“OUTCOME ANALYSIS OF TIMELY CONSERVATIVE MANAGEMENT OF HAEMOPHILIC KNEE ARTHROPATHY WITH FACTOR REPLACEMENT AND PHYSIOTHERAPY.”

INTRODUCTION: Haemophilia is a disorder of the initiation of coagulation, and is due to reductions in the concentrations of, or the presence of a less active version of, one of two coagulation factors, factor VIII and factor IX. There are several orthopaedic problems linked to haemophilia including recurrent hemarthroses, chronic synovitis, exion deformities, hypertrophy of the growth epiphyses, damage to the articular cartilage and hemophilic arthropathy MATERIALS AND METHODS : 290 patients of all age group of haemophilia A and B coming to orthopaedic OPD with Knee Haemarthosis between October 2018 to May 2020 were included in our study. These patients were prospectively analyzed for complications and severity. HJHS Scoring system were used to assess the severity of joint disease. RESULTS : . out of 290 patients it was found that haemophilia was more prevalent in rural population (53.10%) as compared to urban population (46.90%). In our study it was found that majority of the patients with haemophilia had single joint involved (57.94%) as compared to 42.06% who had multiple joint involved. It was revealed that in majority right knee was involved (52.41%) followed by left joint in 47.58% patients with haemophilia. It was found that most common complication in patients of knee haemarthrosis was recurrent haemarthrosis (57.24%) followed by synovitis (27.93%). arthropathy (9.31%) . It was found that most common complication in patients of knee haemarthrosis was recurrent haemarthrosis (57.24%) followed by synovitis (27.93%). arthropathy (9.31%) . It was found that out of 290 patients with haemophilia, majority were performing regular physiotherapy (57.59%) followed by 42.41% of the patients who were occasional in physiotherapy. It was found that mean HJHS score was increasing with increasing the severity of the disease. Mean HJHS score for mild cases was 10.53±4.495 as compared to 13.06±7.575 of moderate cases and 17.82±7.991 of severe cases. CONCLUSION In present study haemophilia was more prevalent in rural population. Majority of the patients with haemophilia had single joint and in majority right knee was involved. Most common complication in patients of haemophilia was recurrent haemarthrosis followed by synovitis and arthropathy. Majority of our patients were having severe form of the disease. Adequate factor replacement along with good active physiotherapy early detection and prompt treatment with active life style makes muscles and joints healthier and stronger reduces tendancy of bleeding and further damage of joint. reduce the frequency and longterm complications of knee haemarthrosis like recurrent haemarthosis , synovitis ,arthropathy, fracture and deformity. Prophylactic factor replacement is having denitely positive role as per available literature over western countries, unfortunately it needs more specic clinical trial to know about longterm good results in India.

Download Full-text

Nonacog Alpha - an Efficient Therapeutic Option in Hemostase Management for Hemophilia Type B in Patients with Elective Arthropalsties

Revista de Chimie ◽

10.37358/rc.18.7.6444 ◽

2018 ◽

Vol 69 (7) ◽

pp. 1911-1914

Author(s):

Oana Viola Badulescu ◽

Razvan Tudor ◽

Wilhelm Friedl ◽

Manuela Ciocoiu ◽

Paul Dan Sirbu

Keyword(s):

Therapeutic Option ◽

Coagulation Factors ◽

Factor Ix ◽

Joint Disease ◽

Type B ◽

Total Endoprosthesis ◽

Recombinant Factor Ix ◽

Bleeding Episodes ◽

Low Incidence ◽

Articular Pathology

Hemophilia is a hereditary coagulopathy that is largely in the attention of developing countries, not because of its low incidence, but because of the high costs involved in the treatment of the disease and its disabling consequences of the disease, if treated inappropriately. The concentrates of coagulation factors currently available for the substitution treatment of hemophilic patients have undergone additional viral purification and inactivation techniques, in order to achieve a higher infectious safety, an aspect that also implies an increase in treatment costs for these patients. Currently, the major morbidity of patients with hemophilia is represented by the disabling articular pathology, secondary to repetitive bleeding episodes developed in the articular space. Although it has been proved that the prophylactic administration of coagulation factors helps to prevent joint disease in the case of patients that were not subject to prophylaxis, the repeated bleeding in the joints induces synovitis, which is irreversible and may progress despite subsequent prophylaxis. Under these conditions, total joint arthroplasty remains the only solution to reduce both, pain and subsequent bleeding episodes of hemophilic arthropathy. Effective hemostasis is a basic condition for successful interventions in hemophilic patients. In this regard, this paper aims to highlight the effectiveness of Nonacog Alpha, a product that contains recombinant factor IX, in the management of hemostasis, in the case of a patient with type B hemophilia, with indication of total endoprosthesis of the left hip.

Download Full-text

Biological Rationale for New Drugs in the Bleeding Disorders Pipeline

Hematology ◽

10.1182/asheducation-2011.1.397 ◽

2011 ◽

Vol 2011 (1) ◽

pp. 397-404 ◽

Cited By ~ 21

Author(s):

Patrick F. Fogarty

Keyword(s):

Coagulation Factor ◽

Coagulation Factors ◽

Developed Countries ◽

Factor Ix ◽

New Drugs ◽

Joint Disease ◽

Novel Agents ◽

Clotting Factor ◽

Alternative Pathways ◽

Long Acting

AbstractSince the introduction of replacement coagulation factor infusions for the treatment of hemophilia in the 1970s and subsequent improvements in the safety profile of available factor VIII (FVIII) and factor IX (FIX) concentrates, mortality among patients with hemophilia has improved considerably and now parallels that of the noncoagulopathic population in developed countries. Substantial morbidity, however, continues from the development of inhibitory antibodies, a recognized complication of clotting factor replacement; from infections and thrombosis complicating placement of central venous catheters, which are required in children with hemophilia due to frequent prophylactic infusions of coagulation factors with defined half-lives; and from disabling joint disease in individuals without access to costly prophylaxis regimens. In response to the need for long-acting, more potent, less immunogenic, and more easily administered therapies, an impressive array of novel agents is nearly ready for use in the clinical setting. These therapeutics derive from rational bioengineering of recombinant coagulation factors or from the discovery of nonpeptide molecules that have the potential to support hemostasis through alternative pathways. The number of novel agents in clinical trials is increasing, and many of the initial results are promising. In addition to advancing treatment of bleeding episodes or enabling adherence to prophylactic infusions of clotting factor concentrate, newer therapeutics may also lead to improvements in joint health, quality of life, and tolerability of iatrogenic or comorbidity-associated bleeding challenges.

Download Full-text

Changes Occurring During Coagulation in Glass. I. Normal Human Blood

Thrombosis and Haemostasis ◽

10.1055/s-0038-1654484 ◽

1960 ◽

Vol 4 (01) ◽

pp. 001-016

Author(s):

Jessica H. Lewis ◽

Paul Didisheim ◽

John H. Ferguson ◽

Kenichi Hattori

Keyword(s):

Coagulation Factors ◽

Factor Ix ◽

Factor Vii ◽

Sodium Oxalate ◽

Factor V ◽

Rapid Rise ◽

Rapid Fall ◽

Glass Tubes ◽

Normal Human ◽

The Individual

SummaryNormal whole blood was allowed to stand in glass tubes at 37° C, and the clotting process stopped at various intervals by the addition of sodium oxalate. During the first 15 minutes a marked acceleration of clotting activity was found. Study of the individual coagulation factors showed the following changes: a sustained and rapid fall in platelet count, a sustained and rapid rise in PTC (factor IX), a steady fall in fibrinogen, a more gradual fall in AHF (factor VIII), a rapid rise and subsequent fall in proaccelerin (factor V) activity, a somewhat lesser and slower rise and fall in proconvertin (factor VII) activity, and a slow fall in prothrombin concentration. No changes were noted in Hageman factor or PTA activities.

Download Full-text

HELIOTHERAPY IN THE TREATMENT OF PSORIATIC ARTHRITIS

Knowledge International Journal ◽

10.35120/kij2802483g ◽

2018 ◽

Vol 28 (2) ◽

pp. 483-487

Author(s):

Snezhina Georgieva ◽

Dilyana Zvezdova

Keyword(s):

Psoriatic Arthritis ◽

Clinical Picture ◽

Local Therapy ◽

Severe Form ◽

Climatic Conditions ◽

Joint Disease ◽

Immune Mediated ◽

Social Comfort ◽

Pigment Type ◽

Definition Of

Psoriatic arthritis is an inflammatory joint disease associated with psoriasis vulgaris, with routinely negative rheumatoid factors and the absence of rheumatoid nodules. This is an immune-mediated disease, according to generally accepted definition of Wright and Moll from 1973. American Association against Rheumatism classified psoriatic arthritis as an independent disease in 1964. Psoriatic arthritis is a single disease with a varied clinical picture. It belongs to the group of seronegative spondyloarthropathies with which there are general clinical features. It is believed that similar mechanisms determine the onset of psoriasis and psoriatic arthritis. The clinical picture includes various clinical forms that damage the peripheral and sacroiliac joints, spine, internal organs. The treatment of psoriatic arthritis is directed simultaneously to the influence of skin and joint changes. Purpose: Our study aims to summarize our long-standing experience in the treatment of psoriatic arthritis with heliotherapy. Subject of observation: Monitoring includes 132 patients with moderate and severe form of psoriasis treated at the sanatorium in town of Pomorie for 5 years in the period 2001-2006. Results and discussion: 132 patients with psoriasis with no effect on the local therapy and have proven psoriatic arthritis were selected. In our climatic conditions, heliotherapy is appointed during the warm half-year. Sun treatment was conducted under the conditions of a healing beach, which had shielding, radiation-protective devices. In patients with erythema - pigment and pigment type skin reactivity begins with 1-2 bioadoses reached to 8-10 biodoses, carried out in the area of overcomfort. Conclusion: The studies demonstrated that heliotherapy combined with medications significantly improves the prognosis of patients with this disease. The ultimate success would mean overcoming the frequent depression conditions, better survival and social comfort for patients with psoriatic arthritis.

Download Full-text

EXPRESSION IN ONTOGENESIS OF HUMAN BLOOD COAGULATION FACTORS

10.1055/s-0038-1644610 ◽

1987 ◽

Author(s):

H J Hassan ◽

A Leonardi ◽

C Chelucci ◽

R Guerriero ◽

P M Mannucci ◽

...

Keyword(s):

Blood Coagulation ◽

Protein C ◽

Antithrombin Iii ◽

Liver Homogenate ◽

Coagulation Factor ◽

Coagulation Factors ◽

Factor Ix ◽

Adult Liver ◽

Blood Coagulation Factors ◽

Guanidine Isothiocyanate

We have analyzed the expression of several blood coagulation factors (IX, VIII, X, fibrinogen chains) and inhibitors (antithrombin III, protein C) in human embryonic and fetal livers, obtained from legal abortions at 6-11 week post-conception. The age was established by morphologic staging and particularly crown-rump lenght measurement.Total cellular RNA was isolated from partially purified hepatocytes or total liver homogenate using the guanidine isothiocyanate method. Poly(A)+ RNA was selected by oligodT cellulose chromatography. The size and the number of the embryonic and fetal transcripts are equivalent to those observed in adult liver, as evaluated by Northern blot analysis of total or poly(A)+ RNA hybridized to human cDNA probes.The level of coagulation factor transcripts in embryonic and fetal liver was evaluated by dot hybridization of total RNA (0.5-10 ug), as compared to RNA extracted from normal adult liver biopsies. The expression of blood coagulation factors in embryos is generally reduced for all factors, but at a different degree. In 5-11 wk liver, the level of factor IX is 5-10% of that observed in adults, while fibrinogen, protein C, antithrombin III RNA level rises from 25 to 50% and factor X is expressed at a level comparable to that observed in adult liver.We conclude that during these stages of development blood coagulation factors are expressed according to three different time, curves, possibly due to the effect of different types of regulatory mechanisms.

Download Full-text

In Hemophilia Α Plasma Treated with Emicizumab, Factor IXa in Activated Prothrombin Complex Concentrates Is the Dominant Contributor to Enhanced Thrombin Generation

Blood ◽

10.1182/blood-2020-139586 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 16-17

Author(s):

Dougald Monroe ◽

Mirella Ezban ◽

Maureane Hoffman

Keyword(s):

Thrombin Generation ◽

Hemophilia A ◽

State Level ◽

Peak Level ◽

Coagulation Factors ◽

Major Effect ◽

Factor Ix ◽

Factor X ◽

Factor Ixa ◽

Activated Prothrombin Complex Concentrates

Background. Recently a novel bifunctional antibody (emicizumab) that binds both factor IXa and factor X has been used to treat hemophilia A. Emicizumab has proven remarkably effective as a prophylactic treatment for hemophilia A; however there are patients that still experience bleeding. An approach to treating this bleeding in hemophilia A patients with inhibitors is to give an activated prothrombin complex concentrate (APCC; FEIBA) (disfavored in NHF MASAC #255). APCC contains a number of coaguation factors including prothrombin, factor X (FX), and factor IX (FIX). APCC also contains activated factor X (FXa) and factor IX (FIXa). Previous work has shown that when APCCs are added to hemophilia A plasma containing emicizumab there is a significant increase in thrombin generation [J Thromb Haemost 2018;16:1580-1591]. The goal of this work was to study thrombin generation in hemophilia A plasma with emicizumab and to examine the role of the zymogen and activated components of an APCC in the increased thrombin generation. Methods. In hemophilia A plasma, thrombin generation assays were done using 100 µM lipid and 420 µM Z-Gly-Gly-Arg-AMC with or without emicizumab at 55 µg/mL which is the clinical steady state level. The reactions were initiated with low (1 pM) tissue factor (TF). The components of APCC were studied at concentrations that should mimic the levels seen in the plasma of a patient given a dose of 50 U/kg: prothrombin 1800 nM; FX 130 nM; FIX 90 nM; and FIXa 0.4 nM. Results. When initiated with low TF, hemophilia A plasma alone had essentially no thrombin generation. As expected, adding emicizumab enhanced thrombin generation. The addition of zymogen coagulation factors, prothrombin, FIX, and FX, separately or together gave a small increase in thrombin generation. However, addition of FIXa to emicizumab gave a large increase in peak thrombin. In hemophilia A plasma with emicizumab and FIXa, addition of prothrombin further increased thrombin generation and specifically increased the peak level of thrombin. Further addition of FX or FIX, separately or together, only minimally increased thrombin generation. Discussion. The strong contribution of factor IXa to the effects of APCCs on thrombin generation in hemophilia A plasma depends on the presence of emicizumab. In the absence of emicizumab, a study of the individual components of APCC showed that a combination of FXa and prothrombin at levels found in APCCs had the major effect on thrombin generation [Haemophilia. 2016;22:615-24]. That study found that FIXa did not increase thrombin generation. However, in the presence of emicizumab, despite the weak solution phase affinity of the bifunctional antibody for FIXa, small amounts of FIXa were the most significant contributor to thrombin generation. Disclosures Monroe: Novo Nordisk:Research Funding.Ezban:Novo Nordisk:Current Employment.Hoffman:Novo Nordisk:Research Funding.

Download Full-text

Home treatment for haemophilia

Drug and Therapeutics Bulletin ◽

10.1136/dtb.16.13.49 ◽

1978 ◽

Vol 16 (13) ◽

pp. 49-50

Keyword(s):

Factor Viii ◽

Coagulation Factors ◽

Home Treatment ◽

Factor Ix ◽

Coagulation Cascade ◽

Haemophilia A ◽

Haemophilia B ◽

Prolonged Bleeding ◽

Factor Deficiency ◽

Spontaneous Haemorrhage

Haemophilia A is caused by faulty synthesis of Factor VIII of the coagulation cascade. Haemophilia B (Christmas disease) is caused by a deficiency of Factor IX. The two conditions are clinically similar; all patients suffer from prolonged bleeding after trauma and in the more severely affected there is also spontaneous haemorrhage, particularly into joints and muscles. Correction of factor deficiency by plasma concentrates restores haemostasis but the intermittent nature of the haemorrhage, the scarcity of the transfused coagulation factors and their short plasma half-lives in most cases limit treatment to episodes of bleeding.

Download Full-text

Home Treatment for Children with Hemophilia

10.1055/s-0039-1682561 ◽

1977 ◽

Author(s):

N.B. McWilliams ◽

R. Ownby ◽

L.C. Anderson

Keyword(s):

Hepatitis B ◽

Severe Disease ◽

Symptomatic Improvement ◽

Home Treatment ◽

Factor Ix ◽

Chronic Synovitis ◽

Hepatitis B Antigen ◽

The Mean ◽

Mean Cost ◽

Disease Family

Twenty-four hemophilic boys between the ages of 2 and 21, 4 with factor IX and 20 with factor VIII deficiency, have been on a home transfusion program for 2 to 22 months. Criteria for participation include: moderate or severe disease, family cooperation, accessible veins and attendance at Comprehensive Hemophilia Clinic. Strict guidelines are given to families for treating hemorrhages without physician consultation at home, versus those that must be seen by a physician.Only 1 child has required hospitalization for bleeding. One child has had clinical hepatitis on 2 occasions. No patient has developed an inhibitor. No complications related to nonprofessional I.V. administration have occurred. Of 18 boys tested for hepatitis B antibodies, 17 were positive. None has been positive for hepatitis B antigen. Of 12 boys with established severe arthropathy, 8 have had symptomatic improvement and 4 are stable. Of 12 boys with minimal or no arthropathy, all are stable except 1 who has developed chronic synovitis.Psycho-social benefits include a new found independence, improved living routine for family units and opportunities to participate in more activities. The mean cost/boy/month was $397.We conclude that home treatment for hemophilic children is both safe and effective and should be available to all children meeting the above criteria.

Download Full-text

Degenerative joint disease in a Jamaican rural population.

Annals of the Rheumatic Diseases ◽

10.1136/ard.27.4.326 ◽

1968 ◽

Vol 27 (4) ◽

pp. 326-332 ◽

Cited By ~ 52

Author(s):

J M Bremner ◽

J S Lawrence ◽

W E Miall

Keyword(s):

Rural Population ◽

Degenerative Joint Disease ◽

Joint Disease

Download Full-text

Defective Gp130-Mediated Signal Transducer and Activator of Transcription (Stat) Signaling Results in Degenerative Joint Disease, Gastrointestinal Ulceration, and Failure of Uterine Implantation

Journal of Experimental Medicine ◽

10.1084/jem.194.2.189 ◽

2001 ◽

Vol 194 (2) ◽

pp. 189-204 ◽

Cited By ~ 155

Author(s):

Matthias Ernst ◽

Melissa Inglese ◽

Paul Waring ◽

Ian K. Campbell ◽

Shisan Bao ◽

...

Keyword(s):

Tyrosine Phosphatase ◽

Degenerative Joint Disease ◽

Joint Disease ◽

Cytokine Signaling ◽

Signal Transducer ◽

Joint Pathology ◽

Stat Signaling ◽

Chronic Synovitis ◽

Src Homology 2 Domain ◽

Gastrointestinal Ulceration

The receptor subunit gp130 transduces multiple cell type–specific activities of the leukemia inhibitory factor (LIF)/interleukin (IL)-6 family of cytokines through the signal transducer and activator of transcription (STAT) and src homology 2 domain–bearing protein tyrosine phosphatase (SHP)-2/ras/Erk pathways. To define STAT-dependent physiological responses, we generated mice with a COOH-terminal gp130ΔSTAT “knock-in” mutation which deleted all STAT-binding sites. gp130ΔSTAT mice phenocopyed mice deficient for IL-6 (impaired humoral and mucosal immune and hepatic acute phase responses) and LIF (failure of blastocyst implantation). However, unlike mice with null mutations in any of the components in the gp130 signaling pathway, gp130ΔSTAT mice also displayed gastrointestinal ulceration and a severe joint disease with features of chronic synovitis, cartilaginous metaplasia, and degradation of the articular cartilage. Mitogenic hyperresponsiveness of synovial cells to the LIF/IL-6 family of cyto-kines was caused by sustained gp130-mediated SHP-2/ras/Erk activation due to impaired STAT-mediated induction of suppressor of cytokine signaling (SOCS) proteins which normally limits gp130 signaling. Therefore, the joint pathology in gp130ΔSTAT mice is likely to arise from the disturbance of the otherwise balanced activation of the SHP-2/ras/Erk and STAT signaling cascades emanating from gp130.

Download Full-text