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Immune thrombocytopenia comprises

§   Drug induced

§   Neonatal alloimmune thrombocytopenia

§   Post-transfusion purpura

§   ITP

§   Acute ITP

§   Secondary ITP


Incidence 6/100,000



§        Immunne dysregulation

§        Accelerated platelet destruction

§        Abnormalities in megakaryocyte growth and development

§        Poorly compensated thrombopoiesis

§        TPO is produced by the liver and binds to its receptor c-MPL on platelet membrane. At high platelet counts, TPO is internalised by platelets. In ITP, low TPO levels are found.

§        Acute ITP usually occurs in children following viral illness or immunisaton, the majority do not require treatment and 80% resolve within 6 months. (20% go on to develop chronic ITP)

§        Secondary ITP occur in patients with other immune disorders (eg SLE or CLL), viral illneses or bacterial (H. pylori)


Adult ITP

§   Clinical features

§   Predominantly occurs in women of childbearing age

§   Insidious onset, with no preceding viral or other illnesses



§   Mucocutaneous bleeding (rather than coagulation type haematomas)

§   Recent transfusion (PTP)

§   Alcohol / liver disease

§   FH – inherited thrombocytopenia

§   Marrow infiltration

§   Type 2B VWD

§   Drugs

§   Viruses (HIV)

§   Other AI disease

§   Malignancy



Blood film

§   To exclude other causes (acute / chronic leukaemia; MDS; megaloblastic anaemia; MAHA; inherited thrombocytopenias and pseudothrombocytopenia)


Bone marrow

§   Contentious (unless over 60 and in those in whom splenectomy is being considered)

o        May also be considered if refractory to first line treatment / relapse after CR

§   In one study 61 of 66 patients had marrows consistent with ITP; 4 had hypocellular aspirates and one had giant metamyelocytes and neutrophil hypersegmentation.


Antiplatelet assays

§   Direct platelet immunofluorescence test (PIFT) is used to investigate referred samples for the presence of platelet associated immunoglobulin (PAIg) (indirect testing against normal platelets of little use)

§   Can be detected in most patients with ITP but not very specific (esp when septic)

§   Assays for GP IIb/IIIa and Ib/IX (most commonly identified antigenic targets)are less sensitive (50-60%) but more specific (90%)

§   Can be useful in distinguishing immune from non immune in complex cases but routine use not justified

§   Recommended in:

§   Bone marrow failure with ITP

§   ITP patients refractory to first and second line treatment – recommended when third line therapy being considered

§   Drug dependent immune mediated thrombocytopenia (DDITP) – serological investigations are important particularly for Heparin / Quinine and Teicoplanin


TPO assays

§   Can be useful in distinguishing between reduced production (high level) and increased destruction (normal level) but currently not routinely available.


Reticulated platelets

§   Measurement of platelet RNA by flow gives measure of platelet maturity.

§   Role not established yet


Helicobacter pylori infection

§   Conflicting evidence but some studies suggest that H. pylori infection is associated with ITP and that treatment of the H. Pylori caused remission of ITP. 

§   May be worthwhile performing screening

§   Urea breath test and antigen detection in stools are the most accurate

§   serology - but antibody levels only fall slowly

§        Eradication therapy is successful in about 50%

§        More likely to respond the shorter the duration of ITP and if not severe


Investigations for other causes:

§   UE

§   LFT

§   Inflammatory markers


§   Clotting screen

§   AI screen (lupus)


§   Virology (HIV, Hep B/C)


§   Antiphospholipid screen

§   vWF levels (Type IIB)



§   Risk of fatal haemorrhage 1.6-3.9 %  per patient year when the platelet count is <30

§   85% achieve platelet counts >30 and have the same mortality as the general population

§   9% with severe ITP have a mortality risk of 4.2

§   Recent review found that more patients died of infection than bleeding


Safe platelet counts

§        Dentistry  >10

§        Extraction/ regional dental block >30

§        Minor surgery >50

§        Major surgery >80


Platelet counts >30 require no treatment (unless undergoing surgery)


First line - Prednisolone (1mg /kg) and IVIg (0.4g for 5 d or 1g for 2 d)


1. Prednisolone

§   50% response rate

§   Dose should be tapered at 2-4 weeks

§   Long term remission only seen in 10-20%


2. IVIg

§   75% response rate

§   Responses only transient – lasting 3-4 weeks

§   Mechanism largely unknown but is believed to involve blockade of Fc receptors on macrophages

§   Pooled blood product – cases of Hep C but has excellent safety record


Second line



§   60% achieve a normal platelet count

§   Platelet count should be >30 preop (treat with pred / IVIg pre op)

§   Donor random platelets can be given intraoperatively once the splenic artery has been clamped

§   2% mortality on case series

§   Response to splenectomy can be predicted using indium-labelled platelets – if destruction was splenic then >90% response rate to splenectomy – if elsewhere <10% responded

§   Accessory splenic tissues may cause patients to fail to respond (seen on imaging in 12% of those who fail to respond) or to relapse


Prevention of infection post splenectomy


1. Vaccinations (should be given 2 weeks pre surgery)

§   Pneumococcal vaccine (revaccination every 5 years)

§   Hib (no need for booster)

§   Meningococcal C (no need for booster)

§   Annual influenza vaccine recommended


2. Pen V / erythromicin


Refractory disease = failure to maintain platelet >30 after 6-12 months of standard therapy


Second line therapy

1. High dose corticosteroids

§   Dexamethsone 40mg 4d repeated every 28d for 6 cycles

§   Methylprednisolone e.g. 30mg/kg for 3d then 20mg/kg for 4d the 5, 2, 1 mg/kg for a week each

§   Small studies showing good response rates but transient responses


2. Anti-D

§   Only used in RhD positive patients who do not have a splenectomy

§   Elevates the platelet count in around 80%

§   Mechanism – causes haemolysis with the red cells being preferentially taken up by the reticuloendothelial system.

§   Can cause severe haemolysis

§        Check Hb and DAT

§        If transfusion required, use RhD negative red cells


3. Vinca alkaloids

§   Cause a transient increase in platelet count lasting 1-3 weeks

§   50% respond but only 10% sustained


4. Danazol

§        60% response rate

§        Down regulates Fc receptors on splenic macrophages

§        When given for more than 1 year induced remissions lasting for years after discontinuation


5. Immunosuppressants

§        Azathioprine (60% response rate but slow – several months)

§        Cyclosporine A

o        Use limited by side effect profile

§        Cyclophosphamide


6. Dapsone

§        50% response rate in a small study


Third line treatment

1. IFN-alpha

              Not currently recommended, case report of a fatality

2. Anti-CD20 antibody – rituximab

3. Campath-1H (CD52)

4. MMF

5. Protein A immunoadsorption

6. Combination chemotherapy (eg CVP)!


Emergency treatment

§   Platelet transfusion

§   Methylpred

§   IVIg



§        3 large cohorts of adults who had failed multiple therapies

§        50% had a PR or CR and 33% had durable remissions

§        Prospective multicentre study in children

§        31% achieved a sustained plt count >50

§        Mechanism

§        Elimination of B lymphocytes, but doesn’t explain very rapid responses

§        B-cells opsonized with anti CD20 cause Fc receptor blockade


Platelet growth Factors

§        Romiplostim

§        TPO peptide mimetic

§        Binds at the endogenous TPO-binding site

§        Weekly subcutaneous administration

§        Adverse events of increased marrow reticulin

§        Continuing in an extended open label trial for continued surveillance of efficacy and safety in ITP

§        Also in trial for MDS and chemo related thrombocytopenia

§        Approved by the FDA for chronic ITP

§        Eltrombopag

§        TPO non-peptide mimetic

§        Binds at the intramembrane portion of the TPO receptor

§        Daily oral administration

§        Eltrombopag is a new, orally active thrombopoietin-receptor agonist that stimulates thrombopoiesis. It interacts with the transmembrane domain of the thrombopoietin receptor inducing proliferation and differentiation of megakaryocytes.

§        Randomised placebo controlled study of 118 adults with chronic ITP and platelet counts <30 x109/l who had had relapses or were refractory to at least one standard ITP treatment. Primary end point was a platelet count >50 x109/l at day 43.

§        In the Eltrombopag groups receiving 30, 50, and 75 mg per day, the primary end point was achieved in 28%, 70%, and 81%, whilst in the placebo group only 11% reached the primary end point.  Median platelet counts for eltrombopag were 26 x109/l in 30mg group, 128 x109/l in 50mg group and 183 x109/l, compared to 16 x109/l in placebo group.

§        By day 15, >80% responses were seen for 50 or 75 mg Eltrombopag. Incidence and severity of adverse events were similar in the placebo and Eltrombopag groups.

§        Eltrombopag seems effective at increasing platelet counts in a dose-dependent manner in patients with relapsed or refractory ITP.

§        It has also been used with good effect in HCV patients, increasing the platelet count to adequate levels to enable anti-viral treatment.



§        Prior to HAART, thrombocytopenia occurred in 15-30%

§        More prevalent in patients with a CD4 <200, clinical AIDS, IVDUs

§        Pathology

§        Increased platelet clearance due to immune complex disease

§        Anti-platelet glycoprotein antibodies

§        Anti-HIV antibodies that show antigenic mimicry with platelet glycoprotein antibodies

§        Direct infection of megakaryocytes results in defective platelet production and mega apoptosis

§        ITP early on in disease more commonly resembles classical ITP, whereas when it occurs later it is often associated with additional cytopenias

§        Usually respond to HAART and if necessary to conventional ITP treatment

§        Long term steroids should be avoided due to the risk of immunosupression, but IVIG and anti-D are effective alternatives



§        In the largest series published, 30% of patients diagnosed with chronic ITP had HCV antibodies

§        Possible pathology

§        High affinity binding of HCV to platelet membrane which binds to anti-HCV and phagocytosis by ‘innocent bystander’ mechanism

§        Splenic sequestration secondary to portal hypertension

§        Immune dysregulation resulting in auto-antibodies to platelet glycoproteins

§        Controversial results with steroids, and should be avoided if possible as it can increase viral load and worsen liver damage

§        Anti-D and IVIG seem to be effective and eltrombopag has had promising results

§        Interferon for HCV is also effective


ITP in Children


Differential diagnosis

Neonatal period

§   Maternal ITP

§   NAIT

§   Wiscott Aldrich

§   Bernard Soulier disease

§   Unspecified hereditary thrombocytopenias



§   Viral infection (varicella can cause more complex coagulation changes with antibodies to protein C and S)

§   Post vaccination (MMR – 1:24,000) – should check serological levels prior to second vaccine if this occurs to evaluate need for 2nd dose

§   Evolving Fanconi anaemia

§   Von Willebrands type IIB

§   Leukaemia (esp in Down’s)

§   Aplastic anaemia




Coag screen (if suspected meningococcus, bleeding disorder or NAI)


Bone marrow

§   If child requires no treatment shouldn’t do

§   Indicated if atypical features (ideally pre-prednisolone) or poor response to treatment


Clinical course

§   Only 4% have serious bleeding such as severe epistaxis or GI bleeding

§   Intracranial haemorrhage 0.1-0.5%



§   Treatment should be based on clinical symptoms rather than platelet alone

§        Most would treat if <10 &/or mucosal bleeding

§   If treatment required, intermittent treatment with IVIG or anti-D may be used whilst awaiting spontaneous remission


1. Conservative  (>80% patients – recover spontaneously within 6-8 weeks)

§   Avoid contact sports

§   Repeat FBC at 7-10d to check there is no evidence of serious marrow disorder

§   Otherwise FBC only needs to be repeated if there is a change in symptoms suggesting remission (persisting petechiae indicate that it has not resolved and an FBC is probably not useful).

§   Parents need to have 24h helpline similar to haemophiliacs

§   Card / letter in case of emergency – if chronic


2. Corticosteroids

§   Prednisolone 4mg/kg for 4d or 1-2mg/kg for 14d

§   Brings platelet count up more rapidly than conservative treatment but slower than IVIg (4d v 16d v 2d in one trial).

§   Significant long term effects so courses must be <2-3 weeks


3. Intravenous immunoglobulin (1g/kg for 1 or 2 days)

§   Effective in 80%

§   Expensive and invasive (can transmit hep C)


4. Anti-D (45-50 mcg/kg)

§   Similar speed of rise as IVIg

§   Occasionally severe haemolysis (even causing renal failure)


Chronic ITP in childhood

§   Counts persistently <10 very rare and should be managed in a specialist centre.

§   For those with counts <20

§   Risk of bleeding 0.5% at 12 months in those with a count <20

§   Treatment with IVIg can be given to cover activity holidays

§   Clinic appointments should be spaced out to allow schooling

§   Splenectomy but 25% don’t respond – rarely justified – perhaps in chronic severe ITP that has not resolved in 12-24 months



Differential diagnosis

§   Spurious

§   Gestational thrombocytopenia

§   Pre-eclampsia


§   ITP

§   SLE

§   Drug related (DDITP)

§   Antiphospholipid syndrome

§   Viral (HIV)

§   DIC

§   HUS

§   TTP

§   Folate deficiency

§   Congenital platelet disorders

§   Coincidental bone marrow disease

§   Hypersplenism


Normal platelet count falls 120-150 not uncommon in third trimester


All women with counts <100 should be screened for Pre-eclampsia, coagulopathy or AI disease


Gestational thrombocytopenia (5-8% of all pregnancies)

§   Mild thrombocytopenia >80 (rarely can be 50)

§   Otherwise normal blood counts

§   Third trimester most common

§   Normal platelet counts before and after pregnancy

§   No association with maternal haemorrhage

§   No association with fetal or neonatal thrombocytopenia



§   1-5 cases per 10,000 deliveries (100x less common than GT)

§   May get neonatal thrombocytopenia

§   Need to exclude pre-eclampsia, DIC, SLE, APLS

§   Bone marrow not recommended



Platelet counts >20 do not require treatment until term


>50 for vaginal delivery / C. section

>80 for epidural anaesthesia


Prednisolone 1mg/kg

§   Few fetal side effects (e.g. adrenal suppression) as 90% metabolised in placenta


IVIg – normal adult dose

§   Same time-course as non-pregnant

§   Similar response rates to steroids

§   No good data on effect on neonatal counts

§   Caution with anti-D because of fear of inducing fetal haemolysis


If resistant

§   1g Methyl pred (with IVIg)

§   Azathioprine

§   Splenectomy – now rarely done – difficult after 20 weeks


Management of delivery / new born

§   No evidence C section is safer

§   Ventouse should be avoided – forceps as well - if possible

§   Maternal platelet count does not predict fetal platelet count

§   Just need platelet count on cord blood – should be done on all

§   Usually reach nadir at day 2-5, therefore daily FBCs

§   Avoid fetal blood sampling (more dangerous than neonatal thrombocytopenia itself) and scalp electrodes.

§   Neonatal platelet count rarely <20

§  Should be treated with IVIg 1g/kg

§  If bleeding then should have platelet transfusion and IVIg

§  Exclude NAIT



Anaesthetic recommendations

§   Platelet count for epidural >80 not evidence based and should be evaluated on a case by case basis

§   NSAIDs should be avoided if the platelet count is <100

§   VTE is the commonest cause of maternal mortality therefore if immobilised, undergoing surgical delivery or have thrombophilia esp APLS should have prophylactic clexane when platelet count >50.



§   Tranexamic acid

§   Oral contraceptives

§   Mirena coil


ITP support organisation

§   Factsheets / conventions