Dose-Dependent Influence of Acetylsalicylic Acid on Platelet Functions and Plasmatic Coagulation Factors

1976 ◽  
Vol 5 (4) ◽  
pp. 239-249 ◽  
Author(s):  
D. Loew ◽  
H. Vinazzer
Keyword(s):  
Acetylsalicylic Acid ◽  
Coagulation Factors ◽  
Plasmatic Coagulation ◽  
Dose Dependent ◽  
Platelet Functions

Anticoagulant Effect of Sugammadex

2016 ◽  
Vol 124 (6) ◽  
pp. 1277-1285 ◽  
Author(s):  
Daniel Dirkmann ◽  
Martin W. Britten ◽  
Henning Pauling ◽  
Juliane Weidle ◽  
Lothar Volbracht ◽  
...  
Keyword(s):  
Coagulation Factors ◽  
Clot Lysis ◽  
Fibrinogen Concentration ◽  
Thrombin Time ◽  
Binding Effect ◽  
Coagulation Assays ◽  
Thrombin Generation Assay ◽  
Plasmatic Coagulation ◽  
Dose Dependent

Abstract Background Sugammadex prolongs activated partial thromboplastin time (aPTT) and prothrombin time (PT) suggestive of anticoagulant effects. To pinpoint its presumed anticoagulant site of action, the authors assessed Sugammadex’s impact on a panel of coagulation assays. Methods Sugammadex, Rocuronium, Sugammadex and Rocuronium combined, or saline were added to blood samples from healthy volunteers and analyzed using plasmatic (i.e., aPTT, thrombin time, and fibrinogen concentration) (n = 8 each), PT (quick), activities of plasmatic coagulation factors, and whole blood (extrinsically and intrinsically activated thromboelastometry) assays (n = 18 each). Furthermore, dose-dependent effects of Sugammadex were also assessed (n = 18 each) in diluted Russel viper venom time (DRVVT) assays with low (DRVVT1) and high (DRVVT2) phospholipid concentrations and in a highly phospholipid-sensitive aPTT assay. Results Sugammadex increased PT (+9.1%; P < 0.0001), aPTT (+13.1%; P = 0.0002), and clotting time in extrinsically (+33.1%; P = 0.0021) and intrinsically (+22.4%; P < 0.0001) activated thromboelastometric assays. Furthermore, activities of factors VIII, IX, XI, and XII decreased (−7%, P = 0.009; −7.8%, P < 0.0001; −6.9%, P < 0.0001; and −4.3%, P = 0.011, respectively). Sugammadex dose-dependently prolonged both DRVVT1 and the highly phospholipid-sensitive aPTT assays, but additional phospholipids in the DRVVT2 assay almost abolished these prolongations. Thrombin time, a thromboelastometric thrombin generation assay, clot firmness, clot lysis, fibrinogen concentration, and activities of other coagulation factors were unaltered. Rocuronium, Sugammadex and Rocuronium combined, and saline exerted no effects. Conclusion Sugammadex significantly affects various coagulation assays, but this is explainable by an apparent phospholipid-binding effect, suggesting that Sugammadex`s anticoagulant effects are likely an in vitro artifact.

scholarly journals Dose-dependent antithrombotic effect of warfarin in rabbits

Blood ◽  
1983 ◽  
Vol 61 (3) ◽  
pp. 435-438 ◽  
Author(s):  
SN Gitel ◽  
S Wessler
Keyword(s):  
Vitamin K ◽  
Coagulation Factors ◽  
Progressive Increase ◽  
Drug Dose ◽  
Mean Value ◽  
Factor X ◽  
Antithrombotic Effect ◽  
Tissue Thromboplastin ◽  
Dose Dependent Decrease ◽  
Dose Dependent

Abstract One-hundred and fifty-one rabbits, divided into controls and animals treated with varying daily doses of warfarin, were subjected to the stasis assay, and the amount of thrombosis quantitated after intravascular coagulation was initiated either by activated factor X or tissue thromboplastin. Following 8–10 days of warfarin administration, there was a significant dose-dependent decrease in the vitamin-K- dependent coagulation factors paralleled by an increase in the prothrombin time ratio. Whether thrombosis was initiated by activated factor X or tissue thromboplastin, there was, with increasing drug dose, a progressive increase in the inhibition of stasis thrombosis. This significant antithrombotic effect occurred even when the vitamin-K- dependent coagulation activities were at a mean value of 50%.

DURATION OF BLEEDING FOLLOWING DENTAL EXTRACTION IN RABBITS:IN FLUENCE OF PLATELET DYSFUNCTION

1987 ◽  
Author(s):  
D Declerck ◽  
F Vinckier ◽  
J Vermylen
Keyword(s):  
Platelet Aggregation ◽  
Oral Administration ◽  
Acetylsalicylic Acid ◽  
Clinical Experience ◽  
Dental Extraction ◽  
Platelet Dysfunction ◽  
Tooth Socket ◽  
Objective Evidence ◽  
Platelet Defects ◽  
Dose Dependent

Clinical experience suggests that acetylsalicylic acid prolongs bleeding after dental extraction, but objective evidence is lacking. We have studied the influence of platelet dysfunction on haemostasis following dental extraction in rabbits. Platelet defects were induced by oral administration of acetylsalicylic acid (ASA) or ticlopidine (T). Duration of bleeding was measured in following groups of Dutch rabbits:(A) control animals (n = 32),animals who received (B) ASA 100 mg/kg/day (n = 31), (C) ASA 300 mg/kg/day (n = 12)(D) T 60 mg/kg/day (n = 8) and (E) T 125 mg/kg/day (n = 12). Inhibition of thromboxane B2-formation was more than 99% in animals receiving ASA. ADP-induced platelet aggregation was inhibited in animals receiving T. Four front teeth were extracted on day 7 and tooth socket bleeding times were determined by inspecting the wounds at 5 min intervals. Oozing sockets were counted. The figure below shows the results.It is concluded that ASA or T prolong bleeding following dental extraction in rabbits. The effect appears to be dose-dependent for T. This model may be useful for evaluating haemostatic procedures applicable to patients with platelet disorders.

PREVENTION OF CORONARY VEIN GRAFT OCCLUSION: LOW-DOSE ACETYLSALICYLIC ACID VERSUS COUMARIN (ASAAC - STUDY)

1987 ◽  
Author(s):  
M A J Weber ◽  
C Taillens ◽  
J Hasford ◽  
M Spannagel ◽  
W Schramm ◽  
...  
Keyword(s):  
Salicylic Acid ◽  
Acetylsalicylic Acid ◽  
Low Dose ◽  
Coagulation Factors ◽  
Graft Patency ◽  
Graft Occlusion ◽  
Antiplatelet Activity ◽  
Antiplatelet Treatment ◽  
Coronary Vein ◽  
Acid Versus

Thrombotic graft occlusion occurs within a few hours after surgery, suggesting a benefit of preoperative start of antiplatelet treatment. We investigated the effectivity and risk of preoperatively started treatment with 100 mg/day acetyl salicylic acid (ASA) compared to anticoagu1 ation started 6 hours postoperatively (heparin followed by coumarin (AC)). The prospective randomized trial yielded the following results:Preoperative low dose ASA increased chest-tube blood loss. This indicates effective antiplatelet activity of low dose ASA. Perioperative platelet consumption and coagulation factors activity was not altered.It is concluded, that graft patency rates are similar with postoperative anticoagu1 ation or antiplatelet treatment with low dose acetylsalicylic acid.

scholarly journals Brain-Derived Microparticles Induce Systemic Coagulation Associated with Traumatic Brain Injury

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1497-1497
Author(s):  
Jing-fei Dong ◽  
Ye Tian ◽  
Breia Salsbery ◽  
Hengjie Yuan ◽  
Min Wang ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Traumatic Brain Injury ◽  
Flow Cytometry ◽  
Coagulation Factors ◽  
Endothelial Barrier ◽  
Dependent Manner ◽  
Activated Platelets ◽  
Dose Dependent ◽  
Made In

Abstract Uncontrolled hemorrhage is a leading cause of the preventable deaths that occur in patients with trauma. The cause of trauma-associated coagulopathy is multifactorial, including blood loss, consumption of coagulation factors and platelets, the dilution of coagulation factors and platelets due to fluid resuscitation, and hypothermia. Traumatic brain injury (TBI) lacks two key causal factors for coagulopathy: heavy blood loss and a large volume of fluid resuscitation, but is associated with a significantly higher incidence of coagulopathy. The pathogenesis of this TBI-associated coagulopathy remains poorly understood. We tested the hypothesis that brain-derived microparticles (BDMPs) released from an injured brain play a causal role in developing systemic coagulopathy after TBI. Here, we report that mice subjected to fluid percussion injury (1.9±0.1 atm) developed a BDMP-dependent hypercoagulable state, with a peak level of plasma glial cell and neuronal microparticles, reaching 17,496 ± 4,833/µl and 18,388 ± 3,657/µl 3 hrs after TBI. BDMPs were measured by flow cytometry using triple gating based on particle size and the expression of neural cell markers and phosphatidylserine (PS). To exclude contributions to the coagulopathy of non-neural cell microparticles released during trauma stress, BDMPs were made from normal brain by freeze-thawing and mechanical injury. BDMPs thus made had below detection levels of microparticles from leukocytes (CD45), endothelial cells (CD144), erythrocytes (CD235a), and platelets (CD42b). Uninjured mice injected with BDMPs made in vitro developed a hyper-turn-hypo-coagulable state in a dose-dependent manner as measured by the rates of clot formation and fibrinogen depletion, resulting in microvascular fibrin deposition in the lungs, kidney and heart. BDMPs measured 50 – 500 nm with relatively intact membranes under transmission electron microscopy and expressed neuronal or glial cell markers and procoagulant PS and tissue factor (TF). BDMPs promoted clot formation in a PS-dependent assay at a maximal activity of ~1 x 105 BDMPs/µl, equivalent to 1.6 µg/µl of purified brain PS. They were equally active in promoting thrombin generation in a PS-and TF-dependent manner, BDMPs at 2.5 x 104 /µl yielding an activity equivalent to 1 pM of soluble TF. The procoagulant activity of BDMPs was significantly stronger than microparticles generated from collagen-stimulated platelets and was blocked by the PS-binding lactadherin in a dose-dependent manner. Consistent with observations made in the mouse models, fetal hippocampal cells in culture produced microparticles upon injury. These microparticles transmigrated through the disrupted endothelial barrier in the presence of live, but not lyophilized platelets. BDMP-bound platelets were detected by flow cytometry and scan electron microscopy. They activated platelets as measured by increases in calcium influx and CD62p expression, but did not induce platelet aggregation directly or in the presence of low doses of collagen. In summary, we have studied acute changes in coagulation associated with TBI using a mouse FPI model combined with in vitro experiments. Focusing on the first 6 hrs post-TBI minimizes confounding changes induced by secondary events, such as ischemic injury. The results define a causal role for BDMPs in the TBI-associated systemic coagulation. We also show that BDMPs activated platelets. Activated platelets may facilitate the transmigration of BDMPs through the disrupted endothelial barrier by releasing pro-inflammatory mediators to promote local inflammation at a site of vascular injury. This notion is supported by the finding that live, but not lyophilized platelets and, to lesser degree, plasma from activated platelets promoted BDMP transmigration through a monolayer of endothelial cells. Finally, the PS binding lactadherin blocked the BDMP-dependent procoagulant activity, raising two interesting perspectives. First, PS scavengers and neutralizing molecules may reduce or prevent coagulopathy associated with TBI. Second, an intrinsic or acquired deficiency in the PS-dependent clearance of microparticles may predispose an individual to consumptive coagulopathy associated with TBI and other conditions. Disclosures No relevant conflicts of interest to declare.

Protective Effect of Pantethine on Experimental Thrombocytopenia in the Rat

1975 ◽  
Vol 33 (03) ◽  
pp. 528-539 ◽  
Author(s):  
Shin-ichiro Ashida ◽  
Yasushi Abiko
Keyword(s):  
Nitrogen Mustard ◽  
Experimental Period ◽  
Significant Degree ◽  
Rabbit Serum ◽  
Dependent Manner ◽  
Essentially Normal ◽  
And Function ◽  
Dose Dependent ◽  
Platelet Functions

SummaryThe effects of pantethine on circulating platelet counts and platelet functions were studied in normal and experimentally produced thrombocytopenic rats.Administration of pantethine to normal animals did not cause any alterations in both platelet count and function except for a slight enhancement of intravascular platelet aggregation induced by collagen or neuraminidase.Injection of anti-rat platelet rabbit serum into rats resulted in acute thrombocytopenia. Administration of pantethine prior to the antiserum promoted recovery from the thrombocytopenia in a dose dependent manner, but administration of the drug after development of the thrombocytopenia was not effective. A similar result was obtained with a transient thrombocytopenia induced by exchange transfusion with platelet poor blood. Regardless of whether animals were treated with pantethine or not, the platelets newly generated during the course of recovery from thrombocytopenia were essentially normal in the function tested in vitro.A more chronic thrombocytopenia induced by repeated injections of the antiserum was prevented, to some significant degree, by daily administration of pantethine throughout the experimental period.In contrast to these, such effect of pantethine was not observed with the thrombocytopenia models produced by nitrogen mustard N-oxide and neuraminidase.These findings were discussed in relation to mechanism of the action of pantethine and to possible clinical application of the drug to thrombocytopenia.

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