Parenteral anticoagulants are routinely indicated for the prevention and treatment of venous thromboembolism. Heparin is typically the preferred agent for inpatient parenteral anticoagulation. Serious side effects include bleeding complications and type 2 heparin-induced thrombocytopenia (HIT), which causes arterial and venous thromboembolism due to an antibody-mediated aggregation of platelets. A drop in platelet count (< 100,000 platelets /μL or decrease of > 50% compared to baseline) may indicate HIT; therefore, the platelet count must be closely monitored in patients on parenteral anticoagulants, especially heparin. If HIT is suspected, treatment involves discontinuing all heparins and beginning nonheparin anticoagulation (usually argatroban).
Unfractionated heparin (UFH)
- Drug: heparin
- Prophylaxis: subcutaneous
- Therapeutic: continuous intravenous infusion
- Monitoring during therapy: activated partial thromboplastin time (aPTT); , platelet count (including baseline before treatment is started)
- Clearance: hepatic (preferred agent for patients with renal insufficiency)
- Antidote: protamine sulfate (a positively-charged protein that can neutralize negatively-charged heparin by forming inactive complexes)
Low molecular weight heparin (LMWH)
- Drugs: enoxaparin, dalteparin, tinzaparin, nadroparin,
- Administration: subcutaneous
- Monitoring during therapy: anti-factor Xa activity; can be assessed in specific cases; not generally recommended
- Clearance: renal (therefore, contraindicated for patients with renal insufficiency)
- Antidote: protamine sulfate (partial reversal)
- Drugs: fondaparinux
- Administration: subcutaneous
Monitoring during therapy:
- Not generally recommended
- Anti-factor Xa activity can be assessed in specific cases
- Antidote: : possibly activated prothrombin complex concentrates (aPCC)
Direct thrombin inhibitors
- Drugs: argatroban, bivalirudin, desirudin; , dabigatran
- Monitoring during therapy: not generally recommended
- Enhances the activity of antithrombin
Indirect inhibitor of
- Factor Xa: antithrombin III potentiation → inhibition of factor Xa → decreased activation of prothrombin; → ↓ thrombin; → ↓ fibrinogen activation; → ↓ fibrin
- Thrombin (factor IIa): UFH binds antithrombin III ; and thrombin simultaneously at two distinct binding sites → antithrombin III and thrombin; held by heparin in close proximity (complex formation) → ↑ thrombin inhibition → ↓ fibrinogen activation → ↓ fibrin
- Short half-life: anticoagulant effect quickly ceases once administration is stopped
- Mechanism of action 
- Higher bioavailability than unfractionated heparin
- Long half-life: 2–4 times longer than unfractionated heparin
- Directly inhibit thrombin (freely circulating and in association with clots)
The effect of most parenteral anticoagulants (except for direct thrombin inhibitors) depends on native antithrombin. In patients with antithrombin III deficiency (e.g., due to nephrotic syndrome), this effect is reduced!
General side effects
- Drug-drug interactions
Specific side effects
|UFH and LMWH|
|Direct thrombin inhibitors|
Heparin-induced thrombocytopenia (HIT)
- Treatment with heparin, especially UFH, can cause thrombocytopenia.
- HIT can be differentiated into type 1 (asymptomatic), and type 2, which is antibody-related and prognostically worse.
|Characteristics||Type 1 HIT||Type 2 HIT|
|Onset|| || |
|Severity of thrombocytopenia|| || |
|Clinical features|| |
The significantly increased risk of bleeding is the main side effect of all anticoagulants.
We list the most important adverse effects. The selection is not exhaustive.
- DVT prophylaxis for prolonged bedrest, peri- and postoperative state, immobility
- Immediate anticoagulation effect for
- Prophylaxis of DVT in orthopedic and abdominal surgery, prolonged immobility
- Treatment of DVT
- Acute coronary syndrome
- Recent stroke
- Uncontrolled hypertension
- Active bleeding
- HIT (except for direct thrombin inhibitors which can be used for anticoagulation in HIT)
We list the most important contraindications. The selection is not exhaustive.
|Overview of advantages and disadvantages|
|Unfractionated heparin (UFH)||Low-molecular-weight heparin (LMWH)|
|Application|| || |
Special patient groups
- Physiological hypercoagulability (e.g., due to increased levels of clotting factors) leads to increased risk of thrombosis.
- UFH and LMWH can be used during pregnancy: neither cross the placenta nor are they transferred through breast milk
- LMWH has fewer side effects.