Thrombin activatable fibrinolysis inhibitor como preditor de sangramento no transplante hepático: estudo piloto observacional / Thrombin activatable fibrinolysis inhibitor as a bleeding predictor in liver transplantation: a pilot observational study

RESUMO Objetivo: Correlacionar os níveis de thrombin activatable fibrinolysis inhibitor no pós-operatório imediato e com 24 horas de pós-operatório com o volume de sangramento tansoperatório. Métodos: Foram analisados vinte e um pacientes alocados imediatamente antes do transplante hepático (eletivo ou de urgência), com coleta de amostras sanguíneas para análise de thrombin activatable fibrinolysis inhibitor em três diferentes momentos: imediatamente antes do transplante hepático (thrombin activatable fibrinolysis inhibitor pré-operatório), imediatamente após o procedimento cirúrgico (thrombin activatable fibrinolysis inhibitor pós-operatório imediato) e após 24 horas do final da cirurgia (thrombin activatable fibrinolysis inhibitor 24 horas pós-operatório). O principal desfecho do estudo foi correlacionar os níveis de thrombin activatable fibrinolysis inhibitor pré-operatório e de thrombin activatable fibrinolysis inhibitor pós-operatório imediato com perda sanguínea no transoperatório. Resultados: Houve correlação entre thrombin activatable fibrinolysis inhibitor pré-operatório e o volume de sangramento (ρ = -0,469; p = 0,05), mas não de thrombin activatable fibrinolysis inhibitor pós-operatório imediato (ρ = -0,062; p = 0,79). Em análise de regressão linear, nenhuma das variáveis incluídas (hemoglobina pré, fibrinogênio pré e thrombin activatable fibrinolysis inhibitor pré-operatório) se mostrou preditor de sangramento. Houve tendência semelhante na variação entre os níveis de thrombin activatable fibrinolysis inhibitor durante os três diferentes momentos e os níveis de fibrinogênio. Pacientes que evoluíram a óbito em até 6 meses (14,3%) apresentaram níveis diminuídos de thrombin activatable fibrinolysis inhibitor pré-operatório e de thrombin activatable fibrinolysis inhibitor pós-operatório imediato, comparando-se aos sobreviventes (pré-operatório: 1,3 ± 0,15 versus 2,55 ± 0,53; p = 0,06; e pós-operatório imediato: 1,2 ± 0,15 versus 2,5 ± 0,42; p = 0,007). Conclusão: Houve correlação moderada entre thrombin activatable fibrinolysis inhibitor pré-operatório e o sangramento transoperatório em transplante hepático, porém seu papel preditivo independente de outras variáveis ainda permaneceu incerto. Thrombin activatable fibrinolysis inhibitor pré-operatório e pós-operatório imediato podem ter um papel na avaliação da sobrevida dessa população, necessitando-se confirmar em novos estudos, de maior tamanho amostral.

ABSTRACT Objective: To correlate the levels of thrombin activatable fibrinolysis inhibitor in the immediate postoperative period and at 24 hours postoperatively with the volume of intraoperative bleeding. Methods: Twenty-one patients allocated immediately before (elective or emergency) liver transplantation were analyzed. Blood samples were collected for thrombin activatable fibrinolysis inhibitor analysis at three different time points: immediately before liver transplantation (preoperative thrombin activatable fibrinolysis inhibitor), immediately after the surgical procedure (immediate postoperative thrombin activatable fibrinolysis inhibitor), and 24 hours after surgery (thrombin activatable fibrinolysis inhibitor 24 hours after surgery). The primary outcome of the study was to correlate the preoperative and immediate postoperative levels of thrombin activatable fibrinolysis inhibitor with intraoperative blood loss. Results: There was a correlation between the preoperative thrombin activatable fibrinolysis inhibitor levels and bleeding volume (ρ = -0.469; p = 0.05) but no correlation between the immediate postoperative thrombin activatable fibrinolysis inhibitor and bleeding volume (ρ = -0.062; p = 0.79). No variable included in the linear regression analysis (prehemoglobin, prefibrinogen and preoperative thrombin activatable fibrinolysis inhibitor) was a bleeding predictor. There was a similar trend in the variation between the levels of thrombin activatable fibrinolysis inhibitor at the three different time points and fibrinogen levels. Patients who died within 6 months (14.3%) showed decreased preoperative and immediate postoperative levels of thrombin activatable fibrinolysis compared with survivors (preoperative: 1.3 ± 0.15 versus 2.55 ± 0.53, p = 0.06; immediate postoperative: 1.2 ± 0.15 versus 2.5 ± 0.42, p = 0.007). Conclusion: There was a moderate correlation between preoperative thrombin activatable fibrinolysis inhibitor and intraoperative bleeding in liver transplantation patients, although the predictive role of this variable independent of other variables remains uncertain. Preoperative and immediate postoperative thrombin activatable fibrinolysis inhibitor levels may have a role in the survival prognosis of this population; however, this possibility requires confirmation in further studies with larger sample sizes.

Correlation analysis of thrombin-activatable fibrinolysis inhibitor single nucleotide polymorphism with venous thromboembolism / 中国实验血液学杂志

This study was aimed to explore the change of single nucleotide polymorphism (SNP) of thrombin-activatable fibrinolysis inhibitor (TAFI) and its correlation of 2 sites (505a/g, 1040c/t) in its gene-coding region with venous thromboembolism (VTE). The genotype distribution of TAFI in 80 patients with VTE and 80 normal controls was detected by allele-specific PCR. The results showed that the distribution of each genotype of 505a/g polymorphism was not significantly different between the VTE and control groups (P > 0.05). However, t allele frequency of 1040c/t in VTE group decreased significantly as compared with the control group (40% vs 53.75%, P < 0.05), mainly due to the decrease of the proportion of tt homozygous in VTE group. It is concluded that obvious relationship is found between the polymorphism of 1040c/t in TAFI gene and VTE patients. t allele genotype may paly a protective role in VTE. The polymorphism of TAFI 505a/g may be not associated with VTE.

Enfermedad tromboembólica venosa en el embarazo y puerperio: parte 2: prevención y tratamiento / Venous thromboembolic disease in pregnancy and puerperium: part 2: prevention and treatment

La enfermedad tromboembólica venosa constituye una causa importante de morbilidad y mortalidad en el período grávido puerperal, lo cual ha generado múltiples controversias en cuanto a su prevención y tratamiento. En este artículo se exponen las medidas preventivas y terapéuticas para tratar a mujeres con enfermedad tromboembólica en el embarazo y puerperio, para lo cual se detallan las medidas generales y el uso de antitrombóticos en la profilaxis de esta afección, así como también su utilización con fines terapéuticos. Se describen nuevos anticoagulantes, inhibidores directos de trombina y Anti/Xa, así como se exponen las modalidades de tratamiento quirúrgico, lo cual permitió como resultado introducir un protocolo de atención a la terapéutica de estas pacientes. Se concluye que si bien la profilaxis en población de riesgo es la piedra angular de la prevención, la anticoagulación eficaz constituye la herramienta básica para reducir la mortalidad.

Venous thromboembolic disease is an important cause of morbidity and mortality in the pregnant-puerperal period, which has given rise to multiple controversies regarding its prevention and treatment. This article outlines the preventive measures and therapies to treat women with thromboembolic disease in pregnancy and puerperium, for which the general measures and the use of antithrombotics in the prophylaxis of this condition are detailed, as well as their use for therapeutics. New anticoagulants, direct thrombin inhibitors and Anti/Xa are described and the surgical treatment modalities are presented as well, allowing as a result to introduce a care protocol for treatment of these patients. It is concluded that although the risk population prophylaxis is the cornerstone of prevention, effective anticoagulation is the basic tool to reduce the mortality.

Effect of levothyroxine suppression therapy on plasma thrombin activatable fibrinolysis inhibitor antigen levels in benign thyroid nodules

The aim of this prospective study was to investigate the effect of LT4 suppression therapy on plasma thrombin activatable fibrinolysis inhibitor [TAFI] antigen and plasminogen activator inhibitor-1 [PAI-1] levels in benign thyroid nodules. We also compared hyperthyroid patients and healthy controls. Twenty premenopausal women with benign thyroid nodules were given LT4 suppression therapy for 1 year. Plasma TAFI and PAI-1 antigen levels were measured at baseline and after LT4 suppression treatment. The endogenous hyperthyroid group was composed of 19 premenopausal females with newly diagnosed endogenous hyperthyroidism. Eighteen age-matched euthyroid healthy premenopausal women were enrolled as the control group. TAFI antigen levels decreased after LT4 suppression treatment; however, the difference was not statistically significant [p = 0.057]. LT4 treatment resulted in a nonsignificant increase in PAI-1 levels. Patients with endogenous hyperthyroidism had decreased levels of TAFI antigen and increased levels of PAI-1 antigen [p < 0.05]. There was a negative correlation between the FT4 and TAFI antigen levels. Serum TSH was positively correlated with the plasma levels of TAFI antigen. LT4 suppression therapy for benign thyroid nodules did not result in a significant decrease in TAFI antigen levels in premenopausal women, but endogenous hyperthyroidism was associated with significantly decreased levels of TAFI antigen

Elevated levels of activated and inactivated thrombin-activatable fibrinolysis inhibitor in patients with sepsis / 대한혈액학회지

BACKGROUND: In sepsis, large scale inflammatory responses can cause extensive collateral damage to the vasculature, because both coagulation and fibrinolysis are activated unevenly. Thrombin-activatable fibrinolysis inhibitor (TAFI) plays a role in modulating fibrinolysis. Since TAFI can be activated by both thrombin and plasmin, it is thought to be affected in sepsis. Hence, activated and inactivated TAFI (TAFIa/ai) may be used to monitor changes in sepsis. METHODS: TAFIa/ai-specific in-house ELISA can detect only the TAFIa/ai form, because the ELISA capture agent is potato tuber carboxypeptidase inhibitor (PTCI), which has selective affinity towards only the TAFIa and TAFIai isoforms. TAFIa/ai levels in plasma from 25 patients with sepsis and 19 healthy volunteers were quantitated with the in-house ELISA. RESULTS: We observed increased TAFIa/ai levels in samples from patients with sepsis (48.7+/-9.3 ng/mL) than in samples from healthy individuals (10.5+/-5.9 ng/mL). In contrast, no difference in total TAFI concentration was obtained between sepsis patients and healthy controls. The results suggest that TAFI zymogen was activated and that TAFIa/ai accumulated in sepsis. CONCLUSION: The detection of TAFIa/ai in plasma could provide a useful and simple diagnostic tool for sepsis. Uneven activation of both coagulation and fibrinolysis in sepsis could be caused by the activation of TAFI zymogen and elevation of TAFIa/ai. TAFIa/ai could be a novel marker to monitor sepsis and other blood-related disturbances.

Assessment of thrombin-activatable fibrinolysis inhibitor (TAFI) activation in acquired hemostatic dysfunction: a diagnostic challenge / 대한혈액학회지

No abstract available.

Soluble CD40 ligand, plasminogen activator inhibitor-1 and thrombin-activatable fibrinolysis inhibitor-1-antigen in normotensive type 2 diabetic subjects without diabetic complications. Effects of metformin and rosiglitazone

To evaluate subclinical inflammation and fibrinolysis in low-risk type 2 diabetic subjects and to assess the efficacy of metformin and rosiglitazone in this group Sixty-one normotensive, normoalbuminuric type 2 diabetic subjects without diabetes-related complications were included in a 4-week standardization period with glimepiride. After the standardization period, 21 subjects were excluded and the remaining 40 were randomly divided into two groups matched for age, gender, body mass index and disease duration. The first group [n = 20] received metformin [1,700 mg/day], the second group [n = 20] rosiglitazone [4 mg/day] for 12 weeks. Patients with low-density lipoprotein-cholesterol higher than 130 mg/dl at the beginning of the randomization period were treated with simvastatin [maximum dose 20 mg/day]. Twenty-three healthy controls were also recruited. Cytokine measurements were performed with ELISA kits Baseline plasma plasminogen activator inhibitor-1 [PAI-1] level of type 2 diabetic subjects was significantly elevated [p = 0.038], but baseline levels of soluble CD40 ligand [sCD40L] and thrombin-activatable fibrinolysis inhibitor-1 [TAFI] antigen did not differ from healthy controls. Twelve weeks of metformin or rosiglitazone therapy did not cause significant changes in sCD40L, PAI-1 and TAFI antigen levels. In simvastatin-treated subjects [n = 9] significant reductions of PAI-1 were achieved [p = 0.028], while sCD40L and TAFI-Ag did not differ from baseline values. Our results showed that nonobese diabetic patients at low cardiovascular risk had similar levels of subclinical markers of inflammation and fibrinolysis as matched healthy controls. Neither metformin nor rosiglitazone caused marked changes in sCD40L, PAI-1 and TAFI antigen levels. A subset of patients who received simvastatin showed a modest decrease in PAI-1 level and could contribute to beneficial vasculoprotective effect of the drug in type 2 diabetics

Study on the association of thrombin activatable fibrinolysis inhibitor and the Thr325Ile and Thr147Ala polymorphisms of its encoding gene CPB2 in patients with coronary heart disease / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the association of thrombin activatable fibrinolysis inhibitor (TAFI) and its encoding gene CPB2 polymorphism in patients with coronary heart disease (CHD).</p><p><b>METHODS</b>The CPB2 gene polymorphisms of Thr325Ile and Thr147Ala were analyzed with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in patients of acute myocardial infarction (n=100), acute angina pectoris (n=110) and a control group (n=190). The antigen (Ag) and activity (Act) of the TAFI were determined by sandwich enzyme link immunosorbent assay specific for human TAFI and chromogenic assay for activated human TAFI in plasma, respectively. The relationship between Thr325Ile and Thr147Ala gene polymorphism and TAFI Ag and Act were also analyzed.</p><p><b>RESULTS</b>Plasma TAFI Act and TAFI Ag in acute myocardial infarction group and acute angina pectoris group (CHD patients group) were both significantly higher than those of the control group. The genotype frequencies of Thr325Ile (C1040T) and Thr147Ala (G505A) were as the following: C1040C (Thr325Thr) 67 (31.9%) and 64 (33.6%); C1040T (Thr325Ile) 109 (51.9%) and 92 (48.4%); T1040T (Ile325Ile) 34 (16.2%) and 34(17.8%); G505G (Ala147 Ala) 75 (35.7%) and 72 (37.8%); G505A(Thr147Ala) 112 (53.3%) and 96 (50.5%); A505A(Thr147Thr)23 (10.9%) and 22 (11.7%), in the CHD patients and control respectively. Chi-square analysis showed no significant difference in the Thr325Ile and Thr147Ala polymorphism distributions (P > 0.05). In addition, at the 325 position, the TAFI antigen of the Thr325Thr was higher than that of the other genotypes (Thr325Ile and Ile325Ile, P < 0.05). There was no statistical significance between the TAFI antigen of the Thr325Ile and Ile325Ile (P > 0.05). No significant correlation was found between the TAFI Act and the Thr325Ile polymorphism. At the position 147, significant correlation between the polymorphism of the Thr147Ala and TAFI Ag and Act was not found.</p><p><b>CONCLUSION</b>TAFI plays an important role in anti-fibrinolysis. It might be a risk factor for acute myocardial infarction and acute angina pectoris. The Thr325Ile polymorphism had obvious effect on TAFI antigen levels, but the Thr325Ile and Thr147Ala polymorphism had no association with coronary heart disease.</p>

Study of fibrinolysis inhibitors in 117 acute leukemia patients / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the clinical significance of fibrinolysis inhibitors including thrombin activatable fibrinolysis inhibitor(TAFI), plasminogen activator inhibitor (PAI) and alpha2-plasmin inhibitor (alpha2-PI) in acute leukemia (AL).</p><p><b>METHODS</b>PAI-1 antigen and TAFI antigen were investigated by enzyme-linked immunosorbent assay and PAI activity, alpha2-PI activity, TAFI activity by chromatography substrate assay in 117 AL patients and 50 normal controls.</p><p><b>RESULTS</b>1) alpha2-PI activities in AL patients were reduced, especially in ALL patients [(96.8 +/- 21.2)%]; 2) PAI-1 antigens in AML patients [(37.8 +/- 9.2) microg/L] were significantly higher than that in normal controls [(33.8 +/- 4.9) microg/L]; 3) PAI-1 antigens in APL [(37.8 +/- 9.0) microg/L] and AML-M5 patients [(39.9 +/- 11.6) microg/L] were higher and TAFI activities in APL patients [(13.3 +/- 4.8) mg/L] were lower than that in normal controls [(16.9 +/- 2.6) mg/L]; 4) PAI-1 antigens of relapsed/refractory patients (39.6 +/- 11.6) microg/L) were significantly elevated; 5) TAFI activities in bleeding patients [(13.2 +/- 5.3) mg/L] were significantly lower than that in normal control as well as non-bleeding patients (17.0 +/- 4.6) mg/L); 6) The severity of bleeding was negatively correlated with TAFI activity (r = - 0.276, P <0.05).</p><p><b>CONCLUSIONS</b>Hyperfibrinolysis caused partially by decrease of alpha2-PI and TAFI activity takes part in the pathogenesis of bleeding in AL.</p>

Evaluación de inhibidores fisiológicos de la coagulación en pacientes diabéticos tipo 2 / Evaluation about coagulation physiological inhibitors in type 2 diabetic patients

La diabetes mellitus está asociada a disturbios en la hemostasis que pueden contribuir al desarrollo de enfermedad vascular diabética. El objetivo de este trabajo fue estudiar la coagulación en una población diabética de Uruguay y compararla con una población de referencia normal. Se trabajó con 100 pacientes diabéticos tipo 2, de ambos sexos (49 mujeres y 51 hombres), con edades comprendidas entre 42 y 79 años, y una población control representada por 130 individuos aparentemente sanos (73 mujeres y 57 hombres) cuyas edades oscilaron entre 37 y 78 años, los que fueron tomados como referencia. Se realizaron las determinaciones de tiempo de protrombina (TP), fibrinógeno (Fib), proteína C (PC), proteína S (PS), antitrombina III (ATIII) e inhibidor del activador de plasminógeno (PAI) en plasma citratado. El TP y el Fib se realizaron por nefelometría, la PC, ATIII y PAI se midieron cromogénicamente y la PS se determinó por coagulometría. Se encontró que los inhibidores fisiológicos de la coagulación PS y ATIII son significativamente menores en la población diabética, en tanto que los factores procoagulantes Fib y PAI son significativamente mayores, comparados con la población de referencia. De los hallazgos precedentes se confirma una tendencia a un disbalance hemostático que contribuiría al estado protrombótico que acompaña a un alto porcentaje de la población diabética.

Diabetes mellitus is associated with disturbances in hemostasis, which may contribute to the development of diabetic vascular disease. Coagulation tests were performed both in diabetic patients and healthy individuals in Uruguay. The results obtained were compared. Diabetic patients were 100, with ages between 42 and 79 years, 49 females and 51 males. Reference population were 130 healthy individuals between 37 and 78 years, 73 females and 57 males. Prothrombin time (PT), fibrinogen( Fib), protein C (PC), protein S (PS), antithrombin III (ATIII) and plasminogen activator inhibitor (PAI) were measured on citrated plasma. PT and Fib were determined nephelometrically, PC, ATIII y PAI were measured cromogenically and PS was determined by coagulometry. Coagulation physiological inhibitors outcomes such as PS and ATIII showed significantly lower levels in the diabetic patient than in the healthy person, and at the same time, Fib and PAI, which are procoagulant factors, have significantly higher concentrations in the diabetic patient than in the healthy person. These findings permit to assess that an impaired haemostatic balance is present in the diabetic population, which may contribute to the hypercoagulability that accompanies a high percentage of these patients.

Antithrombotic mechanisms of holothurian glycosaminoglycan extracted from sea cucumber / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the antithrombotic mechanisms of holothurian glycosaminoglycan (GAG) extracted from sea cucumber.</p><p><b>METHODS</b>Human endothelial cell line EA. hy926 cells were treated with 10 mg/L GAG or 10U/mL unfractionated heparin (UFH) by short-term (15 min - 2 h) and longer-time incubation (6 h - 48 h). Different doses of GAG were used to stimulate EA. hy926. Released free tissue factor pathway inhibitor(TFPI) was determined by ELISA assay. TFPI expression was investigated by immunofluorescent method and TFPI mRNA level by real-time PCR. In a 96-wells microtitre plate, pooled normal plasma containing different concentrations of GAG was allowed to clot by addition of thrombin and calcium chloride, fibrinolysis was induced by addition of t-PA. TRR (TAFI-related retardation of clot lysis) was used to assess thrombin-activatable fibrinolysis inhibitor(TAFI) functional activity.</p><p><b>RESULTS</b>GAG increased TFPI synthesis, expression and secretion in a dose- and time dependent manner. GAG at low concentrations could lengthen while at intermediate concentrations could shorten clot lysis times significantly as compared to control values. TRR was dose-dependently decreased on addition of GAG.</p><p><b>CONCLUSIONS</b>GAG increases TFPI synthesis, expression and secretion of endothelial cells. GAG at intermediate concentrations significantly affects clot stability of a developing clot by means of diminishing TAFI activation.</p>

Effect and mechanism of recombinant hirudin on fibrinolysis / 药学学报

<p><b>AIM</b>To study the effect of recombinant hirudin (rH) on tPA-induced fibrinolysis and the possible mechanism of its action.</p><p><b>METHODS</b>The effect of rH on thrombin-fibrin complex (Th-Fn) was detected by 99mTc labeled rH. In the in vitro clot lysis, tPA as plasminogen activator, and recalcified plasma as plasminogen resource were used to study the influence of rH on fibrinolysis by detecting TAFIa, D-Dimer and FXIII.</p><p><b>RESULTS</b>In a canine model of femoral artery thrombosis, a clear radioactivity strip was imaged in 30 - 60 min on a part image, and the femoral vein thrombosis developed at 30 min. rH efficiently inhibited clot regeneration. Addition of TM could inhibit clot lysis obviously, and CPI could shorten the delay of clot lysis which due to TAFIa. There was a dose-dependent relationship with TM concentration and TAFI activation. FXIII activation was inhibited by low concentration of rH ( < or = 0.2 u x mL(-1)), and the level of fibrinolysis product, D-Dimer, increased.</p><p><b>CONCLUSION</b>rH could inhibit the thrombin binding to fibrin. rH inhibited the activation of TAFI and FXIII by combining with thrombin which resulted in enhancement of thrombolysis.</p>

Inherited Thrombophilia

Inherited thrombophilia has been an area of intense clinical research since the description of deficiency of antithrombin III [1965], protein C [1981] and protein S [1985]. It is now possible to identify the inherited thrombophila in about 50% of cases of venous thrombosis. Certain components of inherited thrombophilia have a major impact on anticoagulant therapy, so basic knowledge about them is necessary in every medical speciality

Plasma Fibrinolysis Inhibitor Levels in Acute Stroke Patients with Thrombolysis Failure

BACKGROUND AND PURPOSE: Thrombolytics-induced recanalization fails in a significant portion of patients with ischemic stroke, which is partly due to the resistance of clots to lysis by thrombolytic agents. The pretreatment level of endogenous fibrinolysis inhibitors may affect such thrombolysis failure. METHODS: We studied 43 stroke patients whose arterial recanalization had been evaluated by angiography, and whose blood had been obtained prior to the administration of thrombolytic agents. Plasma samples from 34 healthy volunteers were used as normal controls. Plasminogen activator inhibitor type 1 (PAI-1) and thrombin-activatable fibrinolysis inhibitor (TAFI) levels were quantified using an enzyme-linked immunosorbent assay. RESULTS: Arteries were recanalized [Thrombolysis in Myocardial Infarction (TIMI) grade 2 or 3] in 30 patients, but not (TIMI grade 0 or 1) in the other 13. The plasma PAI-1 level was significantly higher in patients without recanalization (nonrecanalization) than in those with recanalization and in normal controls. The TAFI levels did not differ among the groups. CONCLUSIONS: The pretreatment PAI-1 levels are increased in acute stroke patients with thrombolysis failure.

Relation between thrombin activatable fibrinolysis inhibitor and haemostatic alterations in patients with chronic liver disease and portal vein thrombosis

Recently, a new inhibitor of fibrinolysis was discovered which down regulates fibrinolysis after its activation by thrombin and was therefore named thrombin activatable fibrinolysis inhibitor [TAFI]. We aimed at evaluating TAFI level in chronic liver disease [CLD] and its relationship to important haemostatic parameters namely: tissue factor [TF], prothrombin fragment 1+2 [Fl+2], thrombomodulin [TM], protein C [PC], protein S [PS], thrombus precursor protein [TpP] and D-dimer [D-di] in a trial to clarify the role of TAFI in haemostatic alterations frequently encountered in CLD. The study included 35 CLD patients [Chid B or C], 15 [out of them] were complicated by portal vein thrombosis [PVT], in addition to 15 healthy controls. Significant reduction in TAFI level was detected in CLD patient with and without PVT in comparison to controls, however a significantly higher values were noticed in patients complicated by PVT when compared to those without thrombosis. Correlation analysis demonstrated a strong correlation between TAFI level and other measured parameters namely PT, PTT, PC, PS and D-dimer in PVT group. It could be concluded that TAFI plays a crucial role in regulation of coagulation and fibrinolysis. Reduced TAFI level in patients with CLD could result in up regulation of fibrinolysis. High TF level, associated with decreased natural anticoagulants namely PC and PS accompanied by a higher TAFI level and its increased activation could play a role in the development of PVT as a complication of CLD

The Significance of Thrombin Activable Fibrinolysis Inhibitor in Ischemic Stroke / 대한진단검사의학회지

BACKGROUND: Thrombin/thrombomodulin complex activates thrombin activable fibrinolysis inhibitor (TAFI) to active TAFI (TAFIa), which in turn catalyzes the hydrolysis of C-terminal lysine residues of partially degraded fibrin. The fibrin that is partially degraded by TAFIa is not degraded by plasmin. Thus, TAFI inhibits fibrinolysis. An increase in plasma TAFI level is suggested to be associated with thrombotic disorders. In this study, we measured TAFI levels and investigated the distribution of C+1542G polymorphism in Korean patients with ischemic stoke. And, we intended to investigated the role of TAFI in the occurrence of ischemic stroke. METHODS: We enrolled 44 patients who had experienced ischemic stroke episodes more than 6 month ago and had not been treated with oral anticoagulant. We also tested 44 age and sex-matched healthy controls. TAFI antigen levels were measured by an enzyme-linked immunosorbent assay (VisulizeTM TAFI antigen kit; Affinity Biologicals Inc., Ancaster, Canada) and TAFI activity levels were measured by a chromogenic assay (Actichrome TAFI activity kit ; American diagnostica Inc., CT, USA). Genotyping of C+1542G polymorphism was performed by an allele-specific polymerase chain reaction. RESULTS: The range of TAFI antigen was 2.4-12.7microgram/mL (mean+/-2SD) and that of TAFI activity was 4.9-17.9microgram/mL (mean+/-2SD) in healthy controls. TAFI antigen level was not correlated with TAFI activity. TAFI activity was the highest in CC polymorphism and the lowest in GG polymorphism (P= 0.03). The levels of TAFI antigen and activity were lower in the patients with ischemic stroke than in healty controls, but the difference was not statistically significant. There was no difference in the distribution of C+1542G polymorphism between the patients with ischemic stroke and healthy persons. CONCLUSIONS: In this study, TAFI antigen and activity were not significantly associated with the occurrence of ischemic stoke in Korean. And, TAFI may not be a risk factor for ischemic stroke in the Korean population.

Potential role of thrombin-activatable fibrinolysis inhibitor [TAFI] in diabetic nephropathy and its relation to degree of albuminuria and to dialysis modality

Diabetic nephropathy has become the most prevalent cause of end-stage renal disease [ESRD] in many countries, and about one third of patients with diabetic nephropathy progress to end stage renal disease. Patients with end-stage renal disease dialyzed due to diabetic nephropathy are at higher risk of death due to cardiovascular complications than dialyzed non-diabetic patients. Hypofibrinolysis is a common finding in patients with diabetes mellitus and a risk factor for diabetic nephropathy and may play a role in the vascular complications in dialyzed diabetic patients. A new potent inhibitor of fibrinolysis, the thrombin-activatable fibrinolysis inhibitor [TAFI], has been isolated from human plasma. However, the relation between plasma TAFI level and diabetic nephropathy has not been well appraised. In the present study, we investigated the plasma levels of TAFI in 50 type 2 diabetic patients: 10 with normoalbuminuria, 10 with microalbuminuria, 10 with macroalbuminuria, 10 with ESRD on haemodialysis, and 10 with ESRD on peritoneal dialysis. Also, we assessed albumin/creatinine ratio in albumiuric patients, blood urea, serum creatinine, serum lipids, and ECG. The plasma level of TAFI in diabetic patients with macroalbuminuria was significantly higher than the level in diabetic patients with microalbuminuria [P < 0.00l], and higher in micro-albuminuric patients than in normolbuminuric patients[P < 0.00l]. Plasma TAFI level was correlated to albumin/craetinine ratio[P < 0.00l], blood urea[P < 0.00l] and serum creatinine[P < 0.00l] in patients with micro-albuminuria [non dialyzed patients]. Moreover, it was significantly higher in patients with diabetic nephropathy and on peritoneal dialysis than those on haemodialysis [P < 0.01] and it was correlated positively with triglycerides [P < 0.05] and negatively with HDL-c[P < 0.05]. These data suggest that TFAI level was increased by the progression of diabetic nephropathy as it was significantly higher in. patients reaching ESRD [haemodialysis and peritoneal dialysis groups]than in those still in the stages of micro and rnacro-albuminuria and higher in macroalbuminuric patients than in microalbuminuric patients. Also TAFI level was significantly positive correlated with tile indicators of decline in renal function [blood urea, serum creatinine, urinary albumin and urinary albumin/creatinine ratio]. So we can concluded that increased plasma level of TAFI may contribute to the pathogenesis and progression of diabetic nephropathy and may have role in tile cardiovascular complications of dialyzed diabetic patients, especially those under peritoneal dialysis

Status of a novel arginine carboxypeptidase generated during coagulation in rheumatoid arthritisIts relationship with fibronection, cerulolasmin and clinical status of the patients

A novel arginine carboxypeptidase which is generated from plasma components during coagulation and possibly during some inflammatory reactions was recently reported to be decreased in rheumatoid arthritis. To further clarify this point, serum and plasma arginine carboxypeptidase together with plasma fibronectin and serum ceruloplasmin were determined in 37 patients with rheumatoid arthritis and 16 healthy controls. The study revealed significantly decreased serum enzyme activity levels as well as serum/plasma enzyme ratio compared with control, while both ceruloplasmin and fibronectin levels were increased significantly. Increased consumption of this enzyme for metabolism of inflammatory peptides such as C3a, C5a and bradykinin may be responsible. Significant negative correlation existed between serum enzyme activity as well as serum/plasma enzyme ratio and both fibronectin and ceruloplasmin. The negative correlation with fibronectin could be due to involvement of the enzyme in removal of this molecule, while negative correlation with ceruloplasmin could be due to the anti-inflammatory function of ceruloplasmin as a metal binding protein. No obvious correlation could be observed between indices of clinical severity, a finding suggesting that arginine carboxypeptidase deficiency could be partly due to inherited or acquired inability to generate this enzyme which results in an accelerated onset of the disease