Thrombocytosis

Synonym: thrombocythaemia.

This is defined as a platelet count exceeding the top of the normal range (400 to 450x10⁹/L).¹

There are two types of thrombocytosis:

• Primary thrombocytosis - this is due to a failure to regulate the production of platelets (autonomous production) and is a feature of a number of myeloproliferative disorders. About a third of patients are asymptomatic at the time of diagnosis.² It is also referred to as essential thrombocytosis.
• Secondary thrombocytosis - this can be secondary to a number of conditions. It is is an exaggerated physiologic response to a primary problem, such as an infection. The trigger factor (e.g. infection) results in the release of cytokines which mediate an increase in platelet production. It is often a transient phenomenon which disappears when the underlying cause is resolved. It is also known as reactive thrombocytosis.

Primary thrombocytosis²

• Myelofibrosis with myeloid metaplasia
• Polycythaemia vera
• Chronic myelocytic leukemia
• Familial essential thrombocytosis

Secondary thrombocytosis¹

• Infection (common infective causes are meningitis, infections of the upper and lower respiratory tract, urinary tract infections, gastroenteritis, septic arthritis, osteomyelitis, and generalised sepsis)
• Chronic inflammations and vasculitis (for example rheumatoid arthritis, Kawasaki syndrome, Henoch-Schönlein purpura, inflammatory bowel disease)
• Tissue damage (for example postsurgical, burns, trauma, fracture)
• Rebound thrombocytosis (for example with iron deficiency anaemia, bleeding, cancer chemotherapy, recovery phase of idiopathic thrombocytopaenic purpura (ITP))
• Postsplenectomy
• Haemolytic anaemia
• Renal disorders (for example nephrotic syndrome, nephritis)
• Malignancy (especially soft tissue sarcoma, osteosarcoma)
• Low birth weight/ preterm infants

Primary thrombocytosis

The prevalence in the general population is approximately 30/100,000. The median age at diagnosis is 65 to 70 years, but the disease may occur at any age. The female to male ratio is about 2:1.³

Secondary thrombocytosis

The incidence is highest during the first 3 months of life, and preterm infants are more prone than term infants. One meta-analysis found that 3-13% of hospitalised paediatric patients had a platelet count of more than 500x10⁹/L.¹

History

• Primary thrombocytosis:
  • The clinical features mainly related to an increased bleeding tendency and, rather oddly, an increased tendency to thrombosis. The mechanisms that cause these two phenomena are poorly understood but are thought to relate to a decrease in aggregation, hyperaggregation, and the presence of high molecular weight von Willebrand factor multimers (substances released by tissue when coagulation is required).
  • About a third of patients are asymptomatic at the time of diagnosis.
  • Symptoms can include:
    • Neurological symptoms:
      • Headache
      • Burning pain and dusky appearance of the extremities (erythromelalgia)
      • Transient ischaemic episodes and paraesthesiae
      • Other transient symptoms (including dizziness, dysarthria, syncope, migraine, seizures etc.)
    • Arterial thrombosis:
      • Cardiac, renal and leg arteries (possible)
      • Pain or gangrene of the toes and fingers
    • Venous thrombosis:
      • Splenic, hepatic, or leg and pelvic veins may be involved
      • Pulmonary hypertension
    • Bleeding:
      • Primarily gastrointestinal
      • May also involve eyes, gums, skin and brain
• Secondary thrombocytosis:
  • A history of the primary condition may be elicited (e.g. infection) but sometimes the causative factor is not obvious.
  • Symptoms prevalent in primary thrombocytosis are notably absent.

Examination

• Primary thrombocytosis:
  • 40-50% of patients have splenomegaly on presentation.
  • 20% have hepatomegaly.
  • Clinical findings are otherwise unremarkable.
• Secondary thrombocytosis:
  • There are no specific clinical findings.

• Full blood count (FBC):
  • The hallmark of essential thrombocytosis is a sustained thrombocytosis. This is usually greater than 600x10⁹/L.
  • Other findings may include leukocytosis, erythrocytosis, and mild anaemia.
  • Immature precursor cells (e.g. myelocytes, metamyelocytes) may occasionally be seen.
  • Large platelets (thrombocytes) may also be identified.
• Bone marrow Aspiration may show:
  • Hypercellularity
  • Megakaryocytic hyperplasia
  • Giant megakaryocytes
  • Hyperplasia of granulocyte and reticulocyte precursors
  • An increase ins bone marrow reticulin
  • An absence of myelofibrosis (this would raise the suspicion of agnogenic myeloid metaplasia)
  • Iron stores may be absent
• Platelet Aggregation Studies:
  • There is an increase in platelet aggregation.
• Red Blood Cell Mass:
  • This is normal in primary thrombocytosis.
  • It is raised in polycythaemia vera.
• Genetic Studies:
  • Philadelphia chromosome is absent (it is present in chronic myeloid leukaemia).
• Imaging:
  • Chest Xray and abdominal ultrasound may be indicated to exclude undetected sources of infection or malignancy.

Primary Thrombocytosis²

See specific article on Primary Thrombocytosis.

Secondary Thrombocytosis¹

This condition is usually transient and self-limiting, and no treatment is required. Rarely, patients with a pre-existing thrombotic condition such as Kawasaki syndrome, may require aspirin if they develop a reactive thrombocytosis.