Simple answer- yes.

Most coagulation cascade enzymes (factors) bind on the surface of phosphatidyl serine containing membranes. These factors often contain a Gla domain which can bind to PS surface using calcium. Co-localization and possibly allosteric effects of the factors enhance the clotting by accelerating the coagulation cascade.

Thank you very much. I just found information about PS work Microparticles in Hemostasis and Thrombosis A. Phillip Owens III, Nigel Mackman.

I recommend following reviews: 

http://www.ncbi.nlm.nih.gov/pubmed/23775696

http://www.ncbi.nlm.nih.gov/pubmed/24759140

http://www.ncbi.nlm.nih.gov/pubmed/15761668

http://www.ncbi.nlm.nih.gov/pubmed/12814644

Thank you very much.

Circulating blood platelets regulate the initial phase of the hemostatic response through adhesive and aggregatory events and by providing the necessary procoagulant surface for prothrombinase complex assembly and thrombin generation. The signaling pathway(s) that regulate platelet procoagulant activity are largely unknown, although they are distinct from platelet aggregatory signals linked to fibrinogen ligation to the conformationally active αIIBβ3 integrin.It is described a intracellular signaling mechanism involving platelet IQGAP1 that specifically regulates the development of platelet procoagulant activity under conditions of mechanical shear stress.. The exaggerated prothrombinase activity is not associated with enhanced platelet microvesiculation (cytoskeletal proteolysis) and occurs independently of the intracellular calcium release, [Ca2+] but it is specifically coupled to the α-granule exocytic pathway without concomitant effects on aminophospholipid exposure. These observations identify platelet IQGAP1 as an important modulator of normal hemostasis and as an appropriate pharmacological target for control of platelet procoagulant function..

The hemostatically neutral surface of quiescent platelets is preserved by an aminophospholipid translocase that maintains phosphatidylserine (PS)1 and phosphatidylethanolamine within the inner platelet leaflet and phosphatidylcholine on the outer leaflet. This asymmetry is abolished by thrombin, collagen, and ionophores, presumably related to changes in the intracytosolic calcium concentration, [Ca2+] The rapid loss of membrane asymmetry is mediated by a calcium-dependent phospholipid scramblase (with inhibition of the translocase), resulting in rapid bidirectional movement of phospholipids, the appearance of procoagulant PS, and an  acceleration of α-thrombin generation via the assembly of cell surface prothrombinase  The importance of the sudden reversal of this membrane phospholipid in the maintenance of normal hemostasis is best exemplified by Scott's syndrome. This syndrome is a rare bleeding disorder caused by an uncharacterized molecular defect associated with a platelet procoagulant deficiency, which is related to defective membrane PS movement .Nonetheless, the aggregatory potential of platelet agonists (mediated by fibrinogen ligation to the conformationally active αIIbβ3 integrin) is distinct from that linked to exposure of the aminophospholipids PS and phosphatidylethanolamine. In thrombin-activated human platelets, for example, PS exposure is mediated by protease-activated receptor-1 (PAR1), with little or no contribution from PAR4 .

Platelet microvesiculatin (generation of platelet microparticles (PMP)) is closely associated with the exposure of anionic PS on the outer surface of the platelet, thereby considerably enhancing the surface area for activation of the coagulation cascade. PMPs can be generated from high shear stress and are able to cross-activate platelets and endothelial cells, and they are elevated in patients with increased thromboembolic risk and in the subsets of those patients undergoing coronary artery bypass grafting . A causal role for PMPs in thrombosis, however, has been difficult to establish because platelet microvesiculation is intimately associated with platelet activation and aggregation. Although the molecular basis of microvesiculation remains poorly characterized, it appears to be calcium-dependent, requires cytoskeletal reorganization, is associated with calpain and caspase-3 activation, and is morphologically similar to the membrane blebbing and phospholipid exposure phase of nucleated cell apoptosis (5). The molecular mechanism of PMP generation remains unknown, although the molecular pathway appears to be distinct from that regulating PS exposure or platelet exocytosis and is associated with cytoskeletal proteolysis. .

 IQGAPs are conserved homologues of an extended family of proteins; their counterparts in yeast (Saccharomyces cerevisiae Iqg1p/Cyk1p) and amoebae (Dictyostelium discoideum DdGAP1) have key roles in actomyosin ring formation and cytokinesis. Two homologous IQGAPs have been identified and characterized, although expression of IQGAP1 appears broad compared with the previously described hepatocyte-restricted distribution of IQGAP2 . IQGAPs are multidomain scaffolding proteins that presumably integrate intracellular signals with actin polymerization by interactions with the Rho GTPases rac1 and cdc42 (through Ras-GAP-related homology domains, or GRD), Ca2+/calmodulin (through IQ motifs), and F-actin (through calponin homology domains). Interactions with E-cadherin (8), β-cateninand the microtubular protein CLIP-170  have been described previously, although the in vivo physiological significance of these interactions and the regulatory mechanisms leading to IQGAP activation remain incompletely characterized. IQGAP1 to a shear stress-restricted (mechanoreceptor) signaling pathway of platelet activation, specifically regulating the procoagulant properties of the platelet membrane.

Thank you for your help

That the presence of PS plates only, or may relate to any such syncytiotrophoblast cells, endothelial cells, leukocytes, monocytes? During pregnancy, the cells are released syncytiotrophoblast - MPs (subtraction STBM) that circulate in the maternal and fetal circulation and transport of TF, the initiator of coagulation activation. Is the process of PS on the outside and reducing the cytoskeleton proteins refers to all cells and not just the tiles.?

TF is a pretty strong trigger of coagulation. Altered blood matrix (especially polynegatively charged or lipophilic molecules) also generates thrombin but generally not so efficient as TF does. Flip flop at the platelet surface alters blood matrix (surrounding of F12/PK).

Phosphatidyllserine is a procoagulant phospholipid moiety on the external surface of the platelets and plays an important role in hemostasis.  Platelets attached to the thrombus via vWF and fibrinogen become activated and express phosphatidylserine (PS) on the outer surface of the platelet membrane.  Circulating activated factor IX binds to its specific receptor on the platelet surface and to its cofactor, VIIIa, as well as to Factor X, in combination with calcium and PS.  This intrinsic tenase complex amplifies production of Xa on the platelet surface.  Both Xa and Va  bind to the platelet surface receptors forming a prothrombinase complex when their zymogenic substracte, Factor II, is then bound together with calcium and PS.  This thrombin generation feeds back on itself to further activate the platelets.and the intrinsic pathway of the coagulation cascade.

Thank you for your help. I found the work Thromb Res. 2010 Apr; 125 Suppl 1: S42-5. doi: 10.1016 / j.thromres.2010.01.035. Epub 2010 Feb 26.

Analysis of tissue factor positive Microparticles.

Key NS. It turns out that TF can bind factor VII without the presence of PS on the surface of MPs. But it could do better microparticle PS (-) at the surface and most (increase the catalytic efficiency), including TF and PS (-)

I am writing to work with an extrinsic  way involving the activation of coagulation TF. Most of the work describes microparticles resulting from platelet MPs and two surface active receptors having procoagulant activity. Question..... Does the presence of PS MPs formed only with tiles. Describes that it is as much as 95% of such microparticles. Is the PS is expressed on the surface of the other MPs produced from leukocytes, monocytes, platelets and above all syncytiotrophoblasts that MPs released into the blood circulation in the area of the bearing.

Kuczynski,

This is a good question.  Although the PS may be specific for the platelets.  All the platelet-derived microparticles will have PS.  However, MP derived from leukocytes, monocytes and for that matter syncytiotrophoblasts may not have PS on their surfaces.  However,  leukocytes will have TF expression on their surfaces in certain conditions like cancer and all the leucocyte-derived microparticles then will have TF on their surfaces.  The same might be true for the syncytiotrophoblasts.

Indeed, the presence of PS recognized more in the literature is the platelets. 95% of platelets derived microparticles, these microparticles it also may PS. 3-5% of the microparticles derived from eukaryotic cells containing the nucleus. Are exchanged leukocytes, monocytes, macrophages and endothelial cells, and microparticles of syncytiotrophoblast. In pregnant these 3% of the microparticles that are on the surface of TF can be quite a problem, causing blood hypercoagulability, and more if it is released it is observed in preeclampsia. Is the PS is syncytiotrophoblast cells? ... that is the question ..... I have not found reports on the subject..

I don't think that syncytiotrophoblast may have PS.  However, TF on syncytiotrophoblast is possible.  You are absolutely right that TF on microparticles from leukocytes and platelets causes hypercoagulability such cancer-associated hypercoagulation.

thank you very much. During extrinsic coagulation cascade operates TF on cells in the initialization phase. Platelets are activated by thrombin in the propagation phase. I'm interested in the fact that the appearance of microparticles of syncytiotrophoblast cells which transport TF into the blood vessels of the bearing and then into the circulation of pregnant. MPs-TF can initiate the formation of thrombin generation that stimulates the platelets to clot.

From the your info I learned that  the professor was in Kaunas  is 80 km from Suwalki greeting

I am glad that all your questions are now addressed.  I hope to visit you and discuss further your research project, when I come to Kaunas.  Thanks.

Thank you. Maybe I'll see you in Kaunas and in Suwalki. Welcome to Polish.

Lithuania is now the European Union and there is no customs border. From Kaunas to Suwalki is an hour's drive away. I am interested in the research  project  In Info is my e-mail

Dear Jaroslaw and Omar,

Trying to answer/comment this question I would say that PS is not only important in Hemostasis but it is mandatory. Indeed, it has been recognized that coagulation reactions in solution are 1000 x less productive than on PS+ membranes, be there provided by activated/stressed/apoptotic cells (e.g. platelets) or their cell-derived PS+ microparticles. PS+ membranes are THE place for coagulation reactions to take place.  Try to make a PT assay using MPFP (MP-deprived Platelet free plasma) and you will see ... no coag at all, no reaction from you coagulometer! MPs (because of PS) are mandatory. Or if ever you add external Annexin V or Lactadherin (PS high affinity binding proteins) you will also inhibit clotting.  

When Dr Iqbal states " I don't think that syncytiotrophoblast may have PS. However, TF on syncytiotrophoblast is possible." he is fully right (see e.g. I. Sargent et al litterature). Syncytiotrophoblast may NOT have PS whenever they remain viable quiescent cells (the same for any viable quiescent cell in which PS stays on the inner cell membrane due to ATP-dependent flip-flop mechanisms). But if they are stressed or induced towards apoptosis, they are likely to send out MPs budding from their surface and expressing PS as most MPs do (although not 100% of those see e.g. E. Boilard litterature, as well as Perez-Pujol et al plus many others). These MPs may also most likely express TF and be potential inducers of coagulation and, at worse, (pre-)thrombotic states. 

Hi Philippe,

That is a very good response.  Best Wishes,

Omer

Phospholipids are cofactors of extrinsic and intrinsic tenase and of prothrombinase. Phospholipids also induce the activation of F12 to F12a and of prekallikrein to kallikrein (altered matrix (intrinsic) coagulation).

The detection of antibodies against phosphatidic acid is an important aid in the diagnosis of the antiphospholipid syndrome (APS).

Phosphatidic acid antibodies appear almost exclusively together with anticardiolipin antibodies and / or phospatidylserine antibodies. Its detection is compatible with a diagnosis of antiphospholipid syndrome (APS) and helps in the assessment of the risk of thrombosis in patients with systemic lupus erythematosus (SLE) ) And lupus-like diseases. AFLs are a heterogeneous group of autoantibodies directed to various compounds such as negatively charged phospholipids, plasma proteins, membrane proteins of endothelial cells or platelets, with which they can form complexes of high affinity for the surfaces of anionic phospholipids; The major antigens against which the antibodies are targeted are β-2 glycoprotein I, prothrombin, prothrombin phosphatidylserine, vimentin / cardiolipin, annexin A5, annexin A2, protein C, protein S, oxidized low density lipoproteins (LDL), acid Lysophosphate (LBPA) and sulfatide levels. The prevalence in the general population of aFL is between 5%; However, only a minority will develop the disease, acute myocardial infarction , deep venous thrombosis , and morbidity in pregnancy

This discussion is going to become a nice Hemostasis course! Thank you Juan Carlos for add-ons. We all agree that anionic phospholipids, the so-called procoagulant PL are major players in our field of Hemostasis. Hopefully meet you next July at ISTH Berlin (?) Philippe