Top

Published in:

01-03-2017 | Original Article

High prevalence of congenital thrombophilia in patients with pregnancy-related or idiopathic venous thromboembolism/pulmonary embolism

Authors: Makoto Ikejiri, Hideo Wada, Norikazu Yamada, Maki Nakamura, Naoki Fujimoto, Kaname Nakatani, Akimasa Matsuda, Yosihito Ogihara, Takeshi Matsumoto, Yuki Kamimoto, Tomoaki Ikeda, Naoyuki Katayama, Masaaki Ito

Published in: International Journal of Hematology | Issue 3/2017

Abstract

Congenital thrombophilia which is characterized by deficiencies in proteins such as antithrombin (AT), protein C (PC) and protein S (PS), is a major cause of venous thromboembolism (VTE). A total of 130 patients with VTE were evaluated for congenital thrombophilia based on the activity of AT, PC, or PS. Fifteen VTE patients with congenital AT deficiency (11.5 %), 16 with congenital PC deficiency (12.3 %) and eight with congenital PS deficiency (6.2 %) were diagnosed using DNA analysis. The frequency of congenital AT deficiency was significantly higher in subjects with pregnancy-related and idiopathic VTE than in those with VTE due to other causes, and congenital PC and PS deficiency were frequently associated with idiopathic VTE. Among the groups examined, the plasma levels of AT were the lowest in subjects with pregnancy-related VTE. Although our findings may have been influenced by some unintentional bias, congenital thrombophilia is nevertheless a major cause of VTE in pregnant patients as well as in young or middle-aged patients without any underlying diseases.

Sevitt S. Fatal road accidents. Injuries, complications, and causes of death in 250 subjects. Br J Surg. 1968;55:481–505.CrossRefPubMed

Spyropoulos AC, Lin J. Direct medical costs of venous thromboembolism and subsequent hospital readmission rates: an administrative claims analysis from 30 managed care organizations. J Manag Care Pharm. 2007;13:475–86.PubMed

van Vlijmen EF, Veeger NJ, Middeldorp S, Hamulyák K, Prins MH, Kluin-Nelemans H, et al. The impact of a male of female thrombotic family history on contraceptive counselling: a cohort study. J Thromb Haemost. 2016 (in press).

Kamimoto Y, Wada H, Ikejiri M, Nakatani K, Sugiyama T, Osato K, et al. High frequency of decreased antithrombin level in pregnant women with thrombosis. Int J Hematol. 2015;102:253–8.CrossRefPubMed

Albayati MA, Grover SP, Saha P, Lwaleed BA, Modarai B, Smith A. Postsurgical inflammation as a causative mechanism of venous thromboembolism. Semin Thromb Hemost. 2015;41:615–20.CrossRefPubMed

Aota T, Naitoh K, Wada H, Yamashita Y, Miyamoto N, Hasegawa M, et al. Elevated soluble platelet glycoprotein VI is a useful marker for DVT in postoperative patients treated with edoxaban. Int J Hematol. 2014;100:450–6.CrossRefPubMed

García-Olivares P, Guerrero JE, Keough E, Galdos P, Carriedo D, Murillo F, et al. PROF-ETEV study investigators.: clinical factors associated with inappropriate prophylaxis of venous thromboembolic disease in critically ill patients. A single day cross-sectional study. Thromb Res. 2016;143:111–7.CrossRefPubMed

Posch F, Königsbrügge O, Zielinski C, Pabinger I, Ay C. Treatment of venous thromboembolism in patients with cancer: a network meta-analysis comparing efficacy and safety of anticoagulants. Thromb Res. 2015;136:582–9.CrossRefPubMed

Bartholomew JR, Schaffer JL, McCormick GF. Air travel and venous thromboembolism: minimizing the risk. Cleve Clin J Med. 2011;78:111–20.CrossRefPubMed

10.

Yusuf HR, Hooper WC, Grosse SD, Parker CS, Boulet SL, Ortel TL. Risk of venous thromboembolism occurrence among adults with selected autoimmune diseases: a study among a US cohort of commercial insurance enrollees. Thromb Res. 2015;135:50–7.CrossRefPubMed

11.

Zöller B, Ohlsson H, Sundquist J, Sundquist K. Family history of venous thromboembolism is a risk factor for venous thromboembolism in combined oral contraceptive users: a nationwide case-control study. Thromb J. 2015;13:34.CrossRefPubMedPubMedCentral

12.

Meyer MR, Witt DM, Delate T, Johnson SG, Fang M, Go A, et al. Thrombophilia testing patterns amongst patients with acute venous thromboembolism. Thromb Res. 2015;136:1160–4.CrossRefPubMedPubMedCentral

13.

Mannucci PM, Franchini M. Classic thrombophilic gene variants. Thromb Haemost. 2015;114:885–9.CrossRefPubMed

14.

Yokoyama K, Kojima T, Sakata Y, Kawasaki T, Tsuji H, Miyata T, et al. A survey of the clinical course and management of Japanese patients deficient in natural anticoagulants. Clin Appl Thromb Hemost. 2012;18:506–13.CrossRefPubMed

15.

Neki R, Miyata T, Fujita T, Kokame K, Fujita D, Isaka S, et al. Nonsynonymous mutations in three anticoagulant genes in Japanese patients with adverse pregnancy outcomes. Thromb Res. 2014;133:914–8.CrossRefPubMed

16.

Adachi T. Protein S and congenital protein S deficiency: the most frequent congenital thrombophilia in Japanese. Curr Drug Targets. 2005;6:585–92.CrossRefPubMed

17.

Kelchtermans H, Pelkmans L, de Laat B, Devreese KM. IgG/IgM antiphospholipid antibodies present in the classification criteria of the antiphospholipid syndrome: a critical review of their association with thrombosis. J Thromb Haemost. 2016 (in press).

18.

Miyakis S, Lockshin MD, Atsumi T, Branch DW, Brey RL, Cervera R, et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost. 2006;4:295–306.CrossRefPubMed

19.

Olds RJ, Lane DA, Caso R, Panico M, Morris HR, Sas G, et al. Antithrombin III Budapest: a single amino acid substitution (429Pro to Leu) in a region highly conserved in the serpin family. Blood. 1992;79:1206–12.PubMed

20.

Erdjument H, Lane DA, Ireland H, Panico M, DiMarzo V, Blench I, et al. Formation of a covalent disulfide-linked antithrombin complex by an antithrombin variant, antithrombin Northwick Park. J Biol Chem. 1987;262:13381–4.PubMed

21.

Koide T, Odani S, Takahashi K, Ono T, Sakuragawa N. Antithrombin III Toyama; replacement of arginine 47 by cysteine in hereditary abnormal antithrombin III that lacks heparin-binding ability. Proc Natl Acad Sci USA. 1984;81:289–93.CrossRefPubMedPubMedCentral

22.

Katayama K, Hashimoto N, Tanaka Y, Ozawa T, Emi Y, Ikeda T, et al. Identification of a novel amino acid deletion mutation and a very rare single nucleotide variant in a Japanese family with type I antithrombin deficiency. Thromb Res. 2005;116:215–21.CrossRefPubMed

23.

Erdjument H, Lane DA, Panico M, diMarzo V, Morris HR. Single amino acid substitutions in the reactive site of antithrombin leading to thrombosis. Congenital substitution of arginine 393 to cysteine in antithrombin Northwick Park and to histidine in antithrombin Glasgow. J Biol Chem. 1988;263:5589–93.PubMed

24.

Muta T, Okamura T, Kawamoto M, Ichimiya H, Yamanaka M, Wada Y, et al. Successful therapy with argatroban for superior mesenteric vein thrombosis in a patient with congenital antithrombin deficiency. Eur J Haematol. 2005;75:167–70.CrossRefPubMed

25.

Miyata T, Sato Y, Ishikawa J, Okada H, Takeshita S, Sakata T, et al. Prevalence of genetic mutations in protein S, protein C and antithrombin genes in Japanese patients with deep vein thrombosis. Thromb Res. 2009;124:14–8.CrossRefPubMed

26.

Ozawa T, Takikawa Y, Niiya K, Fujiwara T, Suzuki K, Sato S, et al. Antithrombin Morioka (Cys 95-Arg): a novel missense mutation causing type I antithrombin deficiency. Thromb. Haemost. 1997;77:403.PubMed

27.

Lind B, Koefoed P, Thorsen S. Symptomatic type 1 protein C deficiency caused by a de novo Ser270Leu mutation in the catalytic domain. Br J Haematol. 2001;113:642–8.CrossRefPubMed

28.

Yamamoto K, Matsushita T, Sugiura I, Takamatsu J, Iwasaki E, Wada H, et al. Homozygous protein C deficiency: identification of a novel missense mutation that causes impaired secretion of the mutant protein C. J Lab Clin Med. 1992;119:682–9.PubMed

29.

Miyata T, Sakata T, Zheng YZ, Tsukamoto H, Umeyama H, Uchiyama S, et al. Genetic characterization of protein C deficiency in Japanese subjects using a rapid and nonradioactive method for single-stand conformational polymorphism analysis and a model building. Thromb Haemost. 1996;76:302–11.PubMed

30.

Matsuda M, Sugo T, Sakata Y, Murayama H, Mimuro J, Tanabe S, et al. A thrombotic state due to an abnormal protein C. N Engl J Med. 1988;319:1265–8.CrossRefPubMed

31.

Yamamoto K, Tanimoto M, Emi N, Matsushita T, Takamatsu J, Saito H. Impaired secretion of the elongated mutant of protein C (protein C-Nagoya). Molecular and cellular basis for hereditary protein C deficiency. J Clin Invest. 1992;90:2439–46.CrossRefPubMedPubMedCentral

32.

Miyata T, Zheng YZ, Sakata T, Tsushima N, Kato H. Three missense mutations in the protein C heavy chain causing type I and type II protein C deficiency. Thromb Haemost. 1994;71:32–7.PubMed

33.

Ikejiri M, Shindo A, Ii Y, Tomimoto H, Yamada N, Matsumoto T, et al. Frequent association of thrombophilia in cerebral venous sinus thrombosis. Int J Hematol. 2012;95:257–62.CrossRefPubMed

34.

Hayashi T, Nishioka J, Shigekiyo T, Saito S, Suzuki K. Protein S Tokushima: abnormal molecule with a substitution of Glu for Lys-155 in the second epidermal growth factor-like domain of protein S. Blood. 1994;83:683–90.PubMed

35.

Ikejiri M, Tsuji A, Wada H, Sakamoto Y, Nishioka J, Ota S, et al. Analysis three abnormal Protein S genes in a patient with pulmonary embolism. Thromb Res. 2010;125:529–32.CrossRefPubMed

36.

Tsuda H, Urata M, Tsuda T, Wakiyama M, Iida H, Nakahara M, et al. Four missense mutations identified in the protein S gene of thrombosis patients with protein S deficiency effect on secretion and anticoagulant activity of protein S. Thromb Res. 2000;105:233–9.CrossRef

37.

Espinosa-Parrilla Y, Yamazaki T, Sala N, Dahlbäck B, de Frutos PG. Protein S secretion differences of missense account for phenotypic heterogeneity. Blood. 2000;95:173–9.PubMed

38.

Kinoshita S, Iida H, Inoue S, Watanabe K, Kurihara M, Wada Y, et al. Protein S and protein C gene mutations in Japanese deep vein thrombosis patients. Clin Biochem. 2005;38:908–15.CrossRefPubMed

39.

Lee ST, Kim HJ, Kim DK, Schuit RJ, Kim SH. Detection of large deletion mutations in the SERPINC1 gene causing hereditary antithrombin deficiency by multiplex ligation-dependent probe amplification (MLPA). J Thromb Haemost. 2008;6:701–3.CrossRefPubMed

40.

Ikejiri M, Wada H, Sakamoto Y, Ito N, Nishioka J, Nakatani K, et al. The association of protein S Tokushima-K196E with a risk of deep vein thrombosis. Int J Hematol. 2010;92:302–5.CrossRefPubMed

Title: High prevalence of congenital thrombophilia in patients with pregnancy-related or idiopathic venous thromboembolism/pulmonary embolism
Authors: Makoto Ikejiri
Hideo Wada
Norikazu Yamada
Maki Nakamura
Naoki Fujimoto
Kaname Nakatani
Akimasa Matsuda
Yosihito Ogihara
Takeshi Matsumoto
Yuki Kamimoto
Tomoaki Ikeda
Naoyuki Katayama
Masaaki Ito
Publication date: 01-03-2017
Publisher: Springer Japan
Published in: International Journal of Hematology / Issue 3/2017
Print ISSN: 0925-5710
Electronic ISSN: 1865-3774
DOI: https://doi.org/10.1007/s12185-016-2111-2

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 3/2017

Phase 2 trial of daily, oral epigallocatechin gallate in patients with light-chain amyloidosis

Eculizumab treatment improved renal hemosiderosis in a patient with paroxysmal nocturnal hemoglobinuria

Outcome differences between children and adolescents and young adults with non-Hodgkin lymphoma following stem cell transplantation

Erratum to: Assessing the safety and efficacy of ruxolitinib in a multicenter, open-label study in Japanese patients with myelofibrosis

Human MutT homologue 1 mRNA overexpression correlates to poor response of multiple myeloma

Bortezomib–dexamethasone versus high-dose melphalan for Japanese patients with systemic light-chain (AL) amyloidosis: a retrospective single-center study

Keynote webinar | Spotlight on antibody–drug conjugates in cancer