Is there a connection between thrombocytosis and Postural Orthostatic Tachycardia Syndrome (POTS)?

Connection Between Thrombocytosis and POTS

There is evidence suggesting a connection between thrombocytosis and Postural Orthostatic Tachycardia Syndrome (POTS), with recent research indicating that POTS patients demonstrate abnormal platelet function and hypercoagulability.

Pathophysiological Mechanisms Linking Platelets and POTS

• Proteomic analysis of POTS patients has identified differentially expressed proteins involved in thrombogenicity and enhanced platelet activity, suggesting a hypercoagulable state may be part of the POTS pathophysiology 1
• POTS patients have been found to have platelet dense granule storage pool deficiency (δ-SPD), which can contribute to bleeding diathesis and may explain several disparate symptoms affecting the severity of the condition 2
• Reactive thrombocytosis is common in conditions with chronic inflammation, which may be relevant as POTS has been characterized as having a proinflammatory state 3, 1
• The hyperadrenergic state seen in some POTS patients may influence platelet activation and aggregation, potentially contributing to thrombotic tendencies 4

Clinical Manifestations and Diagnostic Considerations

• POTS is diagnosed when there is an increase in heart rate ≥30 bpm (or ≥40 bpm in patients aged 12-19 years) within 10 minutes of standing without orthostatic hypotension 5
• Common symptoms include dizziness, light-headedness, weakness, fatigue, palpitations, tremor, and blurred vision 5
• Different POTS phenotypes have been identified, including hypovolemic, neuropathic, and primary hyperadrenergic POTS, representing different pathophysiological mechanisms 5, 6
• When evaluating patients with suspected POTS and thrombocytosis, clinicians should consider:
  • Complete blood count with platelet count and morphology 3
  • Inflammatory markers (ESR, CRP) as inflammation may contribute to both conditions 3, 1
  • Coagulation studies to assess for hypercoagulable state 1

Comorbid Conditions and Associations

• POTS is frequently associated with hypermobile Ehlers-Danlos syndrome (hEDS), with studies showing 25-37.5% of patients with hEDS reporting a diagnosis of POTS 5
• May-Thurner syndrome (MTS), a vascular compression disorder, has been reported in patients with both POTS and EDS, suggesting potential vascular and coagulation abnormalities in this patient population 7
• Up to 40% of patients with POTS may self-report a viral upper respiratory or GI infection as the precipitating event to their symptoms, which could trigger both inflammatory responses and reactive thrombocytosis 3
• Post-COVID-19 POTS patients demonstrate similar platelet abnormalities as non-COVID POTS patients, suggesting a common pathophysiological mechanism 2

Clinical Implications and Management

• For patients with both POTS and thrombocytosis, management should address both conditions:
  • Treat the underlying cause of thrombocytosis if secondary 3
  • Consider the hypercoagulable state when managing POTS patients, especially those with additional risk factors for thrombosis 1
  • Monitor for bleeding symptoms, as POTS patients with platelet storage pool deficiency may paradoxically have increased bleeding tendencies despite elevated platelet counts 2
• Treatment approaches for POTS should be tailored to the underlying pathophysiologic mechanism:
  • Stockings, abdominal binders, and vasoconstrictors for partial neuropathic POTS 4
  • Exercise and volume expansion for hypovolemic POTS 4
  • Beta-blockers and avoidance of norepinephrine reuptake inhibitors for hyperadrenergic POTS 4

Research Gaps and Future Directions

• Further research is needed to understand the exact mechanisms linking thrombocytosis, platelet dysfunction, and POTS 2, 1
• Investigation into whether treating platelet abnormalities improves POTS symptoms could provide new therapeutic targets 1
• The role of autoimmunity in both POTS and platelet dysfunction requires additional study, as autoimmune mechanisms may underlie both conditions 3, 1