What is the next step in managing a 27-year-old female patient with a 1-2 month history of abdominal and back pain, who has developed severe anemia (hemoglobin (Hgb) drop from 11.7 to 8.6, hematocrit (Hct) drop from 40.2 to 32.1) and thrombocytosis (platelet count increase from 588 to 655) over the past month?

Urgent Diagnostic Workup and Management

This patient requires immediate comprehensive evaluation for acute blood loss, hemolysis, or bone marrow pathology, with urgent imaging to identify occult hemorrhage given the severe anemia (Hgb drop of 3.1 g/dL) combined with thrombocytosis and neutrophilia in the setting of persistent abdominal and back pain. 1, 2

Immediate Diagnostic Priorities

Rule Out Acute Hemorrhage First

• Obtain CT abdomen/pelvis with IV contrast immediately to evaluate for occult intra-abdominal or retroperitoneal bleeding, as abdominal pain with documented hematocrit drop almost certainly indicates major hemorrhage, and CT can definitively diagnose hemorrhage by demonstrating mass lesions with characteristic attenuation coefficients 3

• Perform stool guaiac testing to evaluate for gastrointestinal bleeding, as this is a critical first step when iron deficiency or acute blood loss is suspected 1, 2

• Assess for gynecologic bleeding sources given the patient's age and sex, as uterine pathology (fibroids, adenomyosis) can cause severe anemia with reactive thrombocytosis 4

Essential Laboratory Workup

Order the following tests immediately: 1, 2

• Reticulocyte count and reticulocyte index - This is the single most important test to determine if anemia reflects decreased production (low reticulocyte index <2.0) or increased destruction/loss (high reticulocyte index >2.0) 1, 2

• Complete iron studies - serum ferritin, transferrin saturation, serum iron, and TIBC to identify absolute or functional iron deficiency 1, 2

• Hemolysis markers - LDH, haptoglobin, indirect and direct bilirubin, and direct antiglobulin test (Coombs) to evaluate for hemolytic process 2, 5

• Peripheral blood smear - to assess for schistocytes (suggesting microangiopathic hemolysis), abnormal white cells, or platelet clumping 1, 2

• Inflammatory markers - CRP and ESR, as thrombocytosis with neutrophilia suggests reactive process from inflammation or occult malignancy 2

• Renal function tests - creatinine and BUN, as renal pathology can contribute to anemia 1

Interpretation Algorithm Based on Reticulocyte Count

If Reticulocyte Index is LOW (<2.0):

This indicates decreased RBC production, suggesting: 1

• Acute blood loss (early, before marrow compensation)
• Iron deficiency anemia (most likely given severity and thrombocytosis)
• Anemia of chronic inflammation (with functional iron deficiency)
• Early bone marrow failure or infiltrative process
• Medication-induced marrow suppression

Next steps: 1, 2

• If ferritin <30 μg/L (or <100 μg/L with inflammation present) and transferrin saturation <16%, diagnose iron deficiency and investigate source of blood loss aggressively
• If iron studies show ferritin >100 μg/L with transferrin saturation <20%, consider anemia of chronic disease
• Review all medications for marrow suppressants
• Consider bone marrow aspiration and biopsy if pancytopenia develops or no cause identified after comprehensive workup 1, 2

If Reticulocyte Index is HIGH (>2.0):

This indicates normal/increased RBC production with peripheral destruction or loss, suggesting: 1

• Acute hemorrhage (after initial marrow response, typically 3-5 days)
• Hemolytic anemia (immune or non-immune)
• Microangiopathic hemolysis (TMA, DIC)

Next steps: 2, 5

• Check ADAMTS13 activity urgently if schistocytes present on smear to rule out thrombotic thrombocytopenic purpura (TMA)
• Investigate hemolysis with elevated LDH, decreased haptoglobin, elevated indirect bilirubin
• Avoid platelet transfusion if TMA suspected until diagnosis confirmed 5

Critical Differential Diagnosis Considerations

The Combination of Severe Anemia + Thrombocytosis + Neutrophilia Suggests:

1. Occult gastrointestinal or gynecologic bleeding with reactive thrombocytosis (most common) 2, 4

2. Iron deficiency anemia from chronic blood loss, as thrombocytosis (platelets 588→655) is a classic reactive finding in iron deficiency 1, 2, 4

3. Underlying malignancy (GI, gynecologic, or hematologic) causing both blood loss and inflammatory response 2

4. Myeloproliferative neoplasm (less likely but must exclude) - would require bone marrow biopsy with cytogenetic analysis 2

5. Hemolysis with reactive thrombocytosis - check hemolysis markers 2, 5

Management Based on Severity

Immediate Resuscitation

• Transfuse packed red blood cells if hemoglobin <7.5 g/dL or patient has symptoms (dyspnea, chest pain, hemodynamic instability), targeting hemoglobin 7-9 g/dL 6

• Maintain adequate IV hydration during evaluation, as volume depletion can worsen apparent anemia 3

Specific Interventions

• If iron deficiency confirmed: Initiate oral or IV iron supplementation after identifying and addressing bleeding source 1, 2

• If occult hemorrhage identified on CT: Consult surgery or interventional radiology for source control 3

• If hemolysis confirmed: Avoid certain treatments (early platelet transfusion in TTP) and obtain urgent hematology consultation 5

• If gynecologic source identified: Obtain urgent gynecology consultation, as uterine pathology can cause severe anemia with thrombocytopenia or thrombocytosis 4

Common Pitfalls to Avoid

• Do not assume anemia is simply "anemia of chronic disease" without measuring iron studies, as 25-37.5% of patients with chronic conditions have concurrent iron deficiency 1

• Do not attribute hematocrit drop to "hemodilution" or "lab error" without investigation - a hemoglobin drop of 3.1 g/dL over one month represents loss or destruction of approximately 30% of red cell mass 7

• Do not delay imaging in patients with abdominal pain and hematocrit drop, as occult hemorrhage (retroperitoneal, rectus sheath, intra-abdominal) can be life-threatening and easily missed on physical examination 3

• Do not transfuse platelets empirically if microangiopathic hemolysis suspected, as this can worsen thrombotic microangiopathy 5

• Do not use the "rule of 3" (Hct = Hgb × 3) to estimate hematocrit from hemoglobin, as this relationship is age-dependent and inaccurate, particularly in anemia 8

Urgent Consultation Requirements

• Hematology consultation if: 1, 2

  • Pancytopenia or unexplained cytopenias develop
  • Hemolysis confirmed
  • Bone marrow biopsy indicated
  • Myeloproliferative disorder suspected

• Surgery/GI consultation if occult GI bleeding or intra-abdominal pathology identified 3

• Gynecology consultation if uterine pathology suspected as bleeding source 4