What tests should be done for a patient with thrombocytopenia (low platelet count) in the Intensive Care Unit (ICU)?

Diagnostic Testing for Thrombocytopenia in the ICU

When thrombocytopenia is discovered in an ICU patient, immediately confirm true thrombocytopenia by examining the sample tube for clots and performing a peripheral blood smear to exclude pseudothrombocytopenia from platelet aggregates, then proceed with basic coagulation studies (PT, aPTT, fibrinogen, D-dimers) to assess for DIC, followed by targeted testing based on clinical probability of specific etiologies, particularly heparin-induced thrombocytopenia (HIT) if heparin exposure exists. 1, 2

Initial Confirmatory Testing

Rule Out Pseudothrombocytopenia

• Examine the blood sample tube for clots and review the peripheral blood smear to exclude platelet aggregates, as EDTA-induced platelet clumping can cause false thrombocytopenia 1
• Collect a new citrate sample if pseudothrombocytopenia is suspected, as this often resolves the false low platelet count 1
• Perform a complete blood count with differential to confirm thrombocytopenia and assess other cell lines 2, 3

Peripheral Blood Smear Analysis

• Rigorous analysis of the blood smear is necessary to assess platelet morphology, evaluate red and white blood cell morphology, and look for other acute hematological pathologies 1, 2

Basic Coagulation Studies

Order PT, aPTT, fibrinogen, and D-dimers (or fibrin monomers) immediately to evaluate for disseminated intravascular coagulation (DIC), which can occur in severe HIT and other critical conditions 1

Heparin-Induced Thrombocytopenia (HIT) Evaluation

Clinical Probability Assessment (4T Score)

ICU patients with heparin exposure require systematic HIT evaluation, though the 4T score can be compromised in ICU patients with multiple comorbidities and treatments 1:

• Calculate the 4T score based on: degree of thrombocytopenia (>50% fall is highly predictive), timing of platelet fall (5-10 days after heparin initiation), presence of thrombosis, and absence of other causes 1
• Note that ICU patients with multiple pathologies make the 4T score difficult to assess due to competing causes like sepsis, liver disease, chemotherapy, antibiotics, and diuretics 1

Doppler Ultrasound Screening

Perform systematic Doppler ultrasound examination of lower limbs (or upper limbs if catheter present) to detect asymptomatic thromboses, as thrombotic complications may not be clinically obvious 1

Anti-PF4 Antibody Testing

• If clinical probability is intermediate (4T score 4-5) or high (4T score ≥6), test for anti-PF4 antibodies as soon as possible without delaying treatment decisions 1
• Immunological tests (ELISA or chemiluminescent) should be performed first-line as they have excellent sensitivity and negative predictive value, allowing rapid exclusion of HIT 1
• If anti-PF4 antibodies are detected with significant titre and clinical probability is intermediate or high, perform a functional test (SRA or HIPA) to confirm the diagnosis, as these have specificity close to 100% 1

Additional Testing Based on Clinical Context

Infection Screening

Perform HIV testing if immune thrombocytopenia is suspected, as HIV infection is commonly associated with thrombocytopenia 2

Assessment for Alternative Diagnoses

• Consider antiplatelet alloimmunization testing if recent labile blood product administration occurred 1
• Evaluate for sepsis, liver disease, and medication-induced causes as these are common in ICU patients and can cause more severe thrombocytopenia than HIT (often <10 × 10⁹/L with bleeding rather than thrombosis) 1

Critical Pitfalls to Avoid

• Do not delay discontinuation of heparin and initiation of alternative anticoagulation while waiting for laboratory results if clinical probability of HIT is high 1
• Recognize that non-heparin-related drug or transfusion thrombocytopenia is typically more severe (platelet count <10 × 10⁹/L) and presents with bleeding rather than thrombosis, unlike HIT 1
• Remember that thrombocytopenia in ICU patients is multifactorial, requiring consideration of decreased production, sequestration, destruction, consumption, or combinations thereof 4, 5
• Understand that platelet counts >50 × 10⁹/L rarely cause spontaneous serious bleeding (occurs in <5% of patients with counts 50-60 × 10⁹/L), while counts <10 × 10⁹/L carry high bleeding risk 2, 3