scholarly journals Prophylactic Treatment of Severe Haemophilia Á Patients with Inhibitors to FVIII with Peglip-FVIII

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1040-1040
Author(s):  
Margarita Timofeeva ◽  
Nadezhda I. Zozulya ◽  
Tatiana Pospelova ◽  
Marina V Kosinova ◽  
Igor Kurtov ◽  
...  
Keyword(s):  
Prophylactic Treatment ◽  
Conflicts Of Interest ◽  
Ex Vivo ◽  
Haemophilia A ◽  
Severe Haemophilia ◽  
Before And After ◽  
History Of ◽  
Bleeding Episodes ◽  
The Mean ◽  
Bypassing Agents

Abstract Background: FVIII replacement therapy is ineffective for severe haemophilia A (HA) patients who develop inhibitors to FVIII. Patients with intractable inhibitors currently require FVIII mimetics and/or bypassing agents to prevent bleeding. PEGylated liposomes (PEGLip) have been shown to protect FVIII from anti-FVIII antibodies in ex-vivo human studies and in combination with FVIII may present an option for the prophylactic treatment of inhibitor patients. Aims: To (a) demonstrate that PEGLip-FVIII administered intravenously (IV) to severe HA patients with history of inhibitors to FVIII enhances their clotting activity, (b) compare the number of bleeding episodes before and after PEG-Lip treatment, and (c) demonstrate that PEGLip-FVIII is well tolerated with no increase in inhibitor titres. Methods: Stage A: Four patients with a history of inhibitors were given single IV injections of PEGLip-FVIII (simoctocog alfa) at a dose of 22mg/kg PEGLip + 35 IU/kg FVIII and assessed for clotting activity at 0 hours (pre-injection) and at 20min, 1, 2, 4, 8, 24 hours, and daily thereafter up to 7 days using Rotational Thromboelastometry. Stage B: Patients received IV injections of PEGLip-FVIII for 6-weeks at a frequency determined by the investigator based on results obtained during Stage A. Inhibitor titres were monitored throughout. Results: Results are shown below. Treatment with PEGLip-FVIII was highly tolerated with no clinically significant changes in inhibitor titres. No Adverse Drug Reactions were reported. The mean frequency of administration of PEGLip-FVIII was every 5.7±1.4 days. The mean number of bleeding episodes reported during Stage B was 0.5±0.9 per month (due to 1 patient) compared with 0.9±0.4 per month recorded during the 24 weeks prior to enrollment. Conclusion: PEGLip-FVIII in inhibitor patients demonstrated efficacy in preventing spontaneous bleeds without increasing inhibitor titres, indicating a novel FVIII-based treatment for this cohort. Planned studies in a larger cohort may confirm our findings. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Analysis of Hemorrhagic Phenotype and Cardiovascular Risk of Severe Hemophilia a Carriers and Difference with Female Working Population Control Group

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5048-5048
Author(s):  
María Eva Mingot-Castellano ◽  
María Jose Ariza-Corbo ◽  
Álvaro Amo Vázquez de la Torre ◽  
María Inmaculada Alonso-Calderón ◽  
Pedro Valdivielso ◽  
...  
Keyword(s):  
Cardiovascular Risk ◽  
General Population ◽  
Hemophilia A ◽  
Risk Scores ◽  
Control Group ◽  
Haemophilia A ◽  
Severe Haemophilia ◽  
Risk Of Death ◽  
History Of ◽  
The Mean

Abstract INTRODUCTION: Recent studies in male subjects with haemophilia have described a prevalence of cardiovascular risk factors (CVRF) and cardiovascular events (CVE) similar to the general population. This finding has not been tested in severe haemophilia A carriers so far. We have little information about whether there is a particular bleeding profile in this group and if this tendency is able to modify cardiovascular risk in these women. OBJECTIVES: To evaluate bleeding profile from laboratory and clinical point of view in haemophilia A carriers and working population controls; to define and to calculate CVRF, CVE and cardiovascular risk scores in severe haemophilia A carriers and controls; to analyse if there is any difference in cardiovascular risk between symptomatic severe haemophilia A carriers and general population. PATIENTS AND METHODS: This is a descriptive, cross-sectional, non interventional, single center study. Ethics Committee evaluation and written informed consent are requested to be included for carriers and controls. The target population are severe haemophilia A carriers from our area aged between 18 and 70 years old. The control group are women from regular health laboral checkings. We evaluate bleeding, ischemic and thrombotic personal and familiar history, bleeding profile (ISTH/SSC bleeding assessment tool, ISTH BAT), factor VIII (FVIII) genetic study, complete blood count, basic biochemistry, haemostasis (aPTT, PT, fibrinogen, platelet function tests, FVIIIc, FvWAg and FvWRCo, FXIII, homocysteine, resistence to APC, antithrombin, protein C and S, 20210A prothrombin mutation), cardiovascular risk (Framingham score and Systematic Coronary Risk Evaluation Project, SCORE). The controls have been studied in the same way with the exception of laboratory studies of hemostasis. Only in controls with pathologic ISTH BAT (greater than 3), basic and primary hemostasis have been studied. To describe continuous variables we will use mean, median, standard deviation, maximum and minimum. For categorical variables will be used the percentage of every category. RESULTS: Out of a total of 81 carriers have been identified between August 2012 to December 2013. We have evaluated 69 carriers. To achieve a confidence level of 95% with 50% heterogeneity we have recruited 138 controls. The mean age of carriers and controls was 43.7+/-15 and 41.5 +/-11.7 years old (p 0.308). In the group of carriers, the mean and standard deviation (SD) of FVIII levels were 87.2+/-35.7%, FvW:RCo 75.6 +/-30% and vWF:Ag 75.6 +/-30, 1%. We found no relationship between levels of FVIII:c and haemophilia genetic defect (34.8% substitutions, 34.8% intron 22, 27.5% mutations). 20.3% of carriers and 2.2% of controls present a pathologic ISTH BAT score (p 0.001). The table describes CVRF and cardiovascular risk scores of carriers and controls. TableCARRIERSCONTROLSHigh Blood Pressure(HBP)17,4%5%0,001Smoking29%32,6%0,596Sedentariness55,1%37,7%0,025Diabetes8,7%2,9%0,069Metabolic Syndrome(ATPIII)14,5%8%0,143Dyslipemia14,5%12,8%0,474Overweight and Obesity50,7%34,8%0,027Framingham(median, IQR)2 (0,47-7,41)0,4 (0-3,75)0,001SCORE (median, IQR)1 (0,73-1,58)0 (0-0,71)0,001Family history ischemia66,7%28,3%0,001 No personal CVE in carriers group. We found two cases of thrombophilia. They are two women from the same family with high homocysteine levels and family history of heart attack and stroke in haemophiliacs men. Most of family history of ischemia in carriers group comes from haemophiliac male relatives. Among controls only one patient has experienced heart attack and other a deep vein thrombosis. They both were older controls with CVRF. We have analysed separately the 14 symptomatic carriers (pathological ISTH BAT). This particular group has a similar Framingham score to general population but remains in a higher risk of death from vascular event (SCORE) compared to general population. CONCLUSIONS: Low levels of FVIII do not prevent from developing vascular risk factors in syntomatic carriers of severe haemophilia A. In our media, we describe a higher prevalence of HBP, sedentariness, obesity and overweight in the group of carriers than in controls. The risk of suffering a cardiovascular event and the risk of death because of a cardiovascular events is higher in the group of severe hemophilia A carriers than in the working control population, even in symptomatic carriers. Disclosures No relevant conflicts of interest to declare.

Tracheobronchial Foreign Bodies: The Impact of a Postgraduate Educational Program on Diagnosis, Morbidity, and Treatment

PEDIATRICS ◽  
1982 ◽  
Vol 70 (1) ◽  
pp. 96-98
Author(s):  
Marc Puterman ◽  
Rafael Gorodischer ◽  
Alberto Leiberman
Keyword(s):  
Educational Program ◽  
Foreign Bodies ◽  
Final Diagnosis ◽  
Physician Performance ◽  
Postgraduate Educational ◽  
Before And After ◽  
History Of ◽  
The Mean ◽  
Hospital Days ◽  
The Impact

Aspirated foreign bodies (FBs) may remain undetected and cause serious complications. As part of a postgraduate educational program, results of a local survey were presented to the local medical staff in order to increase its awareness of this diagnostic possibility. The present study was carried out in order to evaluate the management of children with tracheobronchial FBs during two 2-year periods, before and after teaching sessions held in December 1976. In comparison with the previous two years during the 1977-1978 period, the percentage of cases in which a positive history of aspiration was obtained increased from 47.6% to 84.0%; the mean number of hospitalizations due to tracheobronchial FBs decreased from 1.9 to 1.04 per infant, and the mean number of hospital days required for final diagnosis decreased from 17.6 to 5.3. The postgraduate educational program had a positive effect on physician performance and patient care.

FRI0488 CLINICAL AND LABORATORY FEATURES OF PATIENTS WITH REMITTING SERONEGATIVE SYMMETRICAL SYNOVITIS WITH PITTING EDEMA COMPARED TO PATIENTS WITH SERONEGATIVE RHEUMATOID ARTHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 842-843
Author(s):  
M. Higashida-Konishi ◽  
K. Izumi ◽  
S. Hama ◽  
Y. Hayashi ◽  
Y. Okano ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Secondary Analysis ◽  
Sudden Onset ◽  
Finger Joints ◽  
Before And After ◽  
History Of ◽  
Rs3pe Syndrome ◽  
The Mean ◽  
Old Females ◽  
Pitting Edema

Background:In the case of seronegative arthritis, it was difficult to make a differential diagnosis between remitting seronegative symmetrical synovitis with pitting edema syndrome (RS3PE) and seronegative rheumatoid arthritis (seronegative RA) because the distribution of affected joints was similar and the patients with RS3PE or seronegative RA may have edema.Objectives:To compare the clinical characteristics of RS3PE and seronegative RAMethods:We retrospectively examine consecutive patients diagnosed with RS3PE or seronegative RA in our hospital from 2007 to 2019. Patients in whom both ACPA and RF were negative were included. The patients with RS3PE met the criteria of McCarty et al.: (1) pitting edema of the dorsum of both hands and both feet, (2) sudden onset of polyarthritis, (3) seronegative for ACPA and RF. (4)no radiologically evident erosions developed. The patients with seronegative RA met the EULAR/ACR 2010 criteria. The patients who were diagnosed with RS3PE at first and then diagnosed with seronegative RA afterward were included in seronegative RA group. The first analysis was performed on the affected joints, CRP, ESR, Hb, LDH, edema, the history of malignancy 2 years before and after the diagnosis, treatment, and the history of infection requiring hospitalization after the start of treatment. The affected joints were shoulders, elbows, wrists, finger joints (the MCP, and PIP joints), hips, knees, ankles, and toe joints (the MTP and PIP joints). The secondary analysis was performed on the above evaluations with a propensity score (PS) matching for age.Results:In the first analysis, 20 patients with RS3PE and 122 patients with seronegative RA were enrolled. The mean ages (RS3PE, seronegative RA) were 81.1, 67.4 years old. Females were 60.0%, 63.1%. The mean observation period was 25.4, 63.6 months. The proportion of affected joints were shoulders (25.0%, 42.6%), elbows (10.0%, 29.5%: p=0.06), wrists (85.0%, 73.8%), finger joints (80.0%, 95.1%: p=0.01), hips (0%, 9.8%), knees (40.0%, 37.7%), ankles (65.0%, 39.3%: p=0.03) and toe joints (40.0%, 32.8%). Edema at diganosis was observed in 100%, 17.21% (p <0.0001). The mean levels of the following blood tests at diagnosis were noted: CRP, 9.0 and 4.8 mg/dL (p=0.02); ESR, 87.6 and 60.7 mm/1h (p=0.003); Hb, 10.4 and 11.8 mg/dl (p=0.001); LDH, 198.3 and 177.9 U/L (p = 0.12); MMP-3, 742.5 and 633.8 ng/mL (p = 0.14). The proportion of patients with high LDH levels (>222 U/L) was 13.6% and 9.0% (p=0.0269). The proportion of patients having the history of malignancy was 20.0%, 8.2% (p=0.10). The patient treated with prednisolone as the initial treatment was 100% and 41.0%; the mean dose was 14.3 and 9.9 mg/d. After the start of treatment, the proportion of infection requiring hospitalization was 20.0 and 3.28% (p=0.002).In the secondary analysis with PS, 17 patients with RS3PE and 17 patients with seronegative RA were enrolled. The mean ages were 80.4, 78.9 years old. Females were 52.9, 76.4%. The affected joints with difference were elbows (11.8, 35.3%: p=0.10), wrists (82.4, 100%: p=0.06), and finger joints (82.4, 100%: p=0.06). The mean levels of Hb at diagnosis was 10.4, 11.4 mg/dL (p=0.01). The proportion of patients having the history of malignancy was 23.5% and 0% (p=0.03). After the start of treatment, the proportion of infection requiring hospitalization was 23.5% and 0% (p=0.03).Conclusion:When the ankles are affected and edema is observed, RS3PE is more likely than seronegative RA. RS3PE had higher levels of CRP, ESR, and LDH. The proportion of anemia was higher in RS3PE. The proportions of infection requiring hospitalization and the history of malignancy were higher in RS3PE.References:[1]McCarty DJ, O’Duffy JD et al. Remitting Seronegative Symmetrical Synovitis with Pitting Edema (RS3PE Syndrome). JAMA 1985; 254: 2763–2767. DOI:10.1001/jama.1985.03360190069027Disclosure of Interests:Misako Higashida-Konishi: None declared, Keisuke Izumi Grant/research support from: Asahi Kasei Pharma, Takeda Pharmaceutical Co., Ltd., Speakers bureau: Asahi Kasei Pharma Corp, Astellas Pharma Inc., Bristol Myers Squibb, Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Mitsubishi Tanabe Pharma Co., Satoshi Hama: None declared, Yutaro Hayashi: None declared, Yutaka Okano: None declared, Hisaji Oshima: None declared

The natural history of the immune response to exogenous factor VIII in severe haemophilia A

Haemophilia ◽  
1998 ◽  
Vol 4 (4) ◽  
pp. 546-551 ◽  
Author(s):  
C. A. Lee ◽  
C. M. Kessler ◽  
D. Varon ◽  
U. Martinowitz ◽  
M. Heim ◽  
...  
Keyword(s):  
Immune Response ◽  
Natural History ◽  
Factor Viii ◽  
Haemophilia A ◽  
Severe Haemophilia ◽  
Exogenous Factor ◽  
History Of

scholarly journals Efficacy and safety of the drug Octofactor in prophylactic treatment in patients with severe haemophilia A

2018 ◽  
Vol 5 (3) ◽  
pp. 60-73 ◽  
Author(s):  
T. A. Andreeva ◽  
V. Yu. Zorenko ◽  
I. L. Davydkin ◽  
V. N. Konstantinova ◽  
O. E. Zalepukhina ◽  
...  
Keyword(s):  
Hemophilia A ◽  
Bleeding Episode ◽  
Coagulation Factor ◽  
Preventive Treatment ◽  
Haemophilia A ◽  
Severe Haemophilia ◽  
Efficacy And Safety ◽  
Spontaneous Bleeding ◽  
Bleeding Episodes ◽  
Blood Coagulation Factor Viii

Relevance.The development of a new recombinant blood coagulation factor VIII preparation is a promising step towards optimizing the treatment of hemophilia A. An introduction of a new medication into clinical practice precedes a clinical trials to evaluate the efficacy and safety.Materials and methods.The efficacy and safety of the domestic recombinant B-domain deleted blood coagulation factor VIII (FVIII) (moroctocog alfa, Octofactor®, JSC “GENERIUM”) were studied in the preventive treatment of 31 patients aged 21 to 52 years with severe haemophilia A. The Octofactor was administered in doses of 40 ± 5 IU/kg 3 times per week at intervals of at least 48 hours for 21 ± 1 weeks.Results.The efficacy of therapy was evaluated in 30 patients, since 1 patient refused to participate in the trial after the first injection of the study medication. There were registered 43 episodes of bleeding among 11 patients in the course of the preventive treatment with Octofactor. The average number of bleeding episodes was 1.4 ± 2.58. There were 43 bleeding episodes, 9 (20.9 %) of them were posttraumatic, 34 (79.1 %) of them were spontaneous. The average number of the spontaneous bleeding episodes (a major criterion of the efficacy) was 1.13 ± 2.19, which showed a low incidence of exacerbations of the hemorrhagic syndrome in the course of preventive treatment with Octofactor. Among all registered bleeding episodes there were 6 (14 %) mild episodes, 37 (86 %) moderate episodes. Among all spontaneous bleedings there were 6 mild episodes (17.6 %), 28 (82.4 %) moderate episodes. All posttraumatic bleedings were moderate. The vast majority (36, or 83.7 %) of bleeding episodes were stopped with administration of the Octofactor. The average number of administrations of the Octofactor for arresting 1 bleeding episode was 1.2 ± 0.56, for 1 spontaneous bleeding episode – 1.2 ± 0.59. On average, it was required to administer 3534.9 ± 2329.02 IU of the Octofactor to stop 1 episode of bleeding. In the vast majority of patients with severe hemophilia A (83.3–86.7 %),  the remaining activity FVIII was 1 % or more after the administration of the Octofactor in 48 hours. The total amount of the Octofactor, introduced for the prevention of bleeding, was 6,107,000 IU, to stop bleeding – 152,000 IU. The safety of therapy was evaluated in 31 patients. There were recorded 25 adverse events (AE) in 17 patients. Among them the laboratory ones prevailed in 23 (92 %) cases, which is not associated with the use of the trial medication. There were noted nausea and an unpleasant aftertaste in the mouth in 1 patient during the first administration of the Octofactor, and therefore he refused to continue to participate in the trial. Causality 2 AE with the study drug was regarded as definite. Such AE are expected and described in the instructions to the preparation. All AE were not serious and mild and resolved without outcomes. There were no presented thromboembolic events and immunogenic reactions.Conclusions.The obtained data testify to the efficacy and safety of the Octofactor both for preventive measures and for stopping bleeding in adult patients with severe hemophilia A.

Effects of primary and secondary prophylaxis on the clinical expression of joint damage in children with severe haemophilia A

2008 ◽  
Vol 99 (01) ◽  
pp. 71-76 ◽  
Author(s):  
Karin Kurnik ◽  
Frauke Friedrichs ◽  
Susan Halimeh ◽  
Anne Krümpel ◽  
Christoph Bidlingmaier ◽  
...  
Keyword(s):  
Bleeding Episode ◽  
Joint Damage ◽  
Primary Prophylaxis ◽  
Secondary Prophylaxis ◽  
Outcome Variable ◽  
Haemophilia A ◽  
Severe Haemophilia ◽  
On Demand ◽  
Haemophilic Arthropathy ◽  
Bleeding Episodes

SummaryPatients with severe haemophilia A (HA) can either be treated by regular FVIII infusions twice or three times per week (prophylaxis), or only in case of bleeding episodes (on-demand). Whereas prophylaxis reduces the number of bleeding episodes and may therefore prevent the development of haemophilic arthropathy, there is still a lot of controversy surrounding recommendations on age and dose at start of prophylactic regimens. The present database study was performed to investigate the role of primary versus secondary prophylaxis in HA children. The outcome variable was imaging-proven haemophilic joint damage. Forty-two children were initially treated with primary prophylaxis following the first bleeding episode, and were frequency-matched (year of birth, catchment area) to 67 pa- tients receiving “on-demand” therapy with an early switch to “secondary prophylaxis”. In multivariate analysis adjusted for the HA mutation type and the presence or absence of thrombophilia, the Pettersson score investigated at a median age of 12.5 years in joints with at least one documented bleeding episode was not significantly different between the two patient groups (p=0.944),and no statistically significant differences were found in patients with target joints (p=0.3), nor in children in whom synovitis had occurred (p=0.77). No conclusion can be drawn from the data presented herein whether primary prophylaxis or an early start of secondary prophylaxis is superior with respect to joint outcome in children with severe HA.

Effect Of Prednisone On Platelet Function In Patients With Bleeding Disorders

1981 ◽  
Author(s):  
R McKenna ◽  
F Bachmann ◽  
O Pichairut ◽  
B Whittaker
Keyword(s):  
Platelet Count ◽  
Platelet Function ◽  
Bleeding Time ◽  
Platelet Factor ◽  
Von Willebrand's Disease ◽  
Von Willebrand’S Disease ◽  
Before And After ◽  
History Of ◽  
The Mean ◽  
One Year

There is considerable controversy regarding the effect of Prednisone on the hemostatic mechanism of normal people versus patients with bleeding diatheses. We administered Prednisone 15 mg TID to patients with a positive history of a bleeding disorder, and evaluated the bleeding time and other in-vitrc tests of platelet function prior to and between the 5th and 7th day after Prednisone.Eleven patients were admitted into this study over a one year period. All patients had a history of excessive bruising, epistaxis, bleeding after dental extractions, and gastrointestinal or other bleeding in various combinations. Two out of the eleven had template bleeding times of greater than 15 minutes both before and after the Prednisone. These two patients were subsequently proven to have von Willebrand’s disease by the washed platelet ristocetin assay. In the remaining 9 patients, the pre-Prednisone bleeding time was 9.3 ±3.7 minutes (x ± 1 S.D.) whereas the post-Prednisone bleeding time was 5.8 ±3.6 minutes (x ±1 S.D.). These results were significant(td=3.83;df:7;p=0.007).Platelet aggregation in response to exogenous ADP (1 μM, 3 μM) Sigma bovine tendon collagen (1.8 mg/ml F) and epinephrine (5.5 × 104M), platelet retention in a glass bead column or platelet factor 3 availability did not improve or worsen after Prednisone therapy. The mean platelet count of 328,000±94,000 (x ±1 S.D.) was significantly (p=0.05) higher than the mean pre-Prednisone platelet count of 268,000±77,000 (x ±1 S.D.).In conclusion, we have shown that large doses of Prednisone appear to shorten the bleeding time in patients with significant defects in the primary hemostatic mechanism. However the bleeding time improvement is not evident in patients with von Willebrand’s disease.

Twenty-five years' experience of prophylactic treatment in severe haemophilia A and B

1992 ◽  
Vol 232 (1) ◽  
pp. 25-32 ◽  
Author(s):  
I. M. NILSSON ◽  
E. BERNTORP ◽  
T. LÖFQVIST ◽  
H. PETTERSSON
Keyword(s):  
Prophylactic Treatment ◽  
Haemophilia A ◽  
Severe Haemophilia
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