A new measure for in vivo thrombin activity in comparison with in vitro thrombin generation potential in patients with hyper- and hypocoagulability

The thrombin generation potential is an in vitro measure for the capacity of an individual to generate thrombin and recognized as a reflection of a hypo- or hypercoagulable status. Measurement of the in vivo thrombin activity, however, may be of clinical significance. We evaluated a new assay for in vivo thrombin activity and compared it to the in vitro thrombin generation potential in patients with hemophilia A (N = 15), oral anticoagulation for atrial fibrillation (AF) (N = 20), subjects with active cancer (N = 21), and healthy volunteers (N = 10). Thrombin activity was measured with a commercially available oligonucleotide enzyme capture assay in argatroban-stabilized plasma samples. Thrombin generation potential was determined with a commercially available assay in citrated plasma. Thrombin activity was detected in 17 (30.4 %) patients (mean 0.30 mU/ml [SD 0.80]), and in 39 patients (69.6 %) no thrombin activity was present. In cancer patients, thrombin activity was detected in 11 patients (52 %) (range 0.14-5.00 mU/ml) and was particularly increased in 3 patients with vessel-invasive tumors (1.2, 1.5, and 5.0 mU/ml). In AF patients, thrombin activity was only measureable in two patients (10 %) (recent hematoma [0.4 mU/ml] and recent ischemic stroke [1.5 mU/ml]). Thrombin activity was detected in four patients (27 %) with hemophilia (range 0.29-1.75 mU/ml), all of whom had received a factor VIII infusion on the same day. Thrombin activity did not correlate with any of the parameters of the thrombin generation potential. Only patients in acute procoagulatory states or after clotting factor replacement had elevated in vivo thrombin activity, which was, however, unrelated to the in vitro thrombin generation potential

Design Management Program Application for Internet Access in STMIK Jakarta Pusyanet

A medium used for the general course requires management to continuity ofoperations, not much different from the means of Internet access that is intended forstudents STMIK Jakarta. By using application programs created with Visual Basiclanguage, management of user identities, the use and timing of each user requests alist of all of them are stored in the database using Microsoft Access

A new measure for in vivo thrombin activity in comparison with in vitro thrombin generation potential in patients with hyper- and hypocoagulability

The thrombin generation potential is an in vitro measure for the capacity of an individual to generate thrombin and recognized as a reflection of a hypo- or hypercoagulable status. Measurement of the in vivo thrombin activity, however, may be of clinical significance. We evaluated a new assay for in vivo thrombin activity and compared it to the in vitro thrombin generation potential in patients with hemophilia A (N = 15), oral anticoagulation for atrial fibrillation (AF) (N = 20), subjects with active cancer (N = 21), and healthy volunteers (N = 10). Thrombin activity was measured with a commercially available oligonucleotide enzyme capture assay in argatroban-stabilized plasma samples. Thrombin generation potential was determined with a commercially available assay in citrated plasma. Thrombin activity was detected in 17 (30.4 %) patients (mean 0.30 mU/ml [SD 0.80]), and in 39 patients (69.6 %) no thrombin activity was present. In cancer patients, thrombin activity was detected in 11 patients (52 %) (range 0.145.00 mU/ml) and was particularly increased in 3 patients with vessel-invasive tumors (1.2, 1.5, and 5.0 mU/ml). In AF patients, thrombin activity was only measureable in two patients (10 %) (recent hematoma [0.4 mU/ml] and recent ischemic stroke [1.5 mU/ml]). Thrombin activity was detected in four patients (27 %) with hemophilia (range 0.291.75 mU/ml), all of whom had received a factor VIII infusion on the same day. Thrombin activity did not correlate with any of the parameters of the thrombin generation potential. Only patients in acute procoagulatory states or after clotting factor replacement had elevated in vivo thrombin activity, which was, however, unrelated to the in vitro thrombin generation potential.(VLID)353387

BMC Medicine / Cardiovascular risk factors are major determinants of thrombotic risk in patients with the lupus anticoagulant

Background Patients with the lupus anticoagulant (LA) are at an increased risk of thrombotic events, which in turn increase the risk of death. Understanding the determinants of thrombotic risk in patients with LA may pave the way towards targeted thromboprophylaxis. In the Vienna Lupus Anticoagulant and Thrombosis Study (LATS), we systematically evaluate risk factors for thrombotic events in patients with LA. Methods We followed 150 patients (mean age: 41.3 years, female gender: n = 122 (81.3%), history of thrombosis or pregnancy complications: n = 111 (74.0%)), who tested repeatedly positive for LA until development of thrombosis, death, or censoring. The primary endpoint was a composite of arterial or venous thrombotic events (TEs). Results During a median follow-up of 9.5 years (range: 12 days13.6 years) and 1076 person-years, 32 TEs occurred (arterial: n = 16, venous: n = 16; cumulative 10-year TE incidence: 24.3%). A prolonged lupus-sensitive activated partial thromboplastin time (aPTT-LA) (adjusted subdistribution hazard ratio (SHR) = 2.31, 95% CI: 1.07-5.02), diabetes (adjusted SHR = 4.39, 95% CI: 1.4213.57), and active smoking (adjusted SHR = 2.31, 95% CI: 1.145.02) emerged as independent risk factors of both arterial and venous thrombotic risk. A risk model that includes a prolonged lupus-sensitive aPTT, smoking, and diabetes enabled stratification of LA patients into subgroups with a low, intermediate, and high risk of thrombosis (5-year TE risk of 9.7% (n = 77), 30.9% (n = 51), and 56.8% (n = 22). Conclusions Long-term thrombotic risk in patients with LA is clustered within subjects harboring typical cardiovascular risk factors in addition to a prolonged lupus-sensitive aPTT, whereas patients with none of these risk factors represent a large subgroup with a low risk of thrombosis.(VLID)484815

Annals of Hematology / Fibrinolysis in patients with a mild-to-moderate bleeding tendency of unknown cause

In more than 50% of patients with a mild-to-moderate bleeding tendency, no underlying cause can be identified (bleeding of unknown cause, BUC). Data on parameters of fibrinolysis in BUC are scarce in the literature and reveal discrepant results. It was the aim of this study to investigate increased fibrinolysis as a possible mechanism of BUC. We included 270 patients (227 females, median age 44 years, 2575th percentile 3258) with BUC and 98 healthy controls (65 females, median age 47 years, 2575thpercentile 3955). Tissue plasminogen activator (tPA-) antigen and activity, plasminogen activator inhibitor type-1 (PAI-1), tPA-PAI-1 complexes, thrombin activatable fibrinolysis inhibitor (TAFI), 2-antiplasmin, and D-dimer were determined. While PAI-1 deficiency was equally frequent in patients with BUC and controls (91/270, 34%, and 33/98, 34%, p = 0.996), tPA activity levels were more often above the detection limit in patients than in controls (103/213, 48%, and 23/98, 23%, p < 0.0001). We found lower levels of tPA-PAI-1 complexes (6.86 (3.9910.00) and 9.11 (7.1713.12), p < 0.001) and higher activity of TAFI (18.61 (15.8022.58) and 17.03 (14.0220.02), p < 0.001) and 2-antiplasmin (102 (94109) and 98 (90106], p = 0.003) in patients compared to controls. Detectable tPA activity (OR 3.02, 95%CI 1.755.23, p < 0.0001), higher levels of TAFI (OR 2.57, 95%CI 1.484.46, p = 0.0008) and 2-antiplasmin (OR 1.03, 95%CI 1.011.05, p = 0.011), and lower levels of tPA-PAI-1 complexes (OR 0.90, 95%CI 0.860.95, p < 0.0001) were independently associated with BUC in sex-adjusted logistic regression analyses. We conclude that the fibrinolytic system can play an etiological role for bleeding in patients with BUC.(VLID)349866

MOESM1 of Alterations of blood coagulation in controlled human malaria infection

Additional file 1: Table S1. Peak thrombin generation at 3 different time points for all 22 individual study subjects who developed parasitemia, including information about PfSZ Challenge route of administration, parasite dose), development of symptoms during infection and parasitemia

Additional file 13: Figure S4. of Cardiovascular risk factors are major determinants of thrombotic risk in patients with the lupus anticoagulant

Calibration bar graph of the proposed empirical risk stratification rule. (DOCX 22 kb