Immune Thrombocytopenia (ITP) (BSH 2003, ash 2011, blood 2017)

definitions

Primary ITP: Acquired immune-mediated disorder characterized by a plt count <100 & absence of any obvious initiating or underlying disorder

It can be:

  • Newly Diagnosed

  • Persistent: 3-12 months

  • Chronic: >12 months

 

Intro

  

Adults – insidious onset, no clear cause, chronic process. 3 per 100,000 per year

Vs

Children – short lived, 2/3 recover in <6 months, 2/3 have a preceding infection

 

Differential

  • Secondary ITP: Hep C, HIV, Infection, SLE, MMR vaccine, Lymphoproliferative disorders

  • Liver disease

  • B12/Folate deficiency

  • Thyroid disease: Hyper —> reduced survival, Hypo —> reduced production

  • Drugs: Antibiotics, Alcohol, Quinine, Environmental toxins

  • BM disorders: AA, MDS, MF, Leukaemia

  • Post-Transfusion Purpura

  • Inherited thrombocytopenias

 

Investigations

 

Standard panel

H. pylori, FBC, Retic, Film, Immunoglobulins, G&S, DAT, HIV, Hep C

ANA: If positive predicts a chronic course in children

TSH + Thyroid antibodies: 10% of ITP patients develop hypothyroidism

Pregnancy Test

 

When to consider BM biopsy

Age >60

Atypical history/examination

Prior to splenectomy

 

Tests Not Required

Antiplatelet antibodies: Glycoprotein-specific antibodies – not specific

Antiphospholipid antibodies: Positive in 40% but does not predict response to treatment

 

Treatment Overview

 

1st Line: Steroids, IVIg, Anti-D

2nd Line: Rituximab, Splenectomy, TPO agonists, Steroid-sparing immunosuppressants

Beyond 2nd Line: TPO agonists or toxic treatments (Campath, HSCT, Chemotherapy)

 

Management of Adult ITP

 

Tailored to patient, no fixed protocol

Haemorrhagic death is rare – 0.01 cases / adult patient / year

1.5-1.8% risk of intracranial haemorrhage

Treatment very rarely required if platelet count >50, or even >30

 

There are no head-to-head trials to enable recommendation of one Rx over another.

But note TPO agonists have gone through proper RCT’s unlike older therapies

 

Supportive Care

Tranexamic Acid, Mirena coil / OCP

Patient support groups

 

Steroids

10-60% respond

Pred 0.5-2mg/kg/day until response, then taper and stop by 4 weeks

Dex 40mg/day for four days and stop

Methylpred if oral route not an option

 

IV Immunoglobulins

Dose: 1g/kg as a single infusion

Quicker time to response than steroids.

 

IV Anti-D

50-75 micrograms/kg as a single dose

Suitable for Rh D+, non-splenectomised patients

Thought to work by coating Rh D+ cells leading to their preferential destruction by the spleen, sparing the platelets.

SE: DIC, Renal failure, Intravascular haemolysis

 

Splenectomy

80% respond, 66% for >5 years. Unmatched by other therapies

10% complication rate with laparoscopic approach. Aim plt >20 prior to surgery.

Vaccination:

  • Hib/Men C, Polyvalent Pneumococcal, Men B, Men ACWY, Annual ‘flu

 

Rituximab

40% respond, 20% for 3-5 years

375mg/m2 weekly for four weeks. May be more effective combined with dex

Given to >1 million patients worldwide with good tolerability

 

TPO Agonists

60-90% response rate but requires maintenance therapy. 1-2 weeks to first effect

Romiplostim: 1-10 microg/kg SC weekly

Eltrombopag: 25-75mg PO daily. 2 hours apart from food, 4 hours from calcium-foods

SE: small number of reports of increased marrow reticulin.

 

NICE Recommendation for TPO Agonists (Romiplostim 2011, Eltrombopag 2013):

Recommended as a treatment for adults with chronic ITP only if:

  • Condition is refractory to standard and rescue therapies, and

  • There is severe disease with high bleeding risk that requires frequent treatment.

 

Management of Childhood ITP

 

Remember diagnosis of exclusion, continue to re-visit over time

After 3-6 months consider:

  • BMAT, Immunoglobulins, ANA, APL Ab, HIV, H. pylori, Hep C

 

General

97% clinically asymptomatic

If bleeding, grade severity 1-4. Treat if grade 3 or 4.

Watch and Wait management should still be consented for

Avoid contact sports, continue all other activities

 

Supportive Care

Tranexamic Acid

OCP

 

Treatment

To raise plt count

  • IVIg – rapid rise in >80% of patients

  • IV Anti-D – Small dose, gives transient rise

  • Steroids

Emergencies

  • Platelet transfusion with IV Steroids + IVIg

Second lines

  • As per adults. No TPO studies in children yet.