Can a vitamin B12 (B12) deficiency affect platelet levels and lead to thrombocytopenia?

Vitamin B12 Deficiency and Thrombocytopenia

Yes, vitamin B12 deficiency can cause thrombocytopenia and affect platelet levels, sometimes severely enough to mimic thrombotic microangiopathy. This relationship is clinically significant and requires prompt recognition and treatment to prevent serious complications.

Pathophysiological Mechanism

B12 deficiency affects platelet production and function through several mechanisms:

• Ineffective hematopoiesis: B12 is essential for DNA synthesis and cell division. Its deficiency impairs the maturation of megakaryocytes in the bone marrow, leading to reduced platelet production 1.

• Hyperhomocysteinemia: Severe B12 deficiency causes elevated homocysteine levels, which can:

  • Promote a prothrombotic state
  • Cause endothelial dysfunction
  • Lead to platelet activation and aggregation 2, 3

• Pseudo-thrombotic microangiopathy: In severe cases, B12 deficiency can present with:

  • Thrombocytopenia
  • Schistocytosis (fragmented red blood cells)
  • Elevated lactate dehydrogenase
  • Hemolytic anemia 4

Clinical Presentation

The hematological manifestations of B12 deficiency can range from mild to severe:

• Mild cases: Isolated thrombocytopenia may be the only finding 1
• Moderate cases: Thrombocytopenia with macrocytic anemia
• Severe cases: Pancytopenia with features mimicking thrombotic thrombocytopenic purpura (TTP) 4, 5, 6

Diagnostic Approach

When evaluating thrombocytopenia, consider B12 deficiency especially when:

1. Laboratory findings include:

   • Low platelet count
   • Macrocytic anemia (may be masked by concurrent conditions like thalassemia) 6
   • Elevated LDH
   • Elevated homocysteine and/or methylmalonic acid

2. Important diagnostic tests:

   • Serum B12 level (levels below 258 pmol/L with elevated homocysteine or methylmalonic acid indicate metabolic B12 deficiency) 2
   • Complete blood count with peripheral smear
   • Homocysteine and methylmalonic acid levels (more sensitive markers)

Treatment Approach

For B12 deficiency-related thrombocytopenia:

1. Immediate treatment:

   • Vitamin B12 supplementation: 1000-2000 μg daily sublingual or IM 7
   • For severe deficiency with neurological symptoms: 1000 μg intramuscularly daily for one week, then weekly until improvement, then monthly 7

2. Monitoring response:

   • Platelet counts typically improve within days to weeks of starting B12 therapy
   • Complete resolution may take 4-8 weeks

3. Important caution:

   • Avoid misdiagnosing as primary TTP, which could lead to unnecessary plasma exchange therapy 4, 5
   • Never administer folic acid before treating B12 deficiency as this may mask hematologic manifestations while allowing neurological damage to progress 7

Special Considerations

• Thrombotic risk: Severe B12 deficiency with hyperhomocysteinemia increases thrombotic risk despite thrombocytopenia 3

• Diagnostic pitfalls:

  • B12 deficiency may present with isolated thrombocytopenia without the classic macrocytic anemia 1
  • In some cases, B12 deficiency-related thrombocytopenia may initially respond to plasma exchange due to B12 present in donor plasma 6

• Metabolic B12 deficiency: This condition (serum B12 below 258 pmol/L with elevated homocysteine or methylmalonic acid) is often missed because serum B12 in the normal range is incorrectly accepted as ruling out B12 deficiency 2

Long-term Management

For patients with confirmed B12 deficiency causing thrombocytopenia:

• Identify and address the underlying cause (pernicious anemia, malabsorption, dietary deficiency)
• Provide maintenance B12 therapy based on the cause:
  • Pernicious anemia: lifelong monthly B12 injections (1000 μg)
  • Ileal resection >20 cm: 1000 μg intramuscularly monthly for life 7
  • Vegans/vegetarians: daily oral B12 supplementation of 250-350 μg 7

Regular monitoring of complete blood count and B12 levels is essential to ensure adequate treatment and prevent recurrence of thrombocytopenia.