What is the interpretation of a peripheral blood smear showing erythrocyte abnormalities, normoblasts, atypical lymphocytes, low platelet count with giant platelets, in a 2-month-old boy with positive anti-dengue IgM?

Interpretation of Peripheral Blood Smear in a 2-Month-Old with Dengue

This peripheral blood smear shows findings consistent with dengue infection complicated by hemolysis and bone marrow stress, with thrombocytopenia being the most clinically significant feature requiring close monitoring for progression to dengue hemorrhagic fever (DHF).

Primary Interpretation: Dengue-Associated Hematologic Changes

The constellation of findings—thrombocytopenia with giant platelets, atypical lymphocytes, and normoblasts—is characteristic of dengue virus infection in the acute phase 1, 2, 3.

Thrombocytopenia with Giant Platelets

• The low platelet count with giant platelets indicates both peripheral consumption and compensatory bone marrow response 1, 4.
• Giant (immature) platelets suggest active thrombopoiesis attempting to compensate for peripheral platelet destruction, which occurs through multiple mechanisms in dengue: direct viral infection of platelets, platelet-leukocyte aggregation, anti-platelet antibody-mediated clearance, and endothelial adhesion 1, 5.
• Thrombocytopenia occurs in 66.5% of dengue cases and is more severe and prolonged in DHF compared to classic dengue 3.
• The presence of anti-dengue IgM antibodies can cross-react with platelets, forming platelet-associated immunoglobulins that accelerate platelet clearance and correlate inversely with platelet counts 5.

Atypical Lymphocytes

• Atypical lymphocytes are found in 67% of dengue cases and represent activated lymphocytes responding to viral infection 3.
• Higher numbers of atypical lymphocytes correlate with DHF severity 3.
• This finding, combined with positive anti-dengue IgM, confirms active dengue infection rather than other viral causes 6.

Normoblasts (Nucleated Red Blood Cells)

• The presence of 2 normoblasts per 100 leukocytes indicates bone marrow stress and compensatory erythropoiesis 7.
• In dengue, this reflects either hemolysis (supported by the polychromasia) or bone marrow suppression with attempted recovery 1, 2.
• Dengue virus directly infects hematopoietic progenitors and stromal cells, compromising both megakaryopoiesis and erythropoiesis 1.

Erythrocyte Abnormalities

The polychromasia with hypochromic anisopoikilocytosis (cigar cells, microcytes, target cells) suggests a mixed picture:

• Polychromasia indicates reticulocytosis from hemolysis or blood loss, consistent with microangiopathic hemolytic anemia that can occur in severe dengue 2.
• Hypochromic microcytes and target cells suggest underlying iron deficiency or thalassemia trait, which is common in this age group and geographic regions where dengue is endemic 7.
• Cigar cells (elliptocytes) may indicate hereditary elliptocytosis or iron deficiency 7.

Critical Clinical Implications

Risk Stratification for Dengue Hemorrhagic Fever

This patient requires close monitoring for progression to DHF based on the following high-risk features:

• Thrombocytopenia is a warning sign for DHF and occurs more severely in DHF grades III-IV (dengue shock syndrome) 2.
• Patients with excessive platelet depletion are at risk for massive bleeding from endothelial dysfunction, thrombocytopenia, and platelet dysfunction 2.
• Monitor for hemoconcentration (rising hematocrit), which combined with thrombocytopenia defines DHF 6, 2.

Immediate Management Priorities

Patients with clinically suspected dengue should receive appropriate management to monitor and treat shock and hemorrhage 6:

• Serial platelet counts and hematocrit monitoring every 6-12 hours during the critical phase (days 3-7 of illness) 6.
• Assess for bleeding manifestations: petechiae, purpura, mucosal bleeding, or internal hemorrhage 2.
• Monitor for plasma leakage: pleural effusion, ascites, hypoalbuminemia 6, 2.
• Maintain adequate hydration to prevent shock from plasma leakage 6.

Coagulation Assessment

In a 2-month-old with severe thrombocytopenia, coagulation studies (PT, aPTT, fibrinogen, D-dimers) should be obtained to evaluate for disseminated intravascular coagulation (DIC) 7:

• DIC is commonly found in complicated dengue patients with prolonged or repeated shock 2.
• Variable reductions in coagulation factors (prothrombin, V, VII, VIII, IX, X) may occur in DHF 2.
• Normal coagulation studies would help exclude DIC and support isolated dengue-associated thrombocytopenia 8.

Differential Considerations in This Age Group

Excluding Alternative Diagnoses

The positive anti-dengue IgM makes dengue the primary diagnosis, but the erythrocyte abnormalities warrant additional consideration 7:

• Iron deficiency anemia is extremely common at 2 months of age and could explain the hypochromic microcytes and target cells 7.
• Hereditary hemolytic anemias (thalassemia trait, hereditary elliptocytosis) should be evaluated after acute dengue resolves 7.
• Bone marrow examination is NOT indicated in this typical dengue presentation with isolated thrombocytopenia and normal physical examination aside from bleeding manifestations 6, 7.

When Bone Marrow Would Be Indicated

Bone marrow examination would only be necessary if 6, 7:

• Fever, bone/joint pain, or systemic symptoms beyond typical dengue 6, 7.
• Lymphadenopathy or hepatosplenomegaly (beyond mild hepatomegaly sometimes seen in dengue) 6, 7.
• Pancytopenia rather than isolated thrombocytopenia 7.
• Failure to recover platelet counts during convalescence (1-2 weeks post-defervescence) 2.

Common Pitfalls to Avoid

• Do not assume thrombocytopenia alone requires platelet transfusion—most dengue patients recover spontaneously with supportive care, and prophylactic platelet transfusion is not indicated unless active bleeding occurs 6, 2.
• Do not overlook the underlying iron deficiency or hemoglobinopathy suggested by the erythrocyte morphology—this should be evaluated after dengue resolves 7.
• Do not miss the critical phase (days 3-7) when plasma leakage and shock are most likely to occur, requiring intensive monitoring 6, 2.
• Do not use aspirin or NSAIDs for fever management, as these impair platelet function and increase bleeding risk 7.

Follow-Up Strategy

After recovery from acute dengue (normalization of platelet count and hematocrit within 1-2 weeks post-defervescence) 2:

• Repeat complete blood count to assess for persistent anemia 7.
• Evaluate iron studies (ferritin, iron, TIBC) to diagnose iron deficiency 7.
• Consider hemoglobin electrophoresis if thalassemia trait is suspected based on persistent microcytosis with normal iron studies 7.
• Family history of anemia or hemolytic disorders should prompt evaluation for hereditary conditions 7.