Cardiac Arrest as the Initial Manifestation of Profound Folate-Deficiency Megaloblastic Anemia in a Chronic Alcohol User: A Case Report

Abstract:

Profound anemia severe enough to precipitate cardiac arrest is an exceptionally uncommon presentation in current clinical practice. We describe a middle-aged man with long-standing alcohol dependence who developed circulatory collapse following a short history of diarrheal illness and poor oral intake. On arrival, he was in cardiac arrest and achieved return of spontaneous circulation (ROSC) after advanced resuscitative measures. Laboratory evaluation demonstrated profound macrocytic anemia with a hemoglobin concentration of 2.3 g/dL. Peripheral blood smear showed macro-ovalocytes, hypersegmented neutrophils, and Howell-Jolly bodies, while biochemical investigations confirmed folate deficiency with normal vitamin B12 levels. Following intensive care management, blood transfusion, folate supplementation, vitamin replacement, and supportive therapy, the patient demonstrated progressive clinical and hematological recovery.

Conclusion:Consider profound anemia as a reversible cause of cardiac arrest; chronic alcoholism predisposes to folate deficiency; peripheral smear remains diagnostically valuable; prompt transfusion and nutritional correction improve outcomes.

Keywords: Profound anemia; Cardiac arrest; Folate deficiency; Megaloblastic anemia; Macrocytic anemia; Chronic alcohol dependence; Return of spontaneous circulation (ROSC); Blood transfusion; Nutritional deficiency.

Introduction:

Megaloblastic anemia is characterized by ineffective erythropoiesis resulting from impaired DNA synthesis, most frequently due to vitamin B12 or folate deficiency. Chronic alcohol consumption is a well-recognized risk factor for folate deficiency because of inadequate dietary intake, impaired intestinal absorption, diminished hepatic stores, and altered folate metabolism.

Case Summary:

Middle-aged chronic alcohol user with 10 days of diarrhea, generalized weakness and poor intake collapsed en route to hospital. ACLS achieved ROSC. Post-ROSC examination revealed shock requiring vasopressors and mechanical ventilation with marked pallor. Hb 2.3 g/dL, MCV >100 fL, WBC 17,000/mm3, platelets 150,000/mm3. Peripheral smear showed macro-ovalocytes, hypersegmented neutrophils and Howell-Jolly bodies. Reticulocyte production index was low. Serum folate was low with normal vitamin B12. LDH and indirect bilirubin were elevated. Iron studies, Coombs test, occult blood and cultures were negative. ECG showed sinus tachycardia; echocardiography demonstrated preserved ventricular function.

Diagnosis:

Severe folate-deficiency megaloblastic anemia causing profound tissue hypoxia leading to cardiac arrest, post-cardiac arrest syndrome, chronic alcoholism and acute diarrheal illness with dehydration.

Management:

The patient was managed according to Advanced Cardiac Life Support guidelines and return of spontaneous circulation achieved within 7 mins. Patient was received in intensive care after return of spontaneous circulation. Treatment included packed red blood cell transfusions, intravenous vitamin B12, thiamine, oral folate, intravenous fluids, correction of electrolyte abnormalities, vasopressor support, nutritional support, and treatment to prevent alcohol withdrawal. The patient’s condition gradually improved, with a steady increase in hemoglobin level and good neurological recovery. Patient got extubated to room air. He was discharged on oral folic acid 5 mg once daily for four months, with advice to stop alcohol intake, maintain a healthy diet, and attend regular follow-up with complete blood count monitoring.

Discussion:

Approach to anemia – single lineage involvement then calculate reticulocyte production index.  RPI is < 2.5 points towards hypoproliferative anemia. MCV > 100 fl means macrocytosis. Iron studies should be done to rule out concurrent iron deficiency anemia. Macrocytosis can be megaloblastic anemia or non megaloblastic anemia which can be confirmed by peripheral smear.

Peripheral smear – Megaloblasts are large erythroid precussors with immature chromatin formation, hypersengmented neutrophils, anisopoikilocytosis, normal reticulocytes (RPI < 2.5),pancytopenia, dyserthyropoisis – cabot ring, basophilic stippling, howell jolly bodies.

Causes of macrocytosis with megaloblastic

• B12 deficiency
• Folate deficiency(methotrexate)
• Drugs directly inhibiting DNA synthesis – cytarabine, 6 mercaptourine, hydroxyurea
• Thiamine deficiency
• Orotic aciduria

Causes of macrocytosis with normoblasts –

Hemolysis, post bleeding, alcoholism, liver disease, aplastic anemia, MDS, hypothyroidism, COPD, scurvy

Mechanisms of folate deficiency in chronic alcoholism

1. Poor dietary intake (most common mechanism)
   • Alcohol-dependent patients often consume diets deficient in fresh vegetables, fruits, legumes, and fortified cereals.
   • Calories are frequently derived predominantly from alcohol rather than nutritious food.
   • Folate stores are relatively small (approximately 2–4 months), so deficiency develops quickly with inadequate intake.
2. Impaired intestinal absorption
   • Ethanol directly damages the intestinal mucosa, especially the proximal jejunum, where folate absorption occurs.
   • Alcohol inhibits the proton-coupled folate transporter (PCFT), reducing intestinal folate uptake.
   • Chronic alcohol exposure causes villous atrophy and decreased brush-border function.
3. Reduced hepatic storage
   • The liver stores nearly half of the body’s folate.
   • Chronic alcohol use causes hepatic steatosis, alcoholic hepatitis, and cirrhosis, which markedly reduce hepatic folate storage capacity.
   • Consequently, folate depletion occurs rapidly during periods of poor intake.
4. Impaired enterohepatic circulation
   • Normally, folate is secreted into bile and efficiently reabsorbed in the intestine.
   • Alcohol disrupts this enterohepatic recycling, increasing net folate loss.
5. Increased urinary folate excretion
   • Acute and chronic alcohol consumption increase renal excretion of folate.
   • This contributes further to depletion of body stores.
6. Impaired folate metabolism
   • Ethanol interferes with hepatic conversion of folate into its active forms, particularly tetrahydrofolate (THF) derivatives.
   • Reduced availability of active folate impairs one-carbon transfer reactions essential for DNA synthesis.
7. Increased folate requirement
   • Chronic inflammation, recurrent infections, liver regeneration, and alcohol-induced oxidative stress increase cellular folate demand.
   • Deficiency develops when increased requirements are not matched by intake.

Mechanism of cardiac arrest in profound anemia

Profound anemia markedly reduces the oxygen-carrying capacity of blood, resulting in inadequate tissue oxygen delivery despite compensatory increases in cardiac output. As anemia worsens, myocardial oxygen demand exceeds supply, leading to myocardial ischemia, impaired cardiac contractility, and electrical instability. Severe tissue hypoxia also promotes metabolic acidosis, lactate accumulation, and electrolyte disturbances, which further increase the risk of malignant cardiac arrhythmias. When compensatory cardiovascular mechanisms become exhausted, progressive circulatory failure ensues, culminating in hypotension, cardiogenic collapse, pulseless electrical activity, ventricular arrhythmias, or asystole, ultimately resulting in cardiac arrest if prompt correction of the anemia and resuscitative measures are not instituted.

Treatment of Folate Deficiency

Folic Acid

• Initial treatment
  • Folic acid 5 mg orally once daily.
  • If oral therapy is not feasible initially (e.g., critically ill or poor gastrointestinal absorption), intravenous folic acid may be administered until oral intake is possible.
• Duration
  • Continue 5 mg daily for approximately 4 months, which is sufficient for complete replacement of body folate stores in most patients.
  • In patients with persistent risk factors (e.g., chronic alcoholism, malabsorption, chronic hemolysis, dialysis), long-term maintenance therapy of 1–5 mg daily may be required.

Vitamin B12

• • • Always exclude vitamin B12 deficiency before initiating folate alone, as folate can correct anemia while allowing irreversible neurological complications of B12 deficiency to progress.
    • If B12 deficiency cannot be excluded immediately, administer vitamin B12 concurrently until laboratory results are available.

Thiamine

• • • In chronic alcohol users:
      • Thiamine 100–200 mg/day (higher doses if Wernicke encephalopathy is suspected).
      • Administer thiamine before glucose-containing fluids whenever possible.

Nutritional Management

• • • High-protein, calorie-adequate diet.
    • Folate-rich foods:
      • Green leafy vegetables
      • Legumes
      • Citrus fruits
      • Liver
      • Fortified cereals
    • Complete alcohol cessation with counseling and de-addiction support.

Expected Hematologic Response

• • • Reticulocytosis: 5–7 days.
    • Hemoglobin rise: Begins within 1–2 weeks.
    • Normalization of hemoglobin: Usually within 6–8 weeks, depending on the severity of anemia and adequacy of transfusion.
    • Normalization of MCV: May take 2–4 months.

Conclusion:

Severe anemia below 3 g/dL can critically impair oxygen delivery and rarely culminate in cardiac arrest. Alcohol-related folate deficiency together with diarrheal illness likely precipitated decompensation. Early recognition, transfusion and vitamin replacement were lifesaving. Consider profound anemia as a reversible cause of cardiac arrest; chronic alcoholism predisposes to folate deficiency; peripheral smear remains diagnostically valuable; prompt transfusion and nutritional correction improve outcomes.

Dr Rajasri
Critical Care Medicine PG,
Kauvery Hospital, Chennai.

Dr Arun Sathish
Consultant Critical Care Medicine,
Kauvery Hospital, Chennai.