How do you confirm a heparin (Heparin Sodium) allergy?

Confirming Heparin Allergy

To confirm heparin allergy, you must first distinguish between true hypersensitivity reactions and heparin-induced thrombocytopenia (HIT), as they require completely different diagnostic approaches and have vastly different clinical implications.

Initial Critical Step: Rule Out Pseudothrombocytopenia

• Examine the blood sample tube for clots and review the peripheral blood smear directly to exclude platelet aggregates, as EDTA-dependent pseudothrombocytopenia is a common laboratory artifact that mimics true thrombocytopenia 1, 2
• If platelet clumping is present on EDTA sample, obtain a new citrate sample to confirm true platelet count 1

Diagnostic Pathway Based on Clinical Presentation

If Thrombocytopenia is Present (Suspected HIT)

This is NOT a true "allergy" but an immune-mediated prothrombotic condition that requires specific testing:

Step 1: Calculate Pre-Test Probability

• Use the 4Ts score (Thrombocytopenia, Timing, Thrombosis, other causes) to assess clinical probability 1, 3
• Score 0-3 = low probability; 4-5 = intermediate; 6-8 = high probability 1
• Note: The 4Ts score is difficult to apply after cardiac surgery; instead analyze the biphasic evolution profile of platelet count postoperatively 1

Step 2: Immunoassay Testing

• Perform anti-PF4/heparin antibody immunoassay immediately for intermediate or high probability cases 1, 3
• A negative high-sensitivity immunoassay (IgG-specific ELISA or particle-gel immunoassay) effectively excludes HIT due to excellent negative predictive value 1, 3
• Positive immunoassays have poor specificity (up to 50% false-positives after cardiac surgery), so confirmation is required 1

Step 3: Functional Assay for Confirmation

• If immunoassay is positive with intermediate/high clinical probability, perform a functional platelet activation assay 1, 3
• Serotonin release assay (SRA) is the gold standard with near 100% specificity 1, 3
• Alternative functional assays include HIPA (heparin-induced platelet activation) or HIMEA (heparin-induced multi-electrode aggregometry) 1
• Blood samples should be collected ≥4 hours after stopping unfractionated heparin or ≥12 hours after low-molecular-weight heparin to avoid test interference 1

HIMEA Protocol (if available):

• Test patient plasma/serum with donor platelets at three heparin concentrations: 0,1 IU/mL, and 200 IU/mL 1
• Positive criteria: AUC ≥30 U at low-dose heparin AND <50% of that AUC at high-dose heparin AND <30 U without heparin 1
• Requires high-responder platelet donors 1

If Cutaneous Reaction Without Thrombocytopenia (True Hypersensitivity)

These are genuine allergic reactions, most commonly delayed-type hypersensitivity:

Delayed-Type Hypersensitivity (Most Common - 96% of heparin allergies)

• Presents as itchy inflammatory plaques at subcutaneous injection sites, typically appearing days after exposure 4, 5, 6
• Diagnosis confirmed by intradermal skin testing with UFH and various LMWHs (nadroparin, dalteparin, enoxaparin) with readings at 20 minutes and 48-72 hours 4, 5, 6
• Broad cross-reactivity between UFH and LMWHs is typical (seen in intradermal testing) 4
• Subcutaneous provocation testing with fondaparinux to identify safe alternative 4, 5
• Critical finding: Intravenous UFH is tolerated in all delayed-type cases despite positive intradermal tests, making IV heparin safe for emergency use 4

Immediate-Type Hypersensitivity (Rare - 4% of heparin allergies)

• Presents as urticaria, angioedema, bronchospasm, or anaphylaxis within minutes to hours 4, 5, 6
• Diagnosis by skin prick testing followed by intradermal testing with immediate readings (15-20 minutes) 5, 6
• Subcutaneous provocation testing may be needed if skin tests are negative but clinical suspicion remains high 5, 6
• In vitro tests have low sensitivity and are not generally available 5

Critical Pitfalls to Avoid

• Do NOT confuse HIT with true heparin allergy - HIT is a prothrombotic condition requiring alternative anticoagulation, while delayed hypersensitivity may still allow IV heparin use 7, 4, 8
• Misdiagnosis of HIT leads to inappropriate "heparin allergy" documentation in 42% of cases, resulting in unnecessary alternative anticoagulant use and 66% major bleeding rate 8
• Never perform skin testing if skin necrosis is present - this suggests HIT with thrombosis requiring immediate laboratory confirmation 5
• Failing to examine the blood smear before diagnosing thrombocytopenia leads to unnecessary HIT workups 1, 2
• Document the specific type of reaction (HIT vs. delayed hypersensitivity vs. immediate reaction) as management differs completely 7, 4, 8

Safe Alternatives After Confirmed Allergy

• For delayed-type hypersensitivity requiring subcutaneous anticoagulation: fondaparinux (only 6.3% cross-reactivity) 4
• For HIT: use non-heparin anticoagulants (argatroban, bivalirudin, fondaparinux, or DOACs) 7
• For emergency situations requiring IV anticoagulation in delayed-type hypersensitivity: IV UFH is safe 4