What is the meaning of poikilocytosis in a patient with anemia or blood disorders?

Poikilocytosis: Definition and Clinical Significance

Poikilocytosis refers to the presence of abnormally shaped red blood cells on peripheral blood smear, indicating underlying red blood cell membrane defects, hemolysis, bone marrow disorders, or systemic disease. 1

Definition and Laboratory Recognition

• Poikilocytosis describes the morphological abnormality where red blood cells display various abnormal shapes rather than the normal biconcave disc configuration 1
• While occasional nonspecific poikilocytes appear in most normal blood smears, dominance of one or more specific poikilocyte forms typically indicates a specific anemia or organ system disease 2
• Poikilocytosis is commonly accompanied by anisocytosis (variation in red blood cell size) in anemic patients 3

Specific Poikilocyte Forms and Their Clinical Associations

Round Poikilocytes

• Spherocytes suggest hereditary spherocytosis, immune hemolytic anemia, or severe burns 1, 2
• Stomatocytes are most commonly associated with acute alcoholism 2
• Target cells indicate liver disease, hemoglobinopathies, or post-splenectomy states 2

Elongated Poikilocytes

• Ovalocytes and elliptocytes point toward hereditary elliptocytosis or iron deficiency anemia 2, 4
• Teardrop cells classically reflect myelofibrosis, "spent" polycythemia vera, or severe marrow infiltration 1, 2
• Sickle cells are pathognomonic for sickle cell disease 2

Fragmented Poikilocytes

• Schistocytes (fragmented red cells) are hallmark findings in thrombotic microangiopathic anemias, particularly thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS) 5
• Schistocytes above 1% can also occur with metastatic carcinoma, chronic renal failure, and mechanical heart valves 5

Clinical Context in Myelodysplastic Syndromes

• In myelodysplastic syndromes (MDS), poikilocytosis appears alongside other red cell abnormalities including dimorphic erythrocytes, polychromasia, hypochromasia, megalocytes, basophilic stippling, nucleated erythroid precursors, tear drop cells, ovalocytes, and fragmentocytes 1
• The presence of poikilocytosis in MDS reflects dysplastic erythropoiesis and ineffective red blood cell production 1

Diagnostic Approach When Poikilocytosis Is Present

• Initial laboratory evaluation should include complete blood count with indices, reticulocyte count, peripheral blood smear examination, lactate dehydrogenase (LDH), haptoglobin, and bilirubin levels 5
• Direct antiglobulin test (DAT) helps differentiate immune from non-immune causes of hemolysis when poikilocytosis suggests hemolytic anemia 5
• If schistocytes are present, immediately order ADAMTS13 activity level and inhibitor titer, as thrombotic microangiopathy requires urgent intervention 5

Hereditary Conditions Causing Severe Poikilocytosis

• Hereditary pyropoikilocytosis presents in neonates with marked poikilocytosis, microcytosis, hyperbilirubinemia requiring exchange transfusions or phototherapy, and nucleated red blood cells 6
• Homozygous hereditary elliptocytosis causes severe hemolytic anemia with marked erythrocyte fragmentation and elliptocytic poikilocytosis, related to deficiency of skeletal membrane protein band 4.1 4
• Red blood cell membrane analysis should be performed in neonates with hemolytic anemia and poikilocytosis when conventional diagnostic examination is noncontributory 6

Common Pitfalls

• Do not dismiss poikilocytosis as a nonspecific finding—the specific morphology pattern provides critical diagnostic clues to the underlying disorder 2
• In patients with schistocytes, do not delay plasma exchange while awaiting ADAMTS13 results if TTP is strongly suspected clinically, as mortality increases with delayed treatment 5
• Normal ferritin, B12, and folate levels with poikilocytosis should prompt consideration of hemolysis, membrane defects, or bone marrow disorders rather than nutritional deficiencies 7