1. Polycythemia vera (PV) is a chronic myeloproliferative neoplasm characterized by an overproduction of red blood cells without an identifiable stimulus. It commonly presents with erythrocytosis, splenomegaly, thrombosis, and pruritus.
2. The main cause of PV is a mutation in the JAK2 gene, but some patients have mutations in exon 12. Diagnosis requires tests to distinguish absolute from relative erythrocytosis. Treatment focuses on phlebotomy and medications to control symptoms and prevent complications.
3. Primary myelofibrosis (PMF) is a chronic myeloproliferative neoplasm involving clonal proliferation and
UAEU - CMHS - Hematology-Oncology Course - MMH 302 - HONC 320. Education material for medical students - It cover basic principles of hematology and oncology, including CAR-T and gene editing. It can be used for study and review. It illustrates main principles of hematology and oncology.
UAEU - CMHS - Hematology-Oncology Course - MMH 302 - HONC 320. Education material for medical students - It cover basic principles of hematology and oncology, including CAR-T and gene editing. It can be used for study and review. It illustrates main principles of hematology and oncology.
MPNs; Definition, Types of MPN Mutations, Aetiology, Clinical features, CMLNawsherwan Mohammad
Polycythemia, essential thrombocythemia, and myelofibrosis are three distinct myeloproliferative neoplasms (MPNs) that affect the bone marrow's production of blood cells. Here's a brief overview of each condition:
1. **Polycythemia (Polycythemia Vera):**
- Polycythemia vera (PV) is a disorder where the bone marrow produces too many red blood cells, white blood cells, and platelets. This leads to an increased thickness of the blood (hyperviscosity), which can cause complications like blood clots, strokes, and heart attacks.
- Symptoms may include fatigue, weakness, headaches, dizziness, itching (especially after a warm bath), and redness or a bluish tint to the skin.
- Treatment aims to reduce the risk of blood clots and manage symptoms. It may include phlebotomy (removing blood to lower red cell count), medications to suppress bone marrow activity, and aspirin to reduce clotting.
2. **Essential Thrombocythemia (ET):**
- Essential thrombocythemia is characterized by the overproduction of platelets in the bone marrow. This condition can lead to abnormal blood clotting or bleeding.
- Symptoms may include headaches, dizziness, tingling or numbness in the hands or feet, vision changes, and easy bruising or bleeding.
- Treatment focuses on reducing the risk of blood clots and managing symptoms. This may involve medications to lower platelet counts, such as hydroxyurea or anagrelide, as well as aspirin therapy.
3. **Myelofibrosis:**
- Myelofibrosis is a condition where the bone marrow is replaced by fibrous tissue, leading to a decrease in the production of normal blood cells. It is often associated with anemia, enlarged spleen, and abnormal blood cell counts.
- Symptoms may include fatigue, weakness, abdominal discomfort due to an enlarged spleen, easy bruising or bleeding, and frequent infections.
- Treatment aims to manage symptoms and improve quality of life. This may involve medications to reduce spleen size and control symptoms, blood transfusions for anemia, and, in some cases, stem cell transplant for eligible patients.
These conditions are chronic and require ongoing monitoring and management by healthcare professionals, often including hematologists or oncologists. Treatment plans are tailored to each individual based on factors such as age, overall health, disease progression, and risk of complications.
We studied the review article about How I investigate eosinophilia, which was published in the International Journal of Laboratory Hematology in August 2018. This paper has clearly and simply introduced how clinicians investigate eosinophilia. Hopefully, it can be helpful to everyone who interested in this field.
Approach to Pancytopenia with cases.pptxYogeetaTanty1
Approach to pancytopenia with case based discussion and brief details regarding each condition. Causes of pancytopenia. Details of congenital causes of aplastic anemia.
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
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.
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
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
4. INTRODUCTION
• PV is a clonal disorder involving a multipotent hematopoietic progenitor cell in which phenotypically normal
red cells, granulocytes, and platelets accumulate in the absence of a recognizable physiologic stimulus.
• Most common of all chronic MPNs
• Incidence : 2.5 per 100,000 persons, increases with age to rates over 10/100,000.
• Age :
• All ages, including early adulthood and occasionally in children and adolescents
• The median age at diagnosis is approximately 60 years
• Approximately one-quarter of cases present before age 50 years and one-tenth before age 40 years.
• Familial transmission : Infrequent
• Sex : F>M (Sporadic)
5. ETIOLOGY
• Unknown
• Mutation in the autoinhibitory pseudo kinase domain of the tyrosine kinase JAK2—that replaces
valine with phenylalanine (V617F) causing constitutive kinase activation.
• JAK2 serves as the cognate tyrosine kinase for the erythropoietin and thrombopoietin receptors.
• JAK2 gene is located on the short arm of chromosome 9, and Loss of heterozygosity on
chromosome 9p due to mitotic recombination is the most common cytogenetic abnormality in
PV.
• More than 95% of PV patients express this mutation, as do approx. 50% of PMF and ET patients.
• Most PV pts who do not express JAK2 V617F express a mutation in exon 12 of the kinase.
6. CLINICAL PRESENTATION
• Incidental discovery of a high hemoglobin or hematocrit.
• Isolated thrombocytosis or leukocytosis
• Splenomegaly : Early satiety , Lt. upper quadrant dragging sensation or mass.
• Aquagenic pruritus : distinguish PV from other causes of erythrocytosis.
• Uncontrolled erythrocytosis hyper viscosity neurologic symptoms such as vertigo,
tinnitus, headache, visual disturbances, and TIAs
• Systolic HTN.
7.
8. Cont..
• Venous or arterial thrombosis : may be the presenting manifestation
• Any vessel can be affected; but cerebral, cardiac, or mesenteric vessels are most commonly
involved
• M/C cause of hepatic vein thrombosis.
• Digital ischemia, easy bruising, epistaxis, PUD, or GI bleed may occur due to vascular stasis or
thrombocytosis.
• Erythema, burning, and pain in the extremities : Erythromelalgia, due to increased platelet
stickiness.
• Hyperuricemia with secondary gout, uric acid stones
9.
10. DIAGNOSIS
• Erythrocytosis in combination with leukocytosis, thrombocytosis, or splenomegaly.
• Red cell mass and plasma volume necessary
• To establish the presence of an absolute erythrocytosis and
• To distinguish from relative erythrocytosis due to a reduction in plasma volume alone
(also known as stress or spurious erythrocytosis or Gaisböck’s syndrome).
• Assay for JAK2 mutations in the presence of a normal SaO2
• A normal serum erythropoietin level does not exclude the presence of PV, but an
elevated EPO level is more consistent with a secondary cause for the erythrocytosis.
11. • Increased LAP.
• Only three situations cause microcytic erythrocytosis: β thalassemia trait, hypoxic erythrocytosis,
and PV.
• A bone marrow aspirate and biopsy provide no specific diagnostic information : may be normal or
indistinguishable from ET or PMF.
• No specific cytogenetic abnormality is associated.
• The absence of a cytogenetic marker does not exclude the diagnosis.
12.
13. COMPLICATIONS
• Hyper-viscosity syndrome
• Pruritus : mast cell activation by JAK2 V617F.
• Sudden increase in spleen size painful splenic infarction.
• Arterial and venous thrombosis.
• PUD and GI bleed.
• Erythromelalgia
• Increased incidence of non-lymphocytic leukemia.
• Secondary Uric acid stones and urate nephropathy.
# Erythrocytosis Thrombosis
# Thrombocytosis Bleeding.
14. TREATMENT
• Indolent disorder.
• Thrombosis due to erythrocytosis is the most significant complication and often the presenting
manifestation.
• Maintenance of the Hb level at ≤ 14 g/dL; (hematocrit <45%) in men and ≤ 12 g/dL; (hematocrit
<42%) in women is mandatory to avoid thrombotic complications.
• Phlebotomy
• Once an iron-deficient state is achieved, phlebotomy is usually only required at 3-month
intervals.
• Anticoagulants are only indicated when a thrombosis has occurred.
15. Cont..
• Asymptomatic hyperuricemia (<10 mg/dL) requires no therapy, but allopurinol s/b
administered when chemotherapy is used.
• Generalized pruritus intractable to antihistamines or antidepressants such as doxepin :
IFN-α, PUVA therapy, and hydroxyurea
• Asymptomatic thrombocytosis requires no therapy unless the platelet count is
sufficiently high to cause bleeding due an acquired form of VWD.
• Symptomatic splenomegaly can be treated with Pegylated IFN-α can also produce
complete hematologic and molecular remissions.
16. Cont..
• ANAGRELIDE
• Phosphodiesterase inhibitor
• Can reduce the platelet count
• Preferable to hydroxyurea because it lacks marrow toxicity and is protective against
venous thrombosis.
• Alkylating agents and radioactive sodium phosphate (32P) are leukemogenic in PV, and
their use should be avoided.
• If a cytotoxic agent must be used, hydroxyurea is preferred, but this drug does not
prevent either thrombosis or myelofibrosis in PV, is itself leukemogenic, and should be
used for as short a time as possible.
17. Cont..
• Non-specific JAK2 inhibitor RUXOLITINIB
• Currently undergoing clinical trials in PV patients intolerant of hydroxyurea.
• A role for allogeneic BMT in PV has not been defined.
19. INTRODUCTION
• Aka
• Idiopathic myelofibrosis
• Agnogenic myeloid metaplasia
• Myelofibrosis with myeloid metaplasia
• Clonal disorder of a multipotent hematopoietic progenitor cell of unknown etiology
characterized by marrow fibrosis, extramedullary hematopoiesis, and splenomegaly.
• Least common chronic MPN.
• PMF primarily afflicts men in their sixth decade or later.
20.
21. ETIOLOGY
• Unknown.
• No cytogenetic abnormality specific to the disease.
• JAK2 V617F is present in approx. 50% of PMF pts.
• Mutations in the thrombopoietin receptor Mpl occur in about 5%.
• Fibrosis in this disorder is a/w overproduction of TGF-β and tissue inhibitors of
metalloproteinases, whereas osteosclerosis is associated with overproduction of osteoprotegerin,
an osteoclast inhibitor.
• Marrow angiogenesis occurs due to increased production of VEGF.
22. CLINICAL PRESENTATION
• Many patients - asymptomatic at presentation.
• Usually detected by the discovery of splenic enlargement and/or abnormal blood counts during a
routine examination.
• Night sweats, fatigue, and weight loss : common.
• Anemia, usually mild initially, is the rule, whereas the leukocyte and platelet counts are either normal
or increased, but either can be depressed.
• Mild hepatomegaly may accompany the splenomegaly but is unusual in the absence of splenic
enlargement.
• Isolated lymphadenopathy suggest another diagnosis.
• Exuberant extramedullary hematopoiesis can cause ascites; portal, pulmonary, or intracranial
hypertension
23. • Causes for anemia : multifactorial
• Ineffective erythropoiesis
• Hemodilution due to splenomegaly
• Splenic sequestration
• Blood loss secondary to thrombocytopenia or portal HTN
• Folic acid deficiency
• Systemic inflammation
• Autoimmune hemolysis
24. DIAGNOSIS
• Diagnosis of PMF is one of exclusion.
• PBS : characteristic features of extramedullary hematopoiesis: teardrop-shaped RBCs,
nucleated RBCs, myelocytes, and promyelocytes.
• The presence of leukocytosis, thrombocytosis with large and bizarre platelets, and
circulating myelocytes suggests the presence of an MPN as opposed to a secondary form
of myelofibrosis
• Marrow aspiration results dry tap but marrow biopsy will reveal a hypercellular marrow
with trilineage hyperplasia.
25.
26. Cont..
• Splenomegaly due to extramedullary hematopoiesis may be sufficiently massive to cause portal
HTN and variceal formation.
• An intriguing feature of PMF is the occurrence of autoimmune abnormalities such as immune
complexes, ANA ,RF, or a positive Coombs’ test.
• Cytogenetic analysis of blood
• Useful to exclude CML
• Prognostic purpose : complex karyotype abnormalities poor prognosis in PMF.
• The number of circulating CD34+ cells is markedly increased in PMF (>15,000/μL) compared to
the other chronic MPNs, unless they too develop myeloid metaplasia.
27.
28. Cont..
• Serum LDH and ALP : can be elevated.
• LAP score : can be low, normal, or high.
• Bone x-rays may reveal osteosclerosis.
• Approx. 50% of PMF pts. express JAK2 V617F mutation.
• PMF pts expressing an MPL mutation tend to be more anemic and have lower leukocyte counts.
• Somatic mutations in exon 9 of the calreticulin gene (CALR) have been found in a majority of
patients with PMF and ET who lack mutations in either JAK2 or MPL.
29.
30.
31. COMPLICATIONS
• Marrow failure
• Huge organomegaly : Portal HTN and/or variceal bleed.
• Transformation into aggressive form of acute leukemia.
32.
33. TREATMENT
• No specific therapy exists for PMF.
• Management of anemia and thrombocytopenia
• Neither recombinant erythropoietin nor androgens such as danazol have proven to be
consistently effective.
• Erythropoietin may worsen splenomegaly and will be ineffective if the serum erythropoietin
level is >125 mU/L.
• Low dose thalidomide with prednisolone effective
• Splenomegaly is by far the most distressing and intractable problem
• Surgical removal of a massive spleen is a/w significant postoperative complications including
mesenteric venous thrombosis, hemorrhage, rebound leukocytosis and thrombocytosis.
• For unexplained reasons, also increases the risk of blastic transformation.
34. • Allopurinol can control significant hyperuricemia
• Bone pain can be alleviated by local irradiation.
• JAK2 inhibitor, RUXOLITINIB : effective in reducing splenomegaly and alleviating constitutional
symptoms while also prolonging survival.
• Allogeneic bone marrow transplantation is the only curative treatment for PMF and should be
considered in younger patients.
36. INTRODUCTION
• Aka
• Essential thrombocythemia
• Idiopathic thrombocytosis
• Primary thrombocytosis
• Hemorrhagic thrombocythemia
•
• Clonal disorder of unknown etiology involving a multipotent hematopoietic progenitor cell manifested
clinically by overproduction of platelets without a definable cause.
• Incidence : 1–2/100,000
• Sex : distinct female predominance
• Age : can occur at any age.
• Approx. 50% of ET patients carry the JAK2 V617F mutation, but its absence does not exclude the disorder.
37.
38. ETIOLOGY
• Unknown
• Uncontrolled thrombopoiesis.
• In addition to its role in thrombopoiesis, thrombopoietin also enhances the survival of
multipotent hematopoietic stem cells and their bone marrow residence.
39. CLINICAL PRESENTATION
• No symptoms or signs are specific for ET.
• Hemorrhagic tendencies : Easy bruising
• Microvascular occlusive events : Erythromelalgia, ocular migraine, or TIA.
• Splenomegaly is indicative of another MPN, in particular PV, PMF, or CML.
40. DIAGNOSIS
• About 50% of ET pts. express the JAK2 V617F mutation.
• CALR mutations are present in most pts. who do not have JAK2 mutations.
• Splenomegaly should suggest the presence of another MPN.
• Marrow biopsy :
• Megakaryocyte hypertrophy and hyperplasia, as well as an overall increase in marrow
cellularity.
• If marrow reticulin is increased consider another diagnosis.
• Absence of stainable iron demands an explanation because iron deficiency alone can cause
thrombocytosis, and absent marrow iron in the presence of marrow hypercellularity is a
feature of PV.
41.
42. TREATMENT
• An elevated platelet count in an asymptomatic patient without cardiovascular risk factors
requires no therapy.
• Bleeding usually responds to EACA.
• Pegylated IFN-α, anagrelide, or hydroxyurea can be used to reduce the platelet count.
• Hydroxyurea and aspirin are more effective than anagrelide and aspirin for prevention of
TIA but not more effective for the prevention of other types of arterial thrombosis and
are actually less effective for venous thrombosis.