Management Of Perioperative Bleeding Research Articles

Perioperative management of a patient with Bernard–Soulier syndrome that has a refractoriness to platelet transfusion

A patient with Bernard–Soulier syndrome (BSS), characterized by extremely large platelets, thrombocytopenia and prolonged bleeding time underwent general anesthesia for platelet adhesion aberration. This patient has developed a refractoriness to platelet transfusion due to a frequent transfusion of platelets; however the operation was completed without abnormal bleeding by transfusing HLA-matched platelets during the procedure. BSS is a very rare syndrome so there are no well-defined protocols for the management of perioperative bleeding associated with this syndrome. In this report, we present the detail of the perioperative management for these patients with BSS who has a refractoriness to platelet transfusion.

Surgical Experience with rFVIIa (NovoSeven) in congenital haemophilia A and B patients with inhibitors to factors VIII or IX

Patients with congenital haemophilia with inhibitors are at risk of peri-operative bleeding complications, since replacement of the missing coagulation factor is ineffective, presenting a therapeutic challenge in elective or emergency surgery. Therefore, the management of peri-operative bleeding requires the use of bypassing agents, such as recombinant activated FVII (rFVIIa, NovoSeven(®) ). This article presents an updated evaluation of the safety and effectiveness of rFVIIa in the treatment of peri-operative bleeding in this patient population. Surgical and other medical procedures managed with rFVIIa from two randomized clinical trials, the Hemophilia Research Society/Hemophilia and Thrombosis Research Society (HRS/HTRS) registry databases and the medical literature were analysed. There were 395 rFVIIa-treated procedures (261 surgical, 89 dental and 45 other medical procedures) reported for 263 congenital haemophilia patients with inhibitors. In trials, initial rFVIIa dosing was 35-90 mcg kg(-1) bolus injection or 50 mcg kg(-1) h(-1) continuous infusion. Dosing in the registries and literature was more variable. Recombinant FVIIa effectiveness was comparable across data sources, with an overall rate of 84% (333/395). The incidence of thrombotic events was very low (0.4% of patients and 0.025% of procedures). Prior to the US approval of rFVIIa in 1999, surgical procedures in congenital haemophilia patients with inhibitors were often considered too risky. Recombinant FVIIa has consistently demonstrated effectiveness in treatment of bleeding in these patients during such procedures. Thrombotic events were rare. This analysis confirms the value of corroborating clinical trial results with post-marketing surveillance registries to assess small patient populations with clinically challenging management decisions.

Fibrinogen concentrate in the treatment of severe bleeding after aortic aneurysm graft surgery

Aortic aneurysm graft surgery involving cardiopulmonary bypass is often associated with substantial coagulopathic perioperative bleeding, requiring hemostatic intervention with allogeneic blood products, such as fresh frozen plasma, platelet concentrate, and red blood cells. We conducted a pilot study to determine the effects of fibrinogen concentrate in patients with microvascular bleeding during aortic valve surgery with ascending aorta replacement. Dosing of fibrinogen concentrate was individualized based on thromboelastometry. First-line therapy with fibrinogen concentrate reduced the need for allogeneic blood product support, including transfusions of fresh frozen plasma, platelet concentrate, and red blood cells. Similar results were seen in a second cohort study conducted in patients undergoing thoraco-abdominal aortic aneurysm surgery: patients who received fibrinogen concentrate required significantly less allogeneic blood product support following surgery. These results prompted the initiation of a randomized placebo-controlled trial in patients undergoing thoraco-abdominal aortic aneurysm surgery, aortic valve surgery with ascending aorta replacement, or aortic arch surgery. Results are expected to be published soon. Larger, multicenter studies are needed to determine the exact role of fibrinogen concentrate in the management of perioperative bleeding following cardiac surgery and cardiopulmonary bypass.

A critical evaluation of cryoprecipitate for replacement of fibrinogen

Maintaining the plasma fibrinogen concentration is important to limit excessive perioperative blood loss. This article considers the evidence for this statement, and questions the justification for using cryoprecipitate rather than virus-inactivated fibrinogen concentrate to support plasma fibrinogen levels. Haemophilia was historically treated with cryoprecipitate, but specific coagulation factor concentrates are now preferred. In contrast, primary fractions of allogeneic donor blood, including cryoprecipitate, are still commonly used to treat perioperative bleeding. When compared with cryoprecipitate and fresh-frozen plasma (FFP), freeze-dried fibrinogen concentrate offers standardized fibrinogen content, faster reconstitution and improved efficacy. Pasteurization and purification processes employed in the preparation of fibrinogen concentrate reduce the risk of pathogen transmission and immune-mediated complications, in comparison with cryoprecipitate and FFP. When all costs associated with administration are taken into consideration, the cost of fibrinogen concentrate is not substantially different to that of cryoprecipitate. In conclusion, wider availability and use of fibrinogen concentrate may improve the management of perioperative bleeding. Further benefits may accrue from more rapid and accurate techniques for monitoring fibrinogen levels. Clinical studies are needed to evaluate methods of measuring fibrinogen and assessing fibrin polymerization, and to define critical haemostatic plasma fibrinogen concentrations in different perioperative situations.

Surgical Experience with Recombinant FVIIa (rFVIIa) in Patients with Hemophilia and Inhibitors to Factors VIII or IX.

Abstract 1304Poster Board I-326 IntroductionPatients with congenital hemophilia with inhibitors (CHwI) are at particularly high risk of intra- and post-operative bleeding complications since replacement of the missing protein is ineffective, presenting a therapeutic challenge in elective or emergency surgical procedures. The management of peri-operative bleeding in CHwI patients therefore requires the use of bypassing agents such as recombinant activated FVII (rFVIIa, NovoSeven®). MethodsSurgical procedures in CHwI patients managed with rFVIIa from two randomized clinical trials, the Hemophilia Research Society/Hemophilia and Thrombosis Research Society (HRS/HTRS) registry databases and published medical literature were analyzed to identify surgical (non-dental), dental and other medical procedures. Demographics, rFVIIa dosing and exposure, efficacy and safety results from the five different data sources were also collected, eliminating publications with any overt potential for overlap. ResultsThere were 400 rFVIIa-treated procedures reported for 267 CHwI patients (51 patients [51 procedures] from two clinical trials, 15 patients [28 procedures] from the HRS/HTRS registry [1999-2004], 66 patients [143 procedures] from the current phase of the HTRS registry [2004 – 2008] and 135 patients [209 procedures] from published literature). Overall, there were 264 surgical, 91 dental and 45 other medical procedures. In trials, initial rFVIIa dosing was 35 or 90 mcg/kg bolus injection or 50 mcg/kg/hr continuous infusion. Dosing in HRS, HTRS, and in the literature was more variable. In the HRS and HTRS, the dosing was 37-300 mcg/kg bolus injection and in published literature dosing was 35-300 mcg/kg bolus injection or 2.5-50 mcg/kg/hr continuous infusion. Recombinant FVIIa effectiveness was comparable across the different data sources with an overall rate of 85% (339/400). In the clinical trials, bleeding was controlled in 80% (41/51) of procedures. In the HRS/HTRS registry, bleeding was reported as “stopped” after treatment with rFVIIa in 86% of procedures (24/28). Bleeding slowed, but did not stop, in three procedures, and not reported for one procedure. In the HTRS registry, bleeding was reported as stopped in 93% (50/54) of dental, 89% (39/44) of surgical and 87% (39/45) of other medical procedures. Bleeding was reported to have slowed but not stopped in 6% of dental, 11% of surgical and 11% of other medical procedures. In only 1 procedure in HTRS, an additional hemostatic product (aPCC) was administered to stop bleeding. In HTRS, rFVIIa was used as second-line rescue therapy in 12 instances (surgery:3, dental:5, other medical procedures:4). In these instances aPCC was administered first in 5 cases, aminocaproic in 5, aminocaproic/rFVIII in 1 and rFVIII in 1). For the published case reports, treatment with rFVIIa was evaluated to be effective in 83% (147/178) of the surgical cases, partially effective in 6%, and ineffective in 8% of the procedures. Effectiveness was not reported in 4% of procedures. Within this analysis of 400 rFVIIa-treated surgical interventions, one thrombotic event was reported for a 4-year-old with CHwI who developed a partially occlusive right internal jugular thrombosis two days after port-a-cath placement. Additionally, there were a total of 5 events of localized thrombophlebitis (1 from clinical trials, 4 from published literature). ConclusionsRecombinant FVIIa has consistently demonstrated effectiveness in treatment of bleeding episodes in CHwI patients undergoing surgery and other procedures. The extent of the risk of thrombotic adverse events after treatment with rFVIIa in patients with hemophilia and inhibitors is not known, but is considered to be low. Within this analysis, the possibility of thrombotic events does not appear to present an overriding clinical risk (0.25% 1400). This analysis confirms the value of corroborating clinical trial results with post-marketing surveillance registries to assess small patient populations with clinically challenging management decisions. DisclosuresCooper:Novo Nordisk: Employment.

Antiplatelet Agents in the Perioperative Period

To determine the use of the 3 major classes of antiplatelet drugs (aspirin, thienopyridines, and glycoprotein IIb/IIIa inhibitors), their management in the perioperative period, and the risks associated with premature withdrawal. We reviewed the PubMed, EMBASE, and Cochrane databases using the terms antiplatelet agents in the perioperative period, antiplatelet agents and management of bleeding, drug-eluting stents and stent thrombosis, substitutes for antiplatelet agents, and premature withdrawal of antiplatelet agents. Randomized, double-blind, placebo-controlled trials; prospective observational studies; review articles; clinical registry data; and guidelines of professional bodies pertaining to antiplatelet agents were included. Two researchers independently read the selected abstracts and selected the studies that matched the inclusion criteria. Any discordance between the 2 researchers was resolved by discussion so that 99 articles were finally included. Aspirin use should not be stopped in the perioperative period unless the risk of bleeding exceeds the thrombotic risk from withholding the drug. With the exception of recent drug-eluting stent implantation, clopidogrel bisulfate use should be stopped at least 5 days prior to most elective surgery. Use of glycoprotein IIb/IIIa inhibitors must be discontinued preoperatively for more than 12 hours to allow normal hemostasis. Premature withdrawal of antiplatelet agents is associated with a 10% risk of all vascular events. Following drug-eluting stent implantation, withdrawal is associated with stent thrombosis and potentially fatal consequences. No definitive guidelines exist to manage patients who are actively bleeding while taking these drugs.

A review of transfusion risks and optimal management of perioperative bleeding with cardiac surgery

TransfusionVolume 48, Issue s1 p. 2S-30S A review of transfusion risks and optimal management of perioperative bleeding with cardiac surgery George Despotis, George Despotis From the Departments of Pathology and Immunology and Anesthesiology, Washington University School of Medicine, St Louis, Missouri.Search for more papers by this authorCharles Eby, Charles Eby From the Departments of Pathology and Immunology and Anesthesiology, Washington University School of Medicine, St Louis, Missouri.Search for more papers by this authorDouglas M. Lublin, Douglas M. Lublin From the Departments of Pathology and Immunology and Anesthesiology, Washington University School of Medicine, St Louis, Missouri.Search for more papers by this author George Despotis, George Despotis From the Departments of Pathology and Immunology and Anesthesiology, Washington University School of Medicine, St Louis, Missouri.Search for more papers by this authorCharles Eby, Charles Eby From the Departments of Pathology and Immunology and Anesthesiology, Washington University School of Medicine, St Louis, Missouri.Search for more papers by this authorDouglas M. Lublin, Douglas M. Lublin From the Departments of Pathology and Immunology and Anesthesiology, Washington University School of Medicine, St Louis, Missouri.Search for more papers by this author First published: 21 February 2008 https://doi.org/10.1111/j.1537-2995.2007.01573.xCitations: 88 George Despotis, MD, Department of Pathology and Immunology, Box 8118, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, MO 63110; e-mail: gdespotis@path.wustl.edu. Disclosure of potential conflicts of interest: Dr Despotis has received speaking honoraria and has served as a consultant for Bayer Pharmaceuticals, Dyax, Ferring, and Talecris. Dr Eby has received speaking honoraria from Beckman and Medicine Shop. Dr Lublin has nothing to disclose. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume48, Issues1Special Issue: Transfusion and Hemostasis in Cardiac Surgery–An UpdateMarch 2008Pages 2S-30S RelatedInformation

Surgical interventions in a cohort of patients with haemophilia A and inhibitors: an experiential retrospective chart review

Strategies for the management of perioperative bleeding in patients with haemophilia and inhibitors have evolved rapidly as a result of the development of the bypassing agents Factor Eight Inhibitor Bypassing Activity, Anti-inhibitor Coagulant Complex (FEIBA) and activated recombinant factor VII (rFVIIa). However, there are currently no established guidelines for perioperative use of bypassing agents, and few controlled clinical studies have been carried out. Thus, case reports, such as those presented here, provide useful anecdotal evidence to guide the treatment of inhibitor patients. The purpose of this report was to describe experiences in the use of bypassing agents in a small cohort of patients with haemophilia A and inhibitors undergoing surgical procedures. Cases from five treatment centres were reviewed. Twenty-two procedures using FEIBA, rFVIIa or a combination of both agents were compiled from seven inhibitor patients (six with an alloantibody inhibitor and one with an acquired autoantibody inhibitor). Eleven procedures used FEIBA monotherapy, two employed rFVIIa monotherapy and nine were performed using combination therapy. Supplemental therapies were required to manage bleeding in some cases. Haemostatic control was achieved in all cases, and treatment regimens were generally well tolerated. One thrombotic adverse event was reported: evidence of disseminated intravascular coagulation (DIC) was found after rFVIIa use in one case, although the direct cause of DIC was unknown. The experiences in this case review demonstrate that both major and minor surgical procedures can be safely performed in patients with haemophilia and high-titre inhibitors under the cover of bypassing agents, with a high expectation of success.

Risks associated with bleeding and transfusion: rationale for the optimal management of bleeding after cardiac surgery

Background and objectives: The main aim of this review is to summarize the literature with respect to transfusion and bleeding risks and the therapeutic strategies with respect to optimal management of perioperative bleeding. Methods: This review was generated using peer-reviewed manuscripts pertinent to this topic that were identified using a computer-based Medline search. Results: Although the pathophysiology of many transfusion-related complications are well-documented, the incidence of these complications is changing. Transfusion Medicine initiatives are being implemented to reduce complications, however, the literature is describing new potential problems related to transfusion in addition to identification of new potential pathogens while blood shortages may limit our ability to adequately manage our anemic and bleeding patients. Excessive bleeding after cardiac surgery can result in increased morbidity and mortality related to transfusion and hypoperfusion related complications as well as injury to critical organ systems. Seven of eight studies have demonstrated that use of point-of-care (POC) tests of hemostatic function can facilitate the optimal management of excessive bleeding and reduce transfusion after cardiac surgery. Two randomized prospective studies have demonstrated that point-of-care tests that assess platelet function can identify patients at risk for acquired, platelet-related bleeding that may be attenuated with pharmacologic agents such as DDAVP. The current literature contains fifty publications with over 400 patients that describe the fairly consistent efficacy of off-label use of recombinant factor VIIa to manage intractable, life-threatening bleeding. Most of these publications involve either case reports or case series that describe the use of this agent and therefore do not adequately address the safety of this agent. Conclusions: There are substantial risks related to excessive bleeding and transfusion. The literature indicates that use of point-of-care diagnostics with a standardized management algorithm can optimize the management of bleeding and reduce transfusion requirements. Recombinant FVIIa has the potential to reduce transfusion and transfusion-related sequelae and may be life-saving in certain circumstances. However, randomized, controlled trials are warranted to assess both the efficacy and, more importantly, the safety of this intervention (i.e., especially with respect to thrombotic complications) in cardiac surgical patients prior to its use as a first line therapy for bleeding or for bleeding prophylaxis. We must continue to carefully investigate the role of new interventions since the ability to reduce use of blood products, to decrease operative time and/or re-exploration rates has important implications for disease prevention and overall patient safety, blood inventory and associated costs as well as overall health care costs.

Perioperative management of a patient with Bernard-Soulier syndrome for third molar surgery

Bernard-Soulier Syndrome (BSS) is a disease characterized by prolonged bleeding time, thrombocytopenia, and extremely large platelets and has a prevalence of less than 1 in 1,000,000. Patients with disorders of coagulation and bleeding can be among the most difficult surgical patients to manage. Perioperative hemorrhage can contribute to life-threatening complications in even the most routine surgical procedures. Because of the rarity of BSS, there are no well-defined protocols for the management of perioperative bleeding associated with this condition. Treatment with preoperative and intraoperative systemic aminocaproic acid, HLA-matched platelets, and topical gelfoam and thrombin resulted in sustained hemostasis and a durable healing response. For those rare few afflicted with this disease, we present a combined systemic and topical approach that may be helpful in the control and prevention of perioperative hemorrhage in this and other similar platelet disorders.

Pathophysiology, prevention, and treatment of bleeding after cardiac surgery: a primer for cardiologists and an update for the cardiothoracic team

Patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) are at increased risk for excessive perioperative blood loss requiring transfusion of blood products. The risk is dependent on the status of the patient, the type of procedure, and the duration of CPB. This brief review will summarize (1) the pathophysiology of abnormalities in the hemostatic system during CPB; (2) important pharmacologic interventions currently available to decrease blood loss, including mechanisms by which these agents lead to preservation of hemostasis during CPB; and (3) the optimal management of perioperative bleeding using point-of-care coagulation tests.