Thrombocytopenic purpura

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Thrombocytopenic purpura

• Huang Honghui
• Dept. of Hematology, Renji Hospital

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• 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

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• BPClt50000/µl----bleeding tendency
• BPClt20000/µl----spontaneous hemorrhage

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Idiopathic Thrombocytopenia Purpura(ITP)
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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.

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Classification

• Acute type (aITP)
• Chronic type (cITP)

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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

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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

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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.

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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

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Etiology and Pathogenesis
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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.

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Etiology and Pathogenesis

• Others
• Role of estrogenic hormones
• Suppress the platelet production.
• Stimulate the clearance ability of
  monocyte-macrophage against the antibody binding
  platelet.

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Clinical Features

• Acute ITP
• Most frequently in children 2 to 6 years.
• A history of viral infection preceding the onset
  of bleeding.
• Acute onset.

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Clinical Features

• The symptoms and signs of bleeding
• Bruises and petechiae are the nearly universal
  presenting clinical symptom.
• lt1/3 epistaxis and gingival bleeding.
• lt10 hematuria, gastrointestinal bleeding.
• lt3 severe (massive purpura, profuse
  epistaxis and retinal hemorrhages.)
• Self-limited, spontaneous remission.

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Clinical Features

• Chronic ITP
• More frequently in females(lt40yrs), FM41.
• Insidious onset.

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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.

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Clinical Features

• Others
• Anemia iron deficiency type.
• Splenomegaly

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Laboratory Finding

• Blood
• Platelet count
• Acute type lt20109/L
• Chronic type 30-80109/L
• Morphology and function of platelet
• Morphologyabnormal large, giant forms, bizarre
  shapes, deeply stained forms.
• Functionsadhesion N/?, aggregation N/?
• Others
• Hb N/?
• WBC normal/eosinophilia

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Laboratory Finding

• Bone marrow
• megakaryocytes increased or normal.
• disturbance of development and maturation
  immature megakaryocytes?, granule in cytoplasm
  ?,size ?.
• platelet-producing megakaryocyte?(lt30)

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Megakaryoblast0Promegakaryocyte0-5Granular
megakaryocyte10-27Platelet-producing
megakaryocyte44-60Platelet
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Acute ITP(BM)

• 1.Megakaryoblast
• 2.Promegakaryocyte
• 3.Granular Megakaryocyte

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Chronic ITP(BM)

• 1.Granular megakaryocyte
• 6.Megakaryoblast in metaphase of mitosis
• 7.Giant platelets

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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.

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Laboratory Finding

• Others
• Platelet survival time (51Cr labeled)
• Normal 7-11days
• Acute type 1-6 hour
• Chronic type 1-3 day

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Laboratory Finding

• Others
• Tests of hemostasis and blood coagulation
• Bleeding time prolonged
• Clot retraction absent or deficient
• PT, PTT, CT normal

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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 ?

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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.

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Feature Acute ITP Chronic ITP
Peak age Children,2-6yr Adults,20-40yr
Ratio of FM 11 2-31
Antecedent infection Common 1-3wk before unusual
Onset of bleeding Abrupt insidious
Platelet count lt20,000/?l 30,000-80,000/?l
duration 2-6wk,rarely longer lt6 mons Months or years gt6 mons
Spontaneous remission Occur in 80 of cases Uncommon
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Treatment

• Supporting measure
• Observation
• Glucocorticoids
• Splenectomy
• Immunosuppressive drugs
• Others
• Emergency treatment

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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.

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Treatment(2)Observation

• Observation
• Platelet count gt 50109/L
• and
• Asymptomatic or have only minor purpura

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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.

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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

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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.

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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)

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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.

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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

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Treatment(5)Immunosuppressive drugs

• Vincristine 0.025mg/kg i.v. Qw4-6w
• (total dose lt2mg)
• 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

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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.
• Dosage0.3-0.6g/d2-3m
• Side effect liver function abnormality,
  headache, nausea, etal.

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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.

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Treatment (7)Emergency treatment

• Indications
• platelet count lt20109/L,
• severe life-threatening bleeding
• serious complications, e.g., intracranial
  hemorrhage
• immediate preoperative treatment of patients or
  pregnant women with serious hemorrhage

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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

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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

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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

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Treatment (7)Emergency treatment

• High-dose methylprednisolone
• Mechanism diminish platelet destruction by the
  reticuloendothelial system
• Regimen 1.0g/day for 3-5 days

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Thank you!