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At least 19 recordsLinked to original sources
PubMed2000

Low-molecular-weight heparins or heparinoids versus standard unfractionated heparin for acute ischaemic stroke.

BACKGROUND: Low molecular weight heparins and heparinoids may be associated with lower risks of haemorrhage and more powerful antithrombotic effects than standard unfractionated heparin. OBJECTIVES: The objective of this review was to compare the effects of low molecular weight heparins or heparinoids with those of unfractionated heparin in people with acute confirmed or presumed ischaemic stroke. SEARCH STRATEGY: We searched the Cochrane Stroke Group trials register and MedStrategy (1995). We also contacted pharmaceutical companies. Date of most recent search: April 1999. SELECTION CRITERIA: Randomised trials comparing heparinoids or low molecular weight heparins with standard unfractionated heparin in people with acute ischaemic stroke. Only trials where treatment was started within 14 days of stroke onset were included. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected studies for inclusion, assessed trial quality and extracted the data. MAIN RESULTS: Five trials involving 705 people were included. Four trials compared a heparinoid (danaparoid), and one compared a low molecular weight heparin (enoxaparin), with standard unfractionated heparin. Overall, 55/414 (13%) of the patients allocated danaparoid or enoxaparin had deep vein thrombosis compared with 65/291 (22%) of those allocated unfractionated heparin. This reduction was significant (odds ratio 0.52, 95% confidence interval 0.56 - 0.79). However, the number of more major events (pulmonary embolism, death, intra-cranial or extra-cranial haemorrhage) was too small to provide a reliable estimate of more important benefits and risks. No information was reported for recurrent stroke or functional outcome in survivors. REVIEWER'S CONCLUSIONS: Low molecular weight heparin or heparinoid appear to decrease the occurrence of deep vein thrombosis compared to standard unfractionated heparin, but there are too few data to provide reliable information on their effect on other important outcomes, including death and intracranial haemorrhage.

Anticoagulants↗
PubMed1996

Tolerance to intravenous administration of heparin and heparinoid in a patient with delayed-type hypersensitivity to heparins and heparinoids.

Delayed-type hypersensitivity reactions to subcutaneously (s.c.) injected heparins are common. Since similar reactions usually occur to different heparin preparations, semisynthetic heparinoids might be a therapeutic alternative. We report a patient exhibiting eczematous reactions to heparins as well as heparinoids; delayed-type hypersensitivity was demonstrated by intracutaneous (i.c.) and patch tests, as well as by s.c. provocation. Remarkably, intravenous (i.v.) administration of heparin as well as heparinoid was well-tolerated.

Anticoagulants↗
PubMed2000

[Effect of heparinoid derived from porcine duodenum on the proliferation of cultured smooth muscle cells].

AIM: To study the antiproliferative effect of haparinoid derived from porcine duodenum (heparinoid) on cultured vascular smooth muscle cells. METHODS: Cultured bovine aortic smooth muscle cells (BASMCs) of 5-10 passages were seeded into 24 and 72-well cluster culture plates and were synchronized by 48 h serum deprivation. Then, the cells were re-stimulated by serum repletion with or without heparinoid. The antiproliferative effect of heparinoid was evaluated by crystal violet staining and MTT assay 72 h after serum repletion. To study the drug action on cytomorphological changes, three kinds of cells [quiescent cells, cells treated with 10% fetal calf serum (FCS) with or without heparinoid] were observed by transmission electron microscopy. After synchronized and re-stimulated as above, BASMCs were treated with heparinoid 0.8 mg.mL-1 at selected points during serum repletion. The cells were harvested at specified times after serum repletion, then cellular DNA contents (to estimate the proportions of cells in different phases of the cell cycle) and the contents of alpha-actin, c-myc and c-fos proteins were measured by flow cytometry. RESULTS: Heparinoid was shown to inhibit the proliferation of BASMCs induced by 10% FCS. The inhibitory effect was weakened when heparinoid was added 2 h after serum repletion, and there was no antiproliferative effect when heparinoid was added 12 h after serum repletion. Electron micrographs showed that cells treated with 10% FCS and heparinoid expressed a contractile phenotype, while cells treated with 10% FCS only expressed a synthetic phenotype. Flow cytometry study showed remarkable increase of alpha-actin, and decrease of c-myc and c-fos proteins in the cells treated with heparinoid. CONCLUSION: Heparinoid was found to inhibit the proliferation of BASMCs. The antiproliferative effect occurred at the early phase of the cell cycle. It might be due to the drug's influence on cell phenotype modulation and the down regulation of c-myc and c-fos proto-oncogenes expression.

Animals↗
PubMed2002

Arthus reaction to lepirudin, a new recombinant hirudin, and delayed-type hypersensitivity to several heparins and heparinoids, with tolerance to its intravenous administration.

The pathogenesis of allergic reactions to heparin is poorly understood. Clinically, this phenomenon is relevant because of its increasing incidence and the resulting therapeutic challenges due to various cross-reactions between unfractionated and low-molecular weight heparins as well as between heparins and heparinoids. A 44-year-old female patient had developed a delayed-type hypersensitivity to certoparin-sodium. Diagnostic allergy testing revealed various cross-reactions between different heparins as well as an intolerance to heparinoids. After subcutaneous challenge with the recombinant hirudin lepirudin (Refludan) the patient developed a local Arthus reaction at the injection site. In general, recombinant hirudins do not cross-react with high- or low-molecular weight heparins and heparinoids because of a different molecular structure and are therefore an alternative in case of adverse reactions to heparins and heparinoids. Whereas a local Arthus reaction has already been described twice for low-molecular weight heparins, this is to the best of our knowledge the first observation of a superficial leukocytoclastic vasculitis due to s.c. applied lepirudin. Intravenous administration of heparins and heparinoids in case of hypersensitivity to these drugs following topical application risks a generalized eczematous reaction in patients with delayed-type allergy to both groups of substances. In our patient with delayed-type hypersensitivity to heparins and heparinoids and superficial vasculitis due to lepirudin, the intravenous challenge with heparin and a heparinoid was justified as an ultima ratio measure and proved to be the useful therapeutical alternative.

Adult↗
PubMed1985

A randomized blind study comparing standard heparin and a new low molecular weight heparinoid in cardiopulmonary bypass surgery in dogs.

Postoperative hemorrhage remains a serious complication in cardiopulmonary bypass (CPB) surgery. In our study, alternative anticoagulation with a new low molecular weight (LMW) heparinoid (Org 10172) was compared with a standardized heparin regimen. A preliminary dose-finding study indicated the minimal effective heparinoid dose to be 260 anti-Xa U/kg body weight, which was comparable to the standardized heparin regime, as revealed by similar plasma anti-Xa values. The following randomized open pilot study in 12 mongrel dogs undergoing CPB showed the heparinoid to be as effective as heparin, with an additional advantageous decrease in postoperative blood loss in the Org 10172 group. Our randomized blind study in 16 mongrel dogs undergoing CPB was performed to confirm previous results. Both antithrombotic agents were effective in the prevention of clot formation within the extracorporeal circuit. Hematocrit values and erythrocyte and platelet counts showed no significant intergroup differences. Post-CPB leukocyte counts revealed a significantly more rapid increase in the group given heparinoid (P less than 0.05). In the group given heparin, the expected prolongations of both the thrombin time (TT) and activated partial thromboplastin time (APTT) were noted, whereas in the group given heparinoid, only a transient peak prolongation of the TT after dose administration was revealed, and no significant prolongation of the APTT. Mean anti-Xa plasma levels were similar during CPB, showing a rapid decrease in the group given heparin on protamine administration, as did the APTT. Assessment of the operating field indicated an elevated intraoperative blood loss in the group given heparin. Postoperative blood loss measured over a period of 2.5 hours after closure of the thorax was significantly lower in the group given heparinoid than in the heparinized animals (625 +/- 100.0 ml, mean +/- SD, and 806 +/- 178.2 ml, respectively; P less than 0.05). Our observations suggest that the LMW heparinoid Org 10172 has an increased benefit/risk ratio over standard heparin and is effective in CPB in dogs. Additional investigations in humans should verify the possibility of use of this substance as an alternative means of anticoagulation during CPB in patients in whom heparin is relatively contraindicated.

Animals↗
PubMed1993

[Heparinoids versus nitroglycerin in the treatment of superficial phlebitis].

The purpose of this study was to evaluate the beneficial effects of transdermal nitroglycerine (TNG) in the treatment of superficial phlebitis caused by endovenous catheters and to compare them with the effects from the application of heparinoid substances. The study performed was prospective, randomized during a six-day period. One hundred patients (73 male and 27 female), aged 28-89 years (mean 67.3), participated in the study; all presented phlebitis, diagnosed by the presence of pain, erythema, edema, and fibrous cord in the area around the catheter. Among 50 subjects, two cm of NTG gel were administered to the affected zone once a day, and for the other 50 subjects, heparinoid substances were applied three times a day. The value parameters were: time for the disappearance of pain and time for reducing erythema, edema, and fibrous cord in half (all measured in hours). We found significant differences between the two treatments with TNG yielding greater improvement in terms of disappearance of pain (TNG: 50.2 +/- 39.7, heparinoids: 72.0 +/- 39.9), time for reducing erythema in half (TNG: 28.0 +/- 24.2, heparinoids: 54.6 +/- 34.5), and time for reducing fibrous cord in half (TNG: 58.3 +/- 38.4, heparinoids: 84.5 +/- 41.5). Edema was reduce before with TNG; however, this difference was not significant (TNG: 31.2 +/- 20.3, heparinoids: 33.0 +/- 25.7). We conclude that transcutaneous TNG should be applied systematically in patients with superficial phlebitis, given that it is more effective than the usual treatment with heparinoid substances.

Adult↗
PubMed2005

Low-molecular-weight heparins or heparinoids versus standard unfractionated heparin for acute ischaemic stroke.

BACKGROUND: Low-molecular-weight heparins and heparinoids are anticoagulants that may be associated with lower risks of haemorrhage and more powerful antithrombotic (anti-clotting) effects than standard unfractionated heparin. OBJECTIVES: The objective of this review was to compare the effects of low-molecular-weight heparins or heparinoids with those of unfractionated heparin in people with acute, confirmed or presumed, ischaemic stroke (sudden blockage of an artery carrying blood to the brain). SEARCH STRATEGY: We searched the Cochrane Stroke Group trials register (last searched November 2003). In addition we searched the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 4, 2003), MEDLINE (1966 to October 2003) and EMBASE (1980 to October 2003). For previous versions of this review we searched MedStrategy (1995) and also contacted pharmaceutical companies. SELECTION CRITERIA: Randomised trials comparing heparinoids or low-molecular-weight heparins with standard unfractionated heparin in people with acute ischaemic stroke. Only trials where treatment was started within 14 days of stroke onset were included. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected studies for inclusion, assessed trial quality and extracted the data. MAIN RESULTS: Six trials involving 740 people were included. Four trials compared a heparinoid (danaparoid), one trial compared a low-molecular-weight heparin (enoxaparin), and one trial compared an unspecified low-molecular-weight heparin with standard unfractionated heparin. Allocation a to low-molecular-weight heparin or heparinoid was associated with a significant reduction in the odds of deep vein thrombosis (Peto odds ratio 0.52, 95% confidence interval 0.56 to 0.79). However, the number of more major events (pulmonary embolism, death, intra-cranial or extra-cranial haemorrhage) was too small to provide a reliable estimate of more important benefits and risks. No information was reported for recurrent stroke or functional outcome. AUTHORS' CONCLUSIONS: Treatment with a low-molecular-weight heparin or heparinoid after acute ischaemic stroke appears to decrease the occurrence of deep vein thrombosis compared to standard unfractionated heparin, but there are too few data to provide reliable information on their effects on other important outcomes, including death and intracranial haemorrhage.

Anticoagulants↗
PubMed1998

[Effect of heparinoid on the proliferation of rabbit vascular smooth muscle cells in vitro].

Proliferation of vascular smooth muscle cells(VSMCs) represents an important event in vascular lesion formation. In the present study, we investigated whether heparinoid abstracted from porcine duodenum inhibits the proliferation of rabbit aortic VSMCs in vitro, using the method of colorimetric MTT (tetrazolium). Our results showed that heparinoid at 1.6-0.05 mg.ml-1 significantly inhibits VSMCs proliferation induced by fetal calf serum(FCS, 10%), basic fibroblast growth factor(bFGF, 50 ng.ml-1) or interleukin-1(IL-1, 50 u.ml-1). In inducing with bFGF, the inhibitive effect of heparinoid was more potent than that of heparin, while in inducing with FCS or IL-1, the inhibitive effect of heparin was more potent than that of heparinoid. Preincubation with heparinoid at 0.2-0.05 mg.ml-1, the vascular smooth muscle cell proliferation induced by FCS was also inhibited. Our results imply that heparinoid may be useful to protect the atherosclerosis and angioplasty restenosis.

Animals↗
PubMed1977

[Effect of heparinoids on the blood sugar level and blood lipids in diabetes mellitus].

The paper is a clinical experimental work, studying the heparinoid effect upon blood sugar level, blood lipid fractions, endogenic heparin and lipo-brigther-becoming activity in diabetics. Heparinoids are applied in acute experiment. A total of 37 subjects were examined--22 diabetics with adult type of diabetes, 10 clinically healthy subjects and 5 diabetics examined only with 500 ml physiologic salt solution. The same patients were examined with heparin as well for a comparison. Blood sugar, NEFA, lipolyzing activity, total lipids, total cholesterol, beta-lipoproteins, total phospholipids, triglycerides and endogenic heparin were determined prior to and post infusion introduction of heparinoids. The results reveal that heparinoids have two basic biochemical effects decrease blood sugar lever in diabetics and change the blood lipid fraction level. They depend on the structural peculiarities of the preparations. Heparinoids stimulate heparin activity as well, through which they realize their biochemical effect to a certain extent. The decreasing effect on blood sugar level of heparinoids is stronger as compared with heparin.

Adolescent↗
PubMed1987

Synthesis of new heparinoids with high anticoagulant activity.

New heparinoids were synthesized by the chemical method starting from ring-opening polymerization of anhydro sugar derivatives. Sulfation of synthetic (1----6)-alpha-linked 3-amino-3-deoxy-D-glucopyranan and its copolymers gave dextran-type heparinoids having a sulfamide group on the C-3 carbon of the sugar unit. Heparinoids with different sulfamide contents indicated that the anticoagulant activity (35.3-41.3 units/mg) is independent of the sulfamide content, while an increase in sulfamide content lowered the toxicity. Sulfation of (1----5)-alpha-D-xylofuranan and -ribofuranan provided furanan-type heparinoids the anticoagulant activities of which were higher than those of the corresponding sulfated pyranan-type polysaccharides (1----4)-beta-D-xylopyranan and -ribopyranan. The highest activity (69.1 units/mg) was shown by sulfated (1----5)-alpha-D-xylofuranan. The dextran-type heparinoid having a sulfamide group showed a high anticoagulant activity also in vivo and high lipemia-clearing activity.

Animals↗
PubMed2002

Effect of heparinoid on the production of tissue inhibitor of metalloproteinases (TIMP)-3 in rheumatoid synovial fibroblasts.

Heparinoid is one of the major contents of Mobilat widely used as an antirheumatic drug. To clarify the precise mechanisms of the antirheumatic effect of heparinoid, we investigated its effects on the production of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) from rheumatoid synovial fibroblasts stimulated (or not) with interleukin-1 alpha (IL-1alpha) at 100 units mL(-1). The expression of TIMP-3 mRNA was also investigated in a similar manner. The production of both MMPs and TIMPs and the expression of TIMP-3 mRNA were investigated by western-blot analysis and northern-blot hybridization, respectively. Under the stimulation of IL-1alpha, heparinoid increased the production of TIMP-3 in a concentration-dependent manner, but not TIMP-1, TIMP-2, MMP-1 or MMP-3. Heparinoid did not affect the expression of TIMP-3 mRNA that was increased by the stimulation of IL-1alpha. These findings suggest that the anti-rheumatoid effect of heparinoid may be due to increased production of TIMP-3. This increase in TIMP-3 may help redress the imbalance between the amounts of MMPs and TIMPs as observed in the joint tissues of rheumatoid arthritis and osteoarthritis patients.

Antirheumatic Agents↗
PubMed1992

Parenteral anticoagulation with the heparinoid Lomoparan (Org 10172) in patients with heparin induced thrombocytopenia and thrombosis.

Progressive thrombocytopenia may develop in as many as 5% of patients receiving heparin anticoagulation. In these patients, the risk of thromboembolic complications as well as continued thrombocytopenia necessitates discontinuation of heparin and initiation of an alternative anticoagulant when indicated. The heparinoid Lomoparan (Org 10172) is a mixture of several non-heparin low molecular weight glycosaminoglycans with proven anticoagulant efficacy that is generally non-reactive with platelets in the presence of plasma from patients with heparin induced thrombocytopenia, whereas standard heparin will induce platelet aggregation. We evaluated the role of heparinoid as a potential alternative anticoagulant in patients with heparin induced thrombocytopenia. During a 6 month period, we identified six patients with heparin induced thrombocytopenia who required an alternative parenteral anticoagulant, four as primary treatment for specific medical problem, and two as anticoagulation during a necessary surgical procedure. Heparinoid was used successfully in both medical and surgical patients requiring parenteral anticoagulation. In no case was there an exacerbation of the thrombocytopenia nor thromboembolic complications while on heparinoid therapy. Three of our patients sustained hemorrhagic complications, predominantly in the post-surgical setting in association with elevated anti-factor Xa levels and additional anticoagulant agents. We feel that these results confirm the utility of heparinoid anticoagulation in a select subset of patients with heparin induced thrombocytopenia who require continued parenteral anticoagulation.

Anticoagulants↗
PubMed2004

Fondaparinux: a suitable alternative in cases of delayed-type allergy to heparins and semisynthetic heparinoids? A study of 7 cases.

Hypersensitivity to unfractionated and low-molecular-weight heparins and semisynthetic heparinoids is increasingly common. 7 female patients between 30 and 74 years with delayed-type allergy to heparins and semisynthetic heparinoids were investigated for (cross)-reactivity to fondaparinux, a new pentasaccharide with selective factor Xa inhibition. All patients showed delayed-type reactions to heparins and some additional cross-reaction to a heparinoid on intracutaneous testing. 6/7 tolerated fondaparinux on intradermal testing as well as on subcutaneous challenge testing. However, the 7th patient developed a characteristic delayed-type reaction to both skin tests with fondaparinux. Fondaparinux is a new synthetic pentasaccharide with a molecular weight of 1.728 Da. In some patients with cross-reactivity between various heparins and semisynthetic heparinoids, lepirudin, a recombinant hirudin, may be a safe and effective alternative. However, combined allergy to hirudin and heparins has been reported. Sometimes, intravenous administration of heparins or heparinoids may be tolerated. However, these patients are at risk of developing a systemic reaction. The pathogenesis of heparin hypersensitivity is not fully understood. Heparins may act as haptens by binding to dermal and/or subcutaneous structural proteins. The chemical structures of heparins and fondaparinux are different concerning their alpha- and beta-configuration and the molecular weight. However, some of their functional groups are nearly identical and therefore similar chemical and pharmacological reactivity is to be expected. Fondaparinux seems to be a valuable alternative in most cases of heparin and hirudin hypersensitivity. The clearly rare cross-reaction between fondaparinux and heparins, now confirmed by us, may be due to differences in the response to haptens.

Adult↗
PubMed2005

Venous thromboembolism in radical prostatectomy: is heparinoid prophylaxis warranted?

OBJECTIVE: To review the incidence of venous thromboembolism (VTE) after radical retropubic prostatectomy (RRP) and evaluate the need for heparinoid prophylaxis as opposed to mechanical compression devices after RRP. PATIENTS AND METHODS: RRP is classified as a category 1 (high risk) procedure for VTE by the American College of Chest Physicians and several international guidelines recommend subcutaneous heparinoids as the preferred prophylaxis. However, this regimen may be associated with a greater risk of bleeding. We have not used heparinoid prophylaxis but place a mechanical compression device for prophylaxis of VTE, and report our clinical experience over a 12-year period. Between 1992 and 2004, all RRPs carried out by one surgeon (M.S.S.) at our centre were retrospectively reviewed after obtaining institutional review board approval. The protocol for prophylaxis of VTE consisted of compression stockings and a sequential compression device from the time of entry into the operating room until complete ambulation (we encourage early ambulation). Patients were evaluated for VTE if they developed any clinical signs or symptoms. Patients were followed at 7 days, 6 weeks and 3 months after RRP in the first year and 6-monthly thereafter. All relevant clinical data and complications were entered in a database. RESULTS: In all there were 1364 RRPs; the mean (sd) age of the patients was 61 (7) years and the mean follow-up 44 (38) months. All patients had a mechanical compression device and ambulated on the first day after surgery. None received heparinoid prophylaxis. Three VTE events were identified (0.21%); two patients had a lower limb VTE and one an upper limb VTE. All were successfully treated with anticoagulation. No patient had a documented pulmonary embolus and none died from VTE. There was one death after RRP, from myocardial infarction. CONCLUSION: The incidence of VTE after RRP is low, possibly related to the use of a mechanical compression device and early aggressive mobilization. Despite the recommendations by some, we feel that routine heparinoid prophylaxis is questionable.

Aged↗