Abstract:
:This epilogue represents a final summary of the issues discussed and highlighted at the International Summit on Differentiation of Low Molecular Weight Heparins (LMWHs). International scientists and physicians presented and discussed the physicochemical differences between LMWHs, and concluded that different production processes result in the formation of distinct drugs with unique preclinical and clinical profiles. Important data was presented showing that different LMWHs continue to show marked differences in antithrombotic action, and pharmacokinetic and pharmacodynamic profiles measured in animal models. Human data also demonstrate that LMWHs are not bioequivalent. Moving to the clinical arena, it is clear that there are issues to be resolved regarding drug inequivalence. No apparent clinical efficacy differences have been observed in deep-vein thrombosis prophylaxis using a number of relatively low doses of LMWH. However, two studies have demonstrated clinical equivalence using different anti-Xa doses of LMWHs, strongly suggesting product inequivalence. This also suggests that anti-Xa doses are not reflective of the entire pharmacologic effects of LMWHs. It is unknown whether the higher dosages employed in the treatment of DVT will help provide evidence of clinical inequivalence. In the management of acute coronary syndromes, higher drug dosages than those used in prophylaxis have revealed an efficacy advantage; while two LMWHs have shown short-term improvement in acute coronary syndromes, only one provided a long-term treatment benefit, suggesting a drug-specific therapeutic advantage. This is in keeping with the position of the United States Food and Drug Administration and the World Health Organization, who regard each individual LMWH as a distinct drug requiring individual clinical trials for use in a specific clinical indication. In this epilogue, the chairpersons, Professors Jawed Fareed, Sylvia Haas and Arthur Sasahara, offer some final thoughts on this intriguing scientific and clinical issues of LMWH differentiation.
journal_name
Semin Thromb Hemostjournal_title
Seminars in thrombosis and hemostasisauthors
Fareed J,Haas S,Sasahar Asubject
Has Abstractpub_date
1999-01-01 00:00:00pages
145-7eissn
0094-6176issn
1098-9064journal_volume
25 Suppl 3pub_type
杂志文章abstract::In order to assess inhibitor development in previously untreated patients (PUPs) with severe (factor VIII [FVIII]<1%) and moderate (FVIII 1 to 5%) hemophilia A, a prospective study was initiated in 1976. During the 23-year study period, 72 hemophiliacs were frequently exposed prophylactically or on demand to plasma-de...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章
doi:10.1055/s-2002-32664
更新日期:2002-06-01 00:00:00
abstract::Pregnancy is associated with a significant procoagulant shift in the hemostatic system balance as well as other metabolic changes. Pregnancy can thereby provoke manifestation of otherwise dormant disorders of hemostasis (e.g., thrombophilia), or even cause new, pregnancy-specific disorders (e.g., HELLP syndrome). Appl...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-0036-1592303
更新日期:2016-10-01 00:00:00
abstract::Sequencing of the gene encoding for von Willebrand factor (VWF) has brought new insight into the physiology of VWF as well as its pathophysiology in the context of von Willebrand disease (VWD). Molecular testing in VWD patients has shown high variability in the overall genetic background of this condition. Almost 600 ...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章
doi:10.1055/s-0039-3402430
更新日期:2020-06-01 00:00:00
abstract::Pulmonary embolism (PE) has long been described in children. Nevertheless, most of the algorithms applied to patients within this age range, from diagnosis to therapy, have been adapted from adult protocols. This article reviews the progresses that occurred to PE in children placing them in historical perspective with...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-0031-1297168
更新日期:2011-10-01 00:00:00
abstract::Morbidity and mortality for cardiovascular disease are likely to be lower in patients with hemophilia than in the general male population. However, their clinical impact is increasing in parallel with the increase of life expectancy due to modern safe replacement treatments and the improvement of comprehensive care of...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-0030-1248728
更新日期:2010-02-01 00:00:00
abstract::In the early 1980s, the first external quality assessment schemes (EQAS) regarding parameters of the coagulation laboratory were established in the daily routine of German laboratories. At present, the EQAS performed by INSTAND offers a wide range of global and single parameters of thrombosis and hemostasis. Only the ...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章
doi:10.1055/s-2007-971812
更新日期:2007-04-01 00:00:00
abstract::Physiologic regulation of fibrinolysis plays an important role in the control of hypercoagulable states and thrombogenesis. Both the hereditary and acquired conditions leading to fibrinolytic deficit result in thrombotic complications leading to arterial and venous occlusive disorders. Several changes in physiologic s...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-2007-994940
更新日期:1999-01-01 00:00:00
abstract::Thrombotic microangiopathy (TMA) after hematopoietic stem-cell transplantation (HSCT) or solid-organ transplantation is a serious complication that may be associated with diverse clinical conditions. The reported incidence varies widely, in part due to different diagnostic criteria. Currently, the diagnosis is based m...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-2005-925475
更新日期:2005-12-01 00:00:00
abstract::In addition to the criteria of the Polycythemia Vera Study Group, positive markers for essential thrombocythemia (ET) include spontaneous BFU-E, splenomegaly, and megakaryocyte morphology in bone marrow smears and biopsy material. The hematologic features of 11 reported cases of ET in childhood showed platelet counts ...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-2007-996102
更新日期:1997-01-01 00:00:00
abstract::Polycystic ovarian syndrome (PCOS) affects 12 to 19% of women and has reproductive and metabolic features (endothelial dysfunction, increased diabetes, and cardiovascular risk factors). It also appears to have altered coagulation and fibrinolysis with a prothrombotic state with epidemiological evidence of increased ve...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 临床试验,杂志文章
doi:10.1055/s-0035-1564837
更新日期:2016-02-01 00:00:00
abstract::The polymorphism in the composition and actions of heparin and the parallel complexity of the thrombotic process have led to the design of a cautious, methodical, and pragmatic program of development of the first low molecular heparin fraction presently available in France (CY 216). The main idea was always to present...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 临床试验,历史文章,杂志文章,随机对照试验
doi:10.1055/s-2007-1002737
更新日期:1989-10-01 00:00:00
abstract::In severe infection and sepsis, activation of coagulation frequently occurs, which contributes to the development of multiple organ dysfunction. Factor V Leiden is a relatively common mutation resulting in a mild prohemostatic state and consequently with an increased tendency to develop thrombosis. Hypothetically, pat...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-0031-1297374
更新日期:2011-11-01 00:00:00
abstract::Atrial fibrillation (AF) can be secondary to acute pulmonary embolism (PE). This study aimed to investigate the prognostic impact of new-onset AF on patients with acute PE. In this study, 4,288 consecutive patients who were diagnosed with acute PE were retrospectively screened. In total, 77 patients with acute PE and ...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章
doi:10.1055/s-0040-1718397
更新日期:2020-11-01 00:00:00
abstract::Thrombosis development in either arterial or venous system remains a major cause of death and disability worldwide. This poorly controlled in vivo clotting could result in many severe complications including myocardial infarction, venous thromboembolism, stroke, and cerebral venous thrombosis, to name a few. These con...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章
doi:10.1055/s-0039-1697949
更新日期:2020-06-01 00:00:00
abstract::In order to obtain a global assessment of circulating clopidogrel-related products and of the excretion of the drug, the pharmacokinetic behavior and the excretion balance of 14C radioactivity following the administration of a single dose of 75 mg of 14C-labeled clopidogrel were compared in 6 clopidogrel-free healthy ...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 临床试验,杂志文章
doi:
更新日期:1999-01-01 00:00:00
abstract::Acquired von Willebrand syndrome (AVWS) is a rare bleeding disorder with laboratory findings similar to those for congenital von Willebrand disease (VWD). Unlike VWD, AVWS usually occurs in individuals with no personal or family history of bleeding. The prevalence of AVWS in the general population is unknown because d...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-0030-1270069
更新日期:2011-02-01 00:00:00
abstract::It is generally accepted that the initial event in coagulation and intravascular thrombus formation is the exposure of the flowing blood to cell-surface protein, such as tissue factor (TF). Vascular injury and/or atherosclerotic plaque complication is responsible for this exposure, leading to clinical manifestations s...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-0035-1564045
更新日期:2015-10-01 00:00:00
abstract::A simple RIA method for B beta 15-42 RPs has been evaluated in our laboratory to investigate experimental and clinical fibrinolytic states. The assay utilizes bentonite precipitation to remove cross-reacting fibrinogen. Due to the heterogeneity in molecular weights of the B beta RPs, the results are expressed as nanog...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章
doi:10.1055/s-2007-1004430
更新日期:1984-10-01 00:00:00
abstract::The two components of biological variability are interindividual variability, which is the variability due to the heterogeneity of physiologic influences among subjects, and intraindividual variability, which is due to the variability in the same individual over time. Analysis of biological variation is crucial for es...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章
doi:10.1055/s-0029-1214155
更新日期:2009-02-01 00:00:00
abstract::Although the current therapeutic armamentarium of venous thrombosis encompasses the use of vitamin K antagonists, heparins, and direct oral anticoagulants, these drugs have several important drawbacks. Antisense oligonucleotides are relatively short single-stranded nucleic acid sequences, which hybridize with a target...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-0035-1546466
更新日期:2015-03-01 00:00:00
abstract::Despite the improved therapeutic advances in the management of acute promyelocytic leukemia (APL), a significant early mortality during induction, also referred to as early death (ED), remains an obstacle for further improvement in outcome. Hemorrhagic complications are the most common cause of morbidity and mortality...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-0039-1693478
更新日期:2019-09-01 00:00:00
abstract::Each bone marrow megakaryocyte (MK) releases thousands of platelets into the circulation, and the underlying molecular and cellular mechanisms recently have received intense scrutiny. Genetic studies are beginning to clarify the mechanisms by which transcription factors help distinguish MK progenitors from other blood...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-2004-833474
更新日期:2004-08-01 00:00:00
abstract::Thrombotic thrombocytopenic purpura (TTP) and atypical hemolytic uremic syndrome (aHUS) are thrombotic microangiopathies (TMAs) that can present in pregnancy. The presentation can be with typical microangiopathic features and thrombocytopenia, but there is also a significant risk of in-utero fetal loss. TTP presents m...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-0036-1587683
更新日期:2016-10-01 00:00:00
abstract::Hip replacement surgery carries a high risk of thromboembolic complications, and pharmacological prophylaxis is routinely adopted in clinical practice. Meta-analyses have indicated that low molecular weight heparins (LMWHs) are clinically superior to conventional prophylaxis with unfractionated heparin. These analyses...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:
更新日期:1999-01-01 00:00:00
abstract::Severe acute inflammation in chronic inflammatory bowel disease is associated with large wound areas and ulcerations that show spontaneous hemorrhage or marked friability. Therefore, an enormous potential of hemostasis and wound healing is required. Coagulation studies demonstrate a deficiency of factor XIII that is i...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-2007-999045
更新日期:1996-01-01 00:00:00
abstract::Tissue factor pathway inhibitor (TFPI) is a Kunitz-type serine protease inhibitor found within the vascular system that is known to be released upon heparin administration. Tissue factor pathway inhibitor regulates the extrinsic pathway by inhibiting both factors VIIa and Xa. The role of TFPI in the prevention of thro...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-2007-999011
更新日期:1996-01-01 00:00:00
abstract::Rheological alterations are commonly found in malignant disease and are most pronounced in advanced-stage cancer. Although most of these changes are caused by cancer-unspecific mechanisms, it has been shown that the extent of these changes in some cancer types is related with the stage of cancer, prognosis of disease,...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-2003-44641
更新日期:2003-10-01 00:00:00
abstract::Pre-eclampsia (P-EC) is a multisystem disorder exclusive to pregnancy. It complicates ~2 to 8% of all pregnancies and remains a major cause of maternal mortality. P-EC is characterized by a profound hypercoagulable state. The delicate hemostatic balance that must be maintained in the uteroplacental circulation during ...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-0030-1270336
更新日期:2011-03-01 00:00:00
abstract::Treatment of patients with inhibitors to FVIII remains a complex clinical problem. Although characterizing the individual patient may aid in the initial development of a care plan, no treatment is uniformly reliable for all patients. Experts in the field are as likely to disagree as agree when it comes to choosing tre...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-2007-994002
更新日期:1993-01-01 00:00:00
abstract::A series of case-control studies in the last decade have shown the role of inherited thrombophilia in the occurrence of adverse obstetric outcomes. In small series of cases, it has been proven that rare inherited causes of thrombophilia such as natural anticoagulant deficiencies can be associated with fetal losses. Th...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-0029-1242717
更新日期:2009-10-01 00:00:00