Lecture 09 - Thrombosis & Anticoag

Lecture 09 - Thrombosis & Anticoag - Lecture 09...

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Hemostasis - Highly regulated interaction between endothelium, platelet, coagulation - Remember the platelet plug formation - Endothelium is releasing molecule that usually keeps the platelet to be inactive Procoagulant Anticoagulant Vessel Contraction Endothelin Thrombospondin-1? Coagulation Factors/Modulation Prot C inhibitor(s), FVIII, vWF Fibronectin Adhesive Antigens Selectins (CD62P, CD62E) PECAM-1 Integrins (beta 1 and 2) Vascular Remodeling Angiopoietin-2 NO Signaling Inhibition Thrombospondin-1 Platelet Inhibition ADPase (CD39) Nitric Oxide Prostacyclin Clot Inhibition/Lysis Heparan sulfates (natural ligand for anti- thrombin) Thrombomodulin Tissue Factor Pathway Inhibitor Plasminogen Activator Inhibitor-1 Tissue Plasminogen Activator Thromnbospondin-1 inhibition of Nitric Oxide Signaling - Major protein released by platelets (25%) - Action not easily understood, multiple targets, multiple actions - Synthesized by endothelium and fibroblasts (do things that are both prothrombotic and antithrombotic) - In the platelet it tends to downregulate NO
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- **platelet flow along and it’s bathe in NO o BUT once agonist hits it receptor Thrombospondin-1 interactions with vWF - In circulation it promotes the degrade / natural processing of large multinomer - ADAMTS13 -- TS stands for thrombospondin-1 repeats, parts in it (very similar to TS) o Processing of vWF in the circulation and when it is interacting with platelets - At high concentration . ..it can foster thrombosis - It’s complicated they way TS interact with vWF - **not clinically approachable molecule VTE (Deep Venous Thromboembolism) - Legs : red, hot, painful and swollen (inflammation) - Ultrasound : common and quick way to confirm the diagnosis o Probe over legs and shoot sound wave to see reflection coming back o Look for compressibility – if veins collapse then there’s no thrombus there. - CT Scans/MRI – venous/sinus thrombi (stroke) - Incidence increases with age (largest risk factor) - Risk of DVT in Hospitalized patients not receiving thromboprophylaxis o Give heparin or low molecular weight heparin o Patient should walk around or have the leg compression (calves muscle and squeeze the air to act compression; not as effective) - In making the diagnosis: o The d-dimer * these d residue float away and can be measured as d-dimers o fibrin molecule and cross-link covalently to different strands --> d-dimers o d-dimer is negative (200-300 nanograms) --> most diagnostic!!! -
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Lecture 09 - Thrombosis & Anticoag - Lecture 09...

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