This document discusses hemophilia, including:
1. Hemophilia is an inherited bleeding disorder caused by deficiencies in coagulation factor VIII or IX.
2. There are two main types - Hemophilia A caused by factor VIII deficiency and Hemophilia B caused by factor IX deficiency.
3. Treatment involves replacing the missing clotting factor through products derived from plasma or recombinant sources to control bleeding and prevent joint damage. Regular prophylactic treatment starting in early childhood has been shown to significantly reduce long-term joint complications.
a powerpoint on hemophilia i needed to make.
**if you want to join an online class if you are interested in history, science, math, english, and other things, join my class!!**
Hemophilia is a common hereditary coagulation disorder due to deficiency or reduce activity of clotting factor VIII or clotting factor IX.
This disorder is a X- linked recessive disorder.
Types:
Hemophilia A- deficiency of clotting factors VIII
Hemophilia B- deficiency of clotting factors IX
Hemophilia C- deficiency of clotting factors XI
Parahaemophilia- deficiency of clotting factor V
Causes of hemophilia
Hemophilia has a sex-linked recessive inheritance.
In most cases Hemophilia caused by a mutation in a gene that encodes for one of the clotting factors .
Since the hemophilia gene is located on the X chromosome, Hemophilia usually occurs in males, and Female is the carrier of hemophilia.
Diagnosis
Complete blood cell count
Coagulation studies
FVIII assay
Normal values for FVIII assays are 50-150%. Values in hemophilia are as follows:
Mild: >5%
Moderate: 1-5%
Severe: <1%
Treatment of Hemophilia
Other Types of Treatment
Desmopressin (DDAVP)
Antifibrinolytic Medicines
Vaccinations- hepatitis A and B.
Gene Therapy
Gene Therapy
New Drugs for Hemophilia treatment
New Drugs for Hemophilia treatment
Bangladesh perspectives
Bangladesh would have 10800 hemophiliacs.
But, initially the patients does not concern about hemophilia.
Patients are usually diagnosed only after bleeding episode and sometimes the episode are causes serious consequences.
Conclusion
Primary diagnosis with the success of gene therapy and availability of the new bioengineered products the prospect of the hemophiliacs will be brighter in near future.
Hemophilia is a genetic bleeding disorder in which body loses the ability to stop bleeding due to low levels or absence of proteins known as ‘’clotting factors’’ which are necessary for clotting of blood. Hemophilia leads to excessive bleeding.
a powerpoint on hemophilia i needed to make.
**if you want to join an online class if you are interested in history, science, math, english, and other things, join my class!!**
Hemophilia is a common hereditary coagulation disorder due to deficiency or reduce activity of clotting factor VIII or clotting factor IX.
This disorder is a X- linked recessive disorder.
Types:
Hemophilia A- deficiency of clotting factors VIII
Hemophilia B- deficiency of clotting factors IX
Hemophilia C- deficiency of clotting factors XI
Parahaemophilia- deficiency of clotting factor V
Causes of hemophilia
Hemophilia has a sex-linked recessive inheritance.
In most cases Hemophilia caused by a mutation in a gene that encodes for one of the clotting factors .
Since the hemophilia gene is located on the X chromosome, Hemophilia usually occurs in males, and Female is the carrier of hemophilia.
Diagnosis
Complete blood cell count
Coagulation studies
FVIII assay
Normal values for FVIII assays are 50-150%. Values in hemophilia are as follows:
Mild: >5%
Moderate: 1-5%
Severe: <1%
Treatment of Hemophilia
Other Types of Treatment
Desmopressin (DDAVP)
Antifibrinolytic Medicines
Vaccinations- hepatitis A and B.
Gene Therapy
Gene Therapy
New Drugs for Hemophilia treatment
New Drugs for Hemophilia treatment
Bangladesh perspectives
Bangladesh would have 10800 hemophiliacs.
But, initially the patients does not concern about hemophilia.
Patients are usually diagnosed only after bleeding episode and sometimes the episode are causes serious consequences.
Conclusion
Primary diagnosis with the success of gene therapy and availability of the new bioengineered products the prospect of the hemophiliacs will be brighter in near future.
Hemophilia is a genetic bleeding disorder in which body loses the ability to stop bleeding due to low levels or absence of proteins known as ‘’clotting factors’’ which are necessary for clotting of blood. Hemophilia leads to excessive bleeding.
Hemophilia is a bleeding disorder that slows down the blood clotting process. People who have hemophilia often have longer bleeding after an injury or surgery. People who have severe hemophilia have spontaneous bleeding into the joints and muscles. Hemophilia occurs more commonly in males than in females.The two most common types of hemophilia are hemophilia A (also known as classic hemophilia) and hemophilia B (also known as Christmas disease). People who have hemophilia A have low levels of a blood clotting factor called factor eight (FVIII). People who have hemophilia B have low levels of factor nine (FIX).
The two types of hemophilia are caused by permanent gene changes (mutations) in different genes. Mutations in the FVIII gene cause hemophilia A. Mutations in the FIX gene cause hemophilia B. Proteins made by these genes have an important role in the blood clotting process. Mutations in either gene keep clots from forming when there is an injury, causing too much bleeding that can be difficult to stop
Hemophilia A is the most common type of this condition. One in 5,000 to 10,000 males worldwide have hemophilia A. Hemophilia B is less common, and it affects 1 in 20,000 to 34,500 males worldwide.
1-Overview of clotting mechanisms.
2-different lab investigation for bleeding disorder.
3-hemophilia, clinical presentation and its types.
4-Molecular basis and inheritance of hemophilia.
5-mechanisims of family and patient pedigree.
Hemophilia is a rare disorder in which your blood doesn't clot normally because it lacks sufficient blood-clotting proteins (clotting factors). If you have hemophilia, you may bleed for a longer time after an injury than you would if your blood clotted normally. Small cuts usually aren't much of a problem.
Hemophilia is a bleeding disorder that slows down the blood clotting process. People who have hemophilia often have longer bleeding after an injury or surgery. People who have severe hemophilia have spontaneous bleeding into the joints and muscles. Hemophilia occurs more commonly in males than in females.The two most common types of hemophilia are hemophilia A (also known as classic hemophilia) and hemophilia B (also known as Christmas disease). People who have hemophilia A have low levels of a blood clotting factor called factor eight (FVIII). People who have hemophilia B have low levels of factor nine (FIX).
The two types of hemophilia are caused by permanent gene changes (mutations) in different genes. Mutations in the FVIII gene cause hemophilia A. Mutations in the FIX gene cause hemophilia B. Proteins made by these genes have an important role in the blood clotting process. Mutations in either gene keep clots from forming when there is an injury, causing too much bleeding that can be difficult to stop
Hemophilia A is the most common type of this condition. One in 5,000 to 10,000 males worldwide have hemophilia A. Hemophilia B is less common, and it affects 1 in 20,000 to 34,500 males worldwide.
1-Overview of clotting mechanisms.
2-different lab investigation for bleeding disorder.
3-hemophilia, clinical presentation and its types.
4-Molecular basis and inheritance of hemophilia.
5-mechanisims of family and patient pedigree.
Hemophilia is a rare disorder in which your blood doesn't clot normally because it lacks sufficient blood-clotting proteins (clotting factors). If you have hemophilia, you may bleed for a longer time after an injury than you would if your blood clotted normally. Small cuts usually aren't much of a problem.
Contents :
General features of genes and chromosomes
General features of genetics
General features of chromosomes
Barr body
Genes
Aneuploidy
Chromosomes
Cytogenetics and DNA recombinant technology
General features of cytogenetic studies
Polymerase chain reaction
Restriction fragment length polymorphism
DNA fingerprinting
Fluorescence and luminence
Karyotyping
Blotting
Hybridoma technology
Genetic studies
Chromosomal studies
Transgenic animals
Gene incorporation
Recombinant technology
Gene therapy
Mode of inheritance of diseases
Inheritance of diseases
Features of inheritance
Mitochondrial inheritance
Genetic disorders
General features of genetic disorders
Rearrangement of transcription factors
Down’s syndrome
Trisomy 13
Trisomy 18
Trisomy 22
Turner syndrome
Klinefelter syndrome
Noonan syndrome
Disorders of DNA repair mechanism
For more details, visit www.medpgnotes.com
You can send your queries to medpgnotes@gmail.com
Class 12 CBSE Biology Investigatory project on the topic "Drug Addiction" which includes the appropriate format and content for the CBSE practical examinations.
Hemophilia is perhaps the most well-known inherited bleeding disorder, although it is relatively rare. It affects mostly males. Many more people are affected by von Willebrand disease, the most common inherited bleeding disorder in America caused by clotting proteins.
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
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New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
2. History
Best known of the hereditary bleeding disorders.
First coined by Schonlein in 1820s.
Originally termed “Haemorraphilia” i.e. love for
haemorrhages but over time contracted to
Hemophilia.
Hemophilia is often called the disease of kings
because it was carried by many members of Europe’s
royal family. Queen Victoria of England was a carrier
of hemophilia.
3. WHAT IS
HEMOPHILIA?
Inherited hemorrhagic disorder caused by deficiency of factor
VIII or factor IX.
X linked recessive inheritance hence affect males exclusively.
Incidence in Hemophilia A 1 in 5000 male live births.
Incidence in Hemophilia B 1 in 30,000 male live births.
Female who carry a single mutated gene, are generally
asymtomatic.
4. TYPES
Disease Factor deficiency Inheritance
Hemophilia A VIII X linked recessive
Hemophilia B IX X linked recessive
Hemophilia C XI Autosomal
recessive
Parahemophilia V Autosomal
recessive
5. International nomenclature for factor VIII based on recommendations of
the International committee on Thrombosis and Haemostasis
Definition International Outmoded synonyms
nomenclature
Protein lacking or aberrant in Factor VIII Anti hemophilic factor
hemophilia A
Functional property of factor Factor VIIIc Factor VIII coagulant activity
VIII that is deficient in
hemophilia A and measured
using coagulation assays.
Antigenic property of factor Factor VIIIAg Factor VIIIcAg
VIII that is measured by
immuno-assays.
6. ACTIVITY
Defined as the activity present in 1 ml of fresh plasma from
normal donors.
Expressed in terms of units.
Concentration of all coagulation factors in native plasma is
thus 1 U/ml or 100 U/dl or 100% activity.
Levels in blood bank plasma- 80 U/dl because of
dilution with anticoagulants.
Normal factor VIII and IX activity in patients older than
infants range between 50% -150%.
7. The severity of hemophilia is defined by the
measured level of clotting factor activity.
Distribution Clotting factor
activity
Severe hemophilia 50% <1%
Moderate 10% 1-5%
hemophilia
Mild hemophilia 30-40% 5-40%
10. CAUSES
Mutations in F8 Mutations in F9
gene gene
Deficiency of Deficiency of
factor VIII factor IX
Hemophilia A Hemophilia B
11. PATHOPHYSIOLOGY
The classic representation of
hemostasis shows factor VII together
with tissue factor activating factor X.
Recent studies suggest that the primary
physiologic pathway of factor X
activation by tissue factor and factor VII
is through the activation of factor IX.
Activated factor IX complexes with
factor VIIIa ,calcium and
phosphatidylserine on physiologic
membranes to generate factor Xa
12. PATHOPHYSIOLOGY
Thus, physiologically, the tissue factor pathway
of factor X activation requires factor VIII and IX
, and the absence of either protein severely
impairs the ability to generate thrombin and
fibrin.
The division of hemostasis into distinct
intrinsic and extrinsic pathways is no longer
accurate.
Because thrombin generation in hemophilia is
markedly delayed, haemorrhage occurs after
minimal or unknown trauma. Also the clot
formed is friable making rebleeding common.
14. Genetics
X-linked recessive inheritance.
30% of hemophilias present as spontaneous mutations.
Gene for FVIII or IX located on fragile and mutation
prone region of X chromosome.
Most common mutation of FVIII gene - inversion of
intron 22.(accounts for 45% cases of severe hemophilia)
Moderate and mild severity hemophilia A are mainly
the result of missense mutations.
16. Hemophilia in females
Very rare.
• Lyonization of factor
VIII or IX alleles in
carriers.
• Hemizygosity of X
Following
chromosome in females
genetic
mechanisms- with Turner’s syndrome.
• Female progeny of
hemophilia carriers &
affected haemophiliac
male.
18. Musculoskeletal bleeding
Deep bleeding into joints and
muscles is the hallmark.
Begin when the child reaches
the toddler age.
In toddlers ankle is the most common
site.
Later knees and elbow become the most
common sites.
preceded by an aura.
Hematomas into muscles of distal part
of limbs leads to external compression
of arteries, veins or nerves that can
evolve to a compertment syndrome.
19. Target joint
A particular joint that has
experienced repeated
bleeds.
at least 4 bleeds within a 6
months period (USA)
at least 3 bleeds within a 3
months period (CANADA)
21. Life threatening haemorrhages
Intracranial haemorrhage, bleeding into and around
the oropharyngeal spaces and exsanguinating
haemorrhage.
Retroperitonial hemorrhages can accumulate large
quantities of blood with formation of masses with
calcification & inflammatory tissue reaction (
Pseudomotor syndrome)
Treatment requires achieving a factor level of 100
U/dL, maintenance of adequate hemostatic levels
(>50-60 U/dL) for minimum 14 days, and a more
prolonged period of prophylactic therapy for
additional 1-2 wk.
22. Miscellaneous haemorrhages
Hematuria- May arise
spontaneously. Therapy consists of
bed rest and increased fluid
intake. If not controlled in 1-2 days
then factor replacement. Avoid
antifibrinolytic agents because of
the risk of intra-ureteral clot
formation.
Traumatic bleeding- bleeding
may persist as slow continuous
ooze for days to months or it may
be massive and life threatening.
Delayed bleeding is common.
23. Hemophilic arthropathy
Three phases
1. Following first episodes of
hemarthrosis absorption of
blood is incomplete, the
retained blood produces
chronic inflammation. Iron is
deposited into the synovium
and chondrocytes of the
articular cartilage.
25. 3. Chronic hemophilic arthropathy - characterised
by progressive and erosive destruction of joint cartilage,
narrowing of joint space,subchondral cyst formation, and
eventual collapse and ankylosis of the joint.
MRI is superior to standard radiography
for assessment of early arthropathy.
26. INVESTIGATIONS
• BASELINE SPECIAL
• Complete hemogram Factor VIII assay
Coagulation time Synovial fluid
PT & APTT investigation
• X-ray of joint Carrier state
• genetic testing
27. BASELINE INVESTIGATIONS
1. Complete hemogram
a. Hb count – decreased
b. TLC – normal
c. DLC – normal
d. Platelet count – normal
2. X- ray of joint
Knee joint
Elbow joint
Ankle joint
28. 3. Coagulation time
Prolonged
4. Prothrombin time
Usually normal
5. Activated partial thromboplastin time
-prolonged to 2-3 times
-In mild to moderate factor IX deficiency it may be normal. Thus if
hemophilia is suspected, a factor IX assay should be performed even if
the PTT is normal.
APTT correction studies
-With control plasma- confirms factor deficiency and not circulating
inhibitors as the cause of APTT prolongation.
-With FVIII deficient plasma (from known patients) - suggests FIX
deficiency.
-With FIX deficient plasma (from known patients) - suggests FVIII
deficiency.
29. SPECIAL INVESTIGATIONS
Factor VIII assays
Types
To determine diagnosis
Monitor treatment
Performing pre and post-infusion clotting factor levels.
Factor levels prior to surgery.
To test quality of cryoprecipitate
Detection of inhibitors
When to suspect- PTT not correcting to normal when
mixed with normal plasma and incubated for 120min
One Bethesda unit is defined as the amount of antibody
that will inactivate 50% of the normal FVIII or FIX in 2hr
when the residual FVIII or FIX level is between 25 and 75
U/dL.
30. Carrier state and Genetic testing
Three approaches:
1. Patient and family history;
2. Coagulation-based assays;
3. DNA testing.
31. Carrier state and Genetic testing
A woman is a definite carrier if (i)her father has
hemophilia, (ii)she has one son with
hemophilia and a 1st degree male relative with
hemophilia, (iii)she has two sons with
hemophilia.
A possible carrier if (i)she has one or more
maternal relatives with hemophilia, (ii)she has
one son with hemophilia & no other affected
relative.
32. - Carrier status based solely on factor levels -
not reliable, significant overlap.
- In severe hemophilia A, perform intron 22
gene inversion analysis and, if negative then
proceed with full FVIII gene sequencing.
- In mild to moderate hemophilia A, full
sequencing of the FVIII gene is recommended.
- In hemophilia B, perform full sequencing of
FIX gene.
33. Prenatal diagnosis
Offered when termination of pregnancy
would be considered if affected fetus
identified.
Obtain chorionic villi samples in 10th-11th
gestational week and perform direct
genotype testing.
Test duration. 1wk / 2wk
34. TREATMENT
Fundamentals
Replacement therapy- Replacement of FVIII or IX to
hemostatically adequate plasma levels for prevention or
treatment of acute bleeding is the basis of the management of
hemophilia.
Knowledge of the half-life, volume of distribution, patient’s
inhibitor status and appropriate replacement material is
necessary.
Table-Biodynamic properties of coagulation factors of concern in
replacement therapy
Factor Hemostatic level (U/dL) Biologic half life (hr)
FVIII 25 - 30 24
FIX 15 - 30 12
35. Calculation of dose
- One unit is defined as amount of FVIII (100 ng/ml)
or FIX (5 microg/ml) in 1 ml of normal plasma.
- FVIII dose (IU) = Target FVIII levels – FVIII baseline
levels x body weight (kg) x 0.5 unit/kg
- FIX dose (IU) = Target FIX levels – FIX baseline
levels x body weight (kg) x 1 unit/kg
Types of factor replacement
-Treatment on demand.
- Prophylaxis.
36. Treatment on demand
For mild to moderate haemorrhages, achieve
FVIII levels of 30-40 U/dL or FIX levels of 30
U/dL.
For life threatening haemorrhages,
immediately correct factor level to 100-150
U/dL and maintain level between 80-100 U/dL
for 5-7 days followed by vigorous maintenance.
37. Type of hemorrhage Hemophilia A Hemophilia B
Hemarthrosis 40 IU/kg on day1; then 20 IU/ kg on days 2, 3, 5 60-80 IU/kg on day 1; then 40 IU/kg on days 2,
until joint function is normal or back to baseline. 4. Consider additional treatment every other
Consider additional treatment every other day day for 7-10 days. Consider prophylaxis.
for 7-10 days. Consider prophylaxis.
Muscle or significant 20 IU/kg; may need every-other-day treatment 40 IU/kg; may need treatment every 2-3 days
until resolved. until resolved.
subcutaneous hematoma
Mouth, deciduous tooth or 20 IU/kg; antifibrinolytic therapy; remove loose 40 IU/kg; antifibrinolytic therapy; remove
deciduous tooth. loose deciduous tooth.
tooth extraction
Apply pressure for 15-20 min; pack with Apply pressure for 15-20 min; pack with
petroleum gauze; give antifibrinolytic therapy; petroleum gauze; give antifibrinolytic
Epistaxis 20 IU/kg if this treatment fails. therapy; 30 IU/kg if this treatment fails.
Major surgery, life 50-75 IU/kg, then initiate continuous infusion of 120 IU/kg, then 50-60 IU/kg every 12-24 hr to
2-4 IU/kg/hr to maintain FVIII >100 IU/dL for maintain FIX >40 IU/dL for 5-7 d and then
threatening hemorrhage 24hr, then give 2-3 IU/kg/hr continuously for 5- >30 IU/dL for 7 d.
7d to maintain the level at >50 IU/dL and an
additional 5-7d at a level of >30 IU/dL
Hematuria Bed rest; 1.5 times maintenance fluids; if not Bed rest; 1.5 times maintenance fluids; if not
controlled in 1-2 d, 20 IU/kg FVIII. controlled in 1-2 d, 40 IU/kg FIX
Prophylaxis 20-40 IU/kg FVIII every other day to achieve a 30-50 IU/kg FIX every 2-3 days to achieve a
trough level of > 1%. trough level of > 1%.
38. Prophylactic factor VIII therapy-Evidence
Manco-Jonson et al in their prospective,
randomised, controlled clinical trial showed
83% reduction in risk for joint damage
(evaluated by MRI) in the prophylaxis
group as compared to on-demand group. In
14% cases of MRI changes, there was no
evidence of any previous clinical
hemarthrosis.
39. Prophylactic factor VIII therapy-Evidence
Fischer et al in their long term outcome
study over 22yr showed that prophylaxis
improves clinical outcome without
significantly increasing treatment cost.
40. Prophylactic factor VIII therapy
Administered by subcutaneous access port
of a central venous line.
Dose of 20-40 U/kg of FVIII
administered every other day or thrice
weekly. Dose and rate adjusted to ensure
that nadir before next infusion is >1U/dL.
Prevents spontaneous bleeding;
haemorrhages caused by trauma may still
require additional replacement.
41. Prophylactic factor VIII therapy
Primary prophylaxis - therapy initiated in young
patients who have hemophilia before joint damage
High cost of primary prophylaxis – hindrance for
developing countries. However, the long term cost
savings may be greater with primary prophylaxis as
joints are preserved, lives are more productive,
expensive surgical interventions avoided.
42. When to start primary prophylaxis ?
no consensus!!
Start before 3 years of age, usually around 14-18
mo, at the time that the child begins to walk.
Secondary prophylaxis
In patients with target joints who are having recurrent
events.
Coagulation factors are administered as in primary
prophylaxis but over limited period of 3-6 months.
43. Tailored prophylaxis
Basic idea.
Tailored to patient’s bleeding pattern, joint involvement and
individual needs.
Once weekly infusion of factor concentrate has been studied
thus reducing the need for CVC placement.
The indwelling venous access devices are the cause of most of
the complications associated with prophylaxis (Systemic
infections, catheter-related thrombosis etc.)
The long term effect on joint outcome using this approach
warrants further scrutiny.
44. TREATMENT PRODUCTS
Plasma
a. Diff. b/w Fresh frozen and frozen.
b. 1 U FFP contains about 160-250ml plasma
with activity of ~80%.
c. Rate and total dose limited by the risk of
acute or chronic circulatory overload.
• Thaw.
• Transfuse over how
many minutes.
d. How to use • Reusing after thawing.
What about ½ or 1/3 unit
FFP ?
45. Cryoprecipitate
Prepared by slowly thawing fresh frozen
plasma at 2-4`C, then harvesting the
precipitate by centrifugation.
Cryo prepared from 200ml of FFP contains
80-100 U of FVIII, ~250mg fibrinogen and
useful amounts of FXIII and vWF per 10-
15ml of precipitate.
Use thawed cryo within 4hr.
Can be stored at -18`C for 1yr.a
46. Factor concentrates
• On basis of source of origin.
• On basis of purity:
Types intermediate, high, ultrahigh.
The safety data to date favour
recommendation to exclusively
use recombinant products.
Infuse FVIII by slow IV push at a
rate not to exceed 100 units per
minute in children.
47. ADJUVANT TREATMENT OPTIONS
Desmopressin (DDAVP)
Increases plasma FVIII and vWF levels.
In mild an moderate Hemophilia A who have shown response in
therapeutic trial.
iv dose - 0.3mcg/kg, in 25-50mL NS over 20-30 min.
For OPD management intranasal route. Dose -150mcg (1 puff)
for<50kg and 300mcg (1 puff in each nostril) >50kg
Tachyphylaxis
S/E - Headache, flushing ,Hyponatremia
Peak effect iv form - 30-60 min; intranasal form 60-90 min
48. Antifibrinolytic therapy
Inhibits fibrinolysis of thrombus by plasmin.
Uses - mucosal bleeding, oral, nasal and menstrual
loss.
Tranexamic acid -effective topically as a mouth wash
C/I in hematuria.
Dose
Tranexamic acid
oral- 25 mg/kg/dose every 6-8hr.
iv - 10 mg/kg/dose every 6-8hr.
EACA
Oral - 100-200mg/kg initially followed by
50-100mg/kg/dose every 6hr
iv - 100mg/kg/dose every 6hr.
49. TREATMENT COMPLICATIONS
Inhibitors
Alloantibodies directed against FVIII or FIX
Clinical hallmark- failure to respond to routine
replacement therapy.
Incidence - hemophilia A ~30%;
hemophilia B ~3%.
Risk factors- severity of hemophilia, age, race, family
history of inhibitors and severe gene defects.
Low titer (<5 BU); usually transient.
High titer (>5 BU); persistent.
Screen once every 3-12 months or every 10-20
exposure days and prior to surgery or when clinical
response to adequate treatment is sub-optimal.
50. Management of inhibitors
Low titer- high dose factor replacement.
High titer
• continuous FVIII infusion.
• bypassing agents- recombinant factor VIIa
or activated prothrombin complex
concentrates.
• Immune tolerance induction (ITI)
• Rituximab- limited data (only 18 patients)
51. Immune Tolerance Induction
Immune system desensitisation technique intended to eradicate
inhibitor.
No general agreement on optimal dosage and frequency of dosage for
ITI. A trial is ongoing to compare 50 IU/kg three times a week to 200
IU/kg daily.
Success of ITI ~90% over 6-12 months for alloFVIII antibody
inhibitors.
Consolidate inhibitor eradication with prolonged prophylaxis.
52. Transfusion transmitted infections
Viral attenuated plasma-derived factor concentrates are free from
lipid enveloped viruses viz. HIV, Hep B, Hep C.
Non-lipid enveloped viruses - Hep A, parvovirus B19 are not
susceptible to these techniques, outbreaks reported.
Recombinant factor concentrates contain albumin as stabiliser-
theoretical risk of transmission of prions (no case ever reported).
Immunization to hepatitis B and A is important for all persons
with hemophilia and can be given s.c. not i.m.
Family members handling treatment products should also be
vaccinated.
53. NEWER TREATMENT MODALITIES
Activated Prothrombin complex concentrates
Have increased amounts of activated FVIIa, factor X &
thrombin.
APCC are effective even in patients with high titer
inhibitors.
risk of thrombosis.
Polyethylene glycol conjugation (Pegylation)
Increases size, decreases renal excretion, extends half life.
Polysialic acid polymers
Forms a “watery cloud” around the target molecule
Biodegradable.
54. Recombinant factor VIIa (rFVIIa)
Marketed and manufactured by NovoNordisk, Denmark as
Novoseven.
Bypasses the FVIII-dependent step in factor X activation
Primary use- Hemophilia with inhibitors.
Other uses- control bleeding in traumatic coagulopathies,
thrombocytopathies, liver disease, liver transplantation,
spontaneous intracerebral hemorrhage and patients
undergoing cardiac surgery.
Dose-90mcg/kg 2hrly till hemostasis.
Cost-Rs 35000/1.2 mg vial; 75000/2.4 mg vial.
55. Gene therapy
Involves transfer of genes that express a particular
product into human cells.
Hemophilia-ideal candidate
caused by mutations in single identified gene.
Wide range of safety if there is an “overshoot”
To date the promise of gene therapy and a cure for
the hemophilia patient have not been realized.
Continues to be a topic of intense investigation.
56. Comprehensive care
Comprehensive team including the
hemophilia specialist, nurse coordinator,
social worker, psychologist, physiotherapist,
orthopaedic surgeon, primary care physician,
financial counsellor and sometimes infectious
disease specialist.
Provided primarily through comprehensive
hemophilia treatment centres.
57. Home therapy
Allows immediate access to treatment.
Teach- recognizing a bleed, dosage
calculation, preparation, storage, and
administration of clotting factor,
aseptic techniques, performing
venipuncture (or access of central
venous catheter), record keeping,
proper storage and disposal of needles
and handling of blood spills
58. Prevention of bleeding
Avoid trauma by adjusting their lifestyle.
Contact sports should be avoided, but swimming and
cycling with appropriate gear should be encouraged.
Avoid use of drugs that affect platelet function viz.
NSAIDs.
Intramuscular injections, difficult phlebotomy, and
arterial punctures must be avoided.
Regular exercise should be encouraged to promote
strong muscles, protect joints, and improve fitness
59. Do the 5 !
Do the 5! is a list of 5 things one can do to help live a
long and healthy life.The NHF started the idea
for Do the 5!
1. Get an annual comprehensive check-up at a hemophilia
treatment centre.
2. Get vaccinated - Hepatitis A and B are preventable.
3. Treat bleeds early and adequately.
4. Exercise and maintain a healthy weight to protect the
joints.
5. Get tested regularly for blood-borne infections.
60. What medical information should be carried by a
hemophiliac ?
A person with hemophilia should
carry information about his health,
including the type of hemophilia,
treatment needed, and allergies.
An international medical card is
available free through the World
Federation of Hemophilia. Tags called
Medic-Alert and Talisman are sold in
some countries
61. World Hemophilia Day 2012
Since 1989, patient groups and
treatment centres have been
coming together on April 17 to
celebrate World Hemophilia Day.
The theme for World Hemophilia
Day 2009 is “Together, we care,”
which emphasizes the importance of
comprehensive care in hemophilia
healthcare delivery.
62. The Sun is Rising
for Patients with
Hemophilia
The Future is
Bright