Haemostasis & Coagulation Flashcards
Haemostasis
The normal response of the vessel to injury by forming a clot that serves to limit haemorrhage
Is coagulation related to the platelet side of things
NO
Intrinsic Pathway of Clotting
Activated when blood comes into contact with foreign tissue - exposed collagen from injured blood vessel wall, test tube
Extrinsic Pathway of Clotting
Tissue is damaged and releases thromboplastin
Purpose of the Amplification Cascade
Each step of clotting is amplified such that a lot of fibrin is released with little prompt
Describe the amplification cascade
Something like one active factor X activates 10,000 Prothrombins into thrombin (amplification)
Thrombin gets you factor XIII and chops up fibrinogen into fibrin, which is stabilised by factor III
Fibrin leads to the clotting
Which is more of a cardiovascular risk; too much or too little fibrinogen?
Too much fibrinogen is a cardiovascular risk as it predisposes to clot formation
Role of platelets (don’t just say clotting!!)
Forming a mechanical plug during blood vessel injury
Two main reactions of platelets
Adhesion
Aggregation
Describe the adhesion reaction of platelets
They adhere to the subendothelial surface on damaged tissue; supported by
Von Willebrand’s factor
They release 5-HT, ADP and thromboxane
Describe the aggregation reaction of platelets
Platelets begin to clump and stick together due to thromboxane and ADP which signal them to stick together
Once ADP binds to a platelet, it results in the expression of glycoprotein IIb-IIIa, allowing them to become cross linked via vWF and fibrinogen
Bleeding time test
Incision made on forearm with venous cuff
Bleeding time increases with platelet dysfunction/thrombocytopaenia
International Normalised Ratio (INR)
Test for Prothrombin time;
Blood test measuring the ability of blood to clot - time for Coagulation following addition of thromboplastin
Standard is 1 (12 seconds is 1); if someone has an INR of 2, they take longer than normal to clot
Prolonged by abnormalities of blood factors, liver disease or warfarin
FOCUS ON THIS ONE!!
Activated Partial Thromboplastin Time (APTT)
Examines the intrinsic pathway of clotting; altered by changes in clotting factors
Outdated mostly and somewhat irrelevant
Thrombosis
Formation of unwanted blood clots in the bloodstream that travel away from site of origin
What happens in atrial fibrillation
SA Node normally fires across the atrium causing a pulse; in this pathology, other tissues take the role of pacemaker and cause a very uncoordinated contraction
Leads to a very irregular heart rate and tachychardia
Usually a result of tissue damage
What is a consequence of atrial fibrillation
Blood is stagnant so a clot forms; it is shot into the brain causing a stroke
High risk of stroke with AF
Think of it like clotty cream getting all mixed up and condensed
What is the main cause of myocardial infarctions
Patient gets atherosclerotic plaque in coronary arteries; blood is blocked from going downstream of that plaque and boom heart attack baby
Compare the relevance of cloagulation factors and platelets in venous vs arterial thrombosis
Venous Thrombosis is more of a coagulation factor event
Arterial thrombosis is more of a platelet event
Examples of arterial thrombosis
Myocardial Infarctions
Ischaemic Strokes
What is the cause of Haemophilia A
X-linked genetic disorder causing low factor VIII of the clotting cascade
How is haemophilia treated
Previously, it was treated via regular infusions of factor VIII
Alternatively, sometimes analogue of ADH was used which increases patients factor VIII release
Then Emicizumab was introduced
How is haemophilia treated
Previously, it was treated via regular infusions of factor VIII
Alternatively, sometimes analogue of ADH was used which increases patients factor VIII release
Then Emicizumab was introduced
Emicizumab
Modern monoclonal antibody treatment of haemophilia A; given via monthly sc injections; activates factor IX and X so bypasses role of factor VIII
Very effective and high half life compared to transfusion
Haemophilia B
(Christmas disease since factor was discovered on christmas)
Deficiency of factor IX
Treated via prophylactic factor IX
Von Willebrand’s Disease
Heridary lack or defect in vWF
Leads to increased bruising, nose bleeds, mucosal bleeding
Treatment of Von Willebrand’s Disease
Analogue of ADH/Vasopressin, factor VIII or vWF
Effect of liver disease on clotting
Reduced synthesis of clotting factors leads to increased bleeding; increased prothrombin time
Thrombocytopaenia
Reduced platelet count; leads to spontaneous skin bleeding
Causes of thrombocytopaenia
Idiopathic
Viral
Drug-induced
Toxins
Can Drugs cause thrombocytopaenia
Yes; if it does, change the prescription
Disseminated Intravascular Coagulation
DIC
Large amounts of fibrin generated by procoagulant material like amniotic fluid
Leads to vast consumption of clotting factors and platelets; causes widespread haemorrhage but also maybe thrombosis
DEATH IS COMING (not always but its very bad - medical emergency)
Treatment of DIC (Disseminated Intravascular Coagulation)
Platelets and fresh frozen plasma
you do defrost the plasma lmao
Factor V Leiden mutation
Single nucleotide polymorphism
Abnormal Factor V
Less susceptible to deactibation so leads to increased risk of venous (only) thrombosis - especially with oral contraceptives/pregnancy
