HHT and Elevated White Blood Cell Counts
Direct Answer
Leukocytosis in HHT patients is not a recognized manifestation of the disease itself and should prompt immediate investigation for alternative causes, particularly infection, as HHT patients have documented immune dysfunction with impaired neutrophil function and anemia-associated T cell deficiency that increases their susceptibility to bacterial infections. 1
Understanding the Immunologic Context in HHT
HHT patients typically present with anemia and lymphopenia, not leukocytosis—the opposite of what you're observing. 1
Approximately 50% of HHT patients develop iron deficiency anemia from chronic bleeding (epistaxis and gastrointestinal), making anemia the dominant hematologic finding rather than elevated white counts. 2, 3
T cell counts are significantly decreased in HHT patients (0.7 vs. 1.3 × 10⁶/mL in healthy controls), and this lymphopenia correlates directly with hemoglobin levels—the lower the hemoglobin, the worse the T cell deficiency. 1
Neutrophil function is impaired in HHT despite normal absolute neutrophil counts, with significantly suppressed neutrophil extracellular trap (NET) release against bacterial pathogens like Pseudomonas aeruginosa due to defective filamentous actin organization. 1
Diagnostic Approach to Leukocytosis in HHT
Primary Evaluation
Screen aggressively for infection as the most likely cause, given the documented increased susceptibility to bacterial infections in HHT patients from both impaired neutrophil function and T cell deficiency. 1
Obtain complete blood count with differential to characterize the leukocytosis pattern (neutrophilic vs. lymphocytic vs. monocytic). 1
Assess for clinical signs of infection including fever, localizing symptoms, and inflammatory markers (CRP, procalcitonin).
Consider occult sources including pulmonary AVMs as potential infection sites, as these create right-to-left shunts that bypass pulmonary capillary filtration and increase risk of paradoxical emboli and cerebral abscess. 4
Secondary Considerations
Evaluate for secondary causes unrelated to HHT:
Reactive leukocytosis from stress, corticosteroid use, or inflammatory conditions
Primary myeloproliferative disorders (polycythemia vera, essential thrombocythemia, chronic myeloid leukemia) that coincidentally coexist with HHT—these are separate entities, not HHT manifestations. 5
Perform JAK2 mutation testing if persistent unexplained leukocytosis with elevated hemoglobin or platelets. 5
HHT-Specific Screening (If Not Previously Completed)
Even in the context of leukocytosis evaluation, ensure mandatory HHT screening has been performed:
Contrast echocardiography or chest CT for pulmonary AVMs, as these can serve as infection sources and cause paradoxical emboli leading to stroke or cerebral abscess. 4, 5
Brain MRI to detect cerebral vascular malformations, as nearly one in five HHT patients develop stroke or cerebral abscess. 6
Doppler ultrasonography for hepatic AVMs (never liver biopsy due to catastrophic hemorrhage risk). 4, 5
Management Algorithm
If Infection Identified
Treat with appropriate antimicrobials, recognizing that HHT patients may require more aggressive or prolonged therapy given their impaired neutrophil function and T cell deficiency. 1
Screen for pulmonary AVMs if not previously done, as these create persistent infection risk through right-to-left shunting. 4
Consider percutaneous transcatheter embolization of pulmonary AVMs to eliminate the shunt and reduce future infection risk. 4
If No Infection Found
Pursue hematology consultation for evaluation of primary myeloproliferative disorders with JAK2 mutation testing and bone marrow evaluation if indicated. 5
Reassess in 1 month with repeat complete blood count to determine if leukocytosis is persistent or transient.
Concurrent HHT Management
Continue standard HHT bleeding management regardless of leukocytosis:
Screen for iron deficiency in all adults with HHT irrespective of bleeding symptoms (strong recommendation). 2
Initiate oral iron (35-65 mg elemental iron daily) for iron deficiency, escalating to intravenous iron for severe anemia or inadequate oral response. 2
Begin nasal moisturization for epistaxis, escalating to oral tranexamic acid (500 mg twice daily, gradually increasing to 1000 mg four times daily) if inadequate. 2, 4
Reserve systemic bevacizumab (5 mg/kg IV every 2 weeks for 4-6 doses, then maintenance) for refractory bleeding failing all other interventions. 2, 4
Critical Pitfalls to Avoid
Do not attribute leukocytosis to HHT itself—this is not a recognized disease manifestation and requires investigation for alternative causes. 1
Do not overlook occult infection, as HHT patients have documented immune dysfunction making them more susceptible to bacterial infections despite normal or elevated white counts. 1
Never perform liver biopsy in HHT patients even during infection workup, due to catastrophic hemorrhage risk from hepatic AVMs. 4, 5
Do not delay pulmonary AVM screening if not previously completed, as these lesions increase infection risk through paradoxical emboli and can cause stroke or cerebral abscess. 4
Recognize that anemia-associated T cell deficiency worsens with lower hemoglobin levels, so aggressive iron replacement may improve immune function in addition to treating anemia. 1