What is the primary adverse effect of heparin (anticoagulant) therapy?

Primary Adverse Effects of Heparin

Heparin causes bleeding as its primary adverse effect, with major hemorrhage occurring in approximately 1-2% of treated patients, and heparin-induced thrombocytopenia (HIT) as the most serious non-hemorrhagic complication. 1

Hemorrhagic Complications

Bleeding is the most important safety concern with heparin therapy, resulting directly from its anticoagulant potency. 2

Major Bleeding Risk

• Major bleeding requiring transfusion occurs in 1.0-2.3% of heparin-treated patients compared to 0.8-1.1% in control groups 1
• High-dose heparin regimens approximately double the absolute risk of major extracranial bleeding 1
• Fatal hemorrhages have been documented, particularly in pediatric patients due to medication errors with concentrated formulations 3

High-Risk Bleeding Sites

• Adrenal hemorrhage with resultant acute adrenal insufficiency 3
• Ovarian hemorrhage 3
• Retroperitoneal hemorrhage 3
• Spinal or epidural hematoma resulting in long-term paralysis, particularly with neuraxial anesthesia 1

Patient-Specific Risk Factors

• Women over 60 years have higher bleeding incidence 1, 3
• Cancer patients experience 12-month cumulative major bleeding of 12.4% versus 4.9% in non-cancer patients (HR 2.2) 1
• One-third of major bleeding occurs during initial 5-10 days of heparinization 1

Heparin-Induced Thrombocytopenia (HIT)

HIT is the most important non-hemorrhagic side effect of heparin, representing a serious antibody-mediated reaction that paradoxically causes thrombosis. 1

Mechanism and Presentation

• HIT develops from antibodies to platelet Factor 4-heparin complexes that induce platelet aggregation 3
• Can progress to heparin-induced thrombocytopenia with thrombosis (HITT) with venous and arterial thromboses 3
• Occurs approximately 10 times less frequently with low-molecular-weight heparins than unfractionated heparin 2

Thrombotic Complications of HIT

• Deep vein thrombosis 3
• Pulmonary embolism 3
• Cerebral vein thrombosis 3
• Limb ischemia and stroke 3
• Myocardial infarction 3
• Gangrene of extremities potentially requiring amputation 3

Management Approach

• Promptly discontinue heparin if platelet count falls below 100,000/mm³ or recurrent thrombosis develops 3
• Evaluate for HIT/HITT and administer alternative anticoagulant if necessary 3
• HIT can occur up to several weeks after heparin discontinuation 3

Additional Adverse Effects

Osteoporosis

• Heparin inhibits osteoblast formation and activates osteoclasts, promoting bone loss 1
• Decreases in bone mineral density of 3.1% at 1-year and 4.8% at 2-year follow-up with chronic enoxaparin therapy 1

Dermatologic Reactions

• Skin lesions from delayed-type hypersensitivity reactions are frequent and clinically important 2
• Skin necrosis can occur as part of HITT syndrome 3

Heparin Rebound

• Period of hypercoagulability after abrupt cessation of unfractionated heparin infusion 1
• Associated with increased thrombin activity and platelet activation persisting after anticoagulant effects decline 1
• Ischemic events cluster around median 9.5 hours after UFH cessation 1

Other Complications

• Transaminasemia 4
• Hyperkalemia and hypoaldosteronism 4
• Eosinophilia 4
• Allergic reactions including anaphylactoid reactions to heparin or pork products 3, 4

Critical Clinical Pitfalls

Medication Errors

• Never use Heparin Sodium Injection as a "catheter lock flush" product 3
• Fatal hemorrhages have occurred from confusion between concentrated 10,000 units/mL vials and 1 mL catheter lock flush vials 3
• Carefully examine all vials to confirm correct strength prior to administration 3

Contraindications

• History of HIT or HITT is an absolute contraindication 3
• Uncontrolled active bleeding (except disseminated intravascular coagulation) 3
• Inability to perform appropriate coagulation monitoring 3

High-Risk Clinical Scenarios Requiring Caution

• During and immediately following spinal tap, spinal anesthesia, or major surgery involving brain, spinal cord, or eye 3
• Subacute bacterial endocarditis and severe hypertension 3
• Hemophilia, thrombocytopenia, and vascular purpuras 3
• Ulcerative gastrointestinal lesions 3
• Menstruation and liver disease with impaired hemostasis 3