Perenteral Anticoagulants (FETT)

Blood Products and Modifiers

Heparin (unfractionated)

ENOXAPARIN

Tinzaparin

• Administration

  • 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)

• Administration: subcutaneous

• Monitoring during therapy: anti-factor Xa activity can be assessed in specific cases; not generally recommended

• Clearance: renal (contraindicated for patients with renal insufficiency)

• Antidote: protamine sulfate (partial reversal)

• 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

  • LMWH: binds to antithrombin III → inhibition of factor Xa → decreased conversion of prothrombin → ↓ thrombin

  • Synthetic heparin: only binds to antithrombin III → selective inhibition of factor Xa

• Higher bioavailability than unfractionated heparin

• Long half-life: 2–4 times longer than unfractionated heparin

• Bleeding

• Drug-drug interactions

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

• Allergic reactions

• Heparin-induced thrombocytopenia: risk of type 2 HIT LMWH:UFH ≈ 1:10

• Osteoporosis —> Dose-dependent; therefore, switch to oral anticoagulants for long-term therapy. Osteoporosis is most likely related to increased osteoclastic activity, but decreased production of calcitriol is another potential cause.

• Drug interactions (e.g., ASA, tetracycline)

• Treatment with heparin, especially UFH, can cause thrombocytopenia.

• Thrombocytopenia may be immune-mediated heparin-induced thrombocytopenia (formerly known as type 2 HIT) or non-immune heparin associated thrombocytopenia (formerly known as type 1 HIT)

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

Low-dose therapy

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

High-dose therapy

• Immediate anticoagulation effect for

  • Atrial fibrillation

  • DVT, acute arterial thrombosis, pulmonary embolism

  • Acute coronary syndrome, myocardial infarction

  • Mechanical heart valve replacement

  • VTE prophylaxis for patients with hemodialysis, heart-lung machine, etc.

• 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)

Pregnancy

• 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.

Patients with decreased renal function

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