THROMBOCYTOPENIA

• Thrombocytopenia


  Decrease in circulating platelets
• Thrombocytopenia


  1. Production = destruction (happens in spleen)

  2. Megakaryopolesis: MK1, II, K1

  3. Trombopoeisis: release of platelet, MM PC (Function)

  4. Lifespan: 8-10 days

  5. Distribution of platelet
• Platelet count reference range is generally 150,000 to 450,000/μL
• Thrombocytopenia


  Platelet count of fewer than 100,000/µL, most common cause of clinically important bleeding
• True thrombocytopenia has to be differentiated from pseudothrombocytopenia artifact
• Manifestations of thrombocytopenia in the skin

  • Petechiae
  • Purpura
  • Ecchymoses
• Severity of clinical bleeding often not closely correlated with platelet count
• Clinically significant bleeding unlikely when platelet count >50,000/µL, high risk when <10,000/µL
• Causes of thrombocytopenia


  • Decreased platelet production
  • Increased platelet destruction
  • Abnormal platelet distribution
• Congenital types of impaired platelet production

  • May-Hegglin anomaly
  • Bernard-Soulier syndrome
  • Fechtner syndrome
  • Sebastian syndrome
  • Epstein syndrome
  • Fanconi anemia
  • Wiskott-Aldrich syndrome
  • Thrombocytopenia with absent radius (TAR) syndrome
  • Congenital amegakaryocytic thrombocytopenia
• May-Hegglin anomaly


  Rare autosomal dominant disorder with large platelets and Döhle-like bodies in neutrophils, thrombocytopenia in 1/3 to 1/2 of patients
• Sebastian syndrome, Fechtner syndrome, Epstein syndrome


  Other disorders involving MYH9 gene mutations, with large platelets, thrombocytopenia, and other features
• Thrombocytopenia with absent radii (TAR) syndrome


  Rare autosomal recessive disorder with severe neonatal thrombocytopenia and congenital absence or hypoplasia of radial bones, often with other abnormalities
• Congenital amegakaryocytic thrombocytopenia


  Autosomal recessive disorder with bone marrow failure, platelet counts ≤20,000/μL at birth, often progressing to aplastic anemia or leukemia
• Autosomal dominant thrombocytopenia


  Caused by mutations in ANKRD26 gene, usually mild bleeding, normal platelet morphology and function
• 1. linked thrombocytopenia


  Caused by mutations in WAS or GATA1 genes, ranging from mild thrombocytopenia with small platelets to severe bleeding with large platelets
• Causes of neonatal thrombocytopenia

  • Alloimmune
  • Autoimmune (ITP, SLE)
  • Aneuploidy
  • Bone marrow replacement
  • Congenital infections (TORCH)
  • Congenital inherited disorders
  • Disseminated intravascular coagulation
  • Kasabach-Merritt syndrome
  • Late-onset sepsis
  • Maternal autoimmune conditions
  • Metabolic disease
  • Necrotizing enterocolitis
• Neonatal thrombocytopenia is present in 1-5% of infants at birth, 75% within 72 hours
• TORCH infections are common causes of neonatal thrombocytopenia with small platelets
• Maternal ingestion of certain drugs can cause neonatal thrombocytopenia by direct cytotoxic effect on fetal megakaryocytes
• Most common cause of neonatal thrombocytopenia is impaired platelet production in preterm neonates with placental insufficiency or fetal hypoxia
• Neonatal thrombocytopenia


  Impaired platelet production is the most common cause
• Causes of impaired platelet production in neonatal thrombocytopenia

  • Preterm neonates born after pregnancies complicated by placental insufficiency or fetal hypoxia (preeclampsia and intrauterine growth restriction)
  • These neonates have early-onset thrombocytopenia and impaired megakaryopoiesis in spite of increased levels of thrombopoietin
• Causes of fetal and neonatal thrombocytopenias

  • Alloimmune
  • Autoimmune (ITP, SLE)
  • Aneuploidy (trisomy 13, 18, or 21 or triploidy)
  • Bone marrow replacement (congenital leukemia)
  • Congenital infections (TORCH)
  • Congenital inherited (Wiskott-Aldrich syndrome)
  • Congenital inherited (TAR, CAMT)
  • Disseminated intravascular coagulation
  • Kasabach-Merritt syndrome
  • Late-onset sepsis
  • Maternal autoimmune conditions (ITP, SLE)
  • Metabolic disease (propionic and methylmalonic acidemia)
  • Necrotizing enterocolitis
  • Perinatal asphyxia
  • Perinatal infection (Escherichia coli, group B streptococcus, Haemophilus influenzae)
  • Uteroplacental vascular insufficiency (preeclampsia, IUGR)
  • Severe Rh hemolytic disease
  • Thrombosis (aortic, renal vein)
• Increased platelet consumption or sequestration

  Another mechanism of neonatal thrombocytopenia, accounting for 2% to 25% of cases
• Causes of increased platelet consumption or sequestration

  • Transplacental passage of maternal alloantibodies and autoantibodies (15% to 20% of cases)
  • Disseminated intravascular coagulation (DIC) (10% to 15% of cases)
  • Thrombosis
  • Platelet activation
  • Platelet binding at inflammatory sites such as in necrotizing enterocolitis
  • Splenic sequestration
• Inherited thrombocytopenic syndromes are increasingly being recognized as causes of neonatal thrombocytopenia
• Drug-induced hypoplasia of the bone marrow

  Results in thrombocytopenia
• Chemotherapeutic agents that suppress bone marrow megakaryocyte production

  • Methotrexate
  • Busulfan
  • Cytosine arabinoside
  • Cyclophosphamide
  • Cisplatin
• Recombinant interleukin-11


  Approved for treatment of chemotherapy-induced thrombocytopenia
• Thrombopoietin or its analogs


  May prove to be useful for treatment of chemotherapy-induced thrombocytopenia
• Zidovudine


  Used for the treatment of HIV infection, can cause myelotoxicity and severe thrombocytopenia
• Anagrelide


  Affects megakaryocytopoiesis without significantly affecting other marrow elements, useful for treating thrombocytosis in patients with essential thrombocythemia and other myeloproliferative disorders
• Ethanol


  Long-term ingestion may result in persistent, severe thrombocytopenia by inhibiting megakaryocytopoiesis
• Interferon therapy


  Commonly causes mild to moderate thrombocytopenia, can be severe and life threatening
• Estrogen or estrogenic drugs


  Large doses can cause thrombocytopenia presumably by megakaryocyte suppression
• Certain antibacterial agents, tranquilizers, and anticonvulsants


  Have been associated with thrombocytopenia caused by bone marrow suppression
• Megaloblastic anemias


  Thrombocytopenia is a usual feature, caused by impaired DNA synthesis and ineffective platelet production
• Viruses associated with thrombocytopenia

  • Measles vaccine
  • CMV
  • Varicella-zoster virus
  • Rubella virus
  • Epstein-Barr virus
  • Some serotypes of dengue virus
• Bacterial infections associated with thrombocytopenia

  • Meningococcemia
  • Many cases in childhood