Procoagulant Platelets

Dale, George L.

doi:10.1161/atvbaha.117.309847

Cited by 20 publications

(12 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Platelets play an essential role in thrombosis in both haemostatic and pathological conditions, including cancer-associated thrombosis. There is cumulative evidence demonstrating platelet heterogeneity with the existence of platelet subpopulations after stimulation with strong agonists [65,66,67,68,69]: aggregatory platelets contribute to the formation of platelet aggregation via activation of GPIIb-IIIa whilst procoagulant platelets participate in the coagulation processes leading to thrombin generation. The subset that form procoagulant platelets respond to potent agonist stimulation by an increase in intracellular Ca 2+ which leads to externalisation of phosphatidylserine (PS) on the outer plasma membrane [65,67,69,70] and supports prothrombinase activity to generate the thrombin burst [65,69] (see Section 2).…”

Section: Host-specific Factors Contributing To Thrombin Generationmentioning

confidence: 99%

Thrombin Generation and Cancer: Contributors and Consequences

Reddel

Tan

Chen

2019

Cancers

View full text Add to dashboard Cite

The high occurrence of cancer-associated thrombosis is associated with elevated thrombin generation. Tumour cells increase the potential for thrombin generation both directly, through the expression and release of procoagulant factors, and indirectly, through signals that activate other cell types (including platelets, leukocytes and erythrocytes). Furthermore, cancer treatments can worsen these effects. Coagulation factors, including tissue factor, and inhibitors of coagulation are altered and extracellular vesicles (EVs), which can promote and support thrombin generation, are released by tumour and other cells. Some phosphatidylserine-expressing platelet subsets and platelet-derived EVs provide the surface required for the assembly of coagulation factors essential for thrombin generation in vivo. This review will explore the causes of increased thrombin production in cancer, and the availability and utility of tests and biomarkers. Increased thrombin production not only increases blood coagulation, but also promotes tumour growth and metastasis and as a consequence, thrombin and its contributors present opportunities for treatment of cancer-associated thrombosis and cancer itself.

show abstract

Section: Host-specific Factors Contributing To Thrombin Generationmentioning

confidence: 99%

Thrombin Generation and Cancer: Contributors and Consequences

Reddel

Tan

Chen

2019

Cancers

View full text Add to dashboard Cite

show abstract

“…To our knowledge, the capacity of procoagulant COAT platelet formation in GT patients has been poorly evaluated, in particular, it has not been comprehensively compared to reference ranges established in healthy subjects [25,33]. In the few publications present in the literature, the number of procoagulant platelets in GT patients differ and they have lower values than the ones we obtained [34][35][36][37][38].…”

Section: Discussionmentioning

confidence: 68%

Characterization of Procoagulant COAT Platelets in Patients with Glanzmann Thrombasthenia

Aliotta

Krüsi

Calderara

et al. 2020

IJMS

View full text Add to dashboard Cite

Patients affected by the rare Glanzmann thrombasthenia (GT) suffer from defective or low levels of the platelet-associated glycoprotein (GP) IIb/IIIa, which acts as a fibrinogen receptor, and have therefore an impaired ability to aggregate platelets. Because the procoagulant activity is a dichotomous facet of platelet activation, diverging from the aggregation endpoint, we were interested in characterizing the ability to generate procoagulant platelets in GT patients. Therefore, we investigated, by flow cytometry analysis, platelet functions in three GT patients as well as their ability to generate procoagulant collagen-and-thrombin (COAT) platelets upon combined activation with convulxin-plus-thrombin. In addition, we further characterized intracellular ion fluxes during the procoagulant response, using specific probes to monitor by flow cytometry kinetics of cytosolic calcium, sodium, and potassium ion fluxes. GT patients generated higher percentages of procoagulant COAT platelets compared to healthy donors. Moreover, they were able to mobilize higher levels of cytosolic calcium following convulxin-plus-thrombin activation, which is congruent with the greater procoagulant activity. Further investigations will dissect the role of GPIIb/IIIa outside-in signalling possibly implicated in the regulation of platelet procoagulant activity.

show abstract

“…Interestingly, PLT aggregates showed two different PLT phenotypes, namely procoagulant PLT (Annexin V-positive/DiOC 6 -negative) and non-procoagulant PLT (Annexin V-negative/DiOC 6 -positive). 30 , 31 Recent evidence highlights that procoagulant PLT primarily evolve on the surface of the growing thrombus where they promote thrombin generation. 40 In our model, circulating HIT Ab-induced procoagulant PLT attached directly to the collagen surface and later incorporated directly into the growing thrombus.…”

Section: Discussionmentioning

confidence: 99%

Platelet phosphatidylserine is the critical mediator of thrombosis in heparin-induced thrombocytopenia

Zlamal¹,

Singh²,

Weich³

et al. 2023

haematol

View full text Add to dashboard Cite

Heparin-induced thrombocytopenia (HIT) is a severe immune-mediated prothrombotic disorder caused by antibodies reactive to complexes of platelet factor 4 and heparin. Platelets (PLTs) and their interaction with different immune cells contribute to prothrombotic conditions in HIT. However, the exact mechanisms and the role of different PLT subpopulations in this prothrombotic environment remain poorly understood. In this study, we observed that HIT patient antibodies (Abs) induce a new PLT population that is characterized by increased P-Selectin expression and phosphatidylserine (PS) externalization. Formation of this procoagulant PLT subpopulation was dependent on engagement of PLT Fc-gamma-RIIA by HIT Abs and resulted in significant increase of thrombin generation on the PLT surface. Using an ex vivo thrombosis model and multi-parameter assessment of thrombus formation, we observed that HIT Ab-induced procoagulant PLTs propagated formation of large PLT aggregates, leukocyte recruitment and most importantly, fibrin network generation. These prothrombotic conditions were prevented via the upregulation of PLTs intracellular cAMP with Iloprost, a clinically approved prostacyclin analogue. Additionally, the functional relevance of P-Selectin and PS was dissected. While inhibition of P-Selectin did not affect thrombus formation, the specific blockade of PS prevented HIT Ab-mediated thrombin generation and most importantly procoagulant PLT-mediated thrombus formation ex vivo. Taken together, our findings indicate that procoagulant PLTs are critical mediators of prothrombotic conditions in HIT. Specific PS targeting could be a promising therapeutic approach to prevent thromboembolic events in HIT patients.

show abstract

Procoagulant Platelets

Cited by 20 publications

References 17 publications

Thrombin Generation and Cancer: Contributors and Consequences

Thrombin Generation and Cancer: Contributors and Consequences

Characterization of Procoagulant COAT Platelets in Patients with Glanzmann Thrombasthenia

Platelet phosphatidylserine is the critical mediator of thrombosis in heparin-induced thrombocytopenia

Contact Info

Product

Resources

About