What is the management of leukocytosis (elevated white blood cell count) during pregnancy?

Management of Leukocytosis in Pregnancy

Leukocytosis during pregnancy is most commonly physiologic and requires no treatment, but systematic evaluation is essential to exclude pathologic causes including infection, hematologic malignancy, or other serious conditions that demand immediate intervention.

Understanding Physiologic Leukocytosis in Pregnancy

Pregnancy causes substantial increases in white blood cell counts that are entirely normal:

• The upper reference limit for total WBC increases by 36% during pregnancy, with neutrophils increasing by 55% 1
• Leukocyte counts progressively rise from first to third trimester and peak in the immediate postpartum period 2
• WBC counts can reach 20×10⁹/L or higher during normal pregnancy, particularly in the third trimester and postpartum period 3, 2

This physiologic leukocytosis results from pregnancy-induced immunoregulation and typically resolves spontaneously after delivery, often within 24 hours 3.

Initial Evaluation Algorithm

Step 1: Determine if Leukocytosis is Pathologic

Obtain a complete blood count with differential to assess:

• Absolute neutrophil count, lymphocyte count, eosinophil count, and presence of immature forms (bands, blasts) 4
• Peripheral blood smear to evaluate cell morphology, maturity, uniformity, and toxic granulations 4
• Gestational age, as normal ranges vary significantly by trimester 1, 2

Step 2: Assess for Infection

If the patient has symptoms (fever, dysuria, cough, abdominal pain), pursue infectious workup:

• For urinary symptoms with moderate leukocytes on urinalysis: obtain urine culture before initiating antibiotics, using clean-catch midstream or catheterized specimen 1
• Pyuria (WBCs in urine) plus bacteriuria plus symptoms indicates true UTI requiring treatment 1
• If symptomatic, initiate empirical antibiotics while awaiting culture results to prevent maternal and fetal complications 1

Common pitfall: Negative nitrites do not rule out UTI, as nitrite testing has only 53% sensitivity 1.

Step 3: Evaluate for Hematologic Malignancy

Red flags requiring immediate hematology referral include:

• Fever, unexplained weight loss, bruising, fatigue, or night sweats 4
• Presence of immature white blood cells (blasts, promyelocytes) on peripheral smear 5
• Persistent leukocytosis >20×10⁹/L that does not resolve or worsens over time 3, 4
• Abnormal differential showing marked left shift, eosinophilia, or lymphocytosis 4

Management of Specific Hematologic Malignancies in Pregnancy

Acute Leukemia (AML/ALL)

Treatment must begin immediately without delay regardless of trimester, as any delay compromises maternal survival 6:

First Trimester:

• Discuss therapeutic termination once patient is hemodynamically stable, allowing immediate standard therapy 5, 6
• If pregnancy continuation desired: use daunorubicin monotherapy (NOT idarubicin) 5, 6
• Idarubicin is absolutely contraindicated due to higher lipophilicity causing increased placental transfer and fetal toxicity 5, 6
• ATRA is contraindicated in first trimester due to high teratogenicity 5, 6

Second and Third Trimesters:

• Standard 3+7 regimen: daunorubicin 60 mg/m² days 1-3 plus cytarabine 100-200 mg/m² days 1-7 6
• For acute promyelocytic leukemia: doxorubicin plus ATRA can be used starting in second trimester 5
• In third trimester: consider inducing labor and initiating therapy after delivery 5

Critical pitfall: Never delay treatment to reach a "safer" gestational age—maternal mortality increases with delays 6.

Chronic Myeloid Leukemia (CML)

Management varies by trimester 5:

• First trimester: interferon-alpha is safe and preferred 5
• Second and third trimesters: interferon-alpha OR imatinib can be used 5, 7
• Acute leukocytapheresis can be used for rapid cytoreduction if needed 7

Lymphoma

For non-Hodgkin lymphoma requiring treatment:

• CHOP chemotherapy starting in second trimester shows favorable pregnancy outcomes 5

For Hodgkin lymphoma:

• ABVD chemotherapy starting in second trimester without significant fetal impairment 5

Management of Benign Leukocytosis

For asymptomatic leukocytosis without evidence of infection or malignancy:

• Serial monitoring with repeat CBC every 2-4 weeks to ensure stability 3, 2
• No treatment required for physiologic pregnancy-induced leukocytosis 3, 2
• Reassure patient that counts typically normalize within 24 hours postpartum 3

Common pitfall: Avoid unnecessary antibiotic treatment for asymptomatic leukocytosis, as this may cause more harm than benefit 1.

Special Considerations

Multidisciplinary involvement is mandatory for malignant causes:

• Hematologist, obstetrician, and neonatologist must collaborate from diagnosis 6, 8

For deliveries before 36 weeks:

• Administer antenatal corticosteroids to reduce respiratory distress syndrome risk 5, 8

Postpartum:

• Breastfeeding is contraindicated if chemotherapy or arsenic trioxide continues after delivery 5, 8

Never use arsenic trioxide at any trimester due to severe embryotoxicity 5, 6.