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catastrophic consequences during CPB [ 4 ]. Inadequate anticoagulation due to HR can lead to the formation of thrombi , increasing the risk of embolization and subsequent organ damage .
Heparin resistance during cardiac surgery can compromise surgical outcomes , particularly by contributing to increased bleeding and the need for transfusions . Edwards et al . presented case reports highlighting non-antithrombin-mediated HR , which underscored the challenges in achieving adequate anticoagulation for CPB [ 22 ]. Suboptimal intraoperative anticoagulation can result in excessive post-operative bleeding , requiring additional transfusions and potentially leading to postoperative complications and prolonged recovery .
A retrospective review aimed at assessing the impact of HR on coronary surgery outcomes revealed that HR was relatively frequent and may impact postoperative morbidity and mortality [ 23 ]. Complications arising from inadequate anticoagulation can necessitate extended monitoring , treatment , and recovery periods , ultimately prolonging hospital stays and delaying patient discharge . Heparin resistance in cardiac surgery not only affects patient outcomes but also imposes a financial burden on healthcare systems .
Management of heparin resistance in cardiac surgery OR
Managing HR necessitates a multidisciplinary approach , involving collaboration among surgeons , anesthesiologists , perfusionists and hematologists . Each speciality brings unique perspectives and expertise to optimize anticoagulation therapy . Effective management of HR is of utmost importance in cardiac surgery , particularly when CPB is involved .
There are multiple pathways for HR patients that allow for the safe commencement of CPB including
Additional doses of heparin .
Fresh Frozen Plasma ( FFP ) administration .
ATIII AT supplementation via ATIII concentrate .
Acceptance of a subtherapeutic ACT and commence CPB without additional intervention [ 5 , 24 – 26 ].
Heparin dose usually ranges from 300 to 500 U / kg in an attempt to achieve ACT of 480 s and above [ 27 ].
A survey-based study explored anticoagulation management and HR during CPB among members of the Society of Cardiovascular Anesthesiologists . It found that 74.9 % of the 550 respondents employed empirical weight-based heparin dosing , with most targeting an ACT of 400 – 480 s to initiate CPB . Despite guidelines recommending higher ACT targets , 17.1 % of respondents did not comply , using lower targets or not monitoring heparin effects at all . For HR , which occurs in 4 % to 26 % of cases , 54.2 % used antithrombin concentrates as the first-line treatment [ 24 ]. Higher doses of heparin are associated with an increased risk of heparin rebound and postoperative bleeding .
Fresh frozen plasma is concomitantly considered postheparin therapy for the management of HR . One unit of FFP contains approximately 1 IU of ATIII per ml , and usually 2 units ( 500 ml ) of FFP are administered , to contribute 500 IU of ATIII [ 8 ]. Apart from resolving HR , one should be concerned about the transmission of viral infections , volume overload , and the risk of transfusion-related lung injury while administering FFP .
ATIII concentrate has been widely used since 1980 after being considered safe by the Food and Drug Administration ( FDA ) of the United States . Increasingly , antithrombin concentrates are preferred due to their targeted action and safety profile , offering direct treatment for antithrombin deficiency without the complications associated with FFP . This shift towards specific , less invasive treatments is part of broader clinical practice changes aimed at improving perioperative patient blood management and anticoagulation efficacy [ 28 ]. Presently ATIII is available in two forms : the human concentrate ( hAT ) and recombinant ( rAT ). Both types of ATIII concentrate are identical and have comparable activity in in vitro thrombin and factor Xa inhibition studies . Each vial of ATIII concentrate contains 500 IU units of ATIII . The usual dose of AT is 1 – 2 vials , equivalent to 500 – 1000 IU of ATIII . A formula constituted by Patnik et al . is ATIII dose ( IU ) = ( desired minus current ATIII level as % of normal level ) weight ( kg ) divided by 1.4 [ 29 ]. According to Stammers et al , the average dose of ATIII concentrate required for the treatment of HR is 1,029.0 ± 164.5 IU or 14.1 ± 3.4 IU / Kg , when normalized to body weight [ 26 ]. A major concern regarding ATIII is cost and availability at certain centres .
A number of studies [ 30 – 32 ] have shown the commencement of CPB in heparin-resistant patients , where the conventional methods failed to reach the desired ACT .
Some critically ill patients are referred for IABP insertion preoperatively , or in some cases , a PCI ( Percutaneous coronary intervention ) may have been done . Anticoagulation therapy for these procedures is important to prevent thrombosis and embolization . This does not mean HR is a definite but one should be aware it may occur in these patients [ 33 ]. Communication of possible HR as a result of the above is essential preoperatively and communication should be fed down to all members of staff in respective departments in an appropriate manner . Staff are then able to prepare for possibilities beforehand . Figure 1 displays a flow chart illustrating the management of HR for CPB commencement .
Management of heparin resistance in ICU Pre-operative considerations
There are several challenges to the identification of HR in the ICU . First , the use of UFH has largely been replaced with low molecular weight heparin ( LMWH ) in current practice [ 34 ], and the increasing use of direct oral anticoagulants obviates the need to bridge patients initiated on Warfarin with UFH in many cases . Second , even when a continuous infusion of UFH is required in ICU , e . g ., acute coronary syndrome , pulmonary embolism , extracorporeal membrane oxygenation , etc ., the dose required rarely reaches what has been described as indicative of HR during cardiac surgery ( 300 U / kg ) [ 6 , 7 ]. Third , conventionally , HR is defined based on failure to achieve a set ACT target ( 400 – 480 s ), an assay that is not routinely used in ICUs around the world as confirmed in the recent International Society of Thrombosis and Hemostasis ( ISTH ) survey [ 35 ]. In 2012 , the American College of Chest Physicians