Blood Coagulation Flashcards
(36 cards)
1
Q
What are the main constituents of coagulation?
A
- Vessel wall lined by endothelium.
- Platelets - derived from megakaryocytes in marrow.
- Coagulation factors in un-activated state.
- Inhibitors of coagulation.
- Fibrinolytic system and inhibitors.
2
Q
What are coagulation factors?
A
- Coagulation factors = proteins which circulate in an inactive state and become activated in a cascade reaction and cause clotting.
3
Q
Describe the role of endothelial cells.
A
- Line blood vessels and form a barrier.
- Produce thrombomodulin and heparin sulphate to inhibit thrombin production.
- Enzymes to degrade platelet granule-derived molecules.
- Prostacyclin and nitric oxide (NO) to reduce platelet adhesion.
4
Q
Describe platelets.
A
- Fragments of megakaryocyte cytoplasm.
- Budded off into lumen of marrow sinusoids.
- Production stimulated by thrombopoietin (TPO) - liver derived.
- Cicrulate for 5-10 days with ~30% ‘stored’ in spleen.
- Form a plug when attracted by lowered prostacyclin and by collagen exposure.
- Thromboxane A2 and serotonin from platelets cause vasoconstriction.
5
Q
How do platelets adhere to the vessel wall?
A
Platelets adhere to the vessel wall via Von Willibrand’s factor and Glycoprotein Ib.
6
Q
How do platelets adhere to each other?
A
Platelets adhere to each other via glycoprotein IIb-IIIa and fibrinogen.
7
Q
What are the functions of platelets?
A
- Form a plug when attracted by lowered prostacyclin and by collagen exposure.
- Granule release.
- Fibrin formation.
8
Q
Describe what happens in the coagulation cascade.
A
- Factors present in inactive state - activated by ‘intrinsic or extrinsic’ pathway.
- Fibrin is needed to form a clot.
- Diagram:
- Black = accelerator
- Red = brakes (these try to prevent the coagulation cascade)
9
Q
List the factors which inhibit coagulation.
A
- Protein C activated by thrombomodulin-thrombin complex.
- With co-factor - factor S - Va and VIIIa are degraded.
- Antithrombin (previously antithrombin III) inhibit Xa and IIa.
- Heparin cofactor II inhibits IIa.
- Heparin stimulated antithrombin and heparin cofactor II.
- Only a very small amount of coagulation factor is needed; its effects build faster and faster. Results in coagulation happening faster than it can be inhibited.
10
Q
Describe the fibrinolytic system.
A
- Plasminogen activated to plasmin by tissue plasminogen activator (tPA) - from endothelial cells.
- Fibrin broken down into ‘fibrin degradation products’ including D dimers - a measurement of fibrinolysis (a measure of how well a clot has broken down).
- Inhibitors of fibrinolytic system.
- Theraputic use with eg. streptokinase to tPA for ‘clot busting’ eg acute myocardial infarction or thrombotic stroke.
11
Q
What is fibrin?
A
Fibrin = meshwork of protein that can be brokwn down into its constituent parts.
12
Q
What is the ‘gold-standard’ time frame for thrombolysis in stroke treatment?
A
Gold standard for stroke treatment - ideally in under 3 hours.
13
Q
What is clot retrieval?
A
- Clot retrieval - putting a cathater in to pull the clot out.
- Arguably more effective than dissolving the clot.
14
Q
How do you measure coagulation?
A
- Full blood count - includes platelet count / size / granules, but is a poor assessment of platelet function - specialised tests of aggregation can be done.
- Ref range 150-400 x109 /L
15
Q
What is caused by an FBC <30-50 x109/L?
And <10 x109/L?
A
- Easy bruising and purpura when FBC <30-50 x109 /L (thrombocytopaenia).
- Risk of major bleeding if <10 x109/L.
16
Q
Describe a bleeding time test.
A
- In vivo test of overall clotting - mainly platelet function.
- Lots of poorly controlled variables, so not often done.
17
Q
Describe a prothrombin time (PT) test.
A
- All coagulation tests are done on citrated plasma
- Removes Ca2+
- At 37℃, thromboplastin and Ca2+ are added.
- Measure time until clot forms - extrinsic and common pathway.
- Prolonged by low levels of II, X and VII.
18
Q
Describe an activated partial thromboplastin test (APTT).
A
- Ca2+ kaolin and phospholipids added to citrated plasma.
- Measure of intrinsic and common pathway.
- Prolonged in haemophilia and by heparin.
19
Q
What is fibrinogen?
How is it measured?
A
- Fibrinogen is the final substrate for making fibrin.
- It can be measured by:
- Clot density
- Thrombin time - thrombin and Ca2+ added to citrated plasma
20
Q
Describe the further tests which can be carried out on prolonged PT or APTT.
A
- Correction tests and factor assays
- A prolonged PT or APTT can be tested further:
- 50:50 mix with normal plasma to see if the prolongation corrects.
- Factor assays to look for specific deficiencies.
21
Q
Describe the genetic causes of haemophilia A and B?
A
- Haemophilia A and B:
- X-linked defect in VIII or IX gene.
- Commonly a new mutation so no family history.
- Female heterozygotes (carriers) are not affected.
22
Q
What is the prevalence of Haemophilia A&B?
A
~1:5000 males
23
Q
Describe the variation in severity of haemophilia A&B.
A
- Can be very mild - chance finding or issue for surgery.
- Severe (<1% VIII level) - frequent bleeds into joints and soft tissues.
24
Q
Describe Von Willebrand disease.
A
- Usually autosomal dominant.
- Defect in platelet adhesion and binding of VIII.
- Up to 1% population.
- Mild disease - easy bruisingm heavy periods.
- Severe disease - similar to haemophilia.
25
Describe acquired coagulation disease of the liver.
* Liver disease - alcohol / autoimmune / hepatitis.
* All coagulation factors are produced in the liver.
* PT and fibrinogen abnormal, later APPT abnormal.
* Bleeding due to abnormal clotting, low platelets.
* Portal hypertension causing oesophageal varices and upper GI bleeding.
26
Describe acquired coagulation disease - disseminated intra-vascular coagulation (DIC).
How do you treat it?
* Activation of clotting cascade due to:
* Trauma
* Malignancy eg. prostate cancer
* Sepsis
* Amniotic fluid embolism
* Causes depletion of clotting factors and damage due to the clot.
* Treat the cause and replace the clotting factors.
27
What is thrombocytopaenia?
Low platelets
28
What could thrombocytopaenia be due to?
* Could be due to:
* Under-production
* Increased use
* Abnormal distribution
29
Describe thrombocytopaenia due to under production of platelets.
* Abnormal marrow function - acute leukaemia, metastatic tumour, aplastic anaemia.
* Expected side effect of cytotoxic chemotherapy.
* Idiosyncratic and unexpected drug adverse effect eg. co-trimoxazole, anti-inflammatories.
30
Describe thrombocytopaenia due to increased use.
* Immune thrombocytopaenia (ITP)
* Autoimmune disease of children or adults.
* May be triggered by infection or drug.
* Auto antibodies to platelets.
* Treated by:
* Watch and wait
* Steroids
* Immunoglobulins
* Splenectomy
* Drugs to mimic thrombopoetin
31
Describe thrombocytopaenia due to abnormal distribution.
* Splenomegally (abnormal enlargement of the spleen).
* Examples:
* Portal hypertension
* Leukaemia
* Can have large haemangioma.
32
Describe thrombophilia
* Increased risk of clotting.
* Caused by:
* Inherited defects in coagulation inhibitors, eg. protein C, S, antithrombin.
* Inherited defect in factor V - Factor V Leiden (causes increased clotting).
* Acquired problems - Virchow's triad:
* Abnormal vessel wall
* Abnormal flow
* Abnormal blood component
33
What can cause an abnormal vessel wall?
* Atheroma and plaque
* Varicose veins
* Aneurysm
34
What can cause abnormal flow through a vessel?
* Atrial fibrilation
* Immobility (eg. long distance flight, plaster cast, surgery)
* Varicose veins
35
What can cause an abnormal blood component?
* Increased haemoglobin / red cell count - **polycythaemia**.
* Increased WBC or platelet count - stasis and increased clotting.
* Increased viscosity of plasma.
* Reduced coagulation factor inhibitors.
36
What is polycythaemia?
An abnormally increased concentration of Hb in the blood, either through reduction of plasma volume or increased red cell numbers.
