Patients with the Antiphospholipid Syndrome (APLS) Show Hypercoagulability Due to Hypofibrinolysis and Increased Fibrin Generation, but Thrombin Generation Is Variable

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3833-3833
Author(s):  
Jennifer L Curnow ◽  
Marie-Christine Morel-Kopp ◽  
Ninfa Rojas ◽  
Margaret Aboud ◽  
Christopher Ward
Keyword(s):  
Lupus Anticoagulant ◽  
Thrombin Generation ◽  
Thrombotic Event ◽  
Anticardiolipin Antibodies ◽  
Hypercoagulable State ◽  
Control Group ◽  
Royal North Shore Hospital ◽  
Thrombin Generation Assay ◽  
Healthy Donors ◽  
History Of

Abstract We have previously demonstrated hypercoagulability utilizing a global haemostatic assay, the Overall Haemostatic Potential (OHP) in a heterogenous population of patients with a demonstrable lupus anticoagulant. Our aim in this study was to determine whether the OHP assay demonstrated a persistent hypercoagulable state in a well-defined prospective population with APLS and whether global assays were able to predict the occurrence of thrombotic complications. Informed consent was obtained and blood was collected on three occasions, three months apart from 54 patients with APLS, recruited from Haematology clinics at Royal North Shore Hospital, Sydney, Australia between May 2005 and November 2007. Clinical data was collected including history of prior and subsequent thrombotic events. Two control groups consisted of 200 healthy blood donors and 20 patients with autoimmune disorders, but no history of thrombosis. Assays performed were PT, INR, APTT, FVIIIc, lupus anticoagulant assay (LAC), anticardiolipin antibodies (ACLA), b2-glycoprotein1 antibodies (B2GP1), a thrombin generation assay (Calibrated Automated Thrombogram, CAT) and the OHP assay which utilizes thrombin (0.03 IU/ml) and rt-PA (350 ng/ml) to trigger fibrin generation and fibrinolysis, respectively, in platelet poor plasma. Change in optical density in microtitre wells is measured over 60 minutes. Statistical analysis involved calculation of means, SD, T-tests and paired T-tests utilizing SPSS v16.0. Fifty percent of APLS patients were male, compared with 10% of the autoimmune control group. APLS had been diagnosed on the basis of persistent antiphospholipid antibodies and at least one thrombotic event: VTE (n=46), ATE (n=6) or recurrent late miscarriage (n=2). Number of thrombotic events prior to study entry ranged form 1 to 6 per patient, with 49/66 events unprovoked. Samples from APLS patients on anticoagulation (OAC, n=35) were analysed separately from those not anticoagulated (n=19). Global assay results for samples collected at different time points were stable, with no significant differences on paired T-test. APLS patients had significantly shorter PT, higher fibrinogen, increased fibrin generation and reduced fibrinolysis parameters (p<0.001), compared with healthy donors. The autoimmune control group also showed hypercoagulable OHP parameters compared with healthy donors (p<0.001), with assay results comparable to those in APLS patients, not on OAC. The only thrombin generation assay parameter significantly increased in APLS patients, not on OAC, compared with controls was peak thrombin (266 vs 298 nM, p=0.016). However thrombin generation was significantly suppressed in those on OAC (p<0.001). Only one patient had recurrent DVT during the study. The OHP assay identifies a hypercoagulable state in APLS patients with reduced fibrinolysis and increased fibrin generation, even when anticoagulated. The calibrated automated thrombogram (CAT) showed increased peak thrombin generation in APLS patients not on OAC but endogenous thrombin potential (ETP) was not significantly elevated. Thrombin generation was suppressed by OAC therapy. These global assays show differential results in patients with APLS. More prolonged follow up will be necessary to determine whether the assays predict recurrent thrombotic events and are useful in risk stratification of APLS patients.

scholarly journals Cerebrovascular events in patients with isolated anti-phosphatidyl-serine/prothrombin antibodies

2021 ◽  
Author(s):  
Massimo Radin ◽  
Alice Barinotti ◽  
Silvia Grazietta Foddai ◽  
Irene Cecchi ◽  
Elena Rubini ◽  
...  
Keyword(s):  
Antiphospholipid Syndrome ◽  
Antiphospholipid Antibodies ◽  
Lupus Anticoagulant ◽  
Clinical Utility ◽  
Thrombin Generation ◽  
Phosphatidyl Serine ◽  
Positive Test ◽  
Thrombin Generation Assay ◽  
Cerebrovascular Events ◽  
History Of

AbstractThe interest of extra-criteria antiphospholipid antibodies is growing, especially in patients negative for conventional antibodies. In this study we aimed to assess the clinical utility of anti-phosphatidyl-serine/prothrombin antibodies (aPS/PT) testing in patients negative for Beta2-Glycoprotein 1(β2GPI)-dependent tests, for identifying antiphospholipid syndrome (APS) patients that developed cerebrovascular events (CVE). When screening APS patients attending our center, out of 119 aPS/PT IgG/IgM-positive patients, thus patients negative for aβ2GPI and aCL, 42 patients (35%) tested negative for β2GPI-dependent tests and were tested with thrombin generation assay (TGA). Ten patients (24%), with isolated aPS/PT IgG/IgM, had a history of CVE. Lupus anticoagulant (LA)-positive test was more frequently observed in patients with CVE (8/22 vs. 2/20; p = 0.045). Out of the 10 patients who experienced CVE, 3 patients were aPS/PT IgG positive (all LA positive), and 8 patients were aPS/PT IgM positive (6/8 LA positive). One patient was positive for both aPS/PT IgG and IgM. LA-positive patients had only high titers of aPS/PT IgG/IgM, all of them being ≥ 80 U/ml, while the 2 LA-negative patients were aPS/PT IgM positive with medium titers [40–60 U/ml]. LA-positive patients had significantly altered TGA profile when compared to those who were LA negative, considering all TGA parameters. LA-positive patients had significantly higher tLag (8.4 ± 3.3 min vs. 6.6 ± 1.8 min; p = 0.046), higher tPeak (14 ± 4.3 min vs. 11 ± 2.7 min; p = 0.015) and lower Peak (207 ± 152 nM vs. 356.3 ± 104.7 nM; p < 0.001) and lower AUC (2109.7 ± 1006.9 nM vs. 2772.5 ± 776.8 nM; p = 0.033). The use of aPS/PT might be of help in identifying patients with CVE and APS, as also confirmed by TGA testing.

Application of Thrombomodulin-Thrombin Generation to Diverse Abnormalities of the Protein C System

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 31-32
Author(s):  
Marilyn J Manco-Johnson ◽  
Linda Jacobson ◽  
Dianne Thornhill ◽  
Christine Baird ◽  
Beth Boulden Warren
Keyword(s):  
Family History ◽  
Lupus Anticoagulant ◽  
Protein C ◽  
Thrombin Generation ◽  
Conflicts Of Interest ◽  
Positive Family History ◽  
Factor V Leiden ◽  
Healthy Controls ◽  
Blood Draw ◽  
History Of

Background: Increased thrombin generation is an interesting candidate as a potential indicator of hypercoagulability and thrombosis risk. Increased thrombin generation using the calibrated automated thrombogram (CAT) has been reported in antithrombin deficiency but the CAT does not reflect protein C deficiency without the addition of thrombomodulin (TM). TM activates protein C (PC) in the CAT and reduces thrombin generation. Objective: The objective of this study was to determine the capacity of the TM-augmented CAT to detect defects in various protein C system components; the lupus anticoagulant was also investigated as a cause of decreased protein C activation. Methods: The CAT-TM was performed with reagents and methods per the manufacturer's instructions using 5 pM tissue factor and TM (Stago). Other assays included: PC (chromogenic), free protein S (PS, LIA), activated protein C resistance (aPTT-based clotting assay), factor V Leiden (FVL PCR) and lupus anticoagulant (LA, dRVVT and Staclot LA, Stago). Platelet poor plasma samples were obtained from the biobank of a consented prospective inceptional cohort study of thrombosis and thrombophilia or a positive family history of either (ThromboPICS #05-0339); samples from healthy controls with no personal or family history of thrombosis or thrombophilia were collected on a consented protocol (#09-0816). Samples from participants on therapeutic inhibitors of factor Xa or thrombin were treated with appropriate neutralizers; no sample was tested on warfarin. Clinical data included gender, age (&lt; 18 versus ≥ 18 years), history of thrombosis, timing of sample from most recent thrombosis (acute &lt; 14 days; subacute 14-90 days; or chronic &gt; 90 days) and use of anticoagulants at the time of the blood draw. Tests for violations of normality were negative. Therefore, results of cohorts versus controls were compared with independent sample t-test and subgroup analyses relative to control used One-Way ANOVA. Post-hoc comparisons of each subgroup to the controls were collected for multiple comparisons using the Bonferroni correction. Results: Ninety-nine cases and 45 normal controls were studied. Overall half of the cases had a history of thrombosis and 66% of those with thrombosis were on no anticoagulation at the time of testing. Table 1 displays results of the CAT-TM in the 2 control and 6 study groups. Control adults and children showed a mean 50% thrombin reduction in thrombin generation with CAT-TM; overall, persons with protein C system defects showed approximately 25% reduction, with the least reduction of thrombin generation in the cohort of PC deficiency at 19%. Sensitivity of the CAT-TM was 100% for PC deficiency, 81% for LA positivity, 80% for PS deficiency and 72% for FVL positivity with no difference in degree of thrombin reduction between hetero- and homozygous FVL. In addition, we identified 14 individuals with CAT-TM results similar to protein C system defects but with confirmed normal PC, PS, FVL and LA tests. Although 9 of these unknowns had a personal (7) or family (2) history of thrombosis, five came from the healthy controls. The false positive results in 3 adult and 2 pediatric controls conferred a CAT-TM test specificity of 89%. Furthermore, analyses showed no differences in CAT-TM results related to gender, age group, history of thrombosis, age of clot at blood draw (acute, subacute or chronic) or use of anticoagulation at the time of blood draw. Conclusions: The CAT-TM is a useful screening test for defects in the protein C system, including LA, although this test could not discriminate between heterozygous and homozygous FVL. The etiology of positive CAT-TM in normal individuals or individuals with a personal or family history of thrombosis without identified PC system defects is currently unknown and under ongoing investigation. Disclosures No relevant conflicts of interest to declare.

Performance of a New Global Chromogenic Assay for Protein C Pathway (HemosIL ThromboPath) in the Diagnosis of Lupus Anticoagulant and Antiphospholipid Antibodies.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2279-2279
Author(s):  
Pierre A. Toulon ◽  
Isabelle Martin-Toutain ◽  
Jean-Charles Piette ◽  
Marie-Claude Diemert ◽  
Annick Ankri
Keyword(s):  
Antiphospholipid Antibodies ◽  
Arterial Thrombosis ◽  
Lupus Anticoagulant ◽  
Control Group ◽  
Test Results ◽  
Chromogenic Assay ◽  
Apc Resistance ◽  
Significant Difference ◽  
History Of ◽  
Test Result

Abstract Background: The HemosIL ThromboPath assay (Instrumentation Laboratory) is a new chromogenic assay designed to globally evaluate the functionality of the PC pathway. It is based on the ability of endogenous APC generated after activation of PC by a snake venom extract (Protac) to reduce the thrombin generation induced by a reagent containing tissue factor. Briefly, optical density is measured after addition of a thrombin-specific chromogenic substrate in the presence (OD A) or absence (OD B) of Protac. It is recommended by the test manufacturer to express results as the Protac-Induced Coagulation Inhibition percentage (PICI%) which corresponds to the ratio [OD B - OD A]/OD B x 100. Previous studies demonstrated a high sensitivity (over 96%) for PC pathway abnormalities i.e. PC/PS deficiency, and FV Leiden-related APC Resistance, but also for lupus anticoagulant (LA), known to be associated with acquired APC Resistance. The aim of the present study was to evaluate the sensitivity of that assay for antiphospholipid antibodies (APL), especially in connection with the occurrence of thrombotic complications. Actually, APL is a heterogeneous family of antibodies which have a significant impact on coagulation tests (LA) or could be detected using ELISA anticardiolipin assays (ACL). Methods: We retrospectively evaluated the frozen plasma samples from 178 patients previously diagnosed as positive for LA or as having high ACL levels. There were 48 M and 130 F with a mean age=43 years (range 14 – 87). None was on vitamin K-antagonist. Screening for LA, performed according to the ISTH criteria (Thromb Haemost1995;74:1185), was positive in 126 patients (LA+ patients) and negative in 52 patients, all of the latter having high ACL levels (LA- patients). Among LA+ patients, 41 had antiphospholipid syndrome (APS) i.e. 18 with a history of venous thrombosis (VT), 10 with arterial thrombosis (AT), 7 with obstetrical complication (OB) and 6 with combined vascular complications (CVC). The same applied to 39 LA- patients with high APL levels i.e. VT (n=13), AT (n=8), OB (n=12) and CVC (n=6). The control group consisted of 29 age- and sex-matched healthy subjects without a history of vascular or auto-immune disease. The HemosIL ThromboPath assay was performed by an operator blinded of the specific biological test results and of the clinical status of the patients. Results: Test result was significantly lower in LA+ patients than in LA- patients or in healthy controls (Table). Similarly, the percentage of abnormal test results i.e. PICI% below 85.0% as the cut-off value, was significantly higher in LA+ patients than in the two other groups (p&lt;0.0001 in both cases). That cut-off value for the PICI% was determined, according to the recommendations of the reagent manufacturer, as the mean minus 1 SD of the values measured in the plasma of 29 healthy control subjects. Despite significantly lower PICI% in LA- patients than in controls (p&lt;0.05), the proportion of abnormal test results was not significantly different (p&lt;0.10) in these two groups. LA+ Patients (n=126) LA-Patients (n=52) Controls (n=29) Test Result (PICI%) 74.5 ± 13.1 86.7 ± 9.4 90.3 ± 5.3 PICI%&lt;85% (n, %) 99 (78.6%) 15 (28.8%) 3 (10.3%) Moreover, test result was not significantly different in LA+ patients with and without a history of vascular thrombosis (PICI%=74.4 ± 12.9, n=51 vs. 74.5 ± 13.5 n=75, p=0.91) and the same applied for the percentage of abnormal test results (n=41/51 (80.4%) vs. n=58/75 (77.3%); p=0.83). There was no significant difference between LA+ patients with venous, arterial thrombosis and obstetrical complications. Conclusion: The HemosIL ThromboPath assay was highly sensitive for LA (78.6%) but it did not allow to distinguish between LA+ patients those with APS. It was found to be weakly sensitive (28.8%) to high ACL levels without LA activity, despite a higher percentage of abnormal test results. The potential interest of the HemosIL ThromboPath assay as part of the screening strategy of LA deserves to be further investigated prospectively.

Non-Pathogenic Anti-Heparin/PF4 Antibodies Generated by Low Molecular Weight Heparins Mediate Procoagulant Effects.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1091-1091
Author(s):  
Jeanine M. Walenga ◽  
Debra Hoppensteadt ◽  
Evangelos Litinas ◽  
Harry L. Messmore ◽  
Bruce E Lewis ◽  
...  
Keyword(s):  
Thrombin Generation ◽  
Conflicts Of Interest ◽  
Biologically Active ◽  
Control Group ◽  
Heparin Group ◽  
Thrombin Generation Assay ◽  
Enoxaparin Group ◽  
Pre Treatment ◽  
Inhibition Of Thrombin

Abstract Abstract 1091 Introduction: While the incidence of symptomatic heparin-induced thrombocytopenia (HIT) is relatively low with the use of low molecular weights heparins (LMWHs), these agents do generate anti-heparin/PF4 antibodies in 10–20% of treated patients. Dosage, duration, and the pathologic predisposition of the patient influence the quantitative and qualitative nature of these antibodies. It has been suggested that these non-pathogenic antibodies (NPAs) which do not produce symptomatic HIT may, nevertheless, be biologically active and mediate thrombogenic responses. The overall pathophysiologic role of NPAs is unknown at this time. Hypothesis: NPAs generated by LMWHs cause coagulation activation and compromise the anticoagulant effects of the administered LMWH. Study Design: Blood plasma samples collected at baseline and day 10 from patients enrolled in orthopedic surgery clinical trials of LMWHs for the prophylactic management of deep vein thrombosis (Lovenox enoxaparin, sanofi-aventis, n=352; Clivarin reviparin, Abbott, n=380) were retrospectively screened for the presence of anti-heparin/PF4 antibodies using the GTI ELISA method (Waukesha, WI). Positive samples were tested by the 14C-SRA to determine if the antibodies were capable of functionally activating platelets. Both ELISA positive and negative samples were evaluated in an assay of thrombin generation (Technothrombin TGA kit, diaPharma, West Chester, OH). Result: In the enoxaparin study, the baseline pre-treatment samples only showed one patient in the heparin control group to be positive by ELISA. On day 10, 11 of 175 (6.3%) enoxaparin patients had a positive ELISA response, whereas 22 of 177 (12.4%) heparin patients were ELISA positive. None of the samples were 14C-SRA positive. In the thrombin generation assay, the ELISA positive samples showed a lesser inhibition of thrombin generation for both the enoxaparin and heparin groups (270 ± 27 nM TGA enoxaparin group; 220 ± 21 nM TGA heparin group) compared to the thrombin generation response of the ELISA negative samples (190 ± 18 nM TGA enoxaparin group; 160 ± 20 nM TGA heparin group). In the reviparin study, none of the patients were ELISA positive at baseline. On day 10, in the reviparin group 19 of 200 (9.5%) patients were ELISA positive, whereas 28 of 180 (15.6%) heparin control patients had a positive ELISA titer. None of the samples were 14C-SRA positive. In comparison to the baseline (pre-treatment), both the reviparin and heparin treated patients showed an inhibition of thrombin generation (410 ± 27 nM TGA baseline vs 180–290 nM with treatment). However, consistent with the above study, those samples that were ELISA antibody positive showed a lesser inhibition of thrombin generation (240 ± 21 nM TGA reviparin group; 210 ± 16 nM TGA heparin group) in comparison to the ELISA negative samples (190 ± 12 nM TGA reviparin group; 180 ± 14 nM TGA heparin group). Interestingly, the D-dimer levels were found to be higher in the ELISA positive samples in all groups for both studies (p<0.05). Conclusion: These studies suggest a potential pathologic role of NPAs. The results of the thrombin generation studies strongly suggest that the generation of NPAs may result in a reduction of the antithrombotic potential of both LMWH and heparin in treated patients. While the exact mechanism of this process is not clear, dosage adjustment may be useful in those patients who generate NPAs. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Antiphospholipid Antibodies in Iraqi Women with Recurrent Mid-Trimester Abortions

2012 ◽  
Vol 4 (02) ◽  
pp. 078-082
Author(s):  
Amel AA Al-Samarrai ◽  
Ferial A Hilmi ◽  
Nasir AS Al-Allawi ◽  
Amal F Murad
Keyword(s):  
Family History ◽  
Antiphospholipid Antibodies ◽  
Lupus Anticoagulant ◽  
Fetal Loss ◽  
Anticardiolipin Antibodies ◽  
Screening Tests ◽  
Trimester Abortion ◽  
History Of ◽  
Iraqi Women ◽  
Kaolin Clotting Time

ABSTRACT Purpose: Antiphospholipid antibodies are often associated with recurrent pregnancy loss, and although many studies have addressed this association in Western countries, such studies are not so frequent from developing countries. The current study aims to determine the frequency of Antiphospholipid antibodies (Anticardiolipin antibodies and Lupus anticoagulant) among Iraqi women with recurrent mid-trimester abortions and to evaluate various tests used for their detection. Materials and Methods: Two hundred women with recurrent mid-trimester abortions were randomly enrolled from a main referral center in Baghdad-Iraq. The enrollees had their IgG and IgM anticardiolipin antibodies assayed by ELISA, and Lupus anticoagulant by a combination of the following screening tests: Activated Partial Thromboplastine Time (APTT), and Partial Thromboplastine Time-LA (PTT-LA), Kaolin Clotting Time (KCT) and confirmation was made by Hexagonal phospholipid neutralization test. Results: The women were aged between 19 and 45 years (median 30 years). Fifty three (26.5%) had one or both anticardiolipin antibodies present, while 27 (13.5%) were positive for lupus anticoagulant. The KCT and KCT index appeared to be the most sensitive tests, while the KCT index and APTT were the most specific for Lupus anticoagulant. Patients with antiphospholipid antibodies had higher rates of history of thrombosis, thrombocytopenia and family history of recurrent abortion (P = 0.0009, 0.0056 and 0.0003 respectively). Conclusions: Antiphospholipid antibodies constitute an important cause of recurrent mid-trimester abortion in Iraqi women, with frequencies intermediate between Western and Indian reports. While thrombocytopenia and thrombosis are well documented associations of antiphospholipid antibodies, the significant association with family history of recurrent fetal loss is intriguing and requires further scrutiny.

scholarly journals Hypercoagulability Evaluation in Antiphospholipid Syndrome without Anticoagulation Treatment with Thrombin Generation Assay: A Preliminary Study

2021 ◽  
Vol 10 (12) ◽  
pp. 2728
Author(s):  
Paul Billoir ◽  
Sébastien Miranda ◽  
Herve Levesque ◽  
Ygal Benhamou ◽  
Véronique Le Cam Duchez
Keyword(s):  
Antiphospholipid Syndrome ◽  
Protein C ◽  
Thrombin Generation ◽  
Activated Protein C ◽  
Control Group ◽  
Activated Protein C Resistance ◽  
Thrombin Generation Assay ◽  
Clinical Events ◽  
Biological Criteria ◽  
Preliminary Study

Antiphospholipid syndrome (APS) is associated with thrombotic events (tAPS) and/or obstetrical morbidity (oAPS), with persisting antiphospholipid antibodies (aPL). Despite an update of aPL in 2006, several patients had typical clinical events without the classical biological criteria. The aim of our study was to evaluate the hypercoagulability state with both thrombin generation (TG) profiles and activated protein C resistance (aPCR) in different types of APS. Methods: We retrospectively included 41 patients with Sydney criteria classification (tAPS, oAPS) and no clinical manifestation of APS with persistent aPL (biological APS). A thrombin generation assay was performed with a Fluoroskan Ascent fluorometer in platelet-poor plasma (PPP). Activated protein C resistance was measured as a ratio: ETP+aPC/ETP-aPC × 100. Results: Thrombotic APS and oAPS had an increase of global thrombin generation (ETPcontrol = 808 nM.min (756–853) vs. 1265 nM.min (956–1741) and 1863 nM.min (1434–2080), respectively) (Peakcontrol = 78 nM (74–86) vs. 153 nM (109–215) and 254 nM.min (232–289), respectively). Biological APS had only a lag time increase (Tcontrol = 4.89 ± 1.65 min vs. 13.6 ± 3.9 min). An increased aPCR was observed in tAPS (52.7 ± 16.4%), oAPS (64.1 ± 14.6%) as compared to the control group (27.2 ± 13.8%). Conclusion: Our data suggest an increase of thrombin generation in thrombotic and obstetrical APS and no hypercoagulable states in patients with biological APS. The study of a prospective and a larger controlled cohort could determine the TGA useful for APS monitoring and could confirm an aPCR evaluation in PPP.

scholarly journals Characteristics of dental status of patients with inflammatory periodontal diseases

2017 ◽  
Vol 98 (2) ◽  
pp. 204-210
Author(s):  
N A Vasil’eva ◽  
A I Bulgakova ◽  
E S Soldatova
Keyword(s):  
Oral Cavity ◽  
Soft Tissues ◽  
Periodontal Diseases ◽  
Dental Status ◽  
Control Group ◽  
Periodontal Tissues ◽  
Healthy Donors ◽  
Severe Periodontitis ◽  
Local Trauma ◽  
History Of

Aim. Evaluation of dental status in patients with inflammatory periodontal diseases. Methods. The study of dental status was performed with the use of clinical and historical data from 269 patients with inflammatory periodontal diseases at the age of 18-65 years. Among examined patients there were 75 (27.9%) people with gingivitis, 54 (20.1%) with mild periodontitis, 66 (24.5%) with moderate and 74 (27.5%) with severe periodontitis. Control group consisted of practically healthy donors at the age of 18-52 years (40 people) with sanitized oral cavity. Results. From history and interviewing it was found that 72% of the surveyed patients brush their teeth twice a day, 24% - once a day and 4% of patients do not brush their teeth. Family history of periodontal diseases among parents was recorded by 86% of participants. Dental status was characterized by the increase of the values of all dental indices with increasing disease severity regardless of gender. Need for correction of the depth of the vestibule, lips, cords, and bridles was identified in 51.7% of cases in patients with gingivitis and in 96.6% of cases of periodontal diseases. With increasing severity of periodontitis index (sum) of teeth with decay and fillings and removed teeth was increased by 1.5 times in gingivitis, by 2.2 times in mild periodontitis, by 2.6 times in moderate and by 2.9 times in severe periodontitis compared to control group. Partial adentia in gingivitis is 3 times more prevalent in males than in females and in severe periodontitis is 1.6 times more prevalent in females than in males. Conclusion. Dental status of the patients with inflammatory periodontal diseases was characterized by increased values of all dental indices compared to control group that demonstrates typical course of inflammatory periodontal diseases and decrease of local immunologic resistance of oral cavity and the organism in total; timely correction of local factors (local trauma), anatomical and topographical features of dentofacial system and status of oral soft tissues allows prevention of pathologic processes in periodontal tissues.

Thrombin Generation In Patients with Essential Thrombocythemia Treated with Anagrelide

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 5050-5050
Author(s):  
Krystyna M Zawilska ◽  
Agnieszka Skubiszak ◽  
Jolanta M Kurosz ◽  
Jerzy Jaworski
Keyword(s):  
Essential Thrombocythemia ◽  
Thrombin Generation ◽  
Lag Time ◽  
Control Group ◽  
Study Group ◽  
Time To Peak ◽  
History Of ◽  
Wbc Count ◽  
Age Range ◽  
Von Willebrand

Abstract Abstract 5050 Introduction: Thrombosis may be serious and life threatening in patients with essential thrombocythemia (ET). Bleeding is usually from the gastrointestinal tract, and is, in most cases, generally associated with a platelet count greater than 1 million/μL. The mechanism by which thrombocythemia produces hemorrhage or thrombosis is not well defined. Several defects have been described, including a decrease in platelet aggregation or hyperaggregation, a decrease in von Willebrand ristocetin cofactor activity and high molecular weight von Willebrand factor multimers. Some reports show patients with an acquired deficiency of antithrombin, protein C, and acquired APC resistance, probably due to a reduction in free protein S levels. More recently the presence of JAK2V617F mutation and baseline leukocyte (WBC) count have been considered as independent predictors of major thrombosis in ET. Aim of the study: To assess the thrombin generation by the calibrated automated thrombogram method in plasma from ET patients treated with anagrelide. This assay reflects the net results of the procoagulant and anticoagulant forces operating in plasma. The area under the thrombin generation curve (also known as the endogenous thrombin potential (ETP) is a good overall indicator of prothrombotic and hemorrhagic tendency. It could be hypothezised, that platelet-lowering treatment could diminish haemostasis disturbances in ET. Material and methods: The study group consisted of ten ET patients (4 males and 6 females; age range, 24–70 years), diagnosed according to the Polycythemia Vera Study Group criteria. All patients have been treated with anagrelide for mean 4 years (range 1 – 7 years), without antiplatelet drugs. At the time of enrollment their mean platelet number was 344 000/μL (210 000 – 535 000), WBC count 8 600/μL (3 300 – 9 800), and hematocrit 38 (33-47). One patient had a history of splenic vein thrombosis, another had a gastrointestinal bleeding before the start of treatment. Four ET patients (40%) were positive for the JAK2V617F. Ten healthy subjects (4 males and 6 females; age range, 30–70 years) without history of thrombohemorrhagic events, acted as a control group. Thrombin generation (TG) was determined by calibrated automated thrombography (Technothrombin TGA-Technoclone). Thrombin generation curves were described in terms of lag time, peak height, time to peak, slope and ETP. Whole blood thromboelastometry with TEM-ROTEM delta - Pentapharm GmbH has been performed as well. Results: Thrombin generation (ETP) in platelet free plasma was significantly increased in patients with ET (2235 ± 376 nM/min) in comparison with controls (1631 ± 257 nM/min; p=0,0082), the TG lag time, peak, time to peak and slope were also abnormal. Patients with ET showed markedly increased values of INTEM coagulation time-CT, clot formation time-CFT and increased maximum clot firmness, when compared to results of the control group (Table). There were no differences in the EXTEM values. Conclusion: Our results suggest that patients with essential thrombocythemia, in spite of a long-lasting anagrelide treatment, still exhibit an increased thrombin generation as well as formation of a clot with an increased firmness. Disclosures: No relevant conflicts of interest to declare.

scholarly journals P1251THROMBIN GENERATION ASSAY: A POTENTIAL TOOL TO STRATIFY THROMBOTIC RISK IN HEMODIALYSIS PATIENTS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Ileana Kalikatzaros ◽  
Massimo Radin ◽  
Irene Cecchi ◽  
Savino Sciascia ◽  
Giacomo Forneris ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Venous Thrombosis ◽  
Thrombin Generation ◽  
Previous History ◽  
International Normalized Ratio ◽  
Vascular Events ◽  
Thrombotic Risk ◽  
Thrombin Generation Assay ◽  
Autoimmune Conditions ◽  
History Of

Abstract Background and Aims Patients with Chronic Kidney Disease (CKD) in hemodialysis (HD) show both high thrombotic and hemorrhagic risks. However, routine laboratory techniques aimed to evaluate haemostasis, i.e. activated prothrombin time (PT) and activated partial thromboplastin time (aPTT), are not sensitive enough to detect mild hypocoagulable or hypercoagulable states in this population. Indeed, these methods evaluate the start-up phase of the coagulation, but omit the amplification stage in which an exponential increase of thrombin generation occurs. Thrombin generation assay (TGA) is a second-level global coagulative test able to evaluate thrombin generation and decay. So far the TGA has never been used for assessing thrombotic risk in HD patients. Method This is a monocentric observational retrospective study conducted at San Giovanni Bosco Hospital and University of Turin, Italy. After chart-reviewing of all patients with CKD in HD, we enrolled: Group A) 100 Patients with CKD in HD, treated or not treated with warfarin Group B) 60 Patients treated with Warfarin with normal kidney function Group C) 60 Healthy Controls Results Compared to healthy donor patients on hemodialysis that were not treated with warfarin had significantly lower tLag (mean tLag 8.2±3.4 vs. 9.7±2.9, p &lt; 0.05), lower tPeak (mean tPeak 14.3±6 vs. 16.2±4.7, p &lt; 0.05), lower Peak (mean Peak 151.8±77.4 vs. 209.2±103.8, p &lt; 0.001) and lower AUC (mean AUC 1624.5±564.4 vs. 2023±489.2, p &lt; 0.001) (Figure 1). Compared to controls with normal renal function treated with warfarin, HD patients treated with warfarin had higher tLag (mean tLag 10.5±3.3 vs. 8.3±2.1, p &lt; 0.05), higher tPeak (mean tPeak 16.5±4.9 vs. 13±2.9, p &lt; 0.05). Among HD patients who were not treated with warfarin, those with autoimmune conditions showed a pro-thrombotic TGA profile when compared to HD patients without autoimmune diseases, with significantly higher Peak (mean Peak 188.4±30 vs. 149.9±78.7, p &lt; 0.05) and higher AUC (mean AUC 2066.9±138.2 vs. 1601.5±569, p &lt; 0.001). Similarly, compared to patients without previous history of vascular events (59), patients with previous ischemic stroke or venous thrombosis (41), had significantly lower tLag (mean tLag 8±2.9 vs. 14.2±8.5, p &lt; 0.001), lower tPeak (mean tPeak 14±5.6 vs. 21.7±12.3, p &lt;0.05), higher Peak (mean Peak 154.9±76.8 vs. 71.83±49.2, p&lt;0.05) and higher AUC (mean AUC 1653.7±548.7 vs. 863.4±501.4, p &lt; 0.05). Of note, a significant positive relationship was detected between the International Normalized Ratio (INR) and both tLag (Pearson 0.46, p &lt;0.001) and tPeak (Pearson 0.35, p &lt;0.001). INR was inversely correlated to Peak (Pearson -0.47, p &lt;0.001) and AUC (Pearson -0.61, p &lt;0.001) (Figure 2). Conclusion Identifying patients at high risk for cardiovascular diseases and thrombosis has an important impact on the management of patients with CKD in HD. In this study, we observed a prothrombotic TGA profile in patients with CKD in HD, especially those with autoimmune conditions or previous history of arterial events (especially ischemic stroke) or venous thrombosis. Prospective studies are needed to evaluate the possible clinical use of TGA as thrombotic risk stratification tool in HD patients.

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