Transcript Goal of the treatment

Salwa Hindawi
Salwa Hindawi
MSc, MRCPath, CTM RCPE
Director of Blood Transfusion Services
King Abdulaziz University Hospital
Jeddah, Saudi Arabia
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PLATELETS
 Produced from megakaryocytes in the bone marrow
 Mean survival: 8-10 days
 Removed from circulation by cells of the monocyte-
macrophage system
 1/3 of the total platelet mass is found in the spleen
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Electron Micrscopy of Platelet
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DEFINITION
 <150,000 platelets/microliter (nml 150,000-400,000)
 2.5 % of the nml population have this
 If platelet count >20,000, usually no serious
spontaneous bleeding
 If less than <10,000, risk of bleeding increases and may
necessitate transfusion
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MECHANISMS OF
THROMBOCYTOPENIA
 Decreased platelet production
 Increased platelet destruction
 Dilutional/distributional
 Pseudothrombocytopenia
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MEDICATIONS
 Quinidine
 Amphotericin
 Quinine
 Vancomycin
 Rifampin
 Amiodarone
 Bactrim
 Piperacillin
 Methyldopa
 Sulfasalazine
 Acetaminophen
 Ethambutol
 Digoxin
 Lithium
 Diclofenac
 heparin
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MEDICATIONS
 Methicillin
 Haldol
 INH
 Tamoxifen
 Minoxidil
 Diazepam
 Nitroglycerine
 Gold
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ITP
 Autoimmune etiology (IgG antibody to platelets)
 Etiology
 30% drug related
 30% underlying disease (connective tissue disorders,
lymphoma, CLL)
 30% idiopathic
 10% viruses (HIV)
 Platelets are hyperfunctional (spontaneous
bleeding is rare)
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Idiopathic Thrombocytopenic Purpura (ITP)
 Autoimmune disease of children and adults
 Sustained Low platelet count
 No other causes )exclusion)
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Pathophysiology
Immune Mediated Mechanism
 increase HLA-DR expression defects in cellular and
humoral immunity  specific autoantibody production
to GpIIb/IIIa and Gp16-IX Antigens
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Pathophysiology
Platelet  destruction
+
by
platelet
acrophages
Auto Ab
RES

Low
platelet
count
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 bleeding
through mucus
membranes
Clinical Features of ITP in Children and Adults
Feature
Children
Adults
2-4
Equal
15-40
2:6:1
Occurrence
Peak age (yr)
Sex (F:M)
Presentation
Onset
Acute (most with symptoms < 1 week)
Symptoms
Purpura (<10% with severe bleeding)
Platelet count
Most <20 x 109/L
Course
Spontaneous remission
83%
Chronic disease
24%
Response to splenectomy
71%
Eventual complete recovery
89%
Morbidity and mortality
Cerebral hemorrhage
<1%
Hemorrhagic death
<1%
Mortality of chronic refractory 2%
disease
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Insidious (most with symptoms
<2 months)
Purpura (typically bleeding not
severe)
Most <20 x 109/L
2%
43%
66%
64%
3%
4%
5%
APPROACH TO DIAGNOSIS
 HISTORY AND PHYSICAL EXAMINAION
 Recent viral history
 Diagnosed hematological disease
 Family history
 Recent live virus vaccination (measles)
 Poor nutritional states
 Medications
 Pregnancy
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Diagnosis
Diagnosis by Exclusion
1 – Clinical finding
Bleeding and /or purpura
Isolated thrombocytopenia
No evidence of other disease
2 – peripheral blood smear
3 – platelet antibody test
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4-Auto-immune Profile
Antiphospholipid syndrome
5-B.M.A. in the presence of Atypical clinical features
or no response to Rx better before initiation of
steroid therapy
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PERIPHERAL BLOOD SMEAR
 “GOLD STANDARD”
 Check for platelet clumping, platelet size, RBC
morphology, presence of immature WBCs
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Deferential Diagnosis
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Spurious
Congenital Thrombocytopenia
Fanconi anaemia
Aplastic anaemia
Acute leukemia
Autoimmune diseases (SLE)
Hypersplenism
Microangiopathy
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Management
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Important Points to consider:
 Observation & follow up
 Let the treatment fit the patient (treat cases
individually)
 Evidence based medicine through randomized
controlled trials and or clinical practice
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Goal of the treatment

Not to achieve a normal platelet count but to
prevent bleeding
2 options:

1.
2.
Counseling and observation
or Rx if: low platelet and/or bleeding
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Management of ITP


Prednisone1-2 mg/kg daily
60-80% achieve remission
Intravenous immunoglobulin
0.4 g/kg daily x 5 days,
or 1 g/kg/d x 2 days

I.V. Anti-D
50-75 ug/kg
High dose Dexamethasone 40mg/Kg x 4 days for 6 cycles
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 High dose methyle prednisolone (HDMP)
Oral 7 days course (30 mg/kg/d/3 days then 20
mg/kg/d x 4 days) x 6 courses
 platelet count by day 7 > 50 x 104/L
 Splenectomy
Introduced in 1916
Two thirds of patients achieve remission
ineffective medical management or/and therapy
associated toxicity
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Medical therapy after failed splenectomy
or refusal to allow splenectomy
• Oral prednisone (dose as presplenectomy)
• IVIg 0.8-1.0 g/kg; repeat once
if platelet
response at 48-72 hours
inadequate
• IV anti-D IV (Rh(D)-positive
patients only),
50-75g/kg
• Other (eg, azathioprine,
cyclophosphamide,
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vincristine,
danazol).
Emergency therapy
• IV methylprednisolone 30 mg/kg/d
(maximum, 1g) for 3 consecutive days
• IVIg (1-2 g/kg over 2 days)
• Platelet trasfusion
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Rarely used therapies
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Interferon-
Cyclosporine A
Combination chemotherapy
Plasma exchange
Staphylococcal protein A immunoadsorption
Dapsone
Ascorbic acid
Colchicine
Mabthera
Danazol
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Immunosuppressive & Chemotherapy
Azathioprine, cyclosporine
Vincaalkaloid, cyclophosphamide
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Platelet Transfusion
 Evaluate the case
 Life threatened emergency
 IVIG
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Follow-up
 Clinical severity in addition to platelet count, CBC
should be repeated within 7-10 days of diagnosis
and only when there is a clinical indication or
signs of resolution of clinical symptoms.
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Conclusions
 Learn from our mistakes
 Observe the patients, treat only when it is really
needed.
 Treat individual cases.
 Platelet transfusion is contraindicated
 Evidence based medicine randomized control trials for
management of ITP.
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References
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Immune Thrombocytopenic Purpura Let the
treatment fit the patient, George, et al
Editorial – New England Journal of Medicine
January 13,2004.
Initial Treatment of Immune Thrombocytopenia
Purpura with high-dose dexamethasone Cheng,
et al, January 13, 2004.
Guidelines for the Investigation & Management
of Idiopathic Thrombocytopenic Purpura in
adult, children and in pregnancy, British Journal
of Haematology 2003.
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 Pathogenesis and Management of Chronic Idiopathic
Thrombocytopenic Purpura An Update, Renchiyang,
Zhong Chao Han; International Journal of Haematology ,
Aug. 1999.
 Blanchette V, Freedman J, Garvey B., Management of
Chronic ImmuneThrombocytopenic Purpura in Children
and Adults, Semin Haematol, 1998.
 Idiopathic Thrombocytopenic Purpura: A Concise
Summary of the Pathophysiology and Diagnosis in
Children and Adults. James N. George & Gary E. Raskob;
Seminars in Haematology 1998.
 George JN, Woolf SH, Raskob GE, et al: Idiopathic
Thrombocytopenic Purpura. A Practice Guideline
Developed by Explicit Methods For American Society of
Haematology Blood;88:3-40,1996.
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