Coagulation Management Research Articles

Applying the Cell-Based Coagulation Model in the Management of Critical Bleeding

The cell-based coagulation model was proposed 15 years ago, yet has not been applied commonly in the management of critical bleeding. Nevertheless, this alternative model may better explain the physiological basis of current coagulation management during critical bleeding. In this article we describe the limitations of the traditional coagulation protein cascade and standard coagulation tests, and explain the potential advantages of applying the cell-based model in current coagulation management strategies. The cell-based coagulation model builds on the traditional coagulation model and explains many recent clinical observations and research findings related to critical bleeding unexplained by the traditional model, including the encouraging results of using empirical 1:1:1 fresh frozen plasma:platelets:red blood cells transfusion strategy, and the use of viscoelastic and platelet function tests in patients with critical bleeding. From a practical perspective, applying the cell-based coagulation model also explains why new direct oral anticoagulants are effective systemic anticoagulants even without affecting activated partial thromboplastin time or the International Normalized Ratio in a dose-related fashion. The cell-based coagulation model represents the most cohesive scientific framework on which we can understand and manage coagulation during critical bleeding.

Coagulation Management in Jersey Calves: An ex vivo Study

Objective: Jersey calves are frequently used as an experimental animal model for in vivo testing of cardiac assist devices or orthopedic implants. In this ex vivo study, we analyzed the coagulation system of the Jersey calves and the potential of human-based coagulation management to circumvent perioperative bleeding complications during surgery. Experimental Procedure: Blood from 7 Jersey calves was subjected to standard laboratory tests and thromboelastometry analysis. An ex vivo model of dilutional coagulopathy was used to study the effects of fibrinogen or prothrombin complex concentrate supplementation. Fibrinolysis was induced with tissue plasminogen activator to identify potential therapeutic strategies involving tranexamic acid or aprotinin. Furthermore, anticoagulation strategies were evaluated by incubating the blood samples with dabigatran or rivaroxaban. Results: Baseline values for thromboelastometry and standard laboratory parameters, including prothrombin time, activated partial thromboplastin time, fibrinogen, antithrombin III, and D-dimers, were established. Fifty percent diluted blood showed a statistically significant impairment of hemostasis. The parameters significantly improved after the administration of fibrinogen or prothrombin complex concentrate. Tranexamic acid and aprotinin ameliorated tissue plasminogen activator-induced fibrinolysis. Both dabigatran and rivaroxaban significantly prolonged the coagulation parameters. Conclusions: In this ex vivo study, coagulation factors, factor concentrate, antifibrinolytic reagents, and anticoagulants regularly used in the clinic positively impacted coagulation parameters in Jersey calf blood.

The Neurostimulation Appropriateness Consensus Committee (NACC): Recommendations on Bleeding and Coagulation Management in Neurostimulation Devices

The Neurostimulation Appropriateness Consensus Committee (NACC) was formed by the International Neuromodulation Society (INS) in 2012 to evaluate the evidence to reduce the risk of complications and improve the efficacy of neurostimulation. The first series of papers, published in 2014, focused on the general principles of appropriate practice in the surgical implantation of neurostimulation devices. The NACC was reconvened in 2014 to address specific patient care issues, including bleeding and coagulation. The INS strives to improve patient care in an evidence-based fashion. The NACC members were appointed or recruited by the INS leadership for diverse expertise, including international clinical expertise in many areas of neurostimulation, evidence evaluation, and publication. The group developed best practices based on peer-reviewed evidence and, in the absence of specific evidence, on expert opinion. Recommendations were based on international evidence in accordance with guideline creation. The NACC has recommended specific measures to reduce the risk of bleeding and neurological injury secondary to impairment of coagulation in the setting of implantable neurostimulation devices in the spine, brain, and periphery.

Coagulation and Blood Management

Coagulation and Blood Management

Anesthetic management of a patient with factor VII deficiency undergoing laparoscopic colectomy: a case report.

BackgroundCongenital factor VII (FVII) deficiency is a rare autosomal recessive coagulation disorder that is characterized by prolongation of prothrombin time. Recombinant activated FVII (rFVIIa) is widely used in the management of bleeding in patients with congenital FVII deficiency. We experienced anesthetic management of a patient with congenital FVII deficiency who was scheduled for laparoscopic colectomy using rFVIIa.Case presentationWe report a 67-year-old man with rectal cancer who was diagnosed with congenital FVII deficiency. He was scheduled for laparoscopic colectomy. General anesthesia was performed with propofol, remifentanil, and rocuronium without epidural anesthesia. For coagulation management, 1 mg of rFVIIa was intravenously administered before starting surgery. During surgery, FVII activity and prothrombin time-international normalized ratio (PT-INR) were maintained to be above 10 % and within the normal range (0.8–1.2), respectively. The surgery was uneventfully completed.ConclusionsWe reported successful management of a patient with congenital FVII deficiency undergoing laparoscopic colectomy with monitoring of FVII activity and/or PT-INR.

Anesthetic Considerations for Surgery on the Aortic Arch

Aortic arch surgery requires meticulous teamwork in the true perioperative sense. Planning and communication at all phases from preoperative evaluation, through intraoperative management, to postoperative care should be well coordinated between surgical, anesthesia, perfusion, and intensive care unit teams. This review discusses intraoperative management from the anesthesiologist's perspective, with particular emphasis on transesophageal echo evaluation and coagulation management.

Targeted Coagulation Management in Severe Trauma: The Controversies and the Evidence.

Hemorrhage in the setting of severe trauma is a leading cause of death worldwide. The pathophysiology of hemorrhage and coagulopathy in severe trauma is complex and remains poorly understood. Most clinicians currently treating trauma patients acknowledge the presence of a coagulopathy unique to trauma patients-trauma-induced coagulopathy (TIC)-independently associated with increased mortality. The complexity and incomplete understanding of TIC has resulted in significant controversy regarding optimum management. Although the majority of trauma centers utilize fixed-ratio massive transfusion protocols in severe traumatic hemorrhage, a widely accepted "ideal" transfusion ratio of blood to blood products remains elusive. The recent use of viscoelastic hemostatic assays (VHAs) to guide blood product replacement has further provoked debate as to the optimum transfusion strategy. The use of VHA to quantify the functional contributions of individual components of the coagulation system may permit targeted treatment of TIC but remains controversial and is unlikely to demonstrate a mortality benefit in light of the heterogeneity of the trauma population. Thus, VHA-guided algorithms as an alternative to fixed product ratios in trauma are not universally accepted, and a hybrid strategy starting with fixed-ratio transfusion and incorporating VHA data as they become available is favored by some institutions. We review the current evidence for the management of coagulopathy in trauma, the rationale behind the use of targeted and fixed-ratio approaches and explore future directions.

Challenges with Navigating the Precarious Hemostatic Balance during Extracorporeal Life Support: Implications for Coagulation and Transfusion Management.

For the past four decades, extracorporeal life support (ECLS) has been used to treat critically ill adult and pediatric patients with cardiac and/or respiratory failure, and there are increasingly numbers of centers worldwide performing ECLS for numerous indications. Despite the progress with advancing the technology, hemorrhagic and thrombotic complications are frequently reported and associated with worse outcomes, but the exact cause is often elusive or multifactorial. As a result of the interaction between blood and an artificial circuit, anticoagulation is necessary and there is resultant activation of coagulation, fibrinolysis, as well as, an increased inflammatory response. While unfractionated heparin (UFH) remains the mainstay anticoagulant used during ECLS, there is a paucity of published data to develop a universal anticoagulation guideline and centers are forced to create individualized protocols to guide anticoagulation management while lacking expertise. From an international survey, centers often use a combination of tests, which in turn result in discordant results and confused management. Studies are urgently needed to investigate optimization of current anticoagulation strategies with UFH, as well as, use of alternative anticoagulants and non-thrombogenic biomaterials. Blood transfusion during extracorporeal support typically occurs for several reasons, which includes circuit priming, restoration of oxygen carrying capacity, maintenance of a hemostatic balance, and treatment of hemorrhagic complications. As a result, the majority of patients will have been exposed to at least one blood product during extracorporeal support and transfusion utilization is high. ECLS Centers have adopted transfusion thresholds based upon practice rather than evidence as there have been no prospective studies investigating the efficacy of red cell (RBC) transfusion in patients receiving extracorporeal support. In addition, RBC transfusion has been associated with increased mortality in ECLS in several retrospective studies. Additional studies are needed to establish evidence based thresholds for transfusion support and diagnostics to guide transfusion therapy to assess efficacy of transfusion in this population, as well as, exploration of alternatives to transfusion.

Electron Microscopy as a Tool for Assessment of Anticoagulation Strategies During Extracorporeal Life Support: The Proof Is on the Membrane.

Extracorporeal life support (ECLS) is fast becoming more common place for use in adult patients failing mechanical ventilation. Management of coagulation and thrombosis has long been a major complication in the use of ECLS therapies. Scanning electron microscopy (SEM) of membrane oxygenators (MOs) after use in ECLS circuits can offer novel insight into any thrombotic material deposition on the MO. In this pilot study, we analyzed five explanted MOs immediately after use in a sheep model of different acute respiratory distress syndrome (ARDS). We describe our methods of MO dissection, sample preparation, image capture, and results. Of the five MOs analyzed, those that received continuous heparin infusion showed very little thrombosis formation or other clot material, whereas those that were used with only initial heparin bolus showed readily apparent thrombotic material.

Blood transfusion and coagulation management.

Despite impressive progress in surgical technique, aortic surgery is still associated with relatively high morbidity and mortality. One of the most important contributors to this phenomenon is the triad of bleeding, anemia, and transfusion. All three factors are known to influence the outcome of aortic surgery to a great extent. However, over the last few years a multidisciplinary, multimodal concept has been established, which enables the physician to avoid bleeding, anemia, and transfusion as much as possible. The concept of "patient blood management" combines several established measures with the potential to improve perioperative outcome. This chapter describes these measures with regard to aortic surgery and assesses their respective efficacy.

Perioperative management of a bilateral forearm allograft

Composite tissue allotransplantation (CTA) is a complex procedure requiring a multidisciplinary collaboration between surgeons, anesthetists, and transplantation specialists. We will describe the perioperative management of a bilateral forearm allograft performed at our facility. A 40-year-old man who lost both forearms was registered on the transplant waiting list; a suitable graft was available 11months later. Anesthesia required planning for vascular access, hemodynamic monitoring, fluid therapy management and prevention of deep vein thrombosis. Blood loss was not quantifiable, which made coagulation management challenging. Reperfusion syndrome required the use of vasopressors. Postoperatively, moderate rhabdomyolysis without acute renal failure was observed. No complications such as thrombosis, hemorrhage, or opportunistic infections occurred during the early postoperative period. A comprehensive, protocol-driven, patient care strategy is crucial for the proper conduct of the surgical procedure and graft survival.

Cost analysis of patient blood management

Patient blood management (PBM) is amultidisciplinary approach focusing on the diagnosis and treatment of preoperative anaemia, the minimisation of blood loss, and the optimisation of the patient-specific anaemia reserve to improve clinical outcomes. Economic aspects of PBM have not yet been sufficiently analysed. The aim of this study is to analyse the costs associated with the clinical principles of PBM and the project costs associated with the implementation of aPBM program from an institutional perspective. Patient-related costs of materials and services were analysed at the University Hospital Frankfurt for 2013. Personnel costs of all major processes were quantified based on the time required to perform each step. Furthermore, general project costs of the implementation phase were determined. Direct costs of transfusing asingle unit of red blood cells can be calculated to aminimum of €147.43. PBM-associated costs varied depending on individual patient requirements. The following costs per patient were calculated: diagnosis of preoperative anaemia €48.69-123.88; treatment of preoperative anaemia (including iron-deficiency anaemia and megaloblastic anaemia) €12.61-127.99; minimising perioperative blood loss (including point-of-care diagnostics, coagulation management and cell salvage) €3.39-1,901.81; and costs associated with the optimisation of the tolerance to anaemia (including patient monitoring and volume therapy) €28.62. General project costs associated with the implementation of PBM were €24,998.24. PBM combines various alternatives to the transfusion of red blood cells and improves clinical outcome. Costs of PBM vary from institution to institution and depend on the extent to which different aspects of PBM have been implemented. The quantification of costs associated with PBM is essential in order to assess the economic impact of PBM, and thereby, to efficiently re-allocate health care resources. Costs were determined at a single university hospital. Thus, further analyses of both the costs of transfusion and the costs of PBM-principles will be necessary to evaluate the cost-effectiveness of PBM.

Advantages of a Warfarin Protocol for Long-term Care Pharmacists: a Retrospective Cohort Study.

BackgroundWarfarin is an anticoagulant prescribed to 12% of long-term care residents to reduce the risk of thrombo-embolism. This study used indicators to compare warfarin management by pharmacists to usual care.MethodsThis was a retrospective cohort study comparing a pharmacist-managed warfarin protocol with usual care of qualified warfarin recipients at long-term care facilities (two protocol, one control) in Calgary, Alberta. We compared the proportion of international normalized ratio (INR) tests in the range 2.0 to 3.0, time in range, number of tests, and frequency of bleeding at protocol and control sites. Our primary outcome, time in INR therapeutic range, is an indicator for assuring care quality. A cross-sectional survey at these sites compared health professionals’ perceptions of workload and effectiveness of warfarin management.ResultsOf the 197 residents’ charts reviewed in the study period, those on protocol had 45.0 INR tests while those on usual care had 52.7 tests (p = .034, 95% CI for the difference: 0.6 to 14.6 INR tests). No significant difference was found for time in therapeutic range, number of tests in range, or major bleeding events. Of 178 health professionals surveyed, those from protocol facilities were more satisfied with warfarin management (p = .013). Workload and safety were perceived similarly at all sites.InterpretationOur results suggest that a pharmacist-managed warfarin protocol is as effective as usual care and has advantages pertaining to work satisfaction, knowledge of drug interactions, consistent documentation, and fewer INR tests. Further research on teamwork and coagulation management in long-term care facilities is recommended.

Point-of-care thromboelastography/thromboelastometry-based coagulation management in cardiac surgery: a meta-analysis of 8332 patients

ObjectivesSevere bleeding related to cardiac surgery is associated with increased morbidity and mortality. Thromboelastography (TEG) and thromboelastometry (ROTEM) are point-of-care tests (POCT). Bedside ROTEM/TEG can rapidly detect changes in blood coagulation and therefore provide a goal-directed, individualized coagulation therapy. In this meta-analysis, we aimed to determine the current evidence for or against POCT-guided algorithm in patients with severe bleeding after cardiac surgery. MethodsWe performed a meta-analysis of randomized controlled trials and observational trials retrieved from a literature search in PubMed, EMBASE, and Cochrane Library. Only trials comparing transfusion strategy guided by TEG/ROTEM with a standard of care control group undergoing cardiac surgery were included. In addition, at least one clinical outcome had to be mentioned: mortality, surgical re-exploration rate, sternal wound infection, and acute kidney injury (AKI). Also, surrogate parameters such as transfusion requirements and amount of blood loss were analyzed. The pooled treatment effects (odds ratio [OR] and 95% confidence intervals [CI]) were assessed using a fixed or random-effects model. ResultsThe literature search retrieved a total of 17 trials (nine randomized controlled trial and eight observational trials) involving 8332 cardiac surgery patients. POCT-guided transfusion management significantly decreased the odds for patients to receive allogeneic blood products (OR 0.63, 95% CI 0.56-0.71; P < 0.00001) and the re-exploration rate due to postoperative bleeding (OR 0.56, 95% CI 0.45-0.71; P < 0.00001). Furthermore, the incidence of postoperative AKI (OR 0.77, 95% CI 0.61-0.98; P = 0.0278) and thromboembolic events (OR 0.44, 95% CI 0.28-0.70; P = 0.0006) was significantly decreased in the TEG/ROTEM group. No statistical differences were found with regard to inhospital mortality, cerebrovascular accident, or length of intensive care unit and hospital stay. ConclusionsTEG/ROTEM-based coagulation management decreases the risk of allogeneic blood product exposure after cardiac surgery. Furthermore, it results in significantly lower re-exploration rate, decreased incidence of postoperative AKI, and thromboembolic events in cardiac surgery patients. Results of this meta-analysis indicate that POCT-guided transfusion therapy is superior to the current standard of care.

Anaesthetic Considerations in the Perioperative Management of Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy has emerged as one of the primary modalities of treatment of diffuse peritoneal malignancies. It is a complex surgical procedure with the patients facing major and potentially life threatening alterations of haemodynamic, respiratory, metabolic and thermal balance with significant fluid losses and the perioperative management is challenging for anaesthesiologists and intensive care physicians. Though the alterations are short lived, these patients require advanced organ function monitoring and support perioperatively. The anaesthesiologist is involved in the management of haemodynamics, respiratory function, coagulation, haematologic parameters, fluid balance, thermal variations, and metabolic and nutritional support perioperatively. The chemotherapy instillate used are known to cause nephrotoxicity, cardiotoxicity, dyselectrolytemia and lactic acidosis. The preoperative polypharmacy for pain control, previous surgery and/or chemotherapy, malnourished status secondary to feeding problems and tumour wasting syndrome make the task all the more challenging. The anaesthesiologist also needs to consider the perioperative care from a quality of life perspective and proper preoperative counselling is important. The present overview summarizes the challenges faced by the anaesthesiologist regarding the pathophysiological alterations during the Cytoreductive surgery and Hyperthermic intraperitoneal chemotherapy in the preoperative, intraoperative and postoperative periods.

Targeted coagulation management in traumatic haemorrhage

Targeted coagulation management in traumatic haemorrhage

Rotational Thromboelastometry as a Routine Point-of-Care Test Immediately after Cardiopulmonary Bypass Facilitated Earlier Diagnosis of Unexpected Hyperfibrinolysis and Hypofibrinogenemia During Cardiac Surgery

The present case was to show the efficacy of implementing routine intra operative parallel rotational thromboelastometry (ROTEM) assays immediately after cardiopulmonary bypass (CPB) in diagnosis and management of unexpected post-CPB bleeding diathesis in cardiac and major vascular surgery. A 54-year-old male gone under an elective aortic valve repair and graft interposition procedure. The routine INTEM, EXTEM, FIBTEM, and APTEM assays started immediately after CPB and protamine administration showed tracings indicating hyperfibrinolysis and hypofibrinogenemia. Tranexamic acid was administered intravenously within 30 minutes the start of the ROTEM assay and transfusion of cryoprecipitate was decided. The implementation of routine intra operative parallel ROTEM assays immediately after CPB enabled earlier determination of unexpected post-CPB bleeding diathesis due to hyperfibrinolysis and hypofibrinogenemia and facilitated timely and appropriate coagulation management in cardiac and major vascular surgery.

Hemostasis in liver transplantation: Pathophysiology, monitoring, and treatment.

Recent findings in the pathophysiology and monitoring of hemostasis in patients with end stage liver disease have major impact on coagulation management during liver transplantation. There is increasing evidence, that the changes in both coagulation factors and platelet count regularly observed in patients with liver cirrhosis cannot be interpreted as a reliable indicator of diffuse bleeding risk. Instead, a differentiated view on hemostasis has led to the concept of a rebalanced coagulation system: While it is important to recognize that procoagulant factors are reduced in liver cirrhosis, it is also evident that synthesis of anticoagulant factors and fibrinolytic proteins produced in the liver is also diminished. Similarly, the decreased platelet count may be counterbalanced by increased platelet aggregability caused by highly active von Willebrand multimeres. The coagulation system is therefor stated to be rebalanced. While under normal "unstressed" conditions diffuse bleeding is rarely observed, however both diffuse bleeding or thrombus formation may occur when compensation mechanisms are exhausted. While most patients presenting for liver transplantation have severe cirrhosis, liver function and thus production of pro- and anticoagulant factors can be preserved especially in cholestatic liver disease. During liver transplantation, profound changes in the hemostasis system can occur. Surgical bleeding can lead to diffuse bleeding as coagulation factors and platelets are already reduced. Ischemia and tissue trauma can lead to alterations of hemostasis comparable to trauma induced coagulopathy. A further common disturbance often starting with the reperfusion of the transplanted organ is hyperfibrinolysis which can eventually precipitate complete consumption of fibrinogen and an endogenous heparinization by glycocalyx shedding. Moreover, thrombotic events in liver transplantations are not uncommon and contribute to increased mortality. Besides conventional laboratory methods, bed-side monitoring of hemostasis (e.g., thrombelastography, thrombelastometry) is often used during liver transplantation to rapidly diagnose decreases in fibrinogen and platelet count as well as hyperfibrinolysis and to guide treatment with blood products, factor concentrates, and antifibrinolytics. There is also evidence which suggests when algorithms based on bed-side hemostasis monitoring are used a reduction of blood loss, blood product use, and eventual mortality are possible. Notably, the bed-side monitoring of anticoagulant pathways and the thrombotic risk is not possible at time and thus a cautious and restrictive use of blood products is recommended.

Pre-transplant portal vein thrombosis is an independent risk factor for graft loss due to hepatic artery thrombosis in liver transplant recipients

BackgroundHepatic artery thrombosis is an uncommon but catastrophic complication following liver transplantation. We hypothesize that recipients with portal vein thrombosis are at increased risk. MethodsData on all liver transplants in the U.S. during the MELD era through September 2014 were obtained from UNOS. Status one, multivisceral, living donor, re-transplants, pediatric recipients and donation after cardiac death were excluded. Logistic regression models were constructed for hepatic artery thrombosis with resultant graft loss within 90 days of transplantation. Results63,182 recipients underwent transplantation; 662 (1.1%) recipients had early hepatic artery thrombosis; of those, 91 (13.8%) had pre-transplant portal vein thrombosis, versus 7.5% with portal vein thrombosis but no hepatic artery thrombosis (p < 0.0001). Portal vein thrombosis was associated with an increased independent risk of hepatic artery thrombosis (OR 2.17, 95% CI 1.71–2.76, p < 0.001) as was donor risk index (OR 2.02, 95% CI 1.65–2.48, p < 0.001). Heparin use at cross clamp, INR, and male donors were all significantly associated with lower risk. DiscussionPre-transplant portal vein thrombosis is associated with post-transplant hepatic artery thrombosis independent of other factors. Recipients with portal vein thrombosis might benefit from aggressive coagulation management and careful donor selection. More research is needed to determine causal mechanism.

Reduced Transfusion During OLT by POC Coagulation Management and TEG Functional Fibrinogen: A Retrospective Observational Study.

Patients undergoing orthotopic liver transplantation are at high risk of bleeding complications. Several Authors have shown that thromboelastography (TEG)-based coagulation management and the administration of fibrinogen concentrate reduce the need for blood transfusion. We conducted a single-center, retrospective cohort observational study (Modena Polyclinic, Italy) on 386 consecutive patients undergoing liver transplantation. We assessed the impact on resource consumption and patient survival after the introduction of a new TEG-based transfusion algorithm, requiring also the introduction of the fibrinogen functional thromboelastography test and a maximum amplitude of functional fibrinogen thromboelastography transfusion cutoff (7 mm) to direct in administering fibrinogen (2012-2014, n = 118) compared with a purely TEG-based algorithm previously used (2005-2011, n = 268). After 2012, there was a significant decrease in the use of homologous blood (1502 ± 1376 vs 794 ± 717 mL, P < 0.001), fresh frozen plasma (537 ± 798 vs 98 ± 375 mL, P < 0.001), and platelets (158 ± 280 vs 75 ± 148 mL, P < 0.005), whereas the use of fibrinogen increased (0.1 ± 0.5 vs 1.4 ± 1.8 g, P < 0.001). There were no significant differences in 30-day and 6-month survival between the 2 groups. The implementation of a new coagulation management method featuring the addition of the fibrinogen functional thromboelastography test to the TEG test according to an algorithm which provides for the administration of fibrinogen has helped in reducing the need for transfusion in patients undergoing liver transplantation with no impact on their survival.