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  2. I’ve heard that Eliquis and Pradaxa are not really suitable for treating Protein S or C deficiency. Is this true? I’m on Warfarin and want to avoid the regular INR CHECKING AND FLUCTUATION ISSUES.
  3. Anticoagulant protein S – new insights on interactions and functions Magdalena Gierula, Josefin Ahnström First published: 23 July 2020 https://doi.org/10.1111/jth.15025 Protein S is a critical regulator of coagulation that functions as a cofactor for the activated protein C (APC) and tissue factor pathway inhibitor (TFPI) pathways. It also has direct anticoagulant functions, inhibiting the intrinsic tenase and prothrombinase complexes. Through these functions, protein S regulates coagulation during both its initiation and its propagation phases. The importance of protein S in haemostatic regulation is apparent from the strong association between protein S deficiencies and increased risk for venous thrombosis. This is most likely because both APC and TFPIα are inefficient anticoagulants in the absence of any cofactors. The detailed molecular mechanisms involved in protein S cofactor functions remain to be fully clarified. However, recent advances in the field have greatly improved our understanding of these functions. Evidence suggest that protein S anticoagulant properties often depend on the presence of synergistic cofactors and the formation of multicomponent complexes on negatively charged phospholipid surfaces. Their high affinity binding to negatively charged phospholipids helps bringing the anticoagulant proteins to the membranes, resulting in efficient and targeted regulation of coagulation. In this review, we provide an update on protein S and how it functions as a critical haemostatic regulator.
  4. A medical research paper (by Rezende, Simmonds, Lane) suggested Protein S Deficiency may be related to other health conditions besides thrombosis. This is because Protein S interacts with the C4b-binding protein (C4BP). In their conclusion they asked the question: what are the consequences of reduced levels of Protein S on C4BP, and could it be linked to inflammation and autoimmune diseases? Together, we may be able to help answer that question. David Hansson is currently researching this issue and has created an online survey asking about any additional diseases and symptoms affecting us, with a focus on those related to inflammation and autoimmune diseases. Take the Survey at https://proteinsdeficiency.se/ To ensure full anonymity the completed form has to be sent by postal mail Everyone is encouraged to participate
  5. Coagulation, inflammation, and apoptosis: different roles for protein S and the protein S–C4b binding protein complex Suely Meireles Rezende, Rachel Elizabeth Simmonds, David Anthony Lane Blood (2004) 103 (4): 1192–1201. Abstract Protein S (PS) has an established role as an important cofactor to activated protein C (APC) in the degradation of coagulation cofactors Va and VIIIa. This anticoagulant role is evident from the consequences of its deficiency, when there is an increased risk of venous thromboembolism. In human plasma, PS circulates approximately 40% as free PS (FPS) and 60% in complex with C4b-binding protein (C4BP). Formation of this complex results in loss of PS cofactor function, and C4BP can then modulate the anticoagulant activity of APC. It had long been predicted that the complex could act as a bridge between coagulation and inflammation due to the involvement of C4BP in regulating complement activation. This prediction was recently supported by the demonstration of binding of the PS-C4BP complex to apoptotic cells. This review aims to summarize recent findings on the structure and functions of PS, the basis and importance of its deficiency, its interaction with C4BP, and the possible physiologic and pathologic importance of the PS-C4BP interaction. Extract (closing comments) The recent findings establishing an important role for the PS-C4BPβ+ complex in apoptosis suggest that the clinical manifestations of PS deficiency might be more diverse than previously thought. In hereditary PS deficiency, where the severity of the PS defect is anticipated to reflect FPS rather than TPS, this might suggest a requirement to maintain appropriate levels of the PS-C4BPβ+ complex. If so, what are the consequences of reduced levels of the complex? Is there an excess of autoimmune disease and/or inflammation in the affected individuals?105 In this context, it is interesting to note that superficial thrombophlebitis has an inflammatory contribution that might be explained by this new function of PS. The immediate clinical consequences of homozygous PS deficiency are dramatic and may obscure underlying autoimmune or inflammatory sequelae. The new findings also predict that the acquired PS deficiency observed frequently in SLE could be an important modulator of autoimmunity in this debilitating illness. If PS levels are substantially decreased, the level of the PS-C4BPβ+ complex might also be affected, potentially reducing PS-C4BPβ+ binding to the surface of apoptotic cells. This could result in reduced efficiency of cell removal by phagocytic macrophages, and the generation (for example) of anti-DNA antibodies, resulting in autoimmunity. The reported mitogenic activity of PS toward vascular smooth muscle cells170 will also have to be re-examined in the light of the finding that PS exerts a neuroprotective effect in murine models.62 Indeed, the latter observation suggests a possible role of PS as a therapeutic agent with combined anticoagulant and cell protective effects. It is intriguing to speculate how the neuroprotective effects might be modulated by complex formation with C4BPβ+. These newly identified roles for PS and the PS-C4BP complex have exploded the concept that only FPS is the relevant portion in human plasma. Coagulation/anticoagulation is now suggested not to occur in isolation from inflammatory and apoptotic pathways. Indeed, APC has also emerged as an important modulator of these functions, again independently of its anticoagulant role.171 It appears that we have just begun to realize the full potential of PS and C4BP to regulate a wide range of pathophysiologic conditions. Full article: https://ashpublications.org/blood/article/103/4/1192/18113/Coagulation-inflammation-and-apoptosis-different
  6. Last year I started to get problems with loss of sensation in my feet. I thought it was best to get it checked out because of concerns about reduced circulation with my DVT history and post thrombotic syndrome. I had a CT scan and saw an MSK consultant (musculoskeletal), a physio, and then a neurologist. I was subsequently diagnosed with mild peripheral neuropathy. It isn't related to Protein S Deficiency. And there isn't much they can do about it. Just to be sure, the neurologist then requested a wide range of blood tests, and one of the results came back with an odd result. There are three main antibody tests - IgM, IgG, IgA - and my Immunoglobulin M level came back as zero. The tests were repeated several months apart and still zero. Another test showed I had the building blocks for making it (free light chains) and that eliminated the possibility of other related health issues. So I have been waiting for many months to speak to an immunologist to find out how this affects me, and any precautions I need to take. As you can imagine the doctors dealing with immunology are kind of busy right now. Yesterday I was fortunate to have my telephone appointment with an immunologist. They said they don't have previous results to compare with but it appears to be 'normal' for me. Some people without IgM have a tough time dealing with recurrent infections. In my case I am asymptomatic. I don't have IgM but my body still has IgG to fend off infections. This condition is called Selective IgM deficiency (SIgMD). There is nothing to suggest this has anything to do with Protein S Deficiency, we all have other health issues, but hopefully it may inspire some of you to go and see a doctor if a relatively minor ailment is troubling you.
  7. If you are wearing Sigvaris compression stockings please be aware of a product name change. The type known as "Cotton" is now known as "Essential Thermoregulating". This change affects UK prescription re-ordering. Unfortunately the NHS system does not include the article number (which has not changed) so when re-ordering "Cotton" it will appear to be unavailable. Instead your GP needs to search for "Ess Thermo". If they need any assistance they can call Sigvaris UK on +44 1264 326 666
  8. Press release from Bristol-Myers Squibb https://www.bms.com/assets/bms/ca/documents/productmonograph/CANADA-Coumadin-deletion_D-HCP-Communication_FINAL_EN_04.23.2020.pdf Date: April 23, 2020 RE: Discontinuation of Sale and Distribution of Coumadin® (warfarin sodium) Tablets, for oral use. Dear Healthcare Professional, Bristol-Myers Squibb Canada would like to inform you that the sale and distribution of all strengths of Coumadin® (warfarin sodium) tablets will be discontinued in the United States, Canada, Latin America, and Saudi Arabia, due to an unexpected manufacturing issue that could not be resolved expeditiously. Based on stock availability and expiration dates, we anticipate discontinuation of Coumadin® strengths to begin on June 1, 2020. Full discontinuation of all strengths is expected by August 31, 2020. This voluntary action is the result of an unexpected manufacturing issue that cannot be resolved and is not the result of any quality, safety or efficacy issue regarding the product. Indication: COUMADIN (warfarin sodium) is indicated for the prophylaxis and/or treatment of venous thrombosis and its extension, pulmonary embolism, atrial fibrillation with embolization, and as an adjunct in the prophylaxis of systemic embolism after myocardial infarction, including stroke and reinfarction. For your patients currently using Coumadin® (warfarin sodium) tablets,healthcare providers will be required to consider alternatives. BMS cannot recommend a specific product. Prescribing an alternate product is the clinical decision of the healthcare professional in consultation with the patient. In Canada, therapeutic alternatives, including generics, are available. If you have questions or require additional information regarding the discontinuation of Coumadin®Tablets, please contact Bristol-Myers Squibb Canada at 1-800-267-0005 or via e-mail at otc.canada@bms.com. For medical information requests, please contact our Medical Information Services at 1-866-463-6267 or at medical.canada@bms.com. Sincerely, Joseph Atallah Head, Medical Affairs BristolMyers Squibb Canada
  9. RIP my dearest Mumsy Zarin. You are always and shall always be remembered. I miss you. Luv, Ah Chew
  10. Yes you can fly wearing compression stockings. When you are seated you can also do heel-toe exercises to improve circulation. Start with feet on the floor, flat and level, keep the heal on the ground and lift your toes. These also help... https://www.livestrong.com/article/462835-exercises-for-swollen-feet/ Be aware of symptoms after flying for up to six weeks, and act on any concerns by getting checked as soon as possible.
  11. Hi James, I am the first in my family to be diagnosed with PSD My sister was tested and has the possibility but no symptoms yet. I am now switched from coumadin to Pradaxa for life. I have had 4 previous clots, 3 after taking coumadin so that is why I now have Pradaxa. I need to learn more about this condition and drug so that is why I am on this site. Anything you learn and can pass on will be greatly appreciated. Do you know if the University fof N C has any new info? Thanks, Lois Lynda
  12. Hello Mary, Thanks for your reply. Sounds like you are doing fine. I have had 4 blood clots since 2012 and started at the onset with coumadin for life but after my last one in May 2019 my doctor switched me to Pradaxa. It was discovered that I have Protein S Deficiency. I wear compression stockings and lead a most normal life (with a few bumps in the road). I just want to learn more about this condition because I want to live a long and happy life. Thanks and best wishes, Lois Lynda
  13. Thanks for your tips. Yes I am fortunate and my goal is to live to be 100 with a happy life! Lois Lynda
  14. Hi Lois I had my first clot at age 30. Lots of people with PSD have clots in early adulthood so you've done well to get to your 70s before having one. That said, its a shock at any age and having to make accommodations in life is harder the older we get. There's a thread here on the forum where people have posted where they do and which doctors they see. It's a bit old but specialists tends to stick around so have a look there and see if ether is anyone close to you. Wearing compression is good and keeping moving is also good. In the beginning I kept my leg up as much as I could, mainly because it hurt if I didn't! . Any time I sat down I rested by foot on something to my foot was in line with my knee. I lifted the end of my bed so that my foot was higher than my hip when asleep and that way I started the day with a pain free and slim-ish leg. This will help your varicose veins as well as general swelling in your leg. It took years to reduce the swelling in my leg and now I still wear compression because I have what's called Post Thrombotic Syndrome- basically I still have pain if I stand for 5-10 minutes without compression. I can manage a shower then I really have to put my stocking on to go about the rest of my day. As there's nothing we can do about the PSD, the anticoagulants are our shield and everything else is about reducing pain and swelling so that we don't feel limited. Elevation, compression and movement at the things to focus on and bearing weight on your leg to make the 'foot pump' vein in the sole of the foot do the work to push blood back up the leg. I hope some of this helps. Although it can feel lonely and bewildering, you are not alone on this journey. If you are struggling to put stockings on this is a good way to do it. (I think her stocking is loose so easier to get on though!)
  15. Thanks for your reply. I also use my phone to remind me in the evening to take Pradaxa. I take it every A M when I wake up. My doctor recommended this med because you do not have to monitor Vit K intake. I am 77 and had my first clot (of 4) in 2011. My last one was this past May when my doctor switched me to Pradaxa. I live in the San Francisco Bay area and wanted to see a specialist for PSD but none seem to be located here. I read that N C had some . Do you know of any? I am worried about clots developing and traveling to the lungs where I had them before. I have bad varicose veins in my left leg, wear medical support stockings, and try to stay physically active to keep the blood moving. Would you please share any knowledge you may have or comments about treatments/techniques that have worked for you? Thanks so much. LLG
  16. Hello and welcome! Have you had a clot? Is that why you are taking Pradaxa? I take Pradaxa to reduce the risk of having another clot. I have Protein S Deficiency and had a long ankle to groin clot in 2003. There isn't any treatment for PSD and usually you will only be prescribed anticoagulants like coumadin, warfarin, Pradaxa, and Rivaroxaban when you have had a clot and it is likely that you may have another. The only trouble I have with Pradaxa is remembering to take it twice a day! I have an app on my phone to remind me and that helps. This forum is anonymous but if you don't mind being known by your name and friends seeing your posts about PSD you can join our facebook group https://www.facebook.com/groups/2506274438/
  17. Hello All, I am currently on a new medication to treat PSD calle Pradaxa. I would like to know if anyone else is on this medication and what their experiences have been with this new treatment. Also, I'd like to know if you have any advice. I would love to connect with others with PSD to share our experiences.
  18. Tumour-Secreted Protein S (ProS1) Activates a Tyro3-Erk Signalling Axis and Protects Cancer Cells from Apoptosis by Nour Al Kafri and Sassan Hafizi https://www.mdpi.com/2072-6694/11/12/1843/htm Abstract The TAM subfamily (Tyro3, Axl, MerTK) of receptor tyrosine kinases are implicated in several cancers, where they have been shown to support primary tumorigenesis as well as secondary resistance to cancer therapies. Relatively little is known about the oncogenic role of Tyro3, including its ligand selectivity and signalling in cancer cells. Tyro3 showed widespread protein and mRNA expression in a variety of human cancer cell lines. In SCC-25 head and neck cancer cells expressing both Tyro3 and Axl, Western blotting showed that both natural TAM ligands ProS1 and Gas6 rapidly stimulated Tyro3 and Erk kinase phosphorylation, with ProS1 eliciting a greater effect. In contrast, Gas6 was the sole stimulator of Axl and Akt kinase phosphorylation. In MGH-U3 bladder cancer cells, which express Tyro3 alone, ProS1 was again the stronger stimulator of Tyro3 and Erk stimulation but additionally stimulated Akt phosphorylation. Conditioned medium from ProS1-secreting 786-0 kidney cancer cells replicated the kinase activation effects of recombinant ProS1 in SCC-25 cells, with specificity confirmed by ProS1 ligand traps and warfarin. In addition, ProS1 protected cancer cells from acute apoptosis induced by staurosporine, as well as additionally, long-term serum starvation-induced apoptosis in MGH-U3 cells (Tyro3 only), which reflects its additional coupling to Akt signalling in these cells. In conclusion, we have shown that ProS1 is a tumour-derived functional ligand for Tyro3 that supports cancer cell survival. Furthermore, the ProS1-Tyro3 interaction is primarily coupled to Erk signalling although it displays signalling diversity dependent upon its representative expression as a TAM receptor in tumour cells. Extracts from the full text Our data also reveal a greater significance for the role of ProS1 as a TAM ligand than had previously been known in extra-hepatic tissues and beyond its well-established role in regulation of blood coagulation Therefore, our data demonstrate that cancer cells can be a major source of functional ProS1, expressed and modified post-translationally in a vitamin K-dependent process exactly as that which exists for several vitamin K-dependent proteins in the liver
  19. Hi I had a dvt last April 2019. It's cleared now 6 month finished . Treatment heparin raise 7 days. 3 months eliquis 5 mg twise a day and Ecosprin AV 75 mg ONE a day. Pressure tab. Now I am taking only one a day in EcosprinAv 75 mg. Can I fly & wearing compression stockings. Please let me know. Thax
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