Bleeding Disorders Year 4 Internal Medicine Notes OmpathStudy

Bleeding Disorders Year 4 · Internal Medicine Collection: 4TH YEAR ALL NOTES / IMED / I MED BEAUTIFUL NOTES / HEMAT -- Bleeding Disorders\n435 medicine teamwork\n[ ​Important​ ​ ​ ​Notes ​ ​ ​Extra​ ​ ​Editing file​ ]\n\n lecture objectives:\n⇨ Overview of Hemostasis.\n⇨ Congenital Bleeding Disorders.\n⇨ Acquired Bleeding Disorders.\n⇨ Platelet Disorders (Number & Function).\n⇨ Approach to the bleeding patients.\n⇨ Management of Bleeding patients.\n\n★ I highly advise you to view this 1-page lecture summary before starting the lecture.\n\n Done By​: ​Bedoor Julaidan\n& Nouf Altwaijri\nEdited by​:​ Rahaf Binabbad\nRevised By​:​ Luluh Alzeghayer &\nAhmed Alyahya\nReferences: Slides - Master the Boards Essential Haematology- 433 Medicine team \n\n Overview: Hemostasis Definition:\n- The process through which ​bleeding​ is controlled at a site of damaged or disrupted endothelium.\nA dynamic interplay between:\n•​Cellular ​Components: ( Platelets & Endothelium )\n•​Plasma Proteins​ Components: ​3​ protein systems\n1.Blood Coagulation ( Clot Formation )\n2.Fibrinolysis ( Clot Lysing )\n3.Anticoagulant ( Regulating )\nWhenever the vascular integrity is breached (vessel injury) 3 things\nhappen. Firstly, ​vasoconstriction​, secondly ​platelet​ plug formation lastly\nblood clotting (​coagulation cascade​) Platelets:\n- Produced in the ​Bone Marrow​ by fragmentation of the cytoplasm of\nmegakaryocytes​.\n-Each megakaryocyte form ​1000 to 5000​ platelets.\n-Time interval from differentiation of the human stem cell to the\nproduction of platelets ( ~ 10 days )\n-​Thrombopoietin​ → the major regulator of platelets production via\nc-MPL receptor1 (thrombopoietin is produced by liver ​(95%)​ & kidney)\n-Normal platelets counts ( 150 – 400 x 10⁹ )\n-Platelets life span ( ​7 – 10 days​ )\nPlatelets ultrastructure:​ Extremely small & discoid (3 x 0.5 µm in diameter)\nContains 3 types of storage granules:\nα Granules Dense Granules ( δ Granules ) Lysosomes \nClotting Factors ADP & ATP Hydrolytic enzymes\nVWF​ (von willebrand factor) Serotonin\nPDGF2 Histamine\nIGF13 Ionized Ca\nPlatelets Functions:\n1-​Adhesion ​ ( Platelets stick to the vessel Wall )\n-Adhesion is through attachment of ​GP Ib-IX-V4 to ​VWF\n-VWF is synthesized in endothelial cells & megakaryocytes\n-VWF is stored in storage granules of endothelial cells & α granules of\nPlatelets\n-VWF Rises with stress, exercise, adrenaline, infusion of DDAVP\n(desmopressin)\n2-​Aggregation​ ( cross linking of Platelets, platelets stick together )\n-Aggregation is through attachment of​ GP IIb/IIIa​ receptors (found on\nplatelets’ surface) to ​VWF and Fibrinogen​ ​ (mainly fibrinogen)\n3-​Release Reaction & Amplification​ ( aggregation formation & stabilization )\n-​Primary activation by various agonists induces intracellular signaling leading to​ release of α granules\ncontents ​(platelets aggregation and stabilization)​, & ADP ​(platelets activation)​ from dense granules \n1\nThrombopoietin receptor\n2\nPlatelet derived growth factor\n3\nInsulin like growth factor\n4\n​The ​GPIb-IX-V complex​ is a membrane receptor complex present on the platelet surface. \n\n -Formation of Thromboxane A2 by various agonists induces intracellular signaling ​(potentiates platelets\naggregation and causes powerful vasoconstriction)​.\n normally the platelets don’t adhere to the endothelium but when there is injury in the endothelium the circulating\nvWf will attach to subendothelial collagen on one side, and to ​GP Ib​ of platelets on the other side. this binding will\nactivate the platelets. When the platelets are activated, they change in shape and receptor becomes activated\n normally it is inactive . Follows that degranulation of platelets’ granules → fibrinogen, vWF, serotonin (which\ncauses vasoconstriction), ADP (important for platelets activation and aggregation) and Ca ( needed in the secondary\nhemostasis ‘coagulation’). The activated platelets also secretes thromboxane A2 which activates further platelets\nand causes vasoconstriction. lastly, platelets aggregation mediated by GPIIb/IIIa receptor when it binds to fibrinogen.\nMany GP IIb/IIIa receptors will attach to single fibrinogen and this what makes platelet plug.\nPlatelets Inhibitors:\n● Prostacyclin (PGI₂)\n-Synthesized by vascular endothelial cells\n-Potent ​inhibitor​ of Platelets aggregation & causes ​vasodilation​ by rising cAMP\n-​Prevents​ Platelets adhesion to normal vascular endothelium\n● Nitric Oxide (NO)\n-Released from endothelial cells, macrophages, & Platelets\n-​Inhibit​ Platelets activation & promotes ​vasodilation Coagulation cascade:\nIntrinsic pathway:\nWe start by factor 12 which activates factor 11. Factor 11 will activate factor\n9. Factor 9 in the presence of factor 8 will activate factor 10.\nExtrinsic pathway:\nWe start by factor 3 (tissue factor) that activates factor 7. Factor 7 activates\nfactor 10\nCommon pathway:\nStarting by factor 10 that activates factor 2 (prothrombin) in the\npresence of