title: Hyperhomocysteinemia in patients with pulmonary embolism is associated with impaired plasma fibrinolytic capacity.
abstract: Hyperhomocysteinemia (HHcy) affects haemostasis and shifts its balance in favour of thrombosis. In vitro and in vivo studies suggested that HHcy may impair fibrinolysis either by influencing the plasma levels of fibrinolytic factors or by altering the fibrinogen structure. We investigated the influence of mild HHcy levels on plasma fibrinolytic potential by using clot lysis time (CLT) and fibrin susceptibility to plasmin-induced lysis in 94 patients with previous pulmonary embolism and no pulmonary hypertension. CLT was measured as lysis time of tissue factor induced clots exposed to exogenous tissue plasminogen activator (t-PA). The rate of in vitro plasmin-mediated cleavage of fibrin β-chain was assessed over a 6-h period on fibrin clots, which were obtained by exposition to thrombin of purified fibrinogen. Homocysteine plasma levels were measured by Abbott Imx immunoassay and we considered as altered the values above 15 μmol/L according to the literature. In 68 patients homocysteine levels were below 15 μmol/L (NHcy) and in 26 they were above (HHcy). Significant differences were observed between the two groups regarding plasma fibrinolytic potential (p = 0.016), TAFIact (expressed as clot lysis ratio) (p = 0.02), t-PA (0.008) and PLG (0.037), but not for the other assessed components. The HHcy-patients had a threefold higher risk to have an impaired fibrinolysis. Instead, a multivariate logistic regression analysis adjusted for significances of univariate showed that HHcy (OR 5.2 95% CI 1.7-15.9; p = 0.003) and BMI (OR 5.0 95% CI 1.6-15.9; p = 0.006) resulted independently associated with impaired fibrinolytic activity. HHcy affects TAFI-mediated hypofibrinolysis but not fibrin(ogen) structure or function as documented by fibrin degradation analysis.
authors: Department of Heart and Vessels, Thrombosis Centre, Azienda Ospedaliero-Universitaria Careggi, Viale Morgagni 85, 50134, Florence, Italy, annapaolacellai@tiscali.it.
authors: Anna Paola
authors: AP
authors: Cellai
authors: Donatella
authors: D
authors: Lami
authors: Emilia
authors: E
authors: Antonucci
authors: Agatina Alessandrello
authors: AA
authors: Liotta
authors: Angela
authors: A
authors: Rogolino
authors: Sandra
authors: S
authors: Fedi
authors: Claudia
authors: C
authors: Fiorillo
authors: Matteo
authors: M
authors: Becatti
authors: Caterina
authors: C
authors: Cenci
authors: Rossella
authors: R
authors: Marcucci
authors: Rosanna
authors: R
authors: Abbate
authors: Domenico
authors: D
authors: Prisco
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005337:Fibrin / Q000378:metabolism*; D005341:Fibrinolysin / Q000378:metabolism*; D005342:Fibrinolysis; D006801:Humans; D020138:Hyperhomocysteinemia / Q000097:blood / Q000150:complications; D008297:Male; D008875:Middle Aged; D059748:Proteolysis; D011655:Pulmonary Embolism / Q000097:blood / Q000150:complications; D012307:Risk Factors
chemical_list: D005337:Fibrin; D005341:Fibrinolysin
references: Ann Intern Med. 2007 Jan 2;146(1):1-9
references: 17200216
references: Arch Intern Med. 2007 Mar 12;167(5):497-501
references: 17353498
references: Curr Opin Hematol. 2007 May;14(3):242-8
references: 17414214
references: Blood. 2010 Jul 8;116(1):113-21
references: 20385790
references: Arterioscler Thromb Vasc Biol. 2006 Jun;26(6):1397-404
references: 16574890
references: Eur Heart J. 2004 Dec;25(24):2243-78
references: 15589643
references: J Clin Pathol. 1958 Sep;11(5):403-5
references: 13575554
references: Thromb Haemost. 2013 Mar;109(3):565-7
references: 23306795
references: Blood. 2005 Feb 1;105(3):1102-5
references: 15466929
references: Am J Respir Crit Care Med. 2010 May 1;181(9):992-6
references: 20075386
references: Gastroenterology. 2001 Jul;121(1):131-9
references: 11438502
references: Br J Haematol. 2009 Apr;145(1):115-20
references: 19183334
references: Mol Cell Biochem. 2010 Nov;344(1-2):217-20
references: 20658177
references: Semin Thromb Hemost. 2012 Mar;38(2):230-4
references: 22422337
references: Eur Heart J. 2009 Apr;30(8):995-1004
references: 19224934
references: J Thromb Haemost. 2008 Sep;6(9):1571-7
references: 18624976
references: Atherosclerosis. 2012 Sep;224(1):97-101
references: 22800650
references: Clin Appl Thromb Hemost. 2010 Jun;16(3):337-44
references: 19117964
references: Am J Respir Crit Care Med. 2006 Jun 1;173(11):1270-5
references: 16514114
references: Br J Haematol. 2008 May;141(4):529-35
references: 18318759