*3.1.6. Real-world safety aspects*

Safe and effective use of heparin requires maintaining a delicate balance: dosing low enough to minimize the risk of bleeding, yet high enough to treat or prevent thrombosis. Achieving a therapeutic level of heparin within 24 hours significantly reduces the risk for recurrent VTE [52]. However, non-protocol-driven practice achieves this outcome only 40% of the time [53].

Bleeding is the primary untoward effect of heparin. Major bleeding occurs in 1–5% of patients treated with intravenous heparin for venous thromboembolism [54]. The incidence of bleeding is somewhat less in patients treated with LMWH for this indication, although the risk of bleeding appears to increase with higher total daily doses of heparin.

Heparin-induced thrombocytopenia (platelet count <150,000/mL or a 50% decrease from the pre-treatment value) occurs in ~0.5% of medical patients 5–10 days after initiation of therapy with heparin [55]. Although the incidence may be lower, thrombocytopenia also occurs with LMWHs and fondaparinux and platelet counts should be monitored. Thrombotic complications that can be life-threatening or lead to amputation occur in about one-half of the affected heparin-treated patients and may precede the onset of thrombocytopenia. The incidence of heparin-induced thrombocytopenia and thrombosis is higher in surgical patients than in medical patients. Women are twice as likely as men to develop this condition.
