Term
| Name the 3 methods of haemostasis |
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Definition
| Vasoconstriction, primary haemostasis (platelet aggregation) and secondary haemostasis (fibrinogenesis). |
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Term
| What is the purpose of vasoconstriction in haemostasis? |
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Definition
| Decreases blood loss by increasing vascular resistance and allows contact activation of platelets. |
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Term
| Name the three mechanisms of vasoconstriction |
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Definition
| Immediate vasoconstriction platelet secreted factors and fibrinopeptide production. |
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Term
| What are the five mechanisms of primary hameostasis? |
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Definition
Subepithelium exposed- microfibrils and collagen.
vWF binds to microfibrils- makes subepithelium sticky.
Platelets bind to vWF- glycoprotein binding allows for further platelet binding to collagen.
Platelets degranulate- vWF, ADP, thromboxane a-2 and factor V, Ca2 are released.
Platelets aggregate- Form unstable haemostatic plug. |
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Term
| What are the roles of vWF, ADP, Thromboxane a-2 and Factor V, Ca2+? |
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Definition
vWF – Promotes further platelet adherence
ADP – Promotes platelet aggregation
Thromboxane α-2 – Promotes platelet degranulation & vasoconstriction
Factor V, Ca2+ etc – Promotes Fibrinogenesis |
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Term
| What is the role of viatmin K in clot formation? |
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Definition
| Activation of factors 2 (thrombin),7,10 and 11. Thrombin is required for intrinsic, extrinsic and common pathways. |
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Term
| How do you test the extrinsic pathway? |
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Definition
| Tested by Prothrombin (PT) |
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Term
| What are the roles of the extrinsic pathway? |
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Definition
| Fast pathway, initiates clot to form enough thrombin to catalyse the intrinsic pathway. |
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Term
| What factor is involved with the extrinsic pathway and what is its action? |
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Definition
| Tissue Factor (3) released from damaged epithelium and forms a complex with F7 forming active TF-F7a complex by vitamin K. This acyive complex initiates the common pathway catalysis F10-F10a |
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Term
| How do you test the intrinsic pathway? |
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Definition
| Activated Partial Thromboplastin Time |
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Term
| What are the mechanisms of the intrinsic(contact) pathway? |
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Definition
Slower pathway
Tends to be initiated/accelerated by thrombin in vivo (F12 not important)
Provides bulk of thrombin & fibrin for clotting
N.B. Contact Reaction |
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Term
| What factors are involved with the intrinsic pathway and how are they produced? |
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Definition
F12-F12a – Converted by contact reaction
F11-F11a – Converted by Contact + Thrombin + Vitamin K (or contact + F12a + K)
F9-F9a – Converted by Ca2+ + F11a
F8 -F8a – Converted by Thrombin
F8 carried by vWF in circulation. Thrombin causes dissociation & activation
o F9a + F8a form Complex
F9a-F8a Complex initiates common pathway by catalysing F10 – F10a |
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Term
| How do you test for the common pathway? |
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Definition
| Tested by Thrombin Time (TT) |
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Term
| What is the role of protein C in the common pathway and what disease is associated with this? |
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Definition
Protein C inhibits F5-F5a part of the prothrombin converting complex.
Factor 5 Leiden is a disease of protein C resistance therefore causes increased clotting. |
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Term
| What is the role of thrombin in the common pathway and how is it formed? |
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Definition
Thrombin accelerates the intrinsic pathway and catalyses the formation of F13a.
Converted from prothrombin by F10a and F5a complex. |
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Term
| Which reaction results in a meshwork formation stabilising a platelet plug? |
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Definition
| Thrombin catalyses fibrinogen-fibrin. |
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Term
| What is the role of F13a and how is it formed? |
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Definition
| F13-13a catalysed by thrombin, stabilises fibrin web by cross linking. |
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Term
| What are the functions of fibrinolysis? |
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Definition
| Breaks down a no longer needed clot and limits clotting extent. |
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Term
| How is plasmin formed from plasminogen? |
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Definition
| Plasminogen is produced by the liver, its activation to plasmin is catalysed by Fibrin-tPA Complex (Tissue plasminogen activator)and urokinase. |
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Term
| What is the role of fibrin degradation products, how do you test for them and what catalyses their formation? |
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Definition
| Inhibit thrombin formation and fibrin polymerisation. Detected by a D-Dimer test and fibrin-fibrinogen is catalysed by plasmin. |
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Term
| What does Thrombin time (TT) test and how? |
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Definition
Common pathway
Thrombin added to blood plasma sample
Normal time = ~18s
Tests – Action of thrombin, Presence of/quality of fibrinogen, Fibrin quality |
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Term
| What does Prothrombin time (PT/INR) test and how? |
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Definition
Extrinsic pathway.
Tissue Factor (& other chemicals) added to blood plasma sample
Normal time = ~12s
Tests - Extrinsic Pathway (F7) & all of Common Pathway |
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Term
| What does activated partial thromboplastin time test and how? |
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Definition
Intrinsic Pathway.
Kaolin & lipid added to blood plasma sample, act as surface for contact reaction to occur
Normal time = ~30-40s
Tests – Intrinsic Pathway (F12-F8) & all of Common Pathway |
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Term
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Definition
| 1-2mm diameter – Small spots caused by minor haemorrhage |
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Term
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Definition
| 3-10mm diameter – Larger spots |
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Term
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Definition
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Term
| Name examples of primary haemostatic failure. |
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Definition
| Thrombocytopoenia, Von Willebrand's diseasea and Platelet dysfunction |
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Term
| Name examples of secondary haemostatic failure. |
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Definition
Acquired: Liver disease
Congential: Haemophilia |
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Term
| What are the typical symptoms of primary haemostatic failure? |
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Definition
| Immediate bleeding following trauma, mucous membrane bleeding and purpurae/petechiae. |
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Term
| What are the typical symptoms of secondary haemostatic failure? |
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Definition
| Delayed bleeding (platelet plug formed but not reinforced by fibrin), muscle & Joint bleeding and ecchymoses. |
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Term
| Name and example of haemostatic failure which may be considered both primary and secondary? |
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Definition
| Disseminated intravascular coagulation. |
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Term
| What is the prevalence of Von Willebrand Disease and how is it inherited? |
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Definition
1 in 20.
Neither dominant nor recessive, therefore 1 allele = mild disease 2 alleles = severe disease. |
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Term
| How does Von Willebrand Disease present? |
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Definition
May be asymptomatic other than increased bleeding after surgery/dentist.
May be severe and present in childhood with mucosal membrane bleeding, increased bleeding after trauma and purpura/petechiae. |
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Term
| How do you diagnose and manage Von Willebrand Disease? |
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Definition
Investigations- Increased bleeding time, APTT raised sue to F8 involvement.
Management- vWF transfusion, transexamic acid. |
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Term
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Definition
| X-linked recessive secondary haemostatic disease- prevents stabilisation of platelet plug. |
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Term
| What are the two types of haemophilia and which is the most common? |
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Definition
Haemophilia A- F8 deficiency (most common 1 in 5,000)
Haemophilia B- F9 deficiency, christmas disease |
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Term
| How does haemophilia present? |
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Definition
| In childhood, delayed bleeding following trauma, bleeding into joints/muscles and ecchymoses. |
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Term
| How do you diagnose and treat haemophilia? |
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Definition
Diagnose-APTT raised.
Manage- Factor replacement, desmopressin and transexamic acid. |
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Term
| What is disseminated intravascular coagulation and how do you diagnose it? |
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Definition
Continuous stimulation of clotting cascade therefore consumptive coagulopathy with platelets and factors used up.
Diagnosis- Increased bleeding time, TT, PT and APTT with decreased platelet and factor assays. |
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