chondroitin-sulfates and Thromboembolism

Factor Xa (FXa) is a key enzyme that is positioned at the convergence of the intrinsic and extrinsic pathways in the blood coagulation cascade, and inactivation by a specific FXa inhibitor effectively prevents the generation of thrombin. Various types of low molecular weight (LMW) heparin, which function as semi-selective and indirect FXa inhibitors, are replacing unfractionated heparin (UFH) as agents for the prevention and treatment of venous thromboembolism (VTE), as well as in initial treatment for coronary events. Of those, heparinoid has been shown to be safer and more effective for the prevention of postoperative VTE than UFH, especially for treatment of heparin-induced thrombocytopenia (HIT). Further, synthetic pentasaccharide has been found to offer advantages over current thromboprophylactic regimens in a number of patients undergoing major orthopedic surgery. Other studies have shown that pentasaccharide is more effective for overall VTE in comparison with LMW heparin, though it was also associated with an increased rate of major bleeding. Synthetic, selective, and direct inhibitors to FXa, such as DX-9065a, are highly potent and orally bioavailable antithrombotic agents that have demonstrated an improved side effect profile, probably by allowing sufficient thrombin to remain for platelet activation and normal hemostasis, while preventing pathological thrombus formation. For thrombosis therapy, the most desirable type of antithrombotic agent is an orally active drug that has a broad range of effective doses and no hemorrhagic side effects. Presently, many types of direct inhibitors are in various stages of clinical trials and expected to provide significant benefits as compared to currently utilized therapy strategies.

Topics: Animals; Anticoagulants; Bleeding Time; Blood Coagulation; Chondroitin Sulfates; Clinical Trials as Topic; Dermatan Sulfate; Factor Xa Inhibitors; Fibrinolytic Agents; Fondaparinux; Hemostasis; Heparin; Heparin, Low-Molecular-Weight; Heparitin Sulfate; Humans; Models, Biological; Models, Chemical; Platelet Aggregation; Platelet Aggregation Inhibitors; Polysaccharides; Thromboembolism

Clinical outcomes of 1,478 danaparoid treatment case reports for HIT (involving 1,418 patients) treated between 1982 and mid-2004 are analysed. Treatment in 1,291 episodes was for current HIT. Thromboembolism due to HIT was present in 39.4%. The patients include 33 children and 32 pregnancies. Two hundred twenty-six patients required extra-corporeal circuit use for renal failure, 241 patients had a concomitant thrombophilic disorder, and 351 major operations were performed. Clinical outcomes were assessed during danaparoid treatment (range one day to 3.5 years) plus three months of follow-up. Of the danaparoid-treated patients 83.8% survived; 63.7% had no or minor adverse events and 20.1% suffered serious non-fatal adverse events. New thromboses occurred during 9.7% of treatment episodes, and 16.4% of treatment episodes had an inadequate treatment response (i. e. developed one or more of the following: new/extended thrombosis, persistent/new platelet count reduction, unplanned amputation during treatment and follow-up). Major bleeding was reported in 8.1% of treatment episodes. Clinical cross-reactivity of danaparoid (new/persistent platelet count reduction and/or new/extended thrombosis) was confirmed serologically in 23 of 36 patients with positive pretreatment serological danaparoid cross-reactivity and in 22 of 32 additional patients tested at the time of the new event, i.e. a total of 45 patients (3.2%). Clinical outcomes of these case reports of patients given danaparoid because of suspected or confirmed HIT appear to be comparable with those reported by others who used direct thrombin inhibitors, especially when a sufficient danaparoid dosing intensity was used in patients with isolated HIT. Post-operative bleeding limits danaparoid use for cardiopulmonary by-pass surgery. Routine clinical and platelet count monitoring are required to minimise adverse reactions due to cross-reactivity.

Topics: Adolescent; Adult; Adverse Drug Reaction Reporting Systems; Aged; Aged, 80 and over; Anticoagulants; Child; Child, Preschool; Chondroitin Sulfates; Cross Reactions; Dermatan Sulfate; Drug Administration Schedule; Exanthema; Female; Fibrinolytic Agents; Heparin; Heparitin Sulfate; Humans; Infant; Male; Middle Aged; Postoperative Hemorrhage; Practice Guidelines as Topic; Thrombocytopenia; Thromboembolism

Thromboembolic vascular diseases remain the main cause of death in Western industrialized societies. Anticoagulants retard the formation, growth, and embolization of thrombi and are effective agents in the prevention and treatment of thromboembolic disease. Anticoagulants in venous thromboembolism have been investigated extensively with rigorous randomized, controlled trials, while the roles for anticoagulants in arterial thromboembolism generally have evolved through natural history studies and empirical practice. Thus, many current guidelines for anticoagulant use in arterial disease are based on successful established routines and rational therapy. To effectively balance the efficacy and risks of anticoagulation, the vascular surgeon needs a thorough understanding of anticoagulant drugs, their mechanisms of action, and their proven and unproven indications. Since the first use of heparin in arterial surgery, a variety of new and different anticoagulants have become available, including low-molecular-weight heparins, heparin-like drugs, hirudins, and thrombin inhibitors. Despite their diverse actions, they all inhibit some portion of the plasma coagulation cascade, thus distinguishing them from platelet inhibitors or fibrinolytics. Every interference with the coagulation cascade carries a risk of minor, major, or fatal hemorrhage. To date, no drug or therapeutic strategy has succeeded fully in dissociating its antithrombotic effects from its risks of bleeding.

Topics: Anticoagulants; Arteriosclerosis; Blood Coagulation; Chondroitin Sulfates; Coumarins; Dermatan Sulfate; Drug Combinations; Heparin; Heparin, Low-Molecular-Weight; Heparitin Sulfate; Humans; Platelet Activation; Thrombin; Thromboembolism

New platelet antagonists act on the activation by ADP (clopidogrel, ATP analogue) or on the mechanism of aggregation itself, by binding to the IIb/IIIa glycoprotein complex. The new anticoagulants are as follows: saccharide structures such as danaparoïd and the pentasaccharide of antithrombin binding, and direct thrombin inhibitors, such as recombinating hirudines (desirudine, lepirudine), bivalirudine, melagatran.... Other molecular targets are possible, both at platelet and blood clotting levels but, for the moment, the dilemma remains and reinforcement of antithrombotic activity goes hand in hand with a greater decrease in the defensive mechanisms against bleeding. In general, there is no antidote and the products are often associated, which increases the risk of haemorrhage. The research and development in this field are handicapped by the lack of biological tools for pertinent, homogenous, reproducible evaluation of the effects on haemostasis. The present tendency is to do without biological monitoring for adapting dosage in favour of optimisation of the impact in a given situation, perhaps, above all, with respect to the preceding problem.

Topics: Anticoagulants; Blood Coagulation; Chondroitin Sulfates; Dermatan Sulfate; Drug Combinations; Fibrinolytic Agents; Hemorrhage; Heparitin Sulfate; Hirudin Therapy; Humans; Platelet Aggregation; Risk Factors; Thromboembolism

Topics: Chondroitin Sulfates; Dermatan Sulfate; Dextrans; Drug Administration Schedule; Drug Combinations; Fibrinolytic Agents; Heparin, Low-Molecular-Weight; Heparitin Sulfate; Humans; Pulmonary Embolism; Thromboembolism; Thrombophlebitis

To review the role of the laboratory in monitoring therapy with low-molecular-weight heparin, danaparoid, hirudin, and argatroban, as reflected in the medical literature and the consensus opinion of recognized experts in the field.. Review of the medical literature and current clinical practice by a panel of 6 international experts in the field of anticoagulant therapy.. The experts made an extensive review of the published literature and prepared a draft manuscript, which included preliminary recommendations. The draft manuscript was circulated to participants in the College of American Pathologists Conference XXXI on Laboratory Monitoring of Anticoagulant Therapy prior to the conference. The manuscript and recommendations were then presented at the Conference for discussion. Recommendations were accepted if a consensus of the 26 experts attending the Conference was reached. The results of the discussion were used to revise the manuscript into its final form.. This report reviews the mechanism of action and potential uses of these newer anticoagulant agents. General guidelines for monitoring these agents and 9 specific recommendations for laboratory monitoring of low-molecular-weight heparin and danaparoid are provided, along with citation of the appropriate supporting literature. Issues for which a consensus was not reached at the Conference are also discussed.

Topics: Anticoagulants; Arginine; Chondroitin Sulfates; Dermatan Sulfate; Drug Combinations; Drug Monitoring; Heparin; Heparin, Low-Molecular-Weight; Heparitin Sulfate; Hirudin Therapy; Hirudins; Humans; Pathology, Clinical; Pipecolic Acids; Sulfonamides; Thromboembolism

Heparin-induced thrombocytopenia (HIT) is a hypercoagulable syndrome strongly associated with thrombosis that is usually treated with drugs that inhibit factor Xa (danaparoid) or thrombin (lepirudin). In the present study the outcome of HIT-patients treated with danaparoid or lepirudin was compared using the single or combined endpoints of new thromboembolic complications (new TECs), amputations and/or death, and major bleeding. HIT-patients treated with lepirudin were enrolled in two prospective trials and patients, who were identified in the same two laboratories during the same time period, who were not enrolled into these studies but treated with danaparoid, were assessed retrospectively according to a standardized questionnaire. 126 danaparoid (60.3% female) and 175 lepirudin treated patients (58.3% female) fulfilled the same inclusion and exclusion criteria. In a time-to-event-analysis the cumulative risk of combined endpoint was higher in HIT-patients without thromboembolic complication at baseline treated with danaparoid (usually in prophylactic dose 750 anti-factor Xa units b.i.d. or t.i.d.s.c.) as compared to lepirudin (aPTT adjusted) (P = 0.020). Whereas HIT-patients with TEC at baseline who were usually treated with therapeutic dose had a similar outcome in both treatment groups (P = 0.913). Major bleeding occurred in 2.5% (95% CI 0.5-7.0%) of danaparoid treated patients as compared to 10.4% (95% CI 6.3-15.9%) of lepirudin treated patients until day 42 (P = 0.009). This indicates that the efficacies of therapeutic doses of danaparoid or lepirudin in preventing death, amputation or new TEC in HIT-patients do not differ largely, but the risk of bleeding seems to be higher in lepirudin treated patients. The prophylactic dose of danaparoid approved in the European Union for HIT without TEC at baseline seems suboptimal. A prospective comparative trial is required to verify these preliminary conclusions.

Topics: Age Factors; Aged; Amputation, Surgical; Anticoagulants; Chondroitin Sulfates; Dermatan Sulfate; Drug Combinations; Drug Evaluation; Female; Hemorrhage; Heparin; Heparitin Sulfate; Hirudins; Humans; Incidence; Male; Middle Aged; Recombinant Proteins; Retrospective Studies; Surveys and Questionnaires; Thrombocytopenia; Thromboembolism; Treatment Outcome

The study objective was to determine the relative efficacy and safety of a low-molecular-weight heparinoid (Orgaran) compared with aspirin for the prevention of postoperative venous thromboembolism in patients undergoing surgery for fractured hips. A double-blind, randomized, controlled trial was used to study 251 consecutive eligible and consenting patients undergoing surgery for hip fracture in seven participating hospitals.. Patients received either fixed-dose Orgaran by subcutaneous injection every 12 hours in a dose of 750 anti-Factor Xa units or aspirin 100 mg orally twice daily; both regimens were started 12 to 24 hours after surgery and continued for 14 days or until discharge, if sooner. All patients had postoperative 125I-fibrinogen leg scanning and impedance plethysmography. If the results of one or both tests were positive, then venography was performed. Otherwise, venography was done at day 14, or sooner if the patient was ready for discharge. Pulmonary embolism in symptomatic patients was diagnosed on the basis of a high probability perfusion/ventilation lung scan, a positive angiogram, or a clinically significant embolism detected at autopsy. Evaluable venograms were obtained in 90 of the 125 patients randomly assigned to receive Orgaran and in 87 of the 126 patients assigned to receive aspirin. Venous thromboembolism was detected in 25 (27.8%) patients in the Orgaran group and in 39 (44.3%) patients in the aspirin group. Thus, there was a relative risk reduction of 37% with Orgaran (P=.028; 95% confidence interval, 3.7% to 59.7%). Six (6.8%) of 88 patients in the Orgaran group and 12 (14.3%) of 84 patients in the aspirin group developed proximal deep vein thrombosis or pulmonary embolism, a relative risk reduction of 52% with Orgaran (P=.137; 95% confidence interval, -30.7% to 84.6%). Hemorrhagic complications occurred in 2 (1.6%) patients given Orgaran and 8 (6.4%) patients given aspirin (P=.10). There was one major bleed in the Orgaran group compared with four in the aspirin group.. This study demonstrates that Orgaran is significantly more efficacious than aspirin in preventing postoperative venous thromboembolism in patients undergoing surgery for fractured hips, with no evidence of any increase in hemorrhagic complications.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anticoagulants; Aspirin; Chondroitin Sulfates; Dermatan Sulfate; Double-Blind Method; Female; Heparitin Sulfate; Hip Fractures; Humans; Injections, Subcutaneous; Male; Middle Aged; Postoperative Complications; Thromboembolism

Identification of risk factors for bleeding and prospective evaluation of two bleeding risk scores in the treatment of acute venous thromboembolism.. Secondary analysis of a prospective, randomized, assessorblind, multicenter clinical trial.. One university and 2 regional teaching hospitals.. 188 patients treated with heparin or danaparoid for acute venous thromboembolism.. The presenting clinical features, the doses of the drugs, and the anticoagulant responses were analyzed using univariate and multivariate logistic regression analysis in order to evaluate prognostic factors for bleeding. In addition, the recently developed Utrecht bleeding risk score and Landefeld bleeding risk index were evaluated prospectively.. Major bleeding occurred in 4 patients (2.1%) and minor bleeding in 101 patients (53.7%). For all (major and minor combined) bleeding, body surface area < or = 2 m2 (odds ratio 2.3, 95% CI 1.2-4.4; p = 0.01), and malignancy (odds ratio 2.4, 95% CI 1.1-4.9; p = 0.02) were confirmed to be independent risk factors. An increased treatment-related risk of bleeding was observed in patients treated with high doses of heparin, independent of the concomitant activated partial thromboplastin time ratios. Both bleeding risk scores had low diagnostic value for bleeding in this sample of mainly minor bleeders.. A small body surface area and malignancy were associated with a higher frequency of bleeding. The bleeding risk scores merely offer the clinician a general estimation of the risk of bleeding. In patients with a small body surface area or in patients with malignancy, it may be of interest to study whether limited dose reduction of the anticoagulant drug may cause less bleeding without affecting efficacy.

Topics: Acenocoumarol; Acute Disease; Adult; Aged; Body Surface Area; Chondroitin Sulfates; Comorbidity; Dermatan Sulfate; Drug Combinations; Female; Fibrinolytic Agents; Hemorrhage; Heparin; Heparitin Sulfate; Humans; Male; Middle Aged; Neoplasms; Odds Ratio; Prospective Studies; Risk Factors; Single-Blind Method; Thromboembolism; Thrombolytic Therapy

To compare the efficacy and safety of two subcutaneous doses of danaparoid with that of continuous intravenous administration of unfractionated heparin in the treatment of venous thromboembolism.. An open-label, randomized, multicenter clinical trial.. One university hospital and two university-affiliated hospitals.. 209 patients suspected to have venous thromboembolism. Of these, 188 had a confirmed diagnosis (by ventilation-perfusion lung scan and ultrasonography or contrast venography of the leg) and received study medication.. Patients were randomly assigned to either low-dose danaparoid (intravenous loading dose of 1250 U followed by 1250 U administered subcutaneously twice daily [n = 65]); high-dose danaparoid (intravenous loading dose of 2000 U followed by 2000 U administered subcutaneously twice daily [n = 63]); or unfractionated heparin (intravenous loading dose of 2500 U followed by dose-adjusted continuous infusion [n = 60]). Treatment lasted at least 5 days and was continued until anticoagulation (achieved with acenocoumarol) was adequate.. Efficacy determined clinically and by repeated imaging tests on treatment days 5 to 8; safety determined by daily assessment for bleeding.. Two lung scans were done in each of 179 patients; ultrasonography or venography of the leg was done twice in each of 173 patients; and both repeated leg and lung tests were done in 166 patients. A significant reduction in recurrence or extension of venous thromboembolism was seen in patients receiving high-dose danaparoid (8 of 63 [13%]) compared with patients receiving intravenous unfractionated heparin (17 of 60 [28%]; relative risk, 0.45 [95% CI, 0.21 to 0.96]). Four of 61 patients receiving high-dose danaparoid (7%) and 14 of 58 patients receiving unfractionated heparin (24%) had recurrence of pulmonary embolism (relative risk, 0.27 [CI, 0.09 to 0.78]); 3 of 58 patients receiving high-dose danaparoid (5%) and 6 of 54 patients receiving unfractionated heparin (11%) had recurrence of deep venous thrombosis (relative risk, 0.47 [CI, 0.12 to 1.77]). Occurrence of major and minor bleeding was similar in the three groups; major bleeding occurred in 1 patient receiving low-dose danaparoid, 1 patient receiving high-dose danaparoid, and 2 patients receiving heparin.. Our results suggest that high-dose danaparoid is safer and more effective than unfractionated heparin for the treatment of venous thromboembolism.

Topics: Adult; Aged; Aged, 80 and over; Chondroitin Sulfates; Dermatan Sulfate; Drug Administration Schedule; Drug Combinations; Female; Hemorrhage; Heparin; Heparinoids; Heparitin Sulfate; Humans; Infusions, Intravenous; Injections, Subcutaneous; Male; Middle Aged; Pulmonary Embolism; Thromboembolism; Treatment Outcome

Type II of heparin-associated thrombocytopenia (HAT) is well known, but the cardinal symptom, thrombocytopenia, is rarely adequately considered. Serious and potential lethal complications such as pulmonary embolism, cerebral stroke, or limb gangrene are often falsely regarded as insufficient anticoagulation. Guided diagnosis and therapy are of vital importance for the patient's outcome. Based on the experience of patients with HAT Type II treated in the intensive care unit, a diagnostic and therapeutic approach to the cardinal symptom thrombocytopenia is presented. A recently developed heparin-induced platelet activation assay (HIPAA) seems to be a highly sensitive laboratory test. The first therapeutic principle in case of presumed and diagnosed HAT is the cessation of unfractioned or low-molecular-weight heparins. ORG 10172 (Orgaran), a low-sulfated heparinoid with a low cross-reactivity (10%) to heparins, can be regarded as the most effective anticoagulant in patients with HAT Type II.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Arterial Occlusive Diseases; Chondroitin Sulfates; Dermatan Sulfate; Diagnosis, Differential; Female; Gangrene; Heparin; Heparitin Sulfate; Humans; Middle Aged; Phenprocoumon; Platelet Activation; Platelet Aggregation; Platelet Count; Pulmonary Embolism; Recurrence; Systemic Inflammatory Response Syndrome; Thrombocytopenia; Thromboembolism; Thrombophlebitis

Patients who develop heparin-induced thrombocytopenia (HIT) frequently need further anticoagulation to treat an ongoing thromboembolic problem or to prevent one. Orgaran (Org 10172), a low-molecular-weight (LMW) glycosaminoglycuronan, has shown a low frequency (10%) of cross-reactivity in vitro with sera containing the HIT antibody, in contrast to the much higher frequency of cross-reactivity (approximately 80%) shown by the LMW heparins. This paper summarises the results of intravenous or subcutaneous Orgaran treatment in 57 of 67 Australian patients, in whom the diagnosis of HIT was reasonably confirmed by exclusion of other causes of thrombocytopenia and by objective tests. The presenting indications for Orgaran were: continuous venovenous haemofiltration and haemodialysis (n = 21), thrombo-embolism treatment (n = 23), thrombo-embolism prophylaxis (n = 10), and anticoagulation for coronary artery by-pass graft (n = 4), peripheral by-pass graft surgery and plasmapheresis (n = 1 each). The results showed Orgaran to be a safe, well-tolerated, effective (successful treatment in over 90% of patients) anticoagulant in patients with a high thrombotic and/or bleeding risk even if critically ill and requiring haemofiltration. The complete results of the world-wide study in 161 patients confirmed not only these clinical findings in the subgroup of 57 Australian patients, but also the low cross-reactivity (12%) of Orgaran with the HIT serum factor.

Topics: Antibody Specificity; Autoantibodies; Autoimmune Diseases; Chondroitin Sulfates; Cross Reactions; Dermatan Sulfate; Drug Evaluation; Glycosaminoglycans; Hemofiltration; Heparin; Heparinoids; Heparitin Sulfate; Humans; Postoperative Complications; Thrombocytopenia; Thromboembolism

In a prospective, randomized, assessor-blind multicentre study two antithrombotic subcutaneous regimens were compared in patients undergoing total hip replacement. Group 1 (154 patients) received 750 anti-Xa units of a new low molecular weight heparinoid (Lomoparan) subcutaneously twice a day and group 2 (155 patients) received 5000 units heparin and 0.5 mg dihydroergotamine (heparin-DHE 5000) twice a day. The incidence of deep vein thrombosis, assessed by routine bilateral venography on day 10 (+/- 1), was 17 and 32 per cent in groups 1 and 2 respectively (risk reduction 47 per cent; P = 0.007). One patient in each group developed a symptomatic pulmonary embolism confirmed by lung scanning. Major bleeding complications occurred in one patient in each group and no significant difference was observed between the two groups with respect to minor bleeding complications. Subcutaneous Lomoparan appears to be as safe as heparin-DHE 5000 at the above doses with regard to bleeding complications, and is more efficacious with respect to venous thrombosis.

Topics: Aged; Blood Loss, Surgical; Chondroitin Sulfates; Dermatan Sulfate; Dihydroergotamine; Drug Combinations; Female; Fibrinolytic Agents; Glycosaminoglycans; Heparin; Heparin, Low-Molecular-Weight; Heparitin Sulfate; Hip Prosthesis; Humans; Male; Prospective Studies; Thromboembolism; Thrombophlebitis

Life-threatening heparin-induced thrombocytopenia (HIT) is treated with the alternative nonheparin anticoagulants argatroban, lepirudin, or danaparoid. Frequently, the pentasaccharide fondaparinux is used off-label.. The authors sought to investigate the safety and efficacy of the different anticoagulants for treating HIT.. In a national, multicenter registry study, hospitalized patients who were diagnosed with HIT, an at least intermediate clinical HIT-risk (4Ts score ≥4 points), and received treatment with ≥1 dose of the aforementioned anticoagulants were included. Main outcome measures were the incidences of HIT-specific complications (thromboembolic venous/arterial events, amputations, recurrent/persistent thrombocytopenia, skin lesions) and bleedings.. Of 195 patients, 46 (23.6%), 4 (2.1%), 61 (31.3%), and 84 (43.1%) had been treated first-line with argatroban, lepirudin, danaparoid, and fondaparinux, respectively. The composite endpoint of HIT-specific complications (thromboembolic events, amputation, skin necrosis) occurred in 11.7% of patients treated with approved alternative anticoagulation and in 0.0% of fondaparinux-treated patients. The all-cause in-hospital mortality rates were 14.4% during approved alternative anticoagulation and 0.0% during fondaparinux treatment. Bleeding complications occurred in alternatively anticoagulated patients and in fondaparinux-treated patients in 6.3% and 4.8%, respectively. Post hoc analysis of clinical and laboratory features confirmed "true" HIT in at least 74 of 195 (38.0%) patients; 35 of 74 (47.3%) were treated with fondaparinux.. Fondaparinux is effective and safe in suspected acute HIT; no HIT-specific complications occurred in the fondaparinux-treated patients, even among those with a high clinical HIT probability. Further data from randomized controlled trials are urgently needed because lepirudin was recalled from the market; danaparoid access has been limited and is not approved in the United States; and argatroban is contraindicated in patients with impaired liver function, and activated partial thromboplastin time confounding may interfere with monitoring. (Retrospective Registry of Patients With Acute Heparin-induced Thrombocytopenia Type II; NCT01304238).

Topics: Anticoagulants; Arginine; Chondroitin Sulfates; Dermatan Sulfate; Factor Xa Inhibitors; Female; Fondaparinux; Hemorrhage; Heparin; Heparitin Sulfate; Hirudins; Hospital Mortality; Hospitalization; Humans; Male; Necrosis; Off-Label Use; Partial Thromboplastin Time; Patient Safety; Pipecolic Acids; Polysaccharides; Recombinant Proteins; Registries; Retrospective Studies; Sulfonamides; Thrombocytopenia; Thromboembolism; Treatment Outcome

Thromboembolism is an infrequent, yet serious cause of both maternal and fetal morbidity and death during pregnancy and the puerperium. Antithrombotic treatment and prophylaxis both before and during pregnancy are based on unfractionated heparin (UH), low-molecularweight heparin (LMWH), Warfarin and Aspirin. The prevalence and severity of thromboembolism during pregnancy and puerperium warrant special consideration of management and therapy. Such therapy includes the treatment of acute thrombotic events and prophylaxis for those at increased risk of thrombotic events. This paper assesses the safety and efficacy of antithrombotic therapy during pregnancy and the peripartum period. Its cardiovascular and obstetric indications, the evidence of association between thrombophilias and adverse pregnancy outcome, regimens and maternal and fetal side-effects are also discussed.

Topics: Anticoagulants; Aspirin; Bone Density; Breast Feeding; Chondroitin Sulfates; Dermatan Sulfate; Female; Fondaparinux; Heparin; Heparin, Low-Molecular-Weight; Heparitin Sulfate; Humans; Infant, Newborn; Polysaccharides; Pregnancy; Pregnancy Complications, Hematologic; Thromboembolism; Thrombophilia; Warfarin

Topics: Antibodies; Anticoagulants; Chondroitin Sulfates; Dermatan Sulfate; Female; Fondaparinux; Heparin; Heparitin Sulfate; Humans; Male; Platelet Activation; Platelet Factor 4; Polysaccharides; Serotonin; Thrombocytopenia; Thromboembolism

The patient was a 55-year-old female. On the diagnosis of the right acoustic tumor, a subtotal extirpation was performed. Heparinized solution was administered, and on postoperative day 7, an occlusion of the left common femoral artery was confirmed. A continuous administration of heparin was initiated after a thrombectomy. On the following day, the platelet count decreased. Following confirmation of the recurrence of thromboembolism, we again performed a thrombectomy. Considering the possibility of heparin-induced thrombocytopenia (HIT), we terminated the administration of heparin, and treatment with danaparoid and argatroban was initiated. Two days later, she redeveloped thromboembolism. After the administration of danaparoid was terminated, the platelet count improved.

Topics: Anticoagulants; Arginine; Chondroitin Sulfates; Dermatan Sulfate; Female; Heparin; Heparitin Sulfate; Humans; Leg; Middle Aged; Pipecolic Acids; Recurrence; Sulfonamides; Thrombectomy; Thrombocytopenia; Thromboembolism

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

Thrombosis prophylaxis using heparins is mandatory in most trauma patients. However, heparins can induce heparin-induced thrombocytopenia (HIT), the most common and clinically important immune-mediated drug-dependent thrombocytopenia. Affected patients are at risk of developing new thromboembolic complications. HIT has to be considered if platelet counts decrease >50% between day 5-10 of heparin therapy that cannot be explained alternatively or if new thromboses occur in a sufficiently heparinised patient. Immediately changing the anticoagulant to danaparoid or lepirudin is most important. Proof of anti-platelet-factor-4/heparin antibodies secures the diagnosis, usually retrospectively. Diagnosis and therapy are demonstrated in a typical HIT patient. HIT usually occurs in the second week of heparin administration. Heparin-reexposure within 100 days can lead to HIT before day 5. For early recognition of HIT, platelet counts should be monitored regularly. Because of earlier discharge of patients to rehabilitation or outpatient care, the problem of HIT-diagnosis and therapy gains increasing relevance in these sectors.

Topics: Adult; Anticoagulants; Autoantibodies; Chondroitin Sulfates; Dermatan Sulfate; Drug Combinations; Fractures, Bone; Heparin; Heparitin Sulfate; Hirudins; Humans; Male; Multiple Trauma; Platelet Count; Platelet Factor 4; Postoperative Complications; Recombinant Proteins; Thrombocytopenia; Thromboembolism

Patients with malignancy often present with a variety of coagulation abnormalities which may ultimately lead to recurrent arterial and venous thromboses. Recently the presence of antiphospholipid antibodies in cancer patients has been proposed as one of the potential mechanisms promoting hypercoagulability. Here we report two consecutive patients with localized tumors, one suffering from breast cancer and another presenting with colorectal cancer, who experienced dramatic exacerbation of the antiphospholipid antibody syndrome (APAS) within 4 weeks after surgery. In the first patient who had also received one course of adjuvant chemotherapy, major ischemic stroke and recurrent venous thromboembolism were paralleled by the development of ulcerative livedoid vasculitis and pancytopenia, constituting the diagnosis of systemic lupus erythematosus with secondary APAS. In the second patient, progressive thrombotic occlusion of the superior and inferior vena cava was associated with bilateral pulmonary embolism, acute renal failure, and disabling soft tissue edema. Although not fulfilling the classic criteria of "catastrophic" APAS, the clinical features were life threatening and appeared to be refractory to oral anticoagulation with phenprocoumon. In addition, a diagnosis of Trousseau's syndrome was unlikely due to missing evidence of gross metastatic disease. Besides a suggested treatment strategy comprising high doses of low-molecular-weight heparin, potential pathogenic mechanisms are discussed in consideration of a recently proposed "thrombotic storm," which may cause multiple thromboses after an initial provocation in patients with known hypercoagulability.

Topics: Adult; Antiphospholipid Syndrome; Breast Neoplasms; Chemotherapy, Adjuvant; Chondroitin Sulfates; Colorectal Neoplasms; Dermatan Sulfate; Drug Combinations; Female; Heparin, Low-Molecular-Weight; Heparitin Sulfate; Humans; Lupus Erythematosus, Systemic; Middle Aged; Neoplasms; Stroke; Thromboembolism; Thrombophilia

Topics: Chondroitin Sulfates; Dermatan Sulfate; Dose-Response Relationship, Drug; Drug Administration Schedule; Heparin; Heparitin Sulfate; Hirudin Therapy; Humans; Otorhinolaryngologic Diseases; Risk Factors; Thrombocytopenia; Thromboembolism

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

An 80-year-old woman had been hospitalized in a psychiatric clinic where, on the 22nd day, she sustained a fracture of the neck of the left femur, which was treated by internal screw fixation. The postoperative course was at first without complication. But 9 days postoperatively her platelet count had fallen to 59,000/microliter. As heparin induced type II thrombocytopenia (HIT II) was suspected, the thrombosis prophylaxis with low-molecular heparin was replaced by sodium danaparoid (twice 750 units subcutaneously). Despite this, ischaemia of the right lower leg developed and required amputation. On the following day the left lower leg and foot also became ischemic, where upon she was admitted to the author's hospital (37 days after her admission to the psychiatric clinic).. The patient was in a reduced general condition (body-mass index 19.5 kg/m2). She was disoriented as to place and time. Her blood pressure was 140/80 mmHg, her pulse irregular with a ventricular rate of 100/min. The skin below the middle of the left lower leg was cold and livid and the pedal pulses were not palpable.. Haemoglobin content was 9.7 g/dl, the white cell count 9,200/microliter, and platelet count 54,000/microliter. Electrolytes and creatinine were within normal limits.. Thrombendarterectomy was performed once via the left groin under danaparoid anticoagulation. There was no re-occlusion and the patient was able to walk again.--It was ascertained subsequently, she had already been given ordinary heparin in the psychiatric clinic for 20 days. Her platelet count of around 70,000/microliter returned to normal even though heparin administration was continued.. A reduction in platelet count by more than half during heparin treatment suggests heparin-induced thrombocytopenia, in which case heparin should be discontinued at once. In high-risk patients adequate treatment should be initiated with other anticoagulants even before the occurrence of thromboembolism.

Topics: Aged; Aged, 80 and over; Amputation, Surgical; Anticoagulants; Chondroitin Sulfates; Dermatan Sulfate; Drug Combinations; Endarterectomy; Female; Heparin; Heparinoids; Heparitin Sulfate; Humans; Ischemia; Leg; Recurrence; Thrombocytopenia; Thromboembolism; Thrombosis

Heparin-induced thrombocytopenia (HIT) together with simultaneously occurring thromboembolism is a serious complication of heparin treatment. At present an immunologic cause of this side effect of heparin is equivocally accepted. However, further anticoagulation of these patients is still debated. The present article summarizes the treatment of 20 patients with such complications. Two of these patients did not develop thrombocytopenia but presented cutaneous allergy or necrosis. All patients were treated either with intravenous heparinoid (Orgaran) or with low-molecular-weight heparin without/with simultaneous intravenous high-dose immunoglobulins or with intravenous r-hirudin. Based on these experiences the treatment of choice depends at present on the availability of the anticoagulants and on the local experience with the different anticoagulants. In the future r-hirudins and other nonheparin thrombin inhibitors may become the drugs of choice in this indication. Surgical intervention has to be considered additionally.

Topics: Adult; Aged; Anticoagulants; Chondroitin Sulfates; Dermatan Sulfate; Female; Heparin; Heparin, Low-Molecular-Weight; Heparinoids; Heparitin Sulfate; Humans; Injections, Intravenous; Male; Middle Aged; Thrombocytopenia; Thromboembolism

Heparin-induced thrombocytopenia type II (HIT-II) is a serious complication in heparin treatment. Because of arterial and/or venous thromboembolism, HIT-II quite often takes a life-threatening course. This article describes the clinical course of seven trauma patients, who developed HIT-II during thromboembolism prophylaxis with unfractionated heparin (UFH, Heparin-Natrium-Nattermann, 250,000 I.E., Rhone-Poulenc Rorer GmbH), given subcutaneously. Thromboembolic complications occurred in 5 out of 7 cases (71.4%). One case took a fatal course (14.3%). UFH was replaced by Orgaran when HIT-II was suspected or diagnosed. There were no more complications. Thrombocyte count increased to normal values within 3 to 9 days. The importance of HIT-II in heparin therapy during in- and outpatient therapy is discussed with reference to the current literature.

Topics: Aged; Aged, 80 and over; Anticoagulants; Arthroplasty, Replacement, Hip; Chondroitin Sulfates; Dermatan Sulfate; Female; Femoral Neck Fractures; Heparin; Heparitin Sulfate; Hip Fractures; Humans; Male; Middle Aged; Multiple Trauma; Osteoarthritis, Hip; Platelet Count; Postoperative Complications; Thrombocytopenia; Thromboembolism

Topics: Anticoagulants; Chondroitin Sulfates; Dermatan Sulfate; Drug Combinations; Heparin; Heparinoids; Heparitin Sulfate; Humans; Recurrence; Thromboembolism

In patients with heparin-induced thrombocytopenia undergoing cardiac operations, anticoagulation with heparin should be avoided. The low-molecular-weight glycosaminoglycan Orgaran has been used as an alternative, but the overall experience is limited.. Two patients with heparin-induced thrombocytopenia underwent cardiopulmonary bypass using Orgaran for anticoagulation. A 30-year-old woman suffered from emboli to her brain through a secondary atrial septal defect, a 14-year-old boy from ischemia of his left leg due to recurrent embolism originating from the mitral valve. In both cases, cardiopulmonary bypass was performed in a routine manner, except for using low-dose Orgaran instead of heparin. Anticoagulation was monitored during cardiopulmonary bypass by measuring Orgaran plasma levels and activated clotting time.. No thromboembolic or bleeding complications occurred during and after atrial septal defect repair and mitral valve replacement, respectively. In the former case, thrombotic material from the inferior vena cava was removed during hypothermic circulatory arrest within the same procedure. Activated clotting time did not correlate with plasma levels of Orgaran.. Orgaran might be a useful alternative for anticoagulation during extracorporeal circulation. Adequate dosages and measurement of plasma levels are recommended for its use in cardiopulmonary bypass.

Topics: Adolescent; Adult; Anticoagulants; Cardiopulmonary Bypass; Chondroitin Sulfates; Dermatan Sulfate; Female; Heart Septal Defects, Atrial; Heart Valve Diseases; Heparin; Heparitin Sulfate; Humans; Male; Mitral Valve; Thrombocytopenia; Thromboembolism; Treatment Outcome

Topics: Anticoagulants; Chondroitin Sulfates; Dalteparin; Dermatan Sulfate; Disease Susceptibility; Factor V Deficiency; False Negative Reactions; Heparin; Heparin Lyase; Heparitin Sulfate; Heterozygote; Humans; Partial Thromboplastin Time; Polysaccharide-Lyases; Protein C; Reagent Kits, Diagnostic; Sensitivity and Specificity; Thromboembolism

Heparin-associated thrombocytopenia (HAT) is a relative frequent complication of thromboembolic prophylaxis and therapy. There is good evidence that the more severe HAT Type II is caused by an antibody dependent on polysulfated oligosaccharide epitopes. At present, low molecular weight heparins are used with varying success in patients with HAT that require further anticoagulation, although there are several known cases of cross reactivity between standard and low molecular weight heparins. Using our present case as an example, we show that the In-vitro- diagnostic of cross-reactivity is an indispensable precondition for any sufficient therapy. Additionally, we give support to previous findings that the low-grade sulfated heparinoid Org 10,172 shows no (or less) cross reactivity with standard or low molecular weight heparins. Thus, it might be the most appropriate choice if an anticoagulation is necessary before the results of In-vitro-diagnostics are available.

Topics: Adult; Anticoagulants; Cesarean Section; Chondroitin Sulfates; Cross Reactions; Dalteparin; Dermatan Sulfate; Dose-Response Relationship, Drug; Female; Heparin; Heparitin Sulfate; Humans; Platelet Count; Pre-Eclampsia; Pregnancy; Puerperal Disorders; Thrombocytopenia; Thromboembolism

We have previously demonstrated that platelets obtained from patients with anorexia nervosa or severe peripheral vascular disease are hyperaggregable. Since conventional heparins are known to activate platelets in vitro and occasionally induce thrombosis and consumptive thrombocytopenia in vivo, we have investigated the direct effect of a conventional heparin on platelets obtained from patients with anorexia nervosa or severe peripheral vascular disease. Heparin at therapeutic concentrations was found to induce platelet aggregation of such platelets in vitro. In contrast, a recently developed low molecular weight heparinoid (Org 10172), at therapeutic concentrations, had no effect on these hyperaggregable platelets. We conclude that: heparin may be potentially harmful to patients with hyperaggregable platelets; thrombocytopenia and thrombosis associated with heparin therapy may be mediated through a direct effect of heparin on platelets; it is unlikely that heparin induced thrombocytopenia is always mediated by classical immunological mechanisms, especially in patients with hyperaggregable platelets; and low molecular weight heparinoids may be safer anticoagulants in patients with platelet hyperaggregability.

Topics: Adolescent; Adult; Aged; Anorexia Nervosa; Blood Platelets; Chondroitin Sulfates; Collagen; Dermatan Sulfate; Epinephrine; Female; Glycosaminoglycans; Heparin; Heparitin Sulfate; Humans; Immunoglobulin G; In Vitro Techniques; Male; Middle Aged; Platelet Aggregation; Thrombocytopenia; Thromboembolism; Thromboxane B2; Vascular Diseases

A new heparinoid, Org 10172, was given to five patients with hemorrhagic stroke with thromboembolic complications. Treatment did not cause progression of cerebral bleeding, and thrombotic processes were inhibited. No side effects were encountered.

Topics: Aged; Cerebrovascular Disorders; Chondroitin Sulfates; Dermatan Sulfate; Female; Fibrinolytic Agents; Glycosaminoglycans; Heparitin Sulfate; Humans; Male; Middle Aged; Thromboembolism

Topics: Chondroitin Sulfates; Drug Combinations; Heparin; Thromboembolism

Topics: Chondroitin Sulfates; Drug Combinations; Heparin; Obstetrics; Pregnancy; Thromboembolism

Topics: Anticoagulants; Chondroitin Sulfates; Drug Combinations; Female; Heparin; Humans; Obstetrics; Postpartum Period; Pregnancy; Thromboembolism