Idiopathic%20Thrombocytopenic%20Purpura%20(ITP)

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Department of Medicine
MEDICAL GRANDROUNDS
10 January 2008 8 am Ledesma Hall, MMC
Presentor
Karen Nina Ocampo, MD
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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

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GENERAL DATA

• V.A.
• 65 year old
• Female
• Filipino
• Roman Catholic

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History of Present Illness
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
2 weeks PTA
() right leg pain, weakness, Persistence of
hematomas ER consult
One day PTA
ADMISSION
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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

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Past Medical History

• No hypertension, diabetes mellitus, asthma

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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

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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 
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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

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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

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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

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INITIAL IMPRESSION

• Bleeding disorder, to consider coagulopathy
  versus thrombocytopenia

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COURSE IN THE WARDSHEMATOLOGY SERVICE

• On admission CBC showed severe thrombocytopenia
  (platelet count 10,
  000).
• Initially transfused with 4 units platelet
  concentrate.
• Started on Solucortef IV
• BMA done

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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
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• 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

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• Started on cyclophophamide 1 gm in 250cc D5W
• Transfused with plasma pheresis
• Azathioprine 50mg started

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Hematology sheet
CBC 10/20 D1 10/21 D2 10/22 D3 10/23 D4 10/24 D5 10/25 D6 10/26 D7 6H post BT 10/27 D8 10/27 D9 10/28 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 transfused 4units 8units 4units 4units
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11/16 D27 11/21 11/24
9.7 10.7 11.8
31.3 34 35
3.9 4.5 4.5
3660 4680 5150
83 85 85

83 85 85
10 7 10
9T 3T 5T

CBC 11/1 D12 11/4 D15 11/6 D17 11/8 D19 11/9 D20 11/10 D21 11/11 D22 11/12D23 11/13D24 11/14D25 11/15 D26
Hemoglobin 11.1 8.8 11.2 11.4 8.9 9 9.6 7.6 10.7 10.2 9.7
Hematocrit 33.6 27.4 34.3 33 27.3 28.5 29.7 24.3 33.1 31.7 30.3
RBC 5 3.9 4.7 4.8 3.9 4 4.2 3.4 4.4 4.2 4
WBC 9100 8470 9140 10830 4980 4200 8930 7710 9350 6210 4930
Eosinophils 2 3 2 2
Stabs 0
Segmenters 72 67 50 60 79 85 75 78 83 80 70
Lymphocytes 20 21 43 34 16 12 17 15 13 14 20
platelet count 7T 5T 10T 10T 7T 16T 5T 5T 9T 6T 4T

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NeurologyProblem 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

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CardiologyProblem 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

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1. Drug use history -quinidine, quinine,
sulfonamides, rifampin heparin

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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

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(No Transcript)
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Final Diagnosis

• Immune Thrombocytopenic Purpura
• Essential Hypertension
• Degenerative disc disease

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Idiopathic Thrombocytopenic Purpura
(ITP)________________________
Immune Thrombocytopenic Purpura (ITP)
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Incidence

• 1. 1 / 10,000 Population
• 2.Children (age lt 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

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Definition

• 1.Purpura
• 2.Thrombocytopenia
• -Thrombocytes or Platelet
• -Penia or Low
• 3.Idiopathic Immune

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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.

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Clinical Manifestations

• 1.Purpura
• -Petechiae
• -Ecchymoses
• 2.Hemorrhage

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Clinical Appearance

• 1.Acute ITP (children)
• 2.Chronic ITP (adults)
• 3.Secondary ITP (follow other diseases)

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Classification
Acute ITP
Chronic ITP

• Mostly children
• Male/Female 11
• Acute onset
• Plt. Count mostly
• lt20,000/mm3
• Spontaneous
• remission frequent
• Mortality 0.5-1.5

• Mostly adults
• Male/Female 13-4
• Usaully gradual onset
• Plt. Count 2? 5?/mm3
• Spontaneous remission rare
• Chronic recurrent course

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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

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Role of Spleen

• 1.Auto-antibody production
• 2.Platelet destruction
• 3.Platelet storage

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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

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Common Physical Findings

• Nonpalpable petechiae
• Hemorrhage
• Purpura
• Gingival bleeding
• Signs of GI bleeding
• Spontaneous bleeding ( plt. lt 10,000 /mm3)

• Menorrhagia
• Retinal hemorrhage
• Evidence of intracranial hemorrhage
• Nonpalpable spleen

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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

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Laboratory Examination

• 1.Complete Blood Cell Count (CBC)
• -Isolated thrombocytopenia
• -MPV PDW increase (Automate)
• 2.Bone Marrow Examination
• -Megakaryocyte, Megakaryoblast
• Promegakaryocyte --gt increase/normal
• -Other cellular component--gt normal
• 3.Platelet Auto-antibody
• -PAIgG (non-specific)
• -GP specific antibody

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

• PAIgG
• PBIgG

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

• 1.Isolated thrombocytopenia
• 2.No splenomegaly
• 3.Increase megakaryocytes in BM
• 4.No other cause of thrombocytopenia
• 5.Platelet auto-antibody found

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Differential Diagnosis

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

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3.Over platelet destruction -Hypersplenism, TTP,
SLE DIC, Infection -HIV, DHF, Rubella,
Infectious Mononucleosis -Leptospirosis -Malaria
4.Others CLL, Hypogammaglobulinemia
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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 gt 6 months (15 )
  
• ?consider Splenectomy

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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
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Adults first line therapy

• Platelets gt30 x 109/L
• Observe
• Or treat if
• Bleeding
• Planned procedure likely to induce bleeding

• Platelets lt30 x 109/L
• Observe
• Treat if
• Platelets lt10 x 109/L
• Clinical problems
• Planned procedure
• Prednisolone 1mg/kg/day x 2/52 then
• IVIg (effective in 75 but not sustained)

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Adults second line therapy - drugs

• High dose steroids
• Dexamethasone
• Methylprednisolone
• High dose IVIg
• IV anti-D
• Danazol
• Azathioprine
• Cyclosporin
• Vincristine, combination chemoRx, dapsone, etc.

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Adults second line therapy - splenectomy

• 2/3 will respond
• Need platelets gt30 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

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Mechanisms of Action of Therapies for Immune
Thrombocytopenic Purpura
Cines, D. B. et. al. N Engl J Med
2002346995-1008
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Options for severe refractory ITP

• 25 adults
• Intermittent IVIg, combination chemoRx
• Recommend
• Rituximab
• Mycophenolate mofetil
• Campath-1H

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ITP therapy in adults
Fail 1st 2nd Observe Intermittent
IVIg/steroids Combination chemoRx Experimental M
ycophenolate Rituximab Campath
First line Prednisolone IVIg
Second line Observe Dexamethasone Methylprednisolo
ne High dose IVIg Anti-D Dapsone Azathioprine Cycl
osporin Cyclophosphamide Combination
chemoRx Vinca alkaloids
Splenectomy
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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

.
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3. AMG 531 given SQ stimulates platelet
production No being tested in phase III
clinical trial of ITP patients with base line
platelet count lt30000 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
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Guidelines on Platelet Transfusion
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INDICATIONSFOR PLATELET TRANSFUSION

• BLEEDING DUE TO
• THROMBOCYTOPAENIA
• FUNCTIONALLY ABNORMAL PLATELETS
• Thrombocytopenia does not equal Platelet
  Transfusion

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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

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2. FUNCTIONALLY ABNORMAL PLATELETS

• Haematological disorders
• Myeloproliferative Disease
• Myelodysplastic Disease
• Aspirin and other anti-platelet drugs
• Acquired Platelet Dysfunction

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Clinical Practice Guidelines Platelets

• Likely to be appropriate
• lt10 with no risks or lt20 risk factors
• maintain gt 50 during surgery or procedures
• inherited/drug induced defects
• bleeding and thrombocytopenia
• 50 and massive transfusion
• higher counts in neurosurgical/ ophthalmological
  procedures

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Thank you