Hemostasis_importance& clinical significance.pptx

Hemostasis

1. Hemostasis Dr. P. Poojitha & Dr. E. Muralinath

2. Dr. E. Muralinath

3. Definition. 1) Hemostasis is the mechanism that leads to results in cessation of bleeding particularly from a blood vessel. It is a process that is related to multiple interlinked steps. 3) This cascade terminates into the formation of a “plug” that closes up the damaged site of the blood vessel regulating the bleeding. It starts with trauma to the lining of the blood vessel. Stages. The mechanism of hemostasis can divide into four stages. 1) Constriction of the blood vessel. 2) Formation of a temporary “platelet plug." 3) Activation of the coagulation cascade

4. Purpose of Hemostasis Hemostasis enhances  a series of enzymatic activations that result in the formation of a clot with platelets and fibrin polymer. This clot seals the injured area, regulates and stops further bleeding while the tissue regeneration process happens . Once the injury starts to heal, the plug slowly remodels, and it dissolves with the restoration of normal tissue especially at the site of the damage

5. Issues of Concern Hyper-coagulation. The hemostatic cascade is meant to control hemorrhage and be a protective mechanism. At times, this process is triggered inadvertently while the blood is within the lumen of the blood vessel and without any bleeding. This situation leads to a pathologic phenomenon of thrombosis, which can have catastrophic complications by obstructing blood flow leading to ischemia and even infarction of the tissues supplied by the occluded blood vessels. In this way, a physiologic process becomes a pathologic process leading to morbidity and/or mortality. Some of the examples include Antiphospholipid antibody syndrome, Factor 5 Leiden mutation, Protein C deficiency, protein S deficiency, Prothrombin gene mutation, etc.

6. Hypo-coagulation. When there is any defect in the functionality of any component of this hemostatic cascade, it can lead to ineffective hemostasis and inability to control hemorrhage; this can lead to severe blood loss, hemorrhage and also complications that can hence ensue due to the inhibited blood supply to vital organs. Some of the examples include Von Willebrand disease, hemophilia, disseminated intravascular coagulation, deficiency of the clotting factors, platelet disorders, collagen vascular disorders, etc.

7. Iatrogenic Coagulopathy. Medicine is currently in the era of widespread use of antiplatelet agents like aspirin, clopidogrel, ticagrelor and anticoagulants like warfarin, heparin, low molecular weight heparin, rivaroxaban, apixaban, dabigatran, fondaparinux amongst others for various commonly encountered clinical conditions like cardiac stenting/ percutaneous coronary intervention, atrial fibrillation, deep venous thrombosis, pulmonary embolism, and many more. The way these medications affect the functionality of the various components of clotting cascade can help patients with their clinical conditions. Whatever it may be , it can result in bleeding/thrombosis in cases of inappropriate dosage, non-compliance, medication interactions, and result in significant morbidity and mortality.

8. Organ Systems Involved The physiology of hemostasis involves the: Vasculature Liver Bone marrow All of these systems play an important role regarding the production of the clotting factors, vitamins, and cells for appropriate functionality of hemostasis.

9. Function Hemodynamic Stability.  Under normal circumstances, there prevails a fine balance between the procoagulant and anticoagulant pathway. This mechanism ensures control of hemorrhage as needed and cessation of pro-coagulant pathway activation beyond the injury site/or without any bleeding. If this equilibrium becomes compromised particularly under any condition, this may result in thrombotic/bleeding complications. The hemostatic system also assists regarding wound healing.

10. Cardiovascular System. PGA1 and PGA2 lead to peripheral arteriolar dilation. Prostacyclin produces vasodilation, and thromboxane A2 causes vasoconstriction.  Prostacyclin further stops platelet aggregation and produces vasodilation whereas thromboxane A2 and endoperoxides enhance platelet aggregation and cause vasoconstriction. The balance between the prostacyclin and thrombox­ane A2 leads to the detection of the degree of platelet plug forma­tion. Thus, prostaglandins greatly i mpact temporary hemostasis

11. Mechanism Vaso Constriction.  Within about 30 minutes of damage/trauma to the blood vessels, vascular spasm ensues, which results in vasoconstriction. At the site of the disrupted endothelial lining, the extracellular matrix (ECM)/ collagen becomes exposed to the blood components. Platelet Adhesion.  This ECM releases cytokines and inflammatory markers that result in adhesion of the platelets and their aggregation at that site which results in the formation of a platelet plug and sealing of the defect. The platelet adhesion is a complex process mediated by interactions between various receptors and proteins along with tyrosine kinase receptors, glycoprotein receptors, other G-protein receptors as well as the von Willebrand Factor ( vWF ). The von Willebrand Factor shows its actions via binding to the Gp 1b-9 within the platelets.

12. Platelet Activation.  The platelets that have adhered undergo very specific changes. They release their cytoplasmic granules that include ADP, thromboxane A2, serotonin, and multiple other activation factors. They also undergo a transformation of their shape into a pseudopodal shape which in-turn results in the release reactions of various chemokines. P2Y1 receptors assist regarding the conformational changes in platelets. Platelet Aggregation. With the mechanisms mentioned above, various platelets are activated, adhered to each other and the damaged endothelial surface resulting in the formation of a primary platelet plug. Related Testing Indications. The assessment of platelet function as well as its dysfunction has become vital in the current era in multiple clinical scenarios; several examples are: For patients with clotting or bleeding disorders For patients after cardiac stenting or stroke to monitor the activity of the antiplatelet agents For perioperative evaluation.

13. Platelet Specific. Various tests have undergone development for platelet testing; they include Bleeding time (BT) Light transmission platelet aggregation Impedance platelet aggregation Global thrombosis test PFA-100/200 VerifyNow system Thromboelastography (TEG) Flow cytometric analysis of platelet function

14. Clinical Presentations . With the altering of hemostatic physiology, various clinical outcomes including: Pulmonary embolism Deep vein thrombosis Strok e Myocardial infarction

15. REFERENCES RJ, Morrissey JH. How it all starts: Initiation of the clotting cascade. Crit Rev Biochem Mol Biol. 2015;50(4):326-36. [ PMC free article ] [ PubMed ] 2. Holthenrich A, Gerke V. Regulation of von-Willebrand Factor Secretion from Endothelial Cells by the Annexin A2-S100A10 Complex. Int J Mol Sci. 2018 Jun 13;19(6) [ PMC free article ] [ PubMed ] 3. Swieringa F, Spronk HMH, Heemskerk JWM, van der Meijden PEJ. Integrating platelet and coagulation activation in fibrin clot formation. Res Pract Thromb Haemost. 2018 Jul;2(3):450-460. [ PMC free article ] [ PubMed ] 4. Palta S, Saroa R, Palta A. Overview of the coagulation system. Indian J Anaesth. 2014 Sep;58(5):515-23. [ PMC free article ] [ PubMed ] 5. Thon JN, Italiano JE. Platelets: production, morphology and ultrastructure. Handb Exp Pharmacol. 2012;(210):3-22. [ PubMed ] 6. Manco-Johnson MJ. Development of hemostasis in the fetus. Thromb Res. 2005 Feb;115 Suppl 1:55-63. [ PubMed ]

16. 7. Periayah MH, Halim AS, Mat Saad AZ. Mechanism Action of Platelets and Crucial Blood Coagulation Pathways in Hemostasis. Int J Hematol Oncol Stem Cell Res. 2017 Oct 01;11(4):319-327. [ PMC free article ] [ PubMed ] 8. Paniccia R, Priora R, Liotta AA, Abbate R. Platelet function tests: a comparative review. Vasc Health Risk Manag. 2015;11:133-48. [ PMC free article ] [ PubMed ] 9. Lordkipanidz é M, So D, Tanguay JF. Platelet function testing as a biomarker for efficacy of antiplatelet drugs. Biomark Med. 2016 Aug;10(8):903-18. [ PubMed ] 10. Senst B, Tadi P, Basit H, Jan A. StatPearls [Internet]. StatPearls Publishing; Treasure Island (FL): Aug 22, 2023. Hypercoagulability. [ PubMed ]