heparitin-sulfate and Venous-Thrombosis

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: Antibodies; Anticoagulants; Antithrombins; Arthroplasty, Replacement, Knee; Chondroitin Sulfates; Dermatan Sulfate; Fondaparinux; Heparin; Heparin, Low-Molecular-Weight; Heparitin Sulfate; Humans; Immunoglobulin G; Male; Middle Aged; Platelet Activation; Platelet Count; Platelet Factor 4; Polysaccharides; Practice Guidelines as Topic; Thrombocytopenia; Venous Thrombosis; Vitamin K

Type II heparin-induced thrombocytopenia is currently managed by withdrawing heparin and replacing it with danaparoid sodium. Argatroban, a direct thrombin inhibitor anticoagulant (like lepirudin), is now authorised for this indication in France, following authorisation in several other countries since the early 2000s. Argatroban has not been compared with danaparoid in clinical trials. About 700 patients treated with argatroban in 2 trials were compared to historical controls managed by simple withdrawal of heparin and, in some cases, switching to an oral anticoagulant. Argatroban had no apparent advantages in terms of death or the need for amputation. Argatroban did not appear to increase the risk of bleeding in these trials, but evidence provided by historical comparisons is weak. The adverse effect profile includes hepatic disorders (notably fulminant hepatitis). The risk of pharmacokinetic interactions appears to below. In practice, given the absence of a proven therapeutic advantage, it is better to continue to use danaparoid for first-line treatment, reserving argatroban for the rare situations in which danaparoid is inappropriate.

Topics: Anticoagulants; Antithrombins; Arginine; Chondroitin Sulfates; Dermatan Sulfate; Drug Interactions; Drug Substitution; Hemorrhage; Heparin; Heparitin Sulfate; Humans; Patient Selection; Pipecolic Acids; Risk Assessment; Risk Factors; Sulfonamides; Thrombocytopenia; Treatment Outcome; Venous Thrombosis

For patients with heparin-induced thrombocytopenia (HIT), reexposure to heparin is generally not recommended. However, these patients are likely to require anticoagulation therapy at some point in the future. During acute HIT, when thrombocytopenia and anti-heparin-platelet factor 4 antibodies (or HIT antibodies) are present, therapy with heparin must be avoided. In patients with subacute HIT, when platelets have recovered but HIT antibodies are still present, therapy with heparin should be avoided. In patients with a remote history of HIT, when HIT antibodies have cleared, heparin reexposure may be safe, although recurrent HIT has been described in some patients. For all of these patients, the use of alternate anticoagulant agents, including direct thrombin inhibitors and anti-Xa agents, is preferable. There is an increasing amount of data supporting the use of these alternative agents in a wide variety of clinical circumstances, including thromboprophylaxis and treatment of acute thrombosis. Except for a few clinical situations, it is generally possible to avoid heparin reexposure in patients with a history of HIT.

Topics: Angina, Unstable; Antibodies; Anticoagulants; Chondroitin Sulfates; Dermatan Sulfate; Drug Combinations; Female; Fondaparinux; Heparin; Heparitin Sulfate; Hirudins; Humans; Male; Multiple Organ Failure; Platelet Factor 4; Polysaccharides; Pregnancy; Preoperative Care; Recombinant Proteins; Thrombin; Thrombocytopenia; Venous Thrombosis

Heparin is a sulphated glycosaminoglycan currently used as an anticoagulant and antithrombotic drug. It consists largely of 2-O-sulphated IdoA not l&r arrow N, 6-O-disulphated GlcN disaccharide units. Other disaccharides containing unsulphated IdoA or GlcA and N-sulphated or N-acetylated GlcN are also present as minor components. This heterogeneity is more pronounced in heparan sulphate (HS), where the low-sulphated disaccharides are the most abundant. Heparin/HS bind to a variety of biologically active polypeptides, including enzymes, growth factors and cytokines, and viral proteins. This capacity can be exploited to design multi-target heparin/HS-derived drugs for pharmacological interventions in a variety of pathologic conditions besides coagulation and thrombosis, including neoplasia and viral infection. The capsular K5 polysaccharide from Escherichia coli has the same structure as the heparin precursor N-acetyl heparosan. The possibility of producing K5 polysaccharide derivatives by chemical and enzymatic modifications, thus generating heparin/HS-like compounds, has been demonstrated. These K5 polysaccharide derivatives are endowed with different biological properties, including anticoagulant/antithrombotic, antineoplastic, and anti-AIDS activities. Here, the literature data are discussed and the possible therapeutic implications for this novel class of multi-target "biotechnological heparin/HS" molecules are outlined.

Topics: Animals; Anticoagulants; Bacterial Capsules; Heparin; Heparitin Sulfate; Humans; Neoplasms; Polysaccharides, Bacterial; Technology, Pharmaceutical; Venous Thrombosis

All patients with neurologic diseases should receive perioperative VTE prophylaxis. The choice of mechanical, pharmacologic, or combined modalities of prophylaxis depends on both the underlying risk factors and surgical VTE risks. Prophylaxis and treatment options must be individualized to the patient. Prevention of VTE will help minimize the need for therapeutic treatment. Options for treatment include both inpatient and outpatient regimens using UFH or LMWH. In patients with an absolute or relative contraindication to anticoagulation, an IVC filter is an appropriate management strategy. Perioperative bridging therapy should be considered in patients with high or moderate risks for recurrent VTE.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Aspirin; Brain Diseases; Chondroitin Sulfates; Dermatan Sulfate; Dose-Response Relationship, Drug; Drug Combinations; Fibrinolytic Agents; Heparin; Heparitin Sulfate; Humans; Postoperative Complications; Venous Thrombosis; Warfarin

Heparin, and particularly low molecular weight heparin, is widely used for the treatment of patients with deep vein thrombosis (DVT) and the prevention of DVT that commonly accompanies malignancy. Malignant growth has also been linked experimentally to the function of heparin-like glycosaminoglycans (HLGAGs). In addition to the voluminous general literature on this subject, the heparin-cancer link has been the theme of at least three entire journal issues in recent months. These include the June 15, 2001 issue of Thrombosis Research, the November 2001 Supplement to Haemostasis, and the February 2002 issue of Seminars in Thrombosis and Hemostasis. Previous reviews have documented the historical development of this link that includes evidence from basic biochemistry and cell biology, studies in experimental animal model systems, and clinical trials. This concise review updates recent basic and clinical data on the heparin-cancer link that clarify mechanisms by which HLGAGs regulate the malignant behavior of cells. Electronic access to information that is increasing geometrically has become indispensable. Evidence for control of tumor cell growth by heparin-binding growth factors, tumor cell invasion by heparin-inhibitable enzyme systems, tumor cell metastasis by heparin-binding cell surface selectins, tumor angiogenesis, and tumor matrix formation related to deposition of fibrinogen/fibrin provides a secure theoretical foundation for systematic testing of this class of compounds in patients with cancer. HLGAGs may be a fundamental intermediate in the abnormal growth regulation characteristic of neoplasia that is susceptible to targeted intervention.

Topics: Anticoagulants; Comorbidity; Heparin, Low-Molecular-Weight; Heparitin Sulfate; Humans; Neoplasms; Venous Thrombosis

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

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

Topics: Abciximab; Animals; Anistreplase; Antibodies, Monoclonal; Anticoagulants; Aspirin; Chondroitin Sulfates; Clopidogrel; Dermatan Sulfate; Drug Combinations; Fibrinolytic Agents; Heparin, Low-Molecular-Weight; Heparitin Sulfate; Humans; Immunoglobulin Fab Fragments; Intermittent Claudication; Platelet Aggregation Inhibitors; Streptokinase; Ticlopidine; Vascular Diseases; 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

The past decade has seen many important advances in the pathogenesis, clinical and laboratory diagnosis, and management of heparin-induced thrombocytopenia (HIT), one of the most common immune-mediated adverse drug reactions. HIT is caused by IgG antibodies that recognize complexes of heparin and platelet factor 4, leading to platelet activation via platelet Fc gamma IIa receptors. Formation of procoagulant, platelet-derived microparticles, and, possibly, activation of endothelium generate thrombin in vivo. Thrombin generation helps to explain the strong association between HIT and thrombosis, including the newly recognized syndrome of warfarin-induced venous limb gangrene. This syndrome occurs when acquired protein C deficiency during warfarin treatment of HIT and deep venous thrombosis leads to the inability to regulate thrombin generation in the microvasculature. The central role of HIT antibodies in causing HIT, as well as refinements in laboratory assays to detect these antibodies, means that HIT should be considered a clinicopathologic syndrome. The diagnosis can be made confidently when one or more typical clinical events (most frequently, thrombocytopenia with or without thrombosis) occur in a patient with detectable HIT antibodies. The central role of thrombin generation in this syndrome provides a rationale for the use of anticoagulants that reduce thrombin generation (danaparoid) or inhibit thrombin (lepirudin).

Topics: Antibodies; Anticoagulants; Antithrombin III; Chondroitin Sulfates; Dermatan Sulfate; Drug Combinations; Fibrinolytic Agents; Gangrene; Heparin; Heparinoids; Heparitin Sulfate; Hirudin Therapy; Hirudins; Humans; Immunoglobulin G; Leg; Platelet Activation; Platelet Factor 4; Protein C Deficiency; Receptors, IgG; Recombinant Proteins; Retrospective Studies; Syndrome; Thrombin; Thrombocytopenia; Venous Thrombosis; Warfarin

Guidelines for prophylaxis of deep vein thrombosis (DVT) after hip replacement surgery suggest the use of twice-daily low-molecular-weight heparin as one treatment option. Danaparoid, a low-molecular-weight heparinoid, and once-daily enoxaparin are recently released dosage forms that have been evaluated as pharmacoprophylaxis for DVT after hip replacement surgery. Incremental cost-effectiveness ratio calculations using published efficacy and safety data suggest that enoxaparin (40 mg) daily is the more cost effective of these two agents as routine prophylaxis after hip replacement surgery.

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Chondroitin Sulfates; Cost-Benefit Analysis; Dermatan Sulfate; Drug Combinations; Enoxaparin; Heparinoids; Heparitin Sulfate; Humans; Treatment Outcome; Venous Thrombosis

Decreased antithrombin III (ATIII) activity and large splenic vein diameter (SVD) are risk factors for portal vein thrombosis (PVT) after splenectomy in liver cirrhosis with portal hypertension. Antithrombin III concentrates can prevent PVT. This study was designed to stratify risks for PVT after splenectomy in cirrhotic patients and to develop prophylactic protocols for PVT.. In 53 patients (testing cohort), the cutoff level of preoperative ATIII activity (≤60%) was evaluated for administration of ATIII concentrates. Antithrombin III activity and SVD were re-evaluated as criteria for prophylaxis of PVT. In 57 patients (validation cohort), the risk stratification of PVT and prophylactic protocols were validated.. In the testing cohort, 10 (19%) of 53 patients had PVT. Risk level of PVT was stratified and prophylactic protocols were developed. Patients at low risk (ATIII activity ≥70% and SVD <10 mm) were not treated; those at high risk (ATIII activity <70% or SVD ≥10 mm) received ATIII concentrates (1,500 U/day) for 3 days; and those at highest risk (SVD ≥15 mm) received ATIII concentrates for 3 days, followed by danaparoid sodium (2,500 U/day) for 14 days and warfarin. In the validation cohort, 0 of 14 low-risk and 2 of 32 high-risk patients had PVT. Although 8 of 11 patients at highest risk had temporary PVT, it disappeared within 3 months postoperatively. Finally, only 2 (3.5%) of 57 patients had PVT.. Risk stratification of PVT after splenectomy and prophylaxis with ATIII concentrates and danaparoid sodium dramatically reduced the incidence of PVT.

Topics: Adult; Aged; Anticoagulants; Antithrombin III; Chondroitin Sulfates; Clinical Protocols; Decision Support Techniques; Dermatan Sulfate; Drug Therapy, Combination; Female; Fibrinolytic Agents; Heparitin Sulfate; Humans; Hypertension, Portal; Laparoscopy; Liver Cirrhosis; Male; Middle Aged; Portal Vein; Postoperative Complications; Prospective Studies; Risk Assessment; Risk Factors; ROC Curve; Splenectomy; Venous Thrombosis; Warfarin

Orgaran (danaparoid sodium injection) is a novel antithrombotic agent. Early studies suggest that this compound may be beneficial in preventing deep vein thrombosis in predisposed patients. This multicenter, randomized, assessor blinded, clinical trial compared subcutaneous danaparoid with warfarin for the prevention of deep vein thrombosis in patients undergoing hip replacement surgery. Bilateral venography was used to detect thrombi. Patients also underwent follow-up examinations 1, 2, and 3 months after discontinuation of the study to determine the after effects of treatment. Nearly 27% of patients who received warfarin and 14.6% of patients who received danaparoid developed deep vein thrombosis, a risk reduction of 46%. The absolute difference in the incidence of deep vein thrombosis was 12.3% in favor of danaparoid. The incidence of venographically documented proximal deep vein thrombosis was 1.5% for danaparoid and 4.1% for warfarin. These results demonstrate that danaparoid is more effective than warfarin in preventing deep vein thrombosis following hip replacement surgery. The preoperative administration of danaparoid does not increase surgical blood loss compared with warfarin.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Arthroplasty, Replacement, Hip; Blood Loss, Surgical; Chondroitin Sulfates; Dermatan Sulfate; Drug Combinations; Female; Heparitin Sulfate; Humans; Male; Middle Aged; Postoperative Complications; Single-Blind Method; Treatment Outcome; Venous Thrombosis; Warfarin

Portal vein thrombosis (PVT) is a common complication of cirrhosis. However, in patients with PVT and cirrhosis, there is no clear evidence supporting effective treatment modalities. In this study, we examined the effectiveness and safety of anticoagulation therapy using danaparoid sodium for PVT in patients with cirrhosis.. This retrospective study assessed 52 cirrhotic patients with PVT treated with danaparoid sodium for 2 weeks between November 2008 and September 2018. The primary outcome measure was the post-treatment status of PVT assessed by reduction in thrombus volume and safety of the therapeutic intervention. PVT status was evaluated with contrast-enhanced computed tomography (CECT). All patients received 1250 units of danaparoid sodium twice daily by intravenous injection for 14 days. Patients on antithrombin III (AT-III) combination therapy were additionally administered 1500 units of AT-III on days 1-5 and days 8-12. Effectiveness was evaluated by CECT from between days 13 and 18. The secondary outcome measure was the prognosis of PVT.. All patients showed reduction in PVT volume without complications. Return of plasma AT-III level to > 70% during the treatment period contributes to ≥75% reduction of PVT volume. The prognosis in PVT patients depends on hepatic reserve capacity. When limited to Child-Pugh B and C liver cirrhosis patients, a ≥ 75% reduction of PVT volume improved the prognosis.. Danaparoid sodium-based anticoagulation therapy was effective and safe for PVT in patients with cirrhosis. Return of plasma AT-III level to the normal range during the treatment period contributes to reduction of PVT volume. A reduction of ≥75% in PVT volume may improve the prognosis of Child-Pugh B and C decompensated cirrhosis patients with PVT.

Topics: Aged; Anticoagulants; Chondroitin Sulfates; Dermatan Sulfate; Female; Heparitin Sulfate; Humans; Liver Cirrhosis; Male; Portal Vein; Prognosis; Retrospective Studies; Venous Thrombosis

Portal vein thrombosis (PVT) is a serious complication in liver cirrhosis with portal hypertension. We examined the treatment, recurrence and prognosis of PVT in cirrhotic patients.. The study subjects were all 90 cirrhotic patients with PVT treated with danaparoid sodium (DS) at our department between July 2007 and September 2016. The mean age was 68 years and mean Child-Pugh score was 7. All patients received 2500 U/day of DS for 2 weeks, and repeated in those who developed PVT recurrence after the initial therapy.. Complete response was noted in 49% (n = 44), partial response (shrinkage ≥70%) in 33% (n = 30), and no change (shrinkage <70%) in 18% (n = 16) of the patients after the initial course of treatment. DS treatment neither caused adverse events, particularly bleeding or thrombocytopenia, nor induced significant changes in serum albumin, total bilirubin, prothrombin time, and residual liver function. Re-treatment was required in 44 patients who showed PVT recurrence and 61% of these responded to the treatment. The cumulative recurrence rates at 1 and 2 posttreatment years were 26 and 30%, respectively. The recurrence rates were significantly lower in patients with acute type, compared to the chronic type (p = 0.0141). The cumulative survival rates at 1 and 3 years after treatment (including maintenance therapy with warfarin) were 83 and 60%, respectively, and were significantly higher in patients with acute type than chronic type (p = 0.0053).. We can expect prognostic improvement of liver cirrhosis by warfarin following two-week DS therapy for the treatment of PVT in patients with liver cirrhosis safety and effectiveness. An early diagnosis of PVT along with the evaluation of the volume of PVT on CT and an early intervention would contribute to the higher efficacy of the treatment.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Chondroitin Sulfates; Contrast Media; Dermatan Sulfate; Female; Heparitin Sulfate; Humans; Hypertension, Portal; Liver Cirrhosis; Male; Middle Aged; Portal Vein; Recurrence; Survival Rate; Tomography, X-Ray Computed; Treatment Outcome; Venous Thrombosis; Warfarin

Patients can develop thrombocytopenia during heparin therapy.The most frequent form, type I heparin-induced thrombocytopenia, does not require cessation of therapy. Type II heparin-induced thrombocytopenia is immune-mediated. It can cause venous or arterial thrombosis, which may be fatal or require amputation. Type II thrombocytopenia typically develops 5 to 10 days after initiation of treatment, sometimes earlier in patients previously exposed to heparins. The recommendations on platelet-count monitoring during heparin therapy are not based on high-level evidence. The main risk factors for type II thrombocytopenia must be taken into account: unfractionated heparin, previous heparin exposure, surgery, female patient. For patients considered at high risk for heparin-induced thrombocytopenia, platelet-count monitoring is usually recommended at least twice a week for at least 2 weeks. The treatment of immune-mediated heparin-induced thrombocytopenia is based on stopping heparin and replacing it with danaparoid or argatroban. In practice, the decision to initiate treatment with unfractionated or low-molecular-weight heparin is not a trivial one. In addition to the bleeding risk, the risk of type II thrombocytopenia in the short- term, or during subsequent heparin therapy, should be taken into account when assessing the harm-benefit balance.

Topics: Anticoagulants; Arginine; Chondroitin Sulfates; Dermatan Sulfate; Heparin; Heparitin Sulfate; Humans; Pipecolic Acids; Platelet Aggregation Inhibitors; Platelet Count; Sulfonamides; Thrombocytopenia; Venous Thrombosis

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

This case describes the medical history of a 61-year-old woman treated for cerebral venous thrombosis (CVT) leading to diagnosis of essential thrombocythemia (ET). During treatment with unfractionated heparin, after initial improvement of clinical state, signs of cerebral hypertension reappeared. Although the platelet count decreased, heparin-induced thrombocytopenia (HIT) was only suspected 2 days later when it dropped below the standard 150 × 10(9) L(-1) threshold. HIT diagnosis was confirmed by the presence of anti-PF4/heparin IgG. This late finding was the cause of the extension of CVT with worsening of cerebral hypertension necessitating decompressive craniectomy. Elevated basal platelet count due to ET can delay diagnosis and treatment of HIT. In this case, physicians should be more attentive to platelet count variations rather than thrombocytopenia threshold.

Topics: Anticoagulants; Cerebral Veins; Chondroitin Sulfates; Decompressive Craniectomy; Dermatan Sulfate; Female; Heparin; Heparitin Sulfate; Humans; Intracranial Hypertension; Middle Aged; Platelet Count; Radiography; Thrombocythemia, Essential; Thrombocytopenia; Thrombosis; Treatment Outcome; Venous Thrombosis

A 54-year-old man had been admitted to Nara city hospital because of hematemesis and dyspnea caused by physical exertion, and was given a diagnosis of esophago-cardial varices and portal venous thrombosis. He was transferred to our hospital for further examinations and treatments. Ultrasonography (US) and computed tomography (CT) revealed the progression of portal venous thrombosis. Danaparoid sodium was administered to treat the portal vein thrombus. 5 days later, the patient was found to have hematemesis resulting from a cardial varices rupture. After endoscopic variceal ligation (EVL) and endoscopic injection sclerotherapy (EIS) was performed, danaparoid sodium was administered for 2 weeks. After the treatment, portal vein thrombus had almost disappeared. Due to an increased risk of bleeding, cases of esophago-cardial varices with portal venous thrombosis must be treated with care. This is the first report of upper gastrointestinal bleeding due to danaparoid sodium. Danaparoid sodium must be carefully administered when patients have portal venous thrombosis with delicate varices.

Topics: Anticoagulants; Chondroitin Sulfates; Dermatan Sulfate; Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Hematemesis; Heparitin Sulfate; Humans; Liver Cirrhosis, Alcoholic; Male; Middle Aged; Portal Vein; Sclerotherapy; Venous Thrombosis

Itching erythematous or eczematous plaques around injection sites are quite frequent side effects of heparin treatment and are clinical symptoms of a delayed-type hypersensitivity to heparins. In most cases, changing the subcutaneous therapy from unfractionated to low molecular weight heparin or treatment with heparinoids does not provide improvement, due to extensive cross-reactivity. Interestingly, it has been demonstrated that patients with delayed-type hypersensitivity to subcutaneously injected heparins tolerate intravenous application of heparin in controlled challenge tests. A patient with known delayed-type hypersensitivity to heparins received the heparinoid, danaparoid, subcutaneously for thrombosis prophylaxis after orthopedic surgery. After the first few injections, eczematous plaques developed; administration of the anticoagulant was continued and gradually resulted in generalized eczema despite treatment with topical and oral glucocorticoids. However, the patient required further anticoagulation. After discontinuation of subcutaneous injections and a switch to intravenous heparin, rapid improvement and clearing of skin lesions occurred. Therefore, in cases of delayed-type hypersensitivity to subcutaneously injected heparins, the switch from subcutaneous to intravenous heparin administration may be justified.

Topics: Aged; Anticoagulants; Chondroitin Sulfates; Dermatan Sulfate; Dermatitis, Allergic Contact; Eczema; Female; Heparin; Heparitin Sulfate; Humans; Immobilization; Infusions, Intravenous; Injections, Subcutaneous; Postoperative Care; Postoperative Complications; Thrombophilia; Venous Thrombosis

Topics: Abortion, Habitual; Adult; Anticoagulants; Chondroitin Sulfates; Dermatan Sulfate; Factor V; Factor V Deficiency; Female; Heparin; Heparitin Sulfate; Homozygote; Humans; Infant, Newborn; Male; Platelet Count; Point Mutation; Pregnancy; Pregnancy Complications, Hematologic; Thrombocytopenia; Translocation, Genetic; Venous Thrombosis

We report a case of hepatitis B type liver cirrhosis with portal venous thrombosis in which danaparoid sodium was very effective. The portal venous thrombosis in this case disappeared 2 weeks commencing after administration of danaparoid sodium. The patient had not adverse effects or complications such as hemorrhage, and the clinical course was good. We consider that danaparoid sodium is an anticoagulant unlikely to cause adverse effects such as hemorrhage, and that it might be effective for treatment of portal venous thrombosis. We intend to examine the indications of treatment with danaparoid sodium, clarify the best administration method, and establishment of maintenance therapy by investigating more cases.

Topics: Anticoagulants; Chondroitin Sulfates; Dermatan Sulfate; Heparitin Sulfate; Hepatitis B; Humans; Liver Cirrhosis; Male; Middle Aged; Portal Vein; Tomography, X-Ray Computed; Ultrasonography; Venous Thrombosis

Heparin-induced thrombocytopenia (HIT) is the most common form of drug-induced immune-mediated thrombocytopenia. HIT may be aggravated by life-threatening arterial and venous thrombosis and, to a lesser extent, hemorrhagic complications. We investigated the incidence of thromboembolic and hemorrhagic complications in critically ill patients with the multiple organ dysfunction syndrome and HIT.. Case-control study.. A 33-bed general intensive care unit in a university-affiliated teaching hospital.. Twenty consecutive patients with laboratory-proven HIT compared with 20 contemporary, consecutive patients without HIT.. Unfractionated heparin or low-molecular-weight heparin were replaced by danaparoid sodium in patients with HIT.. Heparin-induced thrombocytopenia was proven by a positive platelet aggregation test. The HIT group consisted of 14 males and 6 females aged 65.2+/-10.8 years (mean +/- standard deviation) with APACHE II scores of 26.7+/-5.4. Thrombocytopenia less than 100 x 10(9)/l developed within 6.4+/-7.0 days. In 12 patients thrombocytopenia resolved after discontinuation of unfractionated heparin in 8.8+/-6.4 days. Arterial and venous thromboembolic complications occurred more frequently in HIT patients than in non-HIT patients (10/20 (50%) versus 0/20 (0%); chi-square p<0.001). Hemorrhagic complications also occurred more frequently in HIT patients than in non-HIT patients (17/20 (85%) versus 7/20 (35%); chi-square p=0.001).. In critically ill patients with HIT, the incidence of thromboembolic complications and hemorrhagic complications was remarkably high.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Case-Control Studies; Chondroitin Sulfates; Critical Illness; Dermatan Sulfate; Drug Combinations; Female; Hemorrhage; Heparin; Heparitin Sulfate; Humans; Incidence; Intensive Care Units; Male; Middle Aged; Multiple Organ Failure; Risk Factors; Thrombocytopenia; Venous Thrombosis

Topics: Activated Protein C Resistance; Adult; Anticoagulants; Chondroitin Sulfates; Dermatan Sulfate; Drug Combinations; Factor V; Female; Heparitin Sulfate; Humans; Lactation; Pregnancy; Pregnancy Complications, Hematologic; Safety; Venous Thrombosis

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

Topics: Anticoagulants; Chondroitin Sulfates; Dermatan Sulfate; Diagnosis, Differential; Female; Fondaparinux; Heparinoids; Heparitin Sulfate; Humans; Hypersensitivity, Delayed; Injections; Intradermal Tests; Middle Aged; Polysaccharides; Venous Thrombosis

Several low molecular weight (LMW) heparin preparations, including dalteparin, enoxaparin and nadroparin, as well as the heparinoid danaparoid sodium, are approved for use in Australia. LMW heparins are replacing unfractionated heparin for the prevention and treatment of venous thromboembolism and the treatment of non-ST-segment-elevation acute coronary syndromes. The advantages of LMW heparins over unfractionated heparin include a longer half-life (allowing once-daily or twice-daily subcutaneous dosing), high bioavailability and predictable anticoagulant response (avoiding the need for dose adjustment or laboratory monitoring in most patients), and a low risk of heparin-induced thrombocytopenia and osteoporosis. Laboratory monitoring of LMW heparin therapy should be considered in newborns and children, patients with renal impairment, those who are pregnant, and those at the extremes of bodyweight (eg, < 40 kg or > 100 kg). LMW heparins should: be avoided or used with caution in patients undergoing neuraxial anaesthesia, owing to the potential for epidural haematoma formation; not be used (ie, are contraindicated) in patients with immune heparin-induced thrombocytopenia, as they may cross-react with anti-heparin antibodies. Conventional unfractionated heparin retains a role in the management of patients at high risk of bleeding, undergoing invasive procedures, and patients with renal failure owing to its shorter half-life, reversibility with protamine sulfate, and extrarenal metabolism. The heparinoid danaparoid sodium is effective for the treatment of heparin-induced thrombocytopenia.

Topics: Anticoagulants; Chondroitin Sulfates; Dermatan Sulfate; Drug Combinations; Heparin; Heparin, Low-Molecular-Weight; Heparinoids; Heparitin Sulfate; Humans; Myocardial Infarction; Thrombocytopenia; Venous Thrombosis

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

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

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

Topics: Anticoagulants; Antithrombin III; Antithrombins; Chondroitin Sulfates; Dermatan Sulfate; Drug Combinations; Femoral Vein; Fibrinolytic Agents; Heparin; Heparinoids; Heparitin Sulfate; Hirudin Therapy; Humans; Iliac Vein; Thrombocytopenia; Thrombolytic Therapy; Vena Cava, Inferior; Venous Thrombosis

Topics: Acute Kidney Injury; Aged; Anticoagulants; Chondroitin Sulfates; Dermatan Sulfate; Drug Combinations; Hemorrhage; Heparin; Heparitin Sulfate; Humans; Lung Diseases; Male; Phlebography; Renal Dialysis; Thrombocytopenia; Venous Thrombosis

The treatment of heparin-induced thrombocytopenia in pregnancy is uncertain. Warfarin is contraindicated and ancrod is of unknown safety. Low-molecular-weight heparin should not be used because of cross-reactivity with unfractionated heparin. We report a case of heparin-induced thrombocytopenia during pregnancy treated successfully with danaparoid.. A 25-year-old woman pregnant with twins developed heparin-induced thrombocytopenia after starting heparin therapy for a deep vein thrombosis. Treatment was initiated with danaparoid by subcutaneous injection and was continued until the time of delivery. Treatment was completed with 6 weeks of warfarin therapy postpartum. No fetal or maternal ill effects were observed.. Danaparoid, which has low cross-reactivity for heparin-dependent antibodies and no known fetopathic effects, was used successfully to treat our patient, who developed heparin-induced thrombocytopenia during pregnancy. Danaparoid may be the treatment of choice for this difficult clinical situation in which there are limited therapeutic options.

Topics: Adult; Anticoagulants; Chondroitin Sulfates; Dermatan Sulfate; Drug Combinations; Female; Heparin; Heparinoids; Heparitin Sulfate; Humans; Pregnancy; Pregnancy Complications, Hematologic; Pregnancy, Multiple; Thrombocytopenia; Twins; Venous Thrombosis