Activated FVII-Antithrombin Complex and Tissue Factor mRNA As Potential Markers of Severe Thrombo-Hemorrhagic Syndrome in APL Patients

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1195-1195
Author(s):  
Laura Russo ◽  
Marina Marchetti ◽  
Carmen Julia Tartari ◽  
Eros Di Bona ◽  
Alessandro Rambaldi ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Tissue Factor ◽  
Induction Therapy ◽  
Peripheral Blood ◽  
Plasma Levels ◽  
Factor Vii ◽  
Remission Induction ◽  
Control Group ◽  
Activity Measurement ◽  
D Dimer

Abstract Abstract 1195 Introduction: Tissue Factor (TF) expressed by acute promyelocytic leukemia (APL) cells may have an important role in the pathogenesis of the life-threatening coagulopathy typical of the onset of this disease. In APL patients, the remission induction differentiating therapy with all-trans-retinoic acid (ATRA) downregulates TF expression by APL blasts and produces a simultaneous correction of the hypercoagulation and thrombo-hemorrhagic syndrome (THS). However the rate of early deaths due to the THS is still relevant in this disease. Therefore characterizing the coagulopathy and identifying predictive markers remain a critical issue. Aim: In this study, in newly diagnosed APL patients, we prospectively evaluated the rate of hemorrhage and thrombosis, in the first month after diagnosis, in relation to the plasma levels of activated factor VII-antithrombin complex (FVIIa-AT), a new parameter which may reflect the degree of TF exposure and activity. TF mRNA in the peripheral blood APL cells was also evaluated as well as the plasma levels of thrombin-antithrombin complex (TAT) and D-dimer, as additional coagulation markers. Methods: Fifty-four consecutive APL patients receiving ATRA+Idarubicin for the remission induction (GIMEMA protocol AIDA2000) were enrolled. Blood samples from 26 of these patients (F/M= 10/16) were obtained at the onset (T0) of the disease, and on days 7, 14 and 28 (T7, T14, T28) of remission induction therapy. Twenty-five healthy subjects acted as a control group. Plasma FVIIa-AT, TAT, and D-dimer were measured by ELISA. TF mRNA expression by peripheral blood mononuclear cells (PBMC) was evaluated by real time-polymerase chain reaction. Results: At the disease onset 8/54 patients had early major hemorrhages (15%), including 3 (5.5%) fatal intracranial bleeding and 5 non-fatal major bleeding (9.2%); 3/54 had thrombosis (1 fatal Budd-Chiari syndrome, and 2 non-fatal events). Two more patients developed deep vein thrombosis at 7 and 14 days of induction therapy (3.7%), respectively. Of the 26 patients included in the laboratory study, 3 had thrombosis at the diagnosis of APL. At T0, before starting therapy, the levels of FVIIa-AT as well as those of TAT and D-dimer were significantly higher in APL patients compared to controls (p<0.05). However, while the levels of FVIIa-AT complex were lower in patients with thrombosis than in those without (120±50 vs 332±75 ng/ml), differently the levels of TAT and D-dimer were not different between two groups, indicating that the FVIIa-AT is more sensitive to the consumption coagulopathy compared to the other thrombotic markers. During ATRA therapy the levels of FVIIa-AT were progressively decreased at T7 and T14, and dropped significantly at T28 (p<0.05 vs T0); TAT and D-dimer levels were also decreased starting from T7 to T28 (p<0.05 vs T0). In addition, in APL PBMC from 9 patients, the levels of TF mRNA, initially elevated compared to healthy control PBMC (p<0.05), were significantly decreased by 68% and 90%, at T7 and T28, respectively. Conclusions: These results confirm a significant rate of early deaths in APL due to the coagulopathy. FVIIa-AT complex levels paralleled TF mRNA expression and may therefore be a useful surrogate tool for the TF activity measurement in the peripheral blood. In addition, the study shows that, among hypercoagulation markers, which are overall elevated at the onset of APL, the ‘low’ levels of plasma FVIIa-AT complex is the only parameter able to distinguish patients at highest risk of severe THS. Although the small size of the study did not allow to calculate the predictive value of this marker, FVIIA-AT complex may be a promising simple candidate biomarker to test for the predictive risk of lethal/severe THS in large prospective studies of APL patients. Disclosures: No relevant conflicts of interest to declare.

Marked Increase of Activated Factor VII in Uremic Patients

1995 ◽  
Vol 73 (05) ◽  
pp. 763-767 ◽  
Author(s):  
Kazuomi Kario ◽  
Takefumi Matsuo ◽  
Miyako Matsuo ◽  
Masanobu Koide ◽  
Tsutomu Yamada ◽  
...  
Keyword(s):  
Renal Function ◽  
Endothelial Cell ◽  
Tissue Factor ◽  
Plasma Levels ◽  
Cell Injury ◽  
Factor Vii ◽  
Control Group ◽  
Endothelial Cell Injury ◽  
Activated Factor Vii ◽  
Uremic Patients

SummaryWe investigated plasma activated factor VII (FVIIa) levels in uremic patients (nondialysis group: n = 38; dialysis group: n = 36) and healthy controls (n = 32). We also measured the plasma levels of thrombomodulin (an indicator of endothelial cell injury) and tissue factor. Plasma FVIIa showed a marked increase in the nondialysis group (mean [95% confidence interval]: 4.6 [4.1-5.1] ng/ml, p <0.0001) with the progressive impairment of renal function, as indicated by the serum creatinine level, when compared with the 32 controls (2.8 [2.5-3.1] ng/ml), and was further increased in the dialysis group (6.1 [5.5-6.8] ng/ml, p <0.001 vs. nondialysis group). Plasma levels of thrombomodulin and tissue factor were also higher in the nondialysis group than the control group, and were further increased in the dialysis group. Plasma tissue factor levels did not show any correlation with FVIIa or thrombomodulin in both the nondialysis and dialysis groups. Thus, circulating tissue factor appears to be released by a different mechanism from thrombomodulin and may not contribute to the direct activation of factor VII in uremic patients. On the other hand, the plasma level of thrombomodulin was positively correlated with that of FVIIa in the nondialysis group, and this correlation was independent of renal function. Thus, enhanced conversion of factor VII zymogen to FVIIa, probably related to endothelial cell injury, may be a risk factor for cardiovascular events in uremic patients.

The Effect of Very-low-dose Warfarin on Markers of Hypercoagulation in Metastatic Breast Cancer: Results from a Randomized Trial

1998 ◽  
Vol 79 (01) ◽  
pp. 23-27 ◽  
Author(s):  
M. N. Levine ◽  
R. Consonni ◽  
G. Gritti ◽  
F. Delaini ◽  
E. Oldani ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Randomized Trial ◽  
Plasma Levels ◽  
Low Dose ◽  
Stage Iv ◽  
Factor Vii ◽  
Control Group ◽  
Dose Warfarin ◽  
Stage Iv Breast Cancer ◽  
D Dimer

SummaryMalignancy is a risk factor for thromboembolism and anti-cancer chemotherapy can increase this risk. Prophylaxis of thrombosis with very-low-dose warfarin given concurrently with chemotherapy has a significantly reduced rate of thromboembolism in a randomized trial in women with stage IV breast cancer. In a group of 32 patients randomized in one center (16 subjects on warfarin and 16 on placebo), we have prospectively studied the plasma levels of: 1. Markers of ‘in vivo’ clotting activation (thrombin-antithrombin complex [TAT], prothrombin fragment 1+2 [F1+2] and D-dimer), 2. Factor VII (FVII), and 3. Natural anticoagulants (protein C [PC] and antithrombin [AT]). The aims of this study were: 1. to examine whether laboratory tests predicted those patients who developed thrombosis, and 2. to evaluate the effect of very-low-dose warfarin on hemostatic variables. The patients’ hemostatic parameters were evaluated before entry into the study and after starting chemotherapy ± prophylaxis, before each course for nine courses. Before-treatment results were compared to those of a sex and age-matched non-cancer control group. There was a significant elevation of plasma levels of TAT (p <0.001), F1+2 (p <0.001), D-dimer (p <0.0001) and FVIIa (p <0.05), as well as an increase of FVII proteolysis (p <0.05), whereas plasma PC and AT concentrations were not different from controls. After starting chemotherapy, markers of clotting activation were progressively lower in the group receiving warfarin prophylaxis compared to the group on placebo. Differences between the groups became statistically significant (p <0.01) after the 4th course of chemotherapy. Deep vein thrombosis occurred in two patients in the placebo arm. The results of this study indicate that before therapy, an hypercoagulable state is present in stage IV breast cancer, and after starting chemotherapy, abnormalities of hypercoagulation markers persist, however they are reduced by very-low-dose-warfarin. None of the laboratory variables could predict thrombosis in the single patient.

PROLACTIN IN MAINTENANCE OF THE CORPUS LUTEUM OF EARLY PSEUDOPREGNANCY IN THE GOLDEN HAMSTER

1981 ◽  
Vol 90 (2) ◽  
pp. 145-150 ◽  
Author(s):  
K. H. HARRIS ◽  
B. D. MURPHY
Keyword(s):  
Single Dose ◽  
Corpus Luteum ◽  
Golden Hamster ◽  
Peripheral Blood ◽  
Plasma Levels ◽  
Progesterone Level ◽  
Control Group ◽  
Blood Samples

The role of prolactin in the maintenance of the corpus luteum of pseudopregnancy was studied in the golden hamster. Nine groups of seven to fourteen animals each received 1 mg bromocriptine at 11.00 h on days 1, 2 or 3 of pseudopregnancy (three groups for each day). On each day of treatment with bromocriptine, one group of hamsters was injected with bovine prolactin 4 h before bromocriptine, and one group received prolactin 4 h before bromocriptine for three consecutive days following treatment with bromocriptine. One group received bromocriptine only. These nine groups were compared with a control group of animals given 0·85% saline instead of bromocriptine and prolactin. Peripheral blood samples were taken from all hamsters at 11.00 h on days 3, 4, 5 and 6 of pseudopregnancy and plasma levels of progesterone were determined by radioimmunoassay. Luteolysis, indicated by a decline in progesterone level by 24 or 48 h after treatment with bromocriptine, occurred in all hamsters given bromocriptine alone, whether it was administered on day 1, 2 or 3. Pretreatment with a single dose of prolactin did not mitigate the bromocriptine-induced fall in progesterone. In the majority of cases, pretreatment with prolactin plus daily doses of prolactin maintained the progesterone at levels not different from saline-treated hamsters. These data suggest that prolactin is a necessary luteotrophin during early pseudopregnancy without which luteolysis ensues.

Study of Sequential Treatment of Newly Diagnosed De Novo AML Patients with DA and CAG Regimens as Remission Induction Therapy.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4630-4630
Author(s):  
Hui ping Sun ◽  
Wei Hong Liu ◽  
Jun min Li ◽  
Qiu sheng Chen ◽  
Yu Chen
Keyword(s):  
Bone Marrow ◽  
Induction Therapy ◽  
Peripheral Blood ◽  
De Novo ◽  
Classification Criteria ◽  
Sequential Treatment ◽  
Remission Induction ◽  
Newly Diagnosed ◽  
Fab Classification ◽  
De Novo Aml

Abstract Objectives To evaluate the efficacy and safety of sequential treatment of newly diagnosed de novo AML patients with DA and CAG regimens as induction therapy. Methods Those who were newly diagnosed as de novo AML (FAB classification criteria) were enrolled and DA regimen chemotherapy were administered. Bone marrow aspirates were performed and BM smears were examined at 48 hours since the end of chemotherapy. If severe hypocellularities were not achieved, the percentage of blasts in BM was between 20%–60% and peripheral WBC was in the range of (0.5–10) x109/L, the patients would receive CAG regimen therapy since 72 hours. Patients’ general status and the important parameters, such as peripheral blood count, liver function, renal function, thrombosis and hemostasis parameters were monitored throughout the course of the treatment and thereafter. When the clinical symptoms were relieved and peripheral blood counts returned to normal, or it was the end of the second or third week since the end of the CAG regimen, Bone marrow were examined again to evaluate the efficacy of the sequential therapy. Results 14 patients consisted of 9 male and 5 female patients were enrolled. Out of them, 2 were M1, 5 M2, 4 M4 and 3 M5 according to FAB classification criteria. Median of blasts in BM were 38.5%(20%–60%) before CAG regimen. Of the 14 patients, 10 reached CR, 2 PR and 2 NR. CR rate was 71.4% (10/14) and total response rate was 85.7%(12/14). Time to achieve CR was on 15th(14th–29th)day medianly since the end of the treatment. During the CAG therapy courses, the nadir of peripheral blood cell counts and the time when it occurred were as follows: WBC 1.0(0.2–3.5)(x109/L),10(1–23)(d); Hb 57.5(44–69) (g/L), 10(1–27)(d)and PLT 11.5(10–65)(x109/L), 12(3–23)(d), respectively. Neutropenia (WBC<1.0x109/L) and thrombocytopenia (PLT<20.0x109/L) were lasted for 0(0–24) and 11(0–21)days, respectively. Median units of transfusions of platelets and red blood cells required by each patient were 3(0–10)(u) and 4(0–12)(u), respectively. The most commonly observed side effect of the regimen was bone marrow proliferation inhibition. Infections, usually respiratoy tract infections, were the second. However, sepsis was rare, which appeared in 1 out of 14 patients. Conclusions DA and CAG regimens sequential treatment as remission induction chemotherapy in patients with newly diagnose de novo AML was highly effective and well tolerated. It would be beneficial for those who might not be sensitive enough to DA regimen chemotherapy only.

Assessment of Thalidomide Therapy Effect on Platelet Activation and Selected Blood Coagulation Parameters in Multiple Myeloma Patients

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5181-5181
Author(s):  
Marta Robak ◽  
Jacek Trelinski ◽  
Krzysztof Chojnowski
Keyword(s):  
Multiple Myeloma ◽  
Platelet Count ◽  
Factor Viii ◽  
Platelet Activation ◽  
Factor Vii ◽  
Control Group ◽  
High Dose ◽  
Closure Time ◽  
Therapy Effect ◽  
D Dimer

Abstract Background: Patients with multiple myeloma are at relatively high risk of developing thromboembolic events (TEE). These life-threatening complications may arise from hypercoagulability associated with malignancy and/or may be connected with anticancer therapy. The risk of developing TEE appears to be particularly high during treatment with thalidomide alone or combined with chemotherapy and/or high-dose dexamethasone. The pathogenesis of thalidomide-related thrombosis in myeloma patients remains unexplained. Some authors suggest that platelet activation can contribute to development of this complication in multiple myeloma patients on thalidomide therapy but until now it has not been a subject of investigation. Patients and methods: The study was performed in 20 patients with multiple myeloma. The tests were done at diagnosis and after one month of thalidomide therapy at a dose of 100–200 mg/24h. All patients had normal renal function and did not take drugs affecting platelet function. The control group consisted of 15 healthy subjects of similar age. In each patient closure time with ADP/Collagen and Epinephrine/Collagen cartridges by PFA-100 method was assessed. Platelet expression of membrane activation marker P-selectin (CD62p) on resting platelets and after stimulation with ADP/Collagen and Epinephrine/Collagen was analyzed by flow cytometry. Additionally, activity of factor VII, factor VIII and von Willebrand factor (vWF), concentration of fibrinogen and D-dimer, and platelet count were evaluated. Results: The mean PFA-100 closure time was significantly shortened with ADP/Collagen (87.2 ±17.1 s vs 100.4 ± 19.3 s, p=0.008) and Epinephrine/Collagen cartridges (118.5 ± 20.3 s vs 132.2 ± 27.9 s, p=0.04) after one month of therapy in comparison to baseline. The median CD62p percentage increased markedly after treatment-on resting platelets 5.1 (0.76–22.2) vs 3.6 (0.1–21.5) p=0.03. and after stimulation with Epinephrine/Collagen 16.6 (2.3–57.3) vs 11.1 (1.4–19.5) p=0.03. The observed increased P-selectin expression after ADP/Collagen stimulation 26.3 (8.5–42.8) vs 19.7 (1.0–35.4) was not statistically significant. The median values of P-selectin expression at diagnosis and after thalidomide therapy were also higher than in the control group. The results of factor VIII, vWF activity, fibrinogen and D-dimer concentration did not differ markedly before and after therapy. Significantly lower mean activity of factor VII (p=0.004) and higher mean platelet count (p=0.03) after therapy were observed. Conclusions: These results demonstrate that platelet activation is one of the pathogenetic factor of thalidomide-related thrombotic complications and can explain some observations that acetylsalicylic acid may protect against TEE during myeloma treatment with thalidomide.

mRNA analysis of genes responsible for idiopathic hypogonadotrophic hypogonadism

2016 ◽  
Vol 62 (5) ◽  
pp. 40-41
Author(s):  
Anna S. Loktionova ◽  
Natela G Eneva ◽  
Karina A. Khusniyarova ◽  
Lidia N Nefedova ◽  
Alexander I. Kim ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Peripheral Blood ◽  
Expression Profiles ◽  
Pubertal Development ◽  
Hypogonadotropic Hypogonadism ◽  
Body Weight Loss ◽  
Dna Lesions ◽  
Control Group ◽  
Reproductive Axis ◽  
Development Methods

Background. Hypogonadotropic hypogonadism (HH) is a disorder characterized by delayed or absent pubertal development due to pathology of the hypothalamic-pituitary-gonadal axis. HH may be both congenital (Kallmann’s syndrome) and sporadic. Congenital or isolated HH is divided into with anosmia/hyposmia (KS) and with normal olfaction (nIHH). Nowadays several tens of genes involved in the functioning of the reproductive axis are known. However DNA lesions can be found just in 5-15% of such cases of HH.Aim. So we decided to measure mRNA expression of several genes which can be found in leukocytes of peripheral blood - namely GNRHR and GNRH1 (are necessary for adequate biological effect of GnRH); PROK2 and CHD7 (are responsible for the migration of GnRH neurons), WDR11 and DUSP6 (are involved in normal sexual development).Methods. A quantitative determination of mRNA expression of these genes were comlpeted in the fresh peripheral blood sample by PCR in real time.Results. Examined patients: 9 women with hypogonadotropic hypogonadism (age from 18 to 28 y.o.); duration of the disease from 2 to 15 years; 3 of them – amenorrhea I and 6 – amenorrhea II. Reasons of amenorrhea II were: stress, excessive exercises, rapid body weight loss, past use of oral contraceptives. The control group: 19 healthy women; age from 19 to 37 y.o.; with regular ovalutory menstrual cycle, some of them have children. mRNA expression of examined genes differed from normal patterns in each case of hypogonadotropic hypogonadism. Changes in GNRHR, GNRH1 and DUSP6 mRNA expression were found in most of cases. However variations of mRNA expression were multidirectional in each case and there was no similarity among expression profiles of patients according to amenorrhea type or anamnestic factors.Conclusions. According to our preliminary results, in women with hypogonadotropic hypogonadism the functional activity damage of “reproductive-responsible” genes could be found in each case. Probably mRNA expression measuring could be a perspective method for proving hypothalamo-pituitary level of reproductive disorders and may help to determine which genes should be tested for DNA impairment.

A Comprehensive Study on Hemostasis in CAPD Patients Treated with Erythropoietin

2002 ◽  
Vol 22 (5) ◽  
pp. 582-592 ◽  
Author(s):  
Jolanta Malyszko ◽  
Ewa Suchowierska ◽  
Jacek S. Malyszko ◽  
Michal Mysliwiec
Keyword(s):  
Platelet Aggregation ◽  
Tissue Factor ◽  
Von Willebrand Factor ◽  
Factor Vii ◽  
Clot Lysis ◽  
Control Group ◽  
Primary Role ◽  
Baseline Values ◽  
Von Willebrand ◽  
Willebrand Factor

Objective Bleeding diathesis and simultaneous thrombotic complications may be seen in dialyzed patients. Erythropoietin (EPO) may shift the precarious balance of the hemostatic system toward thrombosis. Platelets and tissue factor (TF) play a major role in plug formation. Tissue factor pathway inhibitor (TFPI) appears to play a primary role in regulating TF-induced coagulation. Thrombin activatable fibrinolysis inhibitor (TAFI) is a key protein linking coagulation and fibrinolysis. The aim of the study was to assess whether 6 months of EPO therapy affects platelet function, that is, platelet aggregation and P-selectin level; moieties of the extrinsic coagulation pathway: TF, TFPI, and TFPI/Xa complexes, and factors VII and X; markers of ongoing coagulation: thrombin–antithrombin complexes (TAT) and prothrombin fragments 1+2; a marker of ongoing fibrinolysis: plasmin–antiplasmin complexes (PAP); fibrinolytic activity: euglobulin clot lysis time (ECLT); and markers of endothelial cell injury: von Willebrand factor, thrombomodulin, E-selectin, and TAFI, in continuous ambulatory peritoneal dialysis (CAPD) patients. Patients and Methods 22 patients on CAPD were given EPO 6000 U/week. 12 patients with chronic renal failure and 12 healthy volunteers served as control groups. All parameters were studied before, and after 1, 3, and 6 months of EPO therapy. Setting Department of Nephrology and Internal Medicine, Medical Academy of Bialystok, Poland. Results Platelet aggregation in whole blood did not change significantly during EPO treatment. A significant rise in arachidonic acid-induced platelet aggregation in platelet-rich plasma was observed after 3 and 6 months, and in collagen-induced platelet aggregation after 6 months of EPO therapy, compared to the baseline values. The TFPI concentration decreased significantly after 6 months of EPO therapy. The activity of factor VII increased transiently after 1 month of EPO therapy, compared to the baseline values. The TAFI concentration and activity in the CAPD group were significantly higher than in the control group. Erythropoietin therapy resulted in a significant decrease in TAFI concentration and activity after 6 months of EPO treatment. The ECLT was shortened significantly as early as after 1 month of EPO therapy. Thrombomodulin, von Willebrand factor concentration and activity, PAP, TAT, TFPI/Xa complexes, prothrombin fragments 1+2, factor X activity, P-selectin, E-selectin, and lipoprotein(a) did not change significantly during EPO treatment. Conclusion Erythropoietin treatment has a minimal effect on hemostasis in CAPD patients. A tendency toward a decline in TAFI is of unknown clinical relevance so far, and awaits further research.

scholarly journals Assessing Circulating Factor VIIa–Antithrombin Complexes in Acute Ischemic Stroke: A Pilot Study

2016 ◽  
Vol 23 (4) ◽  
pp. 351-359 ◽  
Author(s):  
Artur Słomka ◽  
Milena Świtońska ◽  
Władysław Sinkiewicz ◽  
Ewa Żekanowska
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Tissue Factor ◽  
Plasma Levels ◽  
Factor Viia ◽  
Venous Blood ◽  
Factor Vii ◽  
Enzyme Linked Immunosorbent Assay ◽  
Hemostatic Markers ◽  
Total Tissue

Aim: The goal of this study was to determine the levels of factor VII (FVII), factor VIIa–antithrombin complexes (FVIIa-AT), total tissue factor (TF), and tissue factor-bearing microparticles (MPs-TF) in patients with acute ischemic stroke. Further, we sought evidence of an association between hemostatic markers, time of blood sampling, type of treatment, and patient outcomes. Methods: Venous blood samples were collected from 33 patients on the first day and on the seventh day after stroke diagnosis. Age-matched controls were also included (n = 20). Plasma levels of FVII, FVIIa-AT, total TF, and MPs-TF were measured by enzyme-linked immunosorbent assay. We divided patients into 2 groups: thrombolysis group (n = 13) and nonthrombolysis group (n = 20). Furthermore, evaluation of the National Institutes of Health Stroke Scale and the Barthel Index was performed on the first day and the seventh day. Results: Patients with ischemic stroke showed significantly lower plasma FVII, FVIIa-AT, and total TF levels than controls (median, 112.25% vs 132.05%, P = .004; 107.97 pmol/L vs 154.94 pmol/L, P < .001; 81.74 pg/mL vs 105.71 pg/mL, P < .001, respectively). In contrast, levels of plasma MPs-TF were significantly higher in patients with stroke compared to healthy controls (1.60 pg/mL vs 0.74 pg/mL, P < .001). Additionally, the thrombolysis group had lower FVII levels on the seventh day compared to the first day (median, 109.80% vs 115.74%, P = .04). Conclusion: Factor VII, FVIIa-AT, and total TF are decreased, while MPs-TF are elevated in patients with ischemic stroke. We observed a slight but significant effect of alteplase on FVII plasma levels.

scholarly journals Implications of Hemostasis Disorders in Patients with Critical Limb Ischemia—An In-Depth Comparison of Selected Factors

2020 ◽  
Vol 9 (3) ◽  
pp. 659
Author(s):  
Radosław Wieczór ◽  
Arleta Kulwas ◽  
Danuta Rość
Keyword(s):  
Tissue Factor ◽  
Plasminogen Activator ◽  
Critical Limb Ischemia ◽  
Systemic Disease ◽  
Limb Ischemia ◽  
Coagulation System ◽  
Control Group ◽  
Blood Coagulation Disorders ◽  
Plasminogen Activator Inhibitor 1 ◽  
D Dimer

Background: Atherosclerosis is a systemic disease. Among patients with atherosclerosis, those suffering from peripheral arterial disease (PAD) represent a group of individuals with particularly high death risk, especially during the course of critical limb ischemia (CLI). In the pathogenesis of PAD/CLI complications, blood coagulation disorders play a significant role. The study aim was to examine the activation of the coagulation system depending on tissue factor (TF) in patients with CLI as compared with those with intermittent claudication (IC). Methods: Before initiating proper treatment (invasive or maintenance), blood samples were collected from 65 patients with CLI and 15 with IC to measure the following selected hemostasis parameters: concentrations and activation of tissue factor (TF Ag and TF Act) and tissue factor pathway inhibitor (TFPI Ag and TFPI Act), concentrations of thrombin–antithrombin complex (TAT Ag) and fibrinogen, platelet count (PLT), and concentrations of tissue-plasminogen activator (t-PA Ag), plasminogen activator inhibitor 1 (PAI-1), and D-dimer. The control group included 30 healthy volunteers (10 female/20 male). Results: The values of all analyzed parameters (except for lower TFPI Act) were significantly higher in the blood of PAD patients (with respect to PLT only in the CLI subgroup) in comparison with healthy subjects. The blood of patients with CLI as compared to the IC subgroup revealed much higher concentrations of TF Ag (p < 0.001), with slightly decreased TF Act, significantly lower concentrations of TFPI Ag (p < 0.001), slightly increased TFPI Act, and significantly higher levels of TAT Ag (p < 0.001), fibrinogen (p = 0.026), and D-dimer (p < 0.05). Conclusions: In patients with CLI, we can observe coagulation activation and a shifting balance toward prothrombotic processes. Furthermore, increased concentrations of D-dimer suggest a secondary activation of fibrinolysis and confirm the phenomenon as a prothrombotic condition with heightened fibrinolysis.

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