Inhibitor development in previously untreated patients with hemophilia A: a prospective long-term follow-up comparing plasma-derived and recombinant products.

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-derived (pd) (n = 51) or recombinant FVIII (rFVIII) (n = 21) concentrates (median 270 exposure days [ED]). Inhibitor testing was performed before the first exposure and at regular intervals thereafter. Of the 72 hemophilia A patients, 22 (32%) developed an inhibitor after 15 ED in median (range 4 to 195); 17 (77%) were high responders (>5 Bethesda Units [BU]), and the remaining 5 patients (23%) were low responders (>0.6 to 5 BU). The severely affected patients (n = 46) showed a significantly higher frequency of inhibitor formation (43%) than did the moderate ones (8%). Comparing the severely affected patients receiving pd products exclusively (n = 35) with those treated with recombinant concentrate (n = 11), 37% of the pd group developed a high-titer inhibitor (>5 BU, median 290 ED in noninhibitor patients) and 36% of the recombinant group (median 49 ED in the noninhibitor patients). However, the exposure status of the recombinant noninhibitor patients is rather low and therefore remains a high risk of developing further inhibitors in the future. The mutation type profile revealed no difference between the pd- and the recombinant-treated patients.

journal_name

Semin Thromb Hemost

authors

Kreuz W,Ettingshausen CE,Zyschka A,Oldenburg J,Saguer IM,Ehrenforth S,Klingebiel T

doi

10.1055/s-2002-32664

subject

Has Abstract

pub_date

2002-06-01 00:00:00

pages

285-90

issue

3

eissn

0094-6176

issn

1098-9064

journal_volume

28

pub_type

杂志文章
  • Transabdominal measurement of oxygenation of the placenta by near-infrared spectroscopy.

    abstract::Near-infrared spectroscopy (NIRS) has been used as a noninvasive method for monitoring the real-time oxygenation status in areas such as the brain and striated muscle. Because the oxygenation status of the placenta is closely related to the fetal condition, monitoring placental oxygenation through the maternal abdomen...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章

    doi:10.1055/s-2005-872435

    authors: Kakogawa J,Sumimoto K,Ho E,Kanayama N

    更新日期:2005-06-01 00:00:00

  • Multiple roles of tissue plasminogen activator in schizophrenia pathophysiology.

    abstract::Schizophrenia, a disabling mental disorder, is characterized by brain atrophy, especially in the superior temporal gyrus and the medial temporal lobe, which includes the hippocampus and the amygdala. The model that better explains brain atrophy includes a trigger and a predisposing condition. The trigger is exemplifie...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章,评审

    doi:10.1055/s-0033-1357505

    authors: Hoirisch-Clapauch S,Nardi AE

    更新日期:2013-11-01 00:00:00

  • Classic and Global Hemostasis Testing in Pregnancy and during Pregnancy Complications.

    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

    authors: Ataullakhanov FI,Koltsova EM,Balandina AN,Serebriyskiy II,Vuimo TA,Panteleev MA

    更新日期:2016-10-01 00:00:00

  • Protein C and the endothelium.

    abstract::With the continued accumulation of clinical and animal studies, it is becoming abundantly clear that the protein C anticoagulant pathway plays a critical role in the regulation of coagulation. Investigations also indicate that this pathway is intimately involved in the interaction of the coagulation and inflammatory s...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章,评审

    doi:10.1055/s-2007-1002779

    authors: Esmon NL,Esmon CT

    更新日期:1988-04-01 00:00:00

  • Selectins in the HIT syndrome: pathophysiologic role and therapeutic modulation.

    abstract::The pathophysiology of heparin-induced thrombocytopenia (HIT) is now known to be a complex process which involves platelets, vascular endothelium, and leukocytes. The activation products from these sites also contribute to the activation of coagulation and to the fibrinolytic deficit. While many of the markers of hemo...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章,评审

    doi:

    authors: Fareed J,Walenga JM,Hoppensteadt DA,Jeske WP,Lietz H,Ahmad S,Callas D,Messmore HL,Haas S

    更新日期:1999-01-01 00:00:00

  • CD36 and macrophage scavenger receptor a modulate foam cell formation via inhibition of lipid-laden platelet phagocytosis.

    abstract::CD34 (+) progenitor cells are a promising source of regeneration in atherosclerosis or ischemic heart disease. However, as recently published, CD34(+) progenitor cells have the potential to differentiate not only into endothelial cells but also into foam cells upon interaction with platelets. The mechanism of platelet...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章

    doi:10.1055/s-0030-1251499

    authors: Seizer P,Schiemann S,Merz T,Daub K,Bigalke B,Stellos K,Müller I,Stöckle C,Müller K,Gawaz M,May AE

    更新日期:2010-03-01 00:00:00

  • Proposal for revised diagnostic criteria of essential thrombocythemia and polycythemia vera by the Thrombocythemia Vera Study Group.

    abstract::The present study revises the criteria of the Polycythemia Vera Group (PVSG) for the diagnoses of essential thrombocythemia (ET) and polycythemia vera (PV) in view of accumulating data on in vitro cultures of hematopoietic progenitors and by adding histopathology from bone marrow biopsies. The majority of ET patients ...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 指南,杂志文章,实务指引

    doi:10.1055/s-2007-996107

    authors: Michiels JJ,Juvonen E

    更新日期:1997-01-01 00:00:00

  • Molecular weight-dependent influence of heparin on the form of tissue factor pathway inhibitor circulating in plasma.

    abstract::The increase of circulating tissue factor pathway inhibitor (TFPI) in plasma by heparins is thought to contribute to their overall antithrombotic activity. In a clinical study in healthy volunteers, we recently found that the specific potency of a heparin to mobilize TFPI from the vessel wall increases with its molecu...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1055/s-2001-17952

    authors: Alban S

    更新日期:2001-10-01 00:00:00

  • Management strategies for optimal control of anticoagulation in patients with atrial fibrillation.

    abstract::Most patients with atrial fibrillation need anticoagulant treatment with vitamin K antagonists for prevention of thromboembolism, in particular ischemic stroke. Many studies show the efficacy of this treatment but also that it is difficult to keep patients who use vitamin K antagonists in the proper treatment range. B...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章,评审

    doi:10.1055/s-0029-1240016

    authors: Levi M,de Peuter OR,Kamphuisen PW

    更新日期:2009-09-01 00:00:00

  • Travel, venous thromboembolism, and thrombophilia.

    abstract::Current evidence indicates that prolonged air travel predisposes to venous thrombosis and pulmonary embolism. An effect is seen once travel duration exceeds 6 to 9 hours and becomes obvious in long-haul passengers traveling for 12 or more hours. A recent records linkage study found that increase in thrombosis rate amo...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章,评审

    doi:10.1055/s-2005-863810

    authors: Gallus AS

    更新日期:2005-02-01 00:00:00

  • Recombinant FVIIa in the treatment of warfarin bleeding.

    abstract::Patients receiving oral anticoagulant treatment have abnormally low levels of functional vitamin K-dependent coagulation proteins and consequently a clear risk of hemorrhagic complications. The incidence of hemorrhages has been reported to be around 0.6-0.7% per month at a therapeutic International Normalized Ratio (I...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章,评审

    doi:10.1055/s-2000-8464

    authors: Berntorp E

    更新日期:2000-01-01 00:00:00

  • Impact of rheological variables in cancer.

    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

    authors: von Tempelhoff GF,Heilmann L,Hommel G,Pollow K

    更新日期:2003-10-01 00:00:00

  • Impact of Asymptomatic Pulmonary Embolism on the Long-Term Prognosis of Patients with Deep Venous Thrombosis.

    abstract::Asymptomatic pulmonary embolism (PE) is present in at least one-third of patients with deep venous thrombosis (DVT). However, knowledge about its influence on the prognosis of patients is limited. The aim of this study was to assess the prognostic impact of asymptomatic PE in patients with DVT and to explore risk fact...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章

    doi:10.1055/s-0036-1584351

    authors: Boc A,Vene N,Košmelj K,Mavri A

    更新日期:2017-02-01 00:00:00

  • Thrombotic microangiopathy in transplantation and malignancy.

    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

    authors: Qu L,Kiss JE

    更新日期:2005-12-01 00:00:00

  • Inhibitors in Severe Hemophilia A: 25-Year Experience in Slovakia.

    abstract:UNLABELLED:We present 25-year experience with inhibitors in previously untreated patients (PUPs) with severe hemophilia A in Slovakia, where safe factor VIII (FVIII) concentrates have been used since 1990. A prospective study focused on inhibitor incidence in PUPs was established in 1997. Out of a total 61 PUPs born be...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章,多中心研究

    doi:10.1055/s-0036-1581107

    authors: Batorova A,Jankovicova D,Morongova A,Bubanska E,Prigancova T,Horakova J,Machyniakova M,Cervenka J,Chandoga J,Böhmer D,Mistrik M

    更新日期:2016-07-01 00:00:00

  • Molecular biology and pathophysiology of APC resistance: current insights and clinical implications.

    abstract::APC resistance is often associated with the occurrence of a single point mutation in factor V (factor VLeiden) at a predominant cleavage site for the natural anticoagulant, activated protein C (APC). In this article we will discuss the effects of this mutation (Arg506-->Gln) on the down-regulation of factor Va cofacto...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章,评审

    doi:10.1055/s-2007-996021

    authors: Rosing J,Hemker HC,Tans G

    更新日期:1998-01-01 00:00:00

  • Inhibitors in Hemophilia: Treatment Challenges and Novel Options.

    abstract::Hemophilia A (HA) and hemophilia B (HB) are rare congenital severe bleeding disorders, that may be controlled by proper administration of adequate prophylaxis with factor VIII (FVIII), and factor IX (FIX) concentrates, respectively, to prevent joint damage due to recurrent bleeding. However, approximately 30% of patie...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章,评审

    doi:10.1055/s-0037-1612626

    authors: Barg AA,Livnat T,Kenet G

    更新日期:2018-09-01 00:00:00

  • The UK National External Quality Assessment Scheme for heritable bleeding disorders.

    abstract::Molecular genetic analysis of families with hemophilia and other heritable bleeding disorders is a frequently requested laboratory investigation. In the United Kingdom, laboratories undertaking genetic testing must participate in a recognized external quality assessment scheme for formal accreditation. The UK National...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章

    doi:10.1055/s-0034-1365843

    authors: Perry DJ,Cumming T,Goodeve A,Hill M,Jennings I,Kitchen S,Walker I

    更新日期:2014-03-01 00:00:00

  • Developing the First Recombinant Factor XIII for Congenital Factor XIII Deficiency: Clinical Challenges and Successes.

    abstract::Congenital factor XIII (FXIII) deficiency is a rare, autosomal recessive bleeding disorder with potentially life-threatening consequences. FXIII is composed of two subunits (A and B), and a deficiency or dysfunction of either can result in FXIII deficiency. Traditionally, FXIII deficiency has been managed by infusing ...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章

    doi:10.1055/s-0036-1585076

    authors: Carcao M,Fukutake K,Inbal A,Kerlin B,Lassila R,Oldenburg J,Garly ML,Nugent D

    更新日期:2017-02-01 00:00:00

  • Platelet CLEC-2: Roles Beyond Hemostasis.

    abstract::C-type lectin-like receptor 2 (CLEC-2) has been identified on the surface of platelets as a receptor for a platelet activating snake venom, rhodocytin/aggretin. CLEC-2 belongs to a C-type lectin superfamily and binds to a sialoglycoprotein, podoplanin, in vivo. Platelets play a crucial role in hemostasis and thrombosi...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章,评审

    doi:10.1055/s-0037-1604090

    authors: Suzuki-Inoue K,Tsukiji N,Shirai T,Osada M,Inoue O,Ozaki Y

    更新日期:2018-03-01 00:00:00

  • Tissue factor de-encryption, thrombus formation, and thiol-disulfide exchange.

    abstract::Tissue factor (TF) by forming a complex with factor VIIa (FVIIa) initiates blood coagulation. It was traditionally believed that the separation of FVIIa in circulation from subendothelial TF was the main control that was preventing spontaneous initiation of thrombosis and that circulating cells and endothelium did not...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章,评审

    doi:10.1055/s-0032-1333311

    authors: Chen VM

    更新日期:2013-02-01 00:00:00

  • Vatreptacog alfa from conception to clinical proof of concept.

    abstract::Vatreptacog alfa is a genetically engineered variant of recombinant factor VIIa (rFVIIa) containing three amino acid changes. Aspartic acid, valine, and glutamine residues replace valine, glutamic acid, and methionine at positions 158, 296, and 298, respectively. These substitutions result in considerable enhancement ...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章,评审

    doi:10.1055/s-0032-1302442

    authors: Persson E,Olsen OH,Bjørn SE,Ezban M

    更新日期:2012-04-01 00:00:00

  • Detection of aspirin resistance by PFA-100: prevalence and aspirin compliance in patients with chronic stable angina.

    abstract::Most acute coronary syndromes result from a platelet-rich occlusion of the coronary arteries. Antiplatelet drugs are of proven efficacy in preventing myocardial infarction, unstable angina, and stroke. However, not all patients on aspirin (ASA) benefit. We studied the phenomenon of aspirin resistance with a simple and...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章

    doi:10.1055/s-2005-916677

    authors: Crowe B,Abbas S,Meany B,de Haan J,Cahill MR

    更新日期:2005-01-01 00:00:00

  • New insights into the pathogenesis of JAK2 V617F-positive myeloproliferative disorders and consequences for the management of patients.

    abstract::The identification of the JAK2 V617F mutation in patients with myeloproliferative disorders (MPDs) represents a major breakthrough in our understanding of the pathogenesis of these diseases. One year after its discovery, an impressive number of publications appeared. These articles confirmed most of the initial result...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章,评审

    doi:10.1055/s-2006-942755

    authors: Villeval JL,James C,Pisani DF,Casadevall N,Vainchenker W

    更新日期:2006-06-01 00:00:00

  • To mix or not to mix in lupus anticoagulant testing? That is the question.

    abstract::Mixing patient and normal plasma has been used for many years to assist with making decisions on which direction to proceed for further investigation of abnormally prolonged coagulation tests, namely, either individual coagulation factor measurement or the search for circulating anticoagulants. Mixing tests, however, ...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章,评审

    doi:10.1055/s-0032-1304717

    authors: Tripodi A

    更新日期:2012-06-01 00:00:00

  • Disseminated intravascular coagulation and related syndromes: a clinical review.

    abstract::Current concepts of the cause, pathophysiologic mechanisms, diagnosis, and management of acute and chronic DIC have been discussed. Considerable attention has been devoted to interrelationships that have remained confusing. Only by clearly understanding these pathophysiologic interrelationships can the clinician and l...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章,评审

    doi:10.1055/s-2007-1002793

    authors: Bick RL

    更新日期:1988-10-01 00:00:00

  • Emerging issues on comprehensive hemophilia care: preventing, identifying, and monitoring age-related comorbidities.

    abstract::Life expectancy for persons with hemophilia (PWH) has considerably increased in the last decades as a direct result of the availability of modern therapies to control the clotting defect. Because their life expectancy now matches that of the general population, PWH are experiencing age-related comorbidities, such as, ...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章,评审

    doi:10.1055/s-0033-1354424

    authors: Coppola A,Santoro C,Franchini M,Mannucci C,Mogavero S,Molinari AC,Schinco P,Tagliaferri A,Santoro RC

    更新日期:2013-10-01 00:00:00

  • Anticoagulation in the older adult: optimizing benefit and reducing risk.

    abstract::The risk for both arterial and venous thrombosis increases with age. Despite the increasing burden of strokes related to atrial fibrillation (AF) and venous thromboembolism (VTE) among older adults, the use of anticoagulant therapy is limited in this population due to the parallel increase in risk of serious hemorrhag...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章,评审

    doi:10.1055/s-0034-1389083

    authors: Ko D,Hylek EM

    更新日期:2014-09-01 00:00:00

  • Aspects of the laboratory identification of von Willebrand disease in women.

    abstract::The increased prevalence of the laboratory diagnosis of von Willebrand disease (vWD) in women presenting with menorrhagia has raised concerns regarding certain specifics in vWD testing in women, including when vWD testing should be done in relation to menses and whether testing should be done while the patient is not ...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章,评审

    doi:10.1055/s-2006-947861

    authors: Kouides PA

    更新日期:2006-07-01 00:00:00

  • A possible role for thrombopoietin and its receptor c-mpl in the pathobiology of essential thrombocythemia.

    abstract::Essential thrombocythemia (ET) is a clonal myeloproliferative disorder of unknown origin primarily involving the megakaryocyte/platelet lineage. In an attempt to evaluate the role of the receptor c-mpl and its ligand thrombopoietin (TPO) in ET, various studies have been undertaken, the results of which are discussed h...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章,评审

    doi:10.1055/s-2007-996118

    authors: Griesshammer M,Bangerter M,Schrezenmeier H

    更新日期:1997-01-01 00:00:00