heparitin-sulfate and Disseminated-Intravascular-Coagulation

Topics: Anticoagulants; Chondroitin Sulfates; Dermatan Sulfate; Disseminated Intravascular Coagulation; Fibrinolytic Agents; Heparin; Heparitin Sulfate; Protease Inhibitors; Protein C; Thrombomodulin

Topics: Anticoagulants; Chondroitin Sulfates; Dermatan Sulfate; Disseminated Intravascular Coagulation; Heparitin Sulfate; Humans

Topics: Anticoagulants; Antithrombins; Benzamidines; Chondroitin Sulfates; Dalteparin; Dermatan Sulfate; Disseminated Intravascular Coagulation; Gabexate; Guanidines; Heparin; Heparitin Sulfate; Humans; Protease Inhibitors; Protein C; Recombinant Proteins; Thrombomodulin; Tretinoin

Danaparoid (danaparoid sodium) is a low molecular weight heparinoid which has undergone clinical study for use as continued anticoagulant therapy in patients with heparin-induced thrombocytopenia (HIT), for the prophylaxis and treatment of deep vein thrombosis (DVT), and for the treatment of disseminated intravascular coagulation (DIC). A nonblind study in patients with HIT has reported that complete clinical resolution is significantly more likely in patients receiving danaparoid than in patients receiving dextran 70. In addition, retrospective analyses and noncomparative data support the use of danaparoid for continued anticoagulant therapy in patients with HIT. Studies in patients undergoing hip surgery have shown that danaparoid significantly reduces the incidence of postoperative DVT compared with aspirin, warfarin, dextran 70 and heparin-dihydroergotamine, while additional data suggest no difference between danaparoid, enoxaparin and dalteparin. In patients undergoing abdominal or thoracic surgery for removal of a malignancy, danaparoid reduced the incidence of postoperative DVT compared with placebo, but showed no significant difference when compared with unfractionated heparin (UFH). Two studies have compared danaparoid with UFH in the prophylaxis of DVT following acute ischaemic stroke; twice daily danaparoid was significantly superior to UFH whereas there was no significant difference between a once-daily dosage and UFH. Danaparoid did not differ from UFH in terms of efficacy in the treatment of existing DVT. In all comparative studies examining the efficacy of danaparoid in the prophylaxis or treatment of DVT (versus warfarin, dextran 70, enoxaparin, dalteparin, aspirin, heparin-dihydroergotamine, UFH and placebo), the incidence of haemorrhagic complications did not differ between treatment groups. In patients with DIC, 61.9% of those patients receiving danaparoid experienced either disappearance or reduction of symptoms of DIC whereas 62% of those receiving UFH showed either no change or aggravation of their symptoms. There was no significant difference between treatment groups in tolerability or overall improvement of DIC.. Danaparoid is an effective anticoagulant agent which has undergone clinical evaluation in a wide range of disease indications. Current guidelines support the use of danaparoid in prophylaxis of DVT following ischaemic stroke, and in patients who develop HIT. Danaparoid has shown efficacy in DIC, and for DVT prophylaxis in patients undergoing hip surgery although further data are required to establish the role of danaparoid in these indications. In particular, double-blind trials comparing danaparoid with such recommended therapies as the low molecular weight heparins will provide more definitive data on the place of danaparoid in the clinical management of these conditions and ultimately lead to improved patient outcomes.

Topics: Anticoagulants; Biological Availability; Chondroitin Sulfates; Dermatan Sulfate; Disseminated Intravascular Coagulation; Drug Combinations; Heparitin Sulfate; Humans; Injections, Intravenous; Injections, Subcutaneous; Randomized Controlled Trials as Topic; Thrombocytopenia; Treatment Outcome; Venous Thrombosis

The management of chronic disseminated intravascular coagulation( DIC) caused by aortic dissection has not yet been established. We report the successful treatment of a case of aortic dissection with a patent false lumen using danaparoid sodium for acute exacerbation of chronic DIC. 2,000 U danaparoid sodium per day has been stabilizing the coagulative and fibrinolytic parameters and has been relieving bleeding tendencies with no side effects for a long term.

Topics: Aortic Dissection; Chondroitin Sulfates; Dermatan Sulfate; Disseminated Intravascular Coagulation; Heparitin Sulfate; Humans

Danaparoid sodium and synthetic protease inhibitors (SPIs) have been approved for the treatment of disseminated intravascular coagulation (DIC) in Japan.. To compare the clinical results of the treatment of DIC with danaparoid or SPIs.. We retrospectively examined 188 patients with hematological malignancy-related DIC.. DIC resolution rate in the danaparoid group was higher than that in the SPIs group (61.5 vs. 42.6%; p = 0.031) on day 7. Multivariate analysis identified the response to chemotherapy as independent predictive factor for DIC resolution on day 7 (odds ratio, OR, 2.28; 95% confidence interval, CI, 1.21-4.31; p = 0.011). While there was no significant difference in the DIC resolution rate on day 14 (75.0 vs. 62.4%; p = 0.117), in a subgroup analysis of patients who did not show an improvement in the underlying disease, the danaparoid group showed a significantly better DIC resolution rate (OR 3.89; 95% CI 1.15-13.2; p = 0.030). There was no difference in the rate of cumulative mortality from bleeding within 28 days between the 2 groups (6.6 vs. 3.3%; p = 0.278).. Danaparoid may be associated with more frequent resolution of DIC in patients with refractory underlying disease.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Blood Component Transfusion; Chondroitin Sulfates; Dermatan Sulfate; Disseminated Intravascular Coagulation; Female; Fibrin Fibrinogen Degradation Products; Fibrinogen; Hematologic Neoplasms; Hemorrhage; Heparitin Sulfate; Humans; Male; Middle Aged; Plasma; Protease Inhibitors; Prothrombin Time; Retrospective Studies; Treatment Outcome

The case of a 21-year old man who died due to an intracranial thrombosis just after diagnosis of Goodpasture's disease, is reported. Discussion deals with the putative mechanisms, which could be responsible for the thrombosis.

Topics: Anti-Glomerular Basement Membrane Disease; Anticoagulants; Chondroitin Sulfates; Combined Modality Therapy; Dermatan Sulfate; Diabetes Insipidus, Neurogenic; Disseminated Intravascular Coagulation; Enoxaparin; Fatal Outcome; Headache; Heparin; Heparitin Sulfate; Humans; Immunosuppressive Agents; Male; Methylprednisolone; Plasma Exchange; Platelet Factor 4; Sinus Thrombosis, Intracranial; Thrombocytopenia; Young Adult

A 32-year-old woman was admitted with intermittent rectal bleeding with disseminated intravascular coagulation (DIC)-like coagulopathy. CT and MRI revealed a retroperitoneal tumor, and we diagnosed giant retroperitoneal hemangioma complicated with Kasabach-Merritt syndrome, following blood pool scintigraphy. Corticosteroid and interferon-alpha were not effective, and gabexate mesilate was also ineffective for coagulopathy. Immediately after receiving danaparoid sodium, she recovered from DIC. We performed tumor resection successfully, and she had no symptoms of coagulopathy thereafter.

Topics: Adult; Anticoagulants; Chondroitin Sulfates; Dermatan Sulfate; Disseminated Intravascular Coagulation; Female; Hemangioma; Heparitin Sulfate; Humans; Retroperitoneal Neoplasms

Chronic disseminated intravascular coagulation (DIC) is a well-known complication of aortic aneurysm. A 63-year-old man with bleeding tendency and a large palpable abdominal aortic aneurysm (AAA) was diagnosed as having fibrinolysis dominant DIC by the excessive activation of both coagulation and fibrinolysis (plasmin -alpha2 plasmin inhibitor complex concentration is usually >4 microg/ml). Although several treatments were tried, DIC could not be controlled until the patient was given combined therapy of danaparoid (1,250 U/12 h, bolus IV) and tranexamic acid (0.5 g x 3/day, oral administration). This therapy may be beneficial when control for bleeding is required without restricting the ambulatory movement of patients by continuous drip.

Topics: Anticoagulants; Antifibrinolytic Agents; Aortic Aneurysm, Abdominal; Chondroitin Sulfates; Dermatan Sulfate; Disseminated Intravascular Coagulation; Drug Therapy, Combination; Heparitin Sulfate; Humans; Male; Middle Aged; Radiography; Tranexamic Acid

n patients with Kasabach-Merritt syndrome (KMS), local activation of coagulation commonly results in disseminated intravascular coagulation (DIC). Progress of DIC is associated with 30-40% mortality as a result of uncontrollable hemorrhage. A 39-year-old woman with an enlarging giant liver hemangioma was diagnosed as having KMS with DIC. To control the hemorrhagic diathesis, we commenced combination therapy for DIC with danaparoid (1,250 Ux2/day, intravenously (IV)) and tranexamic acid (0.5 g x 3/day, peros (PO). Rapid improvement of the bleeding tendency and coagulopathy occurred in response to this treatment - that is, DIC was controlled without removing the giant hemangioma. The therapy did not restrict the behavior of the patient by continuous drip and angiography could be performed without bleeding. Such therapy may be beneficial in chronic DIC with activation of fibrinolysis.

Topics: Adult; Antifibrinolytic Agents; Blood Proteins; Chondroitin Sulfates; Dermatan Sulfate; Disseminated Intravascular Coagulation; Drug Therapy, Combination; Female; Hemangioma; Hemorrhagic Disorders; Heparitin Sulfate; Hepatic Artery; Humans; Ligation; Liver Neoplasms; Syndrome; Tranexamic Acid

Patients with heparin-induced thrombocytopenia (HIT) (with or without thrombosis) require alternative anticoagulation because of their extreme risk of new thromboembolic complications. The first effective agent for this purpose may be danaparoid, a less-sulfated low molecular weight heparinoid. Recently, direct thrombin inhibitors have been used.. Five HIT patients, who developed new thromboembolic complications while receiving danaparoid, were analyzed to consider possible reasons for treatment failure and to promulgate strategies that improve efficacy.. Three patients had acute HIT, one had recent HIT, and one with remote HIT was re-exposed to heparin during heart surgery. Danaparoid was started as intravenous bolus and infusion in one patient, and as 1250 units subcutaneously twice daily in four patients. The new complications that emerged on danaparoid were new venous thrombi in three patients (one with pulmonary emboli), lower extremity arterial thrombosis in one, myocardial ischemia in one, thromboembolic cardiovascular accidents in one, and fatal bowel necrosis in one (two patients suffered more than one complication). Platelet counts did not improve or worsened in four, improved partially in the other, and parameters of disseminated intravascular coagulation failed to improve in one patient. Four patients responded relatively dramatically when direct thrombin inhibitors were substituted. Possible reasons for danaparoid failure include that: 1) no treatment is expected to completely prevent complications, 2) antithrombin III consumption can blunt efficacy in some patients, 3) low or intermediate doses may be insufficient, and 4) there was clinically significant cross-reactivity of the pathogenic HIT antibodies.. It is emphasized that the possibility of clinically significant antibody cross-reactivity and that low or intermediate dosage may be inadequate when using danaparoid in therapy of HIT. The latter problem probably extrapolates to other anticoagulants used for HIT.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Antithrombins; Chondroitin Sulfates; Cross Reactions; Dermatan Sulfate; Disseminated Intravascular Coagulation; Drug Combinations; Female; Heparin; Heparitin Sulfate; Humans; Male; Middle Aged; Platelet Count; Thrombocytopenia; Thrombosis; Treatment Failure

Danaparoid and heparin, on the basis of anti-activated factor X (anti-FXa) activity, were equipotent in accelerating the rate of interaction of FXa and antithrombin III. In rat tissue factor-induced disseminated intravascular coagulation (DIC) models, an intravenous administration of danaparoid inhibited the decrease in plasma fibrinogen and platelet counts and the increase in serum fibrinogen degradation products. Expressed on the basis of anti-FXa activity, these effects were comparable with those of dalteparin and heparin. In rat mesenteric small artery and vein, less bleeding was observed after intravenous administration of danaparoid than after dalteparin or heparin. Danaparoid did not affect adenosine diphosphate- or collagen-induced platelet aggregation, and showed weaker inhibitory effects on aggregation induced by thrombin, or collagen + thrombin, than did dalteparin or heparin. These findings suggest that danaparoid may be useful for the prevention of DIC and has less tendency to cause bleeding than dalteparin or heparin, probably as a result of its weaker ability to inhibit platelet aggregation.

Topics: Animals; Anticoagulants; Antithrombin III; Bleeding Time; Chondroitin Sulfates; Dalteparin; Dermatan Sulfate; Disease Models, Animal; Disseminated Intravascular Coagulation; Drug Combinations; Drug Evaluation, Preclinical; Enzyme Inhibitors; Factor Xa; Factor Xa Inhibitors; Heparin; Heparitin Sulfate; Kinetics; Male; Platelet Aggregation; Rats; Rats, Wistar; Risk Assessment; Thromboplastin

Danaparoid sodium (danaparoid) is a low molecular weight heparinoid with anticoagulation properties, which mainly consists of heparan sulfate. Compared with heparin sodium (heparin), danaparoid has a much higher anti-Xa/anti-thrombin ratio. We compared the effect of danaparoid on endotoxin-induced experimental disseminated intravascular coagulation (DIC) in rats with heparin. A bolus injection of endotoxin (10 mg/kg) induced gradual decreases in the platelet count, and the plasma fibrinogen, antithrombin III (AT-III) and heparin cofactor II levels, as well as an increase in the fibrinogen/fibrin degradation products level from 1 to 6 hours after the injection, indicating that both coagulation and fibrinolysis were activated. The intravenous administration of danaparoid or heparin 3 hours after the endotoxin injection inhibited the endotoxin-induced decreases in the platelet count and plasma fibrinogen level and also inhibited the endotoxin-induced increase in glomerular fibrin deposition in the kidney. Differences between danaparoid and heparin were observed in their effects on the plasma AT-III level and clotting time. Danaparoid significantly inhibited both the decrease in the plasma AT-III level and the prolongation of the prothrombin time induced by endotoxin, where as heparin showed no effect on those responses. Moreover, danaparoid enhanced the prolongation of the activated partial thromboplast in time induced by endotoxin to a lesser degree than heparin. These findings suggest that the effects of danaparoid on the endotoxin-induced decrease of the plasma AT-III level and the prolongation of the clotting time are more advantageous than those of heparin. The results may have been due to a higher anti-Xa/anti-thrombin ratio of danaparoid than that of heparin, indicating that danaparoid may be useful in the treatment of DIC.

Topics: Animals; Anticoagulants; Chondroitin Sulfates; Dermatan Sulfate; Disseminated Intravascular Coagulation; Drug Combinations; Endotoxins; Heparitin Sulfate; Male; Rats; Rats, Wistar

Four patients with acute promyelocytic leukemia (APL) and clinical and laboratory manifestations of disseminated intravascular coagulation (DIC) were treated during induction chemotherapy with Org 10172 (Organon International), a low molecular weight heparinoid preparation. Plasma anti-Xa levels were maintained between 0.60 and 0.80 U/ml and anticoagulant activities, determined with a diluted activated partial thromboplastin time assay, ranged from 0.00 to 0.20 U/ml. Bleeding symptoms ceased and fibrinogen levels improved in the first week in all patients. In the second week, two patients developed bleeding as a result of primary fibrinolysis. It is concluded that Org 10172 may be useful in the treatment of patients with DIC. In patients with APL, inhibition of DIC will be insufficient to control all bleeding, since primary fibrinolysis may also occur.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chondroitin Sulfates; Cytarabine; Daunorubicin; Dermatan Sulfate; Disseminated Intravascular Coagulation; Drug Evaluation; Glycosaminoglycans; Heparinoids; Heparitin Sulfate; Humans; Leukemia, Myeloid, Acute; Middle Aged; Thioguanine; Time Factors