How is leucocytosis (elevated white blood cell count) managed during pregnancy?

Management of Leukocytosis in Pregnancy

Leukocytosis in pregnancy is most commonly physiologic and requires no treatment, but when pathologic causes are identified—particularly hematologic malignancies—treatment must begin immediately without delay, as any postponement compromises maternal survival. 1

Understanding Physiologic Leukocytosis

Pregnancy normally increases white blood cell counts significantly:

• The upper reference limit for total WBC increases by 36% during pregnancy 1
• Neutrophils specifically increase by 55% 1
• Leukocytosis is particularly common in the third trimester 2
• White blood cell counts can reach 20 × 10⁹/L or higher without pathology 2

Key clinical pearl: Leukocytosis alone is not a predictive marker of infection or appendicitis in pregnancy 3. This is a common pitfall—clinicians often over-interpret elevated WBC counts and initiate unnecessary antibiotic treatment, which may cause more harm than benefit 1.

Initial Diagnostic Approach

When evaluating leukocytosis in pregnancy, differentiate leucocyte subpopulations first 4:

For Suspected Infection (particularly UTI):

• If urinary symptoms present with moderate leukocytes on urinalysis: obtain urine culture using clean-catch midstream or catheterized specimen before initiating antibiotics 1
• Pyuria plus bacteriuria plus symptoms indicates true UTI requiring treatment 1
• Important caveat: Negative nitrites do NOT rule out UTI—nitrite testing has only 53% sensitivity 1
• If symptomatic, initiate empirical antibiotics while awaiting culture to prevent maternal and fetal complications 1

For Unexplained Persistent Leukocytosis:

• Pregnancy-induced leukocytosis without infection can persist throughout pregnancy and resolves spontaneously after delivery 2
• In one documented case, neutrophil count returned to normal one day after cesarean section 2
• Avoid unnecessary antibiotic treatment for asymptomatic leukocytosis 1

Management of Hematologic Malignancies Causing Leukocytosis

Acute Myeloid Leukemia (AML)

Treatment must begin immediately regardless of trimester—delays compromise maternal outcome 5, 1:

First Trimester:

• Discuss therapeutic termination once patient is hemodynamically stable 5, 1
• This allows immediate standard therapy with ATRA and chemotherapy 5, 1
• If pregnancy continuation desired: use daunorubicin monotherapy (NOT idarubicin) 5, 1
• Idarubicin is absolutely contraindicated due to higher lipophilicity causing increased placental transfer and higher DNA affinity, resulting in severe fetal toxicity 5, 1

Second Trimester:

• Standard induction therapy: doxorubicin plus cytarabine 5, 1
• The 3+7 regimen uses daunorubicin 60 mg/m² days 1-3 plus cytarabine 100-200 mg/m² days 1-7 1
• Chemotherapy during second and third trimesters has been reported as safe, though stillbirths and low birthweight remain risks 5

Third Trimester:

• Consider inducing labor and initiating full therapy after delivery 5, 1
• Never delay treatment to reach a "safer" gestational age—maternal mortality increases with delays 1

Acute Promyelocytic Leukemia (APL)

ATRA is highly teratogenic and contraindicated in first trimester 5, 1:

First Trimester:

• Same approach as AML: discuss termination or use anthracycline chemotherapy alone 5, 1
• ATRA should be avoided due to demonstrated teratogenicity with retinoids, particularly isotretinoin 5

Second Trimester:

• Doxorubicin plus ATRA can be used starting in second trimester 5, 1
• ATRA dose of 25 mg/m² per day is recommended in younger patients with lower incidence of pseudotumor cerebri and headache 5

Third Trimester:

• Induce labor and initiate therapy after delivery 5, 1

Chronic Myeloid Leukemia (CML)

Treatment options vary by trimester 5, 1:

• First trimester: Interferon-alpha is safe and preferred 5, 1
• Second and third trimesters: Interferon-alpha OR imatinib can be used 5, 1
• Imatinib appears safe only when administered during second and third trimesters 5

Management of Hyperleukocytosis (WBC >100 × 10⁹/L)

When extreme leukocytosis occurs with leukemia:

• Hydroxyurea at dosages up to 50-60 mg/kg per day until WBCs are less than 10-20 × 10⁹/L 5
• Until WBC reduced, avoid excessive red blood cell transfusions—they increase blood viscosity 5
• Prevent tumor lysis syndrome with hydration, allopurinol or rasburicase, and urine pH control 5

Critical Multidisciplinary Considerations

Mandatory team involvement from diagnosis 5, 1:

• Hematologist
• Obstetrician
• Neonatologist

Delivery timing:

• Avoid delivery while patient and fetus are cytopenic 5
• For deliveries before 36 weeks: administer antenatal corticosteroids to reduce respiratory distress syndrome risk 1

Postpartum:

• Breastfeeding is contraindicated if chemotherapy continues after delivery 1
• Never use arsenic trioxide at any trimester due to severe embryotoxicity 1

Common Pitfalls to Avoid

1. Do not delay treatment waiting for a "better" gestational age—more than 75% of patients achieve complete remission with immediate standard chemotherapy, and pregnancy does not alter AML course 5

2. Do not use idarubicin in pregnancy—always substitute daunorubicin or doxorubicin 5, 1

3. Do not assume all leukocytosis requires antibiotics—physiologic leukocytosis is normal and resolves postpartum 1, 2

4. Do not rely on leukocytosis alone to diagnose appendicitis or infection in pregnancy—it lacks specificity 3