Idiopathic Thrombocytopenic Purpura (ITP)

Report
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
One day
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
(+) right leg pain, weakness,
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 n
or any other pregnancy related complications.
Patient is menopause
8
PHYSICAL EXAMINATION
 General survey : conscious & coherent
not in distress
 Admitting vital 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
Bone Marrow biopsy
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
D1
Hemoglobin
Hematocrit
10/21
D2
10/22
D3
10/23
D4
10/24
D5
12.6
11.4
11.2
37
36.1
RBC
10/25
D6
10/26
D7
6H post
BT
10/27
D8
10/27
D9
10/28
D10
10.7
9
8.6
10.9
10.4
11.1
35.7
34.8
28.9
27.8
34.1
33
33.5
5.5
5.5
5.3
5.1
4.4
4.2
5
4.8
5
6280
5770
5360
9140
8980
8620
1
1
1
2
1
WBC
5400
6050
6320
4930
Eosinophils
8
2
1
1
Stabs
0
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
14T
10T
8T
6T
7T
5T
10T
10T
4T
Platerlet conc
transfused
4units
4units
4units
1
6T
8units
CBC
11/1
D12
11/4
D15
11/6
D17
11/8
D19
11/9
D20
11/10
D21
11/11
D22
11/12
D23
11/13
D24
11/14D
25
11/15
D26
11/16
D27
11/21
11/24
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
Thrombocytopenia
Low platelet
production
-Bone marrow failure
Leukemia/Lymphoma
Platelet
destruction
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
platelet 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
Mostly children
Male/Female = 1:1
Acute onset
Plt. Count mostly
<20,000/mm3
Spontaneous
remission frequent
Mortality : 0.5-1.5 %
Chronic ITP
Mostly adults
Male/Female = 1:3-4
Usaully gradual onset
Plt. Count 2만 – 5만/mm3
Spontaneous remission rare
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
Hemorrhage
Purpura
Gingival bleeding
Signs of GI bleeding
Spontaneous bleeding
( plt. < 10,000 /mm3)
Menorrhagia
Retinal hemorrhage
Evidence of intracranial
hemorrhage
Nonpalpable spleen
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
weeks
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 >30 x 109/L
Platelets <30 x 109/L
 Observe
 Observe
 Or treat if:
 Bleeding
 Planned procedure
likely to induce
bleeding
 Treat if
 Platelets <10 x 109/L
 Clinical problems
 Planned procedure
Prednisolone 1mg/kg/day x
2/52 then ¯
IVIg (effective in 75% but
not 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 109/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 line
Prednisolone
IVIg
Second line
Observe
Dexamethasone
Methylprednisolone
High dose IVIg
Anti-D
Dapsone
Azathioprine
Cyclosporin
Cyclophosphamide
Combination
chemoRx
Vinca alkaloids
Splenectomy
Fail 1st & 2nd
Observe
Intermittent
IVIg/steroids
Combination
chemoRx
Experimental
Mycophenolate
Rituximab
Campath
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

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