From its first introduction as a therapeutic agent for IC in 1963 on treatment results of heparin use have been rarely but constantly reported until today. The preferred route of administration is by intravesical instillation although patients suffering from bladder pain syndrome often fear and wish to avoid repetitive catheterization. Thus, the subcutaneous route of administration as reported for the first time by Gunnar Lose in 1983 and summarized in Chap. 15, offers an alternative, less painful and minimal invasive approach. However, in contrast to subcutaneous administration which requires the monitoring of clotting parameters, no such information is required for the safe use of instillations which increases their feasibility regarding follow up monitoring of patients and has added to their preference as a mode of administration.

The use of heparin in the treatment of bladder pain syndromes is unchanged based on the hypothesis that the glycosaminoglycan-rich bladder surface mucus is the primary regulator of epithelial permeability and that a structurally similar exogenous sulfated polysaccharide such as heparin could effectively treat the painful bladder by compensating for the dysfunction of natural bladder mucus. Heparin is believed to work by replacing or aiding in the recovery of the individual’s dysfunctional bladder mucus, subsequently reducing epithelial permeability and protecting from symptom provocation by noxious molecules.

Intravesical heparin in the management of IC/BPS has been studied in controlled and noncontrolled trials enrolling more than 100 treated patients and demonstrating efficacy rates ranging from 56 to 94%. AUA guidelines recommend intravesical heparin as a second-line treatment option, having potential benefit in a subset of patients with an uncertain benefit/risk ratio. However, adverse events reported were not serious. In a controlled trial, minor events in patients receiving alkalinized lidocaine in combination with heparin were similar to placebo in frequency and type, affecting approximately 30–50% of patients and including headache, dizziness, lightheadedness, and bladder or urethral pain. No increases in activated partial thromboplastin time or prothrombin time were observed. Bladder discomfort occurred with every instillation in 60% of patients treated with intravesical heparin. In an open-label study, gross hematuria was observed only on the day of instillation and was not associated with systemic coagulation disorder.