chondroitin-sulfates and Drug-Hypersensitivity

Topics: Adult; Adverse Drug Reaction Reporting Systems; Animals; Anticoagulants; Asia; Centers for Disease Control and Prevention, U.S.; Chemistry Techniques, Analytical; Child; Chondroitin Sulfates; Complement Activation; Disease Outbreaks; Drug Contamination; Drug Hypersensitivity; Heparin; Humans; Kallikreins; Molecular Structure; Porcine Reproductive and Respiratory Syndrome; Swine; United States; United States Food and Drug Administration

Pregnant patients with acute venous thrombosis or a history of thrombosis may need alternative anticoagulation, when heparin intolerance occurs. Only limited data on the use of the heparinoid danaparoid are available in literature. We reviewed the use of danaparoid in 51 pregnancies of 49 patients identified in literature between 1981 and 2004. All patients had developed heparin intolerance (32 due to heparin-induced thrombocytopenia, 19 mainly due to heparin-induced skin rashes) and had a current and/or past history of thromboembolic complications. The initial danaparoid dose regimens ranged from 1000 to 7500 U/day administered s.c. or i.v.. The median duration of danaparoid use was 10 weeks. Danaparoid was used until delivery of a healthy infant in 37 pregnancies. In the remaining 14 pregnancies it was stopped earlier, because anticoagulant treatment was no longer required (3/14) or an adverse event led to a treatment discontinuation (11/14). Four maternal bleeding events were recorded during pregnancy, delivery or postpartum, two of them were fatal due to placental problems. Three fetal deaths were recorded, all associated with maternal complications antedating danaparoid use. Danaparoid cross-reactivity was suspected in 4 HIT patients and 5 non-HIT patients with skin reactions and was confirmed serologically in one of the two HIT patients tested. In none of five fetal cord blood- and three maternal breast milksamples anti-Xa activity transfer was observed. In conclusion danaparoid can be used as an alternative antithrombotic agent in pregnant women with high thrombotic risk and intolerance to heparins.

Topics: Adult; Chondroitin Sulfates; Cross Reactions; Dermatan Sulfate; Drug Evaluation; Drug Hypersensitivity; Exanthema; Female; Hemorrhage; Heparin; Heparitin Sulfate; Humans; MEDLINE; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy Outcome; Retrospective Studies; Thrombocytopenia; Thrombosis

Delayed hypersensitivity to heparins and heparinoïd is a problem for prophylaxis of thrombo embolic diseases. The hirudins did not seem to have any cross-reactivity with the two others groups of anticoagulants. We present two clinical cases of delayed type reactions to heparins and heparinoïd and we reviewed the literature about adverse reactions to low molecular weight heparins and the alternative possibilities.

Topics: Aged; Anticoagulants; Chondroitin Sulfates; Cross Reactions; Dalteparin; Dermatan Sulfate; Drug Combinations; Drug Hypersensitivity; Enoxaparin; Female; Heparin; Heparin, Low-Molecular-Weight; Heparitin Sulfate; Hirudin Therapy; Hirudins; Humans; Hypersensitivity, Delayed; Nadroparin; Recombinant Proteins; Skin Tests

Despite the progress made in the development of cardiopulmonary bypass (CPB) equipment, systemic anticoagulation with unfractionated heparin and post-bypass neutralization with protamine are still used in most perfusion procedures. However, there are a number of situations where unfractionated heparin, protamine or both cannot be used for various reasons. Intolerance of protamine can be addressed with extracorporeal heparin removal devices, perfusion with (no) low systemic heparinization and, to some degree, by perfusion with alternative anticoagulants. Various alternative anticoagulation regimens have been used in cases of intolerance to unfractionated heparin, including extreme hemodilution, low molecular weight heparins, danaparoid, ancrod, r-hirudin, abciximab, tirofiban, argatroban and others. In the presence of heparin-induced thrombocytopenia (HIT) and thrombosis, the use of r-hirudin appears to be an acceptable solution which has been well studied. The main issue with r-hirudin is the difficulty in monitoring its activity during CPB, despite the fact that ecarin coagulation time assessment is now available. A more recent approach is based on selective blockage of platelet aggregation by means of monoclonal antibodies directed to GPIIb/IIIa receptors (abciximab) or the use of a GPIIb/IIIa inhibitor (tirofiban). An 80% blockage of the GPIIb/IIIa receptors and suppression of platelet aggregation to less than 20% allows the giving of unfractionated heparin and running CPB in a standard fashion despite HIT and thrombosis. Likewise, at the end of the procedure, unfractionated heparin is neutralized with protamine as usual and donor platelets are transfused if necessary. GPIIb/IIIa inhibitors are frequently used in interventional cardiology and, therefore, are available in most hospitals.

Topics: Abciximab; Ancrod; Antibodies, Monoclonal; Anticoagulants; Arginine; Cardiopulmonary Bypass; Chondroitin Sulfates; Cross Reactions; Dermatan Sulfate; Drug Combinations; Drug Hypersensitivity; Factor Xa Inhibitors; Hemodilution; Hemorrhage; Heparin; Heparin, Low-Molecular-Weight; Heparitin Sulfate; Hirudin Therapy; Humans; Immunoglobulin Fab Fragments; Perfusion; Pipecolic Acids; Platelet Aggregation Inhibitors; Protamines; Sulfonamides; Thrombocytopenia; Thrombophilia; Thrombosis; Tirofiban; Tyrosine

We compared anti-IIa activity of a heparin analogue and a reference product was carried out to confirm their biosimilarity. The experiment was based on the method of estimation of anti-IIa activity of a commercial sodium heparin preparation according to United States Pharmacopoeia. High similarity of the two medicinal heparin preparations by this parameter is shown. The method is recommended for the use in comparability studies.

Topics: Analysis of Variance; Animals; Biosimilar Pharmaceuticals; Cattle; Chondroitin Sulfates; Drug Hypersensitivity; Heparin; Prothrombin; Regression Analysis; Russia; Species Specificity; Swine

Beginning in 2007, anaphylactoid reactions associated with unfractionated heparin (UFH) occurred and resulted in some fatalities. These reactions were reported to be linked to the complement and contact system activation induced by certain batches of UFH containing the adulterant oversulphated chondroitin sulphate (OSCS).. Drug-specific secretion of selected cytokines from peripheral blood mononuclear cells (PBMC) of patients with hypersensitivity reactions to contaminated heparin was compared with the respective in vitro cytokine pattern of individuals with or without hypersensitivity to heparin, different glycosaminoglycans or other drugs.. Study individuals (n = 13) were classified as follows: patients with hypersensitivity reactions to contaminated (OSCS) heparin (n = 3), noncontaminated heparin (n = 1) or other compounds (n = 3) and patients with ongoing heparin therapy without symptoms of intolerance (n = 2). Four healthy individuals served as controls. PBMC were incubated with six different glycosaminoglycan structures. Drug-specific intracellular interleukin (IL)-5, interferon (IFN)-γ and IL-10 production was investigated by flow cytometry, while secretion of IL-5, IL-2 and IFN-γ was analysed by enzyme-linked immunosorbent assay.. PBMC from individuals with hypersensitivity reactions to contaminated heparin secreted considerable amounts of IL-2 in vitro. There was a suggestion that ongoing heparin therapy and the Li-heparin in the vials may have an impact on the lymphocyte reactivity of PBMC.. The in vitro lymphocyte reactivity pattern of PBMC from individuals with hypersensitivity reactions to contaminated heparins was neither typical for an immune-mediated nor for a nonimmune-mediated reaction. Possible effects of heparins in the test system itself may require consideration.

Topics: Adult; Aged; Aged, 80 and over; Anaphylaxis; Anticoagulants; Basophils; Chondroitin Sulfates; Cytokines; Drug Contamination; Drug Hypersensitivity; Enzyme-Linked Immunosorbent Assay; Female; Flow Cytometry; Glycosaminoglycans; Heparin; Humans; Interferon-gamma; Interleukin-10; Interleukin-2; Interleukin-5; Lymphocytes; Male; Middle Aged; Pilot Projects; Young Adult

To characterize the nature of a heparin contaminant's clinical effects in cases reported to the Adverse Event Reporting System (AERS). The FDA received reports of heparin-associated adverse events (AEs) starting in late 2007-early 2008 during a national investigation of allergic-type events. The investigation identified Baxter Healthcare-brand heparin product due to its strongest association with the events. Later, oversulfated chondroitin sulfate (OSCS), a heparin-like contaminant, was discovered.. This study was a case series of heparin reports in AERS received 1 January 2008 to 31 March 2008. Variables considered were frequency of treatment settings, AEs, mortality; as well as heparin dose and OSCS contamination.. Five hundred seventy-four AERS cases (unduplicated reports) were identified and included. Of 94 cases with a fatal outcome, 68 reported at least one AE term from the list used to identify an allergic-type event. Nearly 75% of AEs in cases of IV administration (n = 170/233) reportedly occurred within 10 minutes, whereas over half of subcutaneous administration cases (n = 13/23) resulted in times-to-event of greater than 24 hours. Although cases with a time-to-event of less than 10 minutes appeared to correlate with higher levels of OSCS contamination, no clear differences were noted between high- and low-to-absent OSCS concentration lots with respect to AEs observed.. Intravenous administration and a higher OSCS concentration appeared to correlate with a more rapid onset of event. The FDA continues to monitor AEs associated with heparin use and has taken appropriate regulatory action to ensure a safe heparin drug supply.

Topics: Adolescent; Adult; Adverse Drug Reaction Reporting Systems; Aged; Aged, 80 and over; Anticoagulants; Child; Child, Preschool; Chondroitin Sulfates; Drug Contamination; Drug Hypersensitivity; Female; Heparin; Humans; Male; Middle Aged; Retrospective Studies; Time Factors; United States; United States Food and Drug Administration; Young Adult

Severe hypersensitivity reactions have been reported with bolus injection of heparin contaminated with oversulfated chondroitin sulphate, which has been shown to activate the plasma contact system. In this paper, we parallel the pathophysiology of these acute side effects with this of hypersensitivity reaction during hemodialysis or blood product transfusion in patients treated with an angiotensin converting enzyme inhibitor.

Topics: Angiotensin-Converting Enzyme Inhibitors; Anticoagulants; Blood Transfusion; Chemistry, Pharmaceutical; China; Chondroitin Sulfates; Drug Hypersensitivity; Heparin; Humans; Renal Dialysis

Recently, certain batches of heparin have been associated with an acute, rapid onset of serious side-effects indicative of allergic-type reactions. These reports generated significant concern regarding the possible presence of a dangerous contaminant within heparin and highlighted the need to re-assess the purity criteria of heparin preparations for clinical use. Given the nature of the array of all possible contaminants, traditional screening tests cannot safely differentiate between contaminated and uncontaminated heparin preparations. Mono- and bi-dimensional NMR spectroscopy are powerful techniques that are able to detect and quantify a wide variety of potential sulfated polysaccharide contaminants. As such, these techniques are powerful tools for the analysis and assessment of heparin preparations.

Topics: Adult; Adverse Drug Reaction Reporting Systems; Animals; Anticoagulants; Child; Chondroitin Sulfates; Complement Activation; Disease Outbreaks; Drug Contamination; Drug Hypersensitivity; Heparin; Humans; Kallikreins; Molecular Structure; Nuclear Magnetic Resonance, Biomolecular; Porcine Reproductive and Respiratory Syndrome; Sulfates; Swine; United States; United States Food and Drug Administration

Topics: Animals; Chondroitin Sulfates; Disease Outbreaks; Drug Contamination; Drug Hypersensitivity; Heparin; Humans; Nuclear Magnetic Resonance, Biomolecular; Renal Dialysis; Swine

Topics: Adverse Drug Reaction Reporting Systems; Anaphylaxis; Anticoagulants; China; Chondroitin Sulfates; Drug Contamination; Drug Hypersensitivity; Heparin; Heparin, Low-Molecular-Weight; Humans; Infusions, Intravenous; Renal Dialysis; United States

Topics: Aged; Anticoagulants; Chondroitin Sulfates; Dermatan Sulfate; Drug Combinations; Drug Hypersensitivity; Female; Heparin; Heparinoids; Heparitin Sulfate; Humans; Hypersensitivity, Delayed; Injections, Intravenous; Injections, Subcutaneous

Topics: Anticoagulants; Blood Coagulation Factors; Chondroitin Sulfates; Dermatan Sulfate; Dose-Response Relationship, Drug; Drug Combinations; Drug Hypersensitivity; Drug Monitoring; Heparin, Low-Molecular-Weight; Heparitin Sulfate; Humans; Injections, Subcutaneous; Risk Factors; Skin Diseases; Thromboembolism

We report a patient who presented with a left proximal deep vein thrombosis at 25 + 5 weeks gestation. She developed a severe urticarial rash 3 weeks following initiation of therapy with Enoxaparin. The patient was heterozygous for the factor V Leiden mutation. She was treated with subcutaneous twice-daily danaparoid (Orgaran) for the remainder of the pregnancy, achieving anti-Xa levels in the therapeutic range 0.5-1.0 IU/ml. Delivery was at term by caesarean section 2 days after spontaneous rupture of membranes and failure to progress in labour. Danaparoid was withheld during this time. Danaparoid was restarted 3 h post delivery and the patient anticoagulated with warfarin in the post-partum period. There was no recurrence of thrombosis or bleeding events during therapy with danaparoid. No anti-Xa activity was demonstrated in breast milk.

Topics: Adult; Cesarean Section; Chondroitin Sulfates; Dermatan Sulfate; Drug Combinations; Drug Hypersensitivity; Enoxaparin; Factor V; Factor Xa Inhibitors; Female; Gestational Age; Heparitin Sulfate; Heterozygote; Humans; Injections, Subcutaneous; Milk, Human; Mutation; Pregnancy; Venous Thrombosis

Topics: Adult; Anticoagulants; Chondroitin Sulfates; Dalteparin; Dermatan Sulfate; Drug Combinations; Drug Hypersensitivity; Female; Heparitin Sulfate; Humans; Pregnancy; Pregnancy Complications, Hematologic; Venous Thrombosis

Topics: Anticoagulants; Chondroitin Sulfates; Cross Reactions; Dermatan Sulfate; Drug Combinations; Drug Hypersensitivity; Female; Heparin, Low-Molecular-Weight; Heparinoids; Heparitin Sulfate; Hirudins; Humans; Hypersensitivity, Delayed; Recombinant Proteins; Skin Tests

There is no consensus concerning thromboembolic prophylaxis in high-risk pregnant women with a previous history of heparin-induced thrombocytopenia. An alternative anticoagulant therapy is danaparoïd, whereas unfractioned and low-molecular-weight heparin therapy is contraindicated. We report a case of successful thrombosis prophylaxis using danaparoïd in a high-thrombosis-risk pregnant woman with a history of heparin-induced thrombocytopenia during a previous pregnancy and Widal's disease.

Topics: Adult; Anticoagulants; Aspirin; Asthma; Cephalosporins; Chondroitin Sulfates; Dermatan Sulfate; Drug Combinations; Drug Hypersensitivity; Female; Heparin; Heparinoids; Heparitin Sulfate; Humans; Pregnancy; Pregnancy Complications, Hematologic; Risk Factors; Thrombocytopenia; Thromboembolism

Eczematous, infiltrated plaques at the site of subcutaneously administered heparin appear to be common. Heparinoids cannot be recommended in general as a substitute for heparin or low molecular weight heparin because delayed-type skin reactions to these molecules can also occur, as demonstrated in this case report.

Topics: Anticoagulants; Chondroitin Sulfates; Dermatan Sulfate; Drug Combinations; Drug Eruptions; Drug Hypersensitivity; Female; Heparin, Low-Molecular-Weight; Heparinoids; Heparitin Sulfate; Humans; Hypersensitivity, Delayed; Middle Aged

The authors describe a case of heparin-induced skin reaction due to two preparations of low molecular weight heparin in a pregnant woman. The main characteristics of heparin-related cutaneous allergy are reported. The use of an heparinoid, usually indicated for patients with heparin-induced thrombocytopenia, appeared to be efficient and safe for the mother and her fetus. An epidural analgesia was performed for labor analgesia, 24 hours after the last injection of danaparid of sodium.

Topics: Adult; Analgesia, Epidural; Analgesia, Obstetrical; Anticoagulants; Chondroitin Sulfates; Dermatan Sulfate; Drug Combinations; Drug Eruptions; Drug Hypersensitivity; Female; Heparin, Low-Molecular-Weight; Heparitin Sulfate; Humans; Pregnancy; Pregnancy Complications; Thrombocytopenia

Heparin-associated thrombocytopenia (HAT) type II, a severe side effect of heparin therapy, is thought to be induced by an immunological mechanism. By crossreactivity studies we have demonstrated that sera of patients with HAT type II activate platelets in vitro not only after the addition of heparin but also after addition of a chemically polysulphated chondroitin-like substance, Arteparon, used for treatment of degenerative joint disease. In addition here, we describe a patient who developed deep venous thrombosis and pulmonary embolism following administration of Arteparon and typical HAT type II with thrombocytopenia, 36 h after the first administration of heparin. This patient had never received heparin, but had repeatedly been treated with Arteparon for degenerative joint disease. We conclude that this patient had been presensitized by Arteparon, as indicated by his clinical course. In vitro studies again confirm crossreactivity between heparin and Arteparon.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Chondroitin Sulfates; Cross Reactions; Drug Hypersensitivity; Glycosaminoglycans; Heparin; Humans; Male; Middle Aged; Pulmonary Embolism; Thrombocytopenia; Thrombophlebitis

Results of several tests in guinea pigs performed in order to check the hypersensitivity hazard of chondroitin sulfate are reported. As per theoretical expectations, no immuno-enhancing effect leading to hypersensitivity was recorded.

Topics: Anaphylaxis; Animals; Body Weight; Chondroitin Sulfates; Dinitrochlorobenzene; Drug Hypersensitivity; Female; Guinea Pigs; Injections, Intradermal; Male; Skin