10 January 2008

8 am Ledesma Hall, MMC

Karen Nina Ocampo, MD

 Learning Objectives:
 To present a case of chronic ITP
 To discuss the presentation of chronic ITP
 To discuss the pathogenesis, diagnosis and
management of chronic ITP
 To discuss updates on diagnosis and management of

ITP
GENERAL DATA

 V.A.
 65 year old
 Female
 Filipino
 Roman Catholic
History of Present Illness
2 weeks PTA patient noted to have
hematomas over left shoulder
and left arm
Denies history of fever nor
trauma, intake of medications
(+) petechiae lower
extremities
no consult was done

One day (+) right leg pain, weakness,

PTA Persistence of hematomas
ER consult

ADMISSION
Review of System
No weight loss, anorexia
No headache, blurring of vision
No dyspnea, orthopnea
No chest pain, palpitations
No abdominal pain, diarrhea, vomiting
No hematuria, dysuria
No arthralgia, edema

5
Past Medical History
No hypertension, diabetes mellitus, asthma
Family History
No hypertension, diabetes mellitus, asthma
Patient recalled similar symptoms among third
degree relatives

Personal and Social History

non smoker and non alcoholic beverage drinker
OB and Gynecologic History
She had menarche at age 16,
regular lasting for 5 days
consuming about 3 pads a day.

She is a G4P4(4004), all were normal deliveries

assisted by midwife, denies any miscarriages
nor any other pregnancy related complications.
Patient is menopause 

8
 PHYSICAL EXAMINATION
 General survey : conscious & coherent not in distress

 Admittingvital signs
BP 150/80 mmHg , HR 89 bpm , RR 16 cpm , T 37 C

 SHEENT: (+)hematoma, petechiae, ecchymoses on both

upper and lower extremities , pinkish palpebral
conjunctivae, anicteric sclerae,

 HEART: Adynamic precordium, normal rate regular

rhythm, apex beat at 5th ICS, LMCL, no murmur
 PHYSICAL EXAMINATION
 CHEST and LUNGS: Symmetrical chest expansion, no
retractions, clear breath sounds

 ABDOMEN: flabby, soft, normal active bowel sounds,

no tenderness non palpable liver and spleen

EXTREMITIES:
no edema, no cyanosis, full and equal pulses
SALIENT FEATURES
 65 year old
 female
 menopause
no history of trauma/intake of any medicine
 no melena, hematochezia, hemoptysis
 no fever
hematomas, eccymoses, and petechiae on all extremities
No splenomegaly
INITIAL IMPRESSION
 Bleeding disorder, to consider
coagulopathy versus
thrombocytopenia
COURSE IN THE WARDS:
HEMATOLOGY SERVICE
On admission CBC showed severe
thrombocytopenia
(platelet count 10, 000).
Initially transfused with 4 units platelet
concentrate.
Started on Solucortef IV
BMA done
Slightly hypecellular bone marrow 40% with megakaryocytic
Erythroid Hyperplasia and relative increase in
eosinophils 13.7%

Morphologic findings consistent with peripheral

consumption of platelets
Bone marrow diff count
blast 2%
granulocytic 32.6%
eosinophils 13.7%
basophils 0%
lymphocytes 12.1%
plasma cells 1.1%
Noted to have episodes of
gum bleeding and hematuria,

Aside from platelet concentrate,

FFP and PRBC was also transfused

Almost 40 units platelet concentrate

was transfused,development of
platelet antibodies considered.

Given IV Ig
15
Started on cyclophophamide 1 gm in
250cc D5W
Transfused with plasma pheresis
Azathioprine 50mg started

16
 Hematology sheet
CBC 10/20 10/21 10/22 10/23 10/24 10/25 10/26 6H post 10/27 10/27 10/28
D1 D2 D3 D4 D5 D6 D7 BT D8 D9 D10

Hemoglobin 12.6 11.4 11.2 10.7 9 8.6 10.9 10.4 11.1

Hematocrit 37 36.1 35.7 34.8 28.9 27.8 34.1 33 33.5
RBC 5.5 5.5 5.3 5.1 4.4 4.2 5 4.8 5
WBC 5400 6050 6320 4930 6280 5770 5360 9140 8980 8620
Eosinophils 8 2 1 1 1 1 1 2 1

Stabs 0 1
Segmenters 42 73 63 62 66 50 54 63 37 65
Lymphocytes 44 18 32 32 30 40 40 33 57 27

platelet count 10T 6T 14T 10T 8T 6T 7T 5T 10T 10T 4T

Platerlet conc 4units 8units 4units 4units

transfused
CBC 11/1 11/4 11/6 11/8 11/9 11/10 11/11 11/12 11/13 11/14D 11/15 11/16 11/21 11/24
D12 D15 D17 D19 D20 D21 D22 D23 D24 25 D26 D27

Hemoglobin 11.1 8.8 11.2 11.4 8.9 9 9.6 7.6 10.7 10.2 9.7 9.7 10.7 11.8

Hematocrit 33.6 27.4 34.3 33 27.3 28.5 29.7 24.3 33.1 31.7 30.3 31.3 34 35

RBC 5 3.9 4.7 4.8 3.9 4 4.2 3.4 4.4 4.2 4 3.9 4.5 4.5

WBC 9100 8470 9140 10830 4980 4200 8930 7710 9350 6210 4930 3660 4680 5150

Eosinophils 2 3 2 2 83 85 85

Stabs 0

Segmenters 72 67 50 60 79 85 75 78 83 80 70 83 85 85
Lymphocytes 20 21 43 34 16 12 17 15 13 14 20 10 7 10

platelet count 7T 5T 10T 10T 7T 16T 5T 5T 9T 6T 4T 9T 3T 5T

18
Neurology
Problem 2 Right lower leg pain
Initial Impression was Transient Ischemic attack
LMCA branch
Given somazine initially
CT scan of lumbar spine showed spinal canal
stenosis L4 – S1
Lyrica was given, no other interventions done and
was treated symptomatically
Cardiology
Problem 3 Hypertension
Patient on admission noted to have elevated BP
150/100, highest of which is 190/110
ECG showed non specific ST-T wave changes
Started on amlodipine 5 mg 1 tab OD, Clonidine
75mcg BID, Candesartan
1. Drug use history
-quinidine, quinine,
sulfonamides,
rifampin & heparin
2.Hyperslenism
On UTZ no splenomegaly noted
3. Infection
Infectious mononucleosis
HIV --Patients with HIV infection frequently develop
an immunologic form of thrombocytopenia
DHF
Rubella

4. DIC
5.ITP
23
Final Diagnosis
Immune Thrombocytopenic
Purpura
Essential Hypertension
Degenerative disc disease
Immune Thrombocytopenic
Purpura (ITP)

25
 Incidence
1. 1 / 10,000 Population

2.Children (age < 15 yr.) 50%

Girl : Boy = 1 : 1
Mortality 0.5 - 1.5%

3.Adults (age 20-40 yr.) 50%

Female : Male = 3-4 : 1
Mortality rare

26
 Definition

1.Purpura

2.Thrombocytopenia
-Thrombocytes or Platelet
-Penia or Low

3.Idiopathic & Immune

27
 Etiology
.ITP is a disease of increased peripheral
platelet destruction.
.Most patients produce auto-antibodies
to specific platelet membrane
glycoproteins.
.Most patients have either normal or increased p
latelet production in BM.

28
 Clinical Manifestations
1.Purpura
-Petechiae
-Ecchymoses

2.Hemorrhage

29
 Clinical Appearance
1.Acute ITP (children)

2.Chronic ITP (adults)

3.Secondary ITP (follow other diseases)

30
 Classification
Acute ITP Chronic ITP
Mostly children Mostly adults
Male/Female = 1:1 Male/Female = 1:3-4
Acute onset Usaully gradual onset
Plt. Count mostly Plt. Count 2 만 – 5 만 /mm3
<20,000/mm3
Spontaneous Spontaneous remission rare
remission frequent
Mortality : 0.5-1.5 % Chronic recurrent course

31
 Common Signs and Symptoms

1.Purpura
2.Menorrhagia
3.Epitaxis
4.Gingival bleeding
5.Recent virus immunization (acute ITP
)
6.Recent viral illness (acute ITP)
7.Bruising tendency
32
 Role of Spleen
1.Auto-antibody production

2.Platelet destruction

3.Platelet storage

33
 Physical Examination
1.Evaluate the type and the severity of
bleeding
2.Try to exclude other causes of
bleeding
3.Seek evidence of
-liver disease
-thrombosis
-autoimmune diseases and
-infection, particularly HIV

34
 Common Physical Findings

Nonpalpable petechiae Menorrhagia

Hemorrhage Retinal hemorrhage
Purpura Evidence of intracranial
Gingival bleeding hemorrhage
Signs of GI bleeding Nonpalpable spleen
Spontaneous bleeding
( plt. < 10,000 /mm3)

35
 Mortality/Morbidity
1.Hemorrhage represents the most serious
complication

2.Mortality rate from hemorrhage is

approximately 1% in children and 5% in adult

3.Increase risk of severe bleeding in adult ITP

4.Spontaneous remission
: occure in more than 80 % in children
: uncommon in adults 36
 Laboratory Examination
1.Complete Blood Cell Count (CBC)
-Isolated thrombocytopenia
-MPV & PDW increase (Automate)
2.Bone Marrow Examination
-Megakaryocyte, Megakaryoblast &
Promegakaryocyte --> increase/normal
-Other cellular component--> normal
3.Platelet Auto-antibody
-PAIgG (non-specific)
-GP specific antibody

37
Fewer Platelets than normal.
38
Two mature megakaryocytes; one with a very high
N/C ratio, the other with a very low N/C ratio.
39
Mature megakaryocyte containing an NRBC (Emperipolis).
The mature red cell may be superimposed on the
megakaryocyte. 40
Two bare megakaryocyte nuclear masses
41
Platelet Auto-antibodies
PAIgG
PBIgG

Platelet Antigens
GPIb/IX
GPIIb/IIIa
GPIa/IIa
Etc.

42
 Laboratory Findings

1.Isolated thrombocytopenia

2.No splenomegaly

3.Increase megakaryocytes in BM

4.No other cause of thrombocytopenia

5.Platelet auto-antibody found

43
 Differential Diagnosis
1.Drugs induced thrombocytopenia
-Drug use history
-quinidine, quinine, sulfonamides,
rifampin & heparin
2.Low platelet production
-Bone marrow failure
-Leukemia/Lymphoma

44
3.Over platelet destruction

-Hypersplenism, TTP, SLE & DIC, Infection

-HIV, DHF, Rubella,
Infectious Mononucleosis
-Leptospirosis
-Malaria

4.Others :
CLL,
Hypogammaglobulinemia
 Treatment & Prognosis
Acute ITP
1.Self remission 80 %
2.Platelet transfusion in severe
bleeding
3.Corticosteroid therapy within 3-4 w
eeks
4.No response to corticosteroid > 6
months (15 %)
consider Splenectomy
46
Chronic ITP
1.Complete remission (10-20 %)
2.Corticosteroid therapy to reduce
phagocytic activity of RE
system & suppress antibody
production
3.Consider Splenectomy :
-No response to high dose
steroid
-Cerebral hemorrhage
Adults: first line therapy
Platelets
Platelets>30
>30xx10
1099/L
/L Platelets
Platelets<30
<30xx10
1099/L
/L

Observe
Observe 
Observe
Observe

Or
Ortreat
treatif:
if: 
Treat
Treatifif
Bleeding 
Platelets
Bleeding Platelets<10
<10xx10
1099/L
/L
Planned 
Plannedprocedure
procedure Clinical
Clinicalproblems
problems
likely 
likelyto
toinduce
induce Planned
Plannedprocedure
procedure
bleeding
bleeding Prednisolone
Prednisolone1mg/kg/day
1mg/kg/dayxx
2/52
2/52then
then¯¯
IVIg
IVIg(effective
(effectivein
in75%
75%but
but
not
notsustained)
sustained)
Adults: second line therapy -
drugs
High dose steroids

Dexamethasone

Methylprednisolone
High dose IVIg
IV anti-D
Danazol
Azathioprine
Cyclosporin
Vincristine, combination chemoRx, dapsone, etc.
Adults: second line therapy -
splenectomy
2/3 will respond
Need platelets >30 x 1099/L for splenectomy

Vaccination

Pneumovax, Hib, Meningococcal C

2 weeks pre-op

Other prophylaxis

Penicillin 250-500mg bd (or equivalent) ?for life ?2
years

Annual flu vaccine + Pneumovax booster 5 yearly
Mechanisms of Action of Therapies for Immune Thrombocytopenic
Purpura

Cines, D. B. et. al. N Engl J Med 2002;346:995-1008

Options for severe refractory
ITP
25% adults
Intermittent IVIg, combination chemoRx
Recommend
Rituximab
Mycophenolate mofetil
Campath-1H
ITP: therapy in adults
First
Firstline
line Second
Secondlineline Fail
Fail1st
1st&&2nd
2nd
Prednisolone
Prednisolone Observe
Observe Observe
Observe
IVIg
IVIg Dexamethasone
Dexamethasone Intermittent
Intermittent
Methylprednisolone
Methylprednisolone IVIg/steroids
IVIg/steroids
High
Highdose
doseIVIgIVIg Combination
Combination
Anti-D
Anti-D chemoRx
chemoRx
Dapsone
Dapsone
Azathioprine
Azathioprine
Cyclosporin
Cyclosporin Experimental
Experimental
Cyclophosphamide
Cyclophosphamide Mycophenolate
Mycophenolate
Combination
Combination Rituximab
Rituximab
chemoRx
chemoRx Campath
Campath
Vinca
Vincaalkaloids
alkaloids

Splenectomy
Experimental Treatment
1. Stem Cell Transplantation
In patients with chronic ITP who have:
(1) failed to respond to all forms of standard
therapy (2) who have severe thrombocytopenia
with associated mucosal bleeding (nosebleeds,
bleeding from the stomach or bowel, etc.),
consideration may be given to stem cell
transplantation.
2.Thrombopoetin
. stimulating receptors
3. AMG 531
given SQ
stimulates platelet production
No being tested in phase III clinical trial of
ITP patients with base line platelet count
<30000
4. Elthrombopag
oral medication
also stimulates platelet production
An ITP phase III study is starting
5. AKR 501
oral medication
stimulates platelet production
an ITP phase II study is ongoing
Guidelines on Platelet
Transfusion
INDICATIONS
FOR PLATELET TRANSFUSION

BLEEDING DUE TO
THROMBOCYTOPAENIA
FUNCTIONALLY ABNORMAL PLATELETS
Thrombocytopenia does not equal Platelet
Transfusion
1. THROMBOCYTOPENIA
Marrow suppressive chemotherapy
Consumptive coagulopathy
Rarely in situations of rapid platelet destruction
ITP ( Immune Thrombocytopenia)
TTP (Thrombotic Thrombocytopenic Purpura)
Contraindicated in Heparin induced
thrombocytopenia
2. FUNCTIONALLY
ABNORMAL PLATELETS
Haematological disorders:
Myeloproliferative Disease
Myelodysplastic Disease
Aspirin and other anti-platelet drugs

Acquired Platelet Dysfunction

Clinical Practice Guidelines
Platelets
Likely to be appropriate
<10 with no risks or <20 risk factors
maintain > 50 during surgery or procedures
inherited/drug induced defects
bleeding and thrombocytopenia
50 and massive transfusion
higher counts in neurosurgical/ ophthalmological
procedures
Thank you