fondaparinux and Thrombocytopenia

Topics: Anticoagulants; Factor Xa Inhibitors; Fondaparinux; Heparin; Humans; Thrombocytopenia

Heparin-induced thrombocytopenia (HIT) is an immunologically-mediated complication, which usually follows heparin exposition, less frequently exposition to other drugs or even occurs spontaneously. The type of heparin, its dose and mode of application as well as the exposition time, major trauma or operation, and obesity represent the main risk factors for HIT. The probability of HIT correlates with so-called 4T-score. A confirmatory laboratory diagnostic should be exclusively reserved for patients with a medium to a high probability of HIT development (more than 3 points in 4T-score). The screening method is based on serological detection of antibodies against heparin-platelet factor-4 complexes; confirmation tests aim to identify the activation of platelets. The treatment of HIT requires an immediate interruption of heparin application and rigorous antithrombotic treatment with an alternative agent. Herein authors describe a clinical case of HIT manifested as an extreme urticarial reaction in the location of nadroparin application as well as thrombosis of deep subcutaneous veins in a polymorbid obese patient with an extensive and infected burn. Due to timely diagnosis and fondaparinux treatment, no more severe thrombotic events occurred in this patient.

Topics: Anticoagulants; Fondaparinux; Heparin; Humans; Thrombocytopenia; Thrombosis

Heparin-induced thrombocytopaenia (HIT) is a severe and potentially life-threatening adverse drug reaction. Patients become extremely hypercoagulable, and this can lead to life-threatening and limb-threatening thrombosis with a mortality of 5%-10%. HIT is an antibody-mediated process in which platelet activation occurs. Diagnosis requires a high index of suspicion along with a scoring system and laboratory testing. Patients suspected of having HIT must not receive any further heparin or low-molecular weight heparin and must be started on an alternative anticoagulant such as argatroban or danaparoid. Fondaparinux may also be considered but is not licenced for this indication.

Topics: Anticoagulants; Arginine; Chondroitin Sulfates; Dermatan Sulfate; Fondaparinux; Heparin; Heparitin Sulfate; Humans; Pipecolic Acids; Polysaccharides; Sulfonamides; Thrombocytopenia

Direct oral anticoagulants (DOACs) are attractive options for treatment of heparin-induced thrombocytopenia (HIT). We report our continuing experience in Hamilton, ON, Canada, since January 1, 2015 (when we completed our prospective study of rivaroxaban for HIT), using rivaroxaban for serologically confirmed HIT (4Ts score ≥4 points; positive platelet factor 4 [PF4]/heparin immunoassay, positive serotonin-release assay). We also performed a literature review of HIT treatment using DOACs (rivaroxaban, apixaban, dabigatran, edoxaban). We focused on patients who received DOAC therapy for acute HIT as either primary therapy (group A) or secondary therapy (group B; initial treatment using a non-DOAC/non-heparin anticoagulant with transition to a DOAC during HIT-associated thrombocytopenia). Our primary end point was occurrence of objectively documented thrombosis during DOAC therapy for acute HIT. We found that recovery without new, progressive, or recurrent thrombosis occurred in all 10 Hamilton patients with acute HIT treated with rivaroxaban. Data from the literature review plus these new data identified a thrombosis rate of 1 of 46 patients (2.2%; 95% CI, 0.4%-11.3%) in patients treated with rivaroxaban during acute HIT (group A, n = 25; group B, n = 21); major hemorrhage was seen in 0 of 46 patients. Similar outcomes in smaller numbers of patients were observed with apixaban (n = 12) and dabigatran (n = 11). DOACs offer simplified management of selected patients, as illustrated by a case of persisting (autoimmune) HIT (>2-month platelet recovery with inversely parallel waning of serum-induced heparin-independent serotonin release) with successful outpatient rivaroxaban management of HIT-associated thrombosis. Evidence supporting efficacy and safety of DOACs for acute HIT is increasing, with the most experience reported for rivaroxaban.

Topics: Acute Disease; Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Female; Fondaparinux; Heparin; Humans; Male; Middle Aged; Ontario; Polysaccharides; Rivaroxaban; Thrombocytopenia; Treatment Outcome

Patients with chronic kidney disease (CKD) are at increased risk for both thrombotic events and bleeding. The early stages of CKD are mainly associated with prothrombotic tendency, whereas in its more advanced stages, beside the prothrombotic state, platelets can become dysfunctional due to uremic-related toxin exposure leading to an increased bleeding tendency. Patients with CKD usually require anticoagulation therapy for treatment or prevention of thromboembolic diseases. However, this benefit could easily be offset by the risk of anticoagulant-induced bleeding. Treatment of patients with CKD should be based on evidence from randomized clinical trials, but usually CKD patients are excluded from these trials. In the past, unfractionated heparins were the anticoagulant of choice for patients with CKD because of its independence of kidney elimination. However, currently low-molecular-weight heparins have largely replaced the use of unfractionated heparins owing to fewer incidences of heparin-induced thrombocytopenia and bleeding. We undertook this review in order to explain the practical considerations for the management of anticoagulation in these high risk population.

Topics: Administration, Oral; Anticoagulants; Antithrombins; Blood Platelets; Drug Administration Schedule; Factor Xa; Fondaparinux; Glomerular Filtration Rate; Hemorrhage; Heparin; Heparin, Low-Molecular-Weight; Humans; Polysaccharides; Renal Insufficiency, Chronic; Thrombin; Thrombocytopenia; Thrombosis

Heparin induced thrombocytopenia (HIT) remains a rare, but significant, condition related to mortality and morbidity. The incidence has decreased with reduced use of unfractionated heparin, with the exception of cardiac surgery. Due to the high risk of thrombosis, a switch to a non-heparin anticoagulant is required, until platelet counts normalize. Within the acute setting, argatroban, fondaparinux and direct acting oral anticoagulants (DOACS) are therapeutic options. In patients with HIT-associated thrombosis or who require long-term anticoagulation, warfarin remains the preference, but DOACs are attractive alternatives.

Topics: Anticoagulants; Arginine; Disease Management; Fondaparinux; Heparin; Humans; Pipecolic Acids; Polysaccharides; Sulfonamides; Thrombocytopenia; Warfarin

Heparin-induced thrombocytopenia is a profoundly dangerous, potentially lethal, immunologically mediated adverse drug reaction to unfractionated heparin or, less commonly, to low-molecular weight heparin. In this comprehensive review, the authors highlight heparin-induced thrombocytopenia's risk factors, clinical presentation, pathophysiology, diagnostic principles, and treatment. The authors place special emphasis on the management of patients requiring procedures using cardiopulmonary bypass or interventions in the catheterization laboratory. Clinical vigilance of this disease process is important to ensure its recognition, diagnosis, and treatment. Misdiagnosis of the syndrome, as well as misunderstanding of the disease process, continues to contribute to its morbidity and mortality.

Topics: Anticoagulants; Antithrombins; Arginine; Cardiopulmonary Bypass; Fondaparinux; Heparin; Hirudins; Humans; Incidence; Peptide Fragments; Percutaneous Coronary Intervention; Pipecolic Acids; Plasmapheresis; Platelet Function Tests; Platelet Transfusion; Polysaccharides; Recombinant Proteins; Risk Factors; Sulfonamides; Thrombocytopenia

During pregnancy thrombo-prophylaxis could be required in high risk women. If a severe allergic reaction to low-molecular-weight-heparin (LMWH) or a heparin-induced-thrombocytopenia (HIT) occurs, it's mandatory to stop the drug. Fondaparinux could be an effective option. In the present review, the maternal and pregnancy outcomes of 65 pregnancies in women using Fondaparinux were reported. It was well-tolerated and rate of pregnancy complications was similar to that observed in general population. Regarding congenital malformations, further studies are necessary to investigate the safety of the drug.

Topics: Anticoagulants; Female; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Maternal Exposure; Patient Safety; Polysaccharides; Pregnancy; Pregnancy Complications, Cardiovascular; Risk; Thrombocytopenia; Thrombosis

The efficacy and safety of fondaparinux, an emerging therapeutic option for heparin-induced thrombocytopenia (HIT), remain unclear in cardiac surgery patients with HIT.. Using several search criteria, we reviewed all cases of fondaparinux use in patients who developed HIT after any cardiovascular intervention and were indexed in MEDLINE by August 2014. Based on pre-specified criteria, cases were divided into confirmed HIT, probable HIT and possible HIT. The outcome of fondaparinux use in each group was compared using Chi-square test.. Of 43 total cases, 22 had confirmed HIT and 21 had possible HIT. Valve replacement or repair (39%) and heart transplant or ventricular assist device placement (21%) were the most common preceding cardiovascular interventions. Creatinine clearance <30 ml was present in 27% and 52% of confirmed and possible HIT respectively. Overall the risk of new thrombosis and bleeding with fondaparinux were 4.6% and 7% respectively, without any differences in the two subgroups. The majority (86%) of cases improved clinically; of the remainder patients, similar percentage of cases with possible HIT and confirmed HIT died (24% vs. 5%; p= 0.102). None of the deaths were attributed to HIT or complications of bleeding.. Within the limitations of this study, the risk of thrombosis and bleeding with fondaparinux use in cardiac surgery patients with HIT are low and largely comparable to outcomes reported in literature with other agents.

Topics: Anticoagulants; Cardiac Surgical Procedures; Fondaparinux; Heparin; Humans; Polysaccharides; Thrombocytopenia

Regarding anticoagulant therapies there has been a remarkable shift in recent years. The objective of this brief overview is to provide relevant information and guidelines on the advantages and disadvantages of novel anticoagulants addressing specifically the surgical disciplines. Hitherto, conventional anticoagulant therapy in patients with a high thrombosis risk was largely limited to heparins and vitamin-K antagonists (VKA). Their modes of action, the difficulties in managing VKAs (e.g., bridging therapy) and the risk of HIT (heparin-induced thrombocytopenia) associated with heparins are briefly discussed. Novel anticoagulants supposedly eliminate these obstacles. Fondaparinux (Arixtra®) is a fully synthetic pentasaccharide which acts like a heparin but has an increased half life. Fondaparinux has a diminished risk of HIT. However, no specific antidote is currently available for Fondaparinux. The novel oral anticoagulants (NOAC) dabigatran etexilat (Pradaxa®), rivaroxaban (Xarelto®) and apixaban (Eliquis®), also known as "direct" anticoagulants, act independently from antithrombin by inhibiting thrombin, as in the case of dabigatran, or by inhibiting factor Xa, as in the case of rivaroxaban and apixaban. It is assumed that they are suitable for long-term use and do not require laboratory monitoring. Nevertheless, clinical experience is very limited and caution rather than quick conclusions is necessary. Two major drawbacks are on the one hand the risk of drug accumulation in kidney and/or liver disease and, on the other hand, the lack of specific antidotes. In addition, interactions with other medication may have unexpected effects on serum drug levels. Therefore, the analysis of drug levels in the plasma may become necessary in subgroups of patients.. Studies establishing clear recommendations for the desirable and measurable reference range are needed. Similarly, evidence-based recommendations regarding perioperative prevention of thrombosis are required ("bridging": yes or no?). Irrespective of these issues, the authors predict a further expansion of the use of NOACs.

Topics: Administration, Oral; Anticoagulants; Benzimidazoles; Blood Coagulation Tests; Dabigatran; Drug Interactions; Factor Xa Inhibitors; Fondaparinux; Heparin; Humans; International Normalized Ratio; Liver Failure; Metabolic Clearance Rate; Morpholines; Perioperative Care; Polysaccharides; Pyrazoles; Pyridines; Pyridones; Renal Insufficiency; Rivaroxaban; Thiophenes; Thrombocytopenia; Thrombosis; Vitamin K

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

Large licensing trials did not find any association between the use of fondaparinux and the development of heparin-induced thrombocytopenia (HIT). Fondaparinux is in fact recommended as an option for the management of HIT. Since the first report of fondaparinux-associated HIT in 2007, additional reports have been published. However, the rarity of these cases, differences in case definition, and lack of larger case series have prevented better understanding of this disease. The objective of this study was to determine the clinical manifestations of fondaparinux-associated HIT, the predictive value of pretest probability (4Ts) scoring system, and the outcomes associated with current management.. Using several search terms, we reviewed all cases of fondaparinux-associated HIT reported and indexed in PubMed till May 2013. All references were also checked for additional reports. We categorized the cases of fondaparinux-associated HIT as confirmed, probable, and possible based on our case definition.. A total of eight cases of fondaparinux-associated HIT were identified. Fondaparinux-associated HIT occurred in the setting of pro-inflammatory state, prior HIT, or exposure to heparin products. Bilateral adrenal hemorrhage or infarct, reflecting hypercoagulability or disseminated intravascular coagulation, was seen in 25% of patients. The pretest probability (4Ts) scoring system used for HIT appears to correctly risk stratify all the cases. Although functional assays can be used for the diagnosis, in the presence of recent exposure to heparin products, only the demonstration of fondaparinux-dependent platelet activation should be considered confirmatory. Non-heparin anticoagulants are effective therapy; however, one-third of the patients had poor outcomes.. The risk of fondaparinux-associated HIT, although low is real, which along with documented cases of fondaparinux failure mandate its cautious use in the management of HIT.

Topics: Aged; Aged, 80 and over; Anticoagulants; Blood Platelets; Disseminated Intravascular Coagulation; Female; Fondaparinux; Heparin; Humans; Male; Middle Aged; Platelet Activation; Polysaccharides; Thrombocytopenia

Topics: Anticoagulants; Antithrombins; Drug Hypersensitivity; Drug Substitution; Fondaparinux; Heparin; Heparinoids; Humans; Immunologic Tests; Platelet Activation; Platelet Factor 4; Polysaccharides; Thrombocytopenia

Topics: Anticoagulants; Fondaparinux; Heparin; Heparin, Low-Molecular-Weight; Humans; Platelet Count; Polysaccharides; Thrombocytopenia

To describe issues and challenges associated with venous thromboembolism (VTE) risk assessment and the use of drug therapies for VTE prophylaxis.. Patients at risk for VTE are a heterogeneous group. Systems for scoring VTE risk have been developed to identify patients who warrant prophylaxis, but most risk-scoring systems are complex and have not been validated. The optimal drug therapies and dosing strategies for reducing VTE risk are not well defined for many clinical situations, despite the availability of evidence-based guidelines from authoritative sources. Patient characteristics can influence the agent selected, dosing, timing of initiation, and duration of drug therapy. Individualized approaches to prophylaxis in patients undergoing major orthopedic surgery should take into account the presence of severe renal impairment, critical illness, morbid obesity, epidural catheters, and history of heparin-induced thrombocytopenia. To provide safe, effective VTE prophylaxis, clinicians, including health-system pharmacists, should collaborate in developing management plans tailored to patients' needs.. Preventing VTE is a challenge that can be addressed by gaining an understanding of the issues involved in patient assessment and prophylactic drug therapy and using a team approach to optimize patient outcomes.

Topics: Anticoagulants; Aspirin; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Polysaccharides; Risk Assessment; Risk Factors; Risk Reduction Behavior; Thrombocytopenia; Ultrasonography; United States; Venous Thromboembolism; Warfarin

Heparin-induced thrombocytopenia (HIT) is a significant cause of morbidity and mortality in hospitalized patients, due to life and limb-threatening thrombosis. Prompt recognition, laboratory testing, and alternate anticoagulation are essential. At present, HIT remains an underdiagnosed and undertreated condition. This review will discuss the relative merits of the approved treatment options, as well as address additional anticoagulants that show promise for the future.. Argatroban and lepirudin are well studied and approved drugs for treatment of HIT. Both of these drugs are equal in efficacy, and differences in pharmacokinetic profiles allow the choice of drug to be tailored to the clinical scenario. Bivalirudin and fondaparinux have been used to treat HIT in small case series. New oral anticoagulants, such as factor IIa and factor Xa inhibitors, may provide a novel treatment approach in HIT.. First-line therapies for HIT are argatroban or lepirudin. Patient-specific factors determine which drug should be used, and taking advantage of their differences allows effective anticoagulation with minimal risk of bleeding. Bivalirudin and fondaparinux require further study before they can be recommended. Once proven well tolerated and effective for treating thrombosis, these new oral anticoagulants should next be studied for treating HIT.

Topics: Anticoagulants; Fibrinolytic Agents; Fondaparinux; Heparin; Hirudins; Humans; Peptide Fragments; Platelet Aggregation Inhibitors; Polysaccharides; Recombinant Proteins; Thrombocytopenia

Inflammatory plaques at injection sites are frequent side effects of heparin treatment and a clinical symptom of delayed-type hypersensitivity (DTH) to heparin. In most cases, changing the subcutaneous therapy from unfractionated to low-molecular-weight heparin or treatment with heparinoids does not provide improvement because of extensive cross-reactivity. Because of their completely different chemical structure, hirudins are a safe alternative for anticoagulation. Despite DTH to subcutaneously injected heparins, patients tolerate heparin intravenously. Therefore, in case of therapeutic necessity and DTH to heparins, the simple shift from subcutaneous to intravenous heparin administration is justified. Skin necrosis is a rare complication of anticoagulation. Heparin-induced skin necrosis is 1 of the symptoms of immune-mediated heparin-induced thrombocytopenia and should result in the immediate cessation of heparin therapy to prevent potentially fatal thrombotic events. This is in contrast to coumarin-induced skin necrosis, where therapy may be continued or restarted at a lower dose.

Topics: Anaphylaxis; Anticoagulants; Coumarins; Drug Eruptions; Fibrinolytic Agents; Fondaparinux; Heparin; Heparin, Low-Molecular-Weight; Hirudins; Humans; Hypersensitivity, Delayed; Polysaccharides; Thrombin; Thrombocytopenia; Vitamin K

Heparin-induced thrombocytopenia (HIT) is an antibody-mediated prothrombotic disorder triggered by PF4-binding polyanions, usually heparin. The pentasaccharide anticoagulant, fondaparinux, despite its negative charge and structural similarity to heparin, does not usually promote antibody binding to PF4 (owing to absent/weak 'cross-reactivity'). Thus, despite its ability to trigger anti-PF4/heparin antibodies ('immunogenicity'), fondaparinux has low - but not zero - risk of inducing HIT de novo, or of exacerbating HIT when antibodies are already present. Indeed, despite rare reports of fondaparinux-induced HIT, this 'dissociation' between immunogenicity and cross-reactivity suggests that fondaparinux should be effective in treating HIT, as supported by several observational studies. An emerging issue: will clinicians accept this favorable experience of fondaparinux for treating HIT when a lack of randomized trials will hinder regulatory approval for this indication?

Topics: Adolescent; Adult; Aged; Antibodies; Anticoagulants; Antigen-Antibody Complex; Drug Administration Schedule; Drug Dosage Calculations; Female; Fondaparinux; Heparin; Humans; Male; Middle Aged; Platelet Factor 4; Polysaccharides; Risk; Thrombocytopenia

Fondaparinux, a pentasaccharide which selectively binds to antithrombin III, has negligible to no cross-reactivity with heparin-induced thrombocytopenia (HIT) antibodies in in vitro studies. The lack of cross-reactivity suggests a potential role in the management of HIT, and indeed, there are several such case reports and small studies. These published data have used both the prophylactic and weight-based treatment doses. However, due to the small possibility of developing HIT with thromboembolic complications while receiving fondaparinux, it is suggested that the appropriate weight-based treatment dose be used. In all these reports, fondaparinux provided adequate anticoagulation, prevented further thromboembolic events, and platelet counts returned to normal. However, there have been a couple of case reports on possible HIT or HIT-like syndrome secondary to fondaparinux use.. Fondaparinux is an attractive anticoagulant therapy in patients with HIT. There is still the need for larger randomized trials evaluating the true efficacy, appropriate dose, safe duration of treatment, and the true incidence of HIT associated with fondaparinux.

Topics: Adult; Anticoagulants; Clinical Trials as Topic; Female; Fondaparinux; Heparin; Humans; Male; Polysaccharides; Thrombocytopenia; Thromboembolism

Topics: Anticoagulants; Arginine; Autoantibodies; Chondroitin Sulfates; Dermatan Sulfate; Drug Monitoring; Fondaparinux; Heparin; Heparitin Sulfate; Hirudins; Humans; Peptide Fragments; Pipecolic Acids; Platelet Count; Platelet Factor 4; Polysaccharides; Recombinant Proteins; Sulfonamides; Thrombocytopenia; Thrombosis; Warfarin

To review the available literature addressing the role of fondaparinux in the management of heparin-induced thrombocytopenia (HIT).. Primary articles were identified by a MEDLINE search (2004-June 2009) of English-language literature using the MeSH headings fondaparinux, heparin, low-molecular-weight heparin, and thrombocytopenia. Relevant consensus guidelines (2006-June 2009) were also identified.. All published studies and case reports, as well as relevant consensus guidelines, evaluating the use of fondaparinux for the management of HIT were included.. The role of fondaparinux in the management of HIT is a therapeutic controversy challenging clinicians today. An open-label, prospective pilot study of 7 patients with acute HIT supports fondaparinux as an alternative anticoagulant. Additionally, a total of 12 patients with HIT from a larger case study and retrospective cohort were successfully treated with fondaparinux. Much of the supporting data exists in the form of case reports, each demonstrating normalization of platelet counts without any evidence of new thrombosis. The differences in clinical scenarios as well as the role and dose of fondaparinux make interpretation of these reports difficult. Three case reports have been published raising concerns regarding fondaparinux causing or failing to manage HIT appropriately. However, common weaknesses such as small sample sizes and nonuniform definitions of HIT limit the usefulness of these findings. The updated American College of Chest Physicians consensus guidelines now recognize fondaparinux as an option in the management of HIT; however, the level of evidence supporting this is of low quality. The use of fondaparinux as a bridging agent between direct thrombin inhibitor and warfarin therapy has been proposed. A recently published case report gives support to this approach.. Controlled clinical trials evaluating the use of fondaparinux in the management of HIT need to be completed before this therapy can be routinely recommended.

Topics: Anticoagulants; Clinical Trials as Topic; Fondaparinux; Heparin; Humans; Polysaccharides; Practice Guidelines as Topic; Thrombocytopenia

Heparin-induced thrombocytopenia (HIT) is an immune-mediated disorder caused by the development of antibodies to platelet factor 4 (PF4) and heparin. The thrombocytopenia is typically moderate, with a median platelet count nadir of approximately 50 to 60 x 10(9) platelets/L. Severe thrombocytopenia has been described in patients with HIT, and in these patients antibody levels are high and severe clinical outcomes have been reported (eg, disseminated intravascular coagulation with microvascular thrombosis). The timing of the thrombocytopenia in relation to the initiation of heparin therapy is critically important, with the platelet count beginning to drop within 5 to 10 days of starting heparin. A more rapid drop in the platelet count can occur in patients who have been recently exposed to heparin (within the preceding 3 months), due to preformed anti-heparin/PF4 antibodies. A delayed form of HIT has also been described that develops within days or weeks after the heparin has been discontinued. In contrast to other drug-induced thrombocytopenias, HIT is characterized by an increased risk for thromboembolic complications, primarily venous thromboembolism. Heparin and all heparin-containing products should be discontinued and an alternative, non-heparin anticoagulant initiated. Alternative agents that have been used effectively in patients with HIT include lepirudin, argatroban, bivalirudin, and danaparoid, although the last agent is not available in North America. Fondaparinux has been used in a small number of patients with HIT and generally appears to be safe. Warfarin therapy should not be initiated until the platelet count has recovered and the patient is systemically anticoagulated, and vitamin K should be administered to patients receiving warfarin at the time of diagnosis of HIT.

Topics: Anticoagulants; Arginine; Autoantibodies; Contraindications; Disseminated Intravascular Coagulation; Fondaparinux; Heparin; Hirudins; Humans; Pipecolic Acids; Platelet Count; Platelet Factor 4; Polysaccharides; Recombinant Proteins; Sulfonamides; Thrombocytopenia; Thrombophilia; Time Factors; Venous Thromboembolism; Vitamin K; Warfarin

Disseminated intravascular coagulation (DIC) is the physiologic result of pathologic overstimulation of the coagulation system. Despite multiple triggers, a myriad of laboratory abnormalities, and a clinical presentation ranging from gross hemostatic failure to life-threatening thrombosis, or even both simultaneously, a simplified clinical approach augmented by a few readily available tests allows prompt identification of the process and elucidation of treatment opportunities. Platelet counts in DIC may be low, especially in acute sepsis-associated DIC, yet increased in malignancy-associated chronic DIC. Thrombotic risk is not a function of the platelet count, and thrombocytopenia does not protect the patient from thrombosis. The stratification of both thrombotic risk and hemorrhagic risk will be addressed.

Topics: Adenocarcinoma; Aged; Blood Coagulation Factors; Disseminated Intravascular Coagulation; Esophageal Neoplasms; Fatal Outcome; Fondaparinux; Foodborne Diseases; Hemorrhage; Heparin; Hepatitis C, Chronic; Humans; Male; Middle Aged; Multiple Organ Failure; Polysaccharides; Postoperative Complications; Thrombocytopenia; Thrombophlebitis; Thrombosis; Vibrio Infections; Vibrio vulnificus; Young Adult

Topics: Anticoagulants; Antithrombin III; Arginine; Fondaparinux; Heparin; Hirudins; Humans; Pipecolic Acids; Polysaccharides; Recombinant Proteins; Sulfonamides; Thrombin; Thrombocytopenia

For decades, the options for therapeutic anticoagulation were limited to unfractionated heparin (UFH) and vitamin K antagonists (VKA), and their well-known limitations had to be accepted. With the introduction of the various LMWHs, the short- and medium-term anticoagulation could be much improved, but an alternative to VKA is still missing The heparins provided the proof of concept that FXa and thrombin represent suitable targets for therapeutic anticoagulation. Consequently, the search for new anticoagulants focuses on inhibitors of thrombin (DTI) or FXa (DXI). Apart from the VKA, the anticoagulants presently available or in an advanced stage of development can thus be divided in two classes: One are the glyco-anticoagulants with the natural sulfated glycosaminoglycans (GAGs) (UFH, LMWHs, and danaparoid) and the synthetic oligosaccharides (OS) (fondaparinux, idraparinux, and SR123781A). The other class are the xenobiotic anticoagulants, i.e. proteins and synthetic chemical entities. Die glyco-anticoagulants act partially (GAGs) or exclusively (oligosaccharides) by catalysing antithrombin, whereas the xenobiotic anticoagulants are direct inhibitors of either thrombin or FXa. At present, three parenteral DTI (lepirudin, argatroban, and bivalirudin) and since March 2008 one oral DTI (dabigatran etexilate) are clinically used for limited indications. In September 2008 rivaroxaban has been approved as the first oral DXI. This review describes the development of the anticoagualants as well as the pharmacological profile of the clinically used anticoagualants.

Topics: Anticoagulants; Antithrombins; Fondaparinux; Glycosaminoglycans; Heparin; Humans; Oligosaccharides; Partial Thromboplastin Time; Polysaccharides; Recombinant Proteins; Structure-Activity Relationship; Thrombocytopenia

Heparin-induced thrombocytopenia (HIT) is an immune-mediated complication that can occur after exposure to heparin products. Because patients with HIT are at increased risk for thrombosis, anticoagulation is warranted. The direct thrombin inhibitors lepirudin and argatroban are approved by the United States Food and Drug Administration (FDA) for this indication. Bivalirudin, another direct thrombin inhibitor, is approved for use in patients with HIT who must undergo percutaneous coronary intervention. The synthetic pentasaccharide fondaparinux lacks FDA approval for treating patients with HIT; however, a few published reports describe its use. Furthermore, various small-scale, in vitro studies have demonstrated a lack of cross-reactivity between fondaparinux and HIT antibodies. Large, in vivo comparison trials must be performed before fondaparinux can become a standard treatment option in the setting of HIT.

Topics: Anticoagulants; Fondaparinux; Heparin; Humans; Polysaccharides; Thrombocytopenia; Thrombosis

Thromboembolic complications are one of the most severe complications after orthopaedic or trauma surgery. More than 50% of patients undergoing total knee replacement are at risk of suffering deep-vein thrombosis if not provided sufficient prophylaxis. The former standard prophylaxis with unfractionated heparin has been changed over the few last years to low molecular weight heparin or heparinoids, due to the increased incidence of heparin-induced thrombocytopenia under therapy with unfractionated heparin. Risk management is based on different risk levels: highest risk, high risk, intermediate risk and low risk. The probabilities of suffering from deep-vein thrombosis have been determined dependent on the risk level. In patients with total knee replacement, which are at highest risk, a higher dose for the prevention of thromboembolism has been recommended. The synthetic, selective antithrombin-binding pentasaccharide fondaparinux has been successfully used in prophylaxis for the prevention of thrombosis in highest risk patients. However, because of a higher risk of bleeding, this pentasaccharide can be only given 6-8 h after surgery. Low molecular weight heparins and the pentasaccharide are the standard pharmacological prophylaxis for the prevention of venous thromboembolism. Physical therapy, pneumatic compression, A-V impulse systems, passive ankle motion systems and graduated compression stockings are an additional, effective prophylaxis without side effects.

Topics: Adult; Age Factors; Aged; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Fibrinolytic Agents; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Middle Aged; Orthopedic Procedures; Physical Therapy Modalities; Polysaccharides; Postoperative Complications; Risk Assessment; Risk Factors; Stockings, Compression; Thrombocytopenia; Thromboembolism; Time Factors; Venous Thrombosis

Accomplishing a successful percutaneous coronary intervention in a patient with a suspected or diagnosed heparin-induced thrombocytopenia (HIT) requires the selection of an appropriate alternative anticoagulant and a thorough assessment of bleeding and thrombotic risks. In this review, we suggest an evidence-based management algorithm that takes into account the clinical phase of HIT (acute, recent, and remote HIT) and the associated risk when patients present with acute coronary syndrome. The algorithm also integrates preventive measures directed at decreasing the bleeding risk associated with the antithrombotic and invasive therapies used for HIT and percutaneous coronary intervention.

Topics: Algorithms; Angioplasty, Balloon, Coronary; Anticoagulants; Arginine; Chondroitin Sulfates; Comorbidity; Dermatan Sulfate; Drug Therapy, Combination; Fibrinolytic Agents; Fondaparinux; Heparin; Heparinoids; Heparitin Sulfate; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Pipecolic Acids; Polysaccharides; Recombinant Proteins; Sulfonamides; Syndrome; Thrombocytopenia; Vitamin K

Hemorrhage is the most common and best-recognized complication of heparin treatment. However, a potentially more dangerous complication is the development of heparin-induced thrombocytopenia (HIT). All patients exposed to heparin, irrespective of the dose and route of administration, are at risk of developing HIT. It is due to the formation of antibodies against the heparin-platelet factor 4 complex, which cause secondary activation of platelets, coagulation and, finally, increased thrombin production. The main symptom is the sudden onset of thrombocytopenia involving a drop in the platelet count to less than 50% of the basal level, with or without the appearance of thrombotic complications some 5 to 14 days after the start of heparin therapy. Heparin-induced thrombocytopenia can be detected early in patients receiving heparin by monitoring the platelet count. Demonstration of heparin-dependent platelet activation using an antigen or functional assay confirms the clinical diagnosis. Once the diagnosis of HIT has been confirmed serologically or there is a high level of suspicion of HIT, heparin must be suspended and treatment with an alternative anticoagulant should be considered. This review contains a discussion of the diagnosis and treatment of this syndrome.

Topics: Anticoagulants; Arginine; Chondroitin Sulfates; Dermatan Sulfate; Fibrinolytic Agents; Fondaparinux; Heparin; Heparitin Sulfate; Hirudins; Humans; Peptide Fragments; Pipecolic Acids; Polysaccharides; Recombinant Proteins; Sulfonamides; Thrombocytopenia

Topics: Anticoagulants; Azetidines; Benzylamines; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Liver; Polysaccharides; Thrombocytopenia

Elderly patients require special consideration when administered anticoagulants because of age-related alterations in renal function, protein binding, and increased bleeding risk. Unfractionated heparin can be used in most patients but difficulties with dosing and monitoring often lead to inadequate anticoagulation. Low-molecular-weight heparin has more predictable pharmacokinetics than conventional heparin, but requires dose adjustments in renal impairment and obesity. Fondaparinux is a synthetic pentasaccharide that is being used increasingly for both treatment and prophylaxis of venous thromboembolism. The immune-mediated form of heparin-induced thrombocytopenia is a syndrome with thrombocytopenia or thrombosis in the setting of heparin use. Heparin-induced thrombocytopenia must be identified early, and treated with argatroban or lepirudin to avoid life-threatening complications.

Topics: Age Factors; Aged; Aged, 80 and over; Anticoagulants; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Fondaparinux; Geriatric Assessment; Half-Life; Heparin, Low-Molecular-Weight; Humans; Male; Maximum Tolerated Dose; Monitoring, Physiologic; Polysaccharides; Prognosis; Thrombocytopenia; Thromboembolism

Heparin-induced thrombocytopenia (HIT) is an antibody-mediated syndrome associated with heparin exposure, a falling platelet count and a high risk of thrombosis. Cardiovascular patients are at increased risk of HIT due to wide use of heparin in this population. Should HIT be suspected, heparin must be avoided in most situations, and anticoagulation with an alternative anticoagulant should be instituted. Preferred agents include the direct thrombin inhibitors argatroban and lepirudin, whilst bivalirudin or desirudin (other direct thrombin inhibitors) can be used in some situations. The indirect thrombin inhibitors, danaparoid and fondaparinux, can also be considered at times. These agents and their use in cardiac patients, including patients with acute coronary syndrome, percutaneous coronary interventions, acute ST elevation myocardial infarction or cardiac surgery, will be reviewed.

Topics: Angioplasty, Balloon, Coronary; Anticoagulants; Arginine; Cardiovascular Diseases; Chondroitin Sulfates; Dermatan Sulfate; Drug Administration Schedule; Factor Xa Inhibitors; Fondaparinux; Heparin; Heparitin Sulfate; Hirudins; Humans; Pipecolic Acids; Polysaccharides; Postoperative Complications; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Recombinant Proteins; Sulfonamides; Thrombin; Thrombocytopenia

Heparin-induced thrombocytopenia (HIT) is a clinicopathologic condition and adverse drug reaction caused by immunoglobulin G (IgG) antibodies directed against the heparin-platelet factor 4 complex. In most patients, the onset of thrombocytopenia begins while the patient is receiving heparin. In less than 5% of patients, the onset of thrombocytopenia begins several days following heparin discontinuation and has been termed "delayed-onset" HIT. This review summarizes the presentation and clinical course of published reports of delayed-onset HIT occurring in 30 patients. The diagnosis of delayed-onset HIT should be considered in all patients presenting with venous thromboembolism (VTE) and all patients with recent heparin exposure (within the past 14 days) who present with a low platelet count. Most patients with HIT are treated with direct thrombin inhibitors and transitioned to warfarin oral anticoagulation. Administration of direct thrombin inhibitors requires close monitoring for bleeding, dose adjustments based upon coagulation monitoring and is costly. Fondaparinux, a synthetic pentasaccharide and indirect-acting factor-Xa inhibitor, has little to no cross-reactivity with the heparin-platelet factor 4 antibody in in vitro testing. This review summarizes dosing, monitoring and outcomes of preliminary reports of fondaparinux successfully administered to 13 patients with subacute HIT and 22 patients with acute HIT. While several reports have described the treatment and prophylaxis of thrombosis in patients with HIT using fondaparinux, clinical trials should be conducted and reported before fondaparinux becomes a therapy of choice for HIT.

Topics: Anticoagulants; Clinical Trials as Topic; Fondaparinux; Heparin; Humans; Polysaccharides; Thrombocytopenia; Thromboembolism

Topics: Anticoagulants; Arginine; Cardiac Surgical Procedures; Cardiovascular Diseases; Chondroitin Sulfates; Dermatan Sulfate; Diagnosis, Differential; Fondaparinux; Heparin; Heparitin Sulfate; Hirudins; Humans; Peptide Fragments; Pipecolic Acids; Platelet Aggregation Inhibitors; Platelet Factor 4; Polysaccharides; Recombinant Proteins; Sensitivity and Specificity; Sulfonamides; Thrombocytopenia; 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 has been the mainstay of treatment and prevention of venous and arterial thromboembolism for many years. Its use, however, is associated with a serious and potentially fatal immunological drug reaction termed heparin-induced thrombocytopenia (HIT). Current treatment consists of discontinuing heparin therapy and the administration of an alternate anticoagulant (e.g. danaparoid, lepirudin, bivalirudin or argatroban). Fondaparinux is a novel synthetic heparin pentasaccharide capable of inhibiting factor Xa via the action of antithrombin (AT) but devoid of anti-factor IIa (thrombin) activity. Although the drug is identical in structure to the pentasaccharide domain found on unfractionated heparin (UH), it is too small to be recognized by the majority of heparin-reactive antibodies. It is theoretically an excellent candidate agent for the treatment of HIT. Currently, fondaparinux is licensed for orthopaedic venous thromboprophylaxis but not for the treatment of HIT. Successes in the use of fondaparinux in the treatment of HIT, as demonstrated in recent published case reports, warrant further study in larger controlled trials for this indication.

Topics: Anticoagulants; Female; Fondaparinux; Heparin; Humans; Male; Polysaccharides; Thrombocytopenia; Thromboembolism; Venous Thrombosis

Unfractionated heparin, derived from porcine intestine, is the prototype of a rapidly acting anticoagulant. It has been used for over 60 years to arrest or prevent thrombus growth. Low-molecular-weight heparins, available in the last 20 years, are manufactured from unfractionated heparin and have superior dose-response relationships because of fewer nonspecific reactions with plasma proteins and cells. Fondaparinux is a recently approved five-saccharide synthetic molecule that carries the evolution of heparin further. It is a pure Xa inhibitor, with minimal nonspecific interactions. It does not appear to elicit the antibody that leads to heparin-induced thrombocytopenia (HIT). All of these agents are given either intravenously or subcutaneously. They act indirectly by activating the natural plasma inhibitor, antithrombin III. Direct thrombin inhibitors bind directly to thrombin's active site without interaction with the cofactor, antithrombin III. Lepirudin (Refludan; Berlex, Wayne, NJ) and argatroban (Argatroban; GlaxoSmithKline, Research Triangle Park, NC) are given intravenously and are usually used in HIT and thrombosis associated with HIT. Bivalirudin (Angiomax; The Medicines Company, Parsippany, NJ) is a parenteral direct thrombin used in place of heparin in percutaneous coronary interventions. Ximelagatran (Exanta; AstraZeneca, Wilmington, DE) is an oral direct thrombin inhibitor under development for both acute and chronic anticoagulation.

Topics: Anticoagulants; Arginine; Azetidines; Benzylamines; Embolism; Enzyme Inhibitors; Fondaparinux; Heparin; Heparin, Low-Molecular-Weight; Hirudins; Humans; Peptide Fragments; Pipecolic Acids; Polysaccharides; Recombinant Proteins; Sulfonamides; Thrombin; Thrombocytopenia; Venous Thrombosis

In this paper, recent advances in new anticoagulants with the potential to be used for prevention or treatment of venous thrombosis are reviewed.. Numerous novel anticoagulants targeting specific stages of the coagulant pathway are in various stages of development. Fondaparinux, an indirect activated factor VII inhibitor, has been shown to be effective for initial treatment and prevention of venous thromboembolism, but still requires parenteral administration. Ximelagatran, an oral direct thrombin inhibitor, has also been shown to effective for treatment and prevention of venous thrombosis. Both agents are associated with bleeding, however, and ximelagatran is associated with hepatic toxicity with long-term use. Direct activated factor X inhibitors, orally available forms of heparin, and other direct thrombin inhibitors remain in early stages of development. Further data on the clinical utility of these agents are likely to emerge in the next few years, and uptake of their use will be affected by the cost considerations.. Numerous alternative anticoagulants are in varying stages of development. Clinical data have yet to show that these agents have a clearly superior risk-benefit ratio compared with currently used antithrombotics. Many drugs remain in initial stages of development. The ideal anticoagulant agent is being sought but has yet to be discovered.

Topics: Anticoagulants; Azetidines; Benzylamines; Factor VIIa; Fondaparinux; Heparin; Humans; Polysaccharides; Thrombin; Thrombocytopenia; Venous Thrombosis

Anticoagulation is highly effective in the prevention and treatment of venous thromboembolism (VTE). Since decades, vitamin K antagonists (VKA) were the only available oral anticoagulants. Even though VKA are very effective, they have numerous practical problems: Due to their narrow therapeutic window, highly variable dose requirements and drug interactions, close monitoring is mandatory, aiming towards an INR of 2-3 for most indications. At present, new oral anticoagulants are being studied, such as the oral direct thrombin inhibitor Ximelagatran, which in trials for prevention and treatment of VTE appears at least equivalent to heparin and VKA. Heparins have to be administered parenterally, and low molecular-weight heparins have been able to overcome some of the shortcomings of standard heparins, such as limited bioavailability, variable dose response and heparin induced thrombocytopenia (HIT). Heparinoids and hirudins are alternative anticoagulants to treat HIT. With the development of synthetic pentasaccharides, such as Fondaparinux an increase in efficacy could be achieved in high-risk thromboprophylaxis.

Topics: Anticoagulants; Azetidines; Benzylamines; Dose-Response Relationship, Drug; Drug Therapy; Evidence-Based Medicine; Fondaparinux; Heparin; Humans; Patient Care Management; Polysaccharides; Practice Patterns, Physicians'; Thrombocytopenia; Treatment Outcome; Venous Thrombosis; Vitamin K

Multiple options for anticoagulation therapy are now available, placing an additional responsibility on health care workers for choosing the optimal therapy for each patient. The heparins carry a risk of heparin-induced thrombocytopenia (HIT), an immune-mediated reaction to heparin that may lead to pulmonary embolism and death. Fondaparinux, a new, synthetic pentasaccharide, binds to antithrombin III and potentiates antithrombin III's inhibition of factor Xa. Fondaparinux does not bind to platelet factor 4 and thus is theoretically unable to cause immunoallergic HIT. Unlike low-molecular-weight heparins, fondaparinux does not cross-react in vitro with sera from patients with clinical cases of HIT. These findings suggest that fondaparinux would not lead to formation of HIT antibodies and would not provoke clinical thrombosis in patients who had HIT antibodies because of previous exposure to heparins. To date, no cases of immunoallergic HIT have been associated with fondaparinux use in clinical trials. Anecdotal evidence suggests that fondaparinux eventually may prove to be valuable for preventing and treating thrombosis in patients with HIT. The effect of anticoagulants on wound healing is another consideration when choosing a thromboprophylactic strategy after major surgery. There is evidence that thrombin plays a role in wound healing, but fondaparinux is too small to enable antithrombin III to inhibit thrombin. Thus, fondaparinux may be less likely than a low-molecular-weight heparin to interfere with wound healing.

Topics: Anticoagulants; Clinical Trials as Topic; Fondaparinux; Heparin; Humans; Polysaccharides; Thrombocytopenia; Wound Healing

Significant advances in the pharmacological prophylaxis of venous thromboembolism have occurred since warfarin and unfractionated heparin were introduced for this indication nearly 60 years ago. Despite these advances, coumarin derivatives such as warfarin remain the only orally active anticoagulants available for prophylaxis in venous thromboembolism. Although administered orally, coumarin derivatives are not convenient to use, because they have narrow therapeutic indexes and require routine coagulation monitoring and dose adjustment. This is inconvenient for patients and physicians and costly for the healthcare system. Low-molecular-weight heparins, which are administered in fixed or weight-adjusted doses and do not require monitoring, are widely used for the prevention of venous thromboembolism in patients in both the hospital and the outpatient setting. However, these drugs must be given subcutaneously, which can be difficult for outpatients and resource-intensive for in-hospital use. Likewise, fondaparinux, the synthetic pentasaccharide, must be administered subcutaneously. Consequently, there remains a need for new orally active anticoagulants that can be given in fixed doses and do not have a narrow therapeutic index, so that coagulation monitoring is unnecessary. Because such agents would be more convenient for patients and physicians, they would probably expand the use of prophylaxis in venous thromboembolism in those at risk, and would simplify treatment of patients with established venous thromboembolism.

Topics: Administration, Oral; Anticoagulants; Coumarins; Fondaparinux; Heparin; Humans; Injections, Subcutaneous; Polysaccharides; Thrombocytopenia; Thromboembolism

Topics: Anticoagulants; Arginine; Azetidines; Benzylamines; Fondaparinux; Heparin; Hirudin Therapy; Hirudins; Humans; Pipecolic Acids; Polysaccharides; Prodrugs; Recombinant Proteins; Sulfonamides; Thrombin; Thrombocytopenia

The pharmacology and mechanism of action of fondaparinux sodium are described. Fondaparinux sodium is the first agent of a new class of anticoagulants that selectively target factor Xa. It has a linear, dose-dependent pharmacokinetic profile, which provides a highly predictable response. It is 100% bioavailable, has a rapid onset of action, and has a half-life of 14 to 16 hours, allowing for sustained antithrombotic activity over a 24-hour period. The drug does not affect prothrombin time or activated partial thromboplastin time, nor does it affect platelet function or aggregation. Studies in patients with confirmed heparin-induced thrombocytopenia demonstrate that the drug is not associated with in vitro cross-reactivity to heparin antibodies. Fondaparinux sodium appears to meet the criteria for an ideal antithrombotic agent: equal or better effectiveness than currently available agents, a low bleeding risk, no need for laboratory monitoring, and once-daily administration.

Topics: Anticoagulants; Blood Coagulation; Cross Reactions; Factor Xa; Factor Xa Inhibitors; Fibrinolytic Agents; Fondaparinux; Heparin; Humans; Polysaccharides; Thrombocytopenia; Warfarin

Anti-PF4/heparin antibodies are frequently generated after coronary artery bypass grafting (CABG) surgery, with platelet-activating IgG implicated in heparin-induced thrombocytopenia (HIT). It is controversial whether non-platelet-activating antibodies are associated with thrombosis.. To determine in post-CABG patients whether thromboprophylaxis using fondaparinux vs. unfractionated heparin (UFH) reduces the frequency of anti-PF4/heparin antibodies, and whether anti-PF4/heparin antibodies are associated with early graft occlusion.. In a pre-planned secondary analysis of a randomized control trial (RCT) comparing fondaparinux vs. UFH thromboprophylaxis post-CABG, we determined the frequency of anti-PF4/heparin antibody formation by solid-phase enzyme-immunoassay (EIA) and of platelet-activating antibodies by serotonin-release assay (SRA); the SRA and fluid-phase EIA were used to assess fondaparinux cross-reactivity. We also examined whether anti-PF4/heparin antibodies were associated with early arterial or venous graft occlusion (6-week CT angiography).. We found no significant difference in the frequency of antibody formation between patients who received fondaparinux vs. UFH (65.3% vs. 46.0%; P = 0.069), and no significant fondaparinux cross-reactivity. Venous graft occlusion(s) occurred in 6/26 patients who formed 'strong' IgG antibodies (≥ 1.0 optical density [OD] units and ≥ 2× baseline) vs. 3/66 who did not (P = 0.0139). In both unadjusted and adjusted analyses, strong postoperative (but not pre-operative) anti-PF4/heparin IgG responses were associated with a markedly increased risk of early venous (but not arterial) graft occlusion (adjusted OR, 9.25 [95% CI, 1.73, 49.43]; P = 0.0093); notably, none of the three SRA-positive patients developed a venous graft occlusion.. Fondaparinux vs. UFH thromboprophylaxis postCABG does not reduce anti-PF4/heparin antibody formation. Non-platelet-activating anti-PF4/heparin IgG antibodies generated post operatively are associated with early venous graft occlusion.

Topics: Antibodies; Anticoagulants; Coronary Artery Bypass; Cross Reactions; Fondaparinux; Graft Occlusion, Vascular; Heparin; Humans; Immunoenzyme Techniques; Immunoglobulin G; Logistic Models; Odds Ratio; Ontario; Pilot Projects; Platelet Factor 4; Polysaccharides; Risk Assessment; Risk Factors; Thrombocytopenia; Time Factors; Treatment Outcome

The incidence of thromboembolic disease is increasing in children. New anticoagulants have been licensed in adults and need to be studied in children. This report describes the first prospective study of fondaparinux in children.. The purpose of the study was to determine the dosing, pharmacokinetics, and safety of fondaparinux in children with deep vein thrombosis (DVT) or heparin-induced thrombocytopenia (HIT). Hospitalized children between 1 and 18 years of age with DVT or HIT received fondaparinux 0.1 mg/kg once daily. Fondaparinux-based anti-factor Xa levels were assessed at 2, 4, 12, and 24 hr following the first dose, and peak levels were measured twice weekly thereafter. Detailed pharmacokinetic analyses were performed.. Twenty four subjects in 3 age cohorts were enrolled and completed the study. Pharmacokinetic modeling demonstrated that a once-daily dose of fondaparinux at 0.1 mg/kg resulted in similar concentrations known to be efficacious in adults. Safety was demonstrated with only two bleeding events: one which may have pre-dated study drug administration and one which led only to temporary discontinuation of study drug.. Dosing of fondaparinux at 0.1 mg/kg once daily in children resulted in PK profiles comparable to those in adults receiving standard dosing. Fondaparinux can be considered an attractive alternative to LMWH given its once-daily dosing, acceptable safety data, and other favorable properties.

Topics: Adolescent; Child; Child, Preschool; Cohort Studies; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug-Related Side Effects and Adverse Reactions; Fondaparinux; Heparin; Humans; Infant; Polysaccharides; Thrombocytopenia; Time Factors; Venous Thrombosis

Heparin-induced thrombocytopenia (HIT) is a life-threatening immune response to heparin that is associated with a high risk of thromboembolic complications. We prospectively treated seven subjects with acute HIT with fondaparinux and compared the results to a similar historical control population from the same hospital. Six of the seven fondaparinux-treated subjects were transitioned to warfarin, beginning after platelet count recovery occurred. Ten historical controls were treated with a direct thrombin inhibitor (DTI), eight of which were transitioned to warfarin. The primary study outcome was platelet count recovery which was defined as an increase from baseline by at least 30% of nadir to greater than 100,000/mm(3) by day seven. Seven subjects were prospectively treated with fondaparinux for a median of eight days. Six of the seven had HIT with thrombosis at the time of enrollment. All fondaparinux treated subjects had a complete platelet count recovery, and none experienced a new thromboembolic complication, major bleeding or death by week four. One subject underwent limb amputation. Ten historical controls were treated with a DTI for a median duration of eleven days. Platelet count recovery occurred in eight of the ten historical controls. No new thromboembolic complications or major bleeds occurred but limb gangrene occurred in four controls. The development of limb gangrene in the historical controls may have been a result of delayed recognition of HIT and/or inappropriately early institution of warfarin in the historical controls. This pilot study suggests that fondaparinux may be useful in patients with acute HIT.

Topics: Acute Disease; Aged; Anticoagulants; Blood Coagulation; Case-Control Studies; Factor Xa Inhibitors; Feasibility Studies; Female; Fondaparinux; Hemorrhage; Heparin; Humans; International Normalized Ratio; Male; Pilot Projects; Platelet Count; Polysaccharides; Prospective Studies; Thrombocytopenia; Time Factors; Treatment Outcome; Venous Thrombosis; Warfarin

Heparin-induced thrombocytopenia (HIT) is caused by platelet-activating IgG antibodies that recognize platelet factor 4 (PF4) bound to heparin. Immunogenicity of heparins differs in that unfractionated heparin (UFH) induces more anti-PF4/heparin antibodies than low-molecular-weight heparin (LMWH) and UFH also causes more HIT. Fondaparinux, a synthetic anticoagulant modeled after the antithrombin-binding pentasaccharide, is believed to be nonimmunogenic. We tested 2726 patients for anti-PF4/heparin antibodies after they were randomized to receive antithrombotic prophylaxis with fondaparinux or LMWH (enoxaparin) following hip or knee surgery. We also evaluated in vitro cross-reactivity of the IgG antibodies generated against PF4 in the presence of UFH, LMWH, danaparoid, or fondaparinux. We found that anti-PF4/heparin antibodies were generated at similar frequencies in patients treated with fondaparinux or enoxaparin. Although antibodies reacted equally well in vitro against PF4/UFH and PF4/LMWH, and sometimes weakly against PF4/danaparoid, none reacted against PF4/fondaparinux, including even those sera obtained from patients who formed antibodies during fondaparinux treatment. At high concentrations, however, fondaparinux inhibited binding of HIT antibodies to PF4/polysaccharide, indicating that PF4/fondaparinux interactions occur. No patient developed HIT. We conclude that despite similar immunogenicity of fondaparinux and LMWH, PF4/fondaparinux, but not PF4/LMWH, is recognized poorly by the antibodies generated, suggesting that the risk of HIT with fondaparinux likely is very low.

Topics: Anticoagulants; Cross Reactions; Double-Blind Method; Enoxaparin; Fondaparinux; Hip; Humans; Immunoenzyme Techniques; Immunoglobulin G; Knee; Orthopedic Procedures; Platelet Factor 4; Polysaccharides; Thrombocytopenia; Venous Thrombosis

Topics: Adult; Anticoagulants; Fibrinolytic Agents; Fondaparinux; Heparin; Humans; Retrospective Studies; Thrombocytopenia

The literature recommends against the use of fondaparinux in patients with kidney failure and dialysis as it may, with repeated dosing, accumulate and put patients at risk of bleeding. The management of patients with thrombosis in the presence of heparin-induced thrombocytopenia HIT requires the introduction of an alternative anticoagulant like bivalirudin or argatroban. When these drugs are not available, fondaparinux, remains the only alternative. In similar scenarios, there are few studies addressing how to administer it.  METHODS: We developed a protocol for fondaparinux in patients with renal failure where pharmacokinetic parameters are altered, and levels changed only after hemodialysis or in cases of residual renal activity. Patients received a full first dose except for high risk of bleeding. We targeted a peak anti-factor Xa activity level of 0.6-1.3 units/ml and changed the subsequent dose accordingly. Furthermore, we monitored the patients for signs of bleeding, a drop in hemoglobin level, or clinical signs of thrombosis.  DISCUSSION: We described 10 patients with kidney failure and suspected HIT taking fondaparinux. All the patients achieved therapeutic anti-factor Xa activity levels. However, one developed new-onset venous thromboembolism (VTE) despite therapeutic anti-factor Xa levels. Another patient experienced a bleeding episode. We believe that these two patients developed complications due to their medical conditions rather than the use of fondaparinux.. Fondaparinux can be safely used in kidney failure using our protocol. However, despite its safety profile and relative success, this case series was small. More robust studies need to be conducted prior to drawing conclusions.. New Fondaparinux Protocol to Reduce the Risk of Blood Thickening and Blood Clots Formation in Adults with Kidney Disease and Heparin-induced Thrombocytopenia (drop in platelets after the use of heparin): A Test Study.Fondaparinux is a drug used to treat patients suffering from thrombosis (clot in blood) and prevent vessels occlusions. When patients have kidney disease, the ideal treatment for thrombosis would be heparin; and, in case of Heparin Induced Thrombocytopenia (HIT), an unexpected drop in platelets after the use of heparin, the ideal treatment would be argatroban or bivalirudin. Fondaparinux can be used for HIT. However, studies recommend against its use in kidney disease as it might accumulate and cause bleeding.We were put in a challenging situation where we had patients with life-threatening thrombosis, kidney disease, HIT and unavailability of both argatroban and bivalirudin. Our only option was fondaparinux. We had to devise a safe and efficient protocol. The starting dose was the one used had the patient had a normal kidney function. Then, anti-Factor Xa activity was regularly measured with the target level 0.6-1.3units/ml 4 h after a dose. The dose was individualized, changed based on the Factor Xa activity result, the risk of bleeding or thrombosis, the overall kidney function and the need for dialysis.Our protocol was tested on 10 patients. All our patients could reach the target and safe Factor Xa activity. We had 2 exceptions. The first had a clotting event despite having therapeutic Factor Xa activity and the second was a very sick cancer patient who was bleeding despite skipping many doses of fondaparinux. We consider that these 2 cases developed complications due to their medical conditions rather than the use of fondaparinux.We concluded that fondaparinux can be safely used in patients with kidney disease, granted that Factor Xa activity is measured, the risk of bleeding is weighed to the risk of thrombosis and the dose is individualized. However, our sample size is small and further studies with a larger number of patients are needed to draw a conclusion.

Topics: Adult; Anticoagulants; Fondaparinux; Hemorrhage; Heparin; Humans; Renal Insufficiency; Retrospective Studies; Thrombocytopenia; Thrombosis

Heparin-induced thrombocytopenia (HIT) is a serious thrombotic disorder caused by ultralarge immune complexes (ULICs) containing platelet factor 4 (PF4) and heparin that form the HIT antigen, together with a subset of anti-PF4 antibodies. ULICs initiate prothrombotic responses by engaging Fcγ receptors on platelets, neutrophils, and monocytes. Contemporary anti-thrombotic therapy for HIT is neither entirely safe nor entirely successful and acts downstream of ULIC formation and Fcγ receptor-initiated generation of thrombin.. To determine whether HIT antigen and ULIC formation and stability could be modified favorably by inhibiting PF4-heparin interactions with fondaparinux, together with blocking formation of PF4 tetramers using a humanized monoclonal anti-PF4 antibody (hRTO).. Results: The combination of fondaparinux and hRTO inhibited HIT antigen formation, promoted antigen dissociation, inhibited ULIC formation, and promoted ULIC disassembly at concentrations below the effective concentration of either alone and blocked Fcγ receptor-dependent induction of factor Xa activity by monocytic THP1 cells and activation of human platelets in whole blood. Combined with hRTO, fondaparinux inhibited HIT antigen and immune complex formation and activation through Fcγ receptors at concentrations at or below those used clinically to inhibit FXa coagulant activity.. HIT antigen and immune complexes are dynamic and amenable to modulation. Fondaparinux can be converted from an anticoagulant that acts at a downstream amplification step into a rationale, disease-specific intervention that blocks ULIC formation. Interventions that prevent ULIC formation and stability might increase the efficacy, permit use of lower doses, shorten the duration of antithrombotic therapy, and help prevent this serious thrombotic disorder.

Topics: Antibodies, Monoclonal, Humanized; Anticoagulants; Antigen-Antibody Complex; Fondaparinux; Heparin; Humans; Platelet Factor 4; Receptors, IgG; Thrombocytopenia; Thrombosis

Heparin-induced thrombocytopenia (HIT) is a life-threatening complication associated with high medical costs. Factor Xa inhibitors gradually replace approved treatment with intravenous direct thrombin inhibitors despite their off-label indication, because of easier management and favorable economic profile. Whether they are cost-effective remains unclear. We evaluated the cost-effectiveness of approved and off-label anticoagulants in patients with suspected HIT, based on census data from the largest Swiss hospital between 2015 and 2018. We constructed a decision tree model that reflects important clinical events associated with HIT. Relevant cost data were obtained from the finance department or estimated based on the Swiss-wide cost tariff. We estimated averted adverse events (AEs) and incremental cost-effectiveness ratio as primary outcome parameters. We performed deterministic and probabilistic sensitivity analyses with 2000 simulations to assess the robustness of our results. In the base-case analysis, the total cost of averting 1 AE was 49 565 Swiss francs (CHF) for argatroban, 30 380 CHF for fondaparinux, and 30 610 CHF for rivaroxaban; after adjusting for 4Ts score: 41 152 CHF (argatroban), 27 710 CHF (fondaparinux), and 37 699 CHF (rivaroxaban). Fondaparinux and rivaroxaban were more clinically effective than argatroban, with AEs averted of 0.820, 0.834, and 0.917 for argatroban, fondaparinux, and rivaroxaban, respectively. Treatment with fondaparinux resulted in less cost and more AEs averted, hence dominating argatroban. Results were most sensitive to AE rates and prolongation of stay. Monte Carlo simulations affirmed our base-case analysis. This is the first cost-effectiveness analysis comparing argatroban with fondaparinux and rivaroxaban using primary data. Fondaparinux and rivaroxaban resulted in more averted AEs, but fondaparinux had greater cost savings. Fondaparinux could be a viable alternative to argatroban.

Topics: Anticoagulants; Cost-Benefit Analysis; Fondaparinux; Heparin; Humans; Rivaroxaban; Thrombocytopenia

Heparin-induced thrombocytopenia (HIT) is a severe complication caused by heparin. It is characterized by occult onset and missed diagnosis. Misdiagnosis easily occurs.. This paper reported an 85-year-old woman with an intertrochanteric fracture of the femur which was treated with low molecular weight heparin (LMWH) and fondaparinux sodium to prevent venous thrombosis. Then, the patient developed HIT. This is the first case report of HIT induced by LMWH and fondaparinux in a patient with a hip fracture. This case highlights the severity of HIT in elderly patients with hip fractures using LMWH and fondaparinux and the need for platelet monitoring in these patients.. LMWH was ceased in this HIT-confirmed patient, and non-heparin treatment was begun instead. Apixaban was given twice daily for therapeutic anticoagulation therapy. In the end, the platelet levels gradually returned to normal.. We should pay more attention to HIT and platelets during the perioperative period of orthopedic surgery, especially in elderly patients. Once the disease is confirmed, it is necessary to stop heparin-related drugs immediately and administer oral anticoagulants instead.

Topics: Aged; Aged, 80 and over; Anticoagulants; Female; Femur; Fondaparinux; Heparin; Heparin, Low-Molecular-Weight; Hip Fractures; Humans; Thrombocytopenia

Life-threatening thrombotic events at unusual sites have been reported after vector-based vaccinations against severe acute respiratory syndrome coronavirus 2. This phenomenon is now termed vaccine-induced immune thrombotic thrombocytopenia (VITT). The pathophysiology of VITT is similar to that of heparin-induced thrombocytopenia (HIT) and is associated with platelet-activating antibodies (Abs) against platelet factor 4 (PF4). Therefore, current guidelines suggest nonheparin anticoagulants to treat VITT patients. In this study, we investigated the interactions of heparin, danaparoid, fondaparinux, and argatroban with VITT-Ab/PF4 complexes using an ex vivo model for thrombus formation as well as in vitro assays to analyze Ab binding and platelet activation. We found that immunoglobulin Gs (IgGs) from VITT patients induce increased adherent platelets/thrombus formation in comparison with IgGs from healthy controls. In this ex vivo flow-based model, the procoagulant activity of VITT IgGs was effectively inhibited with danaparoid and argatroban but also by heparin. Interestingly, heparin and danaparoid not only inhibited IgG binding to PF4 but were also able to effectively dissociate the preformed PF4/IgG complexes. Fondaparinux reduced the in vitro generation of procoagulant platelets and thrombus formation; however, it did not affect platelet aggregation. In contrast, argatroban showed no effect on procoagulant platelets and aggregation but significantly inhibited VITT-mediated thrombus formation. Taken together, our data indicate that negatively charged anticoagulants can disrupt VITT-Ab/PF4 interactions, which might serve as an approach to reduce Ab-mediated complications in VITT. Our results should be confirmed, however, in a clinical setting before a recommendation regarding the selection of anticoagulants in VITT patients could be made.

Topics: Anticoagulants; COVID-19 Vaccines; Fondaparinux; Heparin; Humans; Immunoglobulin G; Platelet Factor 4; Thrombocytopenia; Thrombosis

The pentasaccharide Fondaparinux, a synthetic selective factor Xa inhibitor, is one of the safest anticoagulants in the heparin family that is recommended as an alternative drug for patients with hypersensitivity to other drugs such as heparin-induced thrombocytopenia (HIT). However, some observations of Fondaparinux-induced thrombocytopenia (FIT) have been reported while others claimed that FIT does not occur in patients with fondaparinux therapy, indicating that the mechanism of FIT remains controversial. Here, we utilized different methodologies including dynamic light scattering, immunosorbent and platelet aggregation assays, confocal laser scanning microscopy, and flow cytometry to gain insights into FIT. We found that at a certain concentration, Fondaparinux formed sufficient large and stable complexes with PF4 that facilitated binding of the HIT-like monoclonal KKO antibody and enhanced platelet aggregation and activation. We proposed a model to describe the role of Fondaparinux concentration in the formation of complexes with platelet factor 4 and how it promotes the binding of KKO. Our results clarify controversial observations of FIT in patients as each contains a dissimilar PF4:Fondaparinux concentration ratio.

Topics: Antibodies, Monoclonal; Anticoagulants; Fondaparinux; Heparin; Humans; Platelet Factor 4; Polysaccharides; Thrombocytopenia

A definitive diagnosis of heparin-induced thrombocytopenia (HIT) is difficult to make, especially in patients undergoing cardiac surgery. In this retrospective cohort study, we assessed the platelet count trends and the response to fondaparinux in a population of patients of suspected HIT after pulmonary endarterectomy (PEA). Patients enrolled in this study were over the age of 18 years, and survived longer than 7 days after PEA between January 1, 2011 and December 31, 2015. HIT likelihood was assessed by the 4 T's score and interpreted by our institutional algorithm. 54 patients were operated, and 49 patients met the inclusion criteria. Six patients met the criteria for suspected HIT and were treated with fondaparinux until the platelet recovered. No significant difference was observed of clinical characteristics between intermediate to high HIT likelihood patients (HIT SUSPECTED) and low HIT likelihood patients (NO HIT SUSPECTED). HIT SUSPECTED patients reached platelet count lowest later (about 5.5 days after PEA), while NO HIT SUSPECTED patients is about 4.0 days after PEA. Percentage of platelet counts decrease (> 50%) was larger than NO HIT SUSPECTED patients (< 50%). There was no difference in mortality or residual pulmonary hypertension between HIT SUSPECTED and NO HIT SUSPECTED patients. Two HIT SUSPECTED patients who used heparin after PEA died, the other four survived by replacing heparin or low molecular weight heparin with fondaparinux. Suspected HIT patients should be surveilled carefully. Platelet counts trends may have some hints in the prevention of HIT. Fondaparinux may be effective for patients with suspected HIT.

Topics: Adult; China; Cohort Studies; Endarterectomy; Factor Xa Inhibitors; Female; Fondaparinux; Heparin; Humans; Hypertension, Pulmonary; Male; Middle Aged; Platelet Count; Postoperative Complications; Pulmonary Embolism; Risk Adjustment; Thrombocytopenia

Heparin-induced thrombocytopenia (HIT) is a highly thrombogenic condition. Cancer patients are already at high risk of thrombosis. The treatment and outcomes of HIT in cancer patients are not well established. We retrospectively identified patients with active cancer who were diagnosed with HIT at our institution. Only patients with a positive HIT assay and intermediate to high 4Ts score were included. We assessed patients for baseline characteristics, HIT characteristics, non-heparin agent usage, and outcomes (recurrent thrombosis, bleeding, and death) up to 180 days after diagnosis of HIT. Between November 1, 2006 and December 31, 2016, 39 patients with active cancer received a diagnosis of HIT. Of these, 35.9% had thrombotic complications at diagnosis. Gastrointestinal cancer was the most common solid organ malignancy while myeloproliferative neoplasm (MPN) was the most common hematological malignancy. Fondaparinux was the most often used parenteral agent at any point of follow-up (87.2%), followed by argatroban (41.0%). Less than half the patients transitioned to an oral agent. The recurrent thrombosis rate was 17.9%, the bleeding rate was 20.5%, the major bleeding rate was 10.3%, and the mortality rate was 15.4% in the entire cohort. HIT in cancer patients is associated with poor outcomes.

Topics: Aged; Anticoagulants; Arginine; Canada; Female; Fondaparinux; Gastrointestinal Neoplasms; Hematologic Neoplasms; Hemorrhage; Heparin; Humans; Male; Patient Acuity; Pipecolic Acids; Platelet Count; Retrospective Studies; Risk Adjustment; Sulfonamides; Thrombocytopenia

To describe the successful recovery from multiple and life-threatening venous thrombosis after ChAdOx1 nCoV-19 vaccination.. Case report.. University Hospital.. Few days after the first dose of the ChAdOx1 nCoV-19 vaccine, a 21-year-old woman experienced massive thrombosis in the deep and superficial cerebral veins together with seizures, neurologic focal deficit, and thrombocytopenia. In the neurointensive care unit, her condition worsened despite early decompressive craniectomy. She developed bilateral segmental pulmonary embolism, left hepatic, and left external iliac venous thrombosis.. Argatroban (0.5-2.2 µg/kg/min) and high-dose IV immunoglobulin (1 g/kg/d for 2 consecutive days) were initiated on day 6 after admission. With these therapies, there was a gradual resolution of multiple sites of venous thrombosis, and platelet count returned to normal. The patient left the ICU with full consciousness, expressive aphasia, and right hemiparesis.. This case of vaccine-induced immune thrombotic thrombocytopenia shows that a good outcome can be obtained even with multiple and life-threatening venous thrombotic lesions. Argatroban and high-dose IV immunoglobulin along with management of severe cerebral venous thrombosis played a major role in this epilogue.

Topics: Antithrombins; Arginine; Cerebral Veins; ChAdOx1 nCoV-19; COVID-19 Vaccines; Drug Therapy, Combination; Female; Fondaparinux; Humans; Immunoglobulins, Intravenous; Pipecolic Acids; Sulfonamides; Thrombocytopenia; Tomography, X-Ray Computed; Venous Thrombosis; Young Adult

Topics: Aged; Autoantibodies; Cross Reactions; Female; Fondaparinux; Heparin; Humans; Immunoglobulin G; Immunoglobulins, Intravenous; Rivaroxaban; Thrombocytopenia; Treatment Outcome; Venous Thromboembolism

Heparin-induced thrombocytopenia (HIT) is the most frequent drug-induced, immune-mediated thrombocytopenia. It is associated with significant morbidity and mortality. Anticoagulation with heparin must be stopped immediately and replaced by some suggested alternative - lepirudin, danaparoid or argatroban. Fondaparinux has been also successfully used in HIT.. We present a cohort of 10 patients diagnosed with HIT and treated in a university hospital in a period of four years. Diagnosis was based on Keeling´s scoring system, screening immunologic test for HIT (STic EXPERT® HIT) and sandwich ELISA (detection of IgG/heparin-PF4 antibodies). While other alternative anticoagulants are not readily available in our hospital, we used fondaparinux in all cases.. From 2014 to 2018, eight males and two females (mean age 67 years, range 46-86 years) were diagnosed with HIT in our hospital. This complication developed in 9 cases after low-molecular-weight heparin and in one after heparin flushes in hemodialysis. A drop-in platelet count developed in all patients, thrombotic complications in 7 and skin necrosis in 2 cases. Fondaparinux was used in all patients, including two cases with severe renal impairment, the dose was chosen individually. We observed complete platelet recovery in all cases. One patient died because of advanced malignancy, others did not have any complication. In 6 cases we switched to oral anticoagulation after platelet recovery.. In our group of 10 HIT patients fondaparinux was shown to be both safe and effective, even in those with severe renal impairment. Additional studies are warranted to confirm this observation.

Topics: Aged; Aged, 80 and over; Anticoagulants; Blood Coagulation; Factor Xa Inhibitors; Female; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Platelet Count; Severity of Illness Index; Thrombocytopenia

Topics: Anticoagulants; Fondaparinux; Heparin; Humans; Thrombocytopenia; Thrombosis

Topics: Aged; Cross Reactions; Fondaparinux; Heparin; Humans; Male; Platelet Factor 4; Stroke; Thrombocytopenia

The off-label use of fondaparinux in patients with heparin-induced thrombocytopenia with thrombosis (HITT) has historically been controversial. We present a case of successful fondaparinux use to treat HITT confirmed by the serotonin-release assay in the setting of other significant clotting and bleeding risk factors.. We report a 19-year-old male with a history of Factor V Leiden and recent neurosurgery treated with fondaparinux after developing HITT confirmed by the serotonin-release assay (SRA). The patient achieved full platelet recovery on fondaparinux and was successfully transitioned to warfarin therapy without further thrombotic nor bleeding complications.. This case demonstrates a clear example of success of fondaparinux use to treat SRA-confirmed HITT in the setting of complicating factors and adds to the existing literature supporting the use of fondaparinux for HIT.

Topics: Adult; Anticoagulants; Blood Coagulation; Factor V; Factor Xa Inhibitors; Fondaparinux; Hemorrhage; Heparin; Humans; Male; Serotonin; Thrombocytopenia; Thrombosis; Young Adult

Heparin-induced thrombocytopenia (HIT) is a not-uncommon adverse effect of heparin exposure, with potentially serious and/or fatal thrombotic consequences. Recent studies looking at the off-label use of fondaparinux for HIT show similar efficacy and adverse-effect profiles, as well as improved costs, compared with some commonly used direct thrombin inhibitors. Although routine laboratory monitoring of fondaparinux-specific anti-Xa levels typically is not recommended, we present a case report that suggests fondaparinux monitoring may be needed in patients with hepatic impairment causing acquired antithrombin deficiency. We performed daily assessment of antithrombin- and fondaparinux-specific anti-Xa levels in a 50-year-old female of unknown ethnicity to ensure that fondaparinux dosing was maintained within an acceptable range. With this management strategy, the patient experienced no thrombotic or hemorrhagic complications during the hospital admission or the following 2 months in outpatient treatment.

Topics: Anticoagulants; Drug Monitoring; Female; Fondaparinux; Heparin; Humans; Middle Aged; ROC Curve; Thrombocytopenia

Essentials Spontaneous HIT syndrome clinically/serologically resembles HIT but without proximate heparin. Rarely, spontaneous HIT syndrome complicates total knee arthroplasty surgery. Mesenteric vein thrombosis is a rare presentation of spontaneous HIT syndrome. IVIg rapidly corrects thrombocytopenia by inhibiting heparin-independent platelet activation. SUMMARY: Spontaneous heparin-induced thrombocytopenia (HIT) syndrome is an autoimmune HIT (aHIT) disorder characterized by thrombocytopenia, thrombosis, and HIT antibodies despite no proximate heparin exposure. For unknown reasons, many cases occur after total knee arthroplasty. A 52-year-old woman presented 12 days posttotal knee replacement (aspirin thromboprophylaxis) with gastrointestinal bleeding (superior mesenteric vein thrombosis); the platelet count was 63 × 10

Topics: Anticoagulants; Arginine; Arthroplasty, Replacement, Knee; Female; Fondaparinux; Gastrointestinal Hemorrhage; Heparin; Humans; Immunoglobulins, Intravenous; Middle Aged; Pipecolic Acids; Platelet Activation; Platelet Count; Serotonin; Sulfonamides; Thrombocytopenia; Thrombosis; Venous Thromboembolism

We present important laboratory testing and clinical management strategies used to safely discharge home a 69-year old woman with heparin-induced thrombocytopenia (HIT) from the hospital. She was admitted for a coronary artery bypass graft procedure for which she was anticoagulated with heparin. Shortly after the procedure she developed thrombocytopenia and was diagnosed with HIT using the 4Ts scoring system, a latex-enhanced immunoassay (LEI) screen and confirmatory serotonin release assay. Her anticoagulation was switched from heparin to argatroban, and response to treatment was monitored in the laboratory using LEI. Unfortunately, she also received platelet transfusions and subsequently developed multifocal deep vein thrombosis with worsening platelet counts with nadir less than 10 x 10^3/μL. After five therapeutic plasma exchange procedures we noted an improvement in platelet counts, which plateaued into the 50s x 10^3/μL. Furthermore, the LEI remained positive. At this juncture we decided to transition from argatroban to fondaparinux so that she could leave the hospital in stable condition. Upon follow-up with hematology she exhibited no worsening clinical signs or symptoms of disease, and platelet counts markedly improved to within normal limits of detection. In this report we examine the utility of LEI in monitoring patients with HIT, therapeutic plasma exchange in the management of severe HIT (with thrombosis), and the use of subcutaneous fondaparinux in managing HIT in the outpatient setting.

Topics: Aged; Arginine; Coronary Artery Bypass; Female; Fondaparinux; Heparin; Humans; Pipecolic Acids; Platelet Count; Platelet Transfusion; Sulfonamides; Thrombocytopenia; Venous Thrombosis

The rate of heparin-induced thrombocytopenia (HIT) on a population basis is unknown. The objective of this study was to characterize the risk for HIT during antepartum, delivery, and postpartum hospitalizations in the United States.. A large administrative database was used to determine the risk of HIT in hospitalized obstetric patients who received unfractionated heparin (UFH) or low molecular weight heparin (LMWH). Patients were presumed to have HIT if they were exposed to UFH or LMWH, received a diagnosis of HIT, and were administered a medication for the treatment of HIT including bivalirudin, argatroban, fondaparinux, or lepirudin. We queried severe complications of HIT including arterial thrombosis, limb amputation, heart failure, and death.. We identified 66,468 antepartum hospitalizations, 66,741 delivery hospitalizations, and 16,325 postpartum readmissions where women received pharmacologic prophylaxis. Of these, 10 antepartum admissions, 1 delivery admission, and 14 postpartum readmissions involved a diagnosis of HIT with treatment of bivalirudin, argatroban, fondaparinux, or lepirudin. There were no deaths and no diagnoses of arterial thrombosis, limb amputation, heart failure, and death.. Risk for HIT among hospitalized obstetric patients is low. In this cohort, no cases of death or severe complications were noted in relation to the diagnosis.

Topics: Adolescent; Adult; Arginine; Databases, Factual; Delivery, Obstetric; Female; Fondaparinux; Heparin; Heparin, Low-Molecular-Weight; Hirudins; Hospitalization; Humans; Middle Aged; Peptide Fragments; Pipecolic Acids; Postpartum Period; Pregnancy; Recombinant Proteins; Risk Assessment; Sulfonamides; Thrombocytopenia; United States; Young Adult

Topics: Anticoagulants; Fondaparinux; Heparin; Polysaccharides; Thrombocytopenia

Topics: Anticoagulants; Fondaparinux; Heparin; Polysaccharides; Thrombocytopenia

Heparin-induced thrombocytopenia (HIT) and heparin-induced thrombocytopenia and thrombosis are potentially fatal adverse reactions to heparin therapy caused by the formation of polyclonal antibodies against the platelet factor 4-heparin complex. Fatal limb and organ damage or death may occur as a result of this immunological drug reaction. Described in this case report is the management of a patient who developed HIT after undergoing a MitraClip transcatheter mitral valve repair. The aim was to encourage clinicians to pay special attention to a frail patient who receives heparin therapy and to advise clinicians that clinical scores and laboratory tests should be used as a complement for certain diagnosis. The decision about continuation or cessation of heparin therapy is an important cornerstone for hospitalized patients with HIT.

Topics: Factor Xa Inhibitors; Fibrinolytic Agents; Fondaparinux; Heart Valve Prosthesis Implantation; Heparin; Humans; Male; Middle Aged; Mitral Valve Insufficiency; Polysaccharides; Postoperative Complications; Thrombocytopenia

Making a definitive diagnosis of heparin-induced thrombocytopenia (HIT) can be problematic. A prompt platelet rise following treatment has been proposed as a "post-test" criterion for diagnosis. However, the platelet response following discontinuation of heparin and initiation of a recommended alternative anticoagulant remains largely undefined and unstudied. This study aimed to characterize platelet response to initial treatment in patients with a low, intermediate, or high likelihood of having HIT. This was a multicenter retrospective cohort study. Patients were over 18 years in age, underwent serologic testing for HIT, and received alternative anticoagulation treatment for HIT. Classification of each patient's likelihood of having HIT was based on an empiric, pre-hoc combination of the 4T score and serology results. The primary outcome for this study was a platelet count response after initiation of direct thrombin inhibitor (DTI) or fondaparinux therapy within 48 h. 124 patients were analyzed. The sensitivity and specificity of having an immediate platelet rise of at least 10,000/µL by day 2 after starting treatment among high-likelihood for HIT patients were 0.71 (95% CI 0.55-0.84) and 0.64 (95% CI 0.5-0.76), respectively. The negative predictive value of no platelet rise was 75.5% (95% CI 0.61-0.86). A prompt platelet count rise may be appropriate to consider along with other known criteria for the clinical diagnosis of HIT. The rise should be immediate following discontinuation of heparin and initiation of recommended treatment, with an upward rise within 48 h.

Topics: Adult; Aged; Antithrombins; Blood Platelets; Factor Xa Inhibitors; Fondaparinux; Heparin; Humans; Middle Aged; Platelet Count; Polysaccharides; Predictive Value of Tests; Retrospective Studies; Thrombocytopenia; Young Adult

Topics: Anticoagulants; Fondaparinux; Heparin; Humans; Off-Label Use; Thrombocytopenia

Topics: Anticoagulants; Fondaparinux; Heparin; Humans; Off-Label Use; Thrombocytopenia

Heparin-induced thrombocytopenia (HIT) is a serious complication of the administration of heparin and its derivatives. Non-heparin anticoagulants such as argatroban and fondaparinux are widely used in the management of HIT to compare the effectiveness of argatroban and fondaparinux in the resolution of thrombocytopenia and to compare clinical outcomes in patients with isolated HIT. A retrospective cohort analysis was performed at King Abdulaziz Medical City (KAMC) on patients diagnosed with isolated HIT between 31 Jan, 2014 and 30 June, 2017. Demographics data, non-heparin anticoagulants, related laboratory results, and clinical outcomes were retrieved and analysed. The cohort comprised a total of 95 adult patients who received either argatroban (56 patients) or fondaparinux (39 patients) for isolated HIT. The median age and sex distribution were similar in both argatroban and fondaparinux groups. The mean (+ SD) time (in days) for the resolution of thrombocytopenia was 3.5 (± 1.8) for patients who received argatroban and 3.7 (± 1.7) for patients administered fondaparinux (p = 0.843). Thromboembolic events occurred in five patients (8.9%) administered argatroban and in three patients (7.7%) administered fondaparinux (p = 0.382). There was no significant difference in the rates of bleeding or death (p = 0.829); however, the small number of cases limits our ability to draw conclusions about these outcomes. In this retrospective study, fondaparinux and argatroban were similarly effective in resolving thrombocytopenia, preventing further thromboembolic events, and maintaining safety in patients with confirmed HIT. To confirm this observation, larger prospective studies are needed.

Topics: Aged; Arginine; Fondaparinux; Heparin; Humans; Middle Aged; Pipecolic Acids; Retrospective Studies; Sulfonamides; Thrombocytopenia; Thromboembolism

Fondaparinux, as a factor Xa-inhibitor, is used off label to manage heparin-induced thrombocytopenia (HIT), but little experience with HIT patients has been reported in the literature. Moreover, the use of fondaparinux for full anticoagulation in critically ill patients with HIT and renal insufficiency is limited.. A trauma patient, who had received low molecular weight heparin (LMWH) and heparin to treat venous thromboembolism, developed thrombocytopenia and multiple organ dysfunction in the intensive care unit (ICU). Also, her deep venous thromboembolism (DVT) continued to progress.. The final diagnosis was HIT.. Fondaparinux was temporarily used for anticoagulation treatment of DVT for 7 days when another anticoagulant (argatroban) was unavailable. Although the patient had kidney dysfunction, a full therapeutic dose of 7.5 mg fondaparinux was administered every morning through subcutaneous injection for consecutive 7 days.. The patient's thrombocytopenia and thrombosis were successfully treated without bleeding complications during therapeutic fondaparinux administration.. This is the first case reporting the successful use of fondaparinux for full anticoagulation for DVT in a critically ill patient with HIT and renal insufficiency. Our experience suggests that fondaparinux might be an alternative for anticoagulation treatment in patients with HIT and kidney dysfunction if another anticoagulant (argatroban) is unavailable.

Topics: Aged, 80 and over; Anticoagulants; Critical Illness; Factor Xa Inhibitors; Female; Fondaparinux; Heparin; Humans; Polysaccharides; Thrombocytopenia; Venous Thromboembolism

Essentials Critically ill cancer patients require pharmacologic prophylaxis for venous thromboembolism (VTE). Patients from 566 hospitals in the United States between 2010 and 2014 were included. Low-molecular-weight heparin (LMWH) prophylaxis was not associated in a reduction of VTE rates. LMWH prophylaxis was associated with a reduction in bleeding and heparin induced thrombocytopenia. SUMMARY: Background Critically ill patients with cancer are at increased risk of venous thromboembolism (VTE) from physical and cellular factors, requiring pharmacologic prophylaxis to reduce the risk of VTE. Objectives To assess whether low-molecular-weight heparin (LMWH) prophylaxis reduces in-hospital rates of VTE or improves clinical outcomes compared with unfractionated heparin (UFH) prophylaxis in critically ill patients with cancer. Methods We used a propensity-matched comparative-effectiveness cohort from the Premier Database. Patients aged 18 years or older with a primary diagnosis of cancer, intensive care unit admission and VTE prophylaxis within 2 days of admission between 1 January 2010 and 31 December 2014 were included. Patients were divided into LMWH or UFH prophylaxis groups. Results A total of 103 798 patients were included; 75 321 (72.6%) patients received LMWH and 28 477 (27.4%) patients received UFH. Propensity analysis matched (2 : 1) 42 343 LMWH patients and 21 218 UFH patients. Overall, LMWH was not associated with a decreased incidence of VTE (5.32% vs. 5.50%). LMWH prophylaxis was associated with a reduction in pulmonary embolism (0.70% vs. 0.99%), significant bleeding (13.3% vs. 14.8%) and heparin-induced thrombocytopenia (HIT) (0.06% vs. 0.19%). In non-metastatic solid disease, LMWH was associated with decreased VTE (4.27% vs. 4.84%) and PE (0.47% vs. 0.95%). Conclusions The use of an LMWH for VTE prophylaxis was not associated with a reduction in the incidence of in-hospital VTE as compared with UFH, but was associated with significant reductions in PE, clinically important bleeding events, and incidence of HIT in critically ill patients with cancer.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Comparative Effectiveness Research; Critical Illness; Databases, Factual; Factor Xa Inhibitors; Female; Fondaparinux; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Neoplasms; Risk Factors; Thrombocytopenia; Time Factors; Treatment Outcome; United States; Venous Thromboembolism; Young Adult

Heparin-induced thrombocytopenia (HIT) is an adverse drug reaction mediated by platelet-activating antibodies that target complexes of platelet factor 4 and heparin. Patients are at markedly increased risk of thromboembolism.. These evidence-based guidelines of the American Society of Hematology (ASH) are intended to support patients, clinicians, and other health care professionals in their decisions about diagnosis and management of HIT.. ASH formed a multidisciplinary guideline panel balanced to minimize potential bias from conflicts of interest. The McMaster University GRADE Centre supported the guideline development process, including updating or performing systematic evidence reviews. The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess evidence and make recommendations, which were subject to public comment.. The panel agreed on 33 recommendations. The recommendations address screening of asymptomatic patients for HIT, diagnosis and initial management of patients with suspected HIT, treatment of acute HIT, and special situations in patients with acute HIT or a history of HIT, including cardiovascular surgery, percutaneous cardiovascular intervention, renal replacement therapy, and venous thromboembolism prophylaxis.. Strong recommendations include use of the 4Ts score rather than a gestalt approach for estimating the pretest probability of HIT and avoidance of HIT laboratory testing and empiric treatment of HIT in patients with a low-probability 4Ts score. Conditional recommendations include the choice among non-heparin anticoagulants (argatroban, bivalirudin, danaparoid, fondaparinux, direct oral anticoagulants) for treatment of acute HIT.

Topics: Administration, Oral; Anticoagulants; Arginine; Cardiovascular Surgical Procedures; Chondroitin Sulfates; Dermatan Sulfate; Evidence-Based Medicine; Fondaparinux; Heparin; Heparitin Sulfate; Hirudins; Humans; Peptide Fragments; Pipecolic Acids; Platelet Count; Recombinant Proteins; Renal Replacement Therapy; Sulfonamides; Thrombocytopenia; Venous Thromboembolism

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

Topics: Anticoagulants; Fondaparinux; Heparin; Humans; Off-Label Use; Thrombocytopenia

Recent studies reveal a high occurrence of overdiagnosis of heparin-induced thrombocytopenia in surgical patients with critical illness. The optimal criteria for diagnosis of heparin-induced thrombocytopenia remain unclear, contributing to unnecessary treatment. We reviewed patients who were admitted to surgical ICUs and were suspected of heparin-induced thrombocytopenia to identify how often patients were correctly treated.. In this clinical prospective study, data were collected including age, sex, antiplatelet factor 4/heparin enzyme-linked immunosorbent assay, serotonin release assay, and Warkentin 4Ts scores. Heparin-induced thrombocytopenia-positive patients were defined as those with both positive antiplatelet factor 4/heparin enzyme-linked immunosorbent assay (optical density, ≥ 0.40) and positive serotonin release assay results.. Urban tertiary medical center.. Patients admitted to the surgical and cardiac ICU who were presumed to have heparin-induced thrombocytopenia and underwent antiplatelet factor 4/heparin enzyme-linked immunosorbent assay and serotonin release assay testing between January 1, 2011, and August 1, 2014.. None.. A total of 135 patients had 4Ts, antiplatelet factor 4/heparin enzyme-linked immunosorbent assay, and serotonin release assay scores. A total of 11 patients (8.1%) had positive serotonin release assay and 80 patients had positive antiplatelet factor 4/heparin enzyme-linked immunosorbent assay; 10 patients were identified as heparin-induced thrombocytopenia positive. Positive serotonin release assay was noted in nine of 11 patients (81.8%) with antiplatelet factor 4/heparin enzyme-linked immunosorbent assay optical density greater than or equal to 2.0, compared with one of 22 patients (4.5%) with optical density values of 0.85-1.99, and one of 102 patients (1.0%) with optical density values of 0-0.84. Out of 135 patients, 29 patients (21.5%) received treatment with argatroban, lepirudin, or fondaparinux: 10 of 10 heparin-induced thrombocytopenia-positive patients (100%) compared with 19 of 125 heparin-induced thrombocytopenia-negative patients (15%).. Overtreatment of heparin-induced thrombocytopenia in the surgical ICU continues even with recent increased caution encouraging a higher antiplatelet factor 4/heparin enzyme-linked immunosorbent assay optical density threshold before initiating treatment. More stringent criteria should be used to determine when to order serologic testing and when the results of such testing should prompt a change in anticoagulant treatment. If antiplatelet factor 4/heparin enzyme-linked immunosorbent assay is used to consider immediate treatment, an optical density greater than or equal to 2.0 may be a more appropriate threshold.

Topics: Academic Medical Centers; Aged; Antibodies; Anticoagulants; Antithrombins; Arginine; Enzyme-Linked Immunosorbent Assay; Female; Fondaparinux; Heparin; Hirudins; Humans; Intensive Care Units; Male; Medical Overuse; Middle Aged; Pipecolic Acids; Platelet Factor 4; Polysaccharides; Prospective Studies; Recombinant Proteins; Serotonin; Sulfonamides; Thrombocytopenia

Heparin-induced thrombocytopenia (HIT) occurs in up to 5% of patients exposed to unfractionated heparin for 5 or more days. Direct thrombin inhibitors (DTIs) are currently the only Food and Drug Administration (FDA)-approved agents for the treatment of HIT. The purpose of this study is to determine whether fondaparinux is an appropriate first-line alternative anticoagulant in patients with suspected or confirmed HIT.. A retrospective study was conducted by identifying all patients who received a DTI or fondaparinux during a 5 year period, August 2009-August 2014. Patients were included if they had a HIT panel/serotonin-release assay analysis (regardless of the result) and were initiated on a DTI or fondaparinux for alternative anticoagulation. The primary outcome was new, recurrent, or progressive thromboembolic event. Secondary outcomes included bleeding events, platelet count recovery, and hospital stay.. A total of 1022 patients were evaluated, and 47 patients met the inclusion criteria. Twelve patients were HIT positive and 35 were HIT negative. Seven (14.9%) of the 47 patients experienced a new thrombosis, none of whom were on fondaparinux only (FONDA). There were 4 new minor bleeds, with 1 bleed as a result of being on fondaparinux. FONDA treatment resulted in a slightly shorter median duration of hospital stay compared to the DTI-only group and the DTI followed by fondaparinux group. There is a potential for cost savings with fondaparinux due to the ease of administration and availability to be given in the outpatient setting.. In this small retrospective review, fondaparinux appeared similarly efficacious and safe compared to DTIs for the treatment of suspected HIT.

Topics: Aged; Aged, 80 and over; Anticoagulants; Female; Fondaparinux; Heparin; Humans; Male; Middle Aged; Polysaccharides; Retrospective Studies; Thrombocytopenia; Treatment Outcome

HIT is an acquired antibody-mediated disorder strongly associated with thrombosis, including microthrombosis secondary to disseminated intravascular dissemination (DIC). The clinical features of HIT are reviewed from the perspective of the 4Ts scoring system for HIT, which emphasises its characteristic timing of onset of thrombocytopenia. HIT antibodies recognize multimolecular complexes of platelet factor 4 (PF4)/heparin. However, a subset of HIT sera recognise PF4 bound to platelet chondroitin sulfate; these antibodies activate platelets in vitro and in vivo even in the absence of heparin, thus explaining: delayed-onset HIT (where HIT begins or worsens after stopping heparin); persisting HIT (where HIT takes several weeks to recover); spontaneous HIT syndrome (a disorder clinically and serologically resembling HIT but without proximate heparin exposure); and fondaparinux-associated HIT (four distinct syndromes featuring thrombocytopenia that begins or worsens during treatment with fondaparinux), with a new patient case presented with ongoing thrombocytopenia (and fatal haemorrhage) during treatment of HIT with fondaparinux, with fondaparinux-dependent platelet activation induced by patient serum ("fondaparinux cross-reactivity"). Ironically, despite existence of fondaparinux-associated HIT, this pentasaccharide anticoagulant is a frequent treatment for HIT (including one used by the author). HIT can be confused with other disorders, including those with a) timing similar to HIT (e. g. abciximab-associated thrombocytopenia of delayed-onset); b) combined thrombocytopenia/thrombosis (e. g. symmetrical peripheral gangrene secondary to acute DIC and shock liver); and c) both timing of onset and thrombosis (e. g. warfarin-associated venous limb gangrene complicating cancer-associated DIC). By understanding clinical and pathophysiological similarities and differences between HIT and non-HIT mimicking disorders, the clinician is better able to make the correct diagnosis.

Topics: Anticoagulants; Fondaparinux; Heparin; Humans; Platelet Activation; Platelet Factor 4; Polysaccharides; Thrombocytopenia

Heparin-induced thrombocytopenia (HIT) is a pro-thrombotic side effect of heparin therapy caused by HIT antibodies with platelet-activating properties. Recent advances in understanding of spontaneous HIT syndrome, which can occur even without any heparin exposure despite its clinical and serological characteristics being similar to those of HIT, reveal the following HIT clinical features atypical for an immune-mediated disease. Heparin-naïve patients can develop IgG antibodies as early as day 4, as in a secondary immune response. Evidence for an anamnestic response upon heparin re-exposure is lacking. In addition, HIT antibodies are relatively short-lived, unlike those in a secondary immune response. Antigen immunoassays are commonly used worldwide for serological diagnosis of HIT. However, such assays do not indicate whether HIT antibodies have platelet-activating properties, leading to low diagnostic specificity for HIT. The detection of platelet-activating antibodies using a washed platelet activation assay is crucial for making a HIT diagnosis. These atypical clinical and serological features should be carefully considered while appropriately diagnosing HIT, which leads to appropriate therapy such as immediate administration of an alternative anticoagulant for preventing thromboembolic events and re-administration of heparin during surgery involving cardiopulmonary bypass when HIT antibodies are no longer detectable.

Topics: Acute Disease; Animals; Fondaparinux; Heparin; Humans; Platelet Factor 4; Polysaccharides; Thrombocytopenia

To assess the frequency of platelet monitoring and bleeding risks associated with the use of injectable anticoagulants in a real life setting and to estimate the associated costs.. An analysis of the 2013 data from a random sample of ≈600,000 patients registered in the French National Health Insurances reimbursement database was conducted to identify platelet counts performed during injectable anticoagulants exposure period and treatment interruptions due to heparin-induced thrombocytopenia or transfusion. Events were then valued to establish associated costs.. Overall 15,985 adult patients representing a cumulated injectable anticoagulants exposure time of 12,264 months were selected. Treatment sequences involved unfractionated heparin (2.8%), low molecular weight heparin (86.9%), and fondaparinux (13.1%). Patients treated with unfractionated heparin were older (77 vs. 57 and 59 years) with longer treatment duration (32.6 vs. 25.1 and 21 days). After statistical adjustment, the average monthly number of platelet counts was 1.36-fold lower in patients treated with fondaparinux compared to low molecular weight heparin (P<0.0001). No difference was found between low molecular weight heparin and fondaparinux regarding the incidence of bleeding with transfusion (P=0.76) or hospitalized thrombocytopenia (P=0.82). Extrapolated for the whole country, the estimated costs for biological monitoring were € 21.6 million for low molecular weight heparin and € 0.9 million for fondaparinux.. Significantly fewer platelet counts were performed among patients treated with fondaparinux than among patients receiving low molecular weight heparin without additional bleeding risk. This finding should be taken into account when assessing the costs of such treatments.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Costs and Cost Analysis; Environmental Monitoring; Female; Fondaparinux; France; Hemorrhage; Heparin; Heparin, Low-Molecular-Weight; Humans; Injections; Male; Middle Aged; Platelet Count; Polysaccharides; Risk Factors; Thrombocytopenia

Topics: Anticoagulants; Fondaparinux; Heparin; Humans; Polysaccharides; Thrombocytopenia

Topics: Aged; Anticoagulants; Female; Fondaparinux; Heparin; Humans; Middle Aged; Multiple Sclerosis; Neuromyelitis Optica; Plasma Exchange; Polysaccharides; Thrombocytopenia; Thrombosis

Current guidelines for heparin-induced thrombocytopenia (HIT) management recommend heparin cessation and switching to a nonheparin anticoagulant (ie, argatroban, danaparoid) upon clinical suspicion. Fondaparinux may be effective but information supporting its use is limited. We retrospectively evaluated 239 patients who received a nonheparin anticoagulant (fondaparinux = 133, danaparoid = 59, and argatroban = 47) for suspected or confirmed HIT. A propensity score was constructed based on age, gender, creatinine, 4T scores, and comorbidity index, and used to match 133 patients to 60 controls. Outcomes were thrombosis or thrombosis-related death and major bleeding. In the matched population there were 22 (16.5%) episodes of thromboses in the fondaparinux group and 13 (21.4%) in the control group (χ(2) P = .424). Bleeding was observed in 28 (21.1%) patients in the fondaparinux group compared with 12 (20%) in the control group (χ(2) P = .867). Survival analysis, and subgroup and unmatched analyses showed similar results. In the fondaparinux group, 60% of patients received prophylactic doses. Fondaparinux has similar effectiveness and safety as argatroban and danaparoid in patients with suspected HIT. Prophylactic fondaparinux doses seem to be effective if no indication for full anticoagulation exists.

Topics: Aged; Anticoagulants; Female; Fondaparinux; Hemorrhage; Heparin; Humans; Male; Middle Aged; Polysaccharides; Propensity Score; Retrospective Studies; Thrombocytopenia; Thrombosis; Treatment Outcome

Topics: Aged, 80 and over; Antibodies; Anticoagulants; Blood Platelets; Dalteparin; Female; Fondaparinux; Hip Fractures; Hirudins; Humans; Immunoglobulins, Intravenous; Immunologic Factors; Morpholines; Peptide Fragments; Platelet Count; Polysaccharides; Recombinant Proteins; Rivaroxaban; Thiophenes; Thrombocytopenia; Venous Thrombosis

Heparin induced thrombocytopenia (HIT) is an immune-mediated adverse reaction characterized by thrombocytopenia and paradoxical arterial or venous thrombosis, due to the formation IgG antibodies directed to a multimolecular complex of heparin-platelet factor 4 (PF4). Fondaparinux is a selective factor Xa inhibitor with little affinity for PF4 and thus less likely to induce an immune response, making fondaparinux a potentially useful drug for the treatment of HIT. Herein we report the case of a 73 years old woman with HIT associated with arterial and venous thrombosis that was successfully treated with fondaparinux, with normalization of the platelet countand without progression of thrombosis.

Topics: Aged; Anticoagulants; Female; Fondaparinux; Heparin; Humans; Necrosis; Platelet Count; Platelet Factor 4; Polysaccharides; Thrombocytopenia; Treatment Outcome; Venous Thrombosis

Heparin-induced skin lesions are common. The majority are delayed-type hypersensitivity reactions to heparin or other components of the injection fluid. Differentiation from heparin-induced thrombocytopenia (HIT) skin lesions is important. The Warkentin 4T's score is helpful for assessment of the risk of HIT.. A 36-year old female was treated with injections of tinzaparin for a deep vein thrombosis. After 16 days, she developed progressive thrombocytopenia and a skin lesion at one of the injection sites. She was diagnosed with "skin lesion consistent with HIT and caused by the use of low-molecular-weight heparin". The platelet count returned to normal and the severity of the skin lesion improved after replacement of tinzaparin with fondaparinux.. In patients with skin lesions suspected of being caused by the use of heparin, a complete blood count needs to be made as quickly as possible. With a 4T's score ≥ 4, it is recommended that a skin biopsy and a laboratory HIT-test are performed. Heparin should be replaced by alternative anticoagulants by way of precaution.

Topics: Adult; Anticoagulants; Female; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Platelet Count; Polysaccharides; Thrombocytopenia; Tinzaparin

Current guidelines provide no recommendations on perioperative bridging for patients after mechanical heart valve replacement (MHVR) who also have a history of heparin-induced thrombocytopenia (HIT). We present a successful case of prolonged bridging with fondaparinux in a 69-year-old Chinese woman.. The patient presented to our department with the aim for radical resection of oesophageal cancer. Fondaparinux has been administered alone at 2·5 mg subcutaneously once daily for 24 days during the interruption of warfarin perioperatively. There were no signs or symptoms of thromboembolic or bleeding throughout and after her hospitalization.. Fondaparinux may offer an option for management of the patients with MHVR who cannot use heparin products, but further clinical investigations are warranted.

Topics: Aged; Anticoagulants; Female; Fondaparinux; Heart Valves; Heparin; Humans; Perioperative Care; Polysaccharides; Thrombocytopenia

To present a case of heparin induced thrombocytopenia in a patient treated with enoxaparin.. A case of heparin-induced thrombocytopenia was examinated with a detailed platelet count analysis over the time and with detection of platelets antibodies.. The detection of platelet antobodies and the recovery of platelet count after cessation of enoxaparin strongly support the diagnosis of heparin-induced thrombocytopenia (HIT).. HIT is a severe side effects of heparin administration. It is more frequent in patients treated with unfractionated heparin however can also be induced by low molecular weight heparin. Guideline suggests the cessation of heparin administration and the treatment of patients with fondaparinux.. Enoxaparin, Heparin induced thrombocytopenia, Thrombocytopenia.. Scopo dell’articolo è la presentazione di un caso di trombocitopenia indotto dall’eparina in un paziente trattato con enoxaparine. L’osservazione in questione è stata analizzata in dettaglio con ripetute conta delle piastrine e con l’individuazione di anticorpi antipiastrine. La scoperta degli anticorpi-antipiastrine ed il restauro della conta piastrinica dopo la cessazione della somministrazione dell’enoxaparina è alla base della diagnosi di trombocitopenia indotta dall’eparina. Questo tipo di trombocitopenia è un grave effetto collaterale della somministrazione di eparina, ed è più frequente nei pazienti trattati con eparina non frazionata, ma può comunque essere provocata dalla somministrazione di eparina a basso peso molecolare. Le linee guida suggeriscono di sospendere la somministrazione di eparina e di trattare i pazienti con fondaparinux.

Topics: Anticoagulants; Autoantibodies; Drug Substitution; Duodenal Neoplasms; Enoxaparin; Female; Fondaparinux; Humans; Immunoglobulin G; Intensive Care Units; Middle Aged; Pancreatitis; Polysaccharides; Postoperative Complications; Thrombocytopenia

Topics: Anticoagulants; Cardiomyopathies; Follow-Up Studies; Fondaparinux; Heart Transplantation; Heart-Assist Devices; Heparin; Humans; Male; Middle Aged; Polysaccharides; Thrombocytopenia; Thrombosis; Treatment Outcome

Heparin-induced thrombocytopenia (HIT) is a rare but severe prothrombotic disorder of heparin treatment that leads to a decline in platelet count and thrombotic complications. If HIT is suspected, then heparin should be stopped and an alternative anticoagulant started. Fondaparinux is a factor Xa-inhibitor that is not FDA-approved for this condition, but preliminary experience in HIT patients has been reported in the literature. The present study describes an experience of anticoagulation management with fondaparinux in postoperative cardiac surgery patients.. Retrospective study.. Tertiary hospital.. Patients who had undergone cardiac surgery from October 2009 to June 2012.. After HIT was suspected clinically, PaGIA and ELISA test were performed in all patients to diagnose HIT. In the patients included, anticoagulation was managed with a low dose of fondaparinux and daily monitoring of platelet count and anti-Xa level.. Of a total of 1,338 postoperative cardiac surgery patients, 15 patients were included (1.1%). Twelve of the 15 patients with HIT presented with renal failure and were under continuous renal replacement therapy. Two major bleeding events occurred during fondaparinux treatment, although platelet count and anti-Xa activity remained within the normal range. No thrombotic episodes were diagnosed.. With daily monitoring of anti-Xa activity, fondaparinux appeared to be a good alternative to heparin in the study group; however, randomized clinical trials are needed to establish the safety and efficacy of this drug in critically ill, previously HIT patients.

Topics: Adult; Aged; Anticoagulants; Blood Coagulation; Cardiac Surgical Procedures; Dose-Response Relationship, Drug; Factor X; Female; Follow-Up Studies; Fondaparinux; Heart Diseases; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Platelet Count; Polysaccharides; Postoperative Complications; Retrospective Studies; Thrombocytopenia; Thrombosis; Treatment Outcome

Recurrent venous thromboembolism (VTE) occurs in some patients despite treatment with the standard drugs, warfarin and low-molecular-weight heparin (LMWH). Fondaparinux is currently licensed by the Food and Drug Administration for the prophylaxis of deep-vein thrombosis in patients undergoing orthopedic or abdominal surgery and also in the treatment of VTE. Well-documented use of this agent beyond these indications and for prolonged periods is currently limited.. Two cases of "refractory" VTE, managed effectively with long-term fondaparinux are described. In the first case, a 43-year-old man developed recurrent thrombosis while receiving warfarin at a higher target international normalized ratio (INR) of 3 to 4. In the second case, a 45-year-old man developed recurrent thrombosis on once-daily dalteparin. Both the patients were successfully managed with fondaparinux for 36 months and 14 months, respectively, with no sign of recurrent thrombosis or adverse effects.. In patients with recurrent VTE, fondaparinux is effective as daily injections as much as twice-daily LMWH or warfarin maintained on higher therapeutic-range INRs. Although the exact mechanism for this effectiveness is not yet understood, it provides a useful alternative to the standard therapies. In addition, the side effect profile is also favorable for fondaparinux, in that it causes less thrombocytopenia and skin reactions in comparison with heparins.. Daily fondaparinux injections may be an effective antithrombotic agent in patients who develop recurrent VTE on anticoagulation with warfarin or LMWH.

Topics: Adult; Anticoagulants; Dalteparin; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Injections, Subcutaneous; Male; Middle Aged; Polysaccharides; Recurrence; Thrombocytopenia; Venous Thromboembolism; Warfarin

In patients with respiratory failure and impairment of the left ventricle, arteriovenous extracorporeal membrane oxygenation (ECMO) offers further therapeutic options. Systemic anticoagulation is mandatory and heparin is routinely administrated. However, repeated exposure to heparin may cause heparin-induced thrombocytopenia (HIT) and carries a risk of thrombotic mortality and morbidity. We present a patient who developed HIT during ECMO support and was treated successfully and safely by fondaparinux. Fondaparinux can be used for thromboembolic treatment or prophylaxis in a patient with HIT.

Topics: Anticoagulants; Device Removal; Drug Substitution; Extracorporeal Membrane Oxygenation; Female; Fondaparinux; Heart Valve Prosthesis Implantation; Heparin; Humans; Mitral Valve; Polysaccharides; Reoperation; Thrombocytopenia; Time Factors; Treatment Outcome; Young Adult

Thromboembolic complications such as systemic embolization and valve thrombosis are a major concern early after mechanical valve replacement; however, the benefit of anticoagulation must be weighed against the risk of early postoperative bleeding complications. Thromboembolic risk is also higher in the early postoperative period (less than 6 mo) compared with the risk in the late postoperative period. Current evidence supports the use of unfractionated heparin or low-molecular-weight heparin early after valve replacement to prevent valve thrombosis or systemic embolization but provides no recommendations for the management of patients with a history of heparin-induced thrombocytopenia (HIT), in which heparin products are contraindicated. We describe the use of fondaparinux early after aortic mechanical valve replacement in a 63-year-old, 95-kg woman with a history of HIT. Fondaparinux was initiated on postoperative day 2 at a prophylactic dose of 2.5 mg subcutaneously daily; the dose was increased to a therapeutic weight-based dose of 7.5 mg subcutaneously daily on postoperative day 3. Warfarin was initiated on postoperative day 1, and fondaparinux was continued until a therapeutic international normalized ratio was achieved. The patient was discharged from the hospital receiving warfarin alone on postoperative day 6. No signs or symptoms of thrombosis or bleeding were noted during or after fondaparinux therapy or at hospital follow-up visits. To our knowledge, this is the first case report to describe the use of fondaparinux within the first 48 hours after mechanical valve replacement in a patient with a history of HIT. This case suggests that fondaparinux may be a safe and effective option to prevent thromboembolic complications early after mechanical valve replacement when heparin products are contraindicated.

Topics: Anticoagulants; Aortic Valve; Female; Follow-Up Studies; Fondaparinux; Heart Valve Prosthesis Implantation; Heparin; Humans; International Normalized Ratio; Middle Aged; Polysaccharides; Postoperative Complications; Thrombocytopenia; Thromboembolism; Treatment Outcome; Warfarin

Thrombotic events are a common complication of left ventricular assist device placement and warrant prophylactic anticoagulation. Heparin is the most common anticoagulant used for prophylaxis of thrombotic events in left ventricular assist device patients as a transition to oral anticoagulants but carries the risk of heparin-induced thrombocytopenia. Limited data is available for the treatment of heparin-induced thrombocytopenia in this patient population. We report an evaluation of 8 left ventricular assist device patients with suspected or confirmed HIT started on fondaparinux at the time of heparin-induced platelet-factor-4 antibody positivity.. Adult patients were reported if they were heparin-induced platelet antibody positive, tested via enzyme-linked immunusorbent assay, post-operative after left-ventricular assist device, and were initiated on fondaparinux at the time of heparin-induced platelet antibody positivity. Waiver of informed consent was granted from the institutional review board. Baseline demographics, clinical course of HIT, safety and efficacy variables were collected.. Eight patients receiving fondaparinux were identified and included in this report. The patient group was on average 49 years old, weighing 95 kg, with calculated BMI 28.8 and consisted primarily of Caucasian males. Three patients developed new thromboses after initiation of fondaparinux for heparin-induced thrombocytopenia. Only one patient had a major bleeding event of an overt bleed after initiation of fondaparinux therapy.. Given the lack of major bleeding in this evaluation, fondaparinux could be a potentially safe treatment option for left ventricular assist device patients that are heparin-induced platelet antibody positive pending confirmatory testing results. Given the development of new thromboses in 3 of 8 patients, concern exists about the efficacy of fondaparinux in this patient population. Significant limitations exist regarding these conclusions in this evaluation. Controlled, systematic evaluations are necessary to delineate safety and efficacy of fondaparinux for heparin-induced thrombocytopenia in this population.

Topics: Adult; Anticoagulants; Female; Fondaparinux; Heart-Assist Devices; Heparin; Humans; Male; Middle Aged; Polysaccharides; Retrospective Studies; Thrombocytopenia

Heparin-induced thrombocytopenia (HIT) is the most frequent drug-induced immune reaction affecting blood cells. Its antigen is formed when the chemokine platelet factor 4 (PF4) complexes with polyanions. By assessing polyanions of varying length and degree of sulfation using immunoassay and circular dichroism (CD)-spectroscopy, we show that PF4 structural changes resulting in antiparallel β-sheet content >30% make PF4/polyanion complexes antigenic. Further, we found that polyphosphates (polyP-55) induce antigenic changes on PF4, whereas fondaparinux does not. We provide a model suggesting that conformational changes exposing antigens on PF4/polyanion complexes occur in the hairpin involving AA 32-38, which form together with C-terminal AA (66-70) of the adjacent PF4 monomer a continuous patch on the PF4 tetramer surface, explaining why only tetrameric PF4 molecules express "HIT antigens". The correlation of antibody binding in immunoassays with PF4 structural changes provides the intriguing possibility that CD-spectroscopy could become the first antibody-independent, in vitro method to predict potential immunogenicity of drugs. CD-spectroscopy could identify compounds during preclinical drug development that induce PF4 structural changes correlated with antigenicity. The clinical relevance can then be specifically addressed during clinical trials. Whether these findings can be transferred to other endogenous proteins requires further studies.

Topics: Antibodies; Antigen-Antibody Complex; Antigens; Circular Dichroism; Fondaparinux; Heparin; Humans; Platelet Factor 4; Polyelectrolytes; Polymers; Polyphosphates; Polysaccharides; Protein Binding; Protein Multimerization; Protein Structure, Secondary; Sulfuric Acid Esters; Thrombocytopenia

In life-threatening immune heparin-induced thrombocytopenia (HIT), treatment with an approved non-heparin anticoagulant is essential. However, off-label use with fondaparinux has been reported in the literature. The study aim was to collect data on "real-life" management of patients with suspected acute HIT regarding diagnostic and therapeutic strategies.. In a national multi-centre registry study, patients with a 4T's HIT-probability score of ≥ 4 points and treatment with at least one dose of (A)rgatroban, (L)epirudin, (D)anaparoid, or (F)ondaparinux were retrospectively evaluated.. Of 195 patients, the 4T's scores were 4/5/6/7/8 points in 46 (23.6%)/50 (25.6%)/74 (38.0%)/13 (6.7%)/7 (3.6%) patients, respectively. During heparin therapy, 47 (24.1%) thromboembolic events, 5 (2.6%) skin lesions, 1 (0.5%) amputation, 24 (12.3%) Hb-relevant bleedings, and 2 (1.0%) fatalities occurred. A functional heparin-induced platelet activation assay was performed in 96.9%, a platelet factor 4/heparin-dependent enzyme immunoassay in 89.2%, a particle gel immunoassay in 12.3%, and a serotonin-release assay in none of the patients. Argatroban was used in 16.4%, lepirudin in 2.1%, danaparoid in 23.6%, fondaparinux in 40.0% of the patients; the sequential therapy strata were: AF (5.6%), DA (5.6%), DF (2.6%), DL (2.1%), ADF (1.5%), and DFL (0.5%).. The current diagnostic laboratory strategy for suspected HIT is mostly (>96%) based on the recommended 2-step strategy (immunoassay plus functional assay). However, there is a wide fondaparinux off-label use (up to 50.3%) for suspected HIT, even in those patients with a high clinical pretest probability. Efficacy and safety of fondaparinux for HIT-treatment require further evaluation.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Female; Fondaparinux; Heparin; Humans; Male; Middle Aged; Off-Label Use; Polysaccharides; Registries; Retrospective Studies; Risk Factors; Thrombocytopenia; Young Adult

Topics: Anticoagulants; Female; Fondaparinux; Heparin; Humans; Male; Off-Label Use; Polysaccharides; Thrombocytopenia

Topics: Anticoagulants; Cardiology; Fondaparinux; Hemorrhage; Heparin; Heparin, Low-Molecular-Weight; Hospitalization; Humans; International Cooperation; Neoplasms; Polysaccharides; Renal Insufficiency; Societies, Medical; Thrombocytopenia; Venous Thromboembolism

Topics: Aged; Antibodies; Anticoagulants; Arthroplasty, Replacement, Knee; Atrial Fibrillation; Biomarkers; Chronic Disease; Drug Administration Schedule; Drug Monitoring; Fondaparinux; Humans; Male; Platelet Activation; Platelet Count; Polysaccharides; Predictive Value of Tests; Severity of Illness Index; Thrombocytopenia; Time Factors; Treatment Outcome; Venous Thrombosis; Warfarin

The optimal anticoagulation regimen for hemodialysis (HD) in patients with heparin-induced thrombocytopenia (HIT) has not been defined. Hemodiafiltration (HDF) adds a large convective component to HD, thereby changing the pharmacokinetics of most anticoagulants. Data on coagulation regimens for HDF are scant. We therefore aimed to study the feasibility, effectiveness, tolerability, and pharmacokinetics of fondaparinux anticoagulation in HDF. This was a prospective observational dose-finding study. Patients were started on fondaparinux at a dose of 0.05 mg/kg postdialysis body weight. Per protocol dose escalation was performed when significant clotting was observed and reduced when the anti-Xa activity postdialysis exceeded 0.4 IU/mL. Dose adjustments were made by steps of 0.01 mg/kg postdialysis weight. Anti-Xa activity was measured using a chromogenic method calibrated with low-molecular-weight heparin and validated against fondaparinux-calibrated anti-Xa activity. Four patients with HIT were followed for 160 sessions in total. At the end of the dose titration study, three patients ended at a maintenance dose of 0.03 mg/kg and one patient at 0.04 mg/kg of fondaparinux. Significant bleeding attributable to fondaparinux did not occur. The occurrence of clotting increased parallel to the reduction of fondaparinux dose, from 0/53 and 0/15 sessions at the higher doses (0.04 and 0.05 mg/kg) to 3/75 (4%) at 0.03 mg/kg and 1/17 (6%) at 0.02 mg/kg. Fondaparinux may be safely used and provides adequate anticoagulation for HDF in patients with HIT. We recommend to adjust dosage of fondaparinux to body weight and to initiate therapy at a dose of 0.03 mg/kg to prevent accumulation. Dose titration can be achieved by targeting postdialysis anti-Xa activity.

Topics: Aged; Aged, 80 and over; Anticoagulants; Belgium; Blood Coagulation; Blood Coagulation Tests; Drug Dosage Calculations; Drug Monitoring; Drug Substitution; Factor Xa Inhibitors; Feasibility Studies; Female; Fondaparinux; Hemodiafiltration; Heparin; Humans; Male; Middle Aged; Pilot Projects; Polysaccharides; Prospective Studies; Thrombocytopenia; Treatment Outcome

Topics: Aged, 80 and over; Female; Fibrinolytic Agents; Fondaparinux; Heparin; Humans; Off-Label Use; Polysaccharides; Thrombocytopenia; Thrombosis; Treatment Outcome

Heparin-induced thrombocytopenia is a potentiallylife-threatening complication of heparin or low-molecular-weight heparin administration. We describe the case of a patient with heparin-induced thrombocytopenia complicated by pulmonary embolism, successfully treated with fondaparinux, a factor Xa inhibitor. We also review the literature regarding the use of this anticoagulant in heparin-induced thrombocytopenia complicated by thrombosis. Few treatment options are available in Belgium, and there is little evidence regarding newer anticoagulants.

Topics: Aged, 80 and over; Anticoagulants; Factor X; Female; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Polysaccharides; Pulmonary Embolism; Thrombocytopenia

Heparin-induced thrombocytopenia (HIT) is caused by heparin exposure and presents with reduced platelet count. Patients undergoing hemodialysis (HD) treatment have increased risk of developing HIT due to prolonged exposure to unfractionated heparin or low-molecular weight heparin. We report a 79-year-old male patient with end-stage renal disease who developed type-II HIT during maintenance HD. Platelet count of the patient decreased gradually and antiplatelet factor IV antibody was found to be positive. The patient was treated with fondaparinux and continued heparin-free HD. Unfortunately, despite favorable initial response without any thrombotic episodes, the patient died due to severe sepsis complicated by gastrointestinal hemorrhage.

Topics: Aged; Anticoagulants; Fatal Outcome; Fondaparinux; Heparin; Humans; Kidney Failure, Chronic; Male; Platelet Count; Polysaccharides; Renal Dialysis; Thrombocytopenia

Heparin-induced thrombocytopenia is a reaction associated with the use of this drug. It occurs in up to 3% of patients treated for at least 5 days. Its treatment is to stop the heparin, and according to patient needs, replace it with another anticoagulant. We present a patient who, after a heart transplant, and the need for a ventricular assist device, required anticoagulation. The patient developed heparin-induced thrombocytopenia. Heparin was stopped and anticoagulation was replaced by fondaparinux. The peri-operative complications and the management of the coagulation are described.

Topics: Anticoagulants; Fondaparinux; Heart-Assist Devices; Heparin; Humans; Male; Middle Aged; Polysaccharides; Thrombocytopenia

Heparin-induced thrombocytopenia (HIT) is a potentially life-threatening condition that can develop after exposure to unfractionated or low-molecular-weight heparins. Treatment options appear to be limited in patients on concurrent intermittent hemodialysis. We report the case of an 88-year-old man newly initiated on high-flux hemodialysis who developed HIT and extracorporeal circuit thrombosis after 3 weeks of exposure to unfractionated heparin. Our patient was successfully treated with fondaparinux 2.5 mg subcutaneously three times per week and citrate during dialysis sessions. Antifactor Xa levels were measured on several occasions while receiving fondaparinux.

Topics: Aged, 80 and over; Anticoagulants; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Male; Polysaccharides; Renal Dialysis; Thrombocytopenia; Thrombosis

There is no in vitro data on the comparison of the effects of danaparoid, argatroban and fondaparinux on thrombin generation in patients with heparin-induced thrombocytopenia. It was the study objective to compare the in vitro anticoagulant potential of argatroban, danaparoid and fondaparinux using a thrombin generation assay TGA on a mixture of control platelet-rich plasma (PRP) and HIT patient platelet-poor plasma (PPP). The plasma of seven patients with a clear HIT diagnosed at our institution was selected. Mixtures of donor PRP and patient PPP were incubated with unfractionated heparin 0.2 U.mL⁻¹, argatroban at 600 ng.mL⁻¹, argatroban at 400 ng.mL⁻¹, danaparoid at 0.65 IU.mL⁻¹ and fondaparinux at 1 μg.mL⁻¹. Thrombin generation was assessed by calibrated thrombinography. The percentage of inhibition of the endogenous thrombin potential observed with argatroban at 600 ng.mL⁻¹ was statistically significantly higher compared with those observed with fondaparinux (median: 53.6% vs. 3.9%; p=0.031) but not compared with argatroban at 400 ng.mL⁻¹ and danaparoid. The percentage of inhibition of the thrombin peak observed with argatroban at 600 ng.mL⁻¹ was statistically significantly higher compared with those observed with danaparoid (median: 71.2 vs. 56.8; p=0.031) and fondaparinux (mean: 71.2 vs. 30; p=0.031) but not with argatroban at 400 ng.mL⁻¹. In conclusion, the in vitro effect of argatroban and danaparoid on thrombin generation seems to corroborate the results of clinical studies of these drugs in the treatment of HIT in term of efficiency. Fondaparinux showed a very small effect on thrombin generation evaluated by calibrated thrombinography.

Topics: Aged; Aged, 80 and over; Anticoagulants; Arginine; Blood Platelets; Calibration; Chondroitin Sulfates; Dermatan Sulfate; Female; Fondaparinux; Heparin; Heparitin Sulfate; Humans; Male; Middle Aged; Pipecolic Acids; Plasma; Platelet-Rich Plasma; Polysaccharides; Recombinant Proteins; Sulfonamides; Thrombin; Thrombocytopenia; Time Factors

The pentasaccharide fondaparinux is widely approved for prophylaxis and treatment of thromboembolic diseases and therapy of acute coronary syndrome. It is also used off-label in patients with acute, suspected or antecedent heparin-induced thrombocytopenia (HIT). The aim of this prospective observational cohort study was to document fondaparinux' prescription practice, tolerance and therapy safety in a representative mixed German single-centre patient cohort.. Between 09/2008 - 04/2009, 231 consecutive patients treated with fondaparinux were enrolled. Medical data were obtained from patient's records. The patients were clinically screened for thrombosis (Wells score), sequelae of HIT (4T's score), and bleeding complications (ISTH-criteria) and subjected to further assessment (i.e. sonography, HIT-diagnostics), if necessary. The mortality rate was assessed 30 days after therapy start.. Overall, 153/231 patients had a prophylactic, 74/231 patients a therapeutic, and 4/231 patients a successive prophylactic/therapeutic indication. In 11/231 patients fondaparinux was used due to suspected/antecedent HIT, in 5/231 patients due to a previous cutaneous delayed-type hypersensitivity to heparins. Other indications were rare. Three new/progressive thromboses were detected. No cases of HIT, major bleedings, or fatalities occurred.. Fondaparinux was well tolerated and was safe in prophylaxis and therapy; prescriptions mostly followed the current approval guidelines and were rarely related to HIT-associated indications (<5% of prescriptions), which is in contrast to previous study results in the U.S. (>94% of prescriptions were HIT-associated). A trend towards an individualised fondaparinux use based on the compound's inherent properties and the patients' risk profiles, i.e., antecedent HIT, bone fractures, heparin allergy, was observed.

Topics: Adult; Aged; Anticoagulants; Drug Hypersensitivity; Drug Prescriptions; Female; Fondaparinux; Germany; Hemorrhage; Heparin; Hospitals, University; Humans; Male; Middle Aged; Polysaccharides; Prospective Studies; Risk Assessment; Risk Factors; Thrombocytopenia; Thrombosis; Time Factors; Treatment Outcome

Heparin-induced thrombocytopenia (HIT) is a rare immune-mediated complication associated with unfractionated heparin and to a lesser extent with low-molecular weight heparins. The American College of Chest Physicians recommends treating patients with suspected HIT with a non-heparin product regardless if thrombosis is present. The direct thrombin inhibitors are the preferred agents for the treatment of acute HIT (lepirudin, argatroban [Grade 1C]). Fondaparinux is also suggested as an alternative with a lower level of evidence (Grade 2C). The evidence supporting the use of fondaparinux in the treatment of HIT is limited, but the evidence of fondaparinux causing HIT is even less. We present a case of a patient who developed complications with fondaparinux when used in the acute setting of HIT.

Topics: Female; Fondaparinux; Heparin; Humans; Middle Aged; Polysaccharides; Thrombocytopenia; Treatment Failure

Topics: Aged; Arginine; Female; Fondaparinux; Heparin; Humans; Immunoenzyme Techniques; Inflammation; Pipecolic Acids; Platelet Factor 4; Polysaccharides; Sulfonamides; Syndrome; Thrombocytopenia; Treatment Outcome

Topics: Anticoagulants; Arginine; Factor Xa Inhibitors; Fondaparinux; Heparin; Humans; Pipecolic Acids; Polysaccharides; Sulfonamides; Thrombocytopenia

The treatment and outcomes of heparin-induced thrombocytopenia (HIT) are not well described in neurosurgery patients. This study reviewed the treatment for HIT in subarachnoid hemorrhage (SAH) patients, and compared outcomes in patients with isolated HIT (iHIT) and HIT with thrombotic syndrome (HITTS).. Adult patients with SAH discharged from the University of Illinois Hospital & Health Sciences System from 2006 to 2009 were included if they had at least one positive HIT antibody test. Patients were categorized with either iHIT or HITTS based on documented evidence of thrombosis. The primary outcome was the incidence of new thromboses prior to discharge. Secondary outcomes included the incidence of major bleeding, new thromboses up to 3 months after discharge, or hospice/death. Patients having any secondary outcome were defined as having a "poor treatment-related effect".. A total of 176 patients were screened and 30 patients met inclusion criteria. Eighteen patients (60 %) were categorized with iHIT and 12 (40 %) with HITTS. Twelve patients (67 %) with iHIT received prophylaxis with fondaparinux and nine patients (75 %) with HITTS were treated with argatroban. There were no differences in the primary (11 vs. 25 %, p = 0.364) or secondary outcomes in the iHIT group versus the HITTS group. Patients with iHIT had a 5.5 % incidence of "poor treatment-related effects" compared to a 33.3 % incidence in patients with HITTS (p = 0.024).. SAH patients with iHIT and HITTS did not differ in the incidence of new thromboses, incidence of hemorrhage, or hospice/death. Patients with iHIT had fewer "poor treatment-related effects" than HITTS patients.

Topics: Adult; Aged; Antibodies, Anti-Idiotypic; Anticoagulants; Arginine; Female; Fondaparinux; Heparin; Humans; Immunoglobulin G; Male; Middle Aged; Pipecolic Acids; Platelet Aggregation Inhibitors; Platelet Factor 4; Polysaccharides; Purpura, Thrombotic Thrombocytopenic; Retrospective Studies; Subarachnoid Hemorrhage; Sulfonamides; Thrombocytopenia; Treatment Outcome

Anticoagulation management of a patient complicated by heparin-induced thrombocytopenia is one of the challenging situations in open heart surgery. A 40-year old male receiving warfarin for anticoagulation was admitted to our clinic with a history of heparin-induced thrombocytopenia and a diagnosis of inferior caval thrombosis. He was scheduled for inferior vena cava thrombectomy via the inflow occlusion technique on the beating heart. Warfarin sodium was stopped three days prior to the operation while fondaparinux sodium was begun twice a day. The operation was successfully performed and no postoperative complications were observed.

Topics: Adult; Anticoagulants; Drug Administration Schedule; Drug Substitution; Fondaparinux; Heparin; Humans; Male; Polysaccharides; Thrombectomy; Thrombocytopenia; Treatment Outcome; Vena Cava, Inferior; Venous Thrombosis; Warfarin

Patients with central nervous system (CNS) malignancies have a substantial risk for developing both thrombotic and bleeding disorders. The risk of venous thromboembolism (VTE) is substantially higher in these patients, both in the perioperative period and throughout their disease course. Patients with CNS malignancy harbor a latent hypercoagulability, which predisposes to VTE, as do postoperative immobility, hemiparesis, and other factors. The management of VTE in these patients is complex, given the significant morbidity and mortality associated with intratumoral hemorrhage. In the past, the perceived risk of intracranial hemorrhage limited the use of anticoagulation for the management of VTE with many favoring nonpharmacologic methods for prophylaxis and treatment. Inferior vena cava (IVC) filters have since lost favor at many centers given significant complications, which appear to be more frequent in patients with CNS malignancy. Recent studies have demonstrated safe and efficacious use of anticoagulation in these patients with a low incidence of intracranial hemorrhage. Treatment of established VTE is now recommended in this population with many centers favoring low-molecular-weight heparin (LMWH) versus oral warfarin for short- or long-term treatment. We advocate a multimodality approach utilizing compression stockings, intermittent compression devices, and heparin in the perioperative setting as the best proven method to reduce the risk of VTE. In the absence of a strict contraindication to systemic anticoagulation, such as previous intracranial hemorrhage or profound thrombocytopenia, we recommend LMWH in patients with newly diagnosed VTE and a CNS malignancy.

Topics: Antibodies, Monoclonal, Humanized; Anticoagulants; Arginine; Bevacizumab; Central Nervous System Neoplasms; Fondaparinux; Glioblastoma; Glioma; Hemorrhage; Heparin, Low-Molecular-Weight; Hirudins; Humans; Pipecolic Acids; Polysaccharides; Postoperative Complications; Pulmonary Embolism; Recombinant Proteins; Sulfonamides; Thrombocytopenia; Vena Cava Filters; Venous Thromboembolism; Venous Thrombosis; Warfarin

Heparin-induced thrombocytopenia (HIT) is a well described side effect of heparin therapy. A 12-year-old boy developed deep-vein thrombosis. Risk factors for initial thrombosis are antiphospholipid syndrome and heterozygous mutation for prothrombin G20210A. Anticoagulant therapy with warfarin for 12 months was effective, but discontinuation of warfarin after 12 months resulted in recurrence of thrombosis. Unfractionated heparin (UFH) was initiated during the acute period, but heparin-induced thrombocytopenia developed. Transition from UFH to fondaparinux resulted in successful anticoagulation for a period of platelet recovery. We report a case of HIT developing with a background of prothrombotic genetic risk factors and antiphospholipid syndrome. This case study highlights several difficulties in pediatric HIT cases.

Topics: Anticoagulants; Antiphospholipid Syndrome; Child; Drug Substitution; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Male; Mutation; Polysaccharides; Prothrombin; Risk Factors; Thrombocytopenia; Venous Thrombosis; Warfarin

Heparin-induced thrombocytopenia (HIT) is a serious complication of heparin administration. As HIT may occur during the thrombolysis of prosthetic heart valve thrombosis (PVHT) due to the administration of heparin, this entity should be considered during and after sessions of this regimen. The study aim was to investigate the development, diagnosis, and management of HIT during thrombolytic therapy (TT) of PHVT.. A diagnosis of HIT was made on a clinical basis and laboratory confirmation based on a particle immunofiltration assay. Serial transthoracic echocardiography and two-dimensional transesophageal echocardiography were used to detect thrombus morphology and hemodynamic changes before and after TT sessions in 214 patients.. Four patients (1.9%) who underwent TT for PHVT were diagnosed with HIT. The mean period of onset of HIT after heparin exposure was 8.7 +/- 3.9 days, while mean platelet levels before and after heparin infusion were 308,000/mm3 and 77,250/mm3, respectively. Fondaparinux was employed as bridging therapy in three patients. TT resulted in a successful outcome in two patients, while two other patients underwent surgery for increased valve gradients (due to progression of obstructive PHVT during TT in one case, and obstructive PHVT resulting in a cerebrovascular accident in the other case).. Details are presented of the development of HIT during TT for PHVT, which resulted in an increased thrombus size immediately after successful TT. Fondaparinux may be considered as an effective bridging treatment in this regimen.

Topics: Adult; Anticoagulants; Aortic Valve; Fondaparinux; Heart Valve Diseases; Heart Valve Prosthesis; Heparin; Humans; Male; Middle Aged; Mitral Valve; Polysaccharides; Thrombocytopenia; Thrombolytic Therapy; Thrombosis

A 69-year-old woman presented to the emergency department with sudden onset of dyspnea. She reported bilateral total knee surgery 12 days prior for gonarthrosis. The patient was recommended low-molecular-weight heparin (LMWH) 0.4 cc (4 milliliter) twice a day. On evaluation, severe thrombocytopenia was detected. An echocardiogram was performed because of her dyspnea, which revealed right ventricular dilatation and hypokinesis. Due to suspicion of a pulmonary embolism (PE), a pulmonary computed tomography (CT) was performed, which revealed bilateral massive PE. This event occurred while the patient was receiving LMWH for prophylaxis of PE. Due to the presence of severe thrombocytopenia, fondaparinux and immunoglobulin were initiated. Her platelet levels improved significantly and she was discharged on warfarin.

Topics: Anticoagulants; Arthroplasty, Replacement, Knee; Echocardiography; Female; Fondaparinux; Heparin; Humans; Immunoglobulin G; Polysaccharides; Pulmonary Embolism; Thrombocytopenia; Tomography, X-Ray Computed

Heparin-induced thrombocytopenia (HIT) related to fondaparinux has been rarely reported, although the ability of fondaparinux to cross-react with heparin antibodies has been often a subject of debate. A patient previously exposed to unfractionated heparin and low-molecular-weight heparin (LMWH) was diagnosed with HIT. During treatment with fondaparinux for 5 consecutive days, his thrombocytopenia significantly deteriorated. A functional platelet activation test in vitro showed clear platelet activation after serum exposure with fondaparinux. After discontinuation of fondaparinux, the platelet count was rapidly reestablished. Fondaparinux cross-reacted with heparin antibodies in this case of HIT, resulting in a deterioration of thrombocytopenia. The implication of this drug in HIT was observed clinically and demonstrated in vitro using a platelet activation test.

Topics: Antibodies; Anticoagulants; Cross Reactions; Fondaparinux; Heparin; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Polysaccharides; Thrombocytopenia

We present a case of a 54 years old female patient after anterior wall left ventricular myocardial infarction in 2005 who underwent coronary artery bypass graft (CABG) surgery requiring cannulation of the right internal jugular vein (IJV). She was admitted to a Department of Pulmonary Diseases with left bronchopneumonia (BPN) following 7 day treatment, with hemoptysis, dyspnoea and fevers. Duplex ultrasound (DUS) was used to diagnose flapping thrombus in the right IJV, severe thrombocytopenia and, in addition, progressing multiple infiltrates on X-ray a few days later. We empirically adjusted the treatment initiated in primary care and observed deterioration of the severe thrombocytopenia during treatment with low molecular weight heparine. We diagnosed heparin-induced thrombocytopenia (HIT) and, even though this indication was not included in our drug formulary, we initiated treatment with Arixtra (fondaparinux) 2.5 mg s.c. daily. Intensive conservative treatment was associated with significant clinical and laboratory improvement of the condition, significant regression of the IJV thrombus as well as the finding on X-ray. The final effective antibiotic treatment lasted 20 (amoxicillin + clavulanate) and 10 (clindamycin) days, respectively. Treatment with Arixtra (fondaparinux) continued in primary care and lasted a total of 65 days until normal thrombocyte levels were achieved, with gradual transition to oral anticoagulation treatment. The patient was discharged to primary care on the 23rd day of hospitalization when she was stabilized, a febrile and her cardiopulmonary functions were compensated. We did not identify any case of treatment of jugular thrombosis and concurrent HIT with fondaparin anywhere in the international literature.

Topics: Anticoagulants; Bronchopneumonia; Catheterization, Central Venous; Coronary Artery Bypass; Female; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Jugular Veins; Middle Aged; Polysaccharides; Thrombocytopenia; Thrombosis

Some patients with acute VTE who may previously have been exposed to heparin products have unrecognized antibodies implicated in heparin-induced thrombocytopenia (HIT). Antibody prevalence and patient consequences upon exposure to heparin, low-molecular-weight heparin, and fondaparinux are uncertain.. In this secondary analysis, we tested patients in the Matisse VTE studies at study entry for heparin-dependent antibodies and further tested patients with enzyme-linked immunosorbent assay (ELISA)-positive results for platelet-activating antibodies. We compared the risk of HIT (> 50% fall in platelet count, heparin-dependent antibodies, no contradicting features) between patients treated with heparin (either unfractionated or low molecular weight [enoxaparin]) vs those who received fondaparinux. Comparison groups for thrombocytopenia occurrence comprised patients with ELISA-positive, platelet-activating, antibody-positive results; ELISA-positive, but platelet-activating antibody-negative results; and randomly selected antibody-negative results.. A total of 127 of 3,994 patients (3.2%) had ELISA-positive results at baseline, but only 14 (0.4%; 95% CI, 0.2%-0.6%) had platelet-activating antibodies. Among these 14, four treated with unfractionated or low-molecular-weight heparin developed HIT compared with zero of 10 fondaparinux-treated patients (OR, 95; 95% CI, 8-1,123; P < .001). This frequency (four of four, 100%) significantly differed from that of both heparin-treated patients whose results were ELISA positive but platelet-activating antibody negative and from heparin-treated antibody-negative control subjects (zero of 15 and zero of 27, respectively; P < .001 for both).. Of patients with VTE, 0.4% had pathologic platelet-activating heparin-dependent antibodies rather than the 3.2% detected by the recommended cutoff of the commercial ELISA. Among study patients with acute VTE who had platelet-activating antibodies, treatment with fondaparinux reduced the risk of precipitating rapid-onset HIT.

Topics: Acute Disease; Antibodies; Anticoagulants; Enzyme-Linked Immunosorbent Assay; Fondaparinux; Heparin; Heparin, Low-Molecular-Weight; Platelet Factor 4; Polysaccharides; Thrombocytopenia; Venous Thromboembolism

A serious complication of heparin treatment, heparin-induced thrombocytopenia (HIT) is rarely observed in pregnant women. Drug therapy during pregnancy should always be chosen to minimize fetal risk. The management of HIT in pregnancy represents a medical challenge. Unlike heparins, the anticoagulants used in patients with HIT do cross the placenta, with unknown fetal effects.. We present a case of a 24-year-old female presenting for care at 34 weeks of gestation with acute pulmonary embolism treated initially with unfractionated heparin (UFH) and low molecular weight heparin (LMWH), who developed HIT. She was then successfully treated with fondaparinux.. To the best of our knowledge, this is one of the first case reports describing a successful use of fondaparinux in the treatment of HIT in a third-trimester pregnant woman, providing a novel approach for this subset of patients.

Topics: Female; Fondaparinux; Heparin; Humans; Polysaccharides; Pregnancy; Pulmonary Embolism; Thrombocytopenia; Ultrasonography; Young Adult

Heparin induced thrombocytopenia is a serious complication of heparin therapy that has a high levels of morbidity and mortality due to thrombotic complications. Heparin induced thrombocytopenia usually develops between days 5 and 14 (inclusive) following initiation of heparin. When heparin induced thrombocytopenia is suspected, heparin should be discontinued and treatment with a direct thrombin inhibitor should be initiated. Heparin induced thrombocytopenia occurs more frequently with unfractionated heparin than with low molecular weight heparin. In this manuscript, we presented a case diagnosis with heparin induced thrombocytopenia who was given low molecular weight heparin for prophylaxis. We tried to make an overview of new treatment choices along with current literature.

Topics: Aged, 80 and over; Anticoagulants; Female; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Polysaccharides; Thrombocytopenia; Treatment Outcome

Fondaparinux is theoretically an attractive agent for the treatment of immune heparin-induced thrombocytopenia (HIT), a prothrombotic disorder caused by platelet-activating anti-platelet factor 4/heparin antibodies. Although reports of the use of fondaparinux for this indication have thus far been favorable, the diagnosis of HIT in most cases was not based on definitive laboratory confirmation of heparin-dependent, platelet-activating antibodies.. To report thrombotic and major bleeding outcomes with fondaparinux in patients with a high likelihood of having acute HIT based on clinical features and a positive result in the confirmatory platelet serotonin-release assay (SRA), a sensitive and specific test for platelet-activating HIT antibodies.. We reviewed consecutive eligible patients with SRA-positive HIT (mean peak serotonin release, 91% [normal, < 20%]; mean IgG-specific PF4/heparin enzyme immunoassay result, 2.53 optical density units [normal, < 0.45 units]) in one medical center over a 30-month period who received fondaparinux for anticoagulation during acute HIT (platelet count, < 150 × 10(9) L(-1)). Where available, plasma samples were used to measure thrombin-antithrombin (TAT) complex levels.. Sixteen patients with SRA-positive HIT received fondaparinux: 14 surgical (11 after cardiac surgery; three after vascular surgery) and two medical (acute stroke). Fifty-six per cent of patients had HIT-associated thrombosis at the time of diagnosis. No patient developed new, recurrent or progressive thrombosis; one patient developed a major bleed (calf hematoma). One patient judged to have irreversible tissue necrosis before receiving fondaparinux therapy ultimately required limb amputation. TAT complex levels were reduced within 24 h of starting fondaparinux, and 13 of 13 patients were successfully switched to warfarin.. Fondaparinux shows promise for the treatment of patients with SRA-positive acute HIT.

Topics: Aged; Aged, 80 and over; Anticoagulants; Female; Fondaparinux; Heparin; History, 17th Century; Humans; Male; Polysaccharides; Serotonin; Thrombocytopenia

Topics: Anticoagulants; Blood Chemical Analysis; Female; Fondaparinux; Heparin; Humans; Immunoenzyme Techniques; Male; Platelet Factor 4; Polysaccharides; Serotonin; Thrombocytopenia

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

Patients with heparin-induced thrombocytopenia (HIT) require anticoagulation with alternative immediate acting anticoagulants such as lepirudin. Lepirudin may generate antibodies that increase risk of bleeding. Fondaparinux, on the other hand, is structurally too short to induce antibody formation, and therefore, it could be a useful agent for the treatment of HIT.. University teaching hospital in Saudi Arabia.. A retrospective study was conducted at a university teaching hospital on HIT cases which were diagnosed between January 2006 and December 2009. The diagnosis was based on clinical findings consistent with HIT presentation (i.e., a confirmed fall in the platelet count to <100 × 10(9)/L or a 50% reduction from baseline, four or more days after starting heparin therapy, with exclusion of other causes of thrombocytopenia) and a positive immunoassay test.. Twelve HIT patients (6 males and 6 females) met the inclusion criteria. Fondaparinux was given to five subjects while lepirudin was utilized in seven patients. The median age was 65 years in the fondaparinux group, and 55 years in the lepirudin group. Nine patients (75%) were on heparin infusion, while three (25%) were on subcutaneous heparin or heparin flushes prior to HIT diagnosis. Frequencies of concomitant chronic diseases as well as other treatments including antiplatelets were similar between the two groups (P > 0.05). The time for platelets recovery was similar between the two groups (Median = 4 days for both arms; P = 0.736). Furthermore, fondaparinux therapy was associated with bigger area under platelet count compared to lepirudin (8,179 vs. 5,768 cell × 10(9)*day/L; P = 0.0303), and higher nadir counts (89 vs. 44 cell × 10(9)/L; P = 0.061).. The current study suggests that fondaparinux is a potential alternative treatment for HIT. Further larger studies are needed to confirm our findings.

Topics: Aged; Anticoagulants; Female; Fibrinolytic Agents; Fondaparinux; Heparin; Hirudins; Hospitals, University; Humans; Male; Middle Aged; Platelet Count; Polysaccharides; Recombinant Proteins; Retrospective Studies; Saudi Arabia; Thrombocytopenia; Treatment Outcome

Heparin-induced thrombocytopenia (HIT) occurs in 1 to 3% of patients after cardiac surgery. In patients with suspected or confirmed HIT, the standard of care is withheld of heparin, and an alternative, non-heparin anticoagulant substituted. An established fact is that currently only direct thrombin inhibitors (lepirudin, bivalirudin and argatroban) and heparinoids like danaparoid are approved for alternative anticoagulation in HIT patients. Herein, we report the case of a patient who developed HIT after coronary artery bypass grafting (CABG) and who was successfully treated by the factor Xa inhibitor fondaparinux. Danaparoid is our first line alternative anticoagulant to treat HIT patients. Normally the recovery from thrombocytopenia began within 24 h. In the present patient, however, platelet counts continued to fall for 3 more days. Discontinuation of danaparoid and anticoagulation with fondaparinux clearly improved platelet counts which normalized. The present patient has been treated for 26 consecutive days, and we have not observed any subsequent fall in platelet counts and any further bleeding or thrombotic complications.

Topics: Anticoagulants; Coronary Artery Bypass; Coronary Artery Disease; Diabetes Mellitus, Type 1; Drug Therapy, Combination; Fondaparinux; Heparin; Humans; Male; Middle Aged; Platelet Count; Polysaccharides; Thrombocytopenia; Treatment Outcome

Unfractionated heparin and low-molecular-weight heparin are currently the anticoagulants of choice for the prevention of recurrent thromboembolic disease during pregnancy. However, heparin-induced thrombocytopenia contraindicates the use of unfractionated heparin and low-molecular-weight heparin. We describe a patient who was admitted to our hospital with deep vein thrombosis at 18 weeks of gestation and who developed heparin-induced thrombocytopenia during her antenatal care. Therapeutic anticoagulation was initially achieved with argatroban, then changed to fondaparinux. During early labor, fondaparinux was discontinued and intravenous argatroban was substituted. Argatroban was discontinued during transition to active labor. After return of a normal partial thromboplastin time, combined spinal-epidural analgesia was induced for routine completion of labor and vaginal delivery. We discuss the decisions made in the maintenance of this patient's anticoagulation during the peripartum period as well as timing of her neuraxial labor analgesia.

Topics: Adult; Anesthesia, Epidural; Anesthesia, Obstetrical; Anesthesia, Spinal; Anticoagulants; Arginine; Female; Fondaparinux; Heparin; Humans; Pipecolic Acids; Platelet Aggregation Inhibitors; Polysaccharides; Pregnancy; Sulfonamides; Thrombocytopenia

Topics: Anticoagulants; Cardiac Surgical Procedures; Cohort Studies; Fondaparinux; Heparin; Humans; Polysaccharides; Retrospective Studies; Thrombocytopenia

Heparin-induced thrombocytopenia (HIT) is a life-threatening immune response to heparin that is associated with a high risk of thromboembolic complications. The syndrome is caused by antibodies that are reactive against complexes of platelet factor 4/heparin (PF4/H). For patients with HIT, the discontinuation of heparin alone is not sufficient and the diagnosis necessitates the administration of an alternative anticoagulant. Fondaparinux is a synthetic pentasaccharide that binds to antithrombin and potentiates inhibition of factor Xa. Data have shown that fondaparinux is structurally too short to induce an antibody response and could be a useful agent to treat HIT. In our hospital, we retrospectively analyzed the use of fondaparinux in the treatment of 24 patients with acute HIT during unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH) administration and compared the results to a similar population of 20 patients who were treated with lepirudin. The treated patients had a complete platelet count recovery, and none experienced a new thromboembolic complication or major bleeding. The development of limb gangrene (2 patients who received lepirudin and 1 who received fondaparinux) likely resulted from a delay in diagnosis and treatment initiation. Our data suggest that fondaparinux may be considered a safe and an effective alternative treatment in HIT complicated with or without thrombosis.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Female; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Polysaccharides; Retrospective Studies; Thrombocytopenia; Young Adult

Essential thrombocythemia is a hematological disorder characterized by clonal hemopoiesis in the bone marrow and increased number of circulating platelets. It is usually discovered accidentally at the time of routine blood examinations or can become clinically evident with either thrombotic or hemorrhagic complications. In the present article, we describe the case of a 66-year-old woman with pneumonia due to Pneumocystis carinii, who experienced deep vein thrombosis and pulmonary embolism during hospitalization with a subsequent heparin-induced thrombocytopenia. Bone marrow examination performed after clinical improvement revealed the patient to be affected by essential thrombocythemia.

Topics: Aged; Anticoagulants; Female; Fondaparinux; Heparin; Humans; Incidental Findings; Platelet Factor 4; Pneumonia, Pneumocystis; Polysaccharides; Pulmonary Embolism; Thrombocythemia, Essential; Thrombocytopenia; Thrombophlebitis; Warfarin

Heparin-induced thrombocytopenia is an antibody-mediated disorder exhibiting variable frequency in different clinical settings. Antibodies recognize PF4/heparin complexes formed at optimal stoichiometric molar ratios.. To identify clinical factors influencing risk of anti-PF4/heparin immunization.. We performed observational studies and exploratory analyses of the frequency of anti-PF4/heparin antibody formation in 6324 patients who received enoxaparin or fondaparinux in four randomized controlled trials of postorthopedic surgery thromboprophylaxis. Variables included surgery type (knee vs. hip), timing of first anticoagulant dose (pre- vs. postsurgery), circumstances of surgery (elective vs. hip fracture), anticoagulant (enoxaparin vs. fondaparinux) and body-mass index (BMI). We applied a stoichiometry-based model that predicts immunization risk based on expected differences in PF4/anticoagulant ratios in different settings, and specifically used this model to predict the effect of increasing BMI quartiles upon relative risk (RR) of immunization for fondaparinux vs. enoxaparin.. Anti-PF4/heparin immunization was more frequent after knee vs. hip surgery (particularly for enoxaparin), and when enoxaparin was given post- rather than pre-elective surgery; however, the opposite occurred with hip fracture surgery, that is, antibody formation was more frequent when enoxaparin or fondaparinux was given presurgery. The RR of immunization for fondaparinux vs. enoxaparin decreased significantly for increasing BMI quartiles, an effect predominantly because of increasing immunization with enoxaparin at increasing BMI quartiles.. Several non-drug factors--including type and circumstances of surgery, timing of first anticoagulant dose and BMI--influence risk of anti-PF4/heparin antibody formation, consistent with a stoichiometry-based immunization model of PF4 and anticoagulant ratios occurring during the early peri-operative period.

Topics: Antibodies; Anticoagulants; Body Mass Index; Drug Administration Schedule; Enoxaparin; Evidence-Based Medicine; Fondaparinux; Humans; Models, Statistical; Orthopedic Procedures; Platelet Factor 4; Polysaccharides; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Thrombocytopenia; Thrombosis

Topics: Anticoagulants; Female; Fondaparinux; Hematocrit; Heparin; Hirudins; Humans; Middle Aged; Platelet Count; Polysaccharides; Recombinant Proteins; Thrombocytopenia; Ultrasonography; Venous Thrombosis

Topics: Anticoagulants; Diagnosis, Differential; Fondaparinux; Humans; Polysaccharides; Thrombocytopenia

The successful use of fondaparinux in a hemodialysis patient with heparin-induced thrombocytopenia type II (HIT II) is reported.. An 85-year-old, 68-kg Caucasian woman came to the emergency department with shortness of breath and exertional chest pain radiating to the neck. Testing revealed non-ST-segment elevation myocardial infarction, severe coronary artery disease, mitral regurgitation, left ventricular dysfunction, an ejection fraction of 25-30%, and pulmonary arterial hypertension. I.V. unfractionated heparin was given for therapeutic anticoagulation per hospital protocol and discontinued on hospital day 3 before mitral valve repair and coronary bypass procedure. Postoperatively unfractionated heparin and low-molecular-weight heparin were avoided because of a reduction in the platelet count and suspicion of HIT. Instead, the patient was placed on sequential compression devices in addition to aspirin for prophylaxis of deep venous thrombosis. By postoperative day 6, the patient's platelet count dropped 76% from baseline, and the patient was found to have heparin-dependent platelet factor 4 antibodies. Argatroban infusion was initiated but discontinued after 2 days due to bleeding. Fondaparinux was ordered for anticoagulation therapy. By hospital day 8, the patient developed renal insufficiency requiring hemodialysis and adjustment of the fondaparinux regimen. During the 30-day course of fondaparinux, the patient did not experience thromboembolic events or bleeding and did not require transfusions. There was no clotting within hemodialysis membranes, and her hepatic function improved by the time of her discharge.. Fondaparinux was used in a hemodialysis patient with HIT II without the development of thromboembolic, hemodialysis-clotting, thrombocytopenic, or hemorrhagic complications. The patient's platelet count remained in the normal range during the 30-day course of fondaparinux.

Topics: Aged, 80 and over; Anticoagulants; Arginine; Coronary Artery Bypass; Female; Fondaparinux; Heparin; Humans; Mitral Valve; Pipecolic Acids; Platelet Aggregation Inhibitors; Platelet Count; Polysaccharides; Renal Dialysis; Sulfonamides; Thrombocytopenia; Venous Thrombosis

The development of heparin-induced thrombocytopenia (HIT) is an antibody-mediated clinicopathologic syndrome. The resultant thrombocytopenia and thrombosis can be severe and life-threatening. Fondaparinux is a parenteral factor Xa inhibitor used for venous thromboembolism prevention and treatment. Fondaparinux has minimal affinity for platelet factor 4, making it an alternative agent to unfractionated heparin (UFH) and low-molecular weight heparin (LMWH) and a plausible consideration for patients with a history of HIT. The use of fondaparinux in patients with mechanical heart valve replacement and a history of HIT has never been discussed in the literature. We report on the case of a patient with a mechanical aortic heart valve replacement and a history of HIT who was successfully bridged postoperatively with fondaparinux. While there is currently no literature to support the use of fondaparinux in patients with mechanical heart valves, this drug may offer an option for management of such patients who cannot use heparin products. However, further clinical investigations are warranted to confirm both the safety and efficacy of this agent in the mechanical heart valve population.

Topics: Adult; Anticoagulants; Aortic Valve; Female; Fondaparinux; Heart Valve Prosthesis Implantation; Heparin; Humans; Polysaccharides; Postoperative Care; Therapeutics; Thrombocytopenia

Topics: Aged; Anticoagulants; Coronary Artery Bypass, Off-Pump; Fondaparinux; Heparin; Humans; Male; Polysaccharides; Thrombocytopenia; Time Factors; Treatment Outcome

Several alternative anticoagulation drugs are now available for patients with heparin induced thrombocytopenia type II (HIT II). However, their indication is not yet reaching a consensus. Moreover, some of them have not yet their marketing approval. The importantly use in hemodialyzed patients should be taken with caution since most of them are excreted by the kidneys. The use of fondaparinux, which exerts high anti-Xa activity, is not well documented. We report here our experience on the use of fondaparinux in an hemodialyzed patient with HIT II, not only as anticoagulation during hemodialysis sessions but also as interdialytic anticoagulation locking solution of her central venous catheter. The use of fondaparinux seems to us simple enough (even if its ready-for-use syringe requires adjustments to deliver the required doses) and its efficacy, safety and economic cost lead us to think that it is an indication of choice for an alternative anticoagulation in hemodialyzed patients with HIT II. Control prospective trials should be performed in order to confirm the preliminary favourable data and to support the proposal of marketing approval in this indication.

Topics: Female; Fondaparinux; Heparin; Humans; Middle Aged; Polysaccharides; Renal Dialysis; Thrombocytopenia

Cardiopulmonary bypass during pregnancy is associated with a high fetal and maternal mortality. We report a successful pulmonary embolectomy in a woman at the 27th week of pregnancy; we performed surgical pulmonary embolectomy under cardiopulmonary bypass to restore adequate hemodynamic stability and to relieve right ventricle strain. We discuss the decision made for the preferred anticoagulation drug in the setting of heparin-induced thrombocytopenia in the gravida. The pregnancy was carried to term and she delivered a healthy boy at 38 weeks of gestation.

Topics: Adult; Anticoagulants; Cardiopulmonary Bypass; Echocardiography, Transesophageal; Embolectomy; Enoxaparin; Female; Fondaparinux; Heart Arrest, Induced; Heparin; Humans; Infant, Newborn; Live Birth; Male; Polysaccharides; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy Trimester, Second; Pulmonary Embolism; Thrombocytopenia; Tirofiban; Treatment Outcome; Tyrosine; Venous Thrombosis; Warfarin

Topics: Aged; Antibodies; Anticoagulants; Arthroplasty, Replacement, Knee; Fondaparinux; Heparin; Humans; Infarction, Middle Cerebral Artery; Male; Platelet Factor 4; Polysaccharides; Stroke; Thrombocytopenia; Thrombosis

Topics: Anticoagulants; Cardiopulmonary Bypass; Embolectomy; Enoxaparin; Female; Fondaparinux; Heart Arrest, Induced; Heparin; Humans; Polysaccharides; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy Trimester, Second; Pulmonary Embolism; Risk Assessment; Thrombocytopenia; Tirofiban; Treatment Outcome; Tyrosine; Ultrasonography; Venous Thrombosis; Warfarin

An 11-year-old female developed heparin induced thrombocytopenia (HIT) with thrombosis during therapy for lower extremity deep vein thrombosis and pulmonary embolism. Transition from bivalirudin, a direct thrombin inhibitor (DTI), to warfarin resulted in extensive re-thrombosis, and fondaparinux therapy similarly failed. She was then treated with argatroban, and transitioned successfully to warfarin after 9 weeks. The risk of re-thrombosis was ultimately reduced by allowing time for the thrombogenic potential to abate. The argatroban/warfarin transition was monitored with chromogenic factor X levels. This case highlights several difficult problems in pediatric thrombosis.

Topics: Anticoagulants; Child; Female; Fondaparinux; Heparin; Humans; Polysaccharides; Thrombocytopenia; Thrombosis; Warfarin

Fondaparinux is an antithrombotic agent with unique properties that may offer benefit to patients beyond the current approved indications. To explore the off-label use versus approved use of fondaparinux, we initiated a single-center registry of fondaparinux use. During the 25-month study period, 219 patients were prescribed fondaparinux: 157 (71.7%) for prophylaxis and 62 (28.3%) patients for the treatment of thrombosis. When fondaparinux was used for prophylaxis in our registry, 94% of patients had documentation of heparin-induced thrombocytopenia (HIT). Fondaparinux warrants further evaluation in patients with HIT or suspected HIT. In the meantime, its off-label use may exceed its use for FDA-approved indications.

Topics: Adult; Aged; Drug Prescriptions; Female; Fibrinolytic Agents; Fondaparinux; Heparin; Hospitals; Humans; Male; Middle Aged; Orthopedic Procedures; Perioperative Care; Polysaccharides; Pulmonary Embolism; Registries; Risk Factors; Thrombocytopenia; Treatment Outcome; Venous Thromboembolism; Venous Thrombosis

Topics: Anticoagulants; Fondaparinux; Humans; Polysaccharides; Thrombocytopenia; Venous Thromboembolism

Heparin is the most commonly used anticoagulant drug for prevention and treatment of thromboembolic diseases. Heparin-induced thrombocytopenia (HIT) is a well-known and potentially fatal side-effect of heparin therapy. HIT type 1 (HIT-1) is transient and relatively common; it usually develops within 1-7 days of initial heparin exposure. Type 2 HIT (HIT-2) is more severe and is associated with thrombocytopenia and thrombosis. HIT-2 usually develops 5 or more days after initial heparin exposure. It is an immune-mediated disorder that is presumably caused by development of platelet activating antibody against platelet factor 4 (PF4)/heparin complex. Fondaparinux (Arixtra) is a fast-acting selective inhibitor of factor Xa believed to be non-reactive to HIT sera and therefore may be used as prophylaxis for thrombosis in patients with a history of HIT-1 or HIT-2. Development of HIT-2 in patients currently taking fondaparinux prophylaxis is rare. Here we present a fatal case of delayed-onset HIT-2 (1 year after heparin exposure) manifesting while on fondaparinux prophylaxis.

Topics: Aged; Anticoagulants; Fatal Outcome; Fondaparinux; Heparin; Humans; Male; Polysaccharides; Thrombocytopenia; Thrombosis

This chapter describes the pharmacology of approved parenteral anticoagulants, including the indirect anticoagulants, unfractionated heparin (UFH), low-molecular-weight heparins (LMWHs), fondaparinux, and danaparoid as well as the direct thrombin inhibitors hirudin, bivalirudin, and argatroban. UFH is a heterogeneous mixture of glycosaminoglycans that bind to antithrombin via a unique pentasaccharide sequence and catalyze the inactivation of thrombin factor Xa and other clotting factors. Heparin also binds to cells and other plasma proteins, endowing it with unpredictable pharmacokinetic and pharmacodynamic properties, and can lead to nonhemorrhagic side effects, such as heparin-induced thrombocytopenia (HIT) and osteoporosis. LMWHs have greater inhibitory activity against factor Xa than thrombin and exhibit less binding to cells and proteins than heparin. Consequently, LMWH preparations have more predictable pharmacokinetic and pharmacodynamic properties, have a longer half-life than heparin, and have a lower risk of nonhemorrhagic side effects. LMWHs can be administered once or twice daily by subcutaneous injection, without anticoagulant monitoring. Based on their greater convenience, LMWHs have replaced UFH for many clinical indications. Fondaparinux, a synthetic pentasaccharide, catalyzes the inhibition of factor Xa, but not thrombin, in an antithrombin-dependent fashion. Fondaparinux binds only to antithrombin; therefore, HIT and osteoporosis are unlikely to occur. Fondaparinux has excellent bioavailability when administered subcutaneously, has a longer half-life than LMWHs, and is given once daily by subcutaneous injection in fixed doses, without anticoagulant monitoring. Three parenteral direct thrombin inhibitors and danaparoid are approved as alternatives to heparin in HIT patients.

Topics: Anticoagulants; Arginine; Biological Availability; Chondroitin Sulfates; Dermatan Sulfate; Fondaparinux; Heparin; Heparin, Low-Molecular-Weight; Heparitin Sulfate; Hirudins; Humans; Infusions, Parenteral; Injections, Subcutaneous; Peptide Fragments; Pipecolic Acids; Polysaccharides; Recombinant Proteins; Sulfonamides; Thrombocytopenia

Topics: Antibodies; Anticoagulants; Fondaparinux; Heparin; Humans; Platelet Count; Platelet Factor 4; Polysaccharides; Thrombocytopenia; Venous Thrombosis

Rivaroxaban is an oral, direct activated Factor Xa (FXa) inhibitor in advanced clinical development for the prevention and treatment of thromboembolic disorders. Currently available anticoagulants include unfractionated heparin (UFH) and low molecular weight heparins (LMWHs); however, their use can be restricted by heparin-induced thrombocytopenia (HIT). HIT is usually caused by the production of antibodies to a complex of heparin and platelet factor-4 (PF4). This study was performed to evaluate, in vitro, the potential of rivaroxaban as an anticoagulant for the management of patients with HIT. UFH, the LMWH enoxaparin, fondaparinux and the direct thrombin inhibitor argatroban were tested to enable comparative analyses. Rivaroxaban did not cause platelet activation or aggregation in the presence of HIT antibodies, unlike UFH and enoxaparin, suggesting that rivaroxaban does not cross-react with HIT antibodies. Furthermore, rivaroxaban did not cause the release of PF4 from platelets and did not interact with PF4, unlike UFH and enoxaparin. These findings suggest that rivaroxaban may be a suitable anticoagulant for the management of patients with HIT.

Topics: Analysis of Variance; Anticoagulants; Antithrombin III; Arginine; Autoantibodies; Enoxaparin; Flow Cytometry; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Morpholines; Pipecolic Acids; Platelet Activation; Platelet Aggregation; Platelet Factor 4; Polysaccharides; Rivaroxaban; Sulfonamides; Thiophenes; Thrombocytopenia

The risk of thromboembolism is increased in inflammatory bowel disease and its symptoms may be overlooked. Furthermore, its treatment can be complex and is not without complications. We describe a case of an adolescent boy who developed a cerebral sinus venous thrombosis during a relapse of his ulcerative colitis and who, while on treatment with heparin, developed heparin-induced thrombocytopenia (HIT). The treatment was then switched to fondaparinux, a synthetic and selective inhibitor of activated factor X.

Topics: Adolescent; Colitis, Ulcerative; Fondaparinux; Heparin; Humans; Intracranial Thrombosis; Male; Polysaccharides; Risk Factors; Thrombocytopenia; Venous Thrombosis

Heparin-induced thrombocytopenia (HIT) is a prothrombotic condition caused by platelet-activating antibodies that react with platelet factor 4 (PF4)/heparin complexes. Delayed-onset HIT occurs after heparin is stopped. Fondaparinux, a synthetic pentasaccharide, is thought to be a safe alternative anticoagulant in HIT. We describe a patient with delayed-onset HIT triggered by low-molecular-weight heparin (LMWH) which occurred during fondaparinux prophylaxis and which was complicated by microangiopathic hemolytic anemia. Patient serum contained high-titer anti-PF4/heparin antibodies demonstrating heparin-dependent platelet activation with serial dilutions. Confirmed delayed-onset HIT with LMWH has not been previously reported. Low dose fondaparinux does not necessarily prevent thrombotic complications of HIT.

Topics: Anticoagulants; Autoantibodies; Blood Platelets; Female; Fibrinolytic Agents; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Middle Aged; Platelet Factor 4; Polysaccharides; Thrombocytopenia

Treatment of heparin-induced thrombocytopenia (HIT), a disorder in which anti-platelet factor 4 (PF4)-heparin antibodies cause platelet activation and hypercoagulability, requires alternative (non-heparin) anticoagulation. Treatment options include direct thrombin inhibitors [lepirudin and argatroban (approved), and bivalirudin], danaparoid (approved) (mixture of anticoagulant glycosaminoglycans), or fondaparinux (synthetic heparin-mimicking pentasaccharide). PF4-heparin complexes form at optimal stoichiometric ratios.. To compare the effects of these various non-heparin anticoagulants in disrupting the formation of PF4-heparin complexes, and PF4-containing immune complexes.. Sera were obtained from patients with serologically confirmed HIT. The effects of the alternative anticoagulants on PF4 and PF4-heparin complex interactions with platelets, as well as HIT antibody binding and platelet activation, were investigated.. Danaparoid at very low concentrations increased PF4 binding to platelets. In therapeutic concentrations, however, it decreased PF4 binding to platelets (P = 0.0004), displaced PF4-heparin complexes from platelets (P = 0.0033) and PF4 from the surface of a PF4-transfected HEK-293 EBNA cell line expressing the PF4 receptor CXCR3-B (P = 0.0408), reduced PF4-heparin complex size (P = 0.025), inhibited HIT antibody binding to PF4-heparin complexes (P = 0.001), and prevented platelet activation by HIT antibodies (P = 0.046). Although fondaparinux also interfered with PF4 binding to platelets, HIT antibody binding to PF4-heparin complexes, and activation of platelets by HIT antibodies, these effects occurred only at supratherapeutic concentrations. The direct thrombin inhibitors had no effect at any concentrations.. Danaparoid uniquely interferes with the pathogenesis of HIT by disrupting PF4-containing immune complexes at therapeutic dose concentrations. It is possible that these effects contribute to its therapeutic efficacy.

Topics: Antibodies; Antibody Affinity; Cells, Cultured; Chondroitin Sulfates; Dermatan Sulfate; Fondaparinux; Heparin; Heparitin Sulfate; Humans; Platelet Activation; Platelet Factor 4; Polysaccharides; Protein Binding; Serine Proteinase Inhibitors; Thrombin; Thrombocytopenia

Topics: Anticoagulants; Fondaparinux; Heparin; Humans; Male; Middle Aged; Polysaccharides; Thrombocytopenia; Thrombophlebitis; Upper Extremity

Heparin-induced thrombocythopenia (HIT) is a potentially serious complication of heparin treatment, rarely observed in cardiological wards. We present a case of a 38-year-old woman with dilated cardiomyopathy and massive pulmonary embolism treated with alteplase and unfractionated heparin. On 12th day an unexpected fall in platelet count was observed, without new signs of thrombosis. The HIT type II was diagnosed. Patient was treated effectively and safely by 7.5 mg of fondaparinux given subcutaneously once daily for 10 days.

Topics: Adult; Anticoagulants; Cardiomyopathy, Dilated; Female; Fondaparinux; Heparin; Humans; Injections, Subcutaneous; Polysaccharides; Pulmonary Embolism; Thrombocytopenia

Topics: Antibody Formation; Anticoagulants; Antiphospholipid Syndrome; Fondaparinux; Heparin; Humans; Platelet Activation; Polysaccharides; Thrombocytopenia

Many factors impact the choice of anticoagulant used for venous thromboembolism prophylaxis following orthopaedic surgery. Thrombocytopenia (TCP) is an important factor from both clinical and economic perspectives, warranting assessment between the available agents. Thus, a retrospective cohort analysis was conducted to: (1) report the occurrence of TCP in a treatment and no treatment group, (2) evaluate the impact of anticoagulant choice on TCP within the treatment group, and (3) assess the clinical and economic implications of TCP in the treatment group.. Administrative claims from a hospital database were used to identify patients with hip replacement, knee replacement, or hip fracture surgery. The treatment group (n = 144,806) included patients receiving one of the following injectable anticoagulants post-operatively: dalteparin (n = 16,109); enoxaparin (n = 97,827); fondaparinux (n = 12,532); or unfractionated heparin (UFH) (n = 18,338). The no treatment group consisted of patients who did not receive one of the four injectable anticoagulants (n = 112,574) post-operatively. Outcomes were assessed for the hospitalization period plus 2 months post-discharge while controlling for relevant demographic and clinical characteristics.. The occurrence of TCP was 1.0% in the no treatment group and 1.7% in the treatment group. Within the treatment group, patients who received dalteparin, enoxaparin, and UFH were significantly more likely to experience coded thrombocytopenia than those in the no treatment group. The risk of TCP among patients who received fondaparinux was not significantly different from the no treatment cohort (odds ratio [OR] = 1.15, 95% CI: 0.96-1.37, P = 0.13). Patients in the treatment group with coded TCP had 22% higher adjusted mean total healthcare costs (relative cost difference) compared to those without ($19,134 vs. $15,400, respectively, P < 0.0001), greater mean length of stay (LOS) (8.4 vs. 5.7, respectively), and a greater likelihood of experiencing a venous thromboembolic (VTE) event (6.1% vs. 2.4%, respectively).. Patients treated with fondaparinux did not have a significant increase in the risk of TCP compared to patients not on prophylaxis. In contrast, the risk was increased in those treated with enoxaparin, dalteparin, and UFH compared to the patients not on prophylaxis. Patients in the treatment group with coded TCP experienced more thrombotic events, incurred greater per patient healthcare costs, and experienced longer LOS than patients without coded TCP. Therefore, the risk of TCP should be considered when evaluating the profile of injectable anticoagulants since TCP may have important clinical and economic implications.

Topics: Aged; Anticoagulants; Cohort Studies; Dalteparin; Enoxaparin; Female; Fondaparinux; Health Care Costs; Heparin; Humans; Incidence; Injections; Length of Stay; Male; Odds Ratio; Orthopedic Procedures; Polysaccharides; Retrospective Studies; Risk Assessment; Thrombocytopenia; Venous Thromboembolism

Topics: Acute Disease; Anticoagulants; Arginine; Blood Coagulation; Factor Xa Inhibitors; Fondaparinux; Hemorrhage; Heparin; Hirudins; Humans; International Normalized Ratio; Pipecolic Acids; Platelet Count; Polysaccharides; Recombinant Proteins; Research Design; Sulfonamides; Thrombin; Thrombocytopenia; Treatment Outcome; Venous Thrombosis; Warfarin

An evidence-based heparin- induced thrombocytopenia (HIT) treatment protocol to standardize the management of confirmed or suspected HIT was developed.. In a retrospective review of 10 patients with known or suspected HIT over a two-year period, medical records were evaluated for baseline laboratory results, treatment selection, initial dosing and monitoring, discontinuation of heparin, and alternative therapies chosen. Six of 10 patients had antibody-confirmed HIT at admission. Nine patients received alternative anticoagulation therapy with one of two formulary direct thrombin inhibitor (DTI) agents, lepirudin and argatroban; 1 patient was given fondaparinux. Medical record analyses revealed deficiencies in both initial and transitional dose administration and renal function monitoring, order omissions, infusion-related medication errors, and treatments that were unsubstantiated, inappropriate, or lacking in regulatory approval. The new treatment protocol developed to assist physicians, pharmacists, and nurses with HIT management focused primarily on the two agents labeled for HIT, lepirudin and argatroban. The protocol established baseline levels for the selection of anticoagulation therapy as well as guidance in DTI selection, use, and monitoring. Guidelines for initial dosing and continuous infusion rates based on weight and detailed instructions in all aspects of therapy discontinuation (transition) were included. HIT treatments unsupported by data ensuring the efficacy and safety of therapies were excluded. Careful review of the relevant literature led to the inclusion of alternative anticoagulant treatments based on issues of safety, efficacy, cost, and convenience of dose forms.. A treatment protocol for HIT was developed and implemented in a tertiary care hospital in an effort to improve the management of patients suffering from this complication.

Topics: Anticoagulants; Arginine; Clinical Protocols; Evidence-Based Medicine; Fondaparinux; Heparin; Hirudins; Humans; Pipecolic Acids; Platelet Count; Platelet Function Tests; Polysaccharides; Recombinant Proteins; Retrospective Studies; Sulfonamides; Thrombocytopenia

Heparin-induced thrombocytopenia (HIT) is caused by platelet-activating antibodies that recognize platelet factor 4 (PF4)/heparin complexes. The frequency of HIT is highly variable in different clinical settings, and is more frequent with unfractionated heparin (UFH) than with low-molecular-weight heparin (LMWH), despite the in vitro observation that HIT antibodies activate platelets similarly well with LMWH as with UFH. An important difference between UFH, LMWH, and fondaparinux is their widely differing plasma concentrations. We aimed to provide a model that included anticoagulant concentrations and PF4 availability as risk factors influencing the anti-PF4/heparin immune response.. By photon correlation spectroscopy we determined the concentrations at which UFH, LMWH, and fondaparinux form complexes optimally with PF4. Plasma concentrations of UFH and LMWH were calculated based on ex vivo pharmacokinetic data, with information on fondaparinux and PF4 concentrations taken from the literature.. The main features of our model are: optimal complex formation occurs at prophylactic-dose UFH and high PF4 levels, whereas therapeutic-dose LMWH concentrations are too high for optimal complex formation; in contrast, concentrations of fondaparinux are usually below the optimal stoichiometric range. Thus, immunization should occur more often in situations with major rather than minor platelet activation, and--for a given degree of platelet activation (PF4 availability)--as: prophylactic-dose UFH>therapeutic-dose UFH>prophylactic-dose LMWH, fondaparinux>therapeutic-dose LMWH. Our model provides a framework for explaining empirical observations that LMWH induces less anti-PF4/heparin antibodies than does UFH, and that anti-PF4/heparin antibodies are more often found in patients undergoing major surgery than in medical patients.

Topics: Anticoagulants; Blood Platelets; Dose-Response Relationship, Drug; Fondaparinux; Heparin; Heparin, Low-Molecular-Weight; Humans; Immune System; Models, Biological; Photons; Platelet Activation; Platelet Factor 4; Polysaccharides; Risk Factors; Thrombocytopenia

Topics: Aged; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Female; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Platelet Count; Polysaccharides; Recurrence; Safety; Thrombocytopenia; Venous Thrombosis

The decision for an anticoagulant for renal replacement therapy (RRT) in patients with acute renal failure and heparin-induced thrombocytopenia (HIT) has to be made carefully. Based on results from the literature argatroban is favoured in patients without hepatic dysfunction, referring to its short halftime and easy feasable monitoring. In the case of coexsisting hepatic disorder, danaparoid provides a safe alternative therapy. However, long halftime and the difficult elimination of the substance are unfavourable. Lepirudin represents another possible anticoagulant therapy. Bleeding complications and monitoring of the ecarin clotting time imposes limitations. Experiences with bivalirudin, fondaparinux and prostaglandines are limited and future trials will have to determine the significance of their application in RRT in HIT patients. Furthermore it has to be proven whether the combination of alternative anticoagulants with citrate prolongates circuit halftime of CVVH.

Topics: Acute Kidney Injury; Anticoagulants; Arginine; Blood Coagulation Tests; Chondroitin Sulfates; Citrates; Critical Care; Dermatan Sulfate; Diagnostic Errors; Dose-Response Relationship, Drug; Epoprostenol; Fondaparinux; Hemofiltration; Heparin; Heparin, Low-Molecular-Weight; Heparitin Sulfate; Hirudins; Humans; Iloprost; Pipecolic Acids; Polysaccharides; Recombinant Proteins; Sodium Citrate; Sulfonamides; Thrombocytopenia; Thrombosis

In critically ill patients, heparin-induced thrombocytopenia (HIT) is estimated to account for approximately 1 to 10% of all causes of thrombocytopenia. HIT exerts a strong procoagulant state. In case of suspected HIT, it is an important clinical decision to stop heparin and start treatment with alternative nonheparin anticoagulation, awaiting the results of laboratory testing for the final diagnosis of HIT (bridging therapy). Fondaparinux acts by factor Xa inhibition and expresses no cross-reactivity with HIT antibodies. Excretion of fondaparinux is mainly renal. We describe our early experience with fixed low-dose fondaparinux bridging therapy and monitoring of anticoagulant activity for safety reasons.. This retrospective cohort study was conducted in a closed format general intensive care unit in a teaching hospital. Consecutive critically ill patients suspected of HIT were treated with fondaparinux after discontinuation of unfractionated heparin or nadroparin. Anti-Xa levels were determined afterwards.. Seven patients were treated with fondaparinux 2.5 mg/day for 1.8 to 6.5 days. Anti-Xa levels varied from 0.1 to 0.6 U/ml. A negative correlation was found between creatinine clearance and mean and maximum anti-Xa levels. No thromboembolic complications occurred. Bleeding complications were only minor during fondaparinux treatment. Transfusion requirements did not differ significantly between treatment episodes with fondaparinux or with heparin anticoagulants.. In this small sample of critically ill patients suspected of HIT, bridging therapy with fixed low-dose fondaparinux resulted in prophylactic and therapeutic anti-Xa levels. Monitoring of anticoagulant activity is advised in patients with renal insufficiency.

Topics: Aged; Aged, 80 and over; Anticoagulants; Chemoprevention; Critical Care; Critical Illness; Dose-Response Relationship, Drug; Drug Monitoring; Female; Fondaparinux; Heparin; Hospitals, Teaching; Humans; Intensive Care Units; Male; Middle Aged; Polysaccharides; Retrospective Studies; Thrombocytopenia

Topics: Adrenal Glands; Anticoagulants; Female; Fondaparinux; Heparin; Humans; Infarction; Middle Aged; Platelet Activation; Polysaccharides; Thrombocytopenia; Venous Thrombosis

Anticoagulant therapy plays an important role in current medical practice. The main types of anticoagulant agents are: heparins, hirudins and vitamin K antagonists. None of the drugs used as anticoagulants meet the criteria of an ideal anticoagulant because they have side effects and they interact with other compounds. The main side effect of anticoagulant therapy is bleeding. The choice of a certain anticoagulant is made by the doctor based on the clinical context and also on the desired effect.

Topics: Anticoagulants; Azetidines; Benzylamines; Fondaparinux; Hemorrhage; Heparin; Hirudins; Humans; International Normalized Ratio; Polysaccharides; Thrombocytopenia; Vitamin K; Warfarin

Topics: Antibodies; Anticoagulants; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Platelet Factor 4; Polysaccharides; Thrombocytopenia; Venous Thrombosis

To describe the clinical characteristics, management, and outcomes of patients with heparin-induced thrombocytopenia with thrombosis (HITTS) or without thrombosis (HIT) who also had an elevated baseline activated partial thromboplastin time (aPTT) due to antiphospholipid antibody syndrome (APS).. Four patients with HIT/HITTS and an elevated baseline aPTT due to APS were identified. Two patients had venous thrombosis, 1 had limb ischemia, and 1 had isolated HIT. All 4 were managed with a weight-based fixed dose of argatroban without laboratory monitoring. None of the patients had thrombotic or bleeding complications once therapy was initiated.. Management of patients with HIT/HITTS and an abnormal baseline aPTT due to APS is problematic. We review alternative management strategies, such as monitoring direct thrombin inhibitors with the ecarin clotting time or thrombin inhibition time or using an alternative anticoagulant, such as fondaparinux. As of March 13, 2006, none of these management strategies has been evaluated in a clinical trial for this patient population. We report the successful use of weight-based, fixed-dose argatroban without laboratory monitoring in patients with APS.. Use of a fixed-dose argatroban regimen without laboratory monitoring is a potential management strategy for patients with HIT/HITTS and an elevated baseline aPTT due to APS.

Topics: Adult; Anticoagulants; Antiphospholipid Syndrome; Arginine; Female; Fondaparinux; Heparin; Humans; Middle Aged; Partial Thromboplastin Time; Pipecolic Acids; Polysaccharides; Sulfonamides; Thrombocytopenia; Thrombosis

Topics: Anticoagulants; Fondaparinux; Heparin; Humans; Polysaccharides; Thrombocytopenia

Topics: Adult; Anticoagulants; Antiphospholipid Syndrome; Female; Fondaparinux; Heparin; Humans; Polysaccharides; Thrombocytopenia

Heparin-induced thrombocytopenia (HIT) is a prothrombotic drug reaction caused by antibodies that recognize positively charged platelet factor 4 (PF4), bound to the polyanion, heparin. The resulting immune complexes activate platelets. Unfractionated heparin (UFH) causes HIT more frequently than low-molecular-weight heparin (LMWH), whereas the smallest heparin-like molecule (the pentasaccharide, fondaparinux), induces anti-PF4/heparin antibodies as frequently as LMWH, but without exhibiting cross-reactivity with these antibodies. To better understand these findings, we analyzed the molecular structure of the complexes formed between PF4 and UFH, LMWH, or fondaparinux.. By atomic force microscopy and photon correlation spectroscopy, we show that with any of the 3 polyanions, but in the order, UFH>LMWH>>fondaparinux--PF4 forms clusters in which PF4 tetramers become closely apposed, and to which anti-PF4/heparin antibodies bind. By immunoassay, HIT antibodies bind strongly to PF4/H/PF4 complexes, but only weakly to single PF4/heparin molecules.. HIT antigens are formed when charge neutralization by polyanion allows positively charged PF4 tetramers to undergo close approximation. Whereas such a model could explain why all 3 polyanions form antibodies with similar specificities, the striking differences in the relative size and amount of complexes formed likely correspond to the observed differences in immunogenicity (UFH>LMWH approximately fondaparinux) and clinically relevant cross-reactivity (UFH>LMWH>>fondaparinux).

Topics: Adsorption; Antibodies; Antibody Formation; Enzyme-Linked Immunosorbent Assay; Fondaparinux; Heparin; Heparin, Low-Molecular-Weight; Humans; Microscopy, Atomic Force; Photons; Platelet Factor 4; Polysaccharides; Spectrum Analysis; Thrombocytopenia

Topics: Acute Disease; Anticoagulants; Antithrombin III; Coronary Disease; Drug Therapy, Combination; Electrocardiography; Fondaparinux; Hemorrhage; Heparin; Humans; Incidence; Myocardial Infarction; Platelet Aggregation Inhibitors; Polysaccharides; Registries; Severity of Illness Index; Syndrome; Thrombocytopenia

43 years old women with tumor of the right ventricle was admitted to ICU due to pulmonary embolism and suspicion for heparin-induced thrombocytopenia. Thrombocytopenia was successfully treated with Arixtra and the patient was qualified for the cardio surgery intervention. Heparin is widely used in treatment and prophylaxis of venous thromboembolism and other diseases. One of the most important adverse effect of treatment with heparin is heparin-inducted thrombocytopenia (HIT), which is one of the most frequent drug-induced, immune-mediated type of thrombocytopenia. If it is unrecognized is associated with significant morbidity and mortality. According to our knowledge this is first report of Arixtra usage in patient with suspicion of HIT in Poland.

Topics: Adult; Anticoagulants; Female; Fondaparinux; Heart Neoplasms; Heart Ventricles; Heparin; Humans; Poland; Polysaccharides; Pulmonary Embolism; Thrombocytopenia; Warfarin

Topics: Anticoagulants; Fondaparinux; Heparin; Humans; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Polysaccharides; Thrombocytopenia; Thrombosis; Treatment Outcome

Topics: Aged; Anticoagulants; Female; Fondaparinux; Heparin; Humans; Middle Aged; Platelet Count; Polysaccharides; Thrombocytopenia; Thrombosis; Time Factors; Treatment Outcome; Warfarin

Anticoagulation of patients with heparin-induced thrombocytopenia (HIT) may be limited by cross-reaction of HIT antibodies with danaparoid and generation of antibodies during therapy with lepirudin. We used fondaparinux to treat 6 patients with a history of HIT with thromboembolism and 2 patients with thrombocytopenia during low-molecular-weight heparin administration.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Polysaccharides; Thrombocytopenia; Treatment Outcome

Topics: Adult; Budd-Chiari Syndrome; Fondaparinux; Hemoglobinuria, Paroxysmal; Heparin; Humans; Male; Polysaccharides; Thrombocytopenia; Treatment Outcome