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Biomedical subjects

A D Shapiro

Publications and source records attributed to A D Shapiro.

At least 19 recordsLinked to original sources
PubMed2003

Type 2B vWD: the varied clinical manifestations in two kindreds.

Type 2B von Willebrand's disease (vWD) is associated with spontaneous binding of large von Willebrand factor (vWF) multimers to platelets in vivo, followed by clearance of both the large multimers and platelets resulting in thrombocytopenia, which may be intermittent, mild to severe, and may be exacerbated by stress such as infection or pregnancy. We report our experience in two kindreds (49 caucasian individuals) with type 2B vWD and discuss their varied clinical manifestations. The largest kindred (45 patients) was traced back five generations to a presumed index case. The genetic defect in this kindred was identified as a missense mutation, with a C to T transition at a CpG dinucleotide (nucleotide 3916) resulting in an amino acid substitution (Arg 543 to Trp) within the glycoprotein Ib binding domain of vWF. Ristocetin cofactor activity varied from < 10 to 28%, and factor VIII activity from 7 to 69%. Analysis of von Willebrand multimers consistently revealed loss of large molecular weight forms. Platelet counts in those with thrombocytopenia varied from 10 x 10(9) L(-1) to 120 x 10(9) L(-1). The severity of thrombocytopenia has also varied within the same individual during the period of follow-up. The clinical manifestations were varied and ranged from mild to moderate spontaneous bleeding episodes, including epistaxis, menorrhagia and gastro-intestinal haemorrhage. Severe bleeding episodes were observed in those undergoing surgery (both elective and non-elective), and in a few patients despite aggressive replacement with exogenous source of intact vWF, antifibrinolytics when indicated, and a near normal platelet count. Thrombotic disease may be a rare and unusual sequela of this disorder as was noted in one of our patients. Obtaining a platelet count at birth in infants of mothers with type 2B vWD who exhibit thrombocytopenia, may help in the earlier detection of infants at risk for thrombocytopenia.

Adolescent↗
PubMed2003

A global view on prophylaxis: possibilities and consequences.

Prophylactic infusion therapy, both primary and secondary, has proven of great benefit to patients with haemophilia, specifically those with severe disease or bleeding episodes and patterns that have lead to development of arthropathy. At this time, optimal outcome in patients with severe haemophilia has been proven achievable with primary prophylaxis initiated at an early age in a regimen of three times weekly or every other day for patients with factor VIII deficiency, and twice weekly for those with factor IX deficiency. Despite the demonstrated benefit of primary prophylaxis, this treatment regimen has not been uniformly adopted into clinical practice even in developed countries. In developing countries, where issues of allocation of precious health care resources are of paramount importance, access to adequate treatment for persons with haemophilia on a programme of on-demand therapy is not commonly available; the cost of primary prophylaxis, even with intermediate purity plasma-derived factor concentrates or plasma fractions such as cryoprecipitate, renders this treatment the exception rather than the rule.

Cost-Benefit Analysis↗
PubMed2002

Haemophilia 2002: emerging risks of treatment.

Haemophilia care and treatment products have greatly improved over the past 2 decades. Transitions in treatment produced by these changes were accompanied by the emergence of unexpected risks and new complications. In order to provide the best comprehensive care to patients with haemophilia, healthcare providers periodically need to re-evaluate and adjust their management and therapeutic products to prevent or minimize the effects produced by the emerging issues. For example, reducing the effects of infectious agents remains the highest priority for the haemophilia community because of the high level of morbidity and mortality that has resulted from earlier therapeutic agents. In many countries, the goal has been to achieve absolute zero risk for infectious agents. In some instances, the screening procedures to achieve these goals reduced the availability of plasma needed for manufactured derivatives and produced another emerging risk, shortages of clotting factor preparations. Similarly, better diagnostic methods identified other potential agents that were not inactivated by current technology. Likewise, immune tolerance regimens and the prophylactic management of haemophilia introduced different therapeutic delivery systems with their own risks. The drugs used to manage diseases such as human immunodeficiency virus (HIV), which were transmitted by products manufactured before mid-1980, create their own set of risks for this community. Topical emerging risks of treatment, including variant Creutzfeldt-Jakob disease, an assessment of its risks and impact, the complications of using indwelling catheters, and the role of protease inhibitors used to treat HIV may have on bleeding complications of haemophilia are discussed.

Acquired Immunodeficiency Syndrome↗
PubMed2001

Pharmacokinetics of recombinant factor IX in relation to age of the patient: implications for dosing in prophylaxis.

The aims of this study were to investigate possible age-related changes in the disposition of factor IX procoagulant activity (FIX:C) after administration of recombinant factor IX (rFIX) and to translate the pharmacokinetic findings into suggestions for dosing of rFIX during prophylactic treatment of haemophilia B. Pharmacokinetic data were available from a previous study on 56 patients, aged 4-56 years (one of whom was excluded from analysis). FIX:C curves during prophylactic dosing were computer-simulated from the single-dose data. Clearance and volume of distribution at steady state of FIX:C increased linearly with body weight of the patients, consequently increasing during childhood and adolescence but remaining fairly constant during adulthood. The terminal half-life of FIX:C showed no correlation with age, while in vivo recovery (in U dL(-1) per U kg(-1) given) tended to increase. Computer-predicted trough levels of exogenous FIX:C during repeated doses of rFIX (50 U kg(-1)) and, conversely, doses (in U kg(-1)) needed to maintain a 1-U dL(-1) trough level showed little or no dependence on age. There was considerable interindividual variation in disposition and required doses of rFIX, emphasizing the need for individual dose titration. Dosing of rFIX according to lean body mass instead of body weight did not reduce this variability. During prophylaxis a 1-U dL(-1) trough level can normally be maintained by dosing every 2-3 days, the former schedule resulting in, on average, a 45% lower consumption of rFIX.

Adolescent↗
PubMed2001

Defining the impact of hemophilia: the Academic Achievement in Children with Hemophilia Study.

OBJECTIVES: We characterized a population-based cohort of school-aged children with severe hemophilia with respect to type of treatment, on-demand versus prophylaxis, and frequency of bleeding episodes in the year before enrollment. We also investigated the association between hemophilia-related morbidity, measured by number of bleeding episodes in the year before enrollment, and academic performance after adjustment for other factors known to have an effect on achievement. Finally, we explored the mechanisms for the association between bleeding episodes and academic achievement. STUDY DESIGN: This study was a multicenter investigation of boys 6 to 12 years old with severe factor VIII deficiency (clotting factor level <2%) receiving care in US hemophilia treatment centers. Children with a history of inhibitor, severe developmental disorder, significant psychiatric disorder, or insufficient fluency in English were excluded from the study. On-demand treatment was defined as administration of clotting factor on the occurrence of a bleeding episode. Prophylactic therapy was defined as a course of regular infusions for >2 months with a goal of preventing bleeding episodes. Academic achievement was measured by the Wechsler Individual Achievement Test. Quality of life was measured by the Child Health Questionnaire. Of particular interest was the Physical Summary (PhS) measure of the Child Health Questionnaire. The type of information captured by the PhS includes limitations in physical activity, limitations in the kind or amount of schoolwork or social activities the child engaged in, and presence of pain or discomfort. RESULTS: One hundred thirty-one children were enrolled, a median center recruitment rate of 77%. The mean age of the participants was 9.6 years, and approximately half of the participants had completed less than the fourth grade at the time of enrollment. Sixty-two percent of the children were on prophylaxis at enrollment, and 9% had previously been on prophylaxis but were currently on on-demand therapy. Two groups were defined: ever treated with prophylaxis and never treated with prophylaxis. For those ever treated, treatment duration ranged from 2.7 months to 7.7 years, with one half of the children treated with prophylaxis for >40% of their lifetimes; 29% had always been on on-demand therapy. Children in both treatment groups were similar with respect to age, clotting factor level, parents' education, and IQ. The median number of bleeding episodes experienced in the year before enrollment for the cohort as a whole was 12. The median number of bleeding episodes in children on prophylaxis at enrollment was significantly lower than in children on on-demand therapy (6 vs 25.5). The mean achievement scores were within the average range of academic performance: reading, 100.4; mathematics, 101.6; language, 108.1; writing, 95.4; and total achievement, 102.5. When children were categorized as above or below the study group median by number of bleeding episodes, those who had a low number of bleeding episodes (< or =11) had better total achievement (104.4 vs 100.6) and mathematics (103.6 vs 99.6) than children in the higher bleeding episode category (> or =12) after adjusting for child's IQ and parents' education. Treatment with prophylaxis per se was not associated with better test scores, but children who had been treated on a regimen of long-term prophylaxis (>40% of lifetime) and reported < or =11 bleeding episodes in the year before enrollment had significantly higher scores in total achievement (104.9 vs 100.6), mathematics (105.2 vs 99.6), and reading (104.0 vs 98.6) than all other children reporting > or =12 bleeding episodes in the same time period. Increased school absenteeism and hemophilia-related limitations in physical functioning among children with greater frequency of bleeding episodes were proposed as the mechanisms for lower scores. The number of bleeding episodes was positively correlated with school absenteeism (Spearman correlation = 0.23), and children with more school absences had lower scores in mathematics, reading, and total achievement, even after adjusting for the child's IQ and parents' education. Children with fewer bleeding episodes also had better PhS scores than children in the high bleeding episode category (48.4 vs 41.3). The mean PhS for children in the low bleeding episode group (48.4) was similar to that of the general US population (50), but the mean PhS for children in the higher bleeding episode group was almost a full standard deviation lower than the mean for the general US population. PhS scores were positively related to reading and total achievement scores after adjusting for IQ and parents' education. Of interest and concern was a group of children who were reportedly being treated with prophylaxis during the year before enrollment (N = 18) but whose bleeding events were not optimally suppressed. These children were 3 times as likely (33.3% vs 11.1%) to be receiving < or =2 infusions per week as children on prophylaxis who reported < or =11 bleeding episodes during the same period. A review of the sites of bleeding reported for the 18 children revealed that 12 (66.6%) experienced > or =25% of their bleeding episodes in the same joint. CONCLUSIONS: Each child should have the opportunity to achieve his or her potential. Control of a chronic disorder must include this important goal as well as the more commonly identified medical outcomes. This study has identified an important association between the number of bleeding episodes experienced and academic achievement in a cohort of school-aged children with severe hemophilia. The data support the assertion that therapeutic care programs in this population must not be evaluated only in terms of financial cost to achieve adequate musculoskeletal outcomes. Also significant are the individual and societal benefits of increased academic accomplishments if adequate suppression of hemorrhagic events can be attained. The number of bleeding episodes experienced, regardless of treatment regimen, should be followed to optimize the child's academic outcome.

Absenteeism↗
PubMed2001

The role of NDR1 in avirulence gene-directed signaling and control of programmed cell death in Arabidopsis.

Arabidopsis plants containing the ndr1-1 mutation are incapable of mounting a hypersensitive response to bacteria carrying avrRpt2, but show an exaggerated cell death response to bacteria carrying avrB (Century et al., 1995). We show here that ndr1-1 plants are severely impaired in induction of systemic acquired resistance and PR1-driven transcription of a reporter gene in response to Pseudomonas syringae strains carrying avrRpt2 but not in response to P. syringae carrying avrB. The ndr1-1 mutation also impaired salicylic acid (SA) accumulation in response to treatments that produced reactive oxygen species (ROS) and impaired induction of systemic acquired resistance in response to in situ production of ROS. Hydrogen peroxide accumulated in wild-type Arabidopsis leaves beginning 4 to 7 h postinoculation with P. syringae carrying either avrRpt2 or avrB. In ndr1-1 plants, P. syringae carrying avrRpt2 elicited no detectable hydrogen peroxide production. Hydrogen peroxide production in response to bacteria carrying avrB was similar to that of Columbia in kinetics but of lesser intensity at early time points. These data are interpreted to indicate that NDR1 links ROS generation to SA production and that the phenotypic consequences of the ndr1-1 mutation are caused by a reduced ability to accumulate SA upon pathogen infection.

Apoptosis↗
PubMed2000

Platelet function disorders.

Platelet function defects comprise a large and heterogeneous group of bleeding disorders that range in severity from mild to severe. Patients may be asymptomatic; however, the majority who are diagnosed present with easy bruising and mucocutaneous bleeding, or with excessive haemorrhage following injury or surgery. As the complex internal biochemical and signal transduction pathways are further understood, and as structural analysis of platelets advances, more of the mechanisms leading to platelet function defects will be uncovered. Despite advances in the understanding of the etiology of these defects in function, treatment remains fairly rudimentary. For platelet function disorders associated with a defect in a plasma coagulation factor, such as vWD and afibrinogenemia, treatment consists of replacement of the deficient coagulation factor. Adjunctive therapies (such as antifibrinolytics, microfibular collagen, fibrin glue, etc.), DDAVP/Stimate, and platelet transfusions remain the mainstay of therapy available at this time. Corticosteroids may play a role in the management of some of these disorders and may lead to a shortening of bleeding time, especially in storage pool defects or release defects failing to respond to DDAVP/Stimate.

Animals↗
PubMed2000

Recombinant factor VIIa in the treatment of bleeding in hemophilic children with inhibitors.

Information contained in this review of the use of recombinant factor VIIa (rFVIIa, NovoSeven) in the pediatric population was obtained through review of literature and abstraction of data available at Novo Nordisk. Pharmacokinetic investigations in hemophilic children suggest that rFVIIa may have a shorter half-life and more rapid clearance in the pediatric population than in adults, with resultant implications for dosing. Analysis of pediatric data from various studies and case reports indicates that rFVIIa is safe and effective for the control of spontaneous or surgical bleeding in hemophilic children with inhibitors, including central nervous system bleeds, and bleeding episodes during immune tolerance induction therapy. The very young pediatric population (less than 1 year of age) poses specific difficulties in treatment, and rFVIIa provides an effective alternative to other therapeutic modalities. In some hemophilia B patients with inhibitors, anaphylactic reaction to FIX infusions is a potentially life-threatening problem, for which rFVIIa may provide the only safe alternative therapy for the control of bleeding episodes. Continuous infusion of rFVIIa has also been used effectively in individual cases. Optimal dosing regimens, both intermittent and continuous, still need to be determined in children.

Autoantibodies↗
PubMed1998

Prospective, randomised trial of two doses of rFVIIa (NovoSeven) in haemophilia patients with inhibitors undergoing surgery.

Recombinant factor VIIa (rFVIIa: NovoSeven; Novo Nordisk) has proven efficacy in the treatment of haemophilic patients with inhibitors. This prospective, double-blind study compared rFVIIa (35 vs. 90 microg/kg) in the initiation and maintenance of haemostasis during and after elective surgery. Patients with inhibitors (FVIII, n = 26; FIX, n = 3) received rFVIIa immediately prior to incision; intraoperatively as needed; every 2 h for the first 48 h; and every 2-6 h for the following 3 days. Haemostasis was evaluated during surgery, at 0, 8, 24 and 48 h and 3, 4 and 5 days after wound closure. After day 5, open-label rFVIIa (90 microg/kg) was available for maintenance. Intraoperative haemostasis was achieved in 28/29 patients. All high-dose patients and 12/15 low dose patients had satisfactory haemostasis during the first 48 h. Twenty-three patients (13/14 high dose) successfully completed the study. Although the 35 microg/kg dose is probably sub-optimal for post-operative management, at least in major procedures, rFVIIa 90 microg/kg is an effective first-line option in surgery for patients with inhibitors.

Adolescent↗
PubMed1998

Home treatment of mild to moderate bleeding episodes using recombinant factor VIIa (Novoseven) in haemophiliacs with inhibitors.

OBJECTIVE: To assess the safety and efficacy of a fixed dose of recombinant activated factor VII (rFVIIa; NovoSeven) in the home setting for mild to moderately severe joint, muscle; and mucocutaneous bleeding episodes in patients with haemophilia A or B with inhibitors. DESIGN: Multicentre, open-label, single arm, phase III study of one year duration. METHODS; Patients or their caregivers administered up to three doses of rFVIIa (90 microg/kg i.v.) at 3 h intervals within 8 h of the onset of a mild to moderate bleeding episode. Once the subject considered that rFVIIa had been "effective" with regard to haemostasis (after 1-3 injections), one further (maintenance) dose of rFVIIa was administered. RESULTS: Of 60 patients enrolled, 56 experienced at least one bleed, and 46 completed the one year study. 614 of 877 bleeds (70%) were evaluable according to protocol definitions. Haemostasis was rated as "effective" in 92% (566/614) of evaluable bleeds after a mean of 2.2 injections. For successfully treated episodes, the time from onset of bleeding until administration of the first injection was 1.1+/-2.0 h (mean+/-SD). Twenty-four hours after initial successful response, haemostasis was reported as having been maintained in 95% of cases. Efficacy was comparable for muscle, joint and target joint, and mucocutaneous bleeding episodes. In an intent-to-treat analysis of all 877 bleeding events, efficacy outcomes were equivalent to the evaluable bleeds, with an effective response in 88% of treated episodes. Treatment-related adverse events occurred in 32 (3% of all) bleeding episodes and consisted of re-bleeds/new bleeds in more than 50% (18/32) of these events. A single episode of superficial thrombophlebitis was the only thrombotic complication encountered, and there were no patient withdrawals due to adverse events. Development of FVII(a) antibodies could not be detected, and hypersensitivity reactions to rFVIIa were not reported. CONCLUSION: rFVIIa is effective and well tolerated when used in the home setting to treat mild to moderate bleeding episodes in patients with haemophilia A or B with inhibitors.

Adolescent↗
PubMed1997

NDR1, a pathogen-induced component required for Arabidopsis disease resistance.

Plant disease resistance (R) genes confer an ability to resist infection by pathogens expressing specific corresponding avirulence genes. In Arabidopsis thaliana, resistance to both bacterial and fungal pathogens, mediated by several R gene products, requires the NDR1 gene. Positional cloning was used to isolate NDR1, which encodes a 660-base pair open reading frame. The predicted 219-amino acid sequence suggests that NDR1 may be associated with a membrane. NDR1 expression is induced in response to pathogen challenge and may function to integrate various pathogen recognition signals.

Amino Acid Sequence↗
PubMed1997

Human plasminogen activator inhibitor-1 (PAI-1) deficiency: characterization of a large kindred with a null mutation in the PAI-1 gene.

Plasminogen activator inhibitor-1 (PAI-1), the primary inhibitor of tissue- and urokinase-type plasminogen activators, is considered a critical regulator of the fibrinolytic system. We previously reported a child with abnormal bleeding and complete PAI-1 deficiency caused by a frame-shift mutation in exon 4 of the PAI-1 gene. The purpose of this study was to provide genetic and clinical data on the extended pedigree of the original proband to better define the phenotype associated with PAI-1 deficiency. Allele-specific oligonucleotide hybridization was used to genotype individuals, and serum PAI-1 antigen was measured by enzyme-linked immunosorbent assay. By this approach we have identified 19 individuals who are heterozygous for the PAI-1 null allele and 7 homozygous individuals with complete PAI-1 deficiency. Clinical manifestations of PAI-1 deficiency were restricted to abnormal bleeding, which was observed only after trauma or surgery in homozygous affected individuals. A spectrum of bleeding patterns was observed, including intracranial and joint bleeding after mild trauma, delayed surgical bleeding, severe menstrual bleeding, and frequent bruising. Fibrinolysis inhibitors, including epsilon-aminocaproic acid and tranexamic acid, were effective in treating and preventing bleeding episodes. Other than abnormal bleeding, no significant developmental or other abnormalities were observed in homozygous PAI-1-deficient individuals. Heterozygous PAI-1 deficiency was not associated with abnormal bleeding, even after trauma or surgery. These observations define the clinical spectrum of PAI-1 deficiency and provide additional evidence to support the hypothesis that the primary function of plasminogen activator inhibitor-1 in vivo is to regulate vascular fibrinolysis.

Adolescent↗
PubMed1996

Pharmacokinetics of von Willebrand factor and factor VIIIC in patients with severe von Willebrand disease (type 3 VWD): estimation of the rate of factor VIIIC synthesis. Cooperative Study Groups.

Nine patients (10 infusions) with a confirmed diagnosis of type 3 VWD were infused with von Willebrand factor (human), a preparation of von Willebrand factor (VWF) with a very low factor VIII content. Each patient was infused with one dose of approximately 50 or 100 iu ristocetin cofactor activity (VWF:RiCoF) per kg body weight. Bleeding times were performed during the 24 h period after infusion. Plasma samples were obtained over the 96 h period after infusion and were analysed for factor VIII coagulant activity (FVIIIC), VWF:RiCoF, von Willebrand factor antigen (VWF:Ag), and multimers. The FVIIIC data were analysed by non-linear least-squares analysis assuming constant FVIIIC 'synthesis' and exponential decay. The VWF data were fitted for exponential decay. The average decay rates for FVIIIC, VWF:RiCoF and VWF:Ag were 0.041, 0.061 and 0.056 respectively. The average calculated 'synthesis' rate for FVIIIC was 6.4 u/dl/h. The synthesis of FVIIIC was slightly faster and the decay slightly slower following the infusion of 100 iu VWF:RiCoF/kg than of 50 iu VWF:RiCoF/kg. Correction of the bleeding time was strongly dose dependent. At 4 h post infusion the median bleeding time was 9 min following a dose of 50 iu VWF:RiCoF/kg versus 3 min with a dose of 100 iu VWF:RiCoF/kg. There was no decrease in the bleeding time until the level of VWF:Ag or VWF:RiCoF reached > 100 u/dl.

Adolescent↗
PubMed1996

American experience with home use of NovoSeven: recombinant factor VIIa in hemophiliacs with inhibitors.

A novel investigational product, recombinant factor VIIa, manufactured by Novo Nordisk, is presently in clinical trial for evaluation of safety and efficacy when used in the home setting in patients with hemophilia A and B with inhibitors for control of hemostasis in mild to moderate joint, muscle and mucocutaneous bleeding episodes. The clinical trial is an open label, multicenter, uncontrolled study in which 60 patients are enrolled and treated for 1 year with the goal of accumulating 120 evaluable bleeding episodes. Reported here is an outline of the study, review of currently enrolled patient demographics, and the data accumulated to date from the Indiana Hemophilia Comprehensive Center.

Antibody Formation↗
PubMed1996

Safety and efficacy of monoclonal antibody purified factor IX concentrate in previously untreated patients with hemophilia B.

The safety and efficacy of a monoclonal antibody purified factor IX concentrate were evaluated in two continuing trials of 32 previously untreated patients with mild, moderate, or severe hemophilia B. Patients were evaluated every 2 weeks for 24 weeks and every 3 months thereafter for at least 1 year. No patients became positive for human immunodeficiency virus antibody or hepatitis C virus antibody during the trial. Two patients developed a false-positive hepatitis B core antibody, one transiently, but neither had elevated levels of alanine aminotransferase (ALT). None of the 25 patients evaluable for non-A, non-B, non-C hepatitis by strict International Society of Thrombosis and Hemostasis criteria developed elevated levels of ALT indicative of posttransfusion infection. Anaphylaxis occurred in one subject who also developed an inhibitor to factor IX (19.3 Bethesda units). Five of the eight adverse events reported (63%) were mild in severity, and the relationship of three of these to therapy was considered remote. Hemostasis with monoclonal antibody purified factor IX concentrate was excellent in all patients.

Adolescent↗
PubMed1995

Quantitative analysis of the interactions between prenyl Rab9, GDP dissociation inhibitor-alpha, and guanine nucleotides.

Rab9 is a Ras-like GTPase required for the transport of mannose 6-phosphate receptors between late endosomes and the trans Golgi network. Rab9 occurs in the cytosol as a complex with GDP dissociation inhibitor (GDI), which we have shown delivers prenyl Rab9 to late endosomes in a functional form. We report here basal rate constants for guanine nucleotide dissociation and GTP hydrolysis for prenyl Rab9. Both rate constants were influenced in part by the hydrophobic environment of the prenyl group. Guanine nucleotide dissociation and GTP hydrolysis rates were lower in the presence of lipid; detergent stimulated intrinsic nucleotide exchange. GDI-alpha inhibited GDP dissociation from prenyl Rab9 by 2.4-fold. GDI-alpha associated with prenyl Rab9 with a KD of 60 nM in 0.1% Lubrol and 23 nM in 0.02% Lubrol. In 0.1% Lubrol, GDI-alpha inhibited GDP dissociation half maximally at 72 +/- 18 nM, consistent with the KD determinations. These data suggest that GDI-alpha associates with prenyl Rab9 with a KD of < or = 23 nM under physiological conditions. Finally, a previously uncharacterized minor form of GDI-alpha inhibited GDP dissociation from prenyl Rab9 by 1.9-fold and bound prenyl Rab9 with a KD of 67 nM in 0.1% Lubrol.

Animals↗
PubMed1995

Safety of high doses of a monoclonal antibody-purified factor IX concentrate. The Mononine Study Group.

This report summarizes safety and efficacy information among patients treated with high doses (> 75 U/kg) of a monoclonal antibody-purified factor IX concentrate [coagulation factor IX (human) monoclonal antibody purified)] in two clinical trials. One hundred infusions of this factor IX concentrate at doses > 75 U/kg were administered to 35 patients, six of whom had experienced thrombotic complications during previous treatment with prothrombin complex concentrate. Hemostasis in all patients was rated as "excellent," and there were no thrombotic complications.

Adult↗