How should you assess a 26-year-old patient with mild thrombocytosis (elevated platelet count) and a 7-year history of headaches, peripheral neuropathy, chest pain, and shortness of breath?

Assessment of a 26-Year-Old Patient with Mild Thrombocytosis and Chronic Symptoms

The initial evaluation of a young patient with mild thrombocytosis and multiple chronic symptoms should include a comprehensive diagnostic workup to distinguish between primary and secondary thrombocytosis, with particular attention to inherited platelet function disorders. 1, 2

Initial Diagnostic Steps

• Obtain a complete blood count with peripheral blood smear to evaluate platelet morphology, particularly noting the presence of large forms 3
• Examine the peripheral blood smear for altered platelet size or structure, which can suggest specific disorders 3
• Assess for pseudothrombocytopenia by examining for platelet clumping, which can cause falsely elevated counts 4
• Review medication history for drugs that might affect platelet function or cause thrombocytosis 3
• Evaluate iron status, as iron deficiency anemia is a common cause of secondary thrombocytosis (11.1% of cases) 5, 6
• Screen for inflammatory markers (ESR, CRP) since chronic inflammatory disorders account for 11.7% of secondary thrombocytosis cases 5, 6

Specialized Testing

• Perform light transmission aggregometry (LTA) with epinephrine, ADP, collagen, arachidonic acid, and ristocetin to assess platelet function 3
• Evaluate platelet granule release by assessing ATP/ADP secretion and α-granule markers 3
• Analyze major platelet surface glycoproteins by flow cytometry 3, 2
• Test for JAK2V617F mutation, which is found in essential thrombocythemia and other myeloproliferative disorders 7, 6
• Consider testing for CALR and MPL mutations if JAK2V617F is negative but clinical suspicion for essential thrombocythemia remains high 6

Risk Assessment

• Evaluate for prior history of thrombosis, which is a significant risk factor 1
• Consider age as a risk factor (patients under 60 years old are generally lower risk) 1
• Assess platelet count - values greater than 1,000 × 10^9/L are associated with bleeding risk rather than thrombosis 1

Special Considerations for This Patient

• The chronic and stable nature of the thrombocytosis (7 years) requires evaluation for both primary and secondary causes 5, 7
• The constellation of headaches, peripheral neuropathy, chest pain, and shortness of breath could represent vascular symptoms associated with thrombocytosis 1, 8
• The presence of occasional large platelet forms may suggest an inherited platelet disorder 3, 2
• Consider rheumatologic evaluation as conditions like rheumatoid arthritis can cause both thrombocytosis and the patient's symptoms 9

Common Pitfalls to Avoid

• Failing to distinguish between primary and secondary thrombocytosis, which have different management approaches and prognoses 5, 6
• Overlooking inherited platelet function disorders, especially when platelet count is only mildly elevated 3, 2
• Premature labeling as "bleeding disorder of unknown cause" without completing a thorough diagnostic evaluation 2
• Not considering that mild thrombocytosis may be part of an underlying disorder rather than a separate issue 2
• Relying solely on first-step tests when results are inconclusive 2

Follow-up Recommendations

• If initial testing is inconclusive, proceed with more specialized testing including VWF multimer analysis, expanded flow cytometry, and transmission electron microscopy 2
• Consider genetic testing if clinical suspicion for inherited disorders remains high 2
• Monitor platelet counts every 3-6 months to assess for progression 1
• Further investigation is warranted if the platelet count exceeds 1,000 × 10^9/L, if there is a progressive increase in platelet count over time, or if symptoms worsen 1