Efficacy and Tolerability of Clarema 1% Cream and Hirudoid 40000？U.APTT Gel in the Topical Treatment of Haematomas and/or Subcutaneous Haematic Extravasations

Ninety-six caucasian both-gender patients with haematomas and/or subcutaneous haematic extravasation of traumatic or surgical origin were randomized to receive local treatment (max 10 days) with heparan sulfate cream or glycosaminoglycan-polysulphate (GAGPS) gel. Signs (oedema, disability, and colour of the lesion) and symptoms (pain at rest and at movement) (scored 0–3), the sum of the scores (primary end point), and the size of the lesion were evaluated at the baseline visit and afterwards every 5 days. The rate of the patients completely healed at the end of the study was also recorded. The results of the study showed that heparan sulfate 1% cream was comparable or superior to GAGPS gel in relieving signs and symptoms. No AEs were recorded. 1. Introduction Heparan sulfate is a mucopolysaccaride present in the arterial and venous wall, provided by fibrinolytic and anticoagulant activities. Heparan sulfate is a member of the glycosaminoglycan family of carbohydrates, and its structure is very closely related to heparin, both consisting of a variable sulfated repeating disaccharide units. The most common disaccharide unit of heparan sulfate is a glucuronic acid linked to N-acetylglucosamine, typically making around 50% of the total disaccharide units [1–3]. In pharmacodynamic studies, heparan sulfate was shown to inhibit thrombogenesis and to promote the fibrinolytic process through both the intrinsic and the extrinsic pathway. The mechanism of action includes alterations of the other steps of the fibrinolytic process by activating the proactivants and antagonising the plasmin inhibitors, thus showing an anti-Xa and anticomplement activity. Given by oral route in patients with chronic venous insufficiency, heparan sulfate proved to be effective in reducing symptoms of itching, oedema, spontaneous pain, and nocturnal cramp, while exerting marked profibrinolytic and prohemorheological effect [4, 5]. A cream formulation of heparan sulfate (SPC Clarema 1% cream) has been obtained by means of specific methods of extraction and purification. This formulation exerts marked antithrombotic properties, which are the result of an intensive profibrinolytic activity and of the activation of antithrombin III (AT III). Heparan sulfate in cream form, when applied in subjects with alteration of the superficial venous circulation, gave clinically significant results in terms of pain remission, and reduction of the local oedema and of phlogistic infiltration. Heparan sulfate 1% cream is actually indicated for the local treatment of sequelae of phlebothrombosis,