Introduction

• It is a condition in which platelet count is more than 4,50,000/cmm
• TPO is produced from liver and its level is inversely proportional to platelet count

Causes:

• Spurious
  • Microspherocytes- Ex: Severe burns
  • Cryoglobulinemia
  • Neoplastic cell cytoplasmic fragments Ex- Acute leukemia
  • Schistocytes
  • Bacteria
  • Pappenheimer bodies
• Clonal disorders:
  • Essential thrombocythemia
  • Polycythemia vera
  • Primary myelofibrosis
  • Myelodysplasia with del 5q
  • Refractory anemia with ringed sideroblasts with marked thrombocytosis
  • Chronic myeloid leukemia (They can have only thrombocytosis)
  • Chronic myelomonocytic leukemia
  • Atypical chronic myeloid leukemia
  • MDS/MPN-U
  • Hereditary essential thrombocytosis due to germline mutation of MPL-  S505A mutation
• Inflammation associated
  • Can be due to infections/ tissue damage
  • It is cause of thrombocytosis in 80% of cases
  • Thrombocytosis occurs due to release of IL6 and Interferon gamma
  • ESR and CRP are increased
• Others
  • Iron deficiency anemia
  • Hyposplenism: Post splenectomy, functional asplenia (amyloidosis, celiac sprue)
  • Post operative
  • Post exercise 
  • Hemorrhage/ blood loss
  • Malignancy including lymphomas
  • Hemolysis
  • Drug therapy: Corticosteroids, adrenaline, vincristine
  • Cytokine administartion Ex: Thrombopoietin
  • Rebound following myelosuppressive chemotherapy
  • Acquired type II vWD
  • Familial thrombocytosis due to mutations in TPO and TPO receptor genes

Clinical manifestations:

• Vasomotor symptoms: Headache, visual symptoms, light headedness, atypical chest pain, acral dysesthesia, erythromelalgia
• Thrombotic symptoms and bleeding- rarely seen with reactive thrombocytosis
• Splenomegaly- Often seen with ET

Investigations:

• CRP and ESR- Elevated in case of inflammatory status
• Iron profile
• Peripheral smear
  • Microcytosis indicates iron deficiency anemia
  • Leucoerythroblastic blood picture- Marrow infiltration/ fibrosis
  • Acanthocytes, target cells- Seen after splenectomy
  • Howell Jolly Bodies- Indicates hyposplenism
  • Neutrophilia with shift to left- Seen in CML and infections
  • Large poorly stained platelets- Seen in ET
  • Tear drop cells- PMF
  • Schistocytes/ circulating progenitor cells- Cause for false increase in platelet count
• Bone marrow aspiration and biopsy
  • Secondary thrombocytosis
    • Megakaryocytic hyperplasia with normal mature and left shifted megakaryocyte morphology
    • Normal interstitial distribution and do not show clustering
    • Reticulin- Not increased
  • Essential thrombocytosis
    • Normocellular/ mildly hypercellular
    • Giant megakaryocytes with hyperlobated (staghorn) nuclei are seen
    • Emperipolesis is often seen
    • Small and also pyknotic megakaryocytes may be seen
    • Normal erythropoiesis and granulopoiesis are seen
    • No dysplasia is seen
    • Iron stores are reduced
    • Megakaryocytes are increased in number and are present as single cells or may form occasional small loose clusters within the interstitium
    • Reticulin- 0-2+/4+
  • Polycythemia vera
    • Panmyelosis is seen
    • Relatively increased erythroids
    • Megakaryocytes are small and show marked pleomorphism with higher than normal nucleo cytoplasmic ratio
    • Loose clustering of megakaryocytes is seen
    • Storage iron is absent
  • Primary myelofibrosis
    • Megakaryocytes are markedly abnormal, with elongated and angulated shapes
    • They are present adjacent to bony trabeculae and within sinuses
    • Megakaryocytes may form dense and often large clusters
    • High nucleocytoplasmic ratio is noted. Nuclei are enlarged, hyperchromatic and poorly lobulated
  • MDS with 5q deletion
    • Macrocytic RBCs with minimal polychromasia
    • Normocellular bone marrow with dyserythropoiesis
    • Increased megakaryocyes, present in the interstitium
    • They are small and have monolobed/ hypolobated nuclei,that is eccentrically placed
  • RARS with thrombocytosis
    • Ringed sideroblasts seen
  • CML
    • Small hypolobulated megakaryocytes

• Cytogenetics
  • Abnormalities indicate clonal disorder
• JAK2 mutation testing
  • Positive in 50% of ET and 97% of PV
• mpl mutation
  • Seen in 10% of ET
• BCR-ABL mutation testing
  • Presence is diagnostic of CML
  • Should be done if there is basophilia or shift to left of neutrophils

Diagnostic algorithm:

Treatment of reactive thrombocytosis:

• Resolves once underlying reactive state has been treated
• No data to support use of Aspirin