Thrombocytopaenia

Question 1

What are platelets?

Answer 1

Anucleate cells. Lifespan 7-10 days. Controlled by thrombopoietin (TPO) produced in liver.

Bleeding problems can be due to either reduced platelet numbers or reduced platelet function.

Question 2

What is the range of normal platelet count?

Answer 2

Normal platelet count is between 150 to 450 x 10^9/L.

Question 3

What is thrombocytopenia?

Answer 3

Not enough platelets.

Question 4

Give 2 causes of thrombocytopenia.

Answer 4

1. Decreased production
2. Increased destruction

Question 5

Platelet dysfunction: what can cause decreased platelet production?

Answer 5

1. Congenital causes e.g. malfunctioning megakaryocytes.
2. Infiltration of bone marrow e.g. leukaemia, lymphoma, myeloma.
3. Reduced production from BM e.g. alcohol, reduced TPO
4. Infection e.g. HIV/TB.

Question 6

Platelet dysfunction: what can cause increased platelet destruction?

Answer 6

1. Autoimmune e.g. ITP.
2. Hypersplenism.
3. Drug related e.g. heparin induced.
4. Consumption of platelets - DIC and TTP.

Question 7

Platelet dysfunction: what can cause reduced platelet function?

Answer 7

1. Congenital abnormality.
2. Medication e.g. aspirin.
3. VWF disease.
4. Uraemia.

Question 8

What is ITP?

Answer 8

Immune Thrombocytopenia Purpura.

Isolated thrombocytopenia thought to be due to anti-platelet autoantibodies, leading to the immune destruction of platelets in spleen - autoimmune disorder.

Question 9

What antibodies are often found in ITP?

Answer 9

IgG.

Question 10

What are 3 other names for ITP?

Answer 10

1. Autoimmune thrombocytopenic purpura.
2. Idiopathic thrombocytopenic purpura.
3. Primary thrombocytopenic purpura.

ALL mean the same condition!!!

Question 11

Describe the epidemiology of ITP.

Answer 11

Typically occurs in children w/preceding viral illness or in middle aged women.

Question 12

What can cause ITP?

Answer 12

1. Viral infection.
2. Malignancy.

Question 13

Give 5 signs + symptoms of ITP.

Answer 13

1. Easy bruising
2. Epistaxis (nose bleed)
3. Menorrhagia (heavy menstruation)
4. Petechiae / Purpura (red or purple spots on the skin caused by bleeding underneath skin)
5. Gum bleeding

Question 14

What investigations are carried out to diagnose ITP?

Answer 14

1. Bloods - FBC - Thrombocytopenia
2. Bone marrow examination:
   * Shows thrombocytopenia with increased or normal megakaryocytes in the marrow
3. Platelet autoantibodies (present in 60-70%) - not needed for diagnosis

Question 15

How would you manage ITP?

Answer 15

• First line:
  1. Corticosteroids e.g. PREDNISOLONE
  2. IV immunoglobulin e.g. IV IgG - raises platelet count more rapidly than steroids - thus: useful for surgery
• Second line:
  3. Splenectomy
  4. If splenectomy fails, then immunosuppression e.g. ORAL/IV AZATHIOPRINE

Question 16

What is TTP?

Answer 16

thrombotic thrombycytopenia purpura
MED EMERGENCY - 95% FATAL. consider in any pt w/haemolytic anaemia + thrombocytopenia.

Question 17

Describe the pathophysiology of TTP.

Answer 17

1. Deficiency of protease that breaks down vWF (ADAMTS-13)
2. Large multimers of vWF form resulting in platelet aggregation and fibrin deposition in small vessels
3. Widespread platelet adhesion/aggregation
4. Leading to microvascular thrombosis + thrombocytopenia + haemolytic anaemia
5. Red cells passing these clots rupture due to shear force.

Question 18

give some causes of TTP. RFs?

Answer 18

congenital
sporadic
autoantibody mediated - pregnancy, SLE, infection

RFs - black, overweight, F, pregnacny

Question 19

Give 5 symptoms of TTP.

Answer 19

1. Florid purpura
2. Fever
3. Fluctuating cerebral dysfunction
   - Coma, Focal neuro, seizures, headaches, confusion
4. Haemolytic anaemia with red cell fragmentation
   - Pallor, jaundice, pruritus
5. Renal failure / AKI.
   - Raised urea/creatinine

Typical pentad of clinical presentation in exam questions

Question 20

Investigations for TTP.

Answer 20

1. FBC
   - Low platelets
   - Hb <8
   - Reticulocyte count raised
2. LDH + bilirubin raised
   - As a result of haemolysis
3. Peripheral blood smear
   - Microangiopathic w/SCHISTOCYTES (RBC fragments)
4. Urea and Creatinine raised
5. Urinalysis
   - Proteinuria
6. Coagulation screen - normal

Question 21

How would you treat a patient with TTP?

Answer 21

1. Plasma exchange (urgent) - within 24 hrs
   - To remove antibody to ADAMTS-13 as well as provide a source of ADAMTS-13
2. IV METHYLPREDNISOLONE (within 24 hrs)
   - Immunosuppression
3. IV RITUXIMAB
   - Antibiotic
4. Aspirin
   - Long term = decreases platelet aggregation