Haematolgy 3

➢The mechanism for dealing with bleeding and clotting ➢Haemostasis comes from the Greek - heme meaning blood and stasis to halt

• Maintain the fluidity of circulating blood • Limit and arrest bleeding following injury by formation of a blood clot whilst at the same time maintaining blood flow through the damaged vessel • Removal of a blood clot upon completion of wound healing

1) the endothelium/blood vessel Wall is destroyed 2)platelets cause coagulation 3)coagulation factors

-anuclear -circulate for 7-10 days -each days 100 billion is produced from megakaryocytes to maintain Normal count

➢Their primary physiological role is in blood clotting ➢Detect damaged vessel endothelium ➢Accumulate at the site of the vessel injury ➢initiate blood clotting to block the circulatory leak ➢They are involved in ALL stages of haemostasis ➢Primary haemostatic plug (platelet to platelet interactions) ➢Secondary haemostatic plug (platelet – coagulation protein interactions) ➢Involved in tissue injury, inflammation and wound healing by attracting and binding leukocytes

-Largest (50-100μm) and rarest cells in BM -Polyploidal (More than one nucleus) -Unique to mammals -Can produce ~3000 platelets (compared to 2 daughter cells in other lineages) -Platelet formation is far more complicated than the production of white cells

Phase I -Megakaryocyte maturation(need to be big to have enough protein) → Endomitosis (DNA replication without cell division) →Cytoplasm enlargement (cytoskeletal proteins and platelet granules) Phase II -Platelet generation → Mature megakaryocytes extend long branching processes (proplatelets) → Organelles and granules are transported to proplatelets → Driven by the cytoskeleton They migrate to blood vessels in bone Marrow Stimulated by thrombopoietin tpo

-nitric oxide ptrostacyclin prevents platelets from being active as well as stops them from sticking -continuous barrier of endothelium which prevents platelets sticking to collagen -natural anticoagulants such as anti thrombotic which stops unwanted coaugulation -platelets are not active

-Platelets become active -Endothelium is damaged to platelets stick to collagen and to Von willebrand factor(vwf) at site of blood vessel damage(it forms a bridge between collagen and platelets sticking, stick to vwf first then collagen) -Platelets become activated, change shape, release granules and aggregate -prothrombotic factors

-Fast series of reactions for stoppage of bleeding -Requires clotting factors, and substances released by platelets andinjured tissues

• Constriction of blood vessels (vasoconstriction) • Platelet plug formation • Coagulation (blood clotting)

➢Direct injury to vascular smooth muscle ➢Chemicals released by endothelial cells and platelets ➢Pain reflexes

12 factors Castcasereaction Fibrinogen,prothrombin Tissue factor

Vessel injury-tissue factor-blood coagulation cascade -thrombin-fibrin(net,sits over blood cloth,stabilising clotting-stable haemostatic plug

Consists of two distinct pathways: -the extrinsic (tissue factor pathway) -the intrinsic pathway X marks the spot and is the common factor

➢Soluble fibrinogen converted to insoluble fibrin ➢Stabilises platelet clot

-Two mechanisms limit clot size >Swift removal and dilution of clotting factors >inhibition of activated clotting factors -Fibrinolysis breakdown of clots >Removes clots after healing >Begins within two days; continues for several

• Thromboembolic disorders: undesirable clot formation • Bleeding disorders: abnormalities that prevent normal clot formation

-clot that develops and persists in unbroken blood vessel –May block circulation leading to tissue death –Deep venous thrombosis (DVT) and pulmonary embolism

thrombus freely floating in bloodstream Formed somewhere else ans a small piece fractured

The fracture get stuck somewhere else

atherosclerosis, inflammation, slowly flowing blood or blood stasis from immobility

-Aspirin= Cyclooxygenase inhibitor, that blocks thromboxane A2 synthesis and inhibits platelet aggregation(arteries ) -heparin = Anticoagulant used clinically for pre- and postoperative cardiac care(venous) -Warfarin= for those prone to atrial fibrillation, interferes with action of vitamin k (its an antagonist)(rat poison),used in old patients -Apixaban, Rivaroxaban= Factor X Inhibitors (DOACs (direct oral anticoagulants)/NOACs (novel oral anticoagulants)

➢Thrombocytopenia - deficient number of circulating platelets ➢Haemophilia includes several similar hereditary bleeding disorders ➢Haemophilia A: most common type (77% of all cases); factor VIII deficiency ➢Haemophilia B: factor IX deficiency ➢Haemophilia C: mild type; factor XI deficiency ➢Von Willebrand’s Disease most common inherited bleeding disorder