This document provides an overview of inherited bleeding disorders, focusing on von Willebrand disease, hemophilia A, and hemophilia B. It classifies inherited bleeding disorders and discusses their prevalence. For von Willebrand disease, it describes the classification, etiology, functions of von Willebrand factor, diagnosis of different types, and management. It also discusses the formation of the primary hemostatic plug. For hemophilia A and B, it covers clinical manifestations, diagnosis, and management, including use of factor replacement therapies.
This would give an idea of the various bleeding disorders, associated clotting factors and more specifically management in the dental office of the patients with bleeding disorders
chronic myeloid leukemia, CML, epidemiology, BCR ABL1 gene, philadelphia chromosome, t(9;22), CML incidence, etiology of CML, pathophysiology of CML, phases of CML, treatment of CML, Allogenic stem cell transplant, TKI therapy for CML, Sokal index for CML,
This would give an idea of the various bleeding disorders, associated clotting factors and more specifically management in the dental office of the patients with bleeding disorders
chronic myeloid leukemia, CML, epidemiology, BCR ABL1 gene, philadelphia chromosome, t(9;22), CML incidence, etiology of CML, pathophysiology of CML, phases of CML, treatment of CML, Allogenic stem cell transplant, TKI therapy for CML, Sokal index for CML,
INTRODUCTION
• Blood must be maintained in a fluid state in order to function as a transport system, but must be able to solidify to form a clot following vascular injury.
• Successful haemostasis is achieved by complex interactions between vascular endothelium, platelets, coagulation factors etc.
HAEMOSTASIS
• The term haemostasis is derived from the Greek word haem= blood and stasis=halt.
• Process of stoppage of bleeding after blood vessels are punctured , cut , or otherwise damaged.
• It is a complex natural physiological response.
• Bleeding disorders are due to altered ability of blood vessels, platelets , and coagulation factors to maintain haemostasis.
• Steps of natural haemostasis:
• Pre-injury conditions-> Early haemostatic response-> Fibrin clot formation-> Limiting clot formation-> Fibrinolysis
This is a precise description regarding anti-coagulants and a short outlook into INR (International Normalized Ratio)............
Hope the points are worthwhile...
For further details, u can communicate me at 8086948729 or in my email address ar rxvichu623@gmail.com or in my fb inbox at "Rx Vichhu"
Thank u!!!
Keep studying well!!
@rxvichu
:)
INTRODUCTION
• Blood must be maintained in a fluid state in order to function as a transport system, but must be able to solidify to form a clot following vascular injury.
• Successful haemostasis is achieved by complex interactions between vascular endothelium, platelets, coagulation factors etc.
HAEMOSTASIS
• The term haemostasis is derived from the Greek word haem= blood and stasis=halt.
• Process of stoppage of bleeding after blood vessels are punctured , cut , or otherwise damaged.
• It is a complex natural physiological response.
• Bleeding disorders are due to altered ability of blood vessels, platelets , and coagulation factors to maintain haemostasis.
• Steps of natural haemostasis:
• Pre-injury conditions-> Early haemostatic response-> Fibrin clot formation-> Limiting clot formation-> Fibrinolysis
This is a precise description regarding anti-coagulants and a short outlook into INR (International Normalized Ratio)............
Hope the points are worthwhile...
For further details, u can communicate me at 8086948729 or in my email address ar rxvichu623@gmail.com or in my fb inbox at "Rx Vichhu"
Thank u!!!
Keep studying well!!
@rxvichu
:)
Coagulation: In medicine, the clotting of blood. The process by which the blood clots to form solid masses, or clots.
More than 30 types of cells and substances in blood affect clotting. The process is initiated by blood platelets. Platelets produce a substance that combines with calcium ions in the blood to form thromboplastin, which in turn converts the protein prothrombin into thrombin in a complex series of reactions. Thrombin, a proteolytic enzyme, converts fibrinogen, a protein substance, into fibrin, an insoluble protein that forms an intricate network of minute threadlike structures called fibrils and causes the blood plasma to gel. The blood cells and plasma are enmeshed in the network of fibrils to form the clot.
By Srivardhan Vanka, Intern - Batch of 2014, J.I.P.M.E.R.
References from UpToDate and Wintrobe's Hematology 13th Edition and various studies done till December 2019. Quoted when appropriate.
Haemophilias: Medically Compromised Children in DentistryRajesh Bariker
Haemophilia is a group of hereditary genetic disorders that impair the body's ability to control blood clotting or coagulation, which is used to stop bleeding when a blood vessel is broken.
Definition of sepsis and septic shock.
The new definition of sepsis 2016 conference.
SIRS, SOFA, QSOFA
Most common pathogen causing sepsis.
Pathogenesis and pathophysiology of sepsis
Biomarkers for detection of sepsis and septic shock
Preseason, sCD14 Subtype marker
Comparison of Procalcitonin and CRP with presepsin.
Mechanism of presepsin detection.
Management of sepsis.
Food hygiene - سلامة الأغذية
تعريف سلامة الأغذية.
أهمية سلامة الأغذية.
العناصر الأساسية لسلامة الأغذية.
أضرار إعادة تسخين الطعام.
الأمراض المنقولة بسبب الغذاء.
الأسباب الرئيسية للأمراض المنقولة بواسطة الغذاء.
العوامل المؤثرة على نمو البكتريا في الأغذية.
أعراض الأمراض الشائعة والمنقولة عن طريق الأطعمة.
فساد الأغذية.
العلامات الدالة على فساد الأغذية.
العوامل التي تسهم في ظهور التسمم الغدائي.
احتياطات الصحة العامة الواجب اتباعها.
العسل ؛ الغذاء الأغنى، الأشهى، والمقاوم للفساد.
حقيقة أم خرافة؟
الإسبوع العالمي للتوعية بالمضادات الحيوية - World antibiotic awareness weekAhmed Al-Abadlah
World antibiotic awareness week - 2016
الإسبوع العالمي للتوعية بالمضادات الحيوية
Gaza - Palestine.
Arabic, Antibiotic, World antibiotic awareness week, الاسبوع العالمي للتوعية ، المضادات الحيوية , د. عبد الرؤوف المناعمة, مشروع الميكروبات الإلكتروني - فلسطين
التوعية العالمية للمضادات
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
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
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.
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
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.
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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
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These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
2. CLASSIFICATION OF INHERITED BLEEDING
DISORDERS
• X-Linked recessive trait
- hemophilia A (factor VIII def.)
- hemophilia B (factor IX def.)
• Autosomal recessive trait
- Afibrinogenemia & Hypofibrinogenemia
- Glanzmann thrombasthenia
- Bernard–Soulier syndrome
- Factor XIII deficiency
- Factor V and VIII Combined Deficiency
• Autosomal dominant trait
- Von-Willbrand disease (Type III recessive)
- Dysfibrinogenemia
- Ehlers-Danlos syndrome
- Hereditary hemorrhagic telangiectasia
- Marfan syndrome
3. PREVALENCE OF BLEEDING DISORDERS
The most common congenital bleeding disorders include:
• Von Willbrand disease
• Hemophilia A
• Hemophilia B
Patients with inherited bleeding disorders recorded in the NRCC-2015
4. 1. VON WILLBRAND DISEASE
• In 1926, Erik von Willebrand first described a hemorrhagic disorder characterized by a
prolonged bleeding time and an autosomal inheritance pattern that distinguished the
disease from classic hemophilias.
• In the early 1950s, an additional component of the disease was identified: a deficiency
of factor VIII procoagulant activity
• These observations distinguish von Willebrand disease from classic factor VIII
deficiency (hemophilia A)
• In addition, evaluation of the multimeric structures of vWF has aided in the
classification of the variant forms of von Willebrand disease.
• Three major types of von Willebrand disease have been identified.
5. VON WILLBRAND DISEASE
• von Willebrand disease is recognized as one of the most common hereditary bleeding
disorders in humans.
• The exact incidence is difficult to determine because milder forms are
often not clinically recognized, but it has been estimated to have
a prevalence as high as 1% in the general population.
• No racial or ethnic predisposition
• Both genders are affected, but women have a higher frequency of
clinical manifestation.
• the primary source of the synthesis and release of plasma vWF is Vascular
endothelium, and stored in Weibel-Palade bodies, while the other cell that synthesizes
vWF is the megakaryocyte.
6. FUNCTIONS OF VWF
• 1. Stabilization of FVIII
• vWF serves as carrier for FVIII in plasma protecting FVIII from proteolytic degradation
and localizing FVIII to sites of vascular injurie.
• (independent of higher multimers)
• 2. Support of platelet adhesion
• vWF mediates platelet adhesion to the vascular endothelium, and plays a role in
platelet aggregation.
• (dependent on higher multimers)
7. ETIOLOGY
• von Willebrand disease may be an acquired or inherited disorder.
• The congenital disorder is autosomally dominant in most cases.
• Inherited abnormalities in von Willebrand disease are associated with a defect of
the vWF gene on chromosome 12
• More than 20 distinct clinical and laboratory subtypes of von Willebrand disease
have been described, and Three broad types of von Willebrand disease are
recognized.
8. ETIOLOGY
• Variant forms of von Willebrand disease can be identified by their patterns of
genetic transmission and the vWF abnormalities in the plasma and the cellular
compartment.
• Distinguishing between various subtypes of von Willebrand disease is important
in determining appropriate therapy
9. FORMATION OF PRIMARY HEMOSTATIC PLUG
1. Adhesion
• Damage to the endothelium of a blood vessel leads to exposed sub endothelial
collagen
• von Willebrand factor is released by damaged endothelial cells and will bind
tightly to the exposed collagen.
• The platelets have a GPIb receptor, bind to the von Willebrand factor which is
bound to the collagen.
10. FORMATION OF PRIMARY HEMOSTATIC PLUG
2. Activation
• The interaction between GPIb platelet receptors and vWF leads to platelets
activation
• This will lead to platelet degranulation of their content
• ADP and thromboxane A2 will bind to other platelets and activate them to
the site of injury.
• Thromboxane and serotonin also serve as vasoconstrictors to reduce the
bleeding that is occurring.
• Morphological changes of platelets shape from discs to spiny spheres
11. FORMATION OF PRIMARY HEMOSTATIC PLUG
3. Aggregation
• As platelets continue to adhere and become activated at the site of injury,
they need a method to bind to each other in order to strengthen the platelet
plug.
• When platelets are activated they express GPIIb/IIIa receptors that serve to
bind fibrinogen to create a cross-link between 2 platelets.
• This will further solidify and strengthen the platelet plug.
12.
13. CLASSIFICATION OF VWD
subclasses
• Type I (70% of cases) Partial quantitative deficiency of vWF
• Mild-moderate disease
• Type II (25%) Qualitative deficiency of vWF
• Mild to moderate disease
• Type III (5%) Total or near total deficiency of vWF
• Severe disease
Additional subclass
• Acquired vWD
14. VWD TYPE 1-QUANTITY
• It is a partial quantitative defect
• Mild to moderate disease
• Usually autosomal dominant
15. TYPE 2A, 2B, 2M, 2N – QUALITY
• Accounts for 15-30% of the population.
• It’s the quality of the VWD, and its Usually autosomal dominant.
Type 2A: there is reduced levels of HMW and intermediate sized multimers
This stops the platelet from making a good plug.
Type 2B: increase affinity of the large vWF multimers for platelet binding (to GpIb)
vWF binds to platelets in the bloodstream, and these large bundles of platelets are removed
from circulation with resultant thrombocytopenia.
This causes a shortage of both platelets and VWF in the blood.
16. TYPE 2A, 2B, 2M, 2N – QUALITY
Type 2M: the VWF is not able to stick to the platelets and a good platelet plug does not form. In this
disorder, there is mutation in the A1 region (which forms the principal binding site for platelet)
resulting in decreased platelet-dependent function. The multimers are present but dysfunctional.
- vWF antigen, FVIII, and multimer analysis are found to be within reference range
17. TYPE 2A, 2B, 2M, 2N – QUALITY
Type 2N: the VWF is not able to be the carrier of factor VIII.
The level of factor VIII in the body will become low
the body has trouble making a fibrin clot due to low levels of factor VIII.
A person with Type 2N can appear to have mild hemophilia with some of the same
symptoms.
FVIII levels reduce to usually around 5% of the reference range
18. VWD TYPE 3-QUANTITY
• Autosomal recessive
• The rarest type where patients have total deficiency of vWF
resulting in sever form of disease.
• This will lead to a secondary deficiency of FVIII
• The patient can have spontaneous bleed
19. ACQUIRED VWD
• This condition typically presents as a sudden onset of
mucocutaneous bleeding in a previously asymptomatic patient.
• occurs mostly often in individuals over 40 years.
• Mechanisms include
• Antibody formation against vWF with resultant increased clearance of the
from circulation or inhibition of function
• Adsorption of vWF by tumor cells. Tumor cells may have aberrant GP Iba
receptor expression
• Defective synthesis and release of vWF
• Increased proteolysis of vWF
20. DIAGNOSIS OF VARIOUS TYPES
• CBC (in certain subtypes, type 2B and platelet thrombocytopenia may be present).
• Bleeding time should be prolonged as vWF is required for platelet adhesion.
• PTT (PTT should be prolonged due to low levels of factor VIII)
• FVIII level is low in type 2N and type 3 individuals (below 10 IU/dl).
21. DIAGNOSIS OF VARIOUS TYPES
• VWF:Ag
• the plasma concentration of VWF is measured by enzyme-linked immunosorbent
assay (ELISA) or automated latex immunoassay (LIA)
• Normal range of VWF:Ag is 50-200 IU/dl
• In type 1, 2A, 2B individuals, the levels are decreased. (type 3: absent)
• VWF:RCo
• it is the most widely accepted test for evaluating VWF function.
• ristocetin induces von Willebrand and Gp1b interaction causing platelet aggregation.
• Normal range is 50-200 IU/dl.
• type 2N individuals have normal levels of VWF:RCo.
22. DIAGNOSIS OF VARIOUS TYPES
• FVIII:C
• It’s a Functional assay used to measure the ability of VWF to serve as a carrier protein for
FVIII.
• Decreased in type 2N and type 3 VWD.
• RIPA
• It is mainly used to diagnose type 2B VWD
• using low concentration ristocetin (usually <0.6 mg/ml).
• Platelets aggregation means either type 2B or mutations in the platelet VWF receptor
(pseudo VWD).
• Multimer analysis by electrophoresis, allows typing and sub-typing of VWD according
to size.
23.
24. MANAGEMENT
• Desmopressin (dDAVP)
• a synthetic analogue of antidiuretic hormone.
• causing release of von Willebrand factor (VWF) from endothelial storage
sites
• Cryoprecipitate
• Plasma-derived FVIII/vWF
26. 2. HEMOPHILIA A (FACTOR VIII DEFICIENCY)
• Hemophilia A is an X-chromosome-linked recessive coagulation disorder included among the
rare diseases and caused by mutations in the factor VIII (FVIII) gene, which is an essential
component of the intrinsic pathway of blood
coagulation.
• The incidence of hemophilia A is 1 in 5000 male live births and affected individuals have severe,
moderate, and mild forms of the disease
• The majority of FVIII is synthesized in liver.
• Factor VIII is a plasma glycoprotein consisting of six domains. The encoding gene is located on
the long arm of the X chromosome (Xq28).
• Multiple mutations leading to hemophilia A have been described, the most common genetic
defect is a large inversion and translocation of exons 1 or 22, which completely
disrupts the gene.
29. CLINICAL MANIFESTATIONS
• patients with a mild form of the disease (6–30% of normal FVIII activity) unlikely
to have unprovoked hemorrhages and experience major bleeding only with
trauma or surgery.
• moderate disease patients (1–5% of normal FVIII activity) will occasionally
demonstrate spontaneous hemorrhages.
• while patients with severe disease (<1% of normal FVIII activity) will develop
spontaneous hemorrhages since early infancy.
• Neither factor VIII nor factor IX crosses the placenta
• therefore, bleeding symptoms may occur from birth or in the fetus
30. CLINICAL MANIFESTATIONS
• Primary;
• early joint and muscle bleeds
• bleeding in the mouth, gums, and nose.
• GIT and urinary hemorrhage
• neck/throat, eye, hip, joint and muscle, testicles, and retro peritoneum bleeds
• Secondary;
• Chronic joint deformities from recurrent bleeding
• Antibodies to transfused factor VIII (inhibitors develop in 20-30% of severe patients)
• AIDS - Over half of hemophilia patients treated with plasma concentrates in the early
1980s became HIV+
• Never purpura and petechiae (because primary hemostasis is not affected)
31. • After repeated bleeding
episodes in the joint, patients
may develop a "target" joint.
33. DIAGNOSIS
• Hemoglobin/hematocrit
• Prothrombin time (PT)
• Extrinsic coagulation pathway screen
• Normal range
• Activated partial thromboplastin time (aPTT)
• Intrinsic pathway screen
• Elevated values expected
• May be normal range in mild disease
• Platelet count
• normal range
34. DIAGNOSIS
• Factor VIII & IX level
• percentage activity (normal 50-150%).
• Expect severe disease with less than 1%, moderate disease with 1-5%,
and mild disease with greater than 5%
• Factor VIII & IX inhibitors
35. Insertion of human factor
VIII DNA into vector system
allowing incorporation into
non-human mammalian cell
lines for continued
propagation
• Recombinant Factor VIII
36. MANAGEMENT
• Cryoprecipitate and fresh frozen plasma
• Hemophilia care should deliver virally inactivated clotting factor concentrates,
• in absence of FVIII concentrate, cryoprecipitate can be used as the source of FVIII.
(each cryoprecipitate unit contains 80–100 IU of FVIII)
• And In the absence of FIX concentrates, fresh frozen plasma should be
Used for hemophilia B patients.
• Desmopressin (DDAVP)
• DDAVP is a vasopressin analogue that can release stored VWF from endothelial
cells and results in a secondary increase in FVIII levels
• Can be used in mild hemophilia A, and type 1 VWD
37. MANAGEMENT
• Tranexamic acid
anti fibrinolytic agent
• Avoid all products that cause platelet dysfunction
( ASA, NSAIDs )
• Avoid intramuscular injections.
38. 3. HEMOPHILIA B (FACTOR IX DEFICIENCY)
• Known as Christmas disease, first reported in the medical literature in 1952 in a
patient with the name of Stephen Christmas.
• occurs in one of every 25,000 to 30,000 live male births.
• As with hemophilia A, hemophilia B is found in all ethnic groups.
• The factor IX gene is located on the long arm of the X chromosome
• Factor IX inhibitor antibodies less common in hemophilia B
39. HEMOPHILIA B (FACTOR IX DEFICIENCY)
• Factor IX is a vitamin K-dependent. It is activated by the factor VIIa–tissue factor
complex, or factor XIa, forming the active enzyme factor Ixa
• factor IXa activates factor X in the presence of factor VIIIa, phospholipid and calcium.
• Factor VIIIa is a necessary cofactor for activity of factor IXa. Therefore, deficiency of
either factor IX or VIII leads to a similar lack of factor X-activating
activity on the platelet surface.
• Factor Xa converts prothrombin to thrombin in the presence of factor Va, activated
platelets, and calcium.
40. HEMOPHILIA B (FACTOR IX DEFICIENCY)
• PT is normal
• aPTT is prolonged.
• specific assay of factor IX coagulant activity is required for definitive diagnosis.
..
41. REFERENCES
1. Thomas G. DeLoughery (eds.), Hemostasis and Thrombosis.
2. Hoffman and Abeloff’s, HEMATOLOGYONCOLOGY REVIEW.
3. Hussain I. Saba, Harold R. Roberts, Hemostasis and Thrombosis Practical
Guidelines in Clinical Management.
4. K. Pavani Bharati* and U. Ram Prashanth, Von Willebrand Disease: An Overview
Acquired
Hemorrhagic disease of Newborn
vitamin K deficiency
Liver disease, Renal disease
Warfarin overdose
Anticoagulant therapy
Disseminated intravascular coagulation
Thrombocytopenia
Massive transfusion
Scurvy
Bernard-Soulier syndrome
Bernard-Soulier syndrome results from a deficiency of platelet glycoprotein protein Ib, which mediates the initial interaction of platelets with the subendothelial components via the von Willebrand protein. It is a rare but severe bleeding disorder. Platelets do not aggregate to ristocetin. The platelet count is low, but, characteristically, the platelets are large, often the size of red blood cells, and may be missed on complete blood counts because most automatic counters do not count them as platelets.
Glanzmann thrombasthenia
Glanzmann thrombasthenia results from a deficiency of the GP IIb/IIIa complex. Platelets do not aggregate to any agents except ristocetin. The more severe type I results from a complete absence of the GP IIb/IIIa complex, whereas in the milder type II, some of the GP IIb/IIIa complex is retained.
Both Bernard-Soulier syndrome and Glanzmann thrombasthenia are characterized by lifelong bleeding. Although platelet transfusions are effective, they should be used only for severe bleeding and emergencies, because alloantibodies often develop in these patients.
The initial pooled, plasma-derived clotting factor concentrates for factor VIII and IX transmitted hepatitis B, hepatitis C, and human immunodeficiency virus (HIV). Over 50% of the U.S. hemophilia population became HIV-positive as a result of contaminated clotting factor concentrates,
Parvovirus can be transmitted by virally inactivated plasma-derived products, and there are still concerns about possible transmission of Creutzfeldt-Jakob disease (CJD)