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Thrombocytopenic purpura
Huang Honghui
Dept. of Hematology, Renji
Hospital
• Definition: Thrombocytopenia is a clinical
syndrome in which a decreased number of
platelets in the circulating blood present
as a bleeding tendency, i.e. skin, mucosa
or internal organ bleeding.
• It is the most common course of abnormal
bleeding(30%).
• Classification: idiopathic/ secondary
– BPC<50000/μl----bleeding tendency
– BPC<20000/μl----spontaneous hemorrhage
Idiopathic
Thrombocytopenia Purpura
(ITP)
Definition
• ITP is an acquired disease of children
and adults characterized by a low
platelet count, an normal or
increased numbers of
megakaryocytes in the bone marrow,
and absence of evidence for other
disease.
Classification
• Acute type (aITP)
• Chronic type (cITP)
Etiology and Pathogenesis
• Infection(bacteria or virus)
– aITP--- antecedent viral infection
– cITP--- state of illness worsen because
of infection
– anti-viral antibody or immunocomplex
in plasma
Etiology and Pathogenesis
• Immunologic processes
– The infusion of plasma from patients with ITP
into normal recipients
→
thrombocytopenia
– The infusion of normal platelets into patients
with ITP
→
destructed within 12-24h
– platelet associated antibodies ( PAIgG, PAIgA,
PAIgM )
– Glucocorticoid, plasmapheresis, HD-Ig --- good
response
Etiology and Pathogenesis
• Role of the liver and spleen
– The site of production of platelet
antibodies.
– The site of platelet clearance.
• Splenic sequestration is the major site of
platelet clearance in ITP.( 51Cr-labeled
isologous platelet )
• Hepatic sequestration ---- severe
thrombocytopenia and markedly shorten
platelet survival.
Etiology and Pathogenesis
51Cr
labeled isologous platelet
Administrate to patients with ITP
External scintillation counting
Rapid accumulation of radioactivity predominantly
in the spleen
Splenic sequestration is the major site of platelet
clearance in ITP
Etiology and Pathogenesis
Etiology and Pathogenesis
• Others
– Impaired thrombopoiesis
• In cITP, an Ig has been demonstrated on the
surface of the megakaryocytes
→the attachment of antibody may impair
platelet production.
Etiology and Pathogenesis
• Others
– Role of estrogenic hormones
• Suppress the platelet production.
• Stimulate the clearance ability of monocytemacrophage against the antibody binding
platelet.
Clinical Features
• Acute ITP
– Most frequently in children 2 to 6 years.
– A history of viral infection preceding the
onset of bleeding.
– Acute onset.
Clinical Features
– The symptoms and signs of bleeding:
• Bruises and petechiae are the nearly
universal presenting clinical symptom.
• <1/3:
bleeding.
epistaxis and gingival
• <10%:
hematuria, gastrointestinal
bleeding.
• <3%:
profuse
hemorrhages.)
severe (massive purpura,
epistaxis and retinal
Clinical Features
• Chronic ITP
– More frequently in females(<40yrs),
F:M=4:1.
– Insidious onset.
Clinical Features
– The symptoms and signs of bleeding:
• Petechiae: asymptomatic, not palpable, most in
dependent regions.
• Purpura
• Menorrhagia
• Epistaxis,gingival bleeding
• Gastrointestinal bleeding and hematuria are less
common.
• Intracerebral hemorrhage is uncommon,but it is the
most common cause of death.
– Fluctuating course,spontaneous remission is
uncommon.
Clinical Features
• Others
– Anemia: iron deficiency type.
– Splenomegaly
Laboratory Finding
• Blood
– Platelet count
• Acute type
<20×109/L
• Chronic type 30-80×109/L
– Morphology and function of platelet
• Morphology:abnormal large, “giant” forms, bizarre
shapes, deeply stained forms.
• Functions:adhesion N/↓, aggregation N/↓
– Others:
• Hb: N/↓
• WBC: normal/eosinophilia
Laboratory Finding
• Bone marrow
– megakaryocytes increased or normal.
– disturbance of development and
maturation: immature megakaryocytes↑,
granule in cytoplasm ↓,size ↓.
– platelet-producing
megakaryocyte↓(<30%)
Megakaryoblast
0%
Promegakaryocyte
0-5%
Granular megakaryocyte
10-27%
Platelet-producing
megakaryocyte
44-60%
Platelet
Acute ITP(BM)
1.Megakaryoblast
2.Promegakaryocyte
3.Granular Megakaryocyte
Chronic ITP(BM)
1.Granular
megakaryocyte
6.Megakaryoblast in
metaphase of mitosis
7.Giant platelets
Laboratory Finding
• Platelet associated antibodies and
complements
– Assay of PAIgG and PAC3
– PAIgG:
• the first sensitive and reproducible method
• increased
• The magnitude of increase is greater in
patients with more severe
thrombocytopenia.
Laboratory Finding
• Others
– Platelet survival time (51Cr labeled)
• Normal: 7-11days
• Acute type: 1-6 hour
• Chronic type: 1-3 day
Laboratory Finding
• Others
– Tests of hemostasis and blood
coagulation
• Bleeding time: prolonged;
• Clot retraction: absent or deficient;
• PT, PTT, CT: normal
Diagnosis and Differential
Diagnosis
• Diagnostic criteria
–
–
–
–
bleeding manifestation
BPC count ↓
No or mild splenomagaly
megakaryocytes increased or normal, having
disturbance of maturation
– Anyone of the followings
•
•
•
•
•
Response to glucocorticoid
Response to splenetomy
PAIg(+)
PAC3(+)
Platelet survival time ↓
Diagnosis and Differential
Diagnosis
– Exclude secondary thrombocytopenia
• Such as: acute infectious illness,
myelodysplastic syndrome, hypersplenism,
disseminated intravascular coagulation,
aplastic anemia, acute leukemia, systemic
lupus erythematous.
Feature
Acute ITP
Chronic ITP
Peak age
Children,2-6yr
Adults,20-40yr
Ratio of F:M
1:1
2-3:1
Antecedent infection Common 1-3wk
before
unusual
Onset of bleeding
Abrupt
insidious
Platelet count
<20,000/l
30,000-80,000/l
duration
2-6wk,rarely longer
<6 mons
Months or years
>6 mons
Spontaneous
remission
Occur in 80% of
cases
Uncommon
Treatment
• Supporting measure
• Observation
• Glucocorticoids
• Splenectomy
• Immunosuppressive drugs
• Others
• Emergency treatment
Treatment:(1)Supporting measure
• Supporting measure
– Physical activity should be restricted to
minimize the hazards of trauma,
particularly head injury.
– Drugs that impair platelet functions
should be avoided.
– Blood loss should be treated as
otherwise indicated.
Treatment:(2)Observation
• Observation
– Platelet count > 50×109/L
and
– Asymptomatic or have only minor
purpura
Treatment:(3)Glucocorticoids
• Mechanism of action:
– significantly diminish immunoglobulin
synthesis.
– inhibit the binding of antibodies to platelets.
– impair reticuloendothelial function and thereby
to diminish platelet destruction.
– Improve the permeability of capillary
– Stimulate the hematopoisis and accelerate the
release of platelet into peripheral blood.
Treatment:(3)Glucocorticoids
• Initial means of therapy
• Response rate: 60-90%
• Dosage and regimen
– Prednisone 1-2mg/kg.d p.o.
– The initial course of glucocorticoids should be
maintained for 3 to 4 weeks, followed by a
gradual tapering of the dosage.
– Therapy course: 6 months
Treatment:(4)Splenectomy
• Mechanism of action
– Removal of the major site of destruction
of antibody-sensitized platelets.
– Removal of a major site of antibody
synthesis.
Treatment:(4)Splenectomy
• Indications
– failure to respond to glucocorticoid therapy,
relapse after discontinuance of glucocorticoid
therapy or reduction in the dosage.
– the necessity of high doses of glucocorticoid
for maintenance of a clinical status free of
serious hemorrhage.
– overriding contraindications due to the use of
glucocorticoids.
– Radioactivity index of spleen ↑(51Cr)
Treatment:(4)Splenectomy
• Contraindications
– in children under 2 years of age
– in many cases of ITP in pregnant
women.
– in patients with cardiac or other
complications who are at risk of serious
sequelae from any major surgical
procedure.
Treatment:
(5)Immunosuppressive drugs
•
Indications
–
Failure to response to glucocorticoid therapy
and splenectomy
–
Contraindications due to glucocorticoid
therapy and splenectomy
–
Combined therapy with glucocorticoid in
order to improve and decrease the dose of
glucocorticoid
Treatment:
(5)Immunosuppressive drugs
• Vincristine: 0.025mg/kg i.v. Qw×4-6w
(total dose <2mg)
• Cyclophosphamide: 50-100mg/day orally ×3-6w
or 400-600 mg i.v. Q3-4w
• Azathioprine: 100-200mg/d p.o. ×3-6w
→ 25-50mg/d p.o. ×8-12w
• CSA: 250-500mg/d p.o. ×3-6w
→ 50-100mg/d p.o. ×6m
Treatment:(6)Others
• Danazol: androgen with minimal virilizing
side effects
– Mechanism of action
• induce reticuloendothelial dysfunction, possibly by
diminishing Fc (IgG) receptors.
• Anti-estrogen effect.
– Dosage:0.3-0.6g/d×2-3m
– Side effect: liver function abnormality,
headache, nausea, etal.
Treatment:(6)Others
• Rh Immune Globulin
– Mechanism of Action
• phagocytic cell blockade due to occupancy of the
phagocytic cell Fc receptors by the IgG-sensitized
RBCs
– Dosage
• The probability of response increases with the dose
administered.
• A common regimen administers 25 µg/kg of anti-D
intravenously and repeats the same dose 2 days later
if no or minimal response is evident.
Treatment:
(7)Emergency treatment
• Indications:
– platelet count <20×109/L,
– severe life-threatening bleeding
– serious complications, e.g., intracranial
hemorrhage
– immediate preoperative treatment of patients
or pregnant women with serious hemorrhage
Treatment:
(7)Emergency treatment
• Platelet transfusions
– produce some increase in platelet numbers
– diminish bleeding for a time
– should be avoided in patients with chronic ITP
Treatment:
(7)Emergency treatment
• High-dose immunoglobulin
– Mechanism of action
• blockade of the Fc receptors of the
reticuloendothelial cells
• neutralization of antiplatelet autoantibodies
by antiidiotypic antibodies in the
preparations
– Regimen: 400mg/kg/day for 5 days
– Response rate: 60-80%
Treatment:
(7)Emergency treatment
• Exchange plasmapheresis
– Mechanism of action
• Remove antiplatelet antibody or immune
complex
– Adverse effect
• allergic reactions to plasma proteins
• a risk for transmissible viral infections
Treatment:
(7)Emergency treatment
• High-dose methylprednisolone
– Mechanism: diminish platelet
destruction by the reticuloendothelial
system
– Regimen: 1.0g/day for 3-5 days
Thank you!

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