What is normal hemostasis?Normal hemostasis- process by which bleeding

at any site arrested by the formation of a hemostatic plug.

1. Followed by removal of plug so that normal flow of blood through vessels is maintained.

Components of hemostasisBlood vessels- vasoconstrictionPlateletsCoagulationFibrinolytic systemInhibitor of coagulation

Blood vesselsEndothelial vessels activate

◦Coagulation cascade◦Fibrinolytic systems◦Protein C systems◦vWF

Properties of blood vesselsProthrombotic prop.

◦vWF◦Tissue factor –factor 3 +

thromboplastin◦Fibrinolysis inhibitor- PAIs

Antithrombotic prop.◦Antiplatelet effect- prostacyclins,

nitric oxide◦Anticoagulant effect –

thrombomodulin Thrombomodulin inactivates thrombin to

make it an anticoagulant!

◦Fibrinolysis properties- t-PA Clear fibrin deposits from endothelial

surfaces.

Role of plateletsPlatelet adhere to exposed subendotheliat

collagenAdhered platelet undergo release reaction

resulting in formation of aggregation.

1. adhesion-vWF- glycoprotein Ib assoc.2. secretion/release- Ca2+ , ADP,

thromboxane A23.aggregation-glycoprotein 2b- 3a

receptors◦Conformational changes of GP2b-3a allows

platelet to bind fibrinogens.

2 pathways of coagulationIntrinsicExtrinsic

*final common pathway=◦Prothrombin

thrombin

Assessment of the pathwaysPT(prothrombin time)- extrinsic

pathway◦Factor 7, 10, 2, 5

PTT(partial thromboplastin time-intrinsic pathway◦Factor 12, 11, 9, 8, 10, 5, 2 +

fibrinogen

Control of coagulationAntithrombin

◦protein C and S

Fibrinolytic cascade◦Plasminogen plasmin FSP

(fibrin split products)◦D-dimer is the most important FSP

Summary of hemostasisPrimary hemostasis

◦BV constriction◦Platelet plug formation

Secondary hemostasis◦Activation of clotting cascade◦Deposition &stabilisation of fibrin

Tertiary hemostasis◦Dissolution of fibrin clot◦Removal of fibrin plug

Bleeding disordersVascular abnormalitiesPlatelet disordersCF (clotting factor) disordersDIC (disseminated intravascular

coagulation)

Vascular abnormalities Infection

◦ Eg: meningococcemia,rickettsiosses, infective endocarditis

Drug reactionHereditary hemorrhagic telangiectesia

◦ Autosomal dominant inheritance

Cushing syndromeHeroch-scholein purpura

◦ Systemic hypersensitivity disease of unknown cause◦ Polyarthralgia and acute glomerulonephritis◦ Palpable purpuric rash, colicly abdomnal pain

◦ =treated with steroids

ITP

ITP (idipathic thrombocutopenic purpura)Autoimmune disorder

accelerated destruction of sensitized platelets by phagocytic cells in the RES.

*very2 important

Clasification of ITPChildren / adult onsetAcute / chronicPrimary / secondary (idiopathic)

Acute-children (post-infection)Chronic-adult (> female, 20-40 yrs.

Old)Autoimmune disordersAntiplatelet Ab (IgG)IgG coated platelets removed by

spleen> megakaryocytes in bone marrow

*blood picture !!! Very important.

Characteristic of ITPSudden onset of bruising /

petechiaeCase history of infectious disease

◦Appear respiratory tract infection in about 3 weeks prior to onset of bleeding

Dangerous-intracerebellar hemorrhage

<20,000 platelet count.

ITP bone marrow aspirate

Additional infost-PA most important

plasminogen. plasminogen is activated by streptokinase.

To prevent excessive thrombi destruction, free plasminogen quickly bind to α2-antiplasmin.

PAIsEndothelial cells regulate

anticoagulation balance by secreting PAIs. (plasminogen activation inhibitor)

PAI-block fibrinolysis, procoagulation efct.◦ increased by certain cytokines.◦ role in I.V thrombosis accompanying

severe inflammation.