Dabigatran Effects on the International Normalized Ratio, Activated Partial Thromboplastin Time, Thrombin Time, and Fibrinogen: A Multicenter, In Vitro Study

The comorbid course of liver cirrhosis and atrial fibrillation causes higher levels of hospitalizations, mortality and ischemic stroke. According to current data, hemostasis in patients with liver cirrhosis is in a rebalanced dynamic state, but there are no data on the effect of atrial fibrillation on the hemostasis in patients with liver cirrhosis. Aims of the study. To assess abnormalities in primary, secondary haemostasis and fibrinolytic system in patients with liver cirrhosis and atrial fibrillation by using standard laboratory coagulation parameters and to investigate their changes depending on the stage of liver cirrhosis A, B, C according to Child-Pugh score. Materials and methods. A cross-sectional prospective study was conducted with the inclusion of 106 patients aged 42 to 83 years: group I (n = 70) - with liver cirrhosis and atrial fibrillation, II (n = 36) - with liver cirrhosis, which were distributed depending on the Child-Pugh score stages of cirrhosis and 20 healthy individuals. The levels of platelets, activated partial thromboplastin time, international normalized ratio, prothrombin time, thrombin time, fibrinogen, D-dimer were assessed on a Steellex M200 coagulometer. Statistical analysis (IBM SPSS Statistics) was performed. Results. The level of platelets in patients of group I was reduced by 37.4% (200 ± 8.33 vs. 274.7 ± 3.4; p,000.001), an activated partial thromboplastin time was prolonged by 38.6% (44.35 ± 1.39 vs. 32.01 ± 0.63, p˂0.001), prothrombin time was prolonged by 73.5% (19.4 ± 0.87 vs. 11.18 ± 0.53, p˂0.001), thrombin time was prolonged by 2.07 (25, 7 ± 1.31 vs. 12.4 ± 0.66, p˂0.001), the international normalized ratio was increased by 24.3% (1.38 ± 0.04 vs.1.11 ± 0.01, p˂0.001) compared to control. The fibrinogen level was 20.9% higher (4.17 ± 0.17 vs. 3.45 ± 0.11, p˂0.001) than in control group and was 83.7% higher (4.17 ± 0.17 vs. 2.27 ± 0.13, p˂0.001) than in group II. The D-dimer level was 83% higher than in control (675 ± 22.3 vs. 368.8 ± 21.85, p˂0.001) and 44% higher (675 ± 22.3 vs. 469 ± 37.18, p ˂0.001) compared with group II. Conclusions. In patients with liver cirrhosis and atrial fibrillation abnormalities of primary hemostasis are detected due to decrease of platelets on the background of portal hypertension. At the secondary stage of hemostasis indicators of external and internal coagulation mechanisms are prolonged due to the reduced synthesis of coagulation factors by the liver. Increased level of fibrinogen is determined at the stage of compensated and subcompensated cirrhosis with a gradual decrease at the stage of decompensation. The high activity of the fibrinolytic system is observed due to increase in the D-dimer levels, which may indicate a prothrombotic state in these patients.

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The International Normalized Ratio calibrated for rivaroxaban has the potential to normalize prothrombin time results for rivaroxaban-treated patients: results of an in vitro study

Journal of Thrombosis and Haemostasis ◽

10.1111/j.1538-7836.2010.04106.x ◽

2011 ◽

Vol 9 (1) ◽

pp. 226-228 ◽

Cited By ~ 86

Author(s):

A. TRIPODI ◽

V. CHANTARANGKUL ◽

C. GUINET ◽

M. M. SAMAMA

Keyword(s):

Prothrombin Time ◽

In Vitro Study ◽

International Normalized Ratio ◽

Vitro Study

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The In Vitro Effects of Pentamidine Isethionate on Coagulation and Fibrinolysis

Molecules ◽

10.3390/molecules24112146 ◽

2019 ◽

Vol 24 (11) ◽

pp. 2146 ◽

Cited By ~ 1

Author(s):

Rami A. Al-Horani ◽

Daytriona Clemons ◽

Madhusoodanan Mottamal

Keyword(s):

Partial Thromboplastin Time ◽

Factor Xa ◽

Activated Partial Thromboplastin Time ◽

Factor Xiiia ◽

Thrombin Time ◽

Normal Plasma ◽

Pentamidine Isethionate ◽

In Vitro Effects ◽

Coagulation And Fibrinolysis

Pentamidine is bis-oxybenzamidine-based antiprotozoal drug. The parenteral use of pentamidine appears to affect the processes of blood coagulation and/or fibrinolysis resulting in rare but potentially life-threatening blood clot formation. Pentamidine was also found to cause disseminated intravascular coagulation syndrome. To investigate the potential underlying molecular mechanism(s) of pentamidine’s effects on coagulation and fibrinolysis, we studied its effects on clotting times in normal and deficient human plasmas. Using normal plasma, pentamidine isethionate doubled the activated partial thromboplastin time at 27.5 µM, doubled the prothrombin time at 45.7 µM, and weakly doubled the thrombin time at 158.17 µM. Using plasmas deficient of factors VIIa, IXa, XIa, or XIIa, the concentrations to double the activated partial thromboplastin time were similar to that obtained using normal plasma. Pentamidine also inhibited plasmin-mediated clot lysis with half-maximal inhibitory concentration (IC50) value of ~3.6 μM. Chromogenic substrate hydrolysis assays indicated that pentamidine inhibits factor Xa and plasmin with IC50 values of 10.4 µM and 8.4 µM, respectively. Interestingly, it did not significantly inhibit thrombin, factor XIa, factor XIIIa, neutrophil elastase, or chymotrypsin at the highest concentrations tested. Michaelis-Menten kinetics and molecular modeling studies revealed that pentamidine inhibits factor Xa and plasmin in a competitive fashion. Overall, this study provides quantitative mechanistic insights into the in vitro effects of pentamidine isethionate on coagulation and fibrinolysis via the disruption of the proteolytic activity of factor Xa and plasmin.

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Copolymers of 2-acryloylamido-2-methylpropanesulfonic acid and acrylic acid with anticoagulant activity

e-Polymers ◽

10.1515/epoly.2003.3.1.665 ◽

2003 ◽

Vol 3 (1) ◽

Cited By ~ 6

Author(s):

Dilyana Paneva ◽

Olya Stoilova ◽

Nevena Manolova ◽

Dobri Danchev ◽

Zdravko Lazarov ◽

...

Keyword(s):

Acrylic Acid ◽

Prothrombin Time ◽

Partial Thromboplastin Time ◽

Anticoagulant Activity ◽

Activated Partial Thromboplastin Time ◽

Thrombin Time

Abstract Copolymers of 2-acryloylamido-2-methylpropanesulfonic acid (AMPS) and acrylic acid (AA), as well as the corresponding homopolymers PAMPS and PAA, were studied in vitro on human pool plasma for their anticoagulant activity. The values of the haemostatic parameters - prothrombin time, activated partial thromboplastin time and thrombin time - depend on the composition and the concentration of the (co)polymers. Reptilase time remains unchanged on adding the (co)polymers. A broad concentration range from 16 μg/ml to 3 mg/ml was studied. The copolymers possess anticoagulant activity, which is higher at higher content of AMPS units. It was found that, at certain concentrations, the haemostatic parameters of PAMPS are close to that of heparin. PAA has the lowest anticoagulant activity.

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Evaluation of Hemocompatibility of Titanium after Various Surface Treatments: An in vitro Study

International Journal of Prosthodontics and Restorative Dentistry ◽

10.5005/jp-journals-10019-1062 ◽

2012 ◽

Vol 2 (4) ◽

pp. 136-142

Author(s):

Yemineni BhavanChand ◽

R Ranzani ◽

H Annapoorani

Keyword(s):

In Vitro Study ◽

Surface Treatments ◽

Vitro Study ◽

Polished Surface ◽

Thrombin Time ◽

Before And After ◽

Phosphate Buffered Saline ◽

Mechanical Surface ◽

Medical Grade

ABSTRACT Objective To evaluate the hemocompatibility of titanium after various surface treatments. Materials and methods A total of 27 disk-shaped specimens (3 ⨯ 10.0 mm) were prepared from a cylindrical rod of medical grade titanium. The disks were divided into three groups, of which one was considered as the control (mechanical surface polished surface). The other groups being sandblasted disks and anodized disks. Surface evaluation was done for sandblasted and anodized disks with scanning electron microscope. The specimens were placed in polystyrene culture plates and agitated with phosphate buffered saline for 5 minutes before they were exposed to blood taken from human volunteer. The materials were under 30 minutes agitation at 75 ± 5 rpm using an Environ shaker thermostated at 35 ± 20°C. The total hemoglobin from the initial sample was measured using automatic hematology analyzer. Percentage hemolysis, thrombin time, platelet adhesion and activation were assessed. Significant differences between different treated titanium materials were determined using Minitab® Version 15.1.1.0. A two-sample t-test was performed to find the p-values for different groups of data. Results After 30 minutes of agitation, cells began to spread on the test surfaces. There was a clear reduction in the number of platelets before and after exposure to titanium samples. Reduction of leukocytes was seen to a least extent on the anodized surface. Rough surface induced higher hemolysis than other groups. Platelet reduction and leukocyte reduction in all the three surfaces was quite higher than that obtained for reference plate. Surface variation has no significance on the thrombogenic capabilities of medical grade titanium (p < 0.05). Significance The hemocompatibility of medical grade titanium did not vary with different surface modifications. How to cite this article BhavanChand Y, Ranzani R, Annapoorani H. Evaluation of Hemocompatibility of Titanium after Various Surface Treatments: An in vitro Study. Int J Prosthodont Restor Dent 2012;2(4):136-142.

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A Comparison of Glass and Plastic Blood Collection Tubes for Routine and Specialized Coagulation Assays: A Comprehensive Study

Archives of Pathology & Laboratory Medicine ◽

10.5858/2006-130-39-acogap ◽

2006 ◽

Vol 130 (1) ◽

pp. 39-44 ◽

Cited By ~ 3

Author(s):

Alexander Kratz ◽

Nancy Stanganelli ◽

Elizabeth M. Van Cott

Keyword(s):

Partial Thromboplastin Time ◽

Protein C ◽

Protein S ◽

International Normalized Ratio ◽

Activated Partial Thromboplastin Time ◽

Blood Collection ◽

Thrombin Time ◽

Coagulation Assays ◽

Glass Tubes ◽

Blood Collection Tubes

Abstract Context.—Blood collection tubes made from plastic are beginning to replace glass tubes. Coagulation test results can be influenced easily by preanalytic factors, including exposure to surfaces that activate the clotting cascade. Objective.—To compare the effects of the blood collection tube material on 22 coagulation assays performed in clinical laboratories. Design.—Paired blood samples from 28 healthy volunteers were drawn into BD Vacutainer Glass Citrate Tubes and BD Vacutainer Plus Plastic Citrate Tubes, and the results of coagulation assays were determined in parallel. Results.—No statistically significant differences were observed between glass and plastic for 14 assays: prothrombin time (and international normalized ratio); activated partial thromboplastin time; activated protein C resistance; antithrombin activity; factors II, V, VIII, and IX; α2-antiplasmin; plasminogen activity; von Willebrand factor antigen; ristocetin cofactor; thrombin time; and reptilase time. Statistically significant differences were found for fibrinogen; chromogenic protein C activity; protein S activity; PTT-LA lupus anticoagulant–sensitive activated partial thromboplastin time; and factors VII, X, XI, and XII. Mean differences ranged from 0.4% to 5.5% and were unlikely to be of clinical significance. Conclusions.—The results of this study suggest that plastic tubes can be used in place of glass tubes for a wide variety of coagulation assays.

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