Can Hypereosinophilic Syndrome with Thrombotic Complications Present with Normal WBC and Eosinophils?
No, hypereosinophilic syndrome (HES) by definition cannot present with normal blood eosinophil counts, as the diagnostic criteria explicitly require persistent peripheral blood eosinophilia ≥1.5 × 10⁹/L on two examinations at least one month apart. 1, 2
Diagnostic Criteria Are Absolute
The diagnosis of HES requires three essential, non-negotiable components 1, 2:
- Peripheral blood eosinophilia ≥1.5 × 10⁹/L documented on two separate occasions at least one month apart
- End-organ damage and/or dysfunction attributable to tissue eosinophilic infiltration (including thrombosis with or without thromboembolism) 1
- Exclusion of other disorders or conditions as the major reason for organ damage 1
Without meeting the eosinophilia threshold in peripheral blood, the diagnosis of HES cannot be made, regardless of clinical presentation. 2, 3
Critical Distinction: Tissue vs. Blood Eosinophilia
While the guidelines acknowledge that tissue hypereosinophilia can occur, the standard diagnostic pathway still requires documentation of peripheral blood hypereosinophilia 2. The NCCN guidelines state that HES is defined as "blood HE with (plus) end-organ damage attributable to tissue HE" 1, emphasizing that blood eosinophilia is the primary criterion.
Thrombotic Complications in HES Context
When thrombotic complications do occur in confirmed HES, they are well-documented 1:
- Thrombosis (with or without thromboembolism) is recognized as a specific form of HE-related organ damage 1
- Thrombotic events occur in approximately 24% of HES patients and are significantly associated with increased mortality 4
- Endomyocardial thrombosis and fibrosis are particularly common in primary (neoplastic) HES variants 3, 5
- Patients with molecular aberrations on next-generation sequencing have 5.4-fold increased odds of thrombosis 4
What to Consider Instead
If a patient presents with thrombotic complications but has normal WBC and eosinophil counts, you must consider alternative diagnoses 1:
- Clonal hematopoiesis of indeterminate potential - somatic mutations associated with hematologic malignancy can be detected in people with normal blood counts 1
- Other hypercoagulable states unrelated to eosinophilia
- Occult malignancy that has not yet manifested with eosinophilia
- Secondary causes of thrombosis requiring standard thrombophilia workup
Common Pitfall to Avoid
Do not diagnose HES based solely on tissue eosinophilia or clinical suspicion without documented peripheral blood eosinophilia ≥1.5 × 10⁹/L. 2, 3 The peripheral blood eosinophil count is the gatekeeper for this diagnosis, and proceeding with HES-specific therapies (such as imatinib for PDGFRA-rearranged disease or corticosteroids) without meeting diagnostic criteria would be inappropriate and potentially harmful 1, 6.