FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W1967301385> ?p ?o ?g. }

• W1967301385 endingPage "1608" @default.
• W1967301385 startingPage "1606" @default.
• W1967301385 abstract "Patients with hemophilia A have a congenital defect in thrombin generation. Only limited data are available on the substitution regimens in hemophilia A patients during and after cardiac operations. There are no data on heparinization of these patients during cardiopulmonary bypass. Whereas most case reports suggest factor VIII replacement in combination with standard heparinization to achieve near-normal physiologic factor VIII activity, we describe the successful management of a hemophilic A patient using a low-level factor VIII replacement combined with a reduced heparin dosage during cardiopulmonary bypass. This approach facilitated adequate anticoagulation and minimized the amount of factor VIII treatment necessary without compromising bleeding control. Patients with hemophilia A have a congenital defect in thrombin generation. Only limited data are available on the substitution regimens in hemophilia A patients during and after cardiac operations. There are no data on heparinization of these patients during cardiopulmonary bypass. Whereas most case reports suggest factor VIII replacement in combination with standard heparinization to achieve near-normal physiologic factor VIII activity, we describe the successful management of a hemophilic A patient using a low-level factor VIII replacement combined with a reduced heparin dosage during cardiopulmonary bypass. This approach facilitated adequate anticoagulation and minimized the amount of factor VIII treatment necessary without compromising bleeding control. Drs Lison, Spannagl, and Dietrich disclose that they have financial relationships with CSL Behring. Drs Lison, Spannagl, and Dietrich disclose that they have financial relationships with CSL Behring. Hemophilia A is a hereditary bleeding disorder caused by a deficiency of coagulation factor VIII (FVIII). Previous case reports of hemophilic A patients undergoing cardiac operations recommended preoperative FVIII replacement combined with standard heparinization during cardiopulmonary bypass (CPB) to achieve nearly normal activity [1Stine K.C. Becton D.L. Use of factor VIII replacement during open heart surgery in a patient with haemophilia A.Haemophilia. 2006; 12: 435-436Crossref PubMed Scopus (20) Google Scholar, 2MacKinlay N. Taper J. Renisson F. Rickard K. Cardiac surgery and catheterization in patients with haemophilia.Haemophilia. 2000; 6: 84-88Crossref PubMed Scopus (70) Google Scholar]. Cardiac operations induce significant alterations in the hemostatic system, and thrombin formation plays a key role in the physiology and pathophysiology of hemostasis [3Edmunds Jr, L.H. Colman R.W. Thrombin during cardiopulmonary bypass.Ann Thorac Surg. 2006; 82: 2315-2322Abstract Full Text Full Text PDF PubMed Scopus (121) Google Scholar]. To suppress thrombin generation and provide anticoagulation during CPB, large amounts of unfractionated heparin are usually administered. Nevertheless, elevated markers of hemostatic activation reveal that systemic thrombin generation is still stimulated during CPB. Because of their underlying disease, patients with hemophilia A have a reduced thrombin capacity. We therefore hypothesized that a reduced heparin dose combined with a low-dose substitution regimen before the operation and considerably diminished FVIII replacement throughout the perioperative period would be a feasible option for hemophilia A patients undergoing cardiac operations. A 67-year-old man presented with signs of unstable angina. Angiography revealed a 2-vessel disease with 60% left main stem occlusion. An aortic stenosis and mild aortic insufficiency was also detected. The obese patient (98 kg) was known to have hemophilia A (FVIII activity 3% to 5%). Before the operation, the patient gave general consent for anonymous scientific evaluation of his case. Anesthesia was performed with sufentanil and midazolam supplemented with sevoflurane inhalation, and neuromuscular blockade was achieved by pancuronium bromide. CPB was performed according to a standard protocol using a membrane oxygenator, an open cardiotomy reservoir, and uncoated tubing. Intraoperatively, the patient received high-dose aprotinin (which is no longer available) to enhance hemostasis. During the perioperative period, blood was drawn at different times to measure prothrombin fragment F1+2 (F1+2; Enzygnost F1+2, DadeBehring, Germany; reference range, 0.4 to 1.1 nmol/L) as an index of ongoing thrombin generation. Anticoagulation for CPB was achieved with only 125 U/kg porcine unfractionated heparin (usual standard dose at our institution is 375 U/kg), and an additional 10,000 U were added to the priming solution. Anticoagulation was controlled simultaneously with a celite-based and a kaolin-based activated clotting time (ACT, Hemochron 800, Intern Technidyne Corp, Edison, NY) every 30 minutes (target ACT, 480 seconds). The celite ACT remained above 480 seconds, whereas the kaolin ACT dropped to 298 seconds after 85 minutes of CPB, possibly due to an effect of the aprotinin. Therefore, an additional bolus of 5000 U heparin was applied. At the end of CPB, the celite ACT was more than 1000 seconds, and the kaolin ACT was 618 seconds. A total of 27,500 U heparin was administered intraoperatively. After CPB, heparin was antagonized by protamine chloride at a dosage equivalent to the initial heparin dose. The total aprotinin dosage was 6.5 × 106 KIU. The preoperative level of FVIII activity was 3%. The selected approach used the patient's reduced thrombin capacity for intraoperative anticoagulation as well as to refrain from full substitution of FVIII until termination of CPB. Thus, for the induction of anesthesia, the patient received only 1000 U purified FVIII concentrate (Haemate, CSL Behring, Germany) to secure central venous cannulation. Simultaneously, a continuous infusion of FVIII concentrate (200 U/h) was started to maintain baseline FVIII activity. FVIII activity was undetectable during CPB, but it should be noted that FVIII measurement is influenced by heparin levels. After protamine reversal, the patient received a further bolus of 2000 U FVIII concentrate. FVIII activity rose to 44% and was 41% at the end of the operation (Fig 1). Intraoperatively, 3800 U FVIII concentrate was substituted. During the 120-minute CPB, the patient received an internal mammary artery graft to the left anterior descending artery, a venous graft to the right coronary artery, and the aortic valve was replaced by a biologic prosthesis. The patient's intraoperative course was free of difficulty. F1+2 (Fig 1) increased during CPB, peaked at the end of CPB, and remained slightly elevated until postoperative day 2. The postoperative blood loss was 100, 200, and 290 mL after 6, 12, and 18 hours, respectively. The patient received 2 U of packed red blood cells on day 2. The FVIII infusion was continued for 40 hours at a rate of 200 U/h. At a peak level of 94% on day 2, the FVIII infusion was reduced to 100 U/h and finally stopped. Thus, the level of FVIII activity was maintained at levels of approximately 50% for the first 3 days (Fig 1). FVIII activity measured at discharge from the hospital on day 7 was 9.7%. The patient received a total of 8500 U FVIII concentrate postoperatively. In recent decades, substantial improvements have been made in the management of patients with hemophilia A, and these improvements have resulted in increased life expectancy. Although conferring some protection, the reduced levels of FVIII in hemophilia A patients do not preclude the presence of coronary artery disease (CAD) in this population. Consequently, with longer life expectancy, the prevalence of CAD is expected to increase, along with the subsequent need for cardiac intervention [4Tuinenburg A. Mauser-Bunschoten E.P. Verhaar M.C. et al.Cardiovascular disease in patients with hemophilia.J Thromb Haemost. 2009; 7: 247-254Crossref PubMed Scopus (97) Google Scholar]. Therapy with concentrates carries its own risks. Aside from those related to blood-borne infection [5Knight R. Stanley S. Wong M. Dolan G. Hemophilia therapy and blood-borne pathogen risk.Semin Thromb Hemost. 2006; 32: 3-9Crossref PubMed Scopus (15) Google Scholar] and the potential of inhibitor development [6Goudemand J. Inhibitor development in haemophilia A: the role of von Willebrand factor/factor VIII concentrates.Haemophilia. 2007; 13: 47-51Crossref PubMed Scopus (12) Google Scholar], patients with hemophilia infrequently experience thrombotic complications, especially in relation to factor substitution and operations [7Dargaud Y. Meunier S. Negrier C. Haemophilia and thrombophilia: an unexpected association!.Haemophilia. 2004; 10: 319-326Crossref PubMed Scopus (67) Google Scholar]. Thus, it is essential to limit the dose and the duration of FVIII administration, which will also lower the cost of treatment. Only limited systematic information exists on safe hemostatic substitution regimens during and after cardiac operations. Previous case reports recommended replacement strategies with target levels of approximately 100% FVIII combined with standard heparinization [2MacKinlay N. Taper J. Renisson F. Rickard K. Cardiac surgery and catheterization in patients with haemophilia.Haemophilia. 2000; 6: 84-88Crossref PubMed Scopus (70) Google Scholar]. During the postoperative period, some authors aim to maintain FVIII levels of approximately 100% [1Stine K.C. Becton D.L. Use of factor VIII replacement during open heart surgery in a patient with haemophilia A.Haemophilia. 2006; 12: 435-436Crossref PubMed Scopus (20) Google Scholar, 2MacKinlay N. Taper J. Renisson F. Rickard K. Cardiac surgery and catheterization in patients with haemophilia.Haemophilia. 2000; 6: 84-88Crossref PubMed Scopus (70) Google Scholar] up to 14 days postoperatively, whereas others prefer to maintain FVIII levels of approximately 50% [8Tang M. Wierup P. Terp K. et al.Cardiac surgery in patients with haemophilia.Haemophilia. 2009; 15: 101-107Crossref PubMed Scopus (48) Google Scholar]. In hemophilia A, FVIII substitution more or less corrects the coagulation defect and thus carries the paradoxic risk of venous thromboembolism [7Dargaud Y. Meunier S. Negrier C. Haemophilia and thrombophilia: an unexpected association!.Haemophilia. 2004; 10: 319-326Crossref PubMed Scopus (67) Google Scholar]. We therefore aimed to maintain FVIII target activity in the lower limit of the normal range. A continuous infusion of low-dose FVIII concentrate provided adequate VIII activity, as determined by daily monitoring. The patient's postoperative course continued uneventfully. However, stopping substitution early resulted in plasma levels of only 9.7% on the day of discharge, 1 week after the operation. It remains debatable whether a longer infusion time is preferable in view of anticipated bleeding and inadequate wound healing. We used the patient's reduced thrombin capacity as part of anticoagulation during CPB and applied only a low continuous infusion of FVIII concentrate in combination with a reduced dosage of heparin. This approach resulted in an uncomplicated operative course. Despite the reduced heparin dosage, the patient demonstrated adequate ACT response and showed F1+2 levels comparable to those that have been described for patients without hemophilia [9Paparella D. Galeone A. Venneri M.T. et al.Activation of the coagulation system during coronary artery bypass grafting: comparison between on-pump and off-pump techniques.J Thorac Cardiovasc Surg. 2006; 131: 290-297Abstract Full Text Full Text PDF PubMed Scopus (66) Google Scholar, 10Dixon B. Santamaria J. Campbell D. Coagulation activation and organ dysfunction following cardiac surgery.Chest. 2005; 128: 229-236Crossref PubMed Scopus (49) Google Scholar]. Unlike previous reports of patients with mild to moderate hemophilia A undergoing cardiac operations, which involved the use of 35,750 to 136,000 U FVIII [2MacKinlay N. Taper J. Renisson F. Rickard K. Cardiac surgery and catheterization in patients with haemophilia.Haemophilia. 2000; 6: 84-88Crossref PubMed Scopus (70) Google Scholar, 8Tang M. Wierup P. Terp K. et al.Cardiac surgery in patients with haemophilia.Haemophilia. 2009; 15: 101-107Crossref PubMed Scopus (48) Google Scholar], our therapeutic regimen that totaled only 12,300 U enabled a considerable reduction in the factor substitution necessary. Our approach using limited factor substitution is not based on a larger clinical study, and should, therefore, only be implemented in cooperation with experienced hematologists. In conclusion, a cardiac operation with minimal target FVIII activity in combination with reduced heparin during CPB was a feasible option in our hemophilia A patient. Using this unique alternative approach, the amount of FVIII was reduced without compromising bleeding control, thereby preventing the risk of thrombosis and limiting treatment costs. In addition, this case report emphasizes the important role of thrombin generation during cardiac operations. Low FVIII activity may be tolerated during CPB when anticoagulation and thrombin inhibition is mandatory. Increasing numbers of cardiac surgical patients with hemophilia are expected in the future [4Tuinenburg A. Mauser-Bunschoten E.P. Verhaar M.C. et al.Cardiovascular disease in patients with hemophilia.J Thromb Haemost. 2009; 7: 247-254Crossref PubMed Scopus (97) Google Scholar]. Thus, additional clinical data will be necessary to define the optimal therapeutic regimen for these patients." @default.
• W1967301385 created "2016-06-24" @default.
• W1967301385 creator A5024942083 @default.
• W1967301385 creator A5029660812 @default.
• W1967301385 creator A5086134082 @default.
• W1967301385 date "2011-05-01" @default.
• W1967301385 modified "2023-10-18" @default.
• W1967301385 title "Hemophilia A in Cardiac Operations: A Model of Reduced Thrombin Generation" @default.
• W1967301385 cites W1976940506 @default.
• W1967301385 cites W1982977436 @default.
• W1967301385 cites W2001694164 @default.
• W1967301385 cites W2002504775 @default.
• W1967301385 cites W2085597036 @default.
• W1967301385 cites W2087249843 @default.
• W1967301385 cites W2105241397 @default.
• W1967301385 cites W2150095265 @default.
• W1967301385 cites W2163732668 @default.
• W1967301385 cites W2169568874 @default.
• W1967301385 doi "https://doi.org/10.1016/j.athoracsur.2010.10.077" @default.
• W1967301385 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/21524474" @default.
• W1967301385 hasPublicationYear "2011" @default.
• W1967301385 type Work @default.
• W1967301385 sameAs 1967301385 @default.
• W1967301385 citedByCount "12" @default.
• W1967301385 countsByYear W19673013852012 @default.
• W1967301385 countsByYear W19673013852014 @default.
• W1967301385 countsByYear W19673013852015 @default.
• W1967301385 countsByYear W19673013852017 @default.
• W1967301385 countsByYear W19673013852018 @default.
• W1967301385 countsByYear W19673013852019 @default.
• W1967301385 countsByYear W19673013852021 @default.
• W1967301385 countsByYear W19673013852022 @default.
• W1967301385 crossrefType "journal-article" @default.
• W1967301385 hasAuthorship W1967301385A5024942083 @default.
• W1967301385 hasAuthorship W1967301385A5029660812 @default.
• W1967301385 hasAuthorship W1967301385A5086134082 @default.
• W1967301385 hasBestOaLocation W19673013851 @default.
• W1967301385 hasConcept C126322002 @default.
• W1967301385 hasConcept C164705383 @default.
• W1967301385 hasConcept C2777292125 @default.
• W1967301385 hasConcept C3018972837 @default.
• W1967301385 hasConcept C71924100 @default.
• W1967301385 hasConcept C89560881 @default.
• W1967301385 hasConceptScore W1967301385C126322002 @default.
• W1967301385 hasConceptScore W1967301385C164705383 @default.
• W1967301385 hasConceptScore W1967301385C2777292125 @default.
• W1967301385 hasConceptScore W1967301385C3018972837 @default.
• W1967301385 hasConceptScore W1967301385C71924100 @default.
• W1967301385 hasConceptScore W1967301385C89560881 @default.
• W1967301385 hasIssue "5" @default.
• W1967301385 hasLocation W19673013851 @default.
• W1967301385 hasLocation W19673013852 @default.
• W1967301385 hasOpenAccess W1967301385 @default.
• W1967301385 hasPrimaryLocation W19673013851 @default.
• W1967301385 hasRelatedWork W104490558 @default.
• W1967301385 hasRelatedWork W1489399279 @default.
• W1967301385 hasRelatedWork W1978866595 @default.
• W1967301385 hasRelatedWork W2023338794 @default.
• W1967301385 hasRelatedWork W2026217387 @default.
• W1967301385 hasRelatedWork W2045638668 @default.
• W1967301385 hasRelatedWork W2089332582 @default.
• W1967301385 hasRelatedWork W2120739142 @default.
• W1967301385 hasRelatedWork W2417206646 @default.
• W1967301385 hasRelatedWork W2592663473 @default.
• W1967301385 hasVolume "91" @default.
• W1967301385 isParatext "false" @default.
• W1967301385 isRetracted "false" @default.
• W1967301385 magId "1967301385" @default.
• W1967301385 workType "article" @default.