Working Group on Thrombocytopenias

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Working Group on Thrombocytopenias

European Hematology Association
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AITP in HCV positive patients

• A study cohort proposal for a muticentric survey

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Abd El Hamid, A. S. MD

• Professor of Clinical Pathology
• Faculty of Medicine
• Suez Canal University Ismailia, Egypt
• alaasaad_at_superlink.com.eg

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Viral infection associated with thrombocytopenia

• 1- Hepatitis viruses (A, B, C)
• 2- HIV (Human immune deficiency virus)
• 3- Varicella-zoster virus
• 4- Epstein-Barr virus

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HCV infection

• HCV hepatotropic Virus
• 1- Hepatic complications
• Chronic hepatitis
• Liver cirrhosis
• Hepatic cell failure
• Hepatocellular carcinoma

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EXTRAHEPATIC MANIFESTATIONS IN HCV INIFECTION

• HCV infection of other types of cells like
  HSC, etc. will be accompanied with dysfunction
  of different organs by direct and indirect
  pathomechanisms.

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EXTRAHEPATIC MANIFESTATIONS IN HCV INIFECTION
Cont.

• Endocrine Hashimoto's disease, Diabetes
  mellitus,
• Muscles and joints Rheumatoid arthritis
• Dermatological Lichen planus, Urticaria
• Ophthalmic Uveitis, corneal ulcers
• Salivary gland Sialadenitis
• Kidney Glomerutonephritis
• Miscellaneous Polyarteritis nodosa

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Hematological and lymphoid complications of HCV
infection

• Thrombocytopenias
• Mixed cryoglobulinemia and vasculitis
• Aplastic anemia
• Non-Hodgkin's B lymphomas

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Causes of TP in CLD

• 1- Hypersplenism sequestration of platelets in
  the enlarged spleen.
• 2- Immunological dysregulation triggering the
  production of platelet autoantibodies
• 3- Hypothrombopoietinemia in advanced liver
  disease.
• 4- HCV direct infection of platelets and
  megakaryocytes
• 5- Myelosuppression due to HCV direct infection
  of the hematopoietic stem cells

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AITP in HCV positive patients

• A study cohort

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Materials and methods

• Place of study Suez canal university hospital
  situated in Ismailia city in the eastern part of
  Egypt serving 5 governorates with a population
  size of 3 million
• Study population 212 HCV positive patients
  attending the hepatology unit in SCU hospital

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Inclusion criteria

• 12 patients had fulfilled the following criteria
  of HCV associated AITP
• Diagnosis of HCV positive anti-HCV detectable
  HCV viraemia.
• Diagnosis of (AITP) Low platelet count, i.e. lt
  50x109/L.

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• Normal or increased number of bone marrow
  megakaryocytes.
• Absence of myelodysplastic features on bone
  marrow.
• Absence of drug intake or coagulopathy.
• Absence of other causes of thrombocytopenia.

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Patients characteristics
12 Total Number of patients
46 (36-69) Age (Mean and range)
7/5 Sex (male/female)
72 IU/L (24-143) 63 IU/L (19-127) AST ALT
43 (34-76 ) 109/L Platelet count at diagnosis (mean, range)
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Hemorrhagic Manifestations
8/12 Patients/total
5/12 Skin, mucosa
1/12 Gastrointestinal
1/12 Gynecological
1/12 Central nervous system
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Autoimmune Markers
D10/12,S3/12, E10/12 Antiplatelet Ab
6/12 Rheumatoid F.
3/12 Antinuclear Ab (ANA)
0/12 Anti-DNA
2/12 Cryoglobulins
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P 456 212 pg/ml C 62 14 pg/ml Thrombopoietin
5-55 ug/ml (15-300 ug/ml) S. ferritin
650 X103 IU/ml ( 250 X103 -1150X 103) IU/ml HCV RNA
Treatment
5/12 IFN therapy
5/12 (3/12 responders) Corticosteroids
2/12 Splenectomy
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HCV associated AITP

• A Proposal for a muticentric survey

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• An increasing interest is being focused on HCV
  associated AITP not only because the high
  prevalence of HCV infection worldwide the high
  frequency Anti-HCV reported in AITP patients,
  
• but also because it represents an obstacle that
  could hamper invasive diagnostic or therapeutic
  procedures.

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Hypothesis

• Clinically, the differentiation of AITP from
  other forms of TP can influence diagnostic
  therapeutic measures.
• Studies that emphasized the association of HCV
  infection with AITP had involved either
  hospital-based populations or had small sample
  sizes

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• or carried out retrospectively in AITP
  patients groups only. Therefore, for better
  definition and characterization of HCV associated
  AITP it is suggested
• to study AITP in HCV infected patients in HCV
  hyperendemic areas which will be complimentary
  for such studies carried out in AITP patients
  groups.

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Aims of the study

• The objectives of this international
  multi-centric study are as follow
• 1- Primary Objective
• Frequency characterization (Clinico-pathological
  , hematological and virologic and response to
  treatment) of AITP in HCV positive patients

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• Secondary Objectives
• To study the natural history of AITP associated
  with HCV infection based on a long-term follow-up
  study to define
• The clinical course
• The cost-effectiveness of testing
  treatment options.

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• Characterization of the platelet auto-antibodies
  associated with AITP in HCV infection as regards
  the following
• The platelet glycoprotein specificity,
  autoantibody titer in relation to therapy.

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Research Questions
1- What is the frequency of TP and AITP in HCV
infection without significant liver damage? 2-
What are the various pathomechanisms that may
result in TP in HCV infection? 3- What are the
clinical lab parameters pertaining to a
possible association of AITP in HCV and may
assist in the diagnosis?
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The study design

• 1-Phase-I Cross sectional study prevalence of
  AITP in HCV infected patients.
• 2- Phase-II Prospective study HCV positive
  patient without AITP will be follow for one year
  to discover the AITP new cases
• 3-Phase III Analytical study characterization
  of the platelet Abs associated with AITP in HVC
  infection regarding the specificity of the
  platelet glycoprotein target in HCV-AITP .

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• The final version of the proposal will be
  available online at the site www.tcpeha.org

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Thrombocytopenia Hot issue!!!!
Is it cold???!!!