Disorders Of Blood Coagulation Flashcards
What is the importance behind clotting?
- Tightly regulated process that stops bleeding at the site of an injury + prevention of pathogen entry
- Remains localized
- Blood loss is stopped by plug formation
- Composed of platelets + fibrin
Describe how clotting is activated and outline the major processes of it?
- Endothelium in blood vessels normally maintains an anticoagulant surface with platelets + fibrinogen circulating + ready
- Injury exposes collagen to come into contact with blood components to activate clotting
- Two main processes of haemostasis - primary and secondary -> fibrin formation
Describe primary haemostasis
- Endothelium continuously releases \ amounts of von Willebrand Factor (circulates in blood) + stores VWF in Weibel-Palade bodies for release when appropriately stimulated
- If collagen becomes exposed to blood (endothelium is damaged), VWF binds to it
- Platelets express receptors for both collagen + VWF & become activated when these proteins bind to them
- Activated platelets express functional fibrinogen receptors
- aggregation + adhesion of platelets
Describe secondary haemostasis
- Endothelial cells come in contact with the blood
- Tissue factor (TF), expressed by nearly all sub-endothelial cells activates coagulation cascade
- Minor burst of thrombin
- Factor FVIla binds to TF
- Conversion of prothrombin to TR
- TR activates receptors on platelets + Endothelium
- amplifying platelet aggregation + initiating release of stored von Willebrand Factor from endothelial cells.
Describe amplification stage?
- Each activated factors activates more of the next
- Thrombin activates two cofactors, Factor VIlla + Factor Va
- Form calcium ion-dependent complexes on the surface of platelets with Factor IXa (tenase complex) + Factor Xa (the prothrombinase complex)
- Increase production of Factor Xa + thrombin, respectively
- Thrombin = fibrinogen
- fibrin mesh formed
- Plug of platelets + fibrin formed
Describe the fibrinolysis stage?
- Plasminogen activated to plasmin via tissue plasminogen activator
- Plasmin degrades the fibrin mesh
- Produces Fibrin degradation products (D-dimers - marker) which are cleared
State 3 natural anticoagulants involved?
Antithrombin, protein C, Protein S
Describe antithrombin, how it works and state a medication that uses the same pathway?
- serpin (serine protease inhibitor)
- Increase Activity via binding heparan to binding sites on endothelial cells
- Major checkpoint to inhibit coagulation (thrombin), IXa, Xa)
- Activity of med heparin
Describe the use of protein C and Protein S as natural anticoagulants?
- Anticoagulant Plasma proteins
- Thrombin bound to thrombomodulin on endothelial cells
- Activates activated protein C (APC)
- Protein S is an APC cofactor which helps binding to cell surfaces
- APC degrades cofactors FVa and FVIlla
Where can defects occur in clotting?
- Coagulation proteins
- Platelets
- Endothelium
What is haemophilia and state 3 disorders that can lead to this?
- Failure to clot (bleeding disorder) -> haemorrhage + bleeding into joints
- Mutations in coagulation factors -> haemophilia A (80% - M FVIII) + B (20% - M FIX)
- Platelet disorders - von Willebrand disease -> Inherited defect/deficiency in vWF -> Affects mucous membranes + varied bleeding
- Collagen abnormalities -> fragile blood vessels + bruising
What is thrombophilia and state 2 ways this can occur?
- Excessive clotting leading to thrombosis
- Inherited: mutations in coagulation factors
- Acquired: malignancy increases clotting factors
- Both lead to DVT
What is Disseminated intravascular coagulation (DIC) and state 2 ways this can occur?
DIC -> whole body clots -> Infection + Depletion of clotting factors + platelets (sepsis) -> bleeding
Describe 4 excessive clotting disorders and describe them?
- Factor V leiden mutation: Antithrombin deficiency, Protein C def. + Protein S def.
- FVLM: Resistance to APC, FVa is not inactivated + increased risk of DVT
- AT def: Thrombin, IXa and FXa are not inactivated + Increases risk of DVT
- Protein C + S def: increased risk of DVT
What is the development of a venous thrombus dependent on?
- Virchow’s trial
- Hypercoagulability, stasis + vessel wall injury
- Alterations in the constituents of the blood, Changes in normal blood flow + Damage to the endothelial layer
