Hemostasis in Pathology

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 hemostasis
Blood vessels- vasoconstriction
Platelets
Coagulation
Fibrinolytic system
Inhibitor of coagulation

Blood vessels
Endothelial vessels activate
Coagulation cascade
Fibrinolytic systems
Protein C systems
vWF

Properties of blood vessels
Prothrombotic 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 platelets
Platelet adhere to exposed subendotheliat collagen
Adhered platelet undergo release reaction resulting in formation of aggregation.
1. adhesion-vWF- glycoprotein Ib assoc.
2. secretion/release- Ca2+ , ADP, thromboxane A2
3.aggregation-glycoprotein 2b- 3a receptors
Conformational changes of GP2b-3a allows platelet to bind fibrinogens.

2 pathways of coagulation
Intrinsic
Extrinsic
*final common pathway=
Prothrombin
thrombin

Assessment of the pathways
PT(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 coagulation
Antithrombin
protein C and S
Fibrinolytic cascade
Plasminogenplasmin FSP (fibrin split products)
D-dimer is the most important FSP

Summary of hemostasis
Primary 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 disorders
Vascular abnormalities
Platelet disorders
CF (clotting factor) disorders
DIC (disseminated intravascular coagulation)

Vascular abnormalities
Infection
Eg: meningococcemia,rickettsiosses, infective endocarditis
Drug reaction
Hereditary hemorrhagic telangiectesia
Autosomal dominant inheritance
Cushing syndrome
Heroch-scholeinpurpura
Systemic hypersensitivity disease of unknown cause
Polyarthralgia and acute glomerulonephritis
Palpable purpuric rash, coliclyabdomnal pain
=treated with steroids

ITP

ITP (idipathicthrombocutopenicpurpura)
Autoimmune disorder accelerated destruction of sensitized platelets by phagocytic cells in the RES.
*very2 important

Clasification of ITP
Children / adult onset
Acute / chronic
Primary / secondary (idiopathic)

Acute-children (post-infection)
Chronic-adult (> female, 20-40 yrs. Old)
Autoimmune disorders
AntiplateletAb (IgG)
IgG coated platelets removed by spleen
> megakaryocytes in bone marrow
*blood picture !!! Very important.

Characteristic of ITP
Sudden onset of bruising / petechiae
Case 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 infos
t-PA most important plasminogen. plasminogen is activated by streptokinase.
To prevent excessive thrombi destruction, free plasminogen quickly bind to α2-antiplasmin.

PAIs
Endothelial cells regulate anticoagulation balance by secreting PAIs. (plasminogen activation inhibitor)
PAI-block fibrinolysis, procoagulationefct.
increased by certain cytokines.
role in I.V thrombosis accompanying severe inflammation.