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• W2034709483 abstract "Dear Sir, Patients with type II heparin-induced thrombocytopenia (HIT), despite their low platelet count, are paradoxically at risk of developing thromboembolic venous and arterial complications. Treatment of these complications remains challenging; it is necessary to discontinue heparin therapy immediately and to initiate an alternative antithrombotic agent [1]. Treatment with vitamin K antagonists takes some days before reaching therapeutic levels and may initially produce a worsening of the hypercoagulable state observed in HIT patients. Therefore, oral anticoagulants should be started only after thrombocytopenia has resolved. For these reasons, in patients suffering from thromboembolic complications of HIT it is mandatory to initiate immediately an antithrombotic drug which covers this initial therapeutic time window. The aim of this letter is to report on the use of dermatan sulfate in six patients with HIT and acute venous thromboembolism. Dermatan sulfate (DS; Mediolanum Farmaceutici, Milan, Italy) is a selective inhibitor of thrombin acting through heparin cofactor II, with low cross-reactivity with heparin-induced antibodies [2]. DS has previously been successfully administered in a few patients with HIT [3, 4]. All the patients, five females and one male, average age 57.5 years, range 6–85 years, had a normal platelet count before the administration of heparin. HIT was defined as a reduction in platelet count to <100 per 109 L−1 or as a ≥ 50% drop from baseline platelet count in patients on heparin treatment in whom other potential causes of thrombocytopenia could be excluded. All the patients had a severe thrombocytopenia with a mean platelet count of 52 500 × 109 L−1 (range 22 000 × 109 L−1 to 87.00 × 109 L−1). HIT developed during the administration of unfractionated heparin in three cases and low-molecular-weight heparin in the three remaining cases. Reasons for giving heparin were prophylaxis of venous thromboembolism after major orthopedic surgery (four cases) or for a medical condition (one case) and treatment of upper limb deep vein catheter-related thrombosis in a child with acute leukemia. In the five patients receiving heparin for prophylaxis, the index thromboembolic event was acute pulmonary embolism in four cases (associated in three cases with a lower limb deep vein thrombosis) and proximal lower limb deep vein thrombosis in one case. A laboratory confirmation of HIT diagnosis was obtained in all patients, in four cases by an in vitro platelet aggregation test [5] and in two cases by an ELISA test for anti-PF4–heparin antibodies [6]. The aggregation test was positive for unfractionated heparin and three different low-molecular-weight heparins, while it was negative for DS. DS was infused intravenously at the initial dose of 0.6 mg kg−1 h−1, targeting an activated partial thromboplastin time (APTT) of 1.3–1.7 times the normal value. This regimen was chosen according to animal model data showing that maximum inhibition of thrombus growth is achieved with DS at less APTT prolongation than with heparin [7], human data on the relationship between DS infusion rate and APTT response [8], and previous experience of DS in the treatment of HIT [3, 4]. The first APTT was obtained after 4 h and then after every 6–24 h; a daily blood cell count was performed. The withdrawal of heparin associated with the infusion of DS allowed a prompt increase of the platelet count in all patients (average platelet count at the end of DS infusion 154 800 × 109 L−1, range 80 000 × 109 L−1 to 215 000 × 109 L−1) (Fig. 1). Time of platelet count rise during treatment with dermatan sulfate. All patients started oral anticoagulants when thrombocytopenia had resolved; DS therapy was stopped when the International Normalized Ratio value was in the therapeutic range for at least 24 h. The mean dose of DS was 0.618 ± 0.17 mg kg−1 h−1 and the infusions were continued for a mean of 174 ± 58.7 h (range 60–216). The level of anticoagulation achieved by DS was stable, making only minor dose adjustments necessary during the infusion. No bleeding complications or other adverse events were observed. In conclusion, in our series DS obtained an effective and safe anticoagulation, allowing a rapid rise in the platelet count. The use of DS should be considered in the treatment of thromboembolic complications during HIT. The stable anticoagulant effect of this agent and its low cost could make it favorite over the alternative anticoagulant drugs currently used for HIT." @default.
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• W2034709483 date "2003-12-01" @default.
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• W2034709483 title "Successful treatment with dermatan sulfate in six patients with heparin-induced thrombocytopenia and acute venous thromboembolism" @default.
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• W2034709483 doi "https://doi.org/10.1111/j.1538-7836.2003.0543l.x" @default.
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