scholarly journals Glycocalyx components affect platelet function, whole blood coagulation, and fibrinolysis: an in vitro study suggesting a link to trauma-induced coagulopathy

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Martin W. Britten ◽  
Laura Lümers ◽  
Kenji Tominaga ◽  
Jürgen Peters ◽  
Daniel Dirkmann
Keyword(s):  
Platelet Aggregation ◽  
Heparan Sulfate ◽  
Chondroitin Sulfate ◽  
Blood Coagulation ◽  
Platelet Function ◽  
Whole Blood ◽  
Dependent Manner ◽  
Trauma Induced Coagulopathy ◽  
Coagulation And Fibrinolysis

Abstract Background The mechanisms of trauma induced coagulopathy (TIC) are considered multifactorial. Amongst others, however, shedding of the endothelial glycocalyx resulting in increased concentrations of glycocalyx fragments in plasma might also play a role. Thus, we hypothesized that shedded glycocalyx components affect coagulation and may act as humoral mediators of TIC. Methods To investigate effects of heparan sulfate, chondroitin sulfate, syndecan-1, versican, and thrombomodulin we added these fragments to in vitro assays of whole blood from healthy volunteers to yield concentrations observed in trauma patients. Platelet function, whole blood coagulation, and fibrinolysis were measured by standard coagulation tests, impedance aggregometry (IA), and viscoelastic tests (VET). To assess dose-response relationships, we performed IA with increasing concentrations of versican and VET with increasing concentrations of thrombomodulin. Results Intrinsically activated clotting times (i.e., activated partial thromboplastin time and intrinsically activated VET with and without heparinase) were unaffected by any glycocalyx fragment. Thrombomodulin, however, significantly and dose-dependently diminished fibrinolysis as assessed by VET with exogenously added rt-PA, and increased rt-PA-induced lysis Indices after 30 (up to 108% of control, p <  0,0001), 45 (up to 368% of control, p <  0,0001), and 60 min (up to 950% of control, p <  0,0001) in VET. Versican impaired platelet aggregation in response to arachidonic acid (up to − 37,6%, p <  0,0001), ADP (up to − 14,5%, p <  0,0001), and collagen (up to − 31,8%, p <  0,0001) in a dose-dependent manner, but did not affect TRAP-6 induced platelet aggregation. Clotting time in extrinsically activated VET was shortened by heparan sulfate (− 7,2%, p = 0,024), chondroitin sulfate (− 11,6%, p = 0,016), versican (− 13%, p = 0,012%), and when combined (− 7,2%, p = 0,007). Conclusions Glycocalyx components exert distinct inhibitory effects on platelet function, coagulation, and fibrinolysis. These data do not support a ‘heparin-like auto-anticoagulation’ by shed glycosaminoglycans but suggest a possible role of versican in trauma-induced thrombocytopathy and of thrombomodulin in trauma-associated impairment of endogenous fibrinolysis.

Effect of Aspirin Infusions on Platelet Function in Humans

1990 ◽  
Vol 79 (1) ◽  
pp. 37-42 ◽  
Author(s):  
K. M. Wilson ◽  
D. M. Siebert ◽  
E. M. Duncan ◽  
A. A. Somogyi ◽  
J. V. Lloyd ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Blood Coagulation ◽  
Platelet Function ◽  
Whole Blood ◽  
Dependent Manner ◽  
Inhibitory Effects ◽  
Concentration Dependent Manner ◽  
Infusion Period

1. The inhibitory effects of aspirin on platelet function in vitro have been shown to be both time (over 3 h) and concentration (1–10 μmol/l) dependent. 2. To determine if these effects occurred in vivo, four volunteers received intravenous infusions on four occasions, to give constant plasma aspirin concentrations of 0, 1, 2 and 4 μmol/l over 3 h. Infusions were performed at intervals of at least 2 weeks. 3. Before and during the infusions, blood was taken for assay of aspirin concentrations, and measurements of platelet aggregation in response to collagen, adenosine 5′-pyrophosphate and arachidonate. Thromboxane generation after stimulated platelet aggregation and whole-blood coagulation was also measured. 4. At each aspirin concentration, both platelet aggregation and thromboxane generation in response to collagen and arachidonate were inhibited progressively over the 3 h infusion period. Greatest inhibition was seen during the 4 μmol/l infusion, which produced maximal or near-maximal inhibition by the third hour. 5. Thromboxane generated during whole-blood coagulation was similarly inhibited in both a time- and concentration-dependent manner throughout all aspirin infusions. 6. The progressive nature of the inhibition of platelet function with these low aspirin concentrations may be due to either slow aspirin transport across the platelet membrane or delayed interaction with cyclo-oxygenase.

Effects of Single and Multiple Moxibustions on Activity of Platelet Function, Blood Coagulation and Fibrinolysis in Mice

1990 ◽  
Vol 18 (01n02) ◽  
pp. 77-85 ◽  
Author(s):  
Masako Okazaki ◽  
Hideharu Sakamoto ◽  
Makoto Suzuki ◽  
Katsuji Oguchi
Keyword(s):  
Platelet Aggregation ◽  
Blood Coagulation ◽  
Host Defense ◽  
Platelet Function ◽  
Fibrinolytic Activity ◽  
Defense Mechanism ◽  
Atp Release ◽  
Host Defense Mechanism ◽  
Coagulation And Fibrinolysis ◽  
Platelet Functions

The effects of single and multiple moxibustions on platelet function, blood coagulation and fibrinolytic activity in ddY mice were studied. The increase in platelet aggregation and ATP-release after a single moxibustion was dependent on moxa weight and the kind of platelet stimulus. Blood coagulative activity tended to increase in the early phase after a single moxibustion. However, multiple moxibustions maintained the homeostasis on blood coagulation and fibrinolytic activiity. This investigation suggests that the effects of moxibustion on platelet functions and coagulative and fibrinolytic activities cause an enhancement of the phagocytic activity in the host defense mechanism.

scholarly journals Mannitol and the Combination of Mannitol and Gelatin Impair Whole Blood Coagulation and the Platelet Function In Vitro

2019 ◽  
Vol 47 (3) ◽  
pp. 199-205
Author(s):  
Thomas Palmaers ◽  
◽  
Elke Kramer ◽  
Julia Hinsenkamp ◽  
Hendrik Eismann ◽  
...  
Keyword(s):  
Blood Coagulation ◽  
Platelet Function ◽  
Whole Blood

scholarly journals In Vitro impairment of whole blood coagulation and platelet function by hypertonic saline hydroxyethyl starch

2011 ◽  
Vol 19 (1) ◽  
pp. 12 ◽  
Author(s):  
Alexander A Hanke ◽  
Stephanie Maschler ◽  
Herbert Schöchl ◽  
Felix Flöricke ◽  
Klaus Görlinger ◽  
...  
Keyword(s):  
Blood Coagulation ◽  
Hypertonic Saline ◽  
Hydroxyethyl Starch ◽  
Platelet Function ◽  
Whole Blood

An Anti-Phosphatidylserine (PS) Antibody, Tarvacin™ That Targets Tumor Blood Vessels Does Not Affect Platelet Function In Vitro.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3950-3950
Author(s):  
Anna M. Dyszkiewicz-Korpanty ◽  
Ravindra Sarode ◽  
Philip E. Thorpe ◽  
Eugene P. Frenkel
Keyword(s):  
Endothelial Cells ◽  
Platelet Aggregation ◽  
Platelet Activation ◽  
Platelet Function ◽  
Whole Blood ◽  
Impedance Method ◽  
Type I ◽  
Tumor Vessels ◽  
Glycoprotein I

Abstract Tarvacin™ is a chimeric anti-PS antibody that is currently in Phase I clinical trials in cancer patients. It acts by targeting PS that becomes exposed on vascular endothelium in tumors in response to oxidative stress in the tumor microenvironment. Tarvacin™ recognizes a complex of PS and the PS-binding protein, β2 glycoprotein I. Host leukocytes are induced to bind to the complex in tumor vessels and destroy tumor vessels by antibody-dependent cellular cytotoxity. However, antibodies directed against PS-associated proteins are also known to elicit anti-phospholipid syndromes (APS). Anti-PS antibodies possibly cause APS by displacing anticoagulant proteins from PS on activated cell or by enhancing the binding of prothrombin; another explanation might be a direct activation of endothelial cells and platelets. The aim of the study was to determine whether Tarvacin ™ induces or interferes with platelet activation caused by ADP, collagen type I or calcimycin in vitro. Blood was drawn from 3 healthy volunteers, aged 31–54, who have not taken any antiplatelet medication for 14 days prior to the study. Dual channel whole blood aggregometer (Chronolog, Havertown, PA, USA) was employed for platelet aggregation studies in whole blood (WB/impedance method) and platelet rich plasma (PRP/optical method). Platelet count in PRP was adjusted to 200 K/μL. Platelet agonists (PS exposure triggers) used in the experiments were as follows: collagen (0.5, 1, 2 μg/mL), ADP (1.25, 2.5, 5, 10 μM), Calcimycin (10, 20, 30 μM) and Calcium ions (1, 2 mmol/L). Tarvacin™ was provided by Peregrine Pharmaceuticals Inc, Tustin, CA. The Anti-CD 20 antibody, Rituxan ™ and physiologic saline were used as controls. Specimens (WB diluted with saline in 1:1 ratio or PRP) with the addition of Tarvacin™ (100 μg/mL) or Rituxan ™ (100 μg/mL) or saline were first incubated on a gentle mixer for 10 minutes; incubation was then continued at 37 ° in the aggregometer well for another 5 minutes. Agonist-induced platelet aggregation was subsequently examined. Platelet aggregation studies in both WB and PRP showed that Tarvacin™ neither induced platelet activation, nor inhibited platelet activation in response to ADP, collagen or calcimycin in vitro. In conclusion, Tarvacin™ does not affect platelet function in the present in vitro assays. Possibly, the epitope on the PS -β2 glycoprotein I complex does not orientate the antibody in a manner that interferes with platelet activation. Alternatively, activated endothelial cells or other factors may be critical to support platelet activation.

Psi Domain of b3 Integrin Has Endogenous Thiol Isomerase Function and Is a Potential New Target for Anti-Thrombotic Therapy

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 382-382
Author(s):  
Guangheng Zhu ◽  
Pingguo Chen ◽  
Adili Reheman ◽  
June Li ◽  
Heyu Ni
Keyword(s):  
Platelet Aggregation ◽  
Recombinant Protein ◽  
Platelet Function ◽  
Intravital Microscopy ◽  
Human Platelet ◽  
Thrombus Formation ◽  
Dependent Manner ◽  
Platelet Surface ◽  
Thrombosis Model

Abstract Abstract 382 Background: Platelets are critical for maintaining hemostasis, but inappropriate platelet activation can lead to pathogenic thrombosis. Integrin aIIbb3, the most abundant protein on the platelet surface, is a key molecule for platelet aggregation and thrombus formation. The PSI domain of b3 integrin is highly conserved among different species but the function of the PSI domain in the integrin family has not been well defined and the role of this domain in hemostasis and thrombosis is poorly understood. It has been reported that b3 integrin possess PDI activity, which may play a role in integrin activation and platelet aggregation. However, whether the PSI domain of b3 integrin has PDI function is currently unknown. Methods: We generated recombinant protein of PSI domain of mouse b3 integrin. Mouse anti-mouse PSI domain mAbs were generated utilising b3 gene deficient mice (b3−/−) immunized with the recombinant protein. Antibody specificity was determined by flow cytometry and western blot. PDI activity assay of mouse PSI domain and native human b3 integrin was performed using reduced and denatured RNase (rdRNase). The effects of the mAbs on platelet function were measured in vitro using aggregometry and in vivo using intravital microscopy thrombosis model. Results: Analysis of the PSI domain of b3 integrin reveals that it contains two CXXC amino acid sequences (the active site motif of PDI), which are highly conserved in different species. Refolding of rdRNase assay showed that the PSI recombinant protein has endogenous PDI activity. Bacitracin, a well-known PDI inhibitor, inhibited PSI domain PDI function in a dose dependent manner. Four anti-PSI domain monoclonal antibodies (mAbs) were generated and showed different inhibitory effects on PDI function of the recombinant PSI domain and purified human platelet b3 integrin. In vitro and ex-vivo studies showed that anti-PSI antibodies inhibited mouse and human platelet aggregation. Using intravital microscopy we demonstrated that anti-PSI mAbs inhibited mouse platelet aggregation and thrombus formation in laser injury thrombosis model. Conclusions: To the best of our knowledge, this is the first time in which it has been demonstrated that the PSI domain of b3 integrin has endogenous PDI activity, which may play important roles in cell biology of platelets and other cells. Our data suggest that the PSI domain of b3 may be a new target in controlling platelet function and our mAbs may have potential in anti-thrombotic therapy. Disclosures: No relevant conflicts of interest to declare.

The Effect of a Medicinal Chinese Herb on Platelet Function

1982 ◽  
Vol 48 (03) ◽  
pp. 301-306 ◽  
Author(s):  
Z Wang ◽  
J M Roberts ◽  
P G Grant ◽  
R W Colman ◽  
A D Schreiber
Keyword(s):  
Platelet Aggregation ◽  
Platelet Function ◽  
Platelet Rich Plasma ◽  
Chinese Herb ◽  
Serotonin Release ◽  
Dependent Manner ◽  
Heat Stable ◽  
Artery Disease ◽  
Dose Dependent

SummaryWe investigated the effect of the Chinese herb Injectio Salvia Miltiorrhizae (ISM) on human platelet function in vitro. ISM inhibited platelet aggregation and serotonin release induced by either ADP or epinephrine in a dose dependent manner. This effect of ISM was observed with both gel-filtered platelets (ID50 = 8–30 μg ISM/ml gel-filtered platelets) and platelets in plasma (ID50 = 400–900 μg ISM/ml of platelet-rich plasma). The active molecule(s) in ISM was heat stable, resistant to acid, base and proteolysis and fractionated on Sephadex 6-25 at MW ~ 280. ISM did not interact with the platelet α-adrenergic receptor, but increased cAMP in intact platelets. The results are consistent with the concept that ISM inhibition of platelet aggregation and release is mediated by an increase in platelet cAMP. The exact mechanism whereby ISM increases platelet cAMP appears to be that of inhibition of cyclic AMP phosphodiesterase. The effect of ISM on platelet function is one mechanism which might explain the therapeutic effect of ISM in experimental and clinical coronary artery disease.

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