Hypercoagulable state (1) Year 4 Internal Medicine Notes

Hypercoagulable state (1) Year 4 · Internal Medicine Collection: 4TH YEAR ALL NOTES / IMED / I MED BEAUTIFUL NOTES / HEMAT -- Thrombophilia\n(Hypercoagulable state)\n435 medicine teamwork\n[ ​Important​ ​ ​ ​Notes ​ ​ ​Extra​ ​ ​Editing file​ ]\n\nlecture objectives:\n⇨ Not given\n\n Done By​: ​Khawla Alammari, Abdulrahman Alshammari\n& ​Rawan Aldhuwayhi\nEdited By​:​ Rahaf Binabbad\nReferences: Slides + Davidson + 434 team \n\n Thrombophilia\n\nBalance of homeostasis:\n- Balance of bleeding and clotting.\n- Imbalance in one direction can lead to:\n1. Hypocoagulable state → ​bleeding\n2. Hypercoagulable state →​ thrombosis \nThe major components of the hemostatic system are:\n1. The vessel wall.\n2. Platelets (and other blood elements).\n3. Plasma proteins (coagulation and fibrinolytic factors).\n\n Stages of normal hemostasis \nPre-injury Fibrin clot formation Limiting clot formation Fibrinolysis \n•​ The endothelium produces •​The endothelium is •​Once hemostasis has been •​The insoluble clot needs to be broken\nanti-thrombotic agents. (thus injured. secured, the propagation of down for vessel recanalization.\nplatelets & coagulation factors •​Platelets are activated. clot is halted by ​natural •​Plasminogen is activated by tissue\ncirculate in non-activated •Then ​Coagulation cascade anticoagulants. plasminogen activator\nstate) is activated. (t-PA)​→plasmin.\n•​Fibrin clot forms. •​Plasmin hydrolyse the fibrin clot,\nproducing fibrin degradation factors\nincluding D-dimer. \nNatural anticoagulants \nAntithrombin Tissue factor pathway inhibitor Protein C & S \n•​Serine protease inhibitor synthesized by the •​Binds to and inactivates ​VIIa & Xa. •​Protein C is activated through binding of\nliver. thrombin to thrombomodulin (structure on the\n•​Destroys activated factors such as ​XIa, Xa & endothelium), activated protein C binds to its\nthrombin (IIa). co-factor ​protein S ​→ then cleaves ​Va & VIIIa.\n•​Both protein C & S are K-dependent and are\ndepleted by warfarin.\n\n ★ Take a deep breath & appreciate this graph while paying attention to the red & green dotted arrows. \n\n Antithrombotic functions of endothelium:​ 1\n\n Prostacyclin (PGI2) Prevents formation of the platelet plug. \nNitrous oxide (NO2) Vasodilation to avoid the stasis of blood and ↓ the chance of thrombus \nThrombomodulin is protein cofactor expressed on endothelial cell surfaces that modifies the substrate specificity\nThrombomodulin of thrombin.The thrombin-thrombomodulin complex activates ​protein C​, initiating an essential anticoagulant\npathway. \nHeparans (proteoglycans) Heparan sulfate (HS) proteoglycans are expressed on cell surfaces and in the extracellular matrix, having essential\nfunctions in development and homeostasis, as well as playing various roles in disease processes. The functions of\nHSPGs are mainly dependent on interactions between the HS-side chains with a variety of proteins including\ncytokines, growth factors, and their receptors. \nTissue factor pathway Inhibit the tissue factor to stop the coagulation\ninhibitors (TFPI) \nPlasminogen activator PAI-1's main function entails the​ inhibition​ of urokinase plasminogen activator (uPA), an enzyme responsible for\nthe cleavage of plasminogen to form plasmin. Plasmin mediates the degradation of the extracellular matrix either\ninhibitors (PAI-1)\nby itself or in conjunction with matrix metalloproteinases.\n\n Coagulation factors:\nI Fibrinogen II Prothrombin III Thromboplastin ​AKA tissue factor \nIV Calcium V Proaccelerin (Labile factor) VII Proconvertin (Stable factor) \nVIII Antihemophilic globulin A IX Christmas factor X Stuart-power factor \nXI Plasma thromboplastin antecedent XII Hageman factor XIII Fibrin stabilizing factor\n\nAltered homeostatic balance:\n- Alteration in the hemostatic balance between blood fluidity and clot formation due to genetic or acquired\ndisorders which shift the balance toward​ excessive platelet aggregation and thrombin generation ​(clot\nformation) that lead to ​thrombosis​. This is known as​ Thrombophilia (Hypercoagulable state)​. Synonyms\nare:​ Hypercoagulable state, prothrombotic state and thrombogenic state. \nRisk factors for thrombosis:\nIn 1856, Rudolf Virchow postulated a triad of factors that leads to intravascular\ncoagulation:\n1. Local trauma to the vessel wall.\n2. Hypercoagulability (Thrombophilia).\n3. Stasis.\nStasis Endothelial injury Hypercoagulable states\n● Immobility. ● Trauma & major ● Conditions that predispose to an increased\n● Paralysis (e.g. CVA). surgery. risk for thrombosis ​either​ venous (most\n● Obesity. ● Central venous common)​, arterial or both.\n● Postoperative & casting. catheters. ● These conditions are being identified more\nHeparin is given up to 2 months after Differentiate between frequently and may be classified as inherited\northopedic surgeries. Risk of DVT is age related thrombosis & cellulitis or acquired.\nthus older pts need prophylaxis more than (especially at catheter site) & P