AT-III Levels Research Articles

Antithrombin Ⅲ is a Novel Predictor for Contrast Induced Nephropathy After Coronary Angiography

Background/Aims: Antithrombin Ⅲ (AT Ⅲ) is an important endogenous anticoagulant and has strong anti-inflammatory properties. Low ATⅢ activity is considered to be a predictor of poor outcomes in several conditions, including acute kidney injury after cardiac surgery. However, the association between the ATⅢ level and the occurrence of contrast induced nephropathy (CIN) has not been elucidated. In this study, our aim was to identify the potential predictive value of ATⅢ for CIN. Methods: We enrolled a total of 460 patients who underwent coronary angiography (CAG) from January 2015 to December 2016 in coronary care units (CCU). ATⅢ activity in plasma collected before CAG was measured and <75% was considered low activity according to reference values. A cross-sectional study on CIN after CAG was conducted and the risk factors were analyzed. CIN was diagnosed according to the KDIGO guideline. Results: Of these 460 patients undergoing CAG, 125 (27.17%) progressed to CIN. The incidence of CIN was significantly higher in patients with low ATⅢ activity compared to patients with normal ATⅢ activity (Pearson’s chi-squared test P=0.002). As ATⅢ activity declined, the prevalence of CIN progressively increased, with the highest value (58.8%) in patients with an ATⅢ activity <60%. Moreover, the ATⅢ activity was significantly lower in CIN patients than in non-CIN patients (84.43±16.3% vs. 92.14±13.94%, P<0.001). After multivariable analysis, ATⅢ activity <75% remained a significant independent predictor of CIN (OR 2.207,95%CI [1.29-3.777]; P=0.004) as well as baseline serum creatinine (OR 1.009,95%CI [1.001-1.016]; P=0.026). Conclusions: Patients with low ATⅢ activity had a higher risk of developing CIN after CAG. The initial ATⅢ activity may be a novel independent predictor for CIN.

Sulfasalazine treatment can cause a positive effect on LPS-induced endotoxic rats.

The aim of this study, was to determine the effect of sulfasalazine for different periods of time reduces disseminated intravascular coagulation, inflammation and organ damages by inhibiting the nuclear factor kappa beta pathway. The study was performed with 30 Wistar albino rats and the groups were established as Control group, LPS group; endotoxemia was induced with LPS, SL5 group: sulfasalazine (300 mg/kg, single dose daily) was administered for 5 days before the LPS-induced endotoxemia, and LS group: sulfasalazine (300 mg/kg, single dose) was administered similtenously with LPS. Hemogram, biochemical, cytokine (IL-1β, IL-6, IL-10, TNF-α) and acute phase proteins (HPT, SAA, PGE2) analyzes and oxidative status values were measured from blood samples at 3 and 6 h after the last applications in the all groups. The rats were euthanized at 6 h and mRNA levels of BCL2 and BAX genes were examined from liver and brain tissues. Sulfasalazine reduced the increased IL-1β, IL-6, TNF-α and PGE2 levels and significantly increased anti-inflammatory cytokine IL-10 levels. In addition, decreasing of ATIII level was prevented in the SL5 group, and decreasing of fibrinogen levels were prevented in the LS and SL5 groups within first 3 h. In LPS group, leukocyte and thrombocyte levels were decreased, however sulfasalazine application inhibited decreases of leukocyte levels in LS and SL5 groups. In addition, sulfasalazine inhibited the decrease of total antioxidant capacity and unchanged apoptosis in brain and liver. In conclusion, the use of sulfasalazine in different durations reduce the excessive inflammation of endotoxemia cases.

Rivaroxaban for the treatment of venous thromboembolism in patients with nephrotic syndrome and low AT-III: A pilot study.

The anticoagulation effect of heparin requires adequate serum antithrombin (AT)-III levels. Rivaroxaban, however, exhibits its anticoagulation effects independent of AT-III. The aim of the present study was to evaluate the efficacy and safety of rivaroxaban as a treatment for venous thromboembolism in patients with AT-III deficiency due to nephrotic syndrome. Patients with nephrotic syndrome and low serum concentration and functional activity of AT-III and venous thromboembolism were randomly assigned to the rivaroxaban group (n=8) and low weight molecular heparin group (n=8). The patients were treated for 4 weeks and evaluated at weeks 2 and 4. The primary endpoint was thrombus dissolution or a >90% decrease in thrombus volume in 4 weeks. Secondary endpoints included an increase in the volume of the pre-existing thrombosis and safety assessments. In each of the two groups, 7/8 patients achieved a primary endpoint. At week 2, 5 patients in the rivaroxaban group and 4 in the low weight molecular heparin group had achieved the primary endpoint. Notably, at week 2 the patients whose AT-III levels and functional activity remained low in the low weight molecular heparin group did not achieve the primary endpoint. The adverse effects were similar in both groups, with no severe hemorrhage observed. In conclusion, the results of this pilot study demonstrate that rivaroxaban may be an effective, safe, single-agent approach for treating vein thromboembolism in patients with nephrotic syndrome and low AT-III levels. The potential benefits of rivaroxaban over low weight molecular heparin treatment require further investigation with a larger sample size in order to validate the findings of the present study.

Is either arterial or venous antithrombin III level linked to outcome in elderly males versus females with severe sepsis?

Objectives: We aimed to study arterial and venous ATIII levels, in elderly males and females with severe sepsis, and their impact upon the patients’ outcomes. Patients and Methods: A cohort study was performed in thirty-nine elderly patients with severe sepsis. Arterial and venous ATIII levels were measured. Sequential Organ Failure Assessment (SOFA) score was calculated. Results: Both arterial and venous ATIII levels were negatively correlated with age in the whole sample (P=0.004 and .05 consecutively) (r = −0.45 and −0.32 consecutively). There was a significant difference between the arterial and venous ATIII levels in males (P=0.04). In males, SOFA score was positively correlated with arterial ATIII and the difference between arterial and venous ATIII levels (P=0.04 and .05 consecutively). Arterial and venous ATIII were the significant predictors of SOFA score, only in males (P &lt;0.001 and 0.003 consecutively). Conclusion: ATIII level decreased with increasing age. In males, both higher arterial and lower venous ATIII levels were significant predictors of worse organ dysfunction. DOI: http://dx.doi.org/10.3126/ajms.v6i1.10795 Asian Journal of Medical Sciences Vol.6(1) 2015 34-39

Low plasma levels of antithrombin III in the early post‐operative period following pediatric liver transplantation: Should they be replaced? A single‐center pilot study

eHAT after LT remains a life-threatening complication. In the majority of anticoagulation protocols, heparin is used to prevent thromboses. Our study aimed to monitor AT-III levels in the early post-LT period to assess the need for the administration of AT-III concentrate to ensure the effectiveness of heparin. We monitored coagulation daily by measuring INR, APTT, fibrinogen, platelets, and AT-III. Anticoagulation therapy consisted of LMWH, AT-III, and dipyridamole. AT-III concentrate was administered when AT-III activity was ≤60%. DUS was performed daily for the first five post-operative days or whenever vascular thrombosis was suspected. Between October 2007 and October 2011, 39 LT were performed in our center. The median age was 26 months (6-196) with a median weight of 9 kg (5.5-49). AT-III activity was ≤60% in 27 patients. Lower levels were particularly observed in partial grafts and recipients weighing less than 10 kg. Patent arterial flow was present in all 39 LT during the first five post-operative days. AT-III levels were low in 70% of pediatric patients following LT, thereby risking heparin ineffectiveness. These results may implicate low AT-III levels in the etiology of eHAT post-LT. However, this is a small single-center pilot study and further larger prospective trials are required to confirm these results.

Impact of Different Types of Resuscitation Fluids on Coagulation and Continuous Venovenous Hemofiltration Hemocompatibility in a Porcine Model

Intensive therapy demanding diseases (organ failure or sepsis) are assumed to be the etiology behind a decreased biocompatibility of extracorporeal systems for renal replacement therapy (RRT). There are also potential interactions between different components of the overall therapy. Volume substitutes are known to influence hemorheology and coagulation. To define a potential net effect of volume substitutes on the hemocompatibility of an RRT, we chose an animal model without interfering pathophysiologies. According to the problem of early filter failure and coagulation disorders in critically ill patients, we focused on the hypothesized interaction between RRT and different volume substitutes with respect to blood cell counts, coagulation parameters and required heparin dose. Forty-eight pigs were assigned to four groups of fluid therapy with either normal saline (NaCl), 6%HES130kD/0.4 (HES130), 6%HES200kD/0.5 (HES200) or 4%gelatin (GEL). Six pigs of each fluid group underwent continuous venovenous hemofiltration (CVVH), the remaining six served as the control group. Anticoagulation was performed with continuous heparin infusion. CVVH was run in a recirculation-mode for 4.5 h to force hemocompatibility reactions, thereafter in a standard-mode for 2 h. During the CVVH-treatment GEL reduced platelet counts and fibrinogen concentration and additionally lowered ATIII levels. Heparin requirements did not differ between different volume substitutes or CVVH and control groups. Severe pathophysiologies are not the only reason for a reduced hemocompatibility of CVVH treatment. Interaction of a particular volume substitute with CVVH should be considered when interpreting study results and evolving new strategies.

Invited Commentary

Invited Commentary

Serum antithrombin III level is well correlated with multiple indicators for assessment of liver function and diagnostic accuracy for predicting postoperative liver failure in hepatocellular carcinoma patients.

Evaluation of preoperative hepatic reserve is critical to avoid a fatal clinical course such as liver failure. We retrospectively evaluated 158 consecutive hepatocellular carcinoma (HCC) patients who underwent initial hepatectomy. The aim of this study was to determine the correlations of multiple indicators for assessment of liver function before hepatectomy. Furthermore, diagnostic probability for the pathological background and prediction of postoperative liver failure/dysfunction was compared between the antithrombin (AT) III level and indocyanine green retention rate at 15 minutes (ICGR15). Between January 2001 and March 2008, 158 HCC patients who underwent initial hepatectomy were enrolled in this study. Spearman's correlation coefficients (r values) were obtained for 15 clinical laboratory tests including ATIII and ICGR15. Receiver operating characteristic (ROC) curve analysis was used for calculating the probability and predictive ability of the tests. All 158 consecutive HCC patients were eligible for hepatectomy based on the Japanese guideline. ATIII is correlated with 13 of 14 other clinical tests, including albumin, bilirubin, prothrombin time, rapid turnover proteins, HGF, ICGR15 and others. The diagnostic probabilities to distinguish between normal liver and other pathological backgrounds of ATIII and ICGR15 were significantly different. The specificity of ATIII to predict postoperative liver failure/dysfunction was higher than that of ICGR15. The serum ATIII level before hepatectomy is valuable to estimate the pathological background and predict postoperative liver failure/ dysfunction. It should be possible to use ATIII as an additional indicator for liver function and substitute for ICGR15 in the future.

Effect of Postmenopausal Hormone Treatment on Serum Lipid Profile and Coagulation Factors

Background & Objectives: To assess the effects of different hormone treatment regimes on blood lipids, lipoproteins, ATIII, fibrinogen in postmenopausal patients. Methods: We studied retrospectively 115 patients who recieved one of four different estrogen treatment protocols. Of the 115 patiens; 25 had received transdermal estradiol patch 3.9 mg/week(TD) (Group-1), 22 patients had received TD + MPA 2.5 (Group-2), 19 patients had received oral CEE 0.625 mg/day (Group-3), 23 patients had received CEE 0.625 mg/day + MPA 2.5 mg/day (Group-4), 26 postmenopausal patients who had no hormonal treatment composed control group. Plasma cholesterol, lipids, lipoproteins, ATIII, and fibrinogen levels before and 6 months after treatment were checked from their recordings retrospectively. Results: Serum cholesterol level increased in control group, decreased in MPA taking Group-2, and Group-4. Serum LDL level decreased significantly in Group 2, 3, and 4 while it increased insignificantly in control group. Serum HDL level increased significantly only in oral CEE taking Group-3 (24% increase). Trigliseride level significantly decreased in Group-2 (10.1% decrease). Fibrinogen decreased in all treatment groups, ATIII did not change in treatment groups but increased in control group by 22.9%. Interpretation and Conclusion: Estrogen alone or in combination with progestin effects plasma lipid levels in a positive way. It also decreases fibrinogen level that might be protective for CVD.

The association with age, human tissue kallikreins 6 and 10 and hemostatic markers for survival outcome from epithelial ovarian cancer

To assess known cancer biomarkers CA-125, human tissue kallikreins KLK6 and KLK10, hemostatic markers and age with 5-year survival outcome from epithelial ovarian cancer. Forty-one benign cyst cohorts and 83 patients diagnosed with ovarian cancer were recruited. The following assays were performed: fibrinogen, vWF antigen, D: -dimer, ATIII activity, tPA, PAI-1, uPAR, KLK6, KLK10 and CA-125. Follow-up visits of cancer patients of more than 60 months were noted. Data between those who survived past 60 months and mortality from cancer were analyzed. Only 24 patients lived past 60 months, and 31 died (advanced stage n = 27). Those living past 60 months were significantly older and associated with similar pre-operative levels seen in benign cyst cohorts especially for KLK6, fibrinogen, vWF, AT levels despite upregulation of D: -dimer, CA-125 and KLK10. Ovarian cancer cohorts living past 60 months were younger than those who died within 12 months (n = 12). Mortality within 12 months was associated with older age, upregulation of KLK6, fibrinogen, D: -dimer, vWF, tPA antigen and reduced ATIII levels. Similarly, mortality within 36 months of disease showed older age with upregulation of CA-125, KLK6 D: -dimer vWF antigen and tPA antigen levels. Late stage cancer (III/IV) showed upregulated CA-125, KLK6, KLK10, D: -dimer and reduced AT compared to early stage cancer (I/II). The 5-year survival rate for early cancer was 80%, advanced 22.9% and overall 5-year survival rate was 43.6%. Older age together with the novel biomarkers studied and their association with adverse outcome from epithelial ovarian cancer was seen especially within 12 and 36 months of disease. Those who lived past 60 months of disease showed similar pre-operative levels seen in benign cyst cohorts despite elevated D: -dimer, CA125 and KLK 10. An enlarged study is needed to confirm these findings.

Analysis of risk factors for venous thrombosis associated with the placement of peripherally inserted central catheters in patients with malignant tumors during the course of chemotherapy

Objective To investigate the induced-factors levels of venous thrombosis associated with the placement of peripherally inserted central catheters (PICC) in patients with malignant tumor,and establish intervention model accordingly. Methods 40 patients complicated with venous thrombosis after PICC were set as the thrombosis group, 40 patients without venous thrombosis were selected as the no-thrombosis group, 30 healthy cases were selected as the control group. All cases' serum samples were ob-tained to measure the levels of molecular biomarkers of the coagulation system, platelet parameters and molecular biomarkers of the fibrinolysis system. The results of the three groups were assessed. Results Patients in the thrombosis group were reported significantly higher levels of vWF, GMP140,TAT than those in both two other groups, but lower levels of ATⅢ. Higher levels of MPV and PCT were found in the throm-bosis group than those in both two other groups.Tthe data also showed higher PLG and PAI levels and lower levels of PLM in the thrombosis group. Conclusions From this study it shows that patients with malig-nant tumors during the placement of PICC have evident hypercoagnlahility, high- activated platelet and se-vere pre- thrombosis state caused by PICC. In treatment of malignant tumor patients with PICC, the level of coag-ulation system molecular markers, platelet parameters,fibrinolysis molecular markers shoud be used as a clinical routine and as the index of early intervention and evaluation of the PICC. Key words: Malignant tumor; Peripherally inserted central catheters; Venous thrombosis; Risk factors

Antithrombin III as a criteria marker in chronic liver disease.

Recently, many studies have reported that the plasma concentrations of natural anticoagulants, such as antithrombin III (AT III), are altered in chronic liver diseases. In addition, the changes in synthesis of AT III occur in liver tissue and are associated with the extent of chronic hepatitis and cirrhosis. In this study, we analyzed the plasma level of АТ III and serum activity of aminotransferase in 60 participants: 20 patients with chronic hepatitis, 20 patients with cirrhosis, and 20 healthy individuals (control). Low levels of AT III and elevated levels of aminotransferase activity were associated with both chronic hepatitis and cirrhosis (P< 0.05). We found that among patients with elevated GGT activity and chronic liver disease, the level of АТIII in plasma is significantly lower in patients with chronic cirrhosis than in patients with chronic hepatitis (P< 0.05) and the level of АТ III in plasma was lower in patients with liver disease in comparison to those in healthy participants (P< 0.05).. Therefore, ATIII level in patients with chronic liver disease may be used as a exist factor for cirrhosis laboratory diagnosis. *This abstract has been accepted in swiss medlab congress at 2008 and published in the journal of Clinical Chemistry and Laboratory Medicine. Volume 46, Issue 8, Pages A69 List of Abbreviations AT III Anti Thrombin III ALT Alanin Aminotransferase AST Aspartate Aminotransferase GGT ?-Glutamiltransfrease DIC Disseminated Intravascular Coagulation

Danapaloid Is Significantly Effective for the Prophylaxis of Hepatic Veno-Occlusive Disease after Allogeneic Hematopoietic Stem Cell Transplantation: A Cohort Study of 85 Children with Hematological Malignancies.

Background: Veno-occlusive disease (VOD) is one of the regimen related toxicities in the early phase of hematopoietic stem cell transplantation (HSCT). Therapeutic modality for established VOD is limited and severe VOD cause multiple organ failure mostly with fatal prognosis despite intensive supportive care. Therefore prophylaxis of VOD is very important to reduce the treatment related mortality (TRM) after HSCT. Danapaloid, a mixture of low molecular weight heparan, dermatan, and chondroitin sulfates, promotes higher anti-coagulant activity with lower bleeding tendency than heparin could have a possibility of the prevention of VOD after HSCT.Patients: Eighty-five children with hematological malignancies (42 in CR1, CR2 or CP1 and 43 at advanced stages) underwent allogeneic HSCT from 2002 to 2008 in our institution. Underlying diseases were ALL(n=46), AML(n=26), CML(n=1), MDS(n=6), and NHL(n=6). They received bone marrow (n=69) or cord blood(n=16) from matched related (n=20), mismatched related(n=8), matched unrelated(n=30) or mismatched unrelated(n=27) donors. For the prophylaxis of VOD, dalteparin was given to 47 patients who underwent HSCT from 2002 to 2005, and danapaloid was given to 38 patients after 2005. In addition to dalteparin or danapaloid, ursodeoxycholic acid, tocopherol acetate, and eicosapentaenoic acid were given to all patients. We defined former 47 patients as dalteparin group and latter 38 patients as danapaloid group.Design: In this study, we compared the incidence of VOD, treatment related mortality at day 100 (day100 TRM) and 2 year overall survival (OS) between danaparoid group and dalteparin group as historical control in 85 consecutive patients with allogeneic HSCT.Results: In our observation, 8 patients (7 in dalteparin group, and 1 in danaparoid group) had VOD by day +30 (median day+22, range day+11 to +28) after HSCT. The probability of developing VOD for all patients was 10% (95% CI: 1–31%). Seven of 8 patients with VOD died and their probability of 2yr OS was 13% (95% CI: 1–42%). Five patients developed >grade3 bleeding (4 in dalteparin group, and 1 in danapaloid group) and there was no significant difference on the probability of severe bleeding between two groups (10% versus 3%, p=0.21). In multivariate analysis by Coxhazard proportional model, the significant risk factor for the development of VOD was >2nd transplant (HR: 17.5, 95%CI: 1.86–165, p=0.012) and the significant favorable factor for development of VOD was administration of danapaloid (HR: 0.09, 95%CI: 0.01–0.85, p=0.036). In the analysis of 85 consecutive HSCT procedures, the probability of day100 TRM was 15% (95% CI: 3–34%) and that of 2yr OS was 69% (95% CI: 56–78%). As for day100 TRM, the significant risk factors were >2nd transplant (HR: 8.73, 95%CI: 1.75–43.5, p=0.008), HLA disparity of >1Ag (HR: 10.3, 95%CI: 1.71–62.5, p=0.011) and posttransplant plasma ATIII level of <96% (HR: 4.68, 95%CI: 1.05–20.8, p=0.042). As for 2yr OS, the only significant risk factor was HLA disparity of >1Ag (HR: 3.26, 95%CI: 1.15–9.26, p=0.026). The danaparoid group had no significant advantage to dalteparin group on day100 TRM (HR: 0.55, 95%CI: 0.10–3.05, p=0.50) and 2yr OS (HR: 0.58, 95%CI: 0.19–1.73, p=0.33).Conclusion: Our findings suggest that administration of danapaloid is promising for the prophylaxis of VOD without increasing hemorrhagic complications. Prospective randomized, controlled study is mandatory to prove these findings.

Analysis of inherited thrombophilic mutations and natural anticoagulant deficiency in patients with idiopathic portal hypertension

Idiopathic portal hypertension (IPH) is characterized by non-cirrhotic presinusoidal intrahepatic portal hypertension. The etiopathogenesis of the disease is poorly understood. Obliteration with microthrombosis of the small portal vein branches may lead to lesions underlying portal hypertension. We aimed to put forward a comprehensive thrombophilic mutation profile in IPH and its probable contribution to pathogenesis. Eleven patients and 12 controls were included. We used the CVD-StripAssay which is based on the reverse-hybridization principle to identify a total of 12 thrombophilic gene mutations: Factor V R506Q, Factor V H1299R, prothrombin G20210A, Factor XIII V34L, beta-Fibrinogen -455 G-A, PAI-1 4G/5G, platelet GPIIIa L33P, MTHFR C677T, MTHFR A1298C, ACE I/D, Apo B R3500Q and Apo E2/E3/E4, respectively. We also evaluated some blood parameters and protein C, protein S, AT-III levels using commercially available assays. IPH patients and controls were similar in respect to gender distribution (P = 1.000). Mean age was 31.2 in patients and 29.1 in controls (P = 0.622). Pica history was present in 54.5% of the patients. Mean protein C and AT-III levels were lower in patients than that of controls (P = 0.002 and 0.001, respectively). Factor XIII V34L, PAI-1, GPIIIa L33P, MTHFR C677T and MTHFR A1298C frequencies of genetic polymorphisms were found to be significantly higher among patients than that of controls. Apolipoprotein E2/E3/E4 analysis showed an inverse relationship with IPH when E2 plus E4 compared with E3. A higher frequency of Beta-Fibrinogen -455G-A mutation was observed in patients, but this difference did not reach a statistical significance. Our data represent the most comprehensive study to date with respect to thrombophilic gene polymorphisms in IPH. The data support a possible pathogenetic role in IPH, at least by some of the prothrombotic mutations. In order to confirm or refuse this proposal, a larger cohort of patients is needed.

Coagulation and inflammation markers during atypical or typical antipsychotic treatment in schizophrenia patients and drug-free first-degree relatives

BackgroundClinical studies suggest that the second generation antipsychotics (APs) clozapine and olanzapine and to a lesser extent the typical antipsychotics may be associated with a procoagulant and proinflammatory state that promotes venous thromboembolism. We evaluated here several blood factors associated with coagulation and inflammation in AP-treated schizophrenia patients and their first-degree relatives. MethodsProcoagulant factors (fibrinogen and plasminogen activator inhibitor [PAI-1]), the anticoagulant factor antithrombin III [AT-III], and inflammation-related factors (C-reactive protein [CRP] and leptin) were assessed in patients chronically treated with clozapine (n=29), olanzapine (n=29), typical APs (n=30) and first degree relatives of clozapine (n=23) and olanzapine subjects (n=11). ResultsThe typical AP group had the highest CRP level (p=0.013) in spite of having the lowest body mass index (BMI). Patients as a single group had higher CRP levels than relatives (p=0.003). The typical AP group also had the highest AT-III levels (p=0.021). Fibrinogen levels did not differ between the groups (p=0.13). Olanzapine patients displayed the highest PAI-1 and leptin levels among the drug-treated subjects, but values were similar to those observed in their relatives, and were significantly correlated with the BMI. ConclusionsA homogeneous negative profile of high inflammation and procoagulant factors along with low levels of anticoagulants was not detected in any group. While preliminary, our results suggest that the observed abnormalities were not related to a direct drug effect, but to elevated BMI (high PAI-1 and leptin in olanzapine-treated patients). We speculate that the high CRP in the typical AP group might be related to poor lifestyle habits, but this must we confirmed in future studies.

Thrombophilias and arteriovenous fistula dysfunction in maintenance hemodialysis

Most episodes of fistula thrombosis are consequences of underlying physioanatomic abnormalities. However, some dialysis access thrombosis develops independent from any obvious anatomic cause. We aimed to clarify the role of thrombophilias in primary and secondary AVF failure. One hundred eighty nine arteriovenous fistulas in 116 adults on maintenance hemodialysis were analyzed. All subjects were evaluated for many thrombotic factors. Fistula information was obtained both from the patients' self reports, and from their medical records. Twenty-seven AVFs in 18 cases (14.3%) had pAVFF. The percentage of subjects with a BMI < 20 kg/m(2) was significantly lower than no-pAVFF group (P = 0.03). ATIII levels and albumin values were significantly lower in patients with sAVFF compared to those with no sAVFF. Other parameters were similar. There was no statistically significant difference between pAFFF versus No-pAFFF and sAFFF versus No-sAFFF groups with respect to all mutant alleles count. Routine extended analyses of all thrombophillic factors are not recommended in AVFF.

Dynamic change of coagulation and anticoagulation markers of patients with acute cerebral infarction during intravenous urokinase thrombolysis

Background and objective: The variations of blood coagulation and anticoagulation are of clinical importance in patients with acute cerebral infarction during intravenous urokinase (UK) thrombolysis. Although intravenous heparin is commonly used after thrombolytic therapy, few reports have addressed the relationship between the degree of anticoagulation and clinical outcomes, specifically the effect of thrombolytic agents on hemostasis. In this study, we dynamically monitored the activated partial thromboplastin time (APTT), the prothrombin time (PT), the thrombin time (TT) and the activated partial thromboplasmin time (APTT) in 56 patients with acute cerebral infarction during intravenous urokinase thrombolysis and analysed the relationship among the blood coagulation biomarkers (APTT, PT, TT, AT-III), as well as baseline patient characteristics and clinical outcomes. This allowed us to explore the valuable biomarkers for securing the thrombolysis regimen in clinical practice.Methods: The levels of PT, APTT, TT and AT-III in peripheral blood of 56 patients with acute cerebral infarction and 50 normal controls were assayed by ELISA. Dynamic transformation of these markers at the baseline and the time points of the first, second, fourth, eighth, 12th, 24th, 48th, 72nd and 96th hour after intravenous UK thrombolysis was monitored serially. The relationship between the levels of these biomarkers and the clinical effectiveness and safety of urokinase thrombolysis was evaluated.Results: The levels of PT, APTT, TT and AT-III in patients before intravenous UK thrombolysis were significantly lower than those in age- and sex-matched normal controls (all p<0.05). After treatment with UK, the levels of PT and APTT rose quickly during the first 4 hours (all p< 0.05), and then gradually recovered, reaching baseline at about the 48th hour. The activity of AT-III was slightly increased and showed fluctuations after UK infusion (p< 0.05), however the fluctuated range was not remarkable and lacked specificity.Conclusions: Dynamic monitoring of PT, APTT and TT can indicate coagulative and anticoagulative functions of patients with acute cerebral infarction during intravenous urokinase thrombolysis. Monitoring of these markers can be helpful both in regulating the infusion speed and the dosage of UK, as well as increasing the efficacy and safety of UK therapy. However, assay for AT-III might be unnecessary.

Role of Congenital and Acquired Thrombophilic Factors in the Failure of Thrombolysis in Patients with Acute Myocardial Infarction.

In patients with acute myocardial infarction, a persistently occluded infarct related coronary artery, despite a correct thrombolysis, is associated with an unfavourable prognosis. Therefore, identification of variables predictive of ineffective thrombolysis is crucial to identify patients at higher risk of thombolysis failure. To investigate whether or not acquired or congenital thrombophilic factors had a role in the ineffective thrombolysis we designed this study in which patients treated with intravenous thrombolysis for a ST segment elevation myocardial infarction were blind tested for the thrombophilic factors on the occasion of the coronary angiography performed within 30 days from the thrombolytic treatment. Patients with known factors influencing metabolism and circulating levels of homocysteine were excluded from this study. From October 2003 to May 2004, 104 consecutive patients treated with intravenous thrombolysis for a ST segment elevation myocardial infarction were available for this study, 3of these refused to participate in the study All patients underwent,within 30 days from thrombolysis, a coronary angiography and of the 101 participating in the study, 40 resulted occluded while 61 had a patent artery. In these 101 patients we blind tested the levels of ATIII,PC,PS; moreover, we determined also the levels of homocysteine, the presence of Lupus Anticoagulant (by mean of DRVVT and Silica Clotting Time) and ACA of IgG type as well as the Plasminogen levels. Furthermore, blood samples were also analysed by PCR technique for the presence of Factor V Leiden, the G20210A Factor II mutation and the C677T mutation in the MTHFR gene. Surprisingly, patients with MTHFR 677TT homozygosis had a significantly higher prevalence of occluded infarct artery (73%) vs those with MTHFR 677CT/CC genotype (30%, P=0.0008); frequency of MTHFR 677TT homozygosis was 4-fold higher in patients with occluded vs those with a patent vessel (40% vs 10%, P=0.0008). MTHFR 677TT genotype predicted the risk of failed thrombolysis with a specificity of 90% and multivariate analysis showed that MTHFR 677TT homozygosis was independently associated with an occluded artery (odds ratio 3.8, 95% confidence interval 1.1–9.1; P=0.03). None of the other studied factors at multivariate analysis influenced the thrombolysis failure. Moreover, patients with occluded infarct vessel and MTHFR 677TT genotype had the highest homocysteine levels (P=0.011). Our findings indicate that in patients with acute myocardial infarction, MTHFR 677TT homozygous is independently associated with a persistently occluded infarct-related artery after thrombolysis.

A prothrombotic phenotype in the Copenhagen rat strain

Introduction Experimental and epidemiologic studies have identified several potential genetic components for increased thrombotic risk. Studies of thrombosis often use rat models without considering the effect of strain differences on thrombotic propensity. Materials and methods A comparison of in vivo thrombotic occlusion after small-vessel anastomosis was made between age/weight-matched male Copenhagen and Lewis rats. Results One-day thrombotic occlusion rates were significantly higher in Copenhagen arteries (67%) and veins (100%) compared to Lewis arteries (8%) and veins (50%), respectively. Single-bolus intravenous heparin (150 units/kg body weight) had a slight effect on reducing occlusion rates in Copenhagen rats (50% and 67% for arteries and veins, respectively), while occlusion was totally prevented by heparin in both vessel types of Lewis rats (0% occlusion). In vitro assays for platelet aggregation and coagulation revealed no apparent differences between these two rats strains, although AT-III levels were slightly higher in Copenhagen rats, contrary to the prothrombotic state. Conclusions These findings indicate a profound prothrombotic tendency in the Copenhagen rat strain and support a broader investigation of the genetic basis of this thrombotic potential.

Hemostatic Side Effects of High-Dose Methotrexate in Childhood Acute Lymphoblastic Leukemia

The purpose of this study is to investigate the hemostatic side effects of HDMTX. Between 2001 and 2002, 20 children with acute lymphoblastic leukemia at the Dr. Sami Ulus Children's Hospital, Department of Pediatric Hematology and Oncology, treated according to the St. Jude ALL XIII protocol were eligible to this study. Methotrexate at a dose of 2 g/m2was infused over 24 hours. Coagulation screening studies included prothrombin time (PT), APTT, fibrinogen, fibrin degradation product (D-Dimer), factor II, factor V, factor VII, factor VIII, factor IX, factor X, PC, PS, AT-III determinations before HDMTX therapy (PreT), 1 day after (PostT1D), and 1 week after (PostT1W) the end of the HDMTX infusion. We found that PT and APTT were prolonged, PC, PS, and AT-III levels were decreased with a slight increase in D-Dimer 1 day after the administration of HDMTX and all of them returned to the normal levels by 7 days. In addition we found that FVII, FIX, FX were significantly decreased 1 day after therapy and normalised by 7 days.