Haematology Flashcards
What are T cells, B cells and NK cells derived from?
Lymphoid stem cells which are derived from pluripotent lymphoid stem cells
What are granulocytes, erythroids and megakaryocytes derived from?
Multipotent myeloid stem cells which are derived from pluripotent myeloid stem cells
How do stem cells produce mature progeny?
They divide to produce another stem cell and a cell capable of differentiating into mature progeny
How do multipotent myeloid stem cells produce erythrocytes?
They differentiate into:
Proerythroblasts
Erythroblasts
Erythrocytes
Where is erythropoietin synthesised?
Mainly by the kidneys in response to hypoxia
How are erythrocytes removed from the circulation at the end of their life cycle?
By phagocytic cells of the spleen
What is the first recognisable cell in white blood cell production?
Myoblasts
How long does a neutrophil spend in the circulation before migrating into tissues?
7-10 hours
What is the main function of an eosinophil?
Defence against parasites
What is the main role of a basophil?
Involved in allergic responses
How long do monocytes spend in the circulation? What are they when they migrate into tissues?
Spend several days in the circulation
Macrophages: Phagocytic and scavenging function. They also store and release iron
How long do platelets spend in the circulation? What is their primary role?
10 days
Haemostasis
What is anisocytosis?
Where red cells show more variation in size than normal
What is poikilocytosis?
Where red cells show more variation in shape than normal
What term is used to describe blood cells that are smaller than normal?
Microcytosis
Smaller than a lymphocyte nucleus
What term is used to describe blood cells that are larger than normal?
Macrocytosis
Larger than a lymphocyte nucleus
What are the different types of macrocyte?
- Round macrocytes
- Oval macrocytes
- Polychromatic macrocytes
What is hypochromia?
Cells have a larger area of central pallor than normal, due to a lower haemoglobin content and concentration and a flatter cell
What is hyperchromia?
Describes cells that lack central pallor. This can be because they are thicker than normal or because their shape is abnormal
What are the two cell types in hyperchromia?
- Spherocytes
- Irregularly contracted cells
What are spherocytes?
Red cells that are approximately round in shape, with a lack of central pallor
They result from the loss of cell membrane without the loss of an equivalent amount of cytoplasm so the cell is forced to round up
What causes irregularly contracted cells?
They usually result from oxidant damage to the cell membrane and to the haemoglobin
What is polyhromasia?
An increased blue tinge to the cytoplasm of a red cell- indicating that the red cell is young
What stain is used in a reticulocyte stain?
Methylene blue
What are target cells? Where are they found?
Cells with an accumulation of haemoglobin in the area if central pallor
What are elliptocytes?
Red cells that are elliptical in shape. They occur in hereditary elliptocytosis and in iron deficiency
What causes the change in shape in sickle cell anaemia?
Results from the polymerisation of haemoglobin S when it is present in a high concentration
What are fragments?
Also known as schistocytes
Small pieces of red cells indicating the red cell has fragmented
What is Rouleaux?
Stacks of red cells resembling a pile of coins resulting from alterations in plasma proteins
What are red cell agglutinates?
Irregular clumps of red cells usually resultant from antibody on the surface of the cells
What is a Howell-Jolly body?
A nuclear remnant in a red cell, commonly caused by a lack of splenic function
What terms describe too many or too few white cells?
Leucocytosis- too many
Leucopenia- too few
What terms describe too many or too few neutrophils?
Neutrophilia- too many
Neutropenia- too few
What terms describe too many lymphocytes?
Lymphocytopenia
What terms describe too many eosinophils?
Eosinophilia
What terms describe too many or too few platelets?
Thrombocytosis- too many
Thrombocytopenia- too few
What terms describe too many red cells?
Erythrocytosis
What terms describe too many reticulocytes?
Reticulocytosis
What is “left shift”? What is it a sign of?
Where there is an increase in non-segmented neutrophils or where there are neutrophil precursors in the blood
Sign of a bacterial infection
How many lobes are there in a hypersegmented neutrophil? What is it usually caused by?
> 5 lobes
Usually due to a lack of vitamin B₁₂ or folic acid
What is mean cell haemoglobin?
The amount of haemoglobin in a given volume of blood divided by the number of red cells in the same volume
What is mean cell haemoglobin concentration?
The amount of haemoglobin in a given volume of blood divided by the proportion of the sample represented by the red cells
How do you interpret a blood count?
1) Leucocytes?
High or low number, which cell line is abnormal
2) Haemoglobin
3) Mean cell volume?
Blood count, large or small cells
4) Platelets
Thrombocytosis/thrombocytopenia, blood count
Look at the clinical history to point to the cause
What is polycythaemia? What are the potential causes?
Too many red cells in the circulation Hb, RBC and PCV are all increased Can present with splenomegaly, abdominal mass or cyanosis Causes: - blood doping - medical negligence - high levels of erythropoietin • hypoxia • illicit erythropoietin (sports) • tumour • polycythaemia vera (abnormal bone marrow function)
What is pseudopolycythaemia?
A decrease in plasma volume makes it look like patient has polycythaemia
When there is an increase in the number of circulating red cells there is a true polycythaemia
What is polycythaemia vera? How is it treated?
An intrinsic bone marrow disorder classified as a myeloproliferative neoplasm
Can lead to hyperviscoscity (“thick blood”) which can cause vascular obstruction
Treatment
- venesection (remove blood)
- drugs (controlling the bone marrow production of blood cells)
What would you suspect as the cause of polycythaemia in a young healthy athlete?
Suspicious (doping)
What would you suspect as the cause of polycythaemia in a breathless cyanosed patient?
Probably due to hypoxia
- an appropriate response
What would you suspect as the cause of polycythaemia in a patient with an abdominal mass?
Could be carcinoma of the kidney
What would you suspect as the cause of polycythaemia in a patient with splenomegaly?
A pointer to polycythaemia vera
What are the different possible mechanisms of anaemia? (4)
1) reduced production of red cells/haemoglobin in the bone marrow
2) Loss of blood from the body
3) Reduced survival of red cells in the circulation
4) Pooling of red cells in a very large spleen
What are the different classifications of anaemia based on size?
Microcytic
Normocytic
Macrocytic
What are the common causes of microcytic anaemia?
1) Defect in haem synthesis
- Iron deficiency
- Anaemia of chronic disease
2) Defect in globin synthesis (thalassaemia)
- Defect in α-chain synthesis (α thalassaemia)
- Defect in β-chain synthesis (β thalassaemia)
What causes macrocytic anaemia?
Abnormal haemopoiesis where red cell precursors continue to synthesise haemoglobin and other cellular proteins but they fail to divide normally. Results in cells that are larger than normal
OR
Premature release of cells from the bone marrow
What is megaloblastic erythropoiesis?
Delay in maturation of the nucleus while the cytoplasm continues to mature and the cell continues to grow
What is a megaloblast?
An abnormal bone marrow erythroblast
What are the common causes of macrocytic anaemia?
1) Lack of folic acid or vitamin B₁₂
2) Use of drugs interfering with DNA synthesis (e.g. chemotherapy)
3) Liver disease and ethanol toxicity
4) Recent major blood loss with adequate iron stores
5) Haemolytic anaemia
What are the mechanisms of normocytic normochromic anaemia?
- Recent blood loss
- Failure of production of red cells
- Pooling of red cells in the spleen
What are the possible causes of normocytic normochromic anaemia?
1) Peptic ulcer, oesophageal varices, trauma
2) Failure of production of red cells
- early stages of iron deficiency
- anaemia of chronic disease
- renal failure
- bone marrow failure or suppression
- bone marrow infiltration
3) Hypersplenism e.g. portal cirrhosis
What is haemolytic anaemia? What can it result from?
Anaemia resulting from shortened survival of red cells in the circulation
- Intrinsic abnormality of the red cells
- Extrinsic factors acting on normal red cells
What is the difference between inherited and acquired haemolytic anaemia?
Inherited- abnormalities in the cell membrane, the haemoglobin or the enzymes in the red cells
Acquired- extrinsic factors such as micro-organisms, chemicals or drugs that damage the red cell
What is the difference between intravascular and extravascular haemolysis?
Intravascular- occurs if there is very acute damage to the red cell
Extravascular- occurs when defective red cells are removed by the spleen
Often haemolysis is partly intravascular and partly extravascular
What are the possible defects in inherited haemolytic anaemia?
- Abnormal red cell membrane (e.g. hereditary spherocytosis)
- Abnormal Hb (e.g. sickle cell anaemia)
- Defect in glycolytic pathway (e.g. pyruvate kinase deficiency)
- Defect in enzymes of pentose shunt (e.g. G6PD deficiency)
What are the possible causes of acquired haemolytic anaemia?
- Damage to red cell membrane (e.g. AIHA or snake bite)
- Damage to whole red cell (e.g. MAHA)
- Oxidant exposure, damage to red cell membrane and Hb (e.g. dapsone or primaquine)
When would you suspect haemolytic anaemia?
- Otherwise unexplained anaemia, which is normochromic and usually normocytic/macrocytic
- Morphologically abnormal red cells (irregularly contracted cells, spherocytosis, sickle cell)
- Increased red cell breakdown (jaundice)
- Increased bone marrow activity
Give an example of a cause of haemolytic anaemia due to a membrane defect.
Hereditary spherocytosis
Give an example of a cause of haemolytic anaemia due to a haemoglobin defect.
Sickle cell anaemia
Give an example of a cause of haemolytic anaemia due to a glycolytic pathway defect.
Pyruvate kinase deficiency
Give an example of a cause of haemolytic anaemia due to a pentose shunt defect.
G6PD deficiency
What is hereditary spherocytosis? How do cells become spherocytic?
Red cells become less flexible and are removed prematurely by the spleen (extravascular spherocytosis)
After entering the circulation the cells lose their membrane in the spleen and become spherocytic
The bone marrow responds to haemolysis by increasing red cell output leading to polychromasia and reticulocytosis
Leads to increased bilirubin production, jaundice and gallstones
What is the treatment for hereditary spherocytosis
Only effective treatment is splenectomy but this has risks so only done in severe cases
Good diet is important so secondary folic acid deficiency does not occur
Alternatively one folic acid tablet to be taken daily
What is G6PD? Why is it important?
Glucose-6-phosphate dehydrogenase
Important enzyme in the pentose phosphate shunt
It is essential for the protection of the red cell from oxidant damage
How does a G6PD deficiency cause haemolysis?
Extrinsic oxidants (e.g. foodstuffs, chemicals or drugs) cause damage to red cells. G6PD is needed for protection against these oxidants. A deficiency usually causes intermittent, severe intravascular haemolysis. The gene for G6PD is on the X chromosome so affected individuals are usually hemizygous males (but occasionally homozygous females)
What cells would be seen in a blood smear from a patient with G6PD deficiency?
Considerable numbers of irregularly contracted cells
Haemoglobin is denatured and forms round inclusions known as Heinz bodies (can be detected by a specific test)
What causes autoimmune haemolytic anaemia?
Production of autoantibodies directed at red cell antigens
The immunoglobulin bound to the red cell membrane is recognised by splenic macrophages, which remove parts of the red cell membrane, leading to spherocytosis
The combination of cell rigidity and recognition of antibody+complement on the red cell surface by splenic macrophages leads to removal of cells from the circulation by the spleen
How do you diagnose autoimmune haemolytic anaemia?
- Finding spherocytes and an increased reticulocyte count
- Immunoglobulin on the red cell surface
- Antibodies to red cell antigens or other autoantibodies in the plasma
How is autoimmune haemolytic anaemia treated?
Corticosteroids and other immunosuppressive agents
Splenectomy for severe cases
A microcytic anaemia is likely to be due to:
1) Vitamin B₁₂ deficiency
2) Folic acid deficiency
3) Iron deficiency
4) Haemolysis
5) Acute blood loss
3) Iron deficiency
Polycythaemia in a patient seeing his GP because he has noticed his urine is red is most likely due to:
1) Chronic renal failure
2) Living at high altitude
3) Hypoxia from COPD
4) Haemolysis
5) Renal carcinoma
5) Renal carcinoma
How much iron is needed per day to produce red cells?
20mg per day (not including recycled iron)
Men- 1mg/day
Women- 2mg/day
What natural foods are a good source of iron?
Meat and fish (haem iron)
Vegetables
Whole grain cereal
Chocolate
Which type of iron can be absorbed and which type can’t? What drinks aids absorption and prevents it?
Fe³⁺ cannot be absorbed
Fe²⁺ can be absorbed
Orange juice helps absorption, tea can prevent it
What factors affect absorption of iron?
Diet: - increase in haem iron or ferrous iron Intestine: - acid (duodenum) - ligand (meat) Systemic: - iron deficiency - anaemia/hypoxia - pregnancy
How does the gut cell alter iron absorption?
High iron = high hepidin = low ferroportin = low absorption
( hepcidin causes ferroportin to be internalised and degraded
Where is ferroportin found?
1) On enterocytes of the duodenum
2) On macrophages of the spleen which extract iron from old or damaged cells
3) On hepatocytes
How is iron transported in the plasma?
Carried by transferrin
What is the normal level of transferrin saturation?
20-40%
How does transferrin transport iron into cells?
Transferrin-iron complexes interact with the transferrin receptor and are internalised. As the pH drops iron is released and the transferrin receptors are recycled
What hormone is released in response to anaemia and tissue hypoxia?
Erythropoietin
What is anaemia of chronic disease?
Anaemia in patients who are unwell
The present with no bleeding, no bone marrow infiltration and no iron, vitamin B₁₂ or folate deficiency
What are the laboratory signs of being ill?
1) C-reactive protein (acute phase protein associated with inflammation)
2) Erythrocyte sedimentation rate
3) Acute phase response: increases in
- ferritin
- FVIII
- fibrinogen
- immunoglobulins
What conditions are associated with anaemia of chronic disease?
1) Chronic infections (e.g. TB/HIV)
2) Chronic inflammation (e.g. RhA/SLE)
3) Malignancy
4) Miscellaneous (e.g. cardiac failure)
What is the pathogenesis of anaemia of chronic disease?
Cytokines prevent the usual flow of iron from the duodenum to red cells:
1) They stop erythropoietin increasing
2) They stop iron flowing out of cells
3) They increase the production of ferritin
4) Increase death of red cells
What cytokines are involved in the pathogenesis of anaemia of chronic disease?
TNF-α
Interleukins
Is iron covalently bound to the globin protein chain in haemoglobin?
No
Where is iron mainly absorbed?
In the colon
In anaemia of chronic disease is ferritin elevated or reduced as part of the acute phase response to illness?
Elevated
What are the causes of iron deficiency?
1) Bleeding (e.g. menstrual/GI)
2) Increased use (e.g. growth/pregnancy)
3) Dietary deficiency (e.g. vegetarian)
4) Malabsorption (e.g. coeliac)
What investigations are conducted if someone presents with anaemia?
Coeliac screen- if negative:
- Upper GI endoscopy: oesophagus, stomach, duodenum
- take duodenal biopsy
- Colonoscopy
- Menstruating woman <40: if heavy periods/multiple pregnancies and no GI symptoms do nothing
- Urinary blood loss?
How do you confirm thalassaemia trait?
Haemoglobin electrophoresis
- confirms an additional type of haemoglobin present
How can ferritin be used to differentiate between iron deficiency and chronic disease anaemia?
LOW in iron deficiency
HIGH in chronic disease
How can transferrin be used to differentiate between iron deficiency and chronic disease anaemia?
Iron deficiency: transferrin goes UP
Chronic disease: NORMAL or even LOW
How can transferrin saturation be used to differentiate between iron deficiency and chronic disease anaemia?
Iron deficiency: LOW saturation
Chronic disease: NORMAL or HIGH
What changes would be seen in a blood test of a patient with classic iron deficiency? Hb MCV Serum iron Ferritin Transferrin Transferrin saturation
Hb: LOW MCV: LOW Serum iron: LOW Ferritin: LOW Transferrin: HIGH Transferrin saturation: LOW
What changes would be seen in a blood test of a patient with anaemia of chronic disease? Hb MCV Serum iron Ferritin Transferrin Transferrin saturation
Hb: LOW MCV: LOW or NORMAL Serum iron: LOW Ferritin: HIGH or NORMAL Transferrin: NORMAL or LOW Transferrin saturation: NORMAL
What is the diagnosis from this blood test result? Hb: 10 MCV: 66 Serum iron: normal Ferritin: normal Transferrin: normal Transferrin saturation: normal
Hb: LOW
MCV: LOW
Thalassaemia trait
What is the diagnosis from this blood test result? Hb: 10 MCV: 78 Serum iron: low Ferritin: normal Transferrin: low Transferrin saturation: normal
Hb: LOW
MCV: LOW
Rheumatoid arthritis with a bleeding ulcer
(Anaemia of chronic disease with iron deficiency)
If you see pencil cells in a blood film what is this indicative of?
Iron deficiency
What is the role of vitamin B₁₂?
Required for:
- DNA synthesis
- Integrity of the nervous system
What happens if deficient in vitamin B₁₂ and folate?
Absence leads to severe anaemia which can be fatal
What is folic acid required for?
- DNA synthesis
- Homocysteine metabolism
What are the clinical features of a vitamin B₁₂ and folate deficiency?
All rapidly dividing cells are affected: - Bone marrow - Epithelial surfaces or mouth and gut - Gonads - Embryos Anaemia (weak, tired, short of breath) Jaundice Glossitis and angular cheilosis Weight loss Change of bowel habit Sterility
What type of anaemia occurs in a patient with a vitamin B₁₂ and folate deficiency?
Macrocytic and megaloblastic anaemia
High MCV
What are the causes of macrocytic anaemia?
1) Vitamin B₁₂ or folate deficiency
2) Liver disease or alcohol
3) Hypothyroid
4) Drugs (e.g. azathioprine)
5) Haematological disorders
- Myelodysplasia
- Aplastic anaemia
- Reticulocytosis (e.g. chronic haemolytic anaemia)
What is normal red cell maturation?
Erythroblast
Normoblast: early / intermediate / late
Reticulocyte
Circulating red blood cell
What is megaloblastic anaemia?
Asynchronous maturation of the nucleus and cytoplasm in the erythroid series of development
Maturing red cells are seen in the bone marrow
What is seen in the peripheral blood of a patient with megaloblastic anaemia?
Anisocytosis (unequal sized red cells)
Large red cells
Hypersegmented neutrophils
Giant metamyelocytes
True or False?
Thyroid disease can be a cause of megaloblastic red blood cells?
FALSE
It can be a cause of macrocytic cells but not megaloblastic change
Give three tests that you would do if someone had a macrocytosis.
Check vitamin B₁₂ and folate
Liver function
Thyroxine
Name two possible underlying clinical disorders that could cause a hypersegmented neutrophil.
Vitamin B₁₂ or folate deficiency
What is a good source of dietary folate? How is this removed from foods?
Fresh leafy vegetables
Destroyed by overcooking / canning / processing
What are the physiological causes for an increased folate demand?
- Pregnancy
- Adolescence
- Premature babies
What are the pathological causes for an increased folate demand?
- Malignancy
- Erythoderma
- Haemolytic anaemias
How is a laboratory diagnosis of a folate deficiency made?
Full blood count and film
Folate levels in the blood
How is the cause of decreased folate assessed?
History (diet / alcohol / illness)
Examination- skin disease / alcoholic liver disease
What are the consequences of a folate deficiency?
1) Megaloblastic, macrocytic anaemia
2) Neural tube defects in developing foetus
3) Increased risk of thrombosis in association with variant enzymes involved in homocysteine metabolism
What are the neural tube defects associated with folate deficiency?
- Spina bifida
- Anencephaly
What dosage of folate are pregnant women advised to take? For how long?
0.4mg prior to conception and for the first 12 weeks
What are very high levels of homocysteine associated with?
- Atherosclerosis
- Premature vascular disease
What are mildly high levels of homocysteine associated with?
- Cardiovascular disease
and potentially: - Arterial thrombosis
- Venous thrombosis
What are the consequences of a vitamin B₁₂ deficiency?
Neurological problems
- Bilateral peripheral neuropathy
- Subacute combined degeneration of the cord
• Posterior and pyramidal tracts of the spinal cord
- Optic atrophy
- Dementia
What would present as an indication of a vitamin B₁₂ deficiency when taking the history and examining a patient?
History - Paraesthesiae - Muscle weakness - Difficulty walking - Visual impairment - Psychiatric disturbance Examination - Absent reflexes - Upgoing plantar responses
What are the possible causes of a vitamin B₁₂ deficiency?
1) Poor absorption
2) Reduced dietary intake
- Stores are large and last for 3-4 years
- Animal produce
- Vegans are at risk
3) Infections / infestations
- Abnormal bacterial flora (stagnant loops)
- Tropical sprue
- Fish tapeworm
Where is vitamin B₁₂ absorbed?
In the small intestine
How is vitamin B₁₂ excreted?
In the urine
How is vitamin B₁₂ absorbed?
B₁₂ combines with intrinsic factor
B₁₂-IF binds to ileal receptors
What three things are needed for vitamin B₁₂ absorption?
1) Intact stomach
2) Intrinsic factor
3) Functioning small intestine
What can cause a reduction of intrinsic factor that would cause impaired vitamin B₁₂ absorption?
1) Post gastrectomy
2) gastric atrophy
3) Antibodies to intrinsic factor or parietal cells (PA)
What is pernicious anaemia? When is the most common age to get it?
Autoimmune condition associated with severe lack of intrinsic factor
(Antibodies to intrinsic factor or parietal cells)
Peak age: 60 years
What is the most common target of antibodies in pernicious anaemia?
90% of adults have antibodies to parietal cells
What diseases of the small bowel would cause impaired vitamin B₁₂ absorption?
1) Crohn’s disease
2) Coeliac disease
3) Surgical resection
What infections are associated with impaired vitamin B₁₂ absorption?
H. pylori
Giardia
Fish tapeworm
Bacterial overgrowth
What drugs are associated with low vitamin B₁₂?
1) Metformin
2) Proton pump inhibitors (e.g. omeprazole)
3) Oral contraceptive pill
In patients with low vitamin B₁₂ what are the first investigations that are carried out to discover the cause?
Test:
1) Antibodies to parietal cells and intrinsic factor
2) Antibodies for coeliac disease
3) Breath-test for bacterial overgrowth
4) Stool for H. pylori
5) Test for Giardia
What is the Shilling Test?
Before the test B₁₂ deficiency must be corrected
1) Patient drinks radiolabelled B₁₂
2) Measure excretion in the urine
(if there is no B₁₂ in the urine either they are not absorbing B₁₂ because have no IF or they have antibodies to IF/parietal cells OR the B₁₂ deficiency was not corrected before the test)
3) Repeat test with additional intrinsic factor (different radiolabel)
4) Measure excretion of B₁₂ in the urine
What is the treatment for a vitamin B₁₂ deficiency?
Injections of B₁₂ (1000μg) 3 times per week for 2 weeks
Thereafter every 2 months
IF NEUROLOGICAL INVOLVEMENT
- B₁₂ injections alternate days until no further improvement - up to 3 weeks
- Thereafter every 2 months
A 49 year old man with grey hair and blue eyes presents with anaemia. Hos blood count is as follows:
Hb: 90g/L
WBC: 4 x 10⁹/L
Platelets: 160 x 10⁹/L
MCV: 110fl
What would be an appropriate set of investigations?
Test:
Folate and vitamin B₁₂
Thyroid function test
Liver function test
What is the general process of haemostatic plug formation?
1) Vessel constriction
2) Formation of an unstable platelet plug
- platelet adhesion
- platelet aggregation
3) Stabilisation of the plug with fibrin
- blood coagulation
4) Dissolution of the clot and vessel repair
- fibrinolysis
What is synthesised by endothelial cells?
Prostacyclin (PGI₂): antiplatelet
Thrombomodulin: membrane glycoprotein
von Willebrand factor
Plasminogen activators
How are platelets produced?
Stem cell precursors undergo nuclear replication to form megakaryocytes and become multinucleate
Maturation with granulation
Each megakaryocyte produces ∼4000 platelets. Lifespan ∼10 days, ⅓ stored in the spleen
What is the action of ADP on platelets?
Amplifies platelet activation
What is the mechanism of platelet adhesion to collagen during formation of a haemostatic plug?
von Willebrand factor binds to exposed collagen and then captures platelets by binding to GlpIb (surface glycoprotein) on their surface
OR
Platelets bind directly to collagen using GlpIa
What is the next step in the formation of a haemostatic plug following platelets binding to exposed collagen?
A signal causes the platelets to be partially activated and initiates the release of ADP and thromboxane
This causes further activation of the platelets
What is the mechanism of platelet aggregation?
Fibrinogen and Ca²⁺ initiate platelet aggregation causing them to bind together through surface glycoproteins GlpIIb and GlpIIIa
Thrombin is released which causes coagulation activation, amplifying the response
What is the pathway of prostaglandin metabolism in endothelial cells? What does this produce?
Membrane phospholipid ↓ phospholipase Arachidonic acid ↓ cyclo oxygenase Endoperoxides (PGG₂, PGH₂) ↓ Prostacyclin synthetase Prostacyclin (PGI₂) PGI₂ is a potent inhibitor of platelet function
What is the pathway of prostaglandin metabolism in platelets? What does this produce?
Membrane phospholipid ↓ phospholipase Arachidonic acid ↓ COX-1 (cyclo oxygenase) Endoperoxides (PGG₂, PGH₂) ↓ Thromboxane synthetase Thromboxane A₂ Endoperoxidases and thromboxane are potent inducers of platelet aggregation when secreted
How does aspirin affect platelet function?
Aspirin is a COX-1 antagonist so it inhibits the production of thromboxane which acts to induce platelet aggregation
What are the possible antiplatelet agents currently used as antithrombotic agents? How do they work?
ADP receptor antagonists: reduce the action of ADP which increases platelet activation
GPIIb/IIIa antagonists: Prevent agglutination of platelets by targeting the surface glycoproteins which crosslink
COX-1 antagonist: Inhibits the production of thromboxane which prevents further activation of platelets