What is the diagnosis for a patient with a high white blood cell (WBC) count and a low platelet (PLT) count?

Differential Diagnosis for High WBC and Low Platelets

The combination of elevated white blood cell count with thrombocytopenia most commonly indicates acute leukemia (particularly acute myeloid leukemia), sepsis with disseminated intravascular coagulation, or heparin-induced thrombocytopenia in the appropriate clinical context. 1

Immediate Life-Threatening Considerations

Hyperleukocytosis with Leukostasis

• WBC >100,000/μL represents a medical emergency due to risk of brain infarction, hemorrhage, and leukostasis requiring immediate cytoreduction 2, 3
• Hyperleukocytosis occurs in up to 18% of acute myeloid leukemia patients and carries adverse prognosis with life-threatening complications including disseminated intravascular coagulation and tumor lysis syndrome 3
• Examine the peripheral blood smear immediately for blast cells, which would indicate acute leukemia requiring urgent hematology consultation 1, 4

Sepsis and Disseminated Intravascular Coagulation

• If neutrophils show vacuolization on blood smear, this is a medical emergency requiring immediate blood cultures and empiric antibiotics, as vacuolated neutrophils indicate active bacterial infection or sepsis with high mortality risk 5
• Sepsis diagnostic criteria include leukocytosis (WBC >12,000/μL) or leukopenia (WBC <4,000/μL) combined with thrombocytopenia (platelet count <100,000/μL) 1
• Order PT, aPTT, fibrinogen, and D-dimers immediately to evaluate for DIC, which commonly presents with thrombocytopenia and can occur in severe sepsis 1

Heparin-Induced Thrombocytopenia (HIT)

• Consider HIT in any patient with thrombocytopenia who has received heparin within the past 3 months, as this condition paradoxically causes thrombosis despite low platelets 1
• Apply the 4T score: thrombocytopenia severity (typically 30-70 G/L, rarely <20 G/L), timing (5-10 days after heparin initiation), thrombosis presence, and other causes of thrombocytopenia 1
• HIT thrombocytopenia is typically moderate (not profound) and associated with thrombotic complications rather than bleeding 1

Primary Hematologic Malignancies

Acute Myeloid Leukemia

• High WBC with low platelets strongly suggests acute leukemia, particularly when WBC is markedly elevated 1, 2
• AML patients commonly present with high WBC counts, and a high WBC (>100,000/μL) at diagnosis is a poor prognostic factor for early death 1
• Examine blood smear for blast cells, left shift with dysplasia, or immature granulocytes 5, 4
• Symptoms suggesting hematologic malignancy include fever, weight loss, bruising, fatigue, or bleeding 4, 2

Myeloproliferative Neoplasms

• Suspect MPN if WBC >100,000/mm³, concurrent unexplained anemia, splenomegaly, constitutional symptoms, or persistent elevations without reactive cause 5
• However, MPNs typically present with thrombocytosis rather than thrombocytopenia, making this less likely in your scenario 5
• Order JAK2 V617F mutation testing if MPN suspected, though thrombocytopenia makes this diagnosis less probable 5

Diagnostic Algorithm

Step 1: Assess Clinical Urgency

• Check WBC absolute value: >100,000/μL requires emergency evaluation for leukostasis 2, 3
• Examine blood smear immediately for blast cells, vacuolated neutrophils, toxic granulations, or dysplastic features 5, 4
• Assess for bleeding or thrombosis: bleeding suggests platelet dysfunction or DIC; thrombosis suggests HIT or antiphospholipid syndrome 1

Step 2: Order Essential Laboratory Tests

• Repeat CBC with manual differential to confirm findings and assess absolute neutrophil count 5, 4
• Peripheral blood smear examination for morphologic abnormalities, blast cells, left shift, or toxic changes 5, 4
• PT, aPTT, fibrinogen, D-dimers to evaluate for DIC 1
• Blood cultures if infection suspected (fever, hypotension, or vacuolated neutrophils) 1, 5

Step 3: Risk Stratify Based on Clinical Context

High-risk features requiring immediate hematology consultation: 1, 2

• WBC >100,000/μL
• Blast cells on peripheral smear
• Concurrent anemia or abnormal red blood cell indices
• Weight loss, bruising, or constitutional symptoms
• Splenomegaly or hepatomegaly

Moderate-risk features requiring urgent evaluation: 1

• Recent heparin exposure (consider HIT)
• Signs of sepsis or infection
• Evidence of DIC on coagulation studies
• Platelet count <20,000/μL with bleeding risk

Common Pitfalls to Avoid

• Do not assume reactive leukocytosis if thrombocytopenia is present—this combination warrants investigation for acute leukemia or bone marrow failure 1, 2
• Do not delay blood smear examination—morphologic evaluation provides critical diagnostic information that automated counts cannot detect 5, 4
• Do not overlook medication history—heparin exposure within 3 months mandates HIT evaluation even without obvious thrombosis 1
• Do not transfuse platelets empirically in suspected HIT—this can worsen thrombotic complications 1
• Do not dismiss mild symptoms in patients with extreme leukocytosis—WBC >100,000/μL can cause asymptomatic microvascular occlusion requiring urgent cytoreduction 2, 3