heparitin-sulfate and Pulmonary-Embolism

Topics: Aged, 80 and over; Aging; Air Pollution; Animals; Cadmium; COVID-19; Cytokine Release Syndrome; Disease Models, Animal; Disease Susceptibility; Endothelium, Vascular; Environmental Pollutants; Female; Gene Expression Regulation, Enzymologic; Glucuronidase; Glycosaminoglycans; Heparitin Sulfate; Humans; Lung; Male; Prognosis; Pulmonary Embolism; SARS-CoV-2; Venous Thromboembolism; Venous Thrombosis

Topics: Acute Disease; Anticoagulants; Brain Ischemia; Chondroitin Sulfates; Databases, Factual; Dermatan Sulfate; Drug Combinations; Enoxaparin; Heparin; Heparin, Low-Molecular-Weight; Heparinoids; Heparitin Sulfate; Humans; Odds Ratio; Pulmonary Embolism; Randomized Controlled Trials as Topic; Stroke; Treatment Outcome; Venous Thrombosis

In the absence of prophylaxis, elective orthopedic surgery is associated with a high risk of venous thromboembolic events that are responsible for substantial morbidity and mortality. Despite the publication of articles questioning the significance of fatal pulmonary embolism (PE) following elective hip replacement, recent reports support the need for effective thromboprophylaxis in this indication. These reports also provide evidence of a significant reduction in fatal PE and overall mortality provided by treatment with low-molecular-weight heparin (LMWH), compared with unfractionated heparin. Even with the most effective prophylaxis currently available, however, deep vein thrombosis still develops in a minority of high-risk patients, indicating a need for improved therapies. Desirudin, a novel recombinant hirudin and direct thrombin inhibitor, has been shown to provide more effective prophylaxis than the most widely used LMWH, enoxaparin, in orthopedic surgery patients with multiple thromboembolic risk factors. This benefit was not associated with any increase in bleeding. Regional anesthesia and use of graduated compression stockings may provide additional independent reductions in thromboembolic risk in elective orthopedic surgery.

Topics: Anesthesia, Conduction; Anticoagulants; Bandages; Chondroitin Sulfates; Dermatan Sulfate; Drug Combinations; Heparin, Low-Molecular-Weight; Heparitin Sulfate; Hirudin Therapy; Hirudins; Humans; Logistic Models; Postoperative Complications; Pulmonary Embolism; Recombinant Proteins; Risk Factors; Venous Thrombosis

Deep-vein thrombosis (DVT) and pulmonary embolism are among the most common complications of heparin-induced thrombocytopenia (HIT), an antibody-mediated adverse effect of heparin that leads paradoxically to in vivo activation of platelets and the coagulation system. Inappropriate treatment of HIT-associated DVT with warfarin can cause the DVT to progress to limb gangrene: this results from impaired ability of the protein C natural anticoagulant pathway to down-regulate thrombin generation, thus leading to microvascular thrombosis and tissue necrosis. Appreciation of the importance of coagulation system activation in HIT provides a rationale for treatments that reduce thrombin generation, either via inhibiting factor Xa (danaparoid) or via inhibiting thrombin directly (lepirudin). Clinicians should know how to distinguish HIT from other thrombocytopenic disorders: for example, thrombocytopenia associated with pulmonary embolism can mimic HIT (pseudo-HIT), and acute dyspnea that can mimic acute pulmonary embolism can result from acute in vivo platelet activation in a patient with HIT antibodies who receives heparin bolus therapy (pseudo-pulmonary embolism).

Topics: Anticoagulants; Chondroitin Sulfates; Dermatan Sulfate; Drug Combinations; Gangrene; Heparin; Heparitin Sulfate; Humans; Leg; Pulmonary Embolism; Thrombocytopenia; Venous Thrombosis; Warfarin

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

After 10 days of intravenous heparin treatment of a 25-year-old woman with recurrent pulmonary emboli, thrombocytopenia occurred with a platelet drop from 1.52 x 10(5)/microliter to 3.6 x 10(4)/microliter. Heparin-induced platelet activation assays confirmed the diagnosis of heparin-induced thrombocytopenia (HIT). The detected heparin-dependent antibodies exhibited in vitro cross-reactivity with low-molecular-weight heparins, but not with danaparoid.. After heparin was stopped and platelet counts were normal, a massive thrombosis of the iliofemoral veins and the inferior vena cava occurred. Under protection of a temporary vena cava filter, systemic anticoagulation with danaparoid (anti-factor Xa-activity 0.4-0.8 U/ml) and transcatheter thrombolysis with urokinase (70,000 U/h) was initiated. Within 8 days of treatment a complete recanalisation of the occluded iliofemoral and caval veins was achieved. Oral anticoagulation with phenprocoumon was started and the patient has since then been free of symptoms.. The case demonstrates successful treatment of massive iliofemoral and caval thrombosis in the HIT syndrome achieved by combined transcatheter administration of urokinase and systemic infusion of danaparoid.

Topics: Adult; Anticoagulants; Chondroitin Sulfates; Dermatan Sulfate; Drug Combinations; Female; Femoral Vein; Heparin; Heparinoids; Heparitin Sulfate; Humans; Iliac Vein; Plasminogen Activators; Pulmonary Embolism; Recurrence; Thrombocytopenia; Thrombolytic Therapy; Thrombosis; Urokinase-Type Plasminogen Activator; Vena Cava Filters; Vena Cava, Inferior

Besides low molecular weight heparins (LMWHs) a number of new antithrombotic agents have been evaluated mainly in the prevention of deep vein thrombosis (DVT) and, to a lesser extent, in the treatment of established DVT. They include the Pentasaccharide, a synthetic ultra LMWH, Dermatan Sulphate, a glycosaminoglycan which activates heparin cofactor II, Orgaran, a mixture of Heparan and of Dermatan Sulphate, Hirulog and Hirudin, two direct thrombin inhibitors. The efficacy and safety of these compounds have been studied in comparison with a placebo or with unfractionated heparin but not with LMWH which is considered as a gold standard for these clinical indications. It is thus difficult at present to appreciate the advantages of these new antithrombotic agents over conventional LMWH therapy.

Topics: Anticoagulants; Antithrombin III; Binding Sites; Chondroitin Sulfates; Clinical Trials as Topic; Dermatan Sulfate; Drug Evaluation, Preclinical; Factor Xa Inhibitors; Fibrinolytic Agents; Heparin; Heparin, Low-Molecular-Weight; Heparitin Sulfate; Humans; Multicenter Studies as Topic; Oligosaccharides; Postoperative Complications; Pulmonary Embolism; Recurrence; Thrombin; Thrombophlebitis

Venous thrombo-embolism is a common complication in patients with acute ischaemic stroke. Without prophylaxis, deep vein thrombosis occurs in 60-75% of patients with dense hemiplegia, usually in the paralyzed limb, and 1-2% suffer fatal pulmonary embolism. Orgaran (Org 10172, low-molecular-weight heparinoid) has been evaluated for the prevention of deep vein thrombosis in patients with acute ischaemic stroke in two studies. In a double-blind study, 75 patients were randomized to receive Orgaran (50 patients) in a loading dose of 1,000 anti-Xa units intravenously followed by 750 anti-Xa units subcutaneously 12-hourly or placebo (25 patients). Deep vein thrombosis occurred in 2 of 50 (4%) in the Orgaran group and 7 of 25 (28%) in the placebo group (p = 0.005). The corresponding rates for proximal deep vein thrombosis were 0 and 16%, respectively (p = 0.01). There was one major haemorrhage in the treated group and one minor haemorrhage in the placebo group. In the second study, the safety and efficacy of Orgaran was compared with unfractionated heparin in the prevention of deep vein thrombosis in a double-blind randomized trial. Eighty-seven patients with marked lower limb paralysis secondary to stroke were randomized to receive Orgaran (45 patients) in a dose of 750 anti-factor Xa units subcutaneously 12-hourly or unfractionated heparin (42 patients) in a dose of 5,000 units subcutaneously 12-hourly. Venous thrombosis occurred in 4 of 45 (8.9%) of the Orgaran group and 13 of 42 (31%) in the unfractionated heparin group (2p = 0.014). The corresponding rates for proximal vein thrombosis were 4.4 and 11.9%, respectively (2p = 0.255).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Aged, 80 and over; Brain Ischemia; Chondroitin Sulfates; Dermatan Sulfate; Double-Blind Method; Female; Glycosaminoglycans; Hemiplegia; Heparin; Heparinoids; Heparitin Sulfate; Humans; Incidence; Male; Middle Aged; Pulmonary Embolism; Thrombophlebitis

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

This double-blind, randomised, multicentre trial in 513 patients having elective surgery for intra-abdominal or intrathoracic malignancy compared the efficacy and safety of venous thrombosis (VT) prophylaxis using 750 anti-factor Xa units of Orgaran (a mixture of low molecular weight heparinoids) given subcutaneously (sc) twice-daily with that of twice-daily injections of 5,000 units standard heparin. The main study endpoints were the development of postoperative VT detected by 125I-fibrinogen leg scanning, and the onset of clinically significant venous thromboembolism or bleeding. "Intent to treat" analysis showed a statistically non-significant trend towards less VT during Orgaran prophylaxis (10.4%) than after heparin (14.9%) and there was no difference in bleeding complications between the two study groups. Results remained similar if only patients who completed the intended course of therapy ("compliant patients") were analysed. Other trials have shown that Orgaran prevents VT after hip surgery and stroke. We now show it is also safe and effective in patients having major surgery for cancer.

Topics: Aged; Anticoagulants; Chondroitin Sulfates; Dermatan Sulfate; Double-Blind Method; Elective Surgical Procedures; Female; Gastrointestinal Neoplasms; Glycosaminoglycans; Hematologic Tests; Hemorrhage; Heparinoids; Heparitin Sulfate; Humans; Lung Neoplasms; Male; Middle Aged; Postoperative Complications; Pulmonary Embolism; Thrombophlebitis

Two studies evaluating the effect of Orgaran prophylaxis on the incidence of postoperative thrombosis in hip fracture surgery are reported. In one Scandinavian study, dextran was used in the comparative group, and in the US study, warfarin was used. In both, Orgaran was significantly more effective in reducing the frequency of deep vein thrombosis without producing an increase in bleeding complications or other side effects.

Topics: Aged; Aged, 80 and over; Chondroitin Sulfates; Dermatan Sulfate; Dextrans; Female; Glycosaminoglycans; Hemorrhage; Heparinoids; Heparitin Sulfate; Hip Fractures; Humans; Incidence; Male; Postoperative Complications; Pulmonary Embolism; Scandinavian and Nordic Countries; Single-Blind Method; Thrombophlebitis; United States; Warfarin

Topics: Chondroitin Sulfates; Dermatan Sulfate; Dihydroergotamine; Glycosaminoglycans; Heparin; Heparinoids; Heparitin Sulfate; Hip Prosthesis; Humans; Incidence; Pulmonary Embolism; Single-Blind Method; Thrombophlebitis; Treatment Outcome

Venous thrombo-embolism is a common complication in patients with acute ischaemic stroke. Without prophylaxis, deep vein thrombosis occurs in 60-75% of patients with dense hemiplegia, usually in the paralyzed limb, and 1-2% suffer fatal pulmonary embolism. Orgaran (Org 10172, low-molecular-weight heparinoid) has been evaluated for the prevention of deep vein thrombosis in patients with acute ischaemic stroke in two studies. In a double-blind study, 75 patients were randomized to receive Orgaran (50 patients) in a loading dose of 1,000 anti-Xa units intravenously followed by 750 anti-Xa units subcutaneously 12-hourly or placebo (25 patients). Deep vein thrombosis occurred in 2 of 50 (4%) in the Orgaran group and 7 of 25 (28%) in the placebo group (p = 0.005). The corresponding rates for proximal deep vein thrombosis were 0 and 16%, respectively (p = 0.01). There was one major haemorrhage in the treated group and one minor haemorrhage in the placebo group. In the second study, the safety and efficacy of Orgaran was compared with unfractionated heparin in the prevention of deep vein thrombosis in a double-blind randomized trial. Eighty-seven patients with marked lower limb paralysis secondary to stroke were randomized to receive Orgaran (45 patients) in a dose of 750 anti-factor Xa units subcutaneously 12-hourly or unfractionated heparin (42 patients) in a dose of 5,000 units subcutaneously 12-hourly. Venous thrombosis occurred in 4 of 45 (8.9%) of the Orgaran group and 13 of 42 (31%) in the unfractionated heparin group (2p = 0.014). The corresponding rates for proximal vein thrombosis were 4.4 and 11.9%, respectively (2p = 0.255).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Aged, 80 and over; Brain Ischemia; Chondroitin Sulfates; Dermatan Sulfate; Double-Blind Method; Female; Glycosaminoglycans; Hemiplegia; Heparin; Heparinoids; Heparitin Sulfate; Humans; Incidence; Male; Middle Aged; Pulmonary Embolism; Thrombophlebitis

Heparin-induced thrombocytopenia (HIT) is a potentially life-threatening prothrombotic complication following heparin administration. We describe a patient, known with idiopathic dilating cardiomyopathy, presenting nine days after a biventricular ICD implantation with dyspnoea and thrombocytopenia. Thirteen days after administration of a single heparin flush during ICD implantation, the patient developed venous thrombosis in two extremities and pulmonary embolism caused by HIT. HIT is the development of thrombocytopenia, caused by IgG antibodies against complexes of platelet factor 4 and heparin, leading to platelet aggregation. HIT may be accompanied by thrombosis in 20-50% of patients and untreated mortality rates are high. Once HIT is suspected, heparin should be replaced by an alternative anti-factor Xa or anti-factor II therapy. Regardless of the low incidence of HIT, because of the widespread use of heparin and the potentially life-threatening course of HIT, all physicians should be aware of it.

Topics: Antibodies; Anticoagulants; Cardiomyopathy, Dilated; Chondroitin Sulfates; Defibrillators, Implantable; Dermatan Sulfate; Female; Follow-Up Studies; Heparin; Heparitin Sulfate; Humans; Immunoglobulin G; Middle Aged; Platelet Aggregation; Platelet Factor 4; Postoperative Complications; Pulmonary Embolism; Thrombocytopenia; Treatment Outcome; Venous Thromboembolism

The authors present the case of a nulliparous 34-year-old patient. At the tenth week of gestation, she developed phlebothrombosis of veins of the right leg and massive pulmonary embolism. After thrombolytic and heparin therapy she developed rethrombosis and heparin-induced thrombocytopenia type II. Lepirudin was introduced in therapy and in the 12th week of gestation acenocumarol was added. After the 34th week, she received danaparoid sodium. After a week, by cesarean section, a healthy and mature female was delivered.

Topics: Acenocoumarol; Adult; Anticoagulants; Cesarean Section; Chondroitin Sulfates; Dermatan Sulfate; Female; Fibrinolytic Agents; Gestational Age; Heparin; Heparitin Sulfate; Hirudins; Humans; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Pulmonary Embolism; Recombinant Proteins; Thrombocytopenia; Venous Thrombosis

During extracorporeal membrane oxygenation, anticoagulation therapy is usually achieved with unfractionated heparin. We report on an extracorporeal membrane oxygenation with danaparoid sodium for a patient with severe respiratory failure due to massive pulmonary embolism and suspected type 2 heparin-induced thrombocytopenia. Danaparoid, a low molecular weight heparinoid, is an alternative to heparin for patients who develop type 2 heparin-induced thrombocytopenia. Danaparoid was given at 400 IU/h with an objective of antifactor Xa activity of 0.6-0.8 U/mL, which was monitored twice a day. No excessive bleeding or clotting of the circuit was noted. The patient was weaned from extracorporeal membrane oxygenation after 9 days of treatment.

Topics: Adult; Anticoagulants; Chondroitin Sulfates; Dermatan Sulfate; Echocardiography, Transesophageal; Extracorporeal Membrane Oxygenation; Factor Xa; Heparitin Sulfate; Humans; Iliac Vein; Male; Portal Vein; Pulmonary Embolism; Thrombocytopenia; Thrombosis; Tomography, X-Ray Computed

We report the case of 64-year-old female patient with pulmonary embolism and bilateral femoropopliteal deep vein thrombosis caused by heparin-induced thrombocytopenia type II (HIT II) resistant to danaparoid sodium and subsequently administered lepirudin in whom a single late plasmapheresis performed on day 6 of the initiation of treatment of HIT reversed the course of the disease, preventing its highly potential fatal outcome. Primarily administered lepirudin was not only ineffective but even led to further aggravation of the patient's clinical state and platelet count drop in the first stage of the HIT treatment. The improvement of the patient's clinical state was not achieved before therapeutic plasma exchange (TPE) had removed the greatest part of pathogenetic circulating substrate. Only after TPE, lepirudin, introduced again, led to the platelet count recovery. In the subsequent course of the treatment, lepirudin was combined with an overlapping oral anticoagulant. Previously positive heparin aggregation test and fast particle gel heparin-platelet factor 4 immunoassay were normalized as well as the patient's clinical status. Early plasmapheresis, administered within 4 days of the onset of thrombocytopenia in HIT, as a beneficial therapeutic measure in certain individual cases, is indisputable. However, our results do not concur with previously reported findings of the so far most comprehensive study on plasmapheresis performed in the management of HIT with thrombosis, discrediting late plasmapheresis administered 4 days after the onset of the disease not only as ineffective, but even as an aggravating factor. Our results suggest the possible beneficial impact of late plasmapheresis as a method that may reverse a prothrombotic process and lead to a fast improvement in the patient's platelet count, especially in cases initially resistant to thrombin inhibitors.

Topics: Arthroplasty, Replacement, Hip; Autoantibodies; Chondroitin Sulfates; Dermatan Sulfate; Drug Resistance; Female; Fibrinolytic Agents; Heparin; Heparitin Sulfate; Hip Fractures; Hirudins; Humans; Middle Aged; Partial Thromboplastin Time; Plasma; Plasmapheresis; Postoperative Complications; Pulmonary Embolism; Purpura, Thrombocytopenic, Idiopathic; Recombinant Proteins; Salvage Therapy; Thrombophilia; Time Factors

Topics: Anticoagulants; Cardiotonic Agents; Child Development; Child, Preschool; Chondroitin Sulfates; Dermatan Sulfate; Dobutamine; Factor V; Female; Follow-Up Studies; Genetic Predisposition to Disease; Gestational Age; Heparitin Sulfate; Humans; Infant; Infant, Newborn; Mutation; Norepinephrine; Pregnancy; Pregnancy Complications, Cardiovascular; Pulmonary Embolism; Respiration, Artificial; Vasoconstrictor Agents

Patients with heparin-induced thrombocytopenia urgently requiring surgery with cardiopulmonary bypass (CPB) present a unique management challenge that must be addressed by the use of alternative anticoagulants. Although clinical success with the direct thrombin inhibitor hirudin has been reported, there is sparse information in the literature supporting the efficacy of this drug as an anti-thrombotic to prevent fibrin formation during CPB. In this report, we describe the efficacy of this drug to prevent thrombin-mediated fibrin formation during CPB.

Topics: Adult; Anticoagulants; Cardiopulmonary Bypass; Chondroitin Sulfates; Contraindications; Dermatan Sulfate; Endarterectomy; Fibrinolytic Agents; Fibrinopeptide A; Heparin; Heparitin Sulfate; Hirudins; Humans; Hypertension, Pulmonary; Hypothermia, Induced; Male; Peptide Fragments; Postoperative Complications; Prothrombin; Pulmonary Embolism; Purpura, Thrombocytopenic, Idiopathic; Recombinant Proteins; Thrombectomy; Thrombin; Thrombosis

Patients with heparin-induced thrombocytopenia requiring urgent cardiac surgery present a unique challenge that must be addressed by the use of nonheparin alternatives for anticoagulation during cardiopulmonary bypass. Although isolated cases have been presented involving the use of antithrombin III independent thrombin inhibitor hirudin in this situation, its ability to completely inhibit thrombin activity has not been demonstrated. In this report we describe the efficacy of this drug in inhibiting thrombin during a case requiring prolonged cardiopulmonary bypass.

Topics: Aged; Anticoagulants; Blood Coagulation; Cardiopulmonary Bypass; Chondroitin Sulfates; Contraindications; Dermatan Sulfate; Endarterectomy; Female; Heparin; Heparitin Sulfate; Hirudins; Humans; Hypertension, Pulmonary; Plasma; Platelet Transfusion; Pulmonary Embolism; Recombinant Proteins; Thrombectomy; Thrombin; Thrombocytopenia; Time Factors; Warfarin

Heparin-induced thrombocytopenia (HIT) is a common immunological drug reaction. After exposure to heparin, some patients develop heparin dependent antibodies with no evidence of thrombosis, while others are at risk of thrombocytopenia, thrombosis, limb loss, and death. We conducted a retrospective chart review on all patients serologically positive for HIT by HPIA ELISA in a single tertiary-care hospital, to determine whether patients with malignancy had an increased risk of thrombotic complications. Medical records of 55 patients who tested positive for HIT and met clinical criteria for HIT were analyzed. All patients had been treated with unfractionated heparin. Malignancy was diagnosed in 11 patients, either at surgery or post-mortem examination. A higher rate of venous thrombosis and pulmonary embolism was observed in patients with HIT and malignant disease when compared to patients with no underlying malignancy (odds ratio 13.6, 95% CI 2.9-63.8).

Topics: Aged; Aged, 80 and over; Anticoagulants; Chondroitin Sulfates; Dermatan Sulfate; Drug Combinations; Female; Heparin; Heparitin Sulfate; Humans; Male; Middle Aged; Neoplasms; Pulmonary Embolism; Retrospective Studies; Risk Factors; Thrombocytopenia; Thrombosis; Venous Thrombosis

We describe a case where danaparoid was used prophylactically in a high-risk twin pregnancy following the development of heparin-allergy while on prophylactic dalteparin. Danaparoid was substituted for dalteparin at 20 weeks of pregnancy following the development of a severe skin reaction while on the low molecular weight heparin. Although there was no significant fall in platelet count, an aggregation assay for heparin-induced thrombocytopaenia was positive. The skin lesions rapidly resolved following the change to subcutaneous danaparoid. Delivery was by emergency caesarian section at 35 weeks under a general anaesthetic, as a dose of danaparoid had been given 6 h prior to delivery. A sample of breast milk showed no anti-activated factor X activity. Danaparoid was continued post-delivery until the patient was fully warfarinized. To our knowledge, there are no previous reports of the use of danaparoid in this setting.

Topics: Adult; Anticoagulants; Cesarean Section; Chondroitin Sulfates; Dermatan Sulfate; Drug Combinations; Drug Eruptions; Emergencies; Female; Heparin; Heparitin Sulfate; Humans; Infant, Newborn; Injections, Subcutaneous; Platelet Count; Pregnancy; Pregnancy Complications, Hematologic; Pregnancy, High-Risk; Pregnancy, Multiple; Puerperal Disorders; Pulmonary Embolism; Thrombocytopenia; Thrombosis; Warfarin

Topics: Aged; Anticoagulants; Arteries; Chondroitin Sulfates; Dermatan Sulfate; Drug Combinations; Fatal Outcome; Heparinoids; Heparitin Sulfate; Humans; Male; Pulmonary Embolism; Thrombocytopenia; Thrombosis

Heparin-induced thrombocytopenia is an immuno-mediated life-threatening side effect of heparin therapy which poses difficulties in diagnosis and major therapeutic problems. Heparin must be instantly discontinued. We describe the case of a 60-year-old male patient with type II heparin-induced thrombocytopenia, complicated by progressive deep venous thrombosis and pulmonary embolism. He failed to improve when therapy was continued with a low molecular weight heparin (Fragmin) and high doses of intravenous immunoglobulins were administered. The test for heparin-dependent platelet aggregation was positive for unfractionated heparin and low molecular weight heparin, but negative for the heparinoid Org 10172. During subsequent anticoagulant therapy with Org 10172 for seven days the number of platelets increased rapidly and the patient recovered. Nine months later Org 10172 was used again in this patient for thrombosis prophylaxis without any adverse effects. In patients with heparin-induced thrombocytopenia requiring immediately acting anticoagulant therapy, Org 10172 can be considered as an effective alternative drug to unfractionated and low molecular weight heparins.

Topics: Anticoagulants; Chondroitin Sulfates; Cross Reactions; Dermatan Sulfate; Dose-Response Relationship, Drug; Heparin; Heparin, Low-Molecular-Weight; Heparitin Sulfate; Humans; Infusions, Intravenous; Male; Middle Aged; Platelet Aggregation; Pulmonary Embolism; Thrombocytopenia; Thrombophlebitis

Heparin-induced thrombocytopenia (HIT) with thrombosis is a rare, but important complication of heparin therapy. We describe the case of a 53-year-old patient hospitalized with complicated pelvic fracture. Intravenous infusion of unfractionated heparin (15'000 IU/24 h) was given for thrombosis prevention. After 11 days' treatment the patient developed deep venous thrombosis of the left calf, complicated 2 days later by massive bilateral pulmonary embolism. Simultaneous with these thromboembolic events, thrombocytopenia, signs of activated coagulation, and antibodies to heparin occurred. In the context of this case the diagnostic and therapeutic possibilities of HIT, and in particular treatment with the heparinoid danaproid (Orgaran), are discussed.

Topics: Chondroitin Sulfates; Dermatan Sulfate; Drug Combinations; Fractures, Bone; Heparin; Heparinoids; Heparitin Sulfate; Humans; Male; Middle Aged; Pelvic Bones; Pulmonary Embolism; Thrombocytopenia; Thrombosis

Venous thrombosis and pulmonary embolism are the two faces of thromboembolic disease. In over 90% of cases, the initial treatment of the pulmonary embolism is anticoagulant therapy, the necessity and efficacy of which were demonstrated over 30 years ago with a reduction of mortality of 25 to 6%. Intravenous heparin relayed rapidly (1st to 3rd day) is still the conventional treatment protocol. Heparin therapy adapted to the result of the activated cephalin time (two to three times the control value) and oral vitamin K antagonists with a dosage adapted to keep the International Normalized Ratio between 2 and 3 is the safest and most effective treatment to date. The efficacy is shown by the low rate of recurrency, about 5% under anticoagulant therapy, lethal recurrence being very rare (less than 1%), and safety is attested by the low rate of severe bleeding complications (3 to 5%). The introduction of low molecular weight heparin and the excellent results observed in the treatment of deep vein thrombosis will probably lead to rapid extension of its indications to mild or moderate but haemodynamically well-tolerated pulmonary embolism. Hirudine and heparinoids will probably be the next step in the treatment of pulmonary embolism.

Topics: Anticoagulants; Chondroitin Sulfates; Coumarins; Dermatan Sulfate; Drug Administration Schedule; Drug Combinations; Heparin; Heparin, Low-Molecular-Weight; Heparitin Sulfate; Hirudin Therapy; Humans; Injections, Intravenous; Partial Thromboplastin Time; Pulmonary Embolism; Thrombolytic Therapy; Thrombosis; Treatment Outcome

Topics: Chondroitin Sulfates; Dermatan Sulfate; Fibrinolytic Agents; Glycosaminoglycans; Heparin; Heparitin Sulfate; Humans; Male; Middle Aged; Pulmonary Embolism; Thrombocytopenia; Thrombosis

Topics: Animals; Carbon Radioisotopes; Disease Models, Animal; Embolism, Fat; Glycosaminoglycans; Heparin; Heparitin Sulfate; Injections, Intravenous; Lipase; Lung; Mice; Pulmonary Embolism; Triolein