Monitorización de factores de la coagulación en cirugía
Resumen
Objetivo: El manejo de las cirugías en pacientes hemofílicos es complejo y requiere de un ajuste adecuado de los factores de coagulación para evitar complicaciones hemorrágicas y un consumo elevado. El objetivo de esta revisión sistemática es analizar los estudios farmacocinéticos publicados en cirugía en pacientes con hemofilia, las metodologías empleadas, las principales covariables farmacocinéticas y las recomendaciones de las guías clínicas.
Método: Se ha realizado una búsqueda estructurada sin restricciones de fecha ni idioma en Pubmed, Cochrane y Database of Abstracts of Reviews of Effects empleado los mismos términos de búsqueda: (hemophilia or haemophilia), surgery y (pharmacokinetics or PK).
Resultados: La búsqueda sistemática obtuvo 186 resultados, de los que seleccionamos 34 artículos. Muchos estudios analizaban el uso de erfusiones continuas con el objetivo de lograr niveles estables de factor VIII o IX y reducir el consumo global, aunque su empleo ha caído en desuso. Durante décadas las guías clínicas recomendaban realizar estudios farmacocinéticos completos previos a la cirugía (9-11 muestras), según los cuales se ajusta la dosis prequirúrgica, así como la velocidad de infusión en caso de perfusión continua basándose en el aclaramiento calculado. Otra aproximación es el empleo de modelos poblacionales farmacocinéticos, ajustando con un número más limitado de muestras. Estas estimaciones farmacocinéticas prequirúrgicas pierden validez tan pronto como se inicia un procedimiento quirúrgico, y tienen que ajustarse con niveles pico y valle periódicos. Además, las guías clínicas recomiendan, en función del populationtipo de cirugía, mantener los niveles de factores VIII y IX por encima de los umbrales específicos durante periodos, por lo que resulta fundamental emplear la farmacocinética durante el proceso pre y postquirúrgico. En los últimos años se han desarrollado modelos poblacionales farmacocinéticos de factores VIII y IX específicos para cirugía. Las principales covariables de estos modelos son la edad, el grupo sanguíneo y el tipo de cirugía para el factor VIII, y la edad y el peso corporal para el factor IX.
Conclusiones: La farmacocinética puede permitir ajustar de forma individual y protocolizada las cirugías en pacientes hemofílicos. El desarrollo de modelos farmacocinéticos poblacionales específicos para cirugía, incluyendo los factores de vida media extendida, permitirá optimizar estos tratamientos, con potencial reducción del consumo y las estancias hospitalarias.
Palabras clave
Referencias
Fischer K, Ljung R. Primary prophylaxis in haemophilia care: Guideline update
Blood Cells Mol Dis. 2017;67:81-5. DOI: 10.1016/j.bcmd.2017.02.004
Manco-Johnson MJ, Abshire TC, Shapiro AD, Riske B, Hacker MR, Kilcoyne R,
et al. Prophylaxis versus episodic treatment to prevent joint disease in boys with
severe hemophilia. N Engl J Med. 2007;357(6):535-44. DOI: 10.1056/NEJMoa067659
Srivastava A, Santagostino E, Dougall A, Kitchen S, Sutherland M, Pipe SW, et al.
WFH Guidelines for the Management of Hemophilia, 3rd edition. Haemophilia.
;26 Suppl 6:1-158.
Iorio A, Edginton AN, Blanchette V, Blatny J, Boban A, Cnossen M, et al. Performing
and interpreting individual pharmacokinetic profiles in patients with Hemophilia
A or B: Rationale and general considerations. Res Pract Thromb Haemost.
;2(3):535-48. DOI: 10.1002/rth2.12106
Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JP, et al.
The PRISMA statement for reporting systematic reviews and meta-analyses of studies
that evaluate healthcare interventions: explanation and elaboration. BMJ.
;339:b2700. DOI: 10.1136/bmj.b2700
Lee M, Morfini M, Schulman S, Ingerslev J; the Factor VIII/ Factor IX Scientific and
Standardization Committee of the International Society for Thrombosis and Haemostasis.
The design and analysis of pharmacokinetic studies of coagulation factors
[Internet]; 2001 [accessed: 04/13/2021]. Available at: https://www.isth.
org/members/group_content_view.asp?group=100348&id=159244
Kasper CK, Boylen AL, Ewing NP, Luck JV Jr, Dietrich SL. Hematologic management
of hemophilia A for surgery. JAMA. 1985;253(9):1279-83.
Ruffo S, Messori A, Longo G, Matucci M, Morfini M, Rossi-Ferrini P. A microcomputer
program for individualizing factor VIII dosage in hemophilia patients undergoing
major surgery. Comput Methods Programs Biomed. 1986;23(1):37-46. DOI:
1016/0169-2607(86)90078-7
Longo G, Messori A, Morfini M, Baudo F, Ciavarella N, Cinotti S, et al. Evaluation
of factor VIII pharmacokinetics in hemophilia-A subjects undergoing surgery and
description of a nomogram for dosing calculations. Am J Hematol. 1989;30(3):140-
DOI: 10.1002/ajh.2830300305
Ruffo S, Messori A, Grasela TH, Longo G, Donati-Cori G, Matucci M, et al.
A calculator program for clinical application of the Bayesian method of predicting
plasma drug levels. Comput Programs Biomed. 1985;19(2-3):167-77. DOI:
1016/0010-468x(85)90008-x
Durisová M, Dedík L, Bátorová A, Sakalová A, Hedera J. Pharmacokinetics of factor
VIII in hemophilia A patients assessed by frequency response method. Methods
Find Exp Clin Pharmacol. 1998;20(3):217-26.
Bolon-Larger M, Chamouard V, Bressolle F, Boulieu R. A limited sampling strategy
for estimating individual pharmacokinetic parameters of coagulation factor VIII in
patients with hemophilia A. Ther Drug Monit. 2007;29(1):20-6. DOI: 10.1097/
FTD.0b013e3180311384
Martinowitz U, Schulman S, Gitel S, Horozowski H, Heim M, Varon D. Adjusted
dose continuous infusion of factor VIII in patients with haemophilia A. Br J Haematol.
;82(4):729-34. DOI: 10.1111/j.1365-2141.1992.tb06951.x
Hay CR, Doughty HI, Savidge GF. Continuous infusion of factor VIII for surgery and
major bleeding. Blood Coagul Fibrinolysis. 1996;7 Suppl 1:S15-9.
Rochat C, McFadyen ML, Schwyzer R, Gillham A, Cruickshank A. Continuous
infusion of intermediate-purity factor VIII in haemophilia A patients undergoing
elective surgery. Haemophilia. 1999;5(3):181-6. DOI: 10.1046/j.1365-2516.
00309.x
Martinowitz U, Luboshitz J, Bashari D, Ravid B, Gorina E, Regan L, et al. Stability,
efficacy, and safety of continuously infused sucrose-formulated recombinant factor
VIII (rFVIII-FS) during surgery in patients with severe haemophilia. Haemophilia.
;15(3):676-85. DOI: 10.1111/j.1365-2516.2008.01978.x
Suzuki N, Hirakawa A, Kishimoto M, Kanematsu T, Ogawa M, Kiyoi H, et al.
Retrospective analysis of in vivo recovery and clearance during continuous infusion
of recombinant factor VIII products: a single-institution study. Haemophilia.
;23(2):215-21. DOI: 10.1111/hae.13082
Kremer Hovinga ICL, Schutgens REG, van der Valk PR, van Vulpen LFD, Mauser-Bunschoten
EP, Fischer K. Continuous infusion of extended half-life factor VIII (efmoroctocog
alpha) for surgery in severe haemophilia A. Haemophilia. 2018;24(4):e280-3.
DOI: 10.1111/hae.13557
Schulman S, Wallensten R, White B, Smith OP. Efficacy of a high purity, chemically
treated and nanofiltered factor IX concentrate for continuous infusion in
haemophilia patients undergoing surgery. Haemophilia. 1999;5(2):96-100. DOI:
1046/j.1365-2516.1999.00284.x
Hoots WK, Leissinger C, Stabler S, Schwartz BA, White G, Dasani H, et al.
Continuous intravenous infusion of a plasma-derived factor IX concentrate (Mononine)
in haemophilia B. Haemophilia. 2003;9(2):164-72. DOI: 10.1046/j.1365-
2003.00721.x
Iorio A, Keepanasseril A, Foster G, Navarro-Ruan T, McEneny-King A, Edginton
AN, et al. Development of a Web-Accessible Population Pharmacokinetic Service-
Hemophilia (WAPPS-Hemo): Study Protocol. JMIR Res Protoc. 2016;5(4):e239.
DOI: 10.2196/resprot.6558
Suzuki N, Takedani H, Hirakawa A, Ushijima Y, Matsushita T. The features of clearance
in recombinant factor IX (BeneFIX®). Haemophilia. 2015;21(5):702-7. DOI:
1111/hae.12672
Mahlangu JN, Ragni M, Gupta N, Rangarajan S, Klamroth R, Oldenburg J, et al.
Long-acting recombinant factor VIII Fc fusion protein (rFVIIIFc) for perioperative haemostatic
management in severe haemophilia A. Thromb Haemost. 2016;116(1):1-8.
DOI: 10.1160/TH15-10-0780
Brand B, Gruppo R, Wynn TT, Griskevicius L, López Fernández MF, Chapman M,
et al. Efficacy and safety of pegylated full-length recombinant factor VIII with extended
half-life for perioperative haemostasis in haemophilia A patients. Haemophilia.
;22(4):e251-8. DOI: 10.1111/hae.12963
Gruppo R, López-Fernández MF, Wynn TT, Engl W, Sharkhawy M, Tangada S.
Perioperative haemostasis with full-length, PEGylated, recombinant factor VIII with
extended half-life (rurioctocog alfa pegol) in patients with haemophilia A: Final
results of a multicentre, single-arm phase III trial. Haemophilia. 2019;25(5):773-81.
DOI: 10.1111/hae.13807
Négrier C, Abdul Karim F, Lepatan LM, Lienhart A, López-Fernández MF, Mahlangu
J, et al. Efficacy and safety of long-acting recombinant fusion protein linking factor
IX with albumin in haemophilia B patients undergoing surgery. Haemophilia.
;22(4):e259-66. DOI: 10.1111/hae.12972
Curtin J, Santagostino E, Karim FA, Li Y, Seifert W, Négrier C. Simplifying surgery
in haemophilia B: Low factor IX consumption and infrequent infusions in
surgical procedures with rIX-FP. Thromb Res. 2020;188:85-9. DOI: 10.1016/
j.thromres.2020.02.011
Powell JS, Apte S, Chambost H, Hermans C, Jackson S, Josephson NC, et al. Longacting
recombinant factor IX Fc fusion protein (rFIXFc) for perioperative management
of subjects with haemophilia B in the phase 3 B-LONG study. Br J Haematol.
;168(1):124-34. DOI: 10.1111/bjh.13112
Diao L, Li S, Ludden T, Gobburu J, Nestorov I, Jiang H. Population pharmacokinetic
modelling of recombinant factor IX Fc fusion protein (rFIXFc) in patients with
haemophilia B. Clin Pharmacokinet. 2014;53(5):467-77. DOI: 10.1007/s40262-
-0129-7
Hazendonk HC, van Moort I, Fijnvandraat K, Kruip MJ, Laros-van Gorkom BA, van
der Meer FJ, et al. The “OPTI-CLOT” trial. A randomised controlled trial on periOperative
PharmacokineTIc-guided dosing of CLOTting factor concentrate in haemophilia
A. Thromb Haemost. 2015;114(3):639-44. DOI: 10.1160/TH14-11-0925
Hazendonk H, Fijnvandraat K, Lock J, Driessens M, van der Meer F, Meijer K, et
al. A population pharmacokinetic model for perioperative dosing of factor VIII in
hemophilia A patients. Haematologica. 2016;101(10):1159-69. DOI: 10.3324/
haematol.2015.136275
Preijers T, Liesner R, Hazendonk HCAM, Chowdary P, Driessens MHE, Hart DP, et
al. Validation of a perioperative population factor VIII pharmacokinetic model with
a large cohort of pediatric hemophilia a patients. Br J Clin Pharmacol. 2021 Apr
DOI: 10.1111/bcp.14864. Epub ahead of print.
Preijers T, Hazendonk HCAM, Liesner R, Chowdary P, Driessens MHE, Hart D, et
al. Population pharmacokinetics of factor IX in hemophilia B patients undergoing
surgery. J Thromb Haemost. 2018;16(11):2196-207. DOI: 10.1111/jth.14292
Collins PW, Møss J, Knobe K, Groth A, Colberg T, Watson E. Population pharmacokinetic
modeling for dose setting of nonacog beta pegol (N9-GP), a glyco-
PEGylated recombinant factor IX. J Thromb Haemost. 2012;10(11):2305-12. DOI:
1111/jth.12000
Guidelines for the management of hemophilia (World Federation of Hemophilia).
World Federation of Hemophilia website [Internet]; 2001 [accessed:
/13/2021]. Available at: http://illinoisaap.org/wp-content/uploads/
guidelines-Hemophilia-WHF- 2005.pdf
Simpson ML, Kulkarni R, Escuriola Ettingshausen C, Medom Meldgaard R, Cooper
DL, Klamroth R. Population Pharmacokinetic Modeling Of On-Demand And
Surgical Use Of Nonacog Beta Pegol (N9-GP) And rFIXFc Based Upon The paradigm
Comparative Pharmacokinetic Study. J Blood Med. 2019;10:391-8. DOI:
2147/JBM.S217539
Srivastava A, Brewer AK, Mauser-Bunschoten EP, Key NS, Kitchen S, Llinas A, et
al. Guidelines for the management of hemophilia. Haemophilia. 2013;19(1):e1-47.
DOI: 10.1111/j.1365-2516.2012.02909.x
Preijers T, Laros-vanGorkom BA, Mathôt RA, Cnossen MH. Pharmacokinetic-guided
dosing of factor VIII concentrate in a morbidly obese severe haemophilia A patient
undergoing orthopaedic surgery. BMJ Case Rep. 2019;12(1):bcr-2018-226812.
DOI: 10.1136/bcr-2018-226812
Van Moort I, Bukkems LH, Nieuwenhuizen L, Cnossen MH. Impact of extreme
weight loss on factor VIII concentrate pharmacokinetics in haemophilia. BMJ Case
Rep. 2021;14(4):e238036. DOI: 10.1136/bcr-2020-238036
White GC 2nd, Shapiro AD, Kurczynski EM, Kim HC, Bergman GE. Variability of
in vivo recovery of factor IX after infusion of monoclonal antibody purified factor IX
concentrates in patients with hemophilia B. The Mononine Study Group. Thromb
Haemost. 1995;73(5):779-84.
Hazendonk HC, Lock J, Mathôt RA, Meijer K, Peters M, Laros-van Gorkom BA, et
al. Perioperative treatment of hemophilia A patients: blood group O patients are
at risk of bleeding complications. J Thromb Haemost. 2016;14(3):468-78. DOI:
1111/jth.13242
Iorio A, Iserman E, Blanchette V, Dolan G, Escuriola Ettingshausen C, Hermans
C, et al. Target plasma factor levels for personalized treatment in haemophilia:
a Delphi consensus statement. Haemophilia. 2017;23:e170-9. DOI: 10.1111/
hae.13215
Hazendonk HCAM, Preijers T, Liesner R, Chowdary P, Hart D, Keeling D, et al.
Perioperative replacement therapy in haemophilia B: An appeal to “B” more precise.
Haemophilia. 2018;24(4):611-8. DOI: 10.1111/hae.13469
Megías-Vericat JE, Bonanad S, Haya S, Cid AR, Marqués MR, Monte-Boquet E, et
al. Cross-sectional comparative study of pharmacokinetics and efficacy between
sucrose-formulated recombinant factor VIII (Kogenate®) and BAY 81-8973 (Kovaltry
®) in patients with severe or moderate haemophilia A in prophylaxis. Haemophilia.
;25(3):e215-8. DOI: 10.1111/hae.13733
Pouplard C, Sattler L, Ryman A, Eschwege V, De Maistre E, Flaujac C, et al.
Multicentre pharmacokinetic evaluation of rFVIII-Fc (efmoroctocog alfa) in a real
life and comparison with non-extended half-life FVIII concentrates. Haemophilia.
;26(2):282-9. DOI: 10.1111/hae.13946
Rodríguez López M, Megías Vericat JE, Albo López C, Bonanad S. Clinical, pharmacokinetic
and economic analysis of the first switch to an extended half-life factor
IX (albutrepenonacog alfa, rFIX-FP) in Spain. BMJ Case Rep. 2020;13(10):e234142.
DOI: 10.1136/bcr-2019-234142
Iorio A, Blanchette V, Blatny J, Collins P, Fischer K, Neufeld E. Estimating and interpreting
the pharmacokinetic profiles of individual patients with hemophilia A or B
using a population pharmacokinetic approach: communication from the SSC of the
ISTH. J Thromb Haemost. 2017;15(12):2461-5. DOI: 10.1111/jth.13867
Von Auer CH, Oldenburg J, von Depka M, Escuriola-Ettinghausen C, Kurnik K,
Lenk H, et al. Inhibitor development in patients with hemophilia A after continuous
infusion of FVIII concentrates. Ann N Y Acad Sci. 2005;1051:498-505. DOI:
1196/annals.1361.094
Batorova A, Holme P, Gringeri A, Richards M, Hermans C, Altisent C, et al.
Continuous infusion in haemophilia: current practice in Europe. Haemophilia.
;18(5):753-9. DOI: 10.1111/j.1365-2516.2012.02810.x
Iorio A, Fischer K, Blanchette V, Rangarajan S, Young G, Morfini M; Pharmacokinetic
(PK) Expert Working Group of the International Prophylaxis Study Group (the
IPSG). Tailoring treatment of haemophilia B: accounting for the distribution and
clearance of standard and extended half-life FIX concentrates. Thromb Haemost.
;117(6):1023-30. DOI: 10.1160/TH16-12-0942
Tiede A, Abdul-Karim F, Carcao M, Persson P, Clausen WHO, Kearney S, et al.
Pharmacokinetics of a novel extended half-life glycoPEGylated factor IX, nonacog
beta pegol (N9-GP) in previously treated patients with haemophilia B: results from two
phase 3 clinical trials. Haemophilia. 2017;23(4):547-55. DOI: 10.1111/hae.13191
Enlaces refback
- No hay ningún enlace refback.
Farmacia Hospitalaria
Sociedad Española de Farmacia Hospitalaria. C/ Serrano n. 40 2º Dcha. - 28001 Madrid
eISSN: 2171-8695
ISSN-L: 1130-6343
Dep. Legal: M-39835-2012
Correo electrónico de contacto: [email protected]
Los artículos publicados en esta revista se distribuyen con la licencia: Creative Commons Attribution 4.0.
La revista Farmacia Hospitalaria no cobra tasas por el envío de trabajos, ni tampoco cuotas por la publicación de sus artículos.