What medication should be discontinued in a patient with hypertension, taking lisinopril (Angiotensin-Converting Enzyme inhibitor), amlodipine (Calcium Channel Blocker), and hydrochlorothiazide (Diuretic), who was recently started on heparin (anticoagulant) and now has an elevated activated partial thromboplastin time (aPTT)?

Discontinue Heparin Immediately

Heparin should be discontinued immediately in this patient with an elevated aPTT, as this indicates either excessive anticoagulation with bleeding risk or potential heparin-induced thrombocytopenia (HIT), both of which require urgent cessation of all heparin products. 1, 2

Clinical Reasoning and Decision Algorithm

Step 1: Assess the Elevated aPTT

An elevated aPTT in a patient recently started on heparin has two primary concerning etiologies:

• Excessive anticoagulation: The aPTT may be supratherapeutic (>70-85 seconds), placing the patient at increased risk of major bleeding, intracranial hemorrhage, and mortality 3, 4
• Heparin-induced thrombocytopenia (HIT): Even with normal platelet counts initially, HIT can develop 2-20 days after heparin initiation and carries a 30-50% risk of life-threatening thrombosis if untreated 1, 5

Step 2: Why Not the Antihypertensive Medications?

The three antihypertensive medications have no clinically significant interaction with heparin or aPTT:

• Lisinopril (ACE inhibitor): Does not affect coagulation parameters or interact with heparin 1
• Amlodipine (calcium channel blocker): No effect on aPTT or bleeding risk 1
• Hydrochlorothiazide (thiazide diuretic): Does not interfere with anticoagulation monitoring 1

None of these medications cause aPTT elevation or require discontinuation in this clinical scenario.

Step 3: Immediate Management Protocol

When heparin causes an elevated aPTT, the following actions are mandatory:

• Stop all heparin immediately, including heparin flushes and heparin-coated catheters 1, 2, 5
• Calculate the 4Ts score to assess HIT probability (thrombocytopenia, timing, thrombosis, other causes) 1
• Check platelet count - if it has dropped >50% from baseline or is <100,000/mm³, HIT is highly suspected 1, 5
• Monitor for bleeding complications - check hemoglobin/hematocrit, assess for occult bleeding 5, 3

Step 4: Risk Stratification for HIT

Even with "normal" laboratory results mentioned in the question, HIT remains a critical concern:

• HIT can occur with normal platelet counts early in the disease course 1
• The elevated aPTT itself may be the first laboratory abnormality detected 5
• Thrombosis risk is 30-50% if HIT is untreated, far exceeding bleeding risk from therapeutic anticoagulation 1, 2

Step 5: Alternative Anticoagulation if Needed

If anticoagulation remains indicated after heparin discontinuation:

• For intermediate or high HIT probability: Initiate non-heparin anticoagulant (argatroban, bivalirudin, fondaparinux, or DOAC) at therapeutic doses immediately without waiting for confirmatory testing 1, 2
• For low HIT probability with excessive aPTT: Hold heparin temporarily, reassess need for anticoagulation, consider alternative agents if required 1, 2

Critical Pitfalls to Avoid

• Do not continue heparin while waiting for HIT antibody results - the thrombotic risk is immediate and potentially fatal 1, 2
• Do not reduce heparin dose as a temporizing measure - partial treatment is inadequate for either scenario (excessive anticoagulation or HIT) 2
• Do not substitute low-molecular-weight heparin (LMWH) - it cross-reacts with HIT antibodies in 80-90% of cases 2
• Do not start warfarin acutely - it can cause venous limb gangrene in acute HIT and should only be initiated after platelet recovery 1

Monitoring After Heparin Discontinuation

• Daily platelet counts for at least 14 days or until stable 1
• Repeat aPTT 4-6 hours after heparin cessation to confirm normalization 5
• Assess for thrombotic complications - deep vein thrombosis, pulmonary embolism, arterial thrombosis 1, 5

Answer: D. Heparin is the only medication that should be discontinued in this clinical scenario.