Here is a very comprehensive lecture about ITP, its types , signs and symptoms and management. This lecture presentation was delivered by Dr Nida TMO in MBW HMC Peshawar Pakistan.
2. OBJECTIVES
• Itp ,its terminologies, pathogenesis and
clinical manifestations
• Diagnostic evaluation and differential
diagnosis in light of itp
• Management of itp according to americian
society pf haematology 2019
• First and second line treatment options
• Different clinical scenarios
3. Immune thrombocytopenia
An acquired autoimmune thrombocytopenia
caused by autoantibodies against platelet antigens;
Gp2b/3a
one of the most common causes of
thrombocytopenia in otherwise asymptomatic
adults
5. Pathogenesis
• Incompletely understood
• Predominant hypothesis is
reduced lifespan of platelets due
to antibody mediated destruction
by b-cell derived igG directed
against glycoprotein 2b3a
• Other likely important mechanism
include autoreactive cytotoxic T
cell, humoral and cellular
autoimmunity directed at
megakaryocytes
6. TERMINOLOGY
●Primary ITP – Primary ITP is acquired immune thrombocytopenia due to autoimmune
mechanisms leading to platelet destruction and platelet underproduction that is not triggered
by an apparent associated condition.
●Secondary ITP – Secondary ITP is ITP associated with another conditions
●Drug-induced immune thrombocytopenia – Drug-induced immune thrombocytopenia (DITP)
is thrombocytopenia due to drug-dependent platelet antibodies that cause platelet
destruction.
1. Acute: children
2. Chronic : female of reproductive age
7. The time elapsed since diagnosis determines whether ITP is referred
to as newly diagnosed, persistent, or chronic.
•Newly diagnosed – Up to three months since diagnosis
•Persistent –3 to 12 months since diagnosis
•Chronic – More than 12 months since diagnosis
8. Inciting events
Infection such as HIV,HCV, CMV VZV - viral antigen may cross react with normal platelets antigen ;
molecular mimicry
Systemic condition that disrupts immune homestasis ; autoimmune or malignancy
Immune alteration ; loss of peripheral tolerance and development of self reactive antibodies ,
APS,SLE,Evans syndrome, CLL
Alternative immunologic mechanisms involving T cells have also been postulated to cause ITP, including
T cell-mediated cytotoxicity and defects in the number and/or function of regulatory T cells (Tregs)
11. CLINICAL
MANIFESTAT
ION
• Bleeding; petechiae, purpura,
epistaxis, critical hemorrhage
• Fatigue
• Thrombosis (rare) —
Thrombocytopenia in people
with ITP is not necessarily
protective against thrombosis.
• Several studies have
documented an increased risk
of thrombosis in people with
ITP compared with controls
• No effects on WBCs or RBCs
12. diagnostic concerns in
an adult
Major diagnostic concerns
in an adult with suspected
ITP are twofold:
Distinguishing ITP from other
causes of thrombocytopenia,
which often have a similar
presentation but may require
completely different
management approaches
Determining whether the ITP
is primary or secondary to an
underlying condition that
might also benefit from
treatment
13. Diagnostic
evaluation
• History : recent infection, underlying condition,
medication
• Physical examination: petechiae, purpura,
mucosal bleeding, menorrhagia
• Laboratory testing: smear, virology, coagulation
studies, h-pylori stool antigen, TFT(before
surgery for occult hypo or hyperthyroidism)
• Bone marrow examination; older than 60 to
exclude myelodysplastic syndrome or
unresposive patients
• Immunologic studies: ANA, APLA,
• Vitaminb12 folate levels
• Antiplatelet antibodies
14.
15. Falsely low platelet counts
(pseudothrombocytopenia)
In vitro platelet clumping caused by ethylenediaminetetraacetic acid
(EDTA)-dependent agglutinins (naturally occurring antibodies)
In vitro platelet clumping caused by an insufficiently anticoagulated
specimen
In vitro platelet clumping caused by glycoprotein IIb/IIIa inhibitors (eg,
abciximab) (NOTE: these can also cause true thrombocytopenia)
Giant platelets counted by automated counter as white blood cells rather
than platelets
16. ITP after
COVID-19
vaccination
(January
2022)
• What's New
• Exacerbations of immune
thrombocytopenia (ITP) as
well as new-onset ITP have
been reported after COVID-
19 vaccination
• Individuals with ITP who
receive any COVID-19
vaccine should be advised
about this risk, and platelet
counts should be
monitored before and after
vaccination
17. OVERVIEW OF DECISION-MAKING
The goal of treatment is
to treat or prevent
significant bleeding, not
to normalize the platelet
count. However,
bleeding risk can be
difficult to estimate.
The overall risk of critical
or severe bleeding in ITP
is relatively low (on the
order of 1 percent for
intracerebral
hemorrhage)
•Risk is greatest in
individuals with the
following:
Prior bleeding
•Platelet count
<10,000/microL
•Older age, especially
>60 years
18.
19. TREATMENT
OF ITP
• FIRST LINE
• Glucocorticoids
• IVIG
• Anti-D immunoglobulin
• SECOND LINE
• Splenectomy
• Rituximab
• TPO-Ab: eltrombopag, romiplostim
• OTHER
• Azathioprine
• MMF
• Danazol
• Fostamatinib
• Vinalkaloids
20. GLUCOCORTICOIDS
Mechanism of action – The mechanism is uncertain but may involve increased apoptotic death of autoantibody-
producing lymphocytes and downregulation of macrophage activity responsible for platelet phagocytosis
Dosing – The most common treatment regimens are
Pulse dexamethasone 40 mg orally or IV OD for 4 days with no taper. This can be repeated for additional cycles, up to
three times in total
Pulse methylprednisolone –1 g IV for 3 days with no taper. This may be used in critical or severe bleeding.
Oral prednisone with a taper –1 mg/kg orally, OD (range, 0.5 to 2 mg/kg daily) for 1-2 weeks, followed by a gradual
taper, typically completed over less than six weeks
Administration of glucocorticoids for longer than six weeks should be avoided to minimize side effects . If there is no
platelet count response after two weeks, a faster taper (over one week) can be used.
21. IVIG
more rapid increase in platelet count,
those who do not have an initial platelet count increase with glucocorticoids
who require therapy to increase the platelet count and cannot tolerate glucocorticoids.
IVIG can raise the platelet count within 12 to 24 hours in many patients with ITP; this effect is reproducible enough that a
platelet count response to IVIG has been used as a diagnostic criterion for ITP
The effect of IVIG usually persists 2-6 weeks
Mechanism of action – IVIG increases the platelet count by interfering with macrophage uptake of autoantibody-coated
platelets
Dosing –1 g/kg OD for 1-2 days. A single dose of 1 g/kg for one day is often sufficient. Alternative dosing : 400 mg/kg OD 5
days.
The IVIG can be stopped when a response occurs (ie, platelet count >30,000/microL), even if the full course has not been
completed.
Adverse effects: Headache, hypertension, chills, allergic reactions, vomiting, and hypotension may occur during or
immediately following the infusion.
22. Anti-D
Alternative to IVIG in RhD positive patients
FDA boxed warning: severe hemolytic transfusion reaction
Mechanism: Anti-D is an immune globulin directed against
the D antigen of the Rh blood group system; it is thought to
raise the platelet count by saturating macrophage Fc
receptors with anti-D-coated red blood cells (RBCs).
Dosage: The usual dose of anti-D is 50 to 75 mcg/kg
intravenously
23. Splenectomy
• potentially curative procedure (response rate, 80 to
90 percent)
• No regular medication but risks of
immunosuppression and venous thromboembolism
(VTE).
• Predictors of efficacy include younger age and
splenic sequestration on radiolabeled liver-spleen
• often wait at least 12 months to allow time for late
spontaneous remissions to occur.
• provide preoperative immunizations atleast 2 weeks
prior
• suggest a laparoscopic rather than an open
procedure
24. Rituximab
• to avoid surgery,
• prefers not to take a medication for an extended
duration of time
• willing to accept risks of immunosuppression and
possible need for retreatment.
• Efficacy is 40 to 60 percent; median duration is
approximately one year
• Patients who will receive rituximab should be
tested for hepatitis B surface antigen (HBSAg)
and hepatitis B core antibody (anti-HBc), may
cause false positive results from passively
acquired anti-HBc antibodies
• The optimal dose is unknown; many clinicians use
375 mg/m2 intravenously once a week for four
consecutive weeks.
25. TPO-RA
• May be a good choice for an individual who wishes to
avoid surgery and immunosuppression and is less
concerned about the costs and burdens of taking a daily
or weekly medication
• Romiplostim – 1mcg/kg Weekly subcutaneous injection.
• Eltrombopag – 25-50mg Oral daily pill taken without
polyvalent cations.
• Avatrombopag – 20mg Oral daily pill taken with food
• Adverse effects include VTE and bone marrow fibrosis
(reversible and generally not clinically significant). Close
platelet count monitoring is used to avoid
thrombocytosis. Eltrombopag requires liver enzyme
testing.
• These agents are expensive
41. Case 1
• 27 years old female presented with
generalized mucocutenous bleed with plt
count of 03 × 10^3/ul . She had no other
symptoms and physical examination was
Unremarkable except for laref bruises on
lower extremities and on bucal mucosa. She
is a diagnosed case of ITP since 15 months.
She was initially started on pred 2mg/kg/day
with a rise in plt count to 100.Her count
dropped again on Steroid tapering. She is
married and want to conceive by next year.
• 1.best 2nd Line therapy in this case?
42. answer
• Rituximab
• Rituximab is potentially a safe treatment
option for the management of immune
thrombocytopenic purpura in pregnancy
with good maternal and neonatal outcome
when conventional treatments have been
unsuccessful.
• TPO-RA, rituximab, or fostamatinib were
possible options. Depending on when she
was considering pregnancy, she may have
wished to avoid TPO-RAs and fostamatinib.
Given evidence indicating that females <40
years of age may have a 73% response rate
(56% complete response), rituximab may be
the most appropriate choice
44. Case 2
• young 06 years old girl presented in opd with history of
nasal bleed for 03 days and single large bruise on right
arm.
• She had history of haematuria 01 month back for which
she was reviewed by pediatrician and relative workup
was advised. At that time her cbc revealed low plt count
of 05k with normal coagulation profile and ultrasound
KUB.
• She was started on Steroid 2mg/kg/day as a suspicion of
ITP and planned for tapering next visit after a week.
There was a rise in her plt count to 75 over the next
week. Steriod was stopped without tapering.
• Resident on Call make a plan for the patient and after
discussing with her consultant she give plan to the
patient.
• 1) treatment plan?
45. Answer
• Start on Steriod with 1mg/kg along with
gastroprotective agent, tranxemic acid and
called after 01 week and immediately in case
of active bleed.
46. Case 3
• 50 years old male patient presented to heam
OPD on his follow up visit for Persistent ITP
on low dose steriod.
• There is no active bleed bleed or brusing.
• O/E
• Cervical lymphadenopathy with
spleenomegaly.
• 1. Next plan
49. Case 4
• 20 years old male patient with steriod
refractory chronic ITP for last 03 years. He
was started on TPO-RA but with no
response. He is planned for splenectomy
next month.
• 1. actions before splenectomy?
51. Case 5
During a routine check-up, a 78-year-old woman had
an abnormal complete blood count and a blood smear
remarkable only for the decreased number of
platelets. She had hypertension, diabetes, and
osteoporosis, and was taking aspirin. Aspirin was
discontinued, and prednisone was initiated at 1 mg/kg
per day. Platelet count increased to 62—109/L after
two weeks. Prednisone was gradually tapered by 5 to
10 mg/day weekly, but the platelet count fell to
pretreatment levels at 10 mg/day, prompting a return
to prednisone dose of 30 mg/day. Her blood sugar
became persistently elevated, requiring addition of
another antidiabetic agent. At a follow-up visit 12
weeks after diagnosis, she was still receiving
prednisone 20 mg/day with a platelet count of 34—
109/L. how to preceed ?
52. Answer
• TPO-RA favored over rituximab and
fostamatinib based on their durable, six-
month response rates.
• Current clinical guidelines recommend
limiting the maximum duration of
corticosteroid treatment to six to eight
weeks. The patient had already been treated
with corticosteroids for three months and
still required a relatively high prednisone
dose to maintain an adequate platelet count.
Her diabetes worsened and required
additional antidiabetic agents.
53. Case 6
• 41-year-old man childhood history of on and
off epistaxis now presented with mucosal
bleed . On examination ecchymosis and rash
over the trunk and upper limbs, with a non-
itchy rash scattered throughout his body.
General laboratory tests were requested for
the patient, which revealed a platelet count
of 3,000/mm3. Pt had elective splenectomy
for itp around 3 months back. He is very
anxious why he is dropping platelets again,
what investigation to go around with?
55. Case 7
• 34years old lady prrsented to clinic with 36week
period of gestation. This is a precious pregnancy
via IVF. She was diagnosed as itp in her 20s and
since then she is on glucocorticoids on and off.
She was started on rituximab where since she
concieved.
• Now she is having blood streaks in sputum after
she caught seasonal allergy, diarrhea and PV
bleed since morning. Fresh Plt count is 5k. On
CTG fetus is in distress
• Mode of delivery?
• How to treat this low plts?
• How to diagnose baby ?
56. Answer
Mode of delivery:
caesarean section
To raise plt to appropriate
level, give glucocorticoids
and IVIG
For baby; take sample
from cord, and do
mannual platelet count
Never diagnose, start or
change treatment on one
cbc reading , mannual
reading is preffered
57. Case 8
• 55 years old male presented with complains of
weakness, fatigue and hematuria. He is retired
pilot by profession, received treatment for HCV .
Exsmoker with 1 pack year for 15 years . Routine
investigations were done and it showed 30k
platelets. After extensive investigations, pt was
labelled as itp . Responded well to
glucocorticoids and IVIG, discharged on tapering
dose.
• After a month he again presented to clinic with
fatigue blood tinged stool dyspnea. This time his
Hb is 9, PLT 5k LDH is 546, Direct coobs positive ,
reticulocyte is 2.5%
• Whats your diagnosis ?
58. Answer
• Evans syndrome is a very rare autoimmune
disorder in which the immune system
destroys the body's red blood cells, white
blood cells and/or platelets. Affected people
often experience thrombocytopenia (too
few platelets) and Coombs' positive
hemolytic anemia (premature destruction of
red blood cells).
