What are the risk factors that cause thrombocytosis?

Risk Factors for Thrombocytosis

Thrombocytosis is primarily caused by either primary (clonal) disorders or secondary (reactive) conditions, with secondary causes accounting for over 80% of cases.

Primary Thrombocytosis

Primary thrombocytosis refers to clonal disorders where abnormal platelet production occurs due to intrinsic abnormalities in bone marrow stem cells:

1. Myeloproliferative Neoplasms (MPNs):

   • Essential thrombocythemia (ET)
   • Polycythemia vera (PV)
   • Primary myelofibrosis
   • Chronic myeloid leukemia 1

2. Genetic Markers:

   • JAK2V617F mutation (common in PV, ET, and primary myelofibrosis)
   • Mutations in exon 12 of JAK2
   • Other driver gene mutations 1

Primary thrombocytosis typically presents with:

• Higher median platelet counts (often >1,000/μL)
• More prolonged elevation (>1 month)
• Higher risk of thrombotic complications
• More extreme thrombocytosis (>800 × 10^9/L) 2

Secondary (Reactive) Thrombocytosis

Secondary thrombocytosis is much more common, accounting for approximately 83% of cases 2. Major causes include:

1. Tissue Injury (32.2%):

   • Trauma
   • Surgery
   • Burns 2

2. Infection (17.1%):

   • Acute or chronic bacterial infections
   • Viral infections
   • Tuberculosis 2, 3

3. Chronic Inflammatory Disorders (11.7%):

   • Inflammatory bowel disease
   • Rheumatoid arthritis
   • Connective tissue diseases
   • Vasculitis 2

4. Iron Deficiency Anemia (11.1%):

   • Iron deficiency can lead to reactive thrombocytosis and potentially increase thromboembolic risk 2, 4

5. Malignancy:

   • Solid tumors (especially gastrointestinal, lung, breast, ovarian)
   • Lymphoma
   • Metastatic disease 1

6. Post-splenectomy:

   • Functional or surgical splenectomy leads to increased circulating platelets 1

7. Drug-Induced:

   • Vincristine
   • Epinephrine
   • All-trans retinoic acid
   • Cytokines (GM-CSF, G-CSF) 5

Risk Factors for Thrombosis in Patients with Thrombocytosis

In patients with thrombocytosis, additional factors that increase thrombotic risk include:

1. Age >60 years 1, 6

2. Prior history of thrombosis 1, 6

3. Cardiovascular risk factors:

   • Hypertension
   • Diabetes
   • Hyperlipidemia
   • Smoking
   • Obesity 6

4. Leukocytosis:

   • Increases thrombotic risk by 65% in ET patients
   • Increases thrombotic risk by 34% in PV patients 7

5. Comorbidities associated with infection-related thrombocytosis:

   • Quadriplegia/paraplegia
   • Indwelling prostheses
   • Dementia
   • Diabetes 3

6. Clinical signs associated with infection-related thrombocytosis:

   • Fever
   • Tachycardia
   • Weight loss
   • Hypoalbuminemia
   • Neutrophilia
   • Leukocytosis
   • Anemia 3

Clinical Implications

1. Primary thrombocytosis carries a higher risk of thrombotic complications and requires specific treatment based on risk stratification 6.

2. Secondary thrombocytosis generally resolves with treatment of the underlying condition, but can still be associated with increased mortality, particularly when related to infection 3.

3. Iron deficiency-associated thrombocytosis is increasingly recognized as a potential thromboembolic risk factor, and iron replacement therapy may be an effective preventive strategy 4.

When evaluating a patient with thrombocytosis, it's essential to determine whether it's primary or secondary, as this distinction guides management decisions and helps predict clinical outcomes.