Haemostasis Prof. K. Sivapalan. June 2013Haemostasis2 Thrombocytes 2 – 4 μm in diameter. Half...
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Transcript of Haemostasis Prof. K. Sivapalan. June 2013Haemostasis2 Thrombocytes 2 – 4 μm in diameter. Half...
Haemostasis
Prof. K. Sivapalan
June 2013 Haemostasis 2
Thrombocytes• 2 – 4 μm in diameter.• Half life – 4 days.• 300,000 / μL.• Break off from
megakaryocytes. • Colony stimulating
factors and thrombopoietin- liver and kidney.
• 60 – 70 % in circulating blood - balance in spleen.
June 2013 Haemostasis 3
Properties of Platelets
• A ring of microtubules in periphery.• Extensively invaginated membrane.• Membrane contains receptors for:
– Collagen, von Willebrand factor and fibrin.• Dense granules in cytoplasm:
– Serotonin, ADP, other nuclear tides.• α – granules in cytoplasm :
– Clotting factors and platelet-derived growth factor [PDGF – stimulates wound healing and mitogen for vascular smooth muscle.]
June 2013 Haemostasis 4
Platelet activation.
• Binds to exposed collagen and von Willebrand factor (when damage to blood vessel). This is platelet adhesion.
• This activates platelets [ADP]• Platelets change shape, put out
psudopodia and release granules and causes platelet aggregation.
June 2013 Haemostasis 5
Changes in the platelet.• Platelet activation results in change in shape, putting out
psseudopodia, release of granules and aehesion to other platelets.
• Platelet Activating Factor secreted by neutrophils and monocytes stimulates G protein which activates phospholipase C to form diacylglycerol. This also causes release of granules.
• Increased cytoplasmic calcium and diacylglycerol activate Phospholipase A2. This causes release of arachidonic acid from membrane phospholipids which is converted into Thromboxan A2
• Thromboxan and other substances released cause vasoconstriction, platelet aggregation, clot formation
• Aspirin prevents the above reaction and alters the balance between thromboxan and prostacycline and prevents clotting in low doses.
June 2013 Haemostasis 6
Effects of platelet aggregation.
• Repair of the blood vessels.
• Block damaged capillaries.
• Vasoconstriction.• Clotting.• [Test for platelet
function: bleeding time.]
June 2013 Haemostasis 7
Thrombocytopenia.
• Results in capillary bleeding [purpura].
• Caused by-– Marrow disorders.– Alcohol, cytotoxic drugs,
viral infections.– Hereditary.– Immunologically mediated
destruction.– Increased consumption of
platelets.
June 2013 Haemostasis 8
Thrombocytosis.
Causes:• Spleanectomy.• Postoperatively, delivery.• Haemorrhage or haemolysis.• Extreme exercise.Risk:• Thrombotic diseases- deep vein
thrombosis.
June 2013 Haemostasis 9
Hemostasis.
• Vascular spasm: local myogenic, serotonin – lasts for about 20 – 30 minutes.
• Platelet plug.• Clotting of blood.• Organization by fibrous tissue.
June 2013 Haemostasis 10
Coagulation of blood – clotting.
• Fibrinogen → Fibrin.• Polymerization of
fibrin with branching.• Loose mesh of
interlacing strands.• Formation of covalent
bonds → dense, tight aggrigate.
June 2013 Haemostasis 11
Important reactions.
Fibrinogen Fibrin.
Thrombin
Prothrombin
Factor x (activated)
Intrinsic system. 2 – 5 minutes.
Extrinsic system. 15 – 30 Seconds.
Platelet Factor, Ca++,
Activated Factor V.
Stabilization.
Factor XIII
Activated XIII
Clot retraction. [platelets] 30 – 60 min.
June 2013 Haemostasis 12
Coagulation cascade.
Contact with wettable, negatively charged surface – Intrinsic system.
Prekallikerin Kallikerin.
HMW Kilinogen
XII XIIa.
XI XIIa
IX IXa
Tissue factor – Extrinsic system.
[Tissue Thromboplastin- TPL+TFI]
VIIa VII
Ca++
TPL+TFI
X Xa
Activated VIII,
Platelet factor (PL),
Ca++
Ca++, PL, TPL
June 2013 Haemostasis 13
Role of liver in clotting.
• Synthesizes:– Fibrinogen.– Prothrombin.– Other clotting factors.
• Needs:– Vitamin K.
• Removes activated clotting factors.
June 2013 Haemostasis 14
Propagation of clot formation.
• Clot formation can be initiated at any vessel by damage to endothelium by platelet plug.
• Activated clotting factors on the surface of the clot can cause further clotting.
• Platelet plug can form on the surface of the clot which can initiate further clotting
• Rapid flow wash off the factors which are diluted and removed in liver.
June 2013 Haemostasis 15
Clotting and Anti clotting mechanisms.
• Clotting and anti clotting mechanisms are balanced under normal circumstances.
• It is essential to maintain blood in liquid form but prevent loss if the vessels are damaged.
June 2013 Haemostasis 16
Anti clotting mechanisms.
• Anti thrombin III [circulating protease] inactivates activated factors IX,X,XI and XII. Heparin facilitates it.
• Prostacycline of Endothelium antagonizes thromboxane A2 of platelets. (aggregation)
• Endothelium has thrombomodulin. It’s reaction with thrombin leads to fibrinolysis, inactivation of factor V and VIII.
June 2013 Haemostasis 17
Fibrinolytic system.Thrombomodulin in endothelium.
Binds to Thrombin
Prtotein C. Activated protein C.[APC]
Inhibitor of tissue plasminogen activator inhibited.
PlasminogenPlasmin.
Lyses of fibrin.
VIIIa Inactive VIIIa
Va Inactive Va
Tissue plasminogen activator
June 2013 Haemostasis 18
Abnormalities of clotting.
Defective clotting:• Abnormalities of platelet function.• Congenital deficiency of clotting factors-
– Hemophelia A – factor VIII [ X linked].– Hemophelia B – factor IX.
• Von Willebrand factor deficiency.• Vitamin K deficiency and Liver diseases.Enhanced clotting: Increased platelets. Absent Protein C.Intravascular Clotting is thrombosis and if carried in blood it
is embolism. Both can obstruct blood vessels and cause ischemia to organs.
June 2013 Haemostasis 19
Anticoagulants.
• Heparin promotes antithrombin III which inactivates factors IX, X, XI and XII.
Warfarin inhibits Vitamin K.Streptokinase activates plasminogen and
disolves fibrin. [snake, bacteria]Aspirin reduces thromboxan A2 formation.