What are the possible causes of a platelet count of 848 × 10⁹/L in a 14‑year‑old female?

Causes of Elevated Platelet Count (848 × 10⁹/L) in a 14-Year-Old Female

In a 14-year-old female with a platelet count of 848 × 10⁹/L, reactive (secondary) thrombocytosis is by far the most likely diagnosis, typically triggered by infection, inflammation, or iron deficiency; primary thrombocythemia is exceedingly rare in this age group and should only be considered after excluding all reactive causes. 1, 2, 3

Immediate Diagnostic Priorities

Confirm True Thrombocytosis

• Verify the elevated platelet count by repeating the complete blood count and reviewing a peripheral blood smear to exclude spurious elevation from platelet clumping, red cell fragments, or other artifacts 4
• A hematopathologist should confirm that the platelets are morphologically normal (not giant platelets, which would suggest inherited disorders) 1, 5

Assess Clinical Context

• Bleeding symptoms: Paradoxically, extreme thrombocytosis can cause both thrombosis and hemorrhage in primary disorders, but reactive thrombocytosis rarely causes vascular complications 2, 6
• Infection history: Recent or current infection (viral, bacterial) is the most common trigger in children 1, 7
• Inflammatory conditions: Kawasaki disease, inflammatory bowel disease, juvenile idiopathic arthritis 3, 6
• Iron deficiency: Check for history of heavy menstrual bleeding (relevant in a 14-year-old female), dietary insufficiency, or gastrointestinal blood loss 1, 3
• Medications: Review all drugs, as certain medications can trigger reactive thrombocytosis 6
• Trauma or surgery: Recent tissue injury or surgical procedures 3, 6

Essential Laboratory Workup

First-Tier Tests

• Complete blood count with differential: Evaluate for anemia (suggests iron deficiency or chronic disease), leukocytosis (suggests infection/inflammation), or eosinophilia (suggests parasitic infection or allergic process) 1, 4
• Peripheral blood smear review: Confirm normal platelet morphology, assess red cell size (microcytosis suggests iron deficiency), and exclude schistocytes or abnormal white cells 5, 4
• Iron studies: Serum ferritin, iron, total iron-binding capacity, and transferrin saturation to identify iron deficiency—a common cause in adolescent females with menstruation 1, 3
• Inflammatory markers: C-reactive protein and erythrocyte sedimentation rate to detect occult inflammation 8, 6

Second-Tier Tests (If First-Tier Unrevealing)

• Stool examination for ova and parasites: Helminth infections can cause marked eosinophilia and reactive thrombocytosis 4
• Infectious workup: Consider testing for occult infections (Epstein-Barr virus, cytomegalovirus, tuberculosis screening) if clinical suspicion exists 3, 6
• Bone marrow examination: Reserved for cases with atypical features (splenomegaly, hepatomegaly, lymphadenopathy, abnormal white cell or red cell parameters, giant platelets, or failure to resolve after treating underlying cause) 1, 5, 4

Differential Diagnosis by Mechanism

Reactive (Secondary) Thrombocytosis—Most Likely 1, 2, 3

Infection/Inflammation

• Acute or chronic bacterial, viral, or fungal infections 3, 7
• Kawasaki disease, inflammatory bowel disease, juvenile idiopathic arthritis 6
• Tissue necrosis or trauma 3

Iron Deficiency

• Heavy menstrual bleeding in adolescent females 1, 3
• Dietary insufficiency or malabsorption 1

Malignancy

• Solid tumors (rare in this age group but must be excluded if constitutional symptoms present) 3, 6

Post-Splenectomy or Hyposplenism

• Functional or anatomic asplenia 3, 6

Medications

• All-trans retinoic acid, epinephrine, corticosteroids 6

Primary (Essential) Thrombocythemia—Rare in Children 2, 6

• Myeloproliferative neoplasm with JAK2, CALR, or MPL mutations 6
• Typically presents with splenomegaly, thrombotic or hemorrhagic complications, and qualitative platelet abnormalities 2, 6
• Diagnosis requires exclusion of all reactive causes and often bone marrow examination with molecular testing 2, 6, 4

Management Algorithm

Step 1: Assess Bleeding and Thrombotic Risk

• No symptoms: Observation with repeat CBC in 4–6 weeks is appropriate; reactive thrombocytosis rarely requires treatment beyond addressing the underlying cause 1, 3
• Bleeding or thrombosis: Urgent hematology consultation; consider plateletpheresis only in life-threatening situations (e.g., intracranial hemorrhage, acute coronary syndrome) 3

Step 2: Identify and Treat Underlying Cause

• Iron deficiency confirmed: Initiate oral iron supplementation (elemental iron 3–6 mg/kg/day divided in 2–3 doses) and investigate the source of iron loss 1
• Active infection: Treat with appropriate antimicrobials; platelet count typically normalizes within weeks after infection resolves 3, 7
• Inflammatory condition: Manage the primary disorder (e.g., NSAIDs or disease-modifying agents for juvenile arthritis); thrombocytosis resolves as inflammation subsides 6

Step 3: Follow-Up Strategy

• Repeat CBC in 4–6 weeks to confirm that thrombocytosis is transient and reactive rather than persistent 1
• If platelet count remains elevated (>600 × 10⁹/L) after 8–12 weeks despite treating underlying causes, refer to pediatric hematology for evaluation of primary thrombocythemia 2, 6

Critical Pitfalls to Avoid

• Do not assume primary thrombocythemia without exhaustive exclusion of reactive causes: The ratio of reactive to primary thrombocytosis in children is approximately 60:1 1
• Do not overlook iron deficiency in adolescent females: Heavy menstrual bleeding is a common and treatable cause 1, 3
• Do not delay hematology referral if atypical features are present: Splenomegaly, hepatomegaly, lymphadenopathy, abnormal white cell or red cell parameters, or giant platelets on smear mandate bone marrow evaluation 5, 4
• Do not initiate platelet-lowering therapy empirically: Reactive thrombocytosis does not require cytoreductive treatment; management focuses on the underlying condition 3, 6
• Do not miss occult malignancy: Constitutional symptoms (fever, weight loss, night sweats, bone pain) require aggressive investigation including imaging and possible bone marrow biopsy 5, 6

When to Refer to Hematology

• Platelet count persistently >1,000 × 10⁹/L (extreme thrombocytosis) 7, 4
• Presence of splenomegaly, hepatomegaly, or lymphadenopathy 5, 4
• Thrombotic or hemorrhagic complications 2, 6
• Abnormal CBC parameters beyond isolated thrombocytosis (unexplained anemia, leukopenia, leukocytosis) 5
• Giant platelets or other abnormal morphology on peripheral smear 5, 4
• Failure of platelet count to normalize after 8–12 weeks of treating underlying cause 2, 6