Vitamin B12 Deficiency and Thrombosis

Year 2009, Volume: 11 Issue: 2, 9 - 14, 01.07.2009

İrfan Yavasoglu Gurhan Kadıkoylu Bilal Acar Zahit Bolaman

Abstract

Purpose: Thromboembolic diseases are multi-factorial. Hyperhomocysteinemia (HH) is one of these factors. Vitamin B12 deficiency is acquired reasons for HH. HH is a risk factor for arterial and venous thrombosis. The incidence of thrombosis is high due to increase of homocystein levels in HH associated with vitamin B12 deficiency. However, this situation is not clear and there are opposing views. In our study, we aimed to determine the frequency of thromboembolic events in individuals with vitamin B12 deficiency. Methods: One hundred forty-three patients (63 female, 80 male, mean age 59±13 years), who were diagnosed as having vitamin B12 deficiency (below 200 pg/ml), were included in the study retrospectively. The history of arterial and venous thrombosis for a period of last three years before the time of diagnosis and was searched. The thromboembolic events, which are detected via clinical and laboratory studies and via imaging, were determined. The control group was consisted of 129 healthy subjects (62 female, 67 male; mean age 58±8) of appropriate age, sex and excluded criteria whose B12 level was normal. Results: In control group, mean B12 level was 244±32 pg/ml. The patients’ mean B12 level was 136±58 pg/ml. Fourteen (9.8%) thromboembolic (10 coronary artery disease, two deep venous thrombosis, two cerebrovascular) events were determined in vitamin B12 deficiency group, whereas this ratio was 3.9% in the control group (four coronary artery disease, one deep venous thrombosis). This ratio was not statistically significant different (p> 0.05). Conclusion: Alone HH due to vitamin B12 deficiency did not increase the risk of thrombosis

Keywords

Arterial thrombosis, venous thrombosis vitamin B12 deficiency

B12 Vitamini Eksikliği ve Tromboz

Abstract

Amaç: Tromboembolik hastalıklar multi-faktöriyeldir. Hiperhomosisteinemi (HH) bu faktörlerdendir. B12 vitamini eksikliği HH için kazanılmış nedenlerinden biridir. HH arteriyel ve venöz tromboz için risk faktörüdür. B12 vitamin eksikliğine bağlı HH’de homosistein düzeylerindeki artışa bağlı olarak tromboz insidansı yüksektir. Ancak bu durum açık değildir karşıt görüşler de vardır. Çalışmamızda B12 vitamini eksikliği saptanan kişilerde tromboembolik olay sıklığını belirlemeyi amaçladık. Yöntem: Retrospektif olarak kazanılmış B12 vitamin eksikliği saptanan (200 pg/ml altında) 143 hasta (63 kadın, 80 erkek, yaş ortalaması 59±13 yıl) çalışmaya alındı. Tanı anında ve 3 yıl önceki arteriyel ve venöz tromboz öyküsü sorgulandı. Klinik, laboratuar ve görüntüleme ile saptanmış tromboembolik olaylar belirlendi. Kontrol gurubu olarak yaş ve cins gurubu uygun, B12 vitamin düzeyi normal, hasta gurubundaki dışlama kriterlerine uyan 129 sağlıklı kişi (62 kadın, 67 erkek, yaş ortalaması 58±8) alındı. Bulgular: Kontrol gurubunda ortalama B12 düzeyi 244±32 pg/ml, olgularımızda ise 136±58pg/ml idi. B12vitamini eksikliği olan olgularda %9.8 oranında tromboembolik (on koroner arter hastalığı, iki derin venöz trombozu, iki serebrovasküler) olay saptanır iken kontrol gurubunda bu oran %3.9 (dört koroner arter hastalığı, bir derin venöz tromboz) idi. Bu oran istatistiksel olarak anlamlı değildi (p>0.05). Sonuç: B vitamin eksikliği nedeni ile oluşan HH tek başına tromboz riskini arttırmamaktadır

Keywords

B12 vitamin eksikliği, arteriyel tromboz, venöz tromboz

References

• Mateo J, Oliver A, Borrell M, Sala N, Fontcuberta J and the EMET Group: Laboratory
• characteristics of 2,132 consecutive unselected patients with venous thromboembolism - results of the Spanish Multicentric Study on Thrombophilia Haemost. 77:444-451, 1997.
• Carmel R, Gren R, Rosenblatt DS, Watkins D: Update on Cobalamin, Folate, and Homocysteine Hematology Am Soc Hematol Educ Program. 62-81, 2003.
• Verhoef P, Kok FJ, Kluijtmans LA, Blom HJ, Refsum H, Ueland PM, Kruyssen DA: The 677C→Tmutation
• tetrahydrofolate reductase gene:associations with plasma total homocysteine levels and risk of Atherosclerosis. 132:105-113, 1997.
• D'Angelo A, Selhub J: Homocysteine and thrombotic disease. Blood. 90:1-11, 1997.
• Schynder G, Roffi M, Pin R, Flammer Y, Lange H, Eberli FL, Meier B, Turi ZG, Hess OM: Decreased rate of coronary restenosis after lowering of plasma homocysteine levels. N Engl J Med. 345:1593-1600, 2001.
• Nygard O, Nordrehaug JE, Refsum H, Ueland PM, Farstad M, Vollset SE: Plasma homocysteine levels and mortality in patients with coronary artery disease. N Engl J Med. 337:230-236, 1997.
• Remacha AF, Souto JC, Ramila E, Perea G, Sarda MP, Fontcuberta J. Enhanced risk of thrombotic disease in patients with acquired vitamin B12 and/or folate deficiency: role of hyperhomocysteinemia. Ann Hematol. 81:616- 21, 2002.
• Lin JS, Shen MC, Cheng WC, Tsay W, Wang YC, Lin BB, Hung MH: Age, sex and vitamin
• homocysteine, but hyperhomocysteinaemia is possibly not an important risk factor for venous thrombophilia in Taiwanese Chinese. Br J Haematol. 117:159-63, 2002.
• Lentz SR: Mechanisms of homocysteine- induced atherothrombosis. J Thromb Haemost. 3: 1646–54, 2005.
• Undas A, Brozek J, Szceklik A: Homocysteine and thrombosis: from basic science to clinical evidence. Thromb Haemost. 94:907-15, 2005.
• Perry IJ, Refsum H, Morris RW, Ebrahim SB, Ueland PM, Shaper AG: Prospective study of serum total homocysteine concentration and risk of stroke in middle-aged British men. Lancet. 346:1395-8, 1995. 12.
• Homocysteine and risk of ischemic heart disease and stroke: a meta-analysis. JAMA. 288:2015-22, 2002.
• Oger E, Lacut K, Le Gal G, Couturaud F, Guenet D, Abalain JH, Roguedas AM; EDITH collaborative
• Hyperhomocysteinemia and low B vitamin levels are independently associated with venous thromboembolism:results from the EDITH study: a hospital-based case–control study. Thromb Haemost. 4:793-9, 2006.
• Seligsohn U, Griffin JH: Hereditary Thrombophili. In: Lichtman M, Kipps T, Kaushansky K, Beutler E, Sligsohn U, Prchal J. (eds). Williams Hematolgy. 7th ed. United States of America, McGraw-Hill Companies. pp: 1981-2007, 2006.
• Ho CH, Kuo BI, Kong CW, Chau WK, Hsu HC, Gau CP, Yu YB: Influence of methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism, B vitamins and other factors on plasma homocysteine and risk of thromboembolic disease in Chinese. J Chin Med Assoc. 68:560-5, 2005.
• Sam RC, Burns PJ, Hobbs SD, Marshall T, Wilmink AB, Silverman SH, Bradbury AW: The prevalence of hyperhomocysteinemia, methylene tetrahydrofolate reductase C677T mutation, and vitamin B12 and folate deficiency in patients with chronic venous insufficiency. J Vasc Surg. 38:904-8, 2003.
• Ridker PM, Hennekens CH, Selhub J, Miletich JP, Malinow MR, Stampfer MJ: Interrelation
• factor V Leiden, and risk of future venous thromboembolism. Circulation. 95:1777-82, 1997.
• Fernandez-Miranda C, Yebra Yebra M, Ribera Casado C, Toledo Urgarte T, Martin Mola M, Gomez Gonzales P: Venous thromboembolism and hyperhomocysteinemia as first manifestation of pernicious anemia. Rev Clin Esp. 205:489-92, 2005.
• Nygard O, Vollst SE, Refsum H, Stensvold I, Tverdal A, Nordrehaug JE, Ueland M, Kvale G
• cardiovascular risk profile. The Hordaland Homocysteine Study. JAMA. 274:1526-33, 1995.
• Znazen R, Guermazi S, Karoui M. Association of now thrombotic risk factors: factor V Leiden and hyperhomocysteinemia. A case report. Pathol Biol (Paris) 2007; 55:163-6 21. Marie I, Levesque H, Le Cam-Duchez V, Borg JY, Ducrotte P, Philippe C: Mesenteric venous thrombosis revealing both factor II G20212A
• hyperhomocysteinemia related to pernicious anemia. Gastroenterology. 118:237-8, 2000.
• Kharchafi A, Oualim Z, Amezvane T, Mahassin F, Ghafir D, Ohavon V, Archane MI: Biermer's disease and venous thrombosis. Report of two cases. Rev Med Interne. 23:563- 6, 2002.
• Dani SI, Thanvi S, Shah JM, Prajapti J, Jain S, Joshi H: Hyperhomocysteinemia masquerading as pulmonary embolism. J Assoc Physicians India. 51:914-5, 2003. 24. Den Heijer M: Are B vitamins a risk factor for VTE? J Thromb Haemost 4:309-11, 2006.
• Nigel SK, Ronald C, McGlennen, MD: Hyperhomocyst(e)inemia and Thrombophilia Arch Pathol Lab Med. 126:1367–1375, 2002.
• Diaz DE Tuesta AM, Ribo MD, Belinchon O, Marchena PJ, Bruscas MJ, Val E, Cortes A, Nieto JA: Low levels of vitamin B12 and venous thromboembolic disease in elderly men. J Intern Med. 258:244-9, 2005.
• Den Heijer M, Lewington S, Clarke R: Homocysteine, MTHFR, risk of venous thrombosis: a meta-analysis of published epidemiological studies. J Thromb Haemost. 3:292-9, 2005.
• Kocabalkan F, Baykal Y, Bozoğlu E. Yaşlılarda Kardiyovasküler Risk Faktörü Olarak Homosistein. Türk Geriatri Dergisi. 3:69-73, 2000. mutation and