Hyperviscosity-related ischemic stroke in TOF with marked secondary erythrocytosis successfully managed with therapeutic phlebotomy

Technical Summary: Hyperviscosity-Related Ischemic Stroke in TOF Managed with Therapeutic Phlebotomy

Problem Statement
Ischemic stroke is a rare but severe complication in adults with cyanotic congenital heart disease (CCHD), specifically Tetralogy of Fallot (TOF). The pathophysiology involves chronic right-to-left shunting leading to persistent hypoxemia, which drives secondary erythrocytosis (polycythemia). While erythrocytosis is a compensatory mechanism to enhance oxygen delivery, excessive red blood cell mass can induce hyperviscosity syndrome, impairing microcirculatory flow and predisposing patients to thrombotic events. The management of this condition is controversial; therapeutic phlebotomy is often reserved for symptomatic patients, yet its application is complicated by the risk of inducing iron deficiency and microcytosis, which can paradoxically increase blood viscosity. Furthermore, the multifactorial nature of stroke in CCHD—encompassing endothelial dysfunction, coagulation abnormalities, and paradoxical embolization—makes isolating hyperviscosity as a primary treatable cause challenging.

Methodology
This study presents a single-case report of a 43-year-old male with TOF and pulmonary atresia who presented with acute ischemic stroke. The methodology involved:

• Clinical Assessment: Evaluation of neurological deficits (right hemiparesis, dysarthria, altered sensorium) and cardiovascular signs (central cyanosis, grade IV clubbing).
• Diagnostic Imaging: Non-contrast CT of the head confirmed a large left middle cerebral artery (MCA) territory infarct and a prior right parietal infarct. Transthoracic echocardiography verified TOF with pulmonary atresia, a large ventricular septal defect with bidirectional shunting, and an overriding aorta.
• Laboratory Analysis: Comprehensive hematological profiling revealed marked secondary erythrocytosis (Hemoglobin 18.9 g/dL, Hematocrit 60%, RBC 7.85 × 10⁶/µL) and elevated erythropoietin (426 mIU/mL). Crucially, iron studies identified concomitant iron deficiency (low ferritin, low transferrin saturation) and thrombocytopenia.
• Intervention: The patient underwent two sessions of therapeutic phlebotomy (350 mL removed per session) on May 4 and May 6, 2026. Each session was accompanied by simultaneous isotonic saline replacement and continuous hemodynamic monitoring to prevent hypovolemia.

Key Results

• Hematological Improvement: Following the two phlebotomy sessions, hematological parameters showed significant reduction: Hematocrit decreased from 60% to 47.6%, and Hemoglobin dropped from 18.9 g/dL to 14.0 g/dL.
• Clinical Outcome: The patient remained hemodynamically stable throughout the procedures with no immediate complications. Clinically, the patient demonstrated improvement in neurological status, though the specific correlation between the phlebotomy and neurological recovery is noted as observational within the context of a single case.
• Safety: The intervention was performed without procedure-related adverse events, supporting the safety of phlebotomy when volume replacement is strictly managed.

Significance and Claims
The paper posits that hyperviscosity is a potentially modifiable contributor to ischemic stroke in adults with cyanotic congenital heart disease. The authors claim that therapeutic phlebotomy, when applied judiciously to patients with symptomatic hyperviscosity and accompanied by adequate volume replacement and iron status evaluation, can serve as an effective adjunctive intervention.

The study emphasizes several critical nuances:

1. Symptom-Guided Management: Consistent with existing literature (e.g., Perloff et al.), the authors argue that therapeutic decisions should be driven by clinical symptoms of hyperviscosity rather than hematocrit values alone.
2. Iron Deficiency Consideration: The case highlights the importance of identifying iron deficiency, as microcytosis can worsen blood viscosity despite lower red cell counts. The authors caution against repeated or unnecessary phlebotomy that could exacerbate this condition.
3. Adjunctive Role: The authors modestly conclude that while phlebotomy may reduce thrombotic risk by lowering viscosity, it is not a definitive cure for the cerebrovascular event itself. It should be viewed as part of an individualized management strategy while definitive treatment for the underlying cardiac defect is pursued.

The case is classified as a TOAST 5 stroke (undetermined etiology), but the authors identify hyperviscosity and erythrocytosis as significant potential contributing factors that were successfully mitigated through the reported intervention.