7.2 Coagulation & Hematological Investigation PDF

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& (7.2) Coagulation Haematological Investigation Haematology http://www.dreamstime.com/stock-photo-heart-circulatory-system-image12065050 1  Learning Outcomes 1. Describe thrombopoiesis and histology of thrombocytes. 2. Discuss function of platelets in haemostasis. 3. Discuss the role of reticuloendothelial system (RES) in the haemopoietic process and atherosclerosis. 4. Discuss the importance of haematological investigations: Complete Blood Count (CBC) and the Peripheral Blood Film (PBF) 5. Explain the significance of abnormal RBCs, WBCs & platelets counts. 2  Haemopoiesis  Hemocytoblasts Erythropoiesis: Thrombopoiesis: The synthesis of RBCs The synthesis of platelets 3 Leukopoiesis: The synthesis of WBCs  Thrombopoiesis: The synthesis of platelets  Differentiated from myeloid stem cells.  Haemopoietic growth factors that regulate differentiation & proliferation of platelets = ? 4  Characteristics of Platelets  Characteristics of platelets:  2-3 um in diameter  Lack a nucleus but contains mitochondria and alpha-granules  function is dependent upon their activation  activated platelets release extracellular vesicles (microparticles) and respiratory-competent mitochondria (both within membrane- encapsulated microparticles and as free organelles) 5 Luc H. Boudreau et al. Blood 2014;124:2173-2183 Mitochondrial distribution within resting platelets.  Hemostasis Process  Requires both platelets and the coagulation system.  Three basic mechanisms: 1. Vascular constriction  Smooth muscle in artery or arteriole walls contracts 2. Platelet plug formation  Platelets stick to parts of damaged blood vessel, become activated and accumulate in large numbers 3. Blood clot formation (coagulation) 6  Coagulation Pathways 1. Both extrinsic and intrinsic pathways will lead to formation of prothrombinase/ thrombokinase (1) 2. Prothrombinase converts prothrombin  thrombin (2) 3. Thrombin converts fibrinogen (soluble)  fibrin (insoluble; 3) forming the threads of the clot 7  Platelet and Coagulation Pathways Figure 2. Potential role of platelets and the different coagulation pathways in the generation of thrombin and fibrin. Platelets have 3 sources of Tissue Factor (TF): cell-derived microparticles (MP) TF, TF stored in α-granules, and de novo synthesized TF. These different sources participate in the initiation and amplification of the clotting cascade. Assembly of the intrinsic pathway on the surface of the platelet also amplifies the clotting cascade. Finally, platelets bind plasma Factor V (FV), which is internalized, processed, and stored as Factor Va (Fva). This FVa is rapidly mobilized to the cell surface after platelet activation. Nigel Mackman et al. Arterioscler Thromb Vasc Biol. 8 Copyright © American Heart Association, Inc. All rights reserved. 2007;27:1687-1693  The Liver & Haemostasis  The liver plays a major role in haemostasis.  Liver synthesizes most of the coagulation factors, anticoagulant proteins and components of the fibrinolytic system.  Reticuloendothelial system (RES) in the liver helps to regulate coagulation and fibrinolysis by clearing activated clotting and fibrinolytic factors from the circulation.  Liver is an highly vascularized organ with vital venous systems, thus liver diseases can affect abdominal blood flow and predispose patients to significant bleeding problems. 9 The Reticuloendothelial System (RES)  A.k.a monocyte-macrophage system; mononuclear phagocytic system, lymohoreticular system  A generalized phagocytic system located in all tissues, esp those with large quantities of particles, toxins and unwanted substances to be destroyed  Function: 1. Phagocytic function – engulf & digest bacteria, other foreign bodies and tissue debris by the lysosomes 2. Destruction of senile RBCs (macrophage in spleen and liver) 3. Storage and metabolism of iron 4. Formation of bile pigments – from Hb (by Kupffer cells) 10 The Reticuloendothelial System (RES)  Cellular components include:  Monocytes  Macrophages  Endothelial cells in bone marrow, spleen and lymph nodes  Immature monocytes are present in blood; with little immunological activity  After 72 hours, monocytes enter tissue  activated & differentiated into macrophage  wandering or tissue macrophage  swell (cell size increases); more golgi apparatus, mitochondria and lysosomes and increase in intracellular digestive enzymes  In tissues: monocytes swell and cytoplasm is filled with lysosomes  act as scavengers 11 Fixed Tissue Macrophages in the RES Organ/Tissue Fixed Tissue Macrophages Skin Langerhans cells Connective tissue histiocytes Liver Kupffer cells Lungs alveolar macrophage CNS microglia spleen, bone marrow, reticular/dendritic lymph nodes cells Bone Osteoclasts Phagocytes ingesting bacteria 12  RES and Atherosclerosis 13 https://www.youtube.com/watch?v=wbShOXhO6p8  Haematological Investigations  Complete blood count (a.k.a FBC, FBE, FNP, CBE, CBP) – as part of a routine medical examination, for diagnostics and monitoring of disease  Peripheral blood film 14 Blood Collection Tubes 15  Complete Blood Count  A panel of tests that evaluate the three types of cells that circulate in the blood  When is it ordered?  Annual health screening  individuals with signs & symptoms related to blood disorders  Fatigue, has an infuction, bruising, bleeding  Monitoring – anemic patients, chemo patients  Therapies, e.g. CT, to monitor 16 Automated CBC 17 Manual WBC Differential Count 18  What is your CBC result? Hemocytometer Hematocrit http://www.mayoclinic.org/tests-procedures/complete-blood- count/basics/results/prc-20014088 19 *CBC = Complete Blood Count  Peripheral Blood Film  Thin smears are used for: a. Differential leukocyte count b. Stained red cell examination c. Platelet count (indirect method) d. Reticulocyte count e. Siderocyte count f. Malarial parasite (blood parasite) examination g. Thorough study of the morphology of blood cells  Thick smears are used in: a. Diagnosis of malaria b. Diagnosis of filarial c. Diagnosis of trypanosomes http://mt-lectures.blogspot.com/2017/08/lecture-13- 20 morphological-examination-of.html Peripheral Blood Film 21 Filaria, Trypanosomes and Plasmodium infections 22  What does the cell count says Cell Type Levels Condition Common Cause(s) RBC Too Low Anemia Mutation in hemoglobin gene Too High Polycythemia Individuals living at higher altitude, smoker WBC Too Low Leukopenia HIV infection, radiation poisoning, HDF Too High Leukocytosis Infection, cancer Platelets Too Low Thrombocytopenia Hemorrhagic Dengue Fever (HDF) Too High Thrombocythemia Mutation in JAK2 gene What are the clinical consequences of the conditions above? 23  At the end of this lecture… …students should be able to: 1. Describe thrombopoiesis and histology of thrombocytes. 2. Discuss function of platelets in haemostasis. 3. Discuss the role of reticuloendothelial system (RES) in the haemopoietic process and atherosclerosis. 4. Discuss the importance of haematological investigations: Complete Blood Count (CBC) and the Peripheral Blood Film (PBF) 5. Explain the significance of abnormal RBCs, WBCs & platelets counts. 24