Low Molecular Weight Heparin Fraction PK10169: A New Therapeutic Means for Anticoagulant Therapy?

Abstract

To test the efficacy and safety of low molecular weight heparin (LMWH) fractions in thromboembolic diseases, 2 pilot studies were performed. The aim of the first was to test the antithrombotic efficacy of the LMWH PK 10169 (Pharmuka Laboratories) in 9 patients (group I) with acute pulmonary embolism documented by pulmonary angiography and scintiscan. The second study was intended to test the safety of the same LMWH fraction in a group (group II) of 30 patients at high risk of bleeding but also requiring antithrombotic therapy. In the 2 groups, the antithrombotic efficacy of PK 10169 was found to be excellent: no recurrence of pulmonary embolism was noted in group I and no thrombotic event occurred in group II. Neither side effects nor major bleeding complications occurred in either group. However, 1 patient in group II had a moderate bleeding in relation to a transient overdosage, and 3 others exhibited minor bleeding which did not necessitate dosage adjustment. In these studies, PK 10169, at the dosage used, proved an effective antithrombotic therapy with few side effects even in a group of patients considered to be at high risk of bleeding.

Laboratory Monitoring of a Low Molecular Weight Heparin (Enoxaparin) with a New Clotting Test (Heptest)

“…The interest in low molecular weight (LMW) heparin is constantly growing for several reasons, but particularly because they show a higher bioavailability [1], Clini cal trials suggest that some LMW heparins are as effective as heparin in postoperative thromboprophylaxis [4], Also, LMW hepa rins have been used in small groups of pa tients with well documented venous throm bosis or pulmonary embolism [3], Although laboratory monitoring is not compulsory in surgical patients receiving a conventional prophylactic regimen, it may be important in the last group of patients [3]. However, the activated partial thromboplas tin time (APTT) is only partially sensitive to LMW heparin, and no other easy routine test is available at this moment.…”

A prospective, open-label, dose-escalating study of low molecular weight heparin during repeat vitrectomy for PVR and severe diabetic retinopathy

“…If no dose-limiting toxicity was identified in the first three patients, the dose was increased in controlled manner to 0.3 IU/cc in the next three patients and subsequently to 1.0 IU/cc, 3.0 IU/cc and 6.0 IU/cc to complete a clinical response curve. We chose our study dose range based on the well-studied therapeutic intravenous dosage [3] and the highest nontoxic dose of LMWH used in animal studies [4]. Additional surgeries were performed at the 3.0 IU/cc and 6.0 IU/cc dose levels in order to gain additional experience with the drug.…”

“…Iverson et al demonstrated that a LMWH (Fragmin, KabiVitrum AB, Stockholm) given at 5 IU/cc in the ocular irrigating solution markedly inhibited post-vitrectomy fibrin in a rabbit model without increasing intraocular hemorrhage [4]. Although no dose escalation study of intravitreal enoxaparin has ever been performed, a number of previous studies have determined the safe and effective intravenous dose of enoxaparin [3]. These studies have generally found an antithrombotic (anti-fibrinogenic) dose of enoxaparin at 0.1 to 0.2 IU/cc.…”

“…Because of the theoretical advantages of low molecular weight heparins, a pilot study was undertaken to explore the effect of enoxaparin used in ocular irrigating solution during vitrectomy. As enoxaparin has been previously administered by intravenous infusion in humans [3], and both heparin and low dose enoxaparin have been administered in the ocular irrigating solution in humans [1,8], we were comfortable in performing dose escalation studies of enoxaparin in the ocular irrigating solution during vitrectomy. Biocompatibility studies were completed by the Pharmacy Department at our institution prior to beginning the study.…”

Monitoring Therapy with LMW Heparin: A Comparison of Three Chromogenic Substrate Assays and the Heptest Clotting Assay

“…Although the antithrom botic effect of various LMWH probably is not directly related to the anti Xa effect mea sured in the patient's plasma, this test princi ple is at present the most convenient [12]. Accordingly, LMWH therapy has mainly been monitored with factor-Xa-based chromogenic substrate (CS) assays [6,7,9,13,14], Preliminary data have suggested that the therapeutic range for some LMWH prepara tions is between 0.2 and 1.0 anti FXa U/ml [15].…”