heparitin-sulfate and Drug-Hypersensitivity

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

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