Transcript Idiopathic Thrombocytopenic Purpura

Idiopathic Thrombocytopenic
Purpura
Dr. Padma Poddutoori,
PGY3 , I.M
Dr. Sohail Chaudhry,
Attending physician, Hemeoncology
Definition
 ITP is
an immune-mediated disorder of platelet
destruction caused by antibodies.
 These antibodies react with platelet glycoproteins,
particularly glycoprotein IIb-IIIa, the platelet
fibrinogen receptor and glycoprotein Ib.
Classification of ITP
Acute and Chronic
 Primary and secondary
 Acute ITP is common in children following viral
exanthems or upper respiratory infections.60% recover in
4-6 wks and >90% in 3-6 m.caused by immune complexes
that contain viral antigens that bind to pl. Fc receptors or
by Ab produced against viral Ag that cross react with pl.
 Chronic : indolent form of thrombocytopenia that persists
for many years
 Secondary: SLE, HIV, Hep C, immunodeficieny or
lymphoproliferative disorders[B cell malignancies-CLL
and large granular leukemias]

Who develops ITP?
 Typically
a woman between 18 and 40 yrs.
 Female to male incidence: 3:1
 Gender disparity disappears largely in elderly
How do we diagnose ITP
ITP is a diagnosis of exclusion
 Isolated thrombocytopenia in an otherwise healthy
individual, with an otherwise unremarkable peripheral
smear, with/without physical findings of evidence of
bleeding.
 What is the best diagnostic test?
 Response to treatment especially to IVIG or IV anti-D,
even if transient is the single best diagnostic test

Diagnosis contd…..
 What
is the role of antiplatelet antibodies in the
diagnosis of ITP?
 We do not rely on measuring anti platelet
antibodies to make or exclude a diagnosis of ITP
 They are also seen in 10-20 % of pts with certain
causes of “non immune” thrombocytopenias[e.g
Chr. Liver dz, MDS]
 These assays lack sensitivity to exclude a diagnosis
of ITP
When do we perform bone marrow
examination
 Over
60 yrs of age[as the incidence of MDS is
significant]
 In those who do not show a robust
response[>50,000] to treatment
 Often prior to splenectomy
 When more than one cell lines are involved
What is the role of H.pylori in ITP?
 Remissions
induced by eradication of
asymptomatic H.pylori were reported in studies
from Japan and Italy, but is not our experience
 Consider testing in those with GI symptoms and in
chronic cases
Who do we treat?
 Our
usual practice is to maintain a somewhat
higher platelet count of 30,000.
 Major bleeding including spontaneous ICH occurs
predominantly in pts with platelet counts<20,000,
generally <10,000
 The risk of bleeding depends on the age of
individual, comorbidities and the medications
Treatment
EmergencyIV methylprednisolone [1 gm/day for 1-3 days]
IVIG [1 gm/kg/day for 2-3 days]
+/-IV anti-D [75mcg/kg]
+/-IV Vincristine[1-2 mg]
+/-Platelet transfusion
+/-Factor VIIa[if unresponsive to other modalities of
treatment, if immediate response is needed, e.g. ICH]

Treatment contd…..
 Initial
treatment for non emergent indications
Prednisone 1 mg/kg/day
+/- IV anti-D[50-75mcg/kg]
+/- IVIG[1 gm/kg/day x 2-3 days as needed]
OR
Dexamethasone[40 mg/day po x 4 days/month]
Treatment contd…..
 Persistent
ITP:
Low dose prednisone[<10 mg/day]
IV anti-D[50-75mcg/kg/dose]
IV anti-CD20[Rituximab] [375mg/m2 q week x 4]
Danazol [10-15 mg/kg/day po]
Treatment for 3-12 months from diagnosis
Splenectomy
Indications:
Whose disease does not abate by 1 yr after diagnosis
Who do not show a durable response to therapy
Who are intolerant to therapy
We use IVIG, IV anti-D or pulse doses of corticosteroids to
boost the pl count prior to surgery
Immunize pts 2 wks prior to surgery with polyvalent
pneumococcal, H.influenzae type b and meningococcus
85% attain hemostatic response after splenectomy and 2/3rds
achieve durable response.

Chronic ITP
Pl count<20-30,000
 First line therapies:
IV anti-CD20[Rituximab]
Or
Danazol +azathioprine or mycophenolate mofetil
Prednisone or IVIG prn
Second line therapy:
Cyclophosphamide or cyclosporine
Third line therapy:
Combination chemotherapy
Stem cell transplantation

Newer therapies
 Thrombopoeitin
receptor agonist- Eltrombopag
It is an oral small-molecule non peptide platelet
growth factor
It increased pl counts[to 50,000 or more] in a dose
dependant manner[50 or 75 mg] in pts with
relapsed or refractory ITP with pl count <30,000
This was attained in 80% of pts within 2 wks
Newer therapies contd…..
Romiplostim[Nplate]
A thrombopoeitin receptor agonist
Should only be used in pt s with chronic ITP with insufficient response
to steroids, IG or splenectomy and in pts whose degree of
thrombocytopenia and clinical condition increase the risk for
bleeding
Dosage: initial dose of 1 mcg/kg s.q q wkly[max of 10 mcg/kg],
increase by 1 mcg/kg/wk as needed to achieve and maintain pl count
>50,000.stop after 4 wks if no improvement in pl counts or if pl
count >400
Adverse reactions:dizziness, insomnia, arthralgia, myalgia, pain in
extremity, abdomen, shoulder,dyspepsia and paresthesia
Precautions: increases the risk for reticulin deposition in bone marrowmay result in marrow fibrosis with cytopenias; may increase risk for

A 70 yr old woman is evaluated for a 4 m h/o easy
bruisability. Her medical history is otherwise non
contributory. Physical exam and vitals are normal.CBC
showed a Hb of 11.5, WBC of 4500 and pl of 35,000.
Evidence of thrombocytopenia is noted on PBS. Pt is treated
with prednisone, 1mg/kg/day. After 3 wks, pl count is
30,000.
Which is the most appropriate next step:
1.Increase prednisone dose
2.Add anti-Rh D Ig
3.Perform bone marrow aspiration and biopsy
4.perform splenectomy
Bone marrow aspirate and biopsy should be
done in pts with suspected ITP who do not
respond to prednisone therapy.
A 32 yr old woman is evaluated during a routine exam. She
feels well and takes no medications. She has not had
excessive bruising, epistaxis or gingival bleeding. She is not
pregnant.PMH is otherwise non contributory. Physical exam
and vitals are normal.CBC is normal except pl 40,000.PBS
shows a decreased no. of pl, otherwise is normal.
Which of the following is the most appropriate next step in
management of this pt?
1.Antiplatelet antibody measurement
2.Bone marrow examination
3.Trial of prednisone
4.Periodic monitoring of pl count
Isolated thrombocytopenia in an otherwise healthy
young pt is most commonly due to ITP
Pts with ITP and low risk of bleeding as
demonstrated by a pl count of >40,000 require only
periodic monitoring of pl count.
Measurement of antiplatelet glycoprotein abs may
occasionally helpful in pt s with complex clinical and
lab findings.
Therapy for ITP is usually not initiated until pl count
falls to <30,000.
A 34 yr old woman is evaluated prior to undergoing
mammoplasty.during her teenage years, she was diagnosed with
“abnormal blood” for which she received prednisone. She does not
believe this therapy reversed her hematologic abnormality. Also has
occasional epistaxis and heavy menses but no prior surgery or
significant trauma.she has no children and takes only OTC
antihistamines and tylenol prn. Her mother and sister had ITP for
which her sister was treated with corticosteroids. Physical exam and
vitals are normal.CBC unremarkable except pl count of 40,000. PBS
shows a giant platelet.
Which of the following is the most likely diagnosis:
1.Inherited thrombocytopenic condition
2.ITP
3.Drug induced thrombocytopenia
4.Pseudothrombocytopenia
An inherited thrombocytopenic disorder should be
suspected in otherwise healthy pts with a low platelet
count, giant pl on PBS, a family history of
thrombocytopenia and who are refractory to steroids.
ITP is not an inherited condition. The May-Hegglin
anomaly, characterized by giant platelets and often
only producing modest bleeding manifestations, is
the likely inherited disorder in this patient.
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