Thrombotic Disorders Flashcards
What are thrombotic disorders?
Thrombotic disorders are disorders involving thrombosis or platelets
How does Ischaemic Heart Disease (IHD) manifest?
IHD manifests with stable and unstable angina, transient ischaemic attacks (TIA) and myocardial infarction
What is ischaemia?
Starving tissue of oxygen that results in its death
What is stable angina?
Blood vessels to the heart are narrowed and do not provide enough blood supply during exercise
What is unstable angina?
Angina that comes and goes
Involves platelets
Dangerous
What are the risk factors for IHD?
“Western” diet
Excessive bodyweight
Smoking
Lack of exercise
Age
Male sex
Describe the epidemiology for IHD
Accounts for 30% of male and 22% female deaths in England and Wales
What did the “Seven Countries” study show?
Mean serum cholesterol (particularly LDL) strongly associated with IHD death rate (r = 0.8)
BMI has variable association
“Central adiposity” (waist-hip ratio) strongly associated with IHD deaths
What does post-mortem examination of the coronary arteries of MI victims show?
Ruptured atherosclerotic plaques
Platelet aggregates
What is primary aggregation?
Primary aggregation is the response to the initiating stimulus for aggregation
What is secondary aggregation?
Secondary aggregation is the further response to released ADP and TxA2
Give examples of aggregating agents used in diagnosis
Collagen - potent aggregating agent
ADP moderate-strength aggregating agent, intermediate doses are dependent on TxA2 production and granule release
Adrenaline - weak aggregating agent, requires supraphysiological concentrations
Ristocetin - an antibiotic which triggers binding of VWF to GPIb/IX/V complex in absence of shear forces and thus agglutination of platelets
Arachidonic acid - precursor to TxA2 – passes into the platelet and is converted by COX-1
What are the benefits of aspirin?
Reduces risk of serious secondary cardiac events by 20 – 40%
Reduces cardiac deaths in unstable angina by 50 – 70%
Beneficial in surgical intervention (PTCA, stents)
Benefit in reducing primary events not proved
Is it better to give clopidogrel, aspirin, or both following an MI?
The CURE (2001) and MATCH (2004) studies showed that the occurrence of a second MI was reduced if both clopidogrel and aspirin were administered, instead of either one alone
Are there any risks to giving both aspirin and clopidogrel?
Giving both drugs together leads to a slightly increased risk of hemorrhage
How can you test whether clopidogrel is affecting platelets?
“Verify Now” test
Flow cytometry for VASP
How does ADP act on the P2Y12 receptor to activate platelets?
When ADP binds to P2Y12, an G-protein moves across the membrane, and binds to Adenylate Cyclase, inhibiting it.
This prevents the conversion of ATP to cAMP, and so removes the inihibitory signal provided to the platelet, allowing the activation signal provided by ADP binding to the P2Y1 receptor, making the activation signal dominant, leading to platelet activation.
How does clopidogrel act on the P2Y12 receptor?
It binds to the P2Y12 receptor, inhibiting it, and so preventing the G-protein from moving across the membrane and inhibiting Adenylate Cyclase.
This prevents the removal of the inhibitory signal provided by P2Y12, and so platelet activation remains inhibited.
What did the ISIS-2 study (1988) show?
The ISIS-2 study showed that in patients with a recent suspected MI, patients who recieved aspirin (compared with placebo) had decreased incidence of vascular and non-vascular deaths, haemorrhagic and non-haemorrhagic strokes, and major and minor bleeding
