What are the causes and treatments of low Red Blood Cell (RBC) count, hemoglobin, hematocrit, and platelets?

Causes and Treatments of Low RBC Count, Hemoglobin, Hematocrit, and Platelets

Low red blood cell count, hemoglobin, hematocrit, and platelets are most commonly caused by bone marrow dysfunction, nutritional deficiencies, or increased destruction/consumption of blood cells, requiring targeted treatment based on the underlying etiology. 1

Common Causes of Low Blood Cell Parameters

Morphologic Classification of Anemia

• Microcytic anemia (MCV <80 fL): Most commonly caused by iron deficiency; other causes include thalassemia, anemia of chronic disease, and sideroblastic anemia 1
• Normocytic anemia (MCV 80-100 fL): May be caused by hemorrhage, hemolysis, bone marrow failure, anemia of chronic inflammation, or renal insufficiency 1
• Macrocytic anemia (MCV >100 fL): Usually megaloblastic, indicating vitamin B12 or folate deficiency; non-megaloblastic causes include alcoholism, myelodysplastic syndrome (MDS), and certain drugs 1

Kinetic Classification of Anemia

• Decreased production: Indicated by low reticulocyte index (RI <1.0), suggesting iron deficiency, vitamin B12/folate deficiency, aplastic anemia, or bone marrow dysfunction from cancer or cancer therapy 1
• Increased destruction/loss: Indicated by high RI (>2.0), suggesting blood loss or hemolysis 1, 2

Causes of Thrombocytopenia

• Decreased production: Bone marrow failure, myelodysplastic syndromes, leukemia, chemotherapy, radiation 3, 4
• Increased destruction: Immune thrombocytopenia (ITP), disseminated intravascular coagulation (DIC), thrombotic thrombocytopenic purpura (TTP) 3, 4
• Sequestration: Hypersplenism, liver disease 3, 4

Specific Disease Entities Causing Pancytopenia

• Myelodysplastic syndromes (MDS): Characterized by ineffective hematopoiesis with anemia (most common), neutropenia, and thrombocytopenia 1
• Leukemia: Malignant cells infiltrate bone marrow and suppress normal blood cell production 1
• Aplastic anemia: Severe bone marrow failure affecting all cell lines 1
• Sepsis: Can cause consumption coagulopathy with decreased platelets and anemia 1

Diagnostic Approach

Initial Evaluation

• Complete blood count (CBC) with differential and reticulocyte count 1
• Peripheral blood smear examination for morphologic abnormalities 1
• Iron studies: serum ferritin, transferrin saturation, total iron binding capacity 1
• Vitamin B12 and folate levels for macrocytic anemia 1
• Kidney function tests (BUN, creatinine) to assess for renal causes 1

Additional Testing Based on Clinical Suspicion

• Hemolysis evaluation: haptoglobin, LDH, indirect bilirubin, Coombs test 2
• Bone marrow aspiration and biopsy for suspected bone marrow disorders 1
• Coagulation studies (PT, PTT, fibrinogen, D-dimer) if DIC is suspected 1

Treatment Approaches

Treatment of Anemia

• Iron deficiency anemia: Oral or IV iron supplementation; investigate and treat underlying cause (e.g., gastrointestinal bleeding) 1
• Vitamin B12/folate deficiency: B12 injections or high-dose oral supplementation; folate supplementation 1
• Anemia of chronic kidney disease: Erythropoiesis-stimulating agents (ESAs) when hemoglobin <10 g/dL 1
• Anemia of chronic disease/inflammation: Treat underlying condition; consider ESAs in selected cases 1
• Hemolytic anemia: Treatment depends on cause (e.g., steroids for autoimmune hemolytic anemia) 2
• MDS-related anemia: ESAs, lenalidomide (for 5q- syndrome), or hypomethylating agents; consider transfusions for symptomatic patients 1

Treatment of Thrombocytopenia

• Immune thrombocytopenia: Corticosteroids, intravenous immunoglobulin, thrombopoietin receptor agonists, or splenectomy in refractory cases 3
• Drug-induced thrombocytopenia: Discontinuation of offending medication 4
• DIC-related thrombocytopenia: Treatment of underlying condition (e.g., sepsis) 1
• MDS-related thrombocytopenia: Consider thrombopoietin receptor agonists in clinical trials; platelet transfusions for severe thrombocytopenia with bleeding 1

Transfusion Therapy

• Red blood cell transfusion: Generally indicated when hemoglobin <7 g/dL in stable patients; higher threshold (8-10 g/dL) may be appropriate in patients with cardiovascular disease or active bleeding 1
• Platelet transfusion: Consider prophylactic transfusion when platelet count <10,000/mm³ in non-bleeding patients; <20,000/mm³ with significant bleeding risk; <50,000/mm³ for active bleeding, surgery, or invasive procedures 1

Special Considerations

• Iron chelation therapy: Consider in patients requiring chronic transfusions to prevent iron overload 1
• Hematocrit and bleeding risk: Low hematocrit can contribute to bleeding tendency in thrombocytopenic patients by affecting platelet margination 1, 5, 6
• Temperature effects: Hypothermia can worsen coagulopathy by decreasing both platelet and coagulation enzyme activities 1
• Acidosis: Even mild acidosis can compromise coagulation function, particularly in the presence of hypothermia 1

Management Pitfalls to Avoid

• Overlooking occult bleeding: Always consider gastrointestinal blood loss in patients with iron deficiency anemia 1
• Missing hemolysis: Reticulocytosis with anemia suggests hemolysis that requires specific evaluation 2
• Inappropriate transfusions: Avoid transfusing based solely on laboratory values without considering clinical status 1
• Neglecting nutritional causes: Ensure evaluation of iron, B12, and folate status in all anemic patients 1
• Failing to investigate pancytopenia: Multiple cell line deficiencies warrant bone marrow evaluation 1