Correspondence 1
QIMR Berghofer Medical Research Institute, 2School of Biomedical Sci-
Keywords: T cell receptor, polymorphism, variable genes, gene
ences, University of Queensland, Brisbane, Qld, 3Department of
expression
Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Vic., Australia, 4Institute of Infection and
First published online 20 March 2014
Immunity, Cardiff University School of Medicine, Cardiff, UK and 5 School of Medicine, University of Queensland, Brisbane, Qld, Australia.
doi: 10.1111/bjh.12830
E-mail: [email protected], [email protected]
References Brzezinski, J.L., Deka, R., Menon, A.G., Glass, D.N. & Choi, E. (2005) Variability in TRBV haplotype frequency and composition in Caucasian, African American, Western African and Chinese populations. International Journal of Immunogenetics, 32, 413–420. Davis, M.M. & Bjorkman, P.J. (1988) T-cell antigen receptor genes and T-cell recognition. Nature, 334, 395–402. Gras, S., Chen, Z., Miles, J.J., Liu, Y.C., Bell, M.J., Sullivan, L.C., Kjer-Nielsen, L., Brennan, R.M., Burrows, J.M., Neller, M.A., Khanna, R., Purcell, A.W., Brooks, A.G., McCluskey, J., Rossjohn, J. & Burrows, S.R. (2010) Allelic polymorphism in the T cell receptor and its impact on immune responses. Journal of Experimental Medicine, 207, 1555–1567. Gras, S., Burrows, S.R., Turner, S.J., Sewell, A.K., McCluskey, J. & Rossjohn, J. (2012) A structural voyage toward an understanding of the MHC-I-restricted immune response: lessons
learned and much to be learned. Immunological Reviews, 250, 61–81. Hallmayer, J., Faraco, J., Lin, L., Hesselson, S., Winkelmann, J., Kawashima, M., Mayer, G., Plazzi, G., Nevsimalova, S., Bourgin, P., Hong, S.S., Honda, Y., Honda, M., Hogl, B., Longstreth, W.T. Jr, Montplaisir, J., Kemlink, D., Einen, M., Chen, J., Musone, S.L., Akana, M., Miyagawa, T., Duan, J., Desautels, A., Erhardt, C., Hesla, P.E., Poli, F., Frauscher, B., Jeong, J.H., Lee, S.P., Ton, T.G., Kvale, M., Kolesar, L., Dobrovolna, M., Nepom, G.T., Salomon, D., Wichmann, H.E., Rouleau, G.A., Gieger, C., Levinson, D.F., Gejman, P.V., Meitinger, T., Young, T., Peppard, P., Tokunaga, K., Kwok, P.Y., Risch, N. & Mignot, E. (2009) Narcolepsy is strongly associated with the T-cell receptor alpha locus. Nature Genetics, 41, 708–711. Mackelprang, R., Carlson, C.S., Subrahmanyan, L., Livingston, R.J., Eberle, M.A. & Nickerson, D.A. (2002) Sequence variation in the human T-cell
receptor loci. Immunological Reviews, 190, 26– 39. Tsai, C.J., Lin, S.L., Wolfson, H.J. & Nussinov, R. (1997) Studies of protein-protein interfaces: a statistical analysis of the hydrophobic effect. Protein Science, 6, 53–64. Wang, H. & Elbein, S.C. (2007) Detection of allelic imbalance in gene expression using pyrosequencing. Methods in Molecular Biology, 373, 157–176. Wang, Z. & Moult, J. (2001) SNPs, protein structure, and disease. Human Mutation, 17, 263– 270. Watson, C.T., Para, A.E., Lincoln, M.R., Ramagopalan, S.V., Orton, S.M., Morrison, K.M., Handunnetthi, L., Handel, A.E., Chao, M.J., Morahan, J., Sadovnick, A.D., Breden, F. & Ebers, G.C. (2011) Revisiting the T-cell receptor alpha/delta locus and possible associations with multiple sclerosis. Genes and Immunity, 12, 59–66.
Activated prothrombin complex concentrate for the prevention of dabigatran- associated bleeding
The use of prothrombin complex concentrates (PCC), activated PCC (aPCC e.g. factor eight inhibitor bypassing activity [FEIBA, Baxter, Vienna, Austria]) or recombinant activated factor VII (rVIIa; NovoSeven, Novo Nordisk, Bagsvaerd, Denmark) to ‘reverse’ anticoagulation in patients bleeding on oral direct inhibitors (ODIs) has little theoretical basis. rFVIIa activates coagulation above the point where the ODIs act. PCCs are not replacing a missing factor but might provide a large amount of the substrate prothrombin, so increasing thrombin generation. FEIBA could be combining the effects of FVIIa and PCC (Marlu et al, 2012) but alternatively, an activated factor X (FXa):prothrombin complex may be the main active component (Turecek et al, 2004). We read with interest the correspondence by Schulman and colleagues (Schulman et al, 2014) in which they described the use of FEIBA in dabigatran-associated bleeding. We would 152
like to report a case where FEIBA prevented bleeding in a patient with high levels of dabigatran who needed a high risk procedure. An 80-year-old patient with septic shock and acute renal failure required urgent percutaneous trans-hepatic drainage of a gallbladder empyema. He had a history of atrial fibrillation (CHADS-VASC score 6 - hypertension, type 2 diabetes, previous stroke and peripheral vascular disease) for which he was on dabigatran 110 mg bd. His last dose of dabigatran was 30 h previously. His creatinine was 430 lmol/l with an estimated creatinine clearance of 17 ml/ min. The activated partial thromboplastin time was 504 s (normal 26–36), thrombin time 212 s and the dabigatran level, measured with a dilute thrombin time assay (Hemoclot, Hyphen Biomed, Neurillesur, Oise, France), was 200 lg/l. He was assessed as needing urgent drainage of the gall-bladder empyema and immediately prior to trans-hepatic ª 2014 John Wiley & Sons Ltd British Journal of Haematology, 2014, 166, 140–153
Correspondence ultrasound-guided drainage, he received 40 units/kg of FEIBA. There were no bleeding complications and the patient’s clinical state dramatically improved. We conclude that, as well as being useful for critical bleeding in patients on dabigatran, FEIBA may allow an emergency procedure with substantial bleeding risk to be undertaken despite significant therapeutic levels of dabigatran.
Oxford Haemophilia and Thrombosis Centre, Oxford, UK. E-mail: [email protected]
Keywords: anticoagulation, dabigatran, FEIBA First published online 12 March 2014 doi: 10.1111/bjh.12831
Henna Wong David Keeling
References Marlu, R., Hodaj, E., Paris, A., Albaladejo, P., Crackowski, J.L. & Pernod, G. (2012) Effect of nonspecific reversal agents on anticoagulant activity of dabigatran and rivaroxaban. A randomised
crossover ex vivo study in healthy volunteers. Thrombosis and haemostasis, 108, 217–224. Schulman, S., Ritchie, B., Goy, J.K., Nahirniak, S., Almutawa, M. & Ghanny, S. (2014) Activated prothrombin complex concentrate for dabigatran-
ª 2014 John Wiley & Sons Ltd British Journal of Haematology, 2014, 166, 140–153
associated bleeding. British Journal of Haematology, 164, 308–310. Turecek, P.L., Varadi, K., Gritsch, H. & Schwarz, H.P. (2004) FEIBA: mode of action. Haemophilia, 10, 3–9.
153
QIMR Berghofer Medical Research Institute, 2School of Biomedical Sci-
Keywords: T cell receptor, polymorphism, variable genes, gene
ences, University of Queensland, Brisbane, Qld, 3Department of
expression
Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Vic., Australia, 4Institute of Infection and
First published online 20 March 2014
Immunity, Cardiff University School of Medicine, Cardiff, UK and 5 School of Medicine, University of Queensland, Brisbane, Qld, Australia.
doi: 10.1111/bjh.12830
E-mail: [email protected], [email protected]
References Brzezinski, J.L., Deka, R., Menon, A.G., Glass, D.N. & Choi, E. (2005) Variability in TRBV haplotype frequency and composition in Caucasian, African American, Western African and Chinese populations. International Journal of Immunogenetics, 32, 413–420. Davis, M.M. & Bjorkman, P.J. (1988) T-cell antigen receptor genes and T-cell recognition. Nature, 334, 395–402. Gras, S., Chen, Z., Miles, J.J., Liu, Y.C., Bell, M.J., Sullivan, L.C., Kjer-Nielsen, L., Brennan, R.M., Burrows, J.M., Neller, M.A., Khanna, R., Purcell, A.W., Brooks, A.G., McCluskey, J., Rossjohn, J. & Burrows, S.R. (2010) Allelic polymorphism in the T cell receptor and its impact on immune responses. Journal of Experimental Medicine, 207, 1555–1567. Gras, S., Burrows, S.R., Turner, S.J., Sewell, A.K., McCluskey, J. & Rossjohn, J. (2012) A structural voyage toward an understanding of the MHC-I-restricted immune response: lessons
learned and much to be learned. Immunological Reviews, 250, 61–81. Hallmayer, J., Faraco, J., Lin, L., Hesselson, S., Winkelmann, J., Kawashima, M., Mayer, G., Plazzi, G., Nevsimalova, S., Bourgin, P., Hong, S.S., Honda, Y., Honda, M., Hogl, B., Longstreth, W.T. Jr, Montplaisir, J., Kemlink, D., Einen, M., Chen, J., Musone, S.L., Akana, M., Miyagawa, T., Duan, J., Desautels, A., Erhardt, C., Hesla, P.E., Poli, F., Frauscher, B., Jeong, J.H., Lee, S.P., Ton, T.G., Kvale, M., Kolesar, L., Dobrovolna, M., Nepom, G.T., Salomon, D., Wichmann, H.E., Rouleau, G.A., Gieger, C., Levinson, D.F., Gejman, P.V., Meitinger, T., Young, T., Peppard, P., Tokunaga, K., Kwok, P.Y., Risch, N. & Mignot, E. (2009) Narcolepsy is strongly associated with the T-cell receptor alpha locus. Nature Genetics, 41, 708–711. Mackelprang, R., Carlson, C.S., Subrahmanyan, L., Livingston, R.J., Eberle, M.A. & Nickerson, D.A. (2002) Sequence variation in the human T-cell
receptor loci. Immunological Reviews, 190, 26– 39. Tsai, C.J., Lin, S.L., Wolfson, H.J. & Nussinov, R. (1997) Studies of protein-protein interfaces: a statistical analysis of the hydrophobic effect. Protein Science, 6, 53–64. Wang, H. & Elbein, S.C. (2007) Detection of allelic imbalance in gene expression using pyrosequencing. Methods in Molecular Biology, 373, 157–176. Wang, Z. & Moult, J. (2001) SNPs, protein structure, and disease. Human Mutation, 17, 263– 270. Watson, C.T., Para, A.E., Lincoln, M.R., Ramagopalan, S.V., Orton, S.M., Morrison, K.M., Handunnetthi, L., Handel, A.E., Chao, M.J., Morahan, J., Sadovnick, A.D., Breden, F. & Ebers, G.C. (2011) Revisiting the T-cell receptor alpha/delta locus and possible associations with multiple sclerosis. Genes and Immunity, 12, 59–66.
Activated prothrombin complex concentrate for the prevention of dabigatran- associated bleeding
The use of prothrombin complex concentrates (PCC), activated PCC (aPCC e.g. factor eight inhibitor bypassing activity [FEIBA, Baxter, Vienna, Austria]) or recombinant activated factor VII (rVIIa; NovoSeven, Novo Nordisk, Bagsvaerd, Denmark) to ‘reverse’ anticoagulation in patients bleeding on oral direct inhibitors (ODIs) has little theoretical basis. rFVIIa activates coagulation above the point where the ODIs act. PCCs are not replacing a missing factor but might provide a large amount of the substrate prothrombin, so increasing thrombin generation. FEIBA could be combining the effects of FVIIa and PCC (Marlu et al, 2012) but alternatively, an activated factor X (FXa):prothrombin complex may be the main active component (Turecek et al, 2004). We read with interest the correspondence by Schulman and colleagues (Schulman et al, 2014) in which they described the use of FEIBA in dabigatran-associated bleeding. We would 152
like to report a case where FEIBA prevented bleeding in a patient with high levels of dabigatran who needed a high risk procedure. An 80-year-old patient with septic shock and acute renal failure required urgent percutaneous trans-hepatic drainage of a gallbladder empyema. He had a history of atrial fibrillation (CHADS-VASC score 6 - hypertension, type 2 diabetes, previous stroke and peripheral vascular disease) for which he was on dabigatran 110 mg bd. His last dose of dabigatran was 30 h previously. His creatinine was 430 lmol/l with an estimated creatinine clearance of 17 ml/ min. The activated partial thromboplastin time was 504 s (normal 26–36), thrombin time 212 s and the dabigatran level, measured with a dilute thrombin time assay (Hemoclot, Hyphen Biomed, Neurillesur, Oise, France), was 200 lg/l. He was assessed as needing urgent drainage of the gall-bladder empyema and immediately prior to trans-hepatic ª 2014 John Wiley & Sons Ltd British Journal of Haematology, 2014, 166, 140–153
Correspondence ultrasound-guided drainage, he received 40 units/kg of FEIBA. There were no bleeding complications and the patient’s clinical state dramatically improved. We conclude that, as well as being useful for critical bleeding in patients on dabigatran, FEIBA may allow an emergency procedure with substantial bleeding risk to be undertaken despite significant therapeutic levels of dabigatran.
Oxford Haemophilia and Thrombosis Centre, Oxford, UK. E-mail: [email protected]
Keywords: anticoagulation, dabigatran, FEIBA First published online 12 March 2014 doi: 10.1111/bjh.12831
Henna Wong David Keeling
References Marlu, R., Hodaj, E., Paris, A., Albaladejo, P., Crackowski, J.L. & Pernod, G. (2012) Effect of nonspecific reversal agents on anticoagulant activity of dabigatran and rivaroxaban. A randomised
crossover ex vivo study in healthy volunteers. Thrombosis and haemostasis, 108, 217–224. Schulman, S., Ritchie, B., Goy, J.K., Nahirniak, S., Almutawa, M. & Ghanny, S. (2014) Activated prothrombin complex concentrate for dabigatran-
ª 2014 John Wiley & Sons Ltd British Journal of Haematology, 2014, 166, 140–153
associated bleeding. British Journal of Haematology, 164, 308–310. Turecek, P.L., Varadi, K., Gritsch, H. & Schwarz, H.P. (2004) FEIBA: mode of action. Haemophilia, 10, 3–9.
153
