• Clinical science

Parenteral anticoagulation


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)

In order to detect heparin-induced thrombocytopenia, platelets must be continuously monitored during heparin therapy and a baseline should be established before commencing treatment.

Low molecular weight heparin (LMWH)

Synthetic heparin

  • Drugs: fondaparinux
  • Administration: subcutaneous
  • Monitoring during therapy:
  • Antidote: : possibly activated prothrombin complex concentrates (aPCC)

Direct thrombin inhibitors



Unfractionated heparin (UFH)

Low molecular weight heparin (LMWH) and synthetic heparin (fondaparinux)

Direct thrombin inhibitors

  • 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!


Adverse effects

General side effects

  • Bleeding
  • Drug-drug interactions

Specific side effects

Agents Side effects

Synthetic heparin

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
  • ∼ 10–20%
  • More commonly occurs with UFH
    • ∼ 1–5% for UFH
    • ∼ 0.1–1% for LMWH
  • Within the first 5 days after beginning treatment
  • Day 5–14
Severity of thrombocytopenia
  • Massive reduction: < 100,000 platelets/μL (or decrease of > 50% compared to baseline)
Clinical features
  • Clinically insignificant
  • Usually none

The significantly increased risk of bleeding is the main side effect of all anticoagulants.

Heparin treatment requires regular monitoring of the platelet count, especially for UFH, even before starting treatment.

We list the most important adverse effects. The selection is not exhaustive.



Low-dose therapy

  • DVT prophylaxis for prolonged bedrest, peri- and postoperative state, immobility

High-dose therapy

Low molecular weight heparin [13]

Direct thrombin inhibitors

Use direct thrombin inhibitors (Bivalirudin, Argatroban, Dabigatran) to treat the BAD HIT (type 2 HIT has a worse prognosis than type 1 HIT).




We list the most important contraindications. The selection is not exhaustive.

Additional considerations

Overview of advantages and disadvantages
Unfractionated heparin (UFH) Low-molecular-weight heparin (LMWH)
  • Subcutaneous or intravenous administration
  • Therapeutic administration requires infusion pump
  • Always administer subcutaneously
  • Low dose: subcutaneous administration every 8–12 hrs
  • High dose: intravenous administration with bolus and continuous application via infusion pump
  • Dosage depends on specific drug used, indication, body weight, and kidney function; adjust to body weight and decreased kidney function
  • Adequate anticoagulation is achieved sooner due to direct effect on thrombin
  • Protamine (the antidote) antagonizes effect of UFH
  • Effect of LMWH lasts for about 12 hours
  • Monitoring of anti-factor Xa is only necessary in patients with decreased kidney function (and significant over- or underweight); anti-factor Xa activity is measured 4 hrs after administration
  • Short half-life means anticoagulant effect quickly ceases once stopped
  • If used therapeutically, PTT levels have to be monitored frequently (target range: 1.5–2.5-fold prolongation)
  • In comparison with LMWH
    • Type 2 HIT is about 10-fold more common
    • Severe bleeding is more common
Preferred use
  • Emergencies (more easily titrated, available as IV infusion)
  • For patients with advanced renal failure (e.g., in patients with severe renal insufficiency (CrCl < 30mL/min) or the elderly)
  • DVT prophylaxis, outpatient care (longer half-life → fewer injections)
  • Generally preferred to UFH (fewer side effects, easier handling) as long as there are no contraindications


Special patient groups


Patients with decreased renal function

  • In severe renal failure: accumulation of LMWH → increased bleeding risk → adjust dose or switch to UFH