A 35-year-old man of African descent presents with acute onset jaundice, dark urine, and severe back pain after taking trimethoprim-sulfamethoxazole for a urinary tract infection. Hemoglobin is 9.8 g/dL (baseline 13.5 g/dL), reticulocyte count 12%, indirect bilirubin 3.8 mg/dL, and LDH 850 U/L. Peripheral blood smear shows bite cells and Heinz bodies on supravital staining. Direct antiglobulin test is negative. What is the most appropriate immediate next step in management?

Question

Accepted Answer

D. Discontinue the offending drug, ensure adequate hydration, monitor urine output, and arrange urinalysis for hemoglobinuria. ## Clinical Diagnosis

This patient has **glucose-6-phosphate dehydrogenase (G6PD) deficiency** with acute hemolytic crisis triggered by an oxidative stressor (trimethoprim-sulfamethoxazole).

**Key Point:** The diagnostic triad is:
1. **Bite cells** — RBCs with a "bitten" appearance from Heinz body removal by splenic macrophages
2. **Heinz bodies** — precipitated denatured hemoglobin (visible only on supravital staining, NOT on routine smear)
3. **Negative DAT** — rules out immune-mediated hemolysis

**High-Yield:** G6PD deficiency is X-linked recessive; African males have the highest prevalence (10–15%). Hemolytic crises are **self-limited** if the oxidative trigger is removed.

## Pathophysiology of G6PD Hemolysis

```mermaid
flowchart TD
  A[G6PD Deficiency]:::outcome --> B[Reduced NADPH production]:::outcome
  B --> C[Impaired glutathione reduction]:::outcome
  C --> D[Accumulation of reactive oxygen species]:::urgent
  D --> E[Hemoglobin denaturation → Heinz bodies]:::outcome
  E --> F[Splenic removal of Heinz bodies]:::outcome
  F --> G[Bite cells on smear]:::outcome
  G --> H[Hemolysis + Hemoglobinuria]:::outcome
  
  I[Oxidative Trigger]:::urgent --> B
  I -->|e.g. TMP-SMX, dapsone, aspirin| J[Acute Hemolytic Crisis]
  J --> K{Remove Trigger?}:::decision
  K -->|Yes| L[Crisis self-resolves in days]:::action
  K -->|No| M[Continued hemolysis]:::urgent
```

## Management of Acute G6PD Crisis

| Step | Intervention | Rationale |
|------|--------------|----------|
| **Immediate** | Discontinue offending drug | Removes oxidative stress; allows RBC recovery |
| **Immediate** | IV hydration (0.9% saline) | Prevents acute kidney injury from hemoglobinuria |
| **Monitoring** | Urinalysis, urine output, serum creatinine | Detect hemoglobinuria and renal dysfunction |
| **Supportive** | Transfusion only if Hb <7 or symptomatic | Avoid unnecessary transfusion; crisis is self-limited |
| **Prevention** | Folic acid 5 mg daily during recovery | Supports RBC regeneration (given AFTER acute phase) |
| **Education** | Avoid triggers: sulfonamides, NSAIDs, fava beans, infections | Prevent future crises |

**Mnemonic: G6PD Crisis Management = DHUM (Discontinue drug, Hydrate, Urine monitor, Manage supportively)**

## Why This Option Is Correct

The four pillars of immediate management are:
1. **Drug discontinuation** — removes the oxidative trigger and allows hemolysis to resolve
2. **Hydration** — prevents acute tubular necrosis from hemoglobin precipitation in renal tubules
3. **Urine monitoring** — detects hemoglobinuria (dark/cola-colored urine) and guides fluid replacement
4. **Observation** — G6PD crises are self-limited; hemolysis stops within 7–10 days if trigger is removed

**Clinical Pearl:** Unlike AIHA (which requires corticosteroids) or hereditary spherocytosis (which may need splenectomy), G6PD hemolysis resolves spontaneously once the oxidative stressor is removed. The patient's reticulocyte count (12%) indicates brisk bone marrow response.

![Hemolytic Anemias diagram](https://mmcphlazjonnzmdysowq.supabase.co/storage/v1/object/public/blog-images/explanation/2623.webp)

Answer

A. Perform hemoglobin electrophoresis and genetic testing for sickle cell trait

Answer

B. Start prednisolone 1 mg/kg/day and arrange splenectomy

Answer

C. Initiate exchange transfusion and folic acid supplementation

Explanation

Clinical Diagnosis

Pathophysiology of G6PD Hemolysis

Management of Acute G6PD Crisis

Why This Option Is Correct

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Step	Intervention	Rationale
Immediate	Discontinue offending drug	Removes oxidative stress; allows RBC recovery
Immediate	IV hydration (0.9% saline)	Prevents acute kidney injury from hemoglobinuria
Monitoring	Urinalysis, urine output, serum creatinine	Detect hemoglobinuria and renal dysfunction
Supportive	Transfusion only if Hb <7 or symptomatic	Avoid unnecessary transfusion; crisis is self-limited
Prevention	Folic acid 5 mg daily during recovery	Supports RBC regeneration (given AFTER acute phase)
Education	Avoid triggers: sulfonamides, NSAIDs, fava beans, infections	Prevent future crises