Immune Thrombocytopenia (BCSH 2003, Blood 2012)

Newly Diagnosed

Persistent: 3-12 months

Chronic: >12 months

 

Intro

 

Primary ITP definition:

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

 

Adults – insidious onset, no clear cause, chronic process

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 à reduced survival, Hypo à 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

 

Not Required

-       Antiplatelet antibodies: Glycoprotein-specific antibodies – not specific

-       Antiphospholipid antibodies: + 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

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:

o   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 if 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 2010 TPO Agonists:

-       Recommended for chronic ITP in adults who have had splenectomy and are refractory to other treatments, or 2nd line in adults who have not had splenectomy because surgery is contraindicated. And only if:

o   Condition is refractory to standard and rescue therapies, and

o   There is severe disease with high bleeding risk that requires frequency 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

-       Tranexamic Acid

-       OCP

 

Treatment

-       To raise plt count

o   IVIg – rapid rise in >80% of patients

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

o   Steroids

-       Emergencies

o   Platelet transfusion with IV Steroids + IVIg

-       Second lines

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