous rise in thrombin-antithrombin complexes, suggesting thrombin generation. Our standard anticoagulant is unfractionated heparin, where the primary mode of action is potentiation of endogenous AT-III. However, AT-III levels are diminished in sepsis and other causes of systemic inflammation. To supplement or prevent consumption of AT-III we use fresh frozen plasma or aprotinin (as cheaper alternatives to AT-III) in situations where filter life span is limited and mechanical obstruction has been excluded. Anticoagulation can be managed in heparin-induced thrombocytopenic patients with danaparoid, prostaglandins and/or predilution.

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“…Critical illness may also result in an inflammatory response; contact activation occurs in intensive care patients 21,22 . However, an observational study of twelve intensive care patients undergoing haemofiltration failed to show contact activation 23 . Contact activation may therefore be more related to an inflammatory response than exposure of blood to a 'foreign' surface of an extracorporeal circulation.…”

Section: Relevance To Intensive Carementioning

confidence: 99%

DX-88, a Novel Kallikrein Inhibitor; Effects on Haemostasis in Blood from Patients Undergoing Cardiopulmonary Bypass

Self¹,

Mythen²,

Mackie

et al. 2006

Journal of the Intensive Care Society

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Background Cardiopulmonary bypass (CPB) results in an inflammatory response propagated by numerous pathways, including coagulation 1. Aprotinin reduces the use of blood products during cardiac surgery 2,3. 'High dose' aprotinin regimes (resulting in kallikrein inhibition) reduce allogeneic blood requirements more than 'low dose' regimes 4,5. DX-88 (Dyax Corp, Cambridge, MA), is a novel kallikrein inhibitor, undergoing trials as a drug to reduce transfusion requirements in cardiac surgery 67. The Thrombelastograph (TEG, Haemoscope) is a global monitor of whole blood coagulation 8 , used to guide blood component therapy in cardiac surgery 9,10. Therefore, this work aims to investigate the effect of DX-88, in vitro, on blood samples taken from patients undergoing CPB using the TEG, and assess the effect of changes in contact factor proteins. Hypothesis DX-88 will have an in vitro effect on thrombelastography, caused by kallikrein inhibition. During CPB, DX-88 will reduce fibrinolysis. Research Questions 1. What is the in vitro effect of DX-88 on whole blood coagulation in CPB? 2. How does contact activation and haemodilution during CPB explain this effect? Methods Twenty-five patients undergoing elective cardiac surgery on CPB were recruited following informed consent, and institutional ethical approval. Blood was sampled via a CVP line into citrated tubes, after induction of anaesthesia and during CPB (at rewarming). Kaolin activated thrombelastography was performed after recalcification, using heparinase cups; DX-88 was added in doses of 5, 10 and 20 µg/ml and compared to a buffer control. TEG analysis of the citrated samples was performed at least 30 minutes after blood sampling 11,12 .

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Continuous venovenous haemofiltration using polyacrylonitrile filters does not activate contact system and intrinsic coagulation pathways

Cited by 54 publications

References 23 publications

Dialyzers Designed to Increase Internal Filtration Do Not Result in Significantly Increased Platelet Activation and Thrombin Generation

Dialyzers Designed to Increase Internal Filtration Do Not Result in Significantly Increased Platelet Activation and Thrombin Generation

Keeping the Circuit Open: Lessons from the Lab

DX-88, a Novel Kallikrein Inhibitor; Effects on Haemostasis in Blood from Patients Undergoing Cardiopulmonary Bypass

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