Thrombocytopenia

Question 1

What is a normal platelet count?

What platelet count would you expect to see in thrombocytopenia?

Answer 1

Normal platelets:
-150-450 x 10^9

Thrombocytopenia = low platelet count
I.e. will have levels below 150

Question 2

What are the 2 main mechanism behind low platelets? What pathologies are associated with this mechanisms?

Answer 2

Problems with production

• SEPSIS= bone marrow suppression occurs in sepsis leading to decreased production
• B12/FOLATE DEF= due to suppression bone marrow production i.e. associated with pancytopenia
• LIVER FAILURE= decreased thromboprotein produced leading to decreased stimulation of platelet production
• LEUKAEMIA
• MYELODYSPLASTIC SYNDROME

Problems with destruction

• MEDICATION
• ALCOHOL
• IMMUNE THROMBOCYTOPENIA PURPURA
• THROMBOTIC THROMBOCYTOPENIA PURPURA
• HERPARIN INDUCED THROMBOCYTOPENIA
• HAEMOLYTIC-URAEMIC SYNDROME

Question 3

What medications can cause thrombocytopenia?

Answer 3

Sodium valproate

Methotrexate

Isotretinoin

Antihistamines

PPI

Question 4

How might someone with thrombocytopenia present?

Answer 4

Can be asymptomatic if it is only mild thrombocytopenia

Platelets <50:
Spontaneous bruising or prolonged bleeding times  
-epistaxis
-menorrhagia 
-bleeding gums 
-blood in stool or urine 

Platelets <10:
High risk of spontaenous bleeds
-ICH
-GI bleeds

Question 5

What is immune thrombocytopenic purpura (ITP)?

What might someone present with?

Answer 5

AI condition where antibodies are formed against platelets
Leads to antibodies opsonising the platelets-> results in platelets being consumed by macrophages

Purpura on legs
-due to haemorrhage of small blood vessels

Question 6

How is ITP managed?

Answer 6

Prednisolone
IV Ig
Rituximab -> MAb against BC which are producing the autoantibodies
Splenectomy
Controlling BP-> decrease risk of spontaneous bleeds
Manage menorrhagia (TXA + mefanamic acid)
Educate patient about red flag signs i.e. persistant headaches and melena

Question 7

What is thrombotic thrombocytopenic purpura?

What causes it?

Answer 7

Tiny blood clots develop in small vessels of the body which uses up platelets -> induces thrombocytopenia

Mutation in ADAMTS13 protein leading to deficiency in ADAMTS13

Question 8

What is the normal function of ADAMTS13 and why does a deficiency lead to thrombocytopenia?
What can be the causes of ADAMTS13 deficiency?

Answer 8

Protein acts to inactivate VWF and reduce platelet adhesion to vessel walls -> decreases clot formation

Lack of ADAMTS13 leads to overactivity of VWF which causes the small clots to form in blood vessels and uses up platelets to induce thrombocytopenia

Inherited genetic mutation
AI condition-> Ab against ADAMTS13 protein

Question 9

What other condition can occur in combination with TTP and why?

Answer 9

Haemolytic anaemia due to the blood clots in small vessels causing RBC passing through these vessels to break up

Question 10

How is TTP managed?

Answer 10

Plasma exchange
Steroids
Rituximab-> if related to Ab

Question 11

What is heparin induce thrombocytopenia? (HIT)

Answer 11

Exposure to heparin leads to development of antibodies against platelets
-antibodies target platelet factor 4 on surface of platelets

Question 12

What action do the anti-PF4 antibodies have?

Answer 12

Antibodies bind to the platelets and activate the clotting cascade
-induces a hypercoagulable state-> thrombosis occurs

Break down plaletes
-induces thrombocytopenia

Question 13

When would you suspect HIT?
How can it be diagnosed?
How are these patients managed?

Answer 13

When patient on heparin starts to have lot platelet count and shows signs of clot formation

Test for HIT antibodoes

Stop heparin and use other anti-coagulent