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Published in: Journal of Thrombosis and Thrombolysis 3/2019

Open Access 01-10-2019

Influence of factor XII deficiency on activated partial thromboplastin time (aPTT) in critically ill patients

Authors: Mirjam Bachler, Christian Niederwanger, Tobias Hell, Judith Höfer, Dominic Gerstmeyr, Bettina Schenk, Benedikt Treml, Dietmar Fries

Published in: Journal of Thrombosis and Thrombolysis | Issue 3/2019

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Abstract

FXII deficiency results in spontaneous prolongation of activated partial thromboplastin time (aPTT), which is widely used to monitor thromboprophylaxis. Misinterpretation of spontaneously prolonged aPTT may result in omission of thromboembolic treatment or even unnecessary transfusion of blood products. This retrospective analysis was performed to calculate a threshold level of FXII resulting in aPTT prolongation. 79 critically ill patients with spontaneous prolongation of aPTT were included. A correlation analysis and a ROC curve for aPTT prolongation predicted by FXII level were created to find the FXII threshold level. Prolongation of aPTT was associated with disease severity. A significant inverse proportionality between FXII and aPTT was seen. A ROC curve for aPTT prolongation, predicted by FXII level (AUC 0.85; CI 0.76–0.93), revealed a FXII threshold level of 42.5%. Of our patients 50.6% experienced a FXII deficiency, in 80.0% of whom we found aPTT to be prolonged without a significantly higher bleeding rate. The FXII deficiency was more common in patients with higher SAPS3 scores, septic shock, transfusion of red blood cells and platelet concentrates as well as in patients receiving renal replacement therapy. Patients with a FXII deficiency and prolonged aPTT less often received anticoagulatory therapy although they were more severely ill. The rate of thromboembolic events was higher in these patients although the difference was not statistically significant. Of all patients with spontaneous aPTT prolongation 50.6% had a FXII level of 42.5% or less. Those patients received insufficient thromboembolic prophylaxis.
Literature
3.
go back to reference Tauber H, Innerhofer P, Breitkopf R, Westermann I, Beer R, El Attal R, Strasak A, Mittermayr M (2011) Prevalence and impact of abnormal ROTEM(R) assays in severe blunt trauma: results of the ‘Diagnosis and Treatment of Trauma-Induced Coagulopathy (DIA-TRE-TIC) study’. Br J Anaesth 107(3):378–387. https://doi.org/10.1093/bja/aer158 CrossRefPubMed Tauber H, Innerhofer P, Breitkopf R, Westermann I, Beer R, El Attal R, Strasak A, Mittermayr M (2011) Prevalence and impact of abnormal ROTEM(R) assays in severe blunt trauma: results of the ‘Diagnosis and Treatment of Trauma-Induced Coagulopathy (DIA-TRE-TIC) study’. Br J Anaesth 107(3):378–387. https://​doi.​org/​10.​1093/​bja/​aer158 CrossRefPubMed
6.
go back to reference van Veen JJ, Laidlaw S, Swanevelder J, Harvey N, Watson C, Kitchen S, Makris M (2009) Contact factor deficiencies and cardiopulmonary bypass surgery: detection of the defect and monitoring of heparin. Eur J Haematol 82(3):208–212CrossRefPubMed van Veen JJ, Laidlaw S, Swanevelder J, Harvey N, Watson C, Kitchen S, Makris M (2009) Contact factor deficiencies and cardiopulmonary bypass surgery: detection of the defect and monitoring of heparin. Eur J Haematol 82(3):208–212CrossRefPubMed
8.
go back to reference Li R, Swaelens C, Vandermijnsbrugge F, Cantinieaux B (2016) Applying a direct aPTT ratio (PlatelinLS/ActinFS) permits to identify rapidly and reliably a bleeding-related factor deficiency or a lupus anticoagulant sequential to an isolated prolongation of aPTT in paediatric pre-operative screening. Eur J Haematol 96(6):578–585. https://doi.org/10.1111/ejh.12634 CrossRefPubMed Li R, Swaelens C, Vandermijnsbrugge F, Cantinieaux B (2016) Applying a direct aPTT ratio (PlatelinLS/ActinFS) permits to identify rapidly and reliably a bleeding-related factor deficiency or a lupus anticoagulant sequential to an isolated prolongation of aPTT in paediatric pre-operative screening. Eur J Haematol 96(6):578–585. https://​doi.​org/​10.​1111/​ejh.​12634 CrossRefPubMed
11.
go back to reference Atallah S, Liebl M, Fitousis K, Bostan F, Masud F (2014) Evaluation of the activated clotting time and activated partial thromboplastin time for the monitoring of heparin in adult extracorporeal membrane oxygenation patients. Perfusion 29(5):456–461CrossRefPubMed Atallah S, Liebl M, Fitousis K, Bostan F, Masud F (2014) Evaluation of the activated clotting time and activated partial thromboplastin time for the monitoring of heparin in adult extracorporeal membrane oxygenation patients. Perfusion 29(5):456–461CrossRefPubMed
12.
go back to reference van Roessel S, Middeldorp S, Cheung YW, Zwinderman AH, de Pont AC (2014) Accuracy of aPTT monitoring in critically ill patients treated with unfractionated heparin. Neth J Med 72(6):305–310PubMed van Roessel S, Middeldorp S, Cheung YW, Zwinderman AH, de Pont AC (2014) Accuracy of aPTT monitoring in critically ill patients treated with unfractionated heparin. Neth J Med 72(6):305–310PubMed
13.
go back to reference Chowdary P, Saayman AG, Paulus U, Findlay GP, Collins PW (2004) Efficacy of standard dose and 30 ml/kg fresh frozen plasma in correcting laboratory parameters of haemostasis in critically ill patients. Br J Haematol 125(1):69–73CrossRefPubMed Chowdary P, Saayman AG, Paulus U, Findlay GP, Collins PW (2004) Efficacy of standard dose and 30 ml/kg fresh frozen plasma in correcting laboratory parameters of haemostasis in critically ill patients. Br J Haematol 125(1):69–73CrossRefPubMed
14.
go back to reference Innerhofer P, Fries D, Mittermayr M, Innerhofer N, von Langen D, Hell T, Gruber G, Schmid S, Friesenecker B, Lorenz IH, Strohle M, Rastner V, Trubsbach S, Raab H, Treml B, Wally D, Treichl B, Mayr A, Kranewitter C, Oswald E (2017) Reversal of trauma-induced coagulopathy using first-line coagulation factor concentrates or fresh frozen plasma (RETIC): a single-centre, parallel-group, open-label, randomised trial. Lancet Haematol 4(6):e258–e271CrossRefPubMed Innerhofer P, Fries D, Mittermayr M, Innerhofer N, von Langen D, Hell T, Gruber G, Schmid S, Friesenecker B, Lorenz IH, Strohle M, Rastner V, Trubsbach S, Raab H, Treml B, Wally D, Treichl B, Mayr A, Kranewitter C, Oswald E (2017) Reversal of trauma-induced coagulopathy using first-line coagulation factor concentrates or fresh frozen plasma (RETIC): a single-centre, parallel-group, open-label, randomised trial. Lancet Haematol 4(6):e258–e271CrossRefPubMed
16.
go back to reference Dara SI, Rana R, Afessa B, Moore SB, Gajic O (2005) Fresh frozen plasma transfusion in critically ill medical patients with coagulopathy. Crit Care Med 33(11):2667–2671CrossRefPubMed Dara SI, Rana R, Afessa B, Moore SB, Gajic O (2005) Fresh frozen plasma transfusion in critically ill medical patients with coagulopathy. Crit Care Med 33(11):2667–2671CrossRefPubMed
18.
go back to reference Attia J, Ray JG, Cook DJ, Douketis J, Ginsberg JS, Geerts WH (2001) Deep vein thrombosis and its prevention in critically ill adults. Arch Intern Med 161(10):1268–1279CrossRefPubMed Attia J, Ray JG, Cook DJ, Douketis J, Ginsberg JS, Geerts WH (2001) Deep vein thrombosis and its prevention in critically ill adults. Arch Intern Med 161(10):1268–1279CrossRefPubMed
19.
go back to reference Shin DY, Lee HR, Kang HJ, Na II, Chang YH, Yang SH (2015) Prevalent factor XII deficiency in cancer patients with isolated aPTT prolongation. Blood Res 50(2):114–117CrossRefPubMedPubMedCentral Shin DY, Lee HR, Kang HJ, Na II, Chang YH, Yang SH (2015) Prevalent factor XII deficiency in cancer patients with isolated aPTT prolongation. Blood Res 50(2):114–117CrossRefPubMedPubMedCentral
20.
go back to reference Halbmayer WM, Haushofer A, Schon R, Mannhalter C, Strohmer E, Baumgarten K, Fischer M (1994) The prevalence of moderate and severe FXII (Hageman factor) deficiency among the normal population: evaluation of the incidence of FXII deficiency among 300 healthy blood donors. Thromb Haemost 71(1):68–72CrossRefPubMed Halbmayer WM, Haushofer A, Schon R, Mannhalter C, Strohmer E, Baumgarten K, Fischer M (1994) The prevalence of moderate and severe FXII (Hageman factor) deficiency among the normal population: evaluation of the incidence of FXII deficiency among 300 healthy blood donors. Thromb Haemost 71(1):68–72CrossRefPubMed
21.
go back to reference Chng WJ, Sum C, Kuperan P (2005) Causes of isolated prolonged activated partial thromboplastin time in an acute care general hospital. Singapore Med J 46(9):450–456PubMed Chng WJ, Sum C, Kuperan P (2005) Causes of isolated prolonged activated partial thromboplastin time in an acute care general hospital. Singapore Med J 46(9):450–456PubMed
22.
go back to reference Stanworth SJ, Walsh TS, Prescott RJ, Lee RJ, Watson DM, Wyncoll D (2011) A national study of plasma use in critical care: clinical indications, dose and effect on prothrombin time. Crit Care (London, England) 15(2):5CrossRef Stanworth SJ, Walsh TS, Prescott RJ, Lee RJ, Watson DM, Wyncoll D (2011) A national study of plasma use in critical care: clinical indications, dose and effect on prothrombin time. Crit Care (London, England) 15(2):5CrossRef
23.
go back to reference Triulzi D, Gottschall J, Murphy E, Wu Y, Ness P, Kor D, Roubinian N, Fleischmann D, Chowdhury D, Brambilla D (2015) A multicenter study of plasma use in the United States. Transfusion 55(6):1313–1319CrossRefPubMed Triulzi D, Gottschall J, Murphy E, Wu Y, Ness P, Kor D, Roubinian N, Fleischmann D, Chowdhury D, Brambilla D (2015) A multicenter study of plasma use in the United States. Transfusion 55(6):1313–1319CrossRefPubMed
24.
go back to reference Anand D, Das S, Ray S, Bhargava S, Srivastava LM (2014) Interrelationship between procalcitonin and organ failure in sepsis. Indian J Clin Biochem 29(1):93–96CrossRefPubMed Anand D, Das S, Ray S, Bhargava S, Srivastava LM (2014) Interrelationship between procalcitonin and organ failure in sepsis. Indian J Clin Biochem 29(1):93–96CrossRefPubMed
25.
go back to reference Jiang L, Feng B, Gao D, Zhang Y (2015) Plasma concentrations of copeptin, C-reactive protein and procalcitonin are positively correlated with APACHE II scores in patients with sepsis. J Int Med Res 43(2):188–195CrossRefPubMed Jiang L, Feng B, Gao D, Zhang Y (2015) Plasma concentrations of copeptin, C-reactive protein and procalcitonin are positively correlated with APACHE II scores in patients with sepsis. J Int Med Res 43(2):188–195CrossRefPubMed
29.
go back to reference Gajsiewicz JM, Smith SA, Morrissey JH (2017) Polyphosphate and RNA differentially modulate the contact pathway of blood clotting. J Biol Chem 292(5):1808–1814CrossRefPubMed Gajsiewicz JM, Smith SA, Morrissey JH (2017) Polyphosphate and RNA differentially modulate the contact pathway of blood clotting. J Biol Chem 292(5):1808–1814CrossRefPubMed
30.
go back to reference Pfeiler S, Stark K, Massberg S, Engelmann B (2017) Propagation of thrombosis by neutrophils and extracellular nucleosome networks. Haematologica 102(2):206–213CrossRefPubMedPubMedCentral Pfeiler S, Stark K, Massberg S, Engelmann B (2017) Propagation of thrombosis by neutrophils and extracellular nucleosome networks. Haematologica 102(2):206–213CrossRefPubMedPubMedCentral
31.
go back to reference Park HS, Gu J, You HJ, Kim JE, Kim HK (2016) Factor XII-mediated contact activation related to poor prognosis in disseminated intravascular coagulation. Thromb Res 138:103–107CrossRefPubMed Park HS, Gu J, You HJ, Kim JE, Kim HK (2016) Factor XII-mediated contact activation related to poor prognosis in disseminated intravascular coagulation. Thromb Res 138:103–107CrossRefPubMed
34.
go back to reference Wiggins RC, Bouma BN, Cochrane CG, Griffin JH (1977) Role of high-molecular-weight kininogen in surface-binding and activation of coagulation Factor XI and prekallikrein. Proc Natl Acad Sci USA 74(10):4636–4640CrossRefPubMedPubMedCentral Wiggins RC, Bouma BN, Cochrane CG, Griffin JH (1977) Role of high-molecular-weight kininogen in surface-binding and activation of coagulation Factor XI and prekallikrein. Proc Natl Acad Sci USA 74(10):4636–4640CrossRefPubMedPubMedCentral
39.
go back to reference Pixley RA, Zellis S, Bankes P, DeLa Cadena RA, Page JD, Scott CF, Kappelmayer J, Wyshock EG, Kelly JJ, Colman RW (1995) Prognostic value of assessing contact system activation and factor V in systemic inflammatory response syndrome. Crit Care Med 23(1):41–51CrossRefPubMed Pixley RA, Zellis S, Bankes P, DeLa Cadena RA, Page JD, Scott CF, Kappelmayer J, Wyshock EG, Kelly JJ, Colman RW (1995) Prognostic value of assessing contact system activation and factor V in systemic inflammatory response syndrome. Crit Care Med 23(1):41–51CrossRefPubMed
40.
go back to reference Kokoye Y, Ivanov I, Cheng Q, Matafonov A, Dickeson SK, Mason S, Sexton DJ, Renne T, McCrae K, Feener EP, Gailani D (2016) A comparison of the effects of factor XII deficiency and prekallikrein deficiency on thrombus formation. Thromb Res 140:118–124CrossRefPubMedPubMedCentral Kokoye Y, Ivanov I, Cheng Q, Matafonov A, Dickeson SK, Mason S, Sexton DJ, Renne T, McCrae K, Feener EP, Gailani D (2016) A comparison of the effects of factor XII deficiency and prekallikrein deficiency on thrombus formation. Thromb Res 140:118–124CrossRefPubMedPubMedCentral
41.
go back to reference Nickel KF, Labberton L, Long AT, Langer F, Fuchs TA, Stavrou EX, Butler LM, Renne T (2016) The polyphosphate/factor XII pathway in cancer-associated thrombosis: novel perspectives for safe anticoagulation in patients with malignancies. Thromb Res 141(2):30353-X Nickel KF, Labberton L, Long AT, Langer F, Fuchs TA, Stavrou EX, Butler LM, Renne T (2016) The polyphosphate/factor XII pathway in cancer-associated thrombosis: novel perspectives for safe anticoagulation in patients with malignancies. Thromb Res 141(2):30353-X
42.
go back to reference Hopp S, Nolte MW, Stetter C, Kleinschnitz C, Siren AL, Albert-Weissenberger C (2017) Alleviation of secondary brain injury, posttraumatic inflammation, and brain edema formation by inhibition of factor XIIa. J Neuroinflamm 14(1):017–0815CrossRef Hopp S, Nolte MW, Stetter C, Kleinschnitz C, Siren AL, Albert-Weissenberger C (2017) Alleviation of secondary brain injury, posttraumatic inflammation, and brain edema formation by inhibition of factor XIIa. J Neuroinflamm 14(1):017–0815CrossRef
Metadata
Title
Influence of factor XII deficiency on activated partial thromboplastin time (aPTT) in critically ill patients
Authors
Mirjam Bachler
Christian Niederwanger
Tobias Hell
Judith Höfer
Dominic Gerstmeyr
Bettina Schenk
Benedikt Treml
Dietmar Fries
Publication date
01-10-2019
Publisher
Springer US
Published in
Journal of Thrombosis and Thrombolysis / Issue 3/2019
Print ISSN: 0929-5305
Electronic ISSN: 1573-742X
DOI
https://doi.org/10.1007/s11239-019-01879-w

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