Hemophilia

Currently, molecular diagnosis of haemophilia A and B (HA and HB) highlights the excess risk-inhibitor development associated with specific mutations, and enables carrier testing of female relatives and prenatal or preimplantation genetic diagnosis. Molecular testing for HA also helps distinguish it from von Willebrand disease (VWD). Next-generation sequencing (NGS) allows simultaneous investigation of several complete genes, even though they may span very extensive regions. This study aimed to evaluate the usefulness of a molecular algorithm employing an NGS approach for sequencing the complete F8, F9 and VWF genes. The proposed algorithm includes the detection of inversions of introns 1 and 22, an NGS custom panel (the entire F8, F9 and VWF genes), and multiplex ligation-dependent probe amplification (MLPA) analysis. A total of 102 samples (97 FVIII- and FIX-deficient patients, and five female carriers) were studied. IVS-22 screening identified 11 out of 20 severe HA patients and ...

Seorang dokter asal Arab, Albucasis, yang hidup pada abad ke 12 telah menulis tentang sebuah keluarga yang setiap anak laki-lakinya meninggal setelah terjadi perdarahan akibat luka kecil. Kemudian pada tahun 1803, Dr. John Conrad Otto, seorang dokter asal Philadelphia menulis sebuah laporan mengenai perdarahan yang terjadi pada suatu keluarga tertentu saja. Ia menyimpulkan bahwa kondisi tersebut diturunkan hanya pada pria. Ia menelusuri penyakit tersebut pada seorang wanita dengan tiga generasi sebelumnya yang tinggal dekat Plymouth, New Hampshire pada tahun 1780. Kata hemofilia pertamakali muncul pada sebuah tulisan yang ditulis oleh Hopff di Universitas Zurich, tahun 1828 dan menurut ensiklopedia Britanica, istilah hemofilia (haemophilia) pertama kali diperkenalkan oleh seorang dokter berkebangsaan Jerman, Johann Lukas Schonlein pada tahun 1928. Hemofilia seringkali disebut dengan " The Royal Diseases " atau penyakit kerajaan. Ini di sebabkan Ratu Inggris, Ratu Victoria adalah seorang pembawa sifat/carrier hemofilia. Anaknya yang ke delapan, Leopold adalah seorang hemofilia dan sering mengalami perdarahan. Keadaan ini di beritakan pada British Medical Journal pada tahun 1868. Leopold meninggal dunia akibat perdarahan otak pada saat ia berumur 31 tahun. Salah seorang anak perempuannya, Alice, ternyata adalah carrier hemofilia dan anak laki-laki dari Alice, Viscount Trematon, juga meninggal akibat perdarahan otak pada tahun 1928. Hal terpenting dalam sejarah hemofilia adalah keberadaan penyakit tersebut di dalam keluarga kerajaan Rusia. Dua dari anak perempuan Ratu Victoria, Alice dan Beatrice, adalah carrier. Mereka menyebarkan penyakit hemofilia ke Spanyol, Jerman dan Keluarga Kerajaan Rusia. Alexandra, cucu perempuan dari Ratu Victoria, menikah dengan Tsar Nicholas II, Kaisar Rusia, pada awal tahun 1900-an. Alexandra seorang yang telah menjadi Ratu Rusia, adalah seorang carrier hemofilia, dan anak laki-lakinya yang pertama, Pangeran Alexei adalah penderita hemofilia. Nicholas dan Alexandra menaruh perhatian penuh terhadap masalah kesehatan anak mereka, pada saat itu Rusia sedang dalam keadaan kacau. Seorang biarawan Rusia, Rasputin, memperoleh keuntungan dengan pengaruhnya yang besar dalam lingkungan kerajaan Rusia, sebagian di karenakan hanya dia satu – satunya yang dapat menolong sang Pangeran Muda. Ia menggunakan ilmu sihirnya-nya untuk menghilngkan rasa sakit Alexei. Penggunaan ilmunya tidak hanya menghilangkan rasa sakit, tapi juga dapat memperlambat dan menghentikan perdarahan Alexei.

Primary Pure red cell aplaisa is a syndrome due to failure of erythropoiesis, normocytic anemia with severe reticulocytopenia due to the marked reduction of erythroid precursors in the bone marrow. Johnson-Blizard syndrome is rare, autosomal recessive or autosomal dominant, multisystem congenital disorder having abnormal development of pancreas, nose and scalp with mental retardation, hearing loss and growth failure. A case reported was a 3 months old male infant having prediagnosed primary pure red cell aplasia and Johnson-Blizard syndrome with marked pancreatic insufficiency. He presented with profuse greenish-bulky stools and severe pallor complexion. Homeopathic medicines Calcarea phos and Podophyllum was given in 3x potencies according to the sign and symptoms. Frequency of stool reduced within a month and his haemoglobin level also increased with passage of time. Medicine continued for almost 10 months and follow-up visits showed no recurrence of pure red cell aplasia. Homeopathic remedy Calcarea phos 3x is highly effective to increase the haemoglobin level and Podophyllum 3x is helpful to manage profuse stools

It is an inherited disorder, in which blood doesn't clot properly. It mean excessive bleeding after any injury or surgery. There is low amount of clotting factors (factor VIII and factor IX) in haemophilic patient. And the severity of disease also depend on the amount of factor.

Intramuscular (IM) administration of an adeno-associated viral (AAV) vector represents a simple and safe method of gene transfer for treatment of the X-linked bleeding disorder hemophilia B (factor IX, F.IX, deficiency). However, the approach is hampered by an increased risk of immune responses against F.IX. Previously, we demonstrated that the drug cocktail of immune suppressants rapamycin, IL-10, and a specific peptide (encoding a dominant CD4+ T cell epitope) caused an induction of regulatory T cells (Treg) with a concomitant apoptosis of antigen-specific effector T cells (Nayak et al., 2009). This protocol was effective in preventing inhibitory antibody formation against human F.IX (hF.IX) in muscle gene transfer to C3H/HeJ hemophilia B mice (with targeted F9 gene deletion). Here, we show that this protocol can also be used to reverse inhibitor formation. IM injection of AAV1–hF.IX vector resulted in inhibitors of on average 8–10BU within 1month. Subsequent treatment with the tolerogenic cocktail accomplished a rapid reduction of hF.IX-specific antibodies to <2BU, which lasted for >4.5months. Systemic hF.IX expression increased from undetectable to >200ng/ml, and coagulation times improved. In addition, we developed an alternative prophylactic protocol against inhibitor formation that did not require knowledge of T cell epitopes, consisting of daily oral administration of rapamycin for 1-month combined with frequent, low-dose intravenous injection of hF.IX protein. Experiments in T cell receptor transgenic mice showed that the route and dosing schedule of drug administration substantially affected Treg induction. When combined with intravenous antigen administration, oral delivery of rapamycin had to be performed daily in order to induce Treg, which were suppressive and phenotypically comparable to natural Treg.

Acquired hemophilia A (AHA) is a rare and severe bleeding disorder characterized by the development of autoantibodies against factor VIII. There is no previous study published in our country for AHA. The aim of this study that to describe the clinical symptoms, diagnostic criteria and treatment strategies in patients with AHA in the south of Tunisia. We retrospectively collected all patients diagnosed with AHA in the Department of Hematology of Hedi Chaker Hospital (Tunisia) from 2000 to 2017. The diagnosis was established in the presence of clinical hemorrhagic features associated with the isolated prolongation of the activated partial thromboplastin time (APTT), not corrected after two hours by incubating patient plasma with equal volumes of normal plasma, and with factor VIII less than 50%. We collected five patients with AHA in the South of Tunisia. There were 4 females and 1 male with the median age of 32 years old. The median FVIII C was 7% and the median value of FVIII inhibitor was 11 UB. The most common clinical symptoms were post-partum hematoma in 3 patients (60%), extensive cutaneous hematoma in one patient and hemorrhagic tooth extraction in one patient. All patients were treated in first-line therapy with bypassing agent FVIIa with successful response in 80% of cases. The first-line treatment of bleeding in AHA requires a bypassing agent and the optimal therapeutic strategy to eradicate the inhibitor include immunosuppression with corticosteroids alone or corticosteroids in combination with cyclophosphamide.

We report an unusual case of a patient with two
combined X-linked diseases, severe hemophilia A (HA)
and Duchenne muscular dystrophy (DMD), of which only
HA was hereditary. There was no family history of muscular
dystrophy. Genetic analysis revealed that HA was
caused by the hereditary coagulation factor VIII (F8) intron
22 inversion (distal/type I inversion), whereas DMD was
caused by a de novo deletion in the dystrophin gene. This is
the first report of a patient with two severe X-linked diseases,
of which only HA was hereditary. Despite the fact
that the probability of acquiring two X-linked abnormalities,
one hereditary and one de novo, is extremely low, the
emergence of such cases indicates that genetic testing for
distinct X-linked diseases could be of importance in
patients with hereditary hemophilia.

Betle leaf (Piper betle L.) is a medicinal plant. It contains essential oil and shows various biological activities, such as antibacterial, anticoagulant, etc. It is further reported to have low anticoagulant activities; thus, it is highly potential as a candidate for coagulant drug. Coagulant is used to prevent bleeding for patients with blood clotting disorders like hemophilia. In Indonesia, 1,236 people were reported with hemophilia. The standard parameters of anticoagulant activity are the freezing period and the compound concentrations. The purpose of this study was to determine the effect of betle leaf's essential oil on blood coagulation in patients with factor VIII and IX of blood plasma disorders. The isolation of essential oil is conducted through steam distillation method with two kinds of solvents, namely distilled water and n-hexane. The obtained n-hexane extract is then separated from the liquid-liquid extraction and rotary evaporator. Essential oil is diluted with citrate plasma solution. The test results of blood clots increase as the concentration of essential oils increase. The results are recorded as such: essential oils ½ times dilution of 99.67 seconds; ¼ times dilution of 127 seconds; 1/8 times dilution of 179 seconds; and 1/16 times dilution of 242.67 seconds. The test above proves that the piper betle extract possesses a coagulant activity. The ethanol extract contained in the piper betle could stimulate clotting in the blood cells. It is caused by the increase of blood plasma concentration which further escalate the plasma fluid into the blood cells. Based on this study, the activity of Mycobacterium tuberculosis can be obstructed by betle leaf in ½ times dilution. The extract significantly reduces acid which accelerates bacteria development. abstrak Daun Sirih (Piper betle L.) merupakan tanaman obat. Daun sirih terdapat kandungan minyak atsiri dan menunjukkan berbagai aktivitas biologi, diantaranya adalah antibakteri, antikoagulan, dan lain sebagainya. Di Indonesia, jumlah penderita hemofilia dilaporkan 1.236 orang. Koagulan digunakan untuk mencegah pendarahan pada penderitan kelainan pembekuan darah seperti hemofilia. Daun sirih dilaporkan memiliki aktivitas antikoagulan rendah, sehingga sangat potensial untuk kandidat obat koagulan. Parameter standar untuk aktifitas antikoagulan adalah waktu pembekuan dan konsentrasi senyawa. Tujuan dari penelitian ini adalah mengetahui pengaruh minyak atsiri daun sirih terhadap pembekuan darah pada penderita kelainan faktor VIII dan IX plasma darah. Isolasi minyak atsiri dilakukan dengan metode destilasi uap menggunakan dua macam pelarut yaitu aquades dan n-heksana. Ekstrak n-heksana yang diperoleh dipisahkan dengan ekstraksi cair-cair dan rotary evaporator. Minyak atsiri didilusi dengan larutan plasma sitrat. Hasil uji pembekuan darah minyak atsiri meningkat seiring konsentrasi minyak atsiri yaitu pengenceran 1/2 kali 99.67 detik; pengenceran 1/4 kali 127 detik; pengenceran 1/8 kali 179 detik; dan pengenceran 1/16 kali 242.67 detik. Pengujian di atas menunjukkan bahwa ekstrak piper betle memiliki aktivitas koagulan. Ekstrak etanol yang terkandung dalam piper betle dapat menyebabkan pembekuan dalam sel-sel darah. Hal ini disebabkan konsentrasi plasma darah naik, yang meningkatkan cairan plasma ke dalam sel darah. Berdasarkan penelitian ini, aktivitas Mycobacterium tuberculosis dapat dihambat oleh ekstrak daun sirih pada pengenceran 1/2 kali. Ekstrak secara signifikan mengurangi sifat asam yang dapat mempercepat perkembangan bakteri.

An increasing amount of evidence demonstrates the beneficial role of oxytocin (OT) in the cardiovascular system. Similar actions are attributed to genistein, an isoflavonic phytoestrogen. The treatment with genistein activates the OT system in the aorta of ovariectomized (OVX) Sprague-Dawley (SD) rats. The objective of this study was to determine the effects of low doses of genistein on the OT-induced effects in rat hypertension. The hypothesis tested was that treatment of OVX spontaneously hypertensive rats (SHRs) with genistein improves heart structure and heart work through a mechanism involving the specific OT receptor (OTR). OVX SHRs or SD rats were treated with genistein (in μg/g body wt sc, 10 days) in the presence or absence of an OT antagonist (OTA) [d(CH2)5, Tyr(Me)2, Orn8]-vasotocin or a nonspecific estrogen receptor antagonist (ICI-182780). Vehicle-treated OVX rats served as controls. RT-PCR and Western blot analysis demonstrated that left ventricular (LV) OTR, downregul...

This paper is an attempt to manage low-volume, high-cost, incurable (genetic) and non-priority diseases like Hemophilia in developing countries by Communication. Though it does not make any medical intervention in patients' life, if properly used it can spread enough awareness which in turn can help in preventing or at least in managing the disease.

Overview: Hemophilia is a genetic bleeding disorder caused by a deficiency of clotting factor and classified to Hemophilia A and B. Nutritional status is very important and proper nutrition among hemophilia patients is highly significant. This study aimed to evaluate nutritional status among adult hemophilia patients enrolled in the European Gaza Hospital in the Gaza strip.

A decrease in bone mass is observed in hemophilic patients. The aim of this study was to evaluate bone mineral density (BMD), parathyroid hormone (PTH), 25-hydroxy vitamin D (vitamin D), and a bone formation and resorption marker, procollagen type I N-terminal propeptide (PINP) and urinary N-terminal telopeptide (uNTX) respectively, in hemophilic patients and healthy controls. Laboratory parameters related to the pathogenesis of bone loss such as neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) were also evaluated. Thirty-five men over 18 years of age, with severe hemophilia (A and B) and receiving secondary prophylaxis, were included in the study. The same number of age-, sex-, and ethnicity-matched healthy controls were evaluated. Anthropometric, biochemical, and hormonal parameters were determined in both groups. No significant difference in anthropometric parameters was found between the two groups. The BMD was low in 34% of hemophilic patients. Vitamin D, calcium, and free testosterone levels were significantly lower (p < 0.001, p = 0.011, p < 0.001, respectively), while PTH, PINP, and activated partial thromboplastin time (aPTT) levels were significantly higher (p < 0.014, p = 0.043, p < 0.001, respectively), in hemophilic patients compared to controls. There was no significant difference between the two groups in NLR, PLR, phosphorus, thyroid-stimulating hormone, and uNTX level. The reduction of bone mass in hemophilic patients may be evaluated using the markers of bone formation and resorption, enabling early detection and timely treatment.

This article describes a sensitive impedimetric method for the determination of human blood coagulation factor IX protein (FIX) which is present in extremely low concentration in serum. An interdigitated electrode (IDE) whose surface was layered with zinc oxide was modified with two kinds of probes. One is an antibody, the other an aptamer against FIX. A comparative study between anti-FIX aptamer and anti-FIX antibody showed the aptamer to possess higher affinity for FIX. A sandwich aptamer assay was worked out by using the FIX-binding aptamer on the surface of the IDE. It has a detection limit as low as 10 pM which makes it 4 to 30-fold more sensitive than any other method reported for FIX. Moreover, to practice detection in clinical samples, FIX was detected from the human blood serum by spiking. In our perception, the sensitivity of the ZnO-modified IDE presented here makes it a promising tool for sensing clinically relevant analytes that are present in very low (sub-pM) concentrations.

Intravenous access for blood sampling or drug administration that requires peripheral venepuncture is perhaps the most common invasive procedure practiced in hospitals, clinics and general practice surgeries. We describe an idealised mathematical framework for modelling the dynamics of the peripheral venepuncture process. Basic assumptions of the model are confirmed through motion analysis of needle trajectories during venepuncture, taken from video recordings of a skilled practitioner injecting into a practice kit. The framework is also applied to the design and construction of a proposed device for accurate needle guidance during venepuncture administration , assessed as consistent and repeatable in application and does not lead to over puncture. The study provides insights into the ubiquitous peripheral venepuncture process and may contribute to applications in training and in the design of new devices, including for use in robotic automation .

Resumen Las enfermedades crónicas como la hemofilia rebasan los marcos institucionales sanitarios y abarcan tanto la vida cotidiana de la persona como su entorno social. Esta situación se agudiza cuando el afectado es un hijo de edad pediátrica. El objetivo de este trabajo fue describir y comparar la estructura de 50 familias que tienen algún miembro que padece hemofilia. Método. Participaron 50 madres y padres de pacientes pediátricos con hemofilia de diferente tipo y grado clínico (27 familias mexicanas y 23 argentinas), quienes respondieron el cuestionario FACES III en un estudio transversal exploratorio descriptivo y correlacional. Resultados. Se en-contró en los índices de cohesión que el 86% de las familias presentan una estructura familiar semirrelacionada; respecto a la adaptación, el 88% presentó una estructura rígida. En la comparación entre países, no hay diferen-cias significativas en los índices de cohesión; sin embargo, en cuanto a la adaptación, el 100% de las familias mexicanas, presentan una estructura rígida. Discusión. Es necesario un trabajo integral y sostenido desde la perspectiva psicológica que promueva un reequilibro saludable para mejorar la calidad de vida familiar.

Intraoperative coagulopathies can be complex and difficult to treat. Its management is further obfuscated in patients with
pre-existing bleeding disorders. Hemophilia C, is an autosomal recessive bleeding disorder. Like in most hemophilias, the
bleeding tendency is variable depending on the activity level of factor XI. However, because hemophilia C is less common
than other coagulopathies, it is usually recognized only after inappropriate bleeding often overcorrected with blood products, exposing the patient to further risks. The purpose of this report is to describe the role of rotational thromboelastometryin the anesthetic management of a patient with hemophilia C undergoing debulking of a recurrent intra-abdominal
and retroperitoneal liposarcoma.
Keywords: Factor XI Deficiency; Hemophilia C; ROTEM; Intraoperative Bleeding.

Despite the improvements in medical treatment over recent decades, hemophilia patients experience deterioration in their quality of life. This study provides a demographic and clinical characterization of hemophilia patients and how this affects their quality of life. This is based on a descriptive cross-sectional study on quality of life of 20
patients with hemophilia from the Province of Curicó, Maule Region.
The following antecedents were obtained from each patient: age, weight, height, severity of hemophilia, presence of hepatitis B virus,
hepatitis C virus, human immunodeficiency virus and Chagas disease.
To measure the quality of life the Short Form-36 survey was applied to
each one of the patients. The average age was 35±16 years old and bodymass index was 25±4 kg/m2. Regarding the severity level of the disease, in 55% of the patient it was found mild. Moreover, 25% of patients had hepatitis C. The most co-morbidity was for articular lesions. Quality of life is affected mainly by lack of sport and also due to the severity level of disease. The current challenge is to provide comprehensive care, both for patients and their families, where the main goal aims at restoring the sense of wellbeing, their right to be perceived as a person with capacity to develop.

Objective: Hemophilia is a common X-linked recessive coagulopathy causing recurrent bleeding into
the synovial joints and results in articular and periarticular abnormalities. To our knowledge, this is the
first comprehensive study aimed at studying the clinico-radiological joint score evaluation in hemophilic arthropathy in children from a developing country and its possible impact on the quality of life.
Methods: In this hospital-based, prospective, descriptive study, all children presenting to the pediatric
rheumatology clinic were studied. The joint physical examination was scored using the Hemophilia
Joint Health Score 2.1 (HJHS 2.1). The patients were then subjected to imaging of the most affected
joint using ultrasonography (USG) and magnetic resonance imaging (MRI). Detailed USG and MRI
radiological evaluation was recorded in the predesigned proforma using the Hemophilia Early Arthropathy Detection with Ultra Sound (HEAD-US) score and MRI DENVER score. The physical quality
of life as per Functional Independence Score in Hemophilia (FISH) was noted. The clinical, radiological,
and functional scores were analyzed with an appropriate statistical measure.
Results: The mean age at presentation was 7.4 years (interquartile range 4.9-10), with the knee being
the most common joint involved. All of the USG score, MRI score, and FISH score have a significant
correlation (p<0.05), with the HJHS 2.1 score with correlation coefficients of 0.7086, −0.8916, and
0.8607, respectively. USG and MRI had a correlation coefficient of −0.7145 and −0.8326 with FISH,
respectively.
Conclusion: The degree of association between HJHS 2.1 score was found to be maximum with HEADUS score, whereas a negative correlation was seen evaluating FISH score with both HEAD-US and MRI
DENVER scores. Use of these scores, specifically HEAD-US score, will result in consistent assessment of
hemophilic joints, optimizing the management of the destructive changes.

Based on our work and that of many other workers, we have developed a model of coagulation in vivo. Many workers have demonstrated mechanisms by which cells can influence the coagulation process. Nonetheless, the prevailing view of hemostasis remains that the protein coagulation factors direct and control the process with cells serving primarily to provide a phosphatidylserine containing surface on which the procoagulant complexes are assembled. By contrast, we propose a model in which coagulation is regulated by properties of cell surfaces. This model emphasizes the importance of specific cellular receptors for the coagulation proteins. Thus, cells with similar phosphatidylserine content can play very different roles in hemostasis depending on their complement of surface receptors. We propose that coagulation occurs not as a " cascade " , but in three overlapping stages: 1) initiation, which occurs on a tissue factor bearing cell; 2) amplification, in which plate-lets and cofactors are activated to set the stage for large scale thrombin generation; and 3) propagation, in which large amounts of thrombin are generated on the platelet surface. This cell based model explains some aspects of hemostasis that a protein-centric model does not. Modeling Hemostasis A model is a way of conceptualizing and understanding a complicated system. A good model should be simple enough to understand, yet complicated enough to accurately reflect the process it was designed to represent. The purpose of this paper is to present a model of coagula-tion which focuses on the roles of specific cell surfaces in controlling the coagulation process. This paper is intended to be part of a series in which different views of the coagulation process are presented. A " Cascade " or " Waterfall " model was a great advance in our understanding of coagulation, and was originally proposed by two groups nearly simultaneously (1, 2). This model was subsequently refined to the scheme shown in Fig. 1 as more was learned about the biochemistry of the coagulation factors. Every model highlights aspects of a process that are viewed as critical by the modeler. The cascade model of coagulation resulted from work that was aimed at elucidating the identity, function and interactions of the individual procoagulant proteins. It accurately represents the overall structure of the coagulation process as a series of proteolytic reactions. Each protease cleaves and activates the subsequent protease in the series. The Cascade model also included the recognition that anionic phospholipid, especially phosphatidylserine, was required for the assembly and optimal function of most of the coagulation complexes (3). This information was absolutely critical to understanding the coagulation reactions. However, the viewpoint that is implicit in this concept of coagulation is that the role of cells, especially platelets, is primarily to provide anionic phospholipid for coagulation complex assembly. The coagulation " Cascade " models very well the screening coagula-tion laboratory tests, the prothrombin time (PT) and activated partial thromboplastin time (aPTT), which correspond to the extrinsic and intrinsic pathways. However, it is clearly inadequate to explain the pathways leading to hemostasis in vivo. As this model currently exists, it is inconsistent with clinical observations in several key respects. If there are separate " intrinsic " and " extrinsic " coagulation pathways in vivo as shown in the Cascade model, why can the activation of factor X by the extrinsic (f.VIIa/TF-initiated) pathway not compensate for a lack of factor VIII or IX in hemophiliacs. In fact the activation of hemo-stasis by an " intrinsic " pathway in vivo must be questioned anyway, since deficiency of f.XII, high molecular weight kininogen (HMK) or pre-kallikrein (PK) does not cause a clinical bleeding tendency. Of course, it is clear that some components of the " intrinsic " pathway, f.VIII and f.IX, are essential for hemostasis, since their deficiency leads to hemophilia. We also know that deficiencies of f.X, f.V and f.VII lead to serious clinical bleeding syndromes. By contrast, f.XI deficiency is much less predictable in causing a bleeding diathesis and leads to a less severe clinical picture than deficiency of f.IX or f.VIII. Therefore, we (4-6) and others (7, 8) concluded that there are very likely not separate " extrinsic " and " intrinsic " pathways operating under normal conditions in vivo, and the overall model of coagulation required rethinking. A key step in understanding how the " extrinsic " and " intrinsic " pathways might be interdependent in vivo was the recognition that the f.VIIa/TF complex can activate f.IX as well as f.X (9). Also important was the finding that thrombin could directly activate factor XI on a charged surface (10). Once it was learned that activated platelets could provide a surface for activation of f.XI by thrombin under physiologic conditions (11, 12), it was clear why factor XII, HMK and PK might not be required for hemostasis. This led to a concept of hemostasis in which tissue factor (TF) was the primary physiologic activator. It was still not clear why direct activation of f.X by f.VIIa/TF could not compensate, at least partially, for a lack of factors IX or VIII. It was hypothesized that tissue factor pathway inhibitor (TFPI) inhibited f.VIIa/TF before it could produce enough f.Xa for hemostasis (7). These modifications to the cascade model reflect the evolution of our understanding of how the

Original Research Article This descriptive exploratory study was conducted to describe the night shift related health problems and other factor of the nurses working at Rajshahi Medical College Hospital, Rajshahi, Bangladesh. A convenience sample of nurses working that Medical wards nurses had a significant difference on sufficient sleep, and interpersonal at specific units (N=50) were studied using a structured questionnaire developed that describe the effect of night shift among nurses working at Rajshahi Medical College Hospital Rajshahi, Bangladesh. The findings showed that female conflicts. In addition, the results indicated that nurses experience health problem and their work performance affected by the night shift. The study findings indicated that night shift affects some specific ward nurses well-being. Consequently, this study emphasizes and urges the need to design proper nursing manager interventions that help nurses to improve quality care of nursing. It was obviously c...

A decrease in bone mass is observed in hemophilic patients. The aim of this study was to evaluate bone mineral density (BMD), parathyroid hormone (PTH), 25-hydroxy vitamin D (vitamin D), and a bone formation and resorption marker, procollagen type I N-terminal propeptide (PINP) and urinary N-terminal telopeptide (uNTX) respectively, in hemophilic patients and healthy controls. Laboratory parameters related to the pathogenesis of bone loss such as neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) were also evaluated. Thirty-five men over 18 years of age, with severe hemophilia (A and B) and receiving secondary prophylaxis, were included in the study. The same number of age-, sex-, and ethnicity-matched healthy controls were evaluated. Anthropometric, biochemical, and hormonal parameters were determined in both groups. No significant difference in anthropometric parameters was found between the two groups. The BMD was low in 34% of hemophilic patients. Vitamin D, c...

Objective: Hemophilia is a common X-linked recessive coagulopathy causing recurrent bleeding into the synovial joints and results in articular and periarticular abnormalities. To our knowledge, this is the first comprehensive study aimed at studying the clinico-radiological joint score evaluation in hemophilic arthropathy in children from a developing country and its possible impact on the quality of life. Methods: In this hospital-based, prospective, descriptive study, all children presenting to the pediatric rheumatology clinic were studied. The joint physical examination was scored using the Hemophilia Joint Health Score 2.1 (HJHS 2.1). The patients were then subjected to imaging of the most affected joint using ultrasonography (USG) and magnetic resonance imaging (MRI). Detailed USG and MRI radiological evaluation was recorded in the predesigned proforma using the Hemophilia Early Arthropathy Detection with Ultra Sound (HEAD-US) score and MRI DENVER score. The physical quality of life as per Functional Independence Score in Hemophilia (FISH) was noted. The clinical, radiological, and functional scores were analyzed with an appropriate statistical measure. Results: The mean age at presentation was 7.4 years (interquartile range 4.9-10), with the knee being the most common joint involved. All of the USG score, MRI score, and FISH score have a significant correlation (p&amp;lt;0.05), with the HJHS 2.1 score with correlation coefficients of 0.7086, −0.8916, and 0.8607, respectively. USG and MRI had a correlation coefficient of −0.7145 and −0.8326 with FISH, respectively. Conclusion: The degree of association between HJHS 2.1 score was found to be maximum with HEADUS score, whereas a negative correlation was seen evaluating FISH score with both HEAD-US and MRI DENVER scores. Use of these scores, specifically HEAD-US score, will result in consistent assessment of hemophilic joints, optimizing the management of the destructive changes.

El nonacog gamma es una forma recombinante del Factor IX de coagulación. Ha sido autorizada para el tratamiento y profilaxis de hemorragias en pacientes con hemofilia B (déficit de Factor IX). Los datos acumulados de los tres estudios clínicos disponibles han demostrado la equivalencia farmacocinética del nonacog gamma con respecto al factor IX de origen extractivo; asimismo, se han establecido adecuadamente su eficacia y su seguridad, tanto en uso profiláctico como a demanda, incluyendo pacientes pediátricos y sometidos a intervenciones quirúrgicas. Aparentemente, no hay diferencias entre el nonacog gamma y los medicamentos con factor IX de origen extractivo disponibles actualmente, ya que a estas alturas las exigencias de seguridad y calidad de estos últimos son lo suficientemente elevadas como para que tal origen condicione su uso clínico.

El albutrepenonocog alfa es una proteína de fusión de origen recombinante formada por una única molécula codificada por una secuencia de ADN producto de la fusión de los genes humanos codificantes del factor IX de coagulación y de la albúmina. La escisión en el interior del cuerpo permite la liberación paulatina de Factor IX. Ha sido autorizada para el tratamiento y profilaxis de hemorragias en pacientes con hemofilia B (déficit de Factor IX). Los datos acumulados de los tres estudios clínicos disponibles han establecido adecuadamente su eficacia y su seguridad, tanto en uso profiláctico como a demanda, incluyendo pacientes pediátricos y sometidos a intervenciones quirúrgicas. El albutrepenonacog alfa presenta un perfil toxicológico benigno, equiparable al de otros factores de coagulación utilizados en clínica. Por el momento, no se ha observado el desarrollo de anticuerpos inhibidores durante la administración de albutrepenonacog. Aparentemente, no hay diferencias en términos clínicos con otras formas extractivas o recombinantes de factor IX, salvo en los que se refiere a la semivida de eliminación, que es de 95 h en adultos y de 86-89 en niños (< 12 años) para el albutrepenonacog alfa, claramente superior a las 17-27 h de las formas extractivas, 24 h del nonacog alfa (16 h en < 12 años) y 25 h del nonacog gamma (tanto en adultos como en niños). Esto se traduce en que en los tratamientos convencionales de profilaxis el albutrepenonacog alfa requiere una infusión IV cada 7-10 días (eventualmente, 14) frente a los 3-4 días del resto de formas extractivas o recombinantes de Factor IX disponibles actualmente. Ello supone una cierta mejora en tanto que reduce la frecuencia de administración al menos a la mitad de lo requerido actualmente.

A letter to the UK Hemophilia Inquiry providing evidence that it was not "infected blood" that was the problem with hemophiliacs in the 1980s and 1990s, but the use of intermediate purity Factor VIII (which ended in the late 1980s, early 1990s) and especially the use of AZT (which became universal among HIV+ hemophiliacs after approval in 1987).

This article describes a sensitive impedimetric method for the determination of human blood coagulation factor IX protein (FIX) which is present in extremely low concentration in serum. An interdigitated electrode (IDE) whose surface was layered with zinc oxide was modified with two kinds of probes. One is an antibody, the other an aptamer against FIX. A comparative study between anti-FIX aptamer and anti-FIX antibody showed the aptamer to possess higher affinity for FIX. A sandwich aptamer assay was worked out by using the FIX-binding aptamer on the surface of the IDE. It has a detection limit as low as 10 pM which makes it 4 to 30-fold more sensitive than any other method reported for FIX. Moreover, to practice detection in clinical samples, FIX was detected from the human blood serum by spiking. In our perception, the sensitivity of the ZnO-modified IDE presented here makes it a promising tool for sensing clinically relevant analytes that are present in very low (sub-pM) concentrations.

This response document will briefly address concerns about the ethical, legal and methodological flaws with past research informing the CDC's recent draft “Recommendations for Providers Counseling Male Patients and Parents Regarding Male Circumcision and the Prevention of HIV Infection, STIs, and other Health Outcomes”; and the special danger posed to newly circumcised baby boys by excessive bleeding, undiagnosed haemophilia and transfusion-transmitted hepatitis B virus [HBV] infection.