Clinical Assessment: Phlebotomy for Tabassum Gori

Patient Summary

Should You Do Phlebotomy?

2025 ACC/AHA Guideline Position on Phlebotomy in Cyanotic ACHD

"Phlebotomy may be considered in patients with refractory symptoms of hyperviscosity syndrome after adequate hydration with oral or IV fluid and adequate correction of iron deficiency."

"Another indication for phlebotomy may be if the patient's hematocrit level is >65% [preoperatively for autologous blood transfusion]."

"Prophylactic phlebotomy should be avoided — it exacerbates iron deficiency and increases stroke risk. It should NOT be used as primary treatment in patients with hyperviscosity symptoms or in asymptomatic patients with elevated hematocrit, as the effect on hematocrit is transient."*

Applying to This Patient

✅ Criteria Met for Phlebotomy

1. HCT 66.5% — crosses the >65% threshold
2. Hb 21.1 g/dL — severely elevated
3. Symptomatic: Fever, chills, rigors, bilateral lower limb edema — active clinical deterioration
4. SpO₂ 70% on RA — severe chronic hypoxemia driving erythrocytosis

⚠️ Critical Concerns Before/During Phlebotomy

1. COAGULOPATHY — Most Urgent Red Flag

• INR 3.77 (current) — severely elevated
• PT 47.7s, APTT 46.6s — both prolonged
• This is characteristic of the intrinsic hemostatic defect in Eisenmenger syndrome: thrombocytopenia tendency, dysfunctional platelets, and coagulation factor depletion
• Phlebotomy in this coagulopathic state carries significant bleeding risk
• Action: Investigate the cause of INR elevation — is she on anticoagulants? Warfarin? If so, what's the indication? Hepatic dysfunction from chronic right heart failure? Correct before phlebotomy if possible, or minimize volume removed

2. IRON DEFICIENCY — Must Rule Out First

• RDW 21.6 (markedly elevated) — strongly suggests mixed picture: secondary erythrocytosis + iron deficiency
• Peripheral smear shows macrocytes + ovalocytes — macrocytes could indicate B12/folate deficiency or dyserythropoiesis; ovalocytes can be seen in iron deficiency
• Paradox: HCT appears high (66.5%) but RDW elevation + morphological changes suggest relative iron deficiency
• Iron-deficient erythrocytes are less deformable, worsening hyperviscosity even at a "normal" HCT
• Iron deficiency in Eisenmenger is associated with worse outcomes
• Action: Check serum iron, ferritin, transferrin saturation BEFORE phlebotomy. If iron-deficient, repleting iron (carefully, with monitoring) may actually reduce HCT and symptoms more safely than phlebotomy

3. HYDRATION STATUS

• Rule out dehydration as a cause of falsely elevated HCT
• Fever + rigors suggest possible infection/sepsis → dehydration likely
• Action: Adequate oral/IV hydration first, recheck HCT after rehydration

4. ACTIVE INFECTION

• Current admission: fever, chills, rigors → sepsis workup is mandatory
• Source of infection? Blood cultures, urine culture, echo to rule out infective endocarditis (high risk in this patient with structural heart disease)
• Do not perform elective phlebotomy during active sepsis — stabilize infection first

5. THROMBOCYTOPENIA TREND

• Platelets declining: 242 (2023) → 194 (2024) → 165 (2026)
• Below 200 and trending down — platelet function is also abnormal in Eisenmenger
• Combined with INR 3.77 → bleeding risk from phlebotomy is substantial

Protocol if Phlebotomy is Decided

• Volume: Remove 250–500 mL (not more) — minimum that achieves symptomatic relief
• Simultaneous volume replacement: Isotonic saline 250–500 mL (use 5% dextrose only if in heart failure to avoid fluid overload)
• Target HCT: Reduce to just below 65%, not normal range — do NOT aggressively drop HCT as this will worsen oxygen delivery
• Do NOT repeat routinely — each phlebotomy worsens iron deficiency and increases stroke risk
• After phlebotomy, check iron stores and replace iron if deficient

Overall Recommendation

A Note on SPO₂ 70%

• Optimizing PAH therapy (PDE5 inhibitors, endothelin receptor antagonists, prostanoids)
• Identifying if there is a residual/recurrent shunt
• Ensuring iron replete state

Revised Management with Corrected Coagulation: PT 24.7s / INR 1.84

What INR 1.84 Means in This Context

• Reduced clotting factor synthesis (chronic liver congestion from right heart failure)
• Qualitative platelet dysfunction
• Reduced von Willebrand factor high-molecular-weight multimers
• Paradoxically, also at risk for both thrombosis AND bleeding

Revised Management Plan

Phlebotomy Decision: PROCEED — with conditions

• ✅ HCT 66.5% → above the >65% threshold
• ✅ Hb 21.1 g/dL → severely elevated
• ✅ Active symptoms (bilateral LL edema, fever, clinical deterioration)
• ✅ INR 1.84 — inherent Eisenmenger coagulopathy, not a contraindication
• ✅ SpO₂ 70% — erythrocytosis is compensatory but HCT >65% is now also a thrombohemorrhagic risk

Stepwise Protocol

Step 1 — Before Phlebotomy (Do These First)

Step 2 — Phlebotomy Technique

• Volume: Remove 250–500 mL (single unit) — start with 250 mL given mild coagulopathy
• Simultaneous replacement: Isotonic saline 250–500 mL IV, run concurrently (not after)
• If in heart failure: Use 5% dextrose instead of saline to avoid volume overload
• Target: Reduce HCT to just below 65% — do NOT target normal HCT; over-reduction worsens oxygen delivery at SpO₂ 70%
• Setting: Monitored bed, SpO₂ and BP monitoring throughout
• Do NOT repeat prophylactically — only repeat if symptoms of hyperviscosity recur AND iron replete AND HCT again >65%

Step 3 — Iron Deficiency Management (Mandatory)

• RDW 21.6 + macrocytes + ovalocytes on smear → this patient almost certainly has coexisting iron deficiency masked by high absolute Hb
• Iron deficiency in Eisenmenger = independent predictor of adverse outcomes
• Repeated phlebotomy without iron repletion → worsens deformability of RBCs → paradoxically increases hyperviscosity symptoms despite lower HCT
• If ferritin is low/transferrin saturation <20%: oral iron (ferrous sulfate 200mg BD) — titrate carefully; monitor for rapid HCT rise
• If severe deficiency: IV iron (Ferric carboxymaltose) with cardiology supervision

Step 4 — Address the Active Presentation

Step 5 — Long-Term PAH Optimization

• Current PAH medications? If not on targeted therapy → start (PDE5i: sildenafil/tadalafil; ERA: bosentan/macitentan)
• 6-minute walk test + NT-proBNP + functional class assessment for risk stratification
• Heart-lung transplant evaluation if refractory

Summary: What Changed with INR 1.84

Indications for Phlebotomy in Secondary Polycythemia

The Fundamental Distinction

A. Physiologically INAPPROPRIATE Secondary Polycythemia

Indications — Liberal

1. Symptomatic hyperviscosity — headache, dizziness, blurred vision, tinnitus, plethora, fatigue
2. HCT persistently >45% — target HCT 42–46% with regular phlebotomy
3. Prior to elective surgery — mandatory phlebotomy to reduce thrombotic/bleeding perioperative risk
4. Thrombotic risk reduction — these patients have increased risk of CVA, MI, DVT, PE
5. Temporary relief while definitive treatment of underlying cause is arranged (e.g. tumor resection)

B. Physiologically APPROPRIATE Secondary Polycythemia

Indications — Restrictive (all 3 ideally present)

1. Symptomatic Hyperviscosity Syndrome

• Visual disturbances, blurred vision
• Severe headache
• Dizziness, vertigo, tinnitus
• Paresthesia, digital numbness
• Profound fatigue, reduced concentration
• ⚠️ Always rule out dehydration first — dehydration falsely elevates HCT and mimics hyperviscosity symptoms

2. HCT Threshold

• HCT >65% — at this level, compensatory benefit plateaus and hyperviscosity overrides O₂ delivery benefit
• Below 65%: viscosity is still within tolerable range; O₂ delivery benefit outweighs risk of phlebotomy

3. Iron-Replete State

• Must confirm iron sufficiency before proceeding
• Iron deficiency → rigid, non-deformable RBCs → worsened viscosity at same or even lower HCT
• Phlebotomy in iron-deficient patient = worsening of the very problem you're trying to treat
• Check ferritin, serum iron, TIBC before each session

Additional Specific Indications (Any Type of Secondary Polycythemia)

Absolute Contraindications / When NOT to Phlebotomize

Phlebotomy Technique When Indicated

Summary Table