CBC | Approach to Anemia

The video introduces red blood cell disorders, focusing on anemia and polycythemia. It emphasizes a systematic approach to diagnosing anemia by using a CBC. Anemia is defined as a low number of red blood cells, leading to low hemoglobin and hematocrit. The primary step in differentiating types of anemia is analyzing the reticulocyte index. A reticulocyte index less than 2% indicates decreased red blood cell production, while an index greater than 2% suggests increased destruction or loss.

This section delves into anemias caused by decreased production, starting with classification based on Mean Corpuscular Volume (MCV). Microcytic anemia (MCV < 80 fL) differentials include iron deficiency anemia, anemia of chronic disease, thalassemia, and sideroblastic anemia. Diagnostic tests involve RDW, red blood cell count, Mincers index, iron studies (ferritin and transferrin saturation), and peripheral blood smear. Specific markers for each type are discussed, such as high RDW and low ferritin for iron deficiency, high ferritin for anemia of chronic disease, and a low Mincers index with basophilic stippling for thalassemia. Sideroblastic anemia is characterized by high RDW, sideroblasts on a peripheral smear, and often linked to lead poisoning or certain medications, requiring a bone marrow biopsy for confirmation.

Normocytic anemia (MCV 80-100 fL) can result from early iron, B12, or folate deficiencies. Other causes include thyroid, liver, and kidney dysfunctions. Initial tests include iron studies, B12, and folate levels. If B12 or folate levels are borderline, methylmalonic acid and homocysteine levels can differentiate. Assessment of thyroid, liver, and kidney function is crucial. If all these systems are normal but the reticulocyte index is extremely low (<0.1%) alongside pancytopenia, a bone marrow biopsy may be necessary to diagnose aplastic anemia, myelodysplastic syndrome, or pure red cell aplasia.

Macrocytic anemia (MCV > 100 fL) is primarily linked to B12 and folate deficiencies, but also thyroid and liver issues, certain medications (e.g., methotrexate, hydroxyurea), and alcohol abuse. Initial tests involve B12 and folate levels. Peripheral blood smear analysis can reveal megaloblastic features (hypersegmented neutrophils), common in B12 and folate deficiencies. Non-megaloblastic macrocytic anemia often points to liver disease (acanthocytes on smear), hypothyroidism, or certain medications. A bone marrow biopsy might be considered if pancytopenia is present, suggesting myelodysplastic syndrome.

Eight case studies are presented to apply the systematic approach for anemias caused by decreased production. Each case guides through determining reticulocyte index, MCV, differential diagnoses, and specific confirmatory tests. Cases covered include iron deficiency anemia due to heavy menstrual periods, anemia of chronic disease in SLE, sideroblastic anemia from isoniazid treatment, thalassemia, macrocytic anemia from medications (phenytoin, Bactrim), liver disease-related macrocytic anemia (cirrhosis), anemia of chronic kidney disease, and aplastic anemia post-chemotherapy.

This segment focuses on anemias with increased red blood cell destruction or loss, identifiable by a reticulocyte index greater than 2%. The initial step is to confirm hemolysis using hemolytic labs: elevated LDH, elevated indirect bilirubin, and low haptoglobin. Hemoglobinuria may also be present. Assessment of the spleen via ultrasound for splenomegaly can indicate hypersplenism. The next step is to determine if hemolysis is autoimmune by performing a Direct Antiglobulin Test (DAT) or Coombs test. A positive DAT indicates autoimmune hemolytic anemia, further sub-classified into warm (IgG and complement positive) or cold (complement positive, IgG negative).

If the DAT is negative, non-autoimmune causes are explored, categorized as intrinsic (red blood cell defect) or extrinsic (external factors). Intrinsic causes include enzyme deficiencies (G6PD deficiency, identified by bite cells/Heinz bodies and low enzyme levels), hemoglobinopathies (sickle cell anemia, identified by sickle cells and hemoglobin electrophoresis), and membrane problems (hereditary spherocytosis, identified by spherocytes and osmotic fragility test; paroxysmal nocturnal hemoglobinuria, identified by venous clots, dark urine, and flow cytometry). Extrinsic causes involve microangiopathic hemolytic anemias (MAHA) like DIC, TTP, HUS, HELLP syndrome, and mechanical heart valves, all characterized by schistocytes and often low platelets. Infections like malaria and babesiosis are also considered, with specific peripheral blood smear findings (inclusions for malaria, Maltese cross for babesiosis).

Blood loss is diagnosed when hemolytic labs are normal, indicating no destruction. Clinical signs of bleeding (pallor, dry mucous membranes, hypotension, tachycardia) and patient history (recent surgery, anticoagulants, frequent blood draws) are crucial. Common sources of blood loss include frequent blood draws (iatrogenic), surgical procedures, and gastrointestinal (GI) bleeds. GI bleeds can manifest as hematemesis, melena, or hematochezia, requiring endoscopy (EGD for upper GI) or colonoscopy (for lower GI). Retroperitoneal bleeds, often associated with trauma or anticoagulation, can be severe and detected via CTA of the abdomen and pelvis.

Multiple case studies demonstrate the diagnostic algorithm for increased destruction/loss anemias. Cases include retroperitoneal bleed after thrombectomy (blood loss), warm autoimmune hemolytic anemia secondary to CLL (autoimmune destruction), cold autoimmune hemolytic anemia due to mycoplasma pneumonia (autoimmune destruction), G6PD deficiency after fava bean consumption (intrinsic destruction), sickle cell anemia (hemoglobinopathy), paroxysmal nocturnal hemoglobinuria, hereditary spherocytosis, malaria (infectious destruction), babesiosis (infectious destruction), DIC (MAHA), and hypersplenism due to non-Hodgkin's lymphoma (extrinsic destruction with splenic involvement).