Week 6 Flashcards
List 3 contents of a platelet?
lysosomes, granules and membrane,
microtubules
Granules are key in primary hemostasis; list some things that they contain (6)
- ADP
- Thromboxane
- Platelet factor 4
- Adhesive and aggregation glycoproteins
- Coagulation factors
- Fibrinolytic inhibitors
What stage in hemostasis does platelet aggregation initiate?
Secondary hemostasis through the coagulation cascade
Coagulation system needs to be regulated
or it would continually produce what?
thrombi.
Clotting factors have antagonists what are they?
Anti-coag agents that can cleave them.
Define thrombosis
inappropriate formation of platelet or fibrin clots that
obstruct blood vessels.
List two resulting risks of thrombosis
ISCHEMIA i.e loss of blood flow,
NECROSIS i.e. tissue death.
List some contributors to thrombosis
- Blood flow e.g. stasis
- Coagulation system
- Platelet function
- Leucocyte activation molecules
- Blood vessel walls
EMBOLI = fragments of thrombi - how can this cause ischemia?
move to right chamber of heart
- lodge in arterial pulmonary vasculature
- cause ischaemia & death of lung tissue
What are 3 types of arterial thrombosis?
Myocardial infarction
Cerebrovascular accidents
Transient ischaemic attacks (TIA)
Atherosclerosis is fatty plaque with what 3 things?
- Activated platelets
- Monocytes
- Macrophages
Atherosclerosis suppresses the release of ___________ molecules like Nitric oxide and Exposes __________ substances like Tissue factors
anti-thrombotic, prothrombotic
In atherosclerosis unstable plaques rupture, releasing what?
thrombotic mediators - platelets + vWF, minimal fibrin
List 3 risk factors for atherosclerosis.
- Total cholesterol
- LDL-cholesterol
- HDL-cholesterol
Factor V Leiden, Prothrombin G20210A are common genetic mutations relating to what?
CONGENITAL thrombosis
APC acts as an anticoagulant by proteolytically inactivating which 2 factors? and which protein enhances this anticoag activity
FVa & FVIIa
Protein S
WARFARIN impacts which proteins?
Prot C, S & Z
Antithrombin is a serine protease inhibitor (serpin) which binds an neutralises all serine proteases except which factor?
FVIIa
What is prothrombin G20210A
Mutation at base 20210 in the
prothrombin (FII) gene.
Mildly increased prothrombin levels leads to increased risk of what?
increased risk of thrombosis
Factor V Leiden is most common inherited cause of increased risk of venous thrombosis. T-F
T
Normally APC breaks down which factor?
FVa
Factor V Leiden is a variant of which factor?
V
Factor V Leiden is a mutation because of a _____ ______ substitution. Factor V Leiden is also a mutation that makes FV resistant to ______ cleavage
amino acid, APC
T-F; FV Leiden mutation also known as APC resistance
T
List some Acute causes of DIC
Hint: Deficiencies of multiple haemostasis components.
Obstetric emergencies, Septicaemia, viraemia
Burns, Acute inflammation, Crush injuries, Aortic aneurysm, Cardiac disorders
List some Chronic causes of DIC
Liver disease, Renal disease, Chronic inflammation, Prosthetic devices, Vascular tumors
DIC is characterised by loss of normal ______ control
in response to sustained systematic injury
haemostatic
In thrombocytopenia what happens to the production, destruction, and distribution of platelets?
Decreased production, increased destruction and abnormal distribution
What are the 2 categories of abnormalities in platelet PRODUCTION?
Megakaryocyte hypoplasia, Ineffective thromobopoiesis
Is Acute ITP (idiopathic thrombocytopenia purpura) primarily seen in children or adults?
children
Acute ITP Usually manifest 1 to 3 weeks after an __________
infection
In Chronic ITP _________ coated platelets are destroyed in RE system
Antibody
Autoantibodies in 50% of cases
ITP patient blood film morphology
• RBC and leucocytes _______
• Platelets _____________
• MPV
RBC and WBC - normal
Platelets - reduced in number, may be large
MPV may be increase
In ITP Coagulation studies what would the results be for tests that rely on platelet function
- Abnormal
* Bleeding time, clot retraction time
Immune mediated thrombocytopaenia can be secondary to what conditions?
- Chronic lymphocytic leukaemia
- System lupus erythematosus
- Parasitic infection e.g. Malaria
The mechanism of _________ is to bind to antithrombin, enhance inhibition of FIIa, FXa. Used for prophylaxis against thrombosis
Heparin
What is the mechanism in Heparin induced thrombocytopenia (HIT)?
develop IgG Antibody to heparin – Platelet Factor 4 complex
Heparin induced thrombocytopenia leads to what 3 things?
Platelet activation
Decreased platelet count
Formation of microvascular thrombi
HELLP syndrome stands for …..
Haemolysis, Elevated Liver enzymes, Low Platelet count
Thrombotic thrombocytopaenic purpura caused by a RARE inherited mutation of which gene?
ADAMTS13
What cleaves vWF into smaller fragments?
ADAMTS13
Cleaved fragments of vWF bind to what?
exposed collagen
Platelets some receptors bind to vWF, others
to what?
fibrinogen
In TTP the ADAMTS13 enzyme is deficient or blocked
by an __________, cleaving of large multimeric vWF chains is inhibited
autoantibody
Large chains of multimeric vWF bind to areas of
endothelial damage, and initiate recruitment of
large numbers of _______ into large aggregates
platelets
Large numbers of sites with large platelet
aggregations cause what 3 potential things?
- Thrombocytopaenia
- Microangiopathic haemolytic anaemia
- Organ ischaemia
Large numbers of sites with large platelet
aggregations cause what 3 potential things?
• Thrombocytopaenia
• Microangiopathic haemolytic anaemia
• Organ ischaemia
TAI
Is TTP intravascular or extravascular
haemolysis?
Intravascular
What would you expect to find on a blood film of a patient with TTP?
Schistocytes, low platelets, polychromasia
What would you expect the PT, APTT and fibrinogen test results be for a patient with TTP
Normal PT, APTT, fibrinogen - note these results differentiate TTP from DIC.
What form of therapy would restore the presence of ADAMTS13 enzyme, reduces platelet aggregation in small vessels.
Plasma infusion
What would dilute the autoantibodies to ADAMST13?
Plasma exchange
What is the name of the CD20 binding
monoclonal antibody that binds to the B-cells that are producing the autoantibody, mediating their destruction
Rituximab
Haemolytic uraemic syndrome (HUS) resembles what other disorder?
TTP
HUS is seen mainly in children 6 mths to 4 years
90% of cases of haemolytic uraemic syndrome relate to presence of bacteria in GI tract. Which bacteria?
- Shigella dysenteriae → Shiga toxin
* Eschericia coli
In HUS and TTP which features predominantly renal and which features predominantly neurological?
HUS - Renal
TTP - Neurological
Give 2 examples of a qualitative disorder of adhesion receptors. (tip) both are - Rare, autosomal recessive disorders
- Bernard-Soulier Syndrome (BSS) or Giant platelet syndrome
2. Glanzmann Thromboasthenia
What would be the treatment for bernand-soulier syndrome, and Glanzmann Thromboasthenia?
Platelet transfusions → Develop allo-antibodies
What would the results of aggregation studies for Bernard-Soulier Syndrome (BSS) be for
ADP, epinephrine, collagen & AA, Ristocetin
Normal to ADP, epinephrine, collagen & AA
NO response to Ristocetin (instab of P :VWF binding)
↓ response to thrombin
What would the lab findings be for Glanzmann Thromboasthenia? FBC, Platelet count, Bleeding time, Platelet aggregation studies
FBC: Normal Platelet count : Normal Bleeding time: prolonged Platelet aggregation: Risto – normal Others NO response
