What are the causes of teardrop red blood cells?

Causes of Teardrop Red Blood Cells (Dacryocytes)

Teardrop-shaped red blood cells (dacryocytes) are most classically associated with primary myelofibrosis and bone marrow infiltrative disorders, but are also commonly seen in autoimmune hemolytic anemia, microangiopathic hemolytic anemia, and conditions with extramedullary hematopoiesis in the spleen. 1, 2

Primary Causes: Bone Marrow Disorders

Myelofibrosis and Myeloproliferative Disorders

• Primary myelofibrosis (agnogenic myeloid metaplasia) is the classic cause of dacryocytes, characterized by bone marrow fibrosis, leukoerythroblastosis, extramedullary hematopoiesis, and splenomegaly 1, 3, 4
• Myelodysplastic syndromes produce dacryocytes as part of dysplastic red cell morphology, including anisocytosis, poikilocytosis, and other abnormal shapes 1
• The teardrop shape results from mechanical deformation as abnormal red cells attempt to exit fibrotic bone marrow through narrowed sinusoids 3

Malignant Bone Marrow Infiltration

• Leukemias, lymphomas, and metastatic solid tumors infiltrating the bone marrow cause dacryocytes by disrupting normal marrow architecture 1, 5
• These infiltrative processes create a leukoerythroblastic blood picture with nucleated red cells and immature white cells alongside dacryocytes 1, 4

Hemolytic Anemias: An Underrecognized Cause

Autoimmune Hemolytic Anemia (AIHA)

• Dacryocytes are present in 89% of AIHA cases, representing a common but underappreciated morphologic feature 2
• The mechanism involves splenic extramedullary hematopoiesis and mechanical deformation of antibody-coated red cells passing through the spleen 6
• Splenectomy or resolution of splenomegaly results in disappearance of dacryocytes in AIHA patients 6

Microangiopathic Hemolytic Anemia (MAHA)

• Dacryocytes appear in 91% of MAHA cases, alongside schistocytes (fragmented red cells) 2
• The dacryocyte count is statistically significantly higher in hemolytic anemias compared to controls (p<0.0001) 2
• MAHA conditions include thrombotic thrombocytopenic purpura, hemolytic uremic syndrome, and disseminated intravascular coagulation 1

Role of the Spleen and Extramedullary Hematopoiesis

Splenic Contribution to Dacryocyte Formation

• Splenectomy in myelofibrosis patients reduces dacryocyte counts by approximately fourfold (from average 42 per 1,000 RBCs to 11 per 1,000 RBCs, p<0.001) 3
• Extramedullary hematopoiesis in the spleen creates abnormal release of incompletely formed red cells that assume teardrop shapes 6, 3
• The spleen's role is independent of bone marrow fibrosis severity, as evidenced by dacryocyte reduction even when marrow fibrosis persists post-splenectomy 3

Reversibility with Treatment

Response to Chemotherapy

• Effective chemotherapy in myelofibrosis can reverse the leukoerythroblastic picture and reduce dacryocyte counts 7
• This reversibility indicates that dacryocytes reflect active disease processes rather than permanent structural damage 7

Diagnostic Algorithm for Dacryocytes

When dacryocytes are identified on peripheral blood smear:

1. Assess for bone marrow pathology:

   • Order bone marrow biopsy if age >60 years, systemic symptoms present, or abnormal blood counts beyond isolated findings 1, 8
   • Look specifically for fibrosis, dysplasia, or infiltrative disease 1

2. Evaluate for hemolytic anemia:

   • Check reticulocyte count, lactate dehydrogenase, haptoglobin, indirect bilirubin 1
   • Perform direct antiglobulin test (Coombs test) to identify AIHA 6, 2
   • Examine smear for schistocytes suggesting MAHA 1, 2

3. Assess splenic involvement:

   • Physical examination for splenomegaly 1, 6
   • Imaging if clinical splenomegaly suspected 5

4. Consider secondary causes:

   • Review for iron deficiency (microcytic hypochromic cells with dacryocytes) 1
   • Evaluate for thalassemia or other hemoglobinopathies 1

Critical Clinical Pearls

• Do not assume dacryocytes always indicate myelofibrosis—they are equally common in AIHA and MAHA, conditions with vastly different prognoses and treatments 2
• The presence of other dysplastic features (pseudo-Pelger-Huët cells, hypogranular neutrophils, giant platelets) alongside dacryocytes strongly suggests myelodysplastic syndrome 1
• In patients with splenomegaly and dacryocytes but without bone marrow fibrosis, consider AIHA with extramedullary hematopoiesis 6
• Dacryocyte counts do not correlate with spleen size in myelofibrosis, but splenectomy consistently reduces them 3
• Failure to recognize hemolytic anemia as a cause of dacryocytes can delay appropriate immunosuppressive therapy in AIHA or plasma exchange in thrombotic microangiopathy 6, 2