Polycythemia vera (Clinical)

Overview

Definition^[12]

Polycythemia Polycythemia An increase in the total red cell mass of the blood. Renal Cell Carcinoma vera ( PV PV Polycythemia vera (PV) is a chronic myeloproliferative neoplasm characterized by the overproduction of rbcs. In addition, the wbc and platelet counts are also increased, which differentiate pv from erythrocytosis seen with chronic hypoxia and other chronic conditions. Polycythemia Vera) is a chronic myeloproliferative neoplasm characterized by the overproduction of RBCs RBCs Erythrocytes, or red blood cells (RBCs), are the most abundant cells in the blood. While erythrocytes in the fetus are initially produced in the yolk sac then the liver, the bone marrow eventually becomes the main site of production. Erythrocytes: Histology (erythrocytosis), WBCs, and platelets Platelets Platelets are small cell fragments involved in hemostasis. Thrombopoiesis takes place primarily in the bone marrow through a series of cell differentiation and is influenced by several cytokines. Platelets are formed after fragmentation of the megakaryocyte cytoplasm. Platelets: Histology. This triad differentiates PV PV Polycythemia vera (PV) is a chronic myeloproliferative neoplasm characterized by the overproduction of rbcs. In addition, the wbc and platelet counts are also increased, which differentiate pv from erythrocytosis seen with chronic hypoxia and other chronic conditions. Polycythemia Vera from erythrocytosis seen with chronic hypoxia Hypoxia Sub-optimal oxygen levels in the ambient air of living organisms. Ischemic Cell Damage and other conditions.

Classification^[10]

• Primary PV Primary Pv Polycythemia Vera is a BCR-ABL–negative myeloproliferative disorder.
• Secondary polycythemia Secondary Polycythemia Polycythemia Vera is due to an increase in erythropoietin Erythropoietin Glycoprotein hormone, secreted chiefly by the kidney in the adult and the liver in the fetus, that acts on erythroid stem cells of the bone marrow to stimulate proliferation and differentiation. Erythrocytes: Histology ( EPO EPO Glycoprotein hormone, secreted chiefly by the kidney in the adult and the liver in the fetus, that acts on erythroid stem cells of the bone marrow to stimulate proliferation and differentiation. Erythrocytes: Histology) caused by environmental circumstances or other conditions:
  • Lung disease/chronic hypoxia Hypoxia Sub-optimal oxygen levels in the ambient air of living organisms. Ischemic Cell Damage
  • Sleep apnea Sleep apnea Repeated cessation of breathing for > 10 seconds during sleep and results in sleep interruption, fatigue, and daytime sleepiness. Obstructive Sleep Apnea
  • Smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases
  • High altitude
  • EPO-secreting tumors EPO-secreting tumors Polycythemia Vera, such as renal cell carcinoma Renal cell carcinoma Renal cell carcinoma (RCC) is a tumor that arises from the lining of the renal tubular system within the renal cortex. Renal cell carcinoma is responsible for 80%-85% of all primary renal neoplasms. Most RCCs arise sporadically, but smoking, hypertension, and obesity are linked to its development. Renal Cell Carcinoma

Epidemiology^[1]

• Affects an estimated 44–57 of 100,000 individuals in the US
• Incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency is slightly higher in men than women for unclear reasons
• Seen in all ages, but the incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency increases with age and peaks between 50 and 70 years; median age at diagnosis is 64.
• Affects all ethnic groups

Etiology and Pathophysiology

Etiology^[6]

• Not fully understood
• Most patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship have a mutation Mutation Genetic mutations are errors in DNA that can cause protein misfolding and dysfunction. There are various types of mutations, including chromosomal, point, frameshift, and expansion mutations. Types of Mutations of the Janus kinase-2 gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics (JAK2) on chromosome 9 Chromosome 9 Friedreich Ataxia, which encodes for a protein essential for RBC production.
• Modifiable risk factors:
  • Smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases
  • Obesity Obesity Obesity is a condition associated with excess body weight, specifically with the deposition of excessive adipose tissue. Obesity is considered a global epidemic. Major influences come from the western diet and sedentary lifestyles, but the exact mechanisms likely include a mixture of genetic and environmental factors. Obesity
  • Hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension
  • Diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus
  • Hyperlipidemia
• Nonmodifiable risk factors
  • Older age
  • Male sex Sex The totality of characteristics of reproductive structure, functions, phenotype, and genotype, differentiating the male from the female organism. Gender Dysphoria

Pathophysiology^[7,9,12]

• The JAK2 gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics is involved in signal transduction Transduction The transfer of bacterial DNA by phages from an infected bacterium to another bacterium. This also refers to the transfer of genes into eukaryotic cells by viruses. This naturally occurring process is routinely employed as a gene transfer technique. Bacteriology for EPO EPO Glycoprotein hormone, secreted chiefly by the kidney in the adult and the liver in the fetus, that acts on erythroid stem cells of the bone marrow to stimulate proliferation and differentiation. Erythrocytes: Histology, thrombopoietin Thrombopoietin A humoral factor that stimulates the production of thrombocytes (blood platelets). Thrombopoietin stimulates the proliferation of bone marrow megakaryocytes and their release of blood platelets. The process is called thrombopoiesis. Platelets: Histology, and granulocyte colony-stimulating factor Granulocyte colony-stimulating factor A glycoprotein of mw 25 kda containing internal disulfide bonds. It induces the survival, proliferation, and differentiation of neutrophilic granulocyte precursor cells and functionally activates mature blood neutrophils. Among the family of colony-stimulating factors, G-CSF is the most potent inducer of terminal differentiation to granulocytes and macrophages of leukemic myeloid cell lines. White Myeloid Cells: Histology (G-CSF).
• A JAK2 alteration with the V617F mutation Mutation Genetic mutations are errors in DNA that can cause protein misfolding and dysfunction. There are various types of mutations, including chromosomal, point, frameshift, and expansion mutations. Types of Mutations, found in 98% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with PV PV Polycythemia vera (PV) is a chronic myeloproliferative neoplasm characterized by the overproduction of rbcs. In addition, the wbc and platelet counts are also increased, which differentiate pv from erythrocytosis seen with chronic hypoxia and other chronic conditions. Polycythemia Vera, results in enhanced cytokine signaling that results in the increased production of all hematopoietic stem cells Hematopoietic stem cells Progenitor cells from which all blood cells derived. They are found primarily in the bone marrow and also in small numbers in the peripheral blood. Bone Marrow: Composition and Hematopoiesis.
• A small minority of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship do not exhibit JAK2 V617F mutation Mutation Genetic mutations are errors in DNA that can cause protein misfolding and dysfunction. There are various types of mutations, including chromosomal, point, frameshift, and expansion mutations. Types of Mutations but have insertions and deletions in JAK2 exon 12.
• Other mutations lead to sustained activation of JAK2 kinase, which causes excess blood cell production independent of EPO EPO Glycoprotein hormone, secreted chiefly by the kidney in the adult and the liver in the fetus, that acts on erythroid stem cells of the bone marrow to stimulate proliferation and differentiation. Erythrocytes: Histology:
  • Calreticulin (CALR) mutations have been found in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with PV PV Polycythemia vera (PV) is a chronic myeloproliferative neoplasm characterized by the overproduction of rbcs. In addition, the wbc and platelet counts are also increased, which differentiate pv from erythrocytosis seen with chronic hypoxia and other chronic conditions. Polycythemia Vera without a JAK2 mutation Mutation Genetic mutations are errors in DNA that can cause protein misfolding and dysfunction. There are various types of mutations, including chromosomal, point, frameshift, and expansion mutations. Types of Mutations.
  • Lymphocytic adaptor protein (LNK) mutations have been found in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with isolated erythrocytosis.

Clinical Presentation

Polycythemia Polycythemia An increase in the total red cell mass of the blood. Renal Cell Carcinoma vera is often diagnosed incidentally when a CBC obtained for other reasons reveals increased hemoglobin and hematocrit Hematocrit The volume of packed red blood cells in a blood specimen. The volume is measured by centrifugation in a tube with graduated markings, or with automated blood cell counters. It is an indicator of erythrocyte status in disease. For example, anemia shows a low value; polycythemia, a high value. Neonatal Polycythemia. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship also present with disease-related symptoms or complications.^[1,6,12]

• Constitutional:
  • Fatigue Fatigue The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. Fibromyalgia (91%)
  • Insomnia Insomnia Insomnia is a sleep disorder characterized by difficulty in the initiation, maintenance, and consolidation of sleep, leading to impairment of function. Patients may exhibit symptoms such as difficulty falling asleep, disrupted sleep, trouble going back to sleep, early awakenings, and feeling tired upon waking. Insomnia (68%)
• Neurologic:
  • Headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess
  • Dizziness Dizziness An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. Lateral Medullary Syndrome (Wallenberg Syndrome)
  • Visual disturbances
  • Erythromelalgia Erythromelalgia A peripheral arterial disease that is characterized by the triad of erythema, burning pain, and increased skin temperature of the extremities (or red, painful extremities). Erythromelalgia may be classified as primary or idiopathic, familial or non-familial. Secondary erythromelalgia is associated with other diseases, the most common being myeloproliferative disorders. Polycythemia Vera, a burning pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways in the feet or hands accompanied by erythema Erythema Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of disease processes. Chalazion, pallor, or cyanosis Cyanosis A bluish or purplish discoloration of the skin and mucous membranes due to an increase in the amount of deoxygenated hemoglobin in the blood or a structural defect in the hemoglobin molecule. Pulmonary Examination, in the presence of palpable pulses (29% of cases)
• Dermatologic and musculoskeletal:
  • Plethora Plethora Neonatal Polycythemia (ruddy complexion)
  • Pruritus Pruritus An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. Atopic Dermatitis (Eczema), especially after a hot bath or shower (36%)
  • Gouty tophi Tophi Msu deposit in the soft tissue and synovium. Gout
  • Petechiae Petechiae Primary Skin Lesions
• GI:
  • Splenomegaly Splenomegaly Splenomegaly is pathologic enlargement of the spleen that is attributable to numerous causes, including infections, hemoglobinopathies, infiltrative processes, and outflow obstruction of the portal vein. Splenomegaly (36%)
  • Hepatomegaly
  • Epigastric pain Epigastric pain Mallory-Weiss Syndrome (Mallory-Weiss Tear)
  • Peptic ulcer Peptic ulcer Peptic ulcer disease (PUD) refers to the full-thickness ulcerations of duodenal or gastric mucosa. The ulcerations form when exposure to acid and digestive enzymes overcomes mucosal defense mechanisms. The most common etiologies include Helicobacter pylori (H. pylori) infection and prolonged use of non-steroidal anti-inflammatory drugs (NSAIDs). Peptic Ulcer Disease disease
• Cardiovascular:
  • Hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension (46%)
  • Venous thrombosis Venous thrombosis The formation or presence of a blood clot (thrombus) within a vein. Budd-Chiari Syndrome (7%)
  • Arterial thrombosis Arterial Thrombosis Hypercoagulable States (16%)
  • Angina pectoris Angina pectoris The symptom of paroxysmal pain consequent to myocardial ischemia usually of distinctive character, location and radiation. It is thought to be provoked by a transient stressful situation during which the oxygen requirements of the myocardium exceed that supplied by the coronary circulation. Stable and Unstable Angina
  • Stroke
  • Intermittent claudication Intermittent claudication A symptom complex characterized by pain and weakness in skeletal muscle group associated with exercise, such as leg pain and weakness brought on by walking. Such muscle limpness disappears after a brief rest and is often relates to arterial stenosis; muscle ischemia; and accumulation of lactate. Thromboangiitis Obliterans (Buerger Disease)
• Hematologic (due to platelet dysfunction):
  • Epistaxis Epistaxis Bleeding from the nose. Granulomatosis with Polyangiitis
  • Ecchymosis Ecchymosis Extravasation of blood into the skin, resulting in a nonelevated, rounded or irregular, blue or purplish patch, larger than a petechia. Orbital Fractures
  • Gingival bleeding
  • Major hemorrhage (4%)

Diagnosis

Polycythemia Polycythemia An increase in the total red cell mass of the blood. Renal Cell Carcinoma vera is suspected in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with characteristic physical findings and/or increased levels of hemoglobin and hematocrit Hematocrit The volume of packed red blood cells in a blood specimen. The volume is measured by centrifugation in a tube with graduated markings, or with automated blood cell counters. It is an indicator of erythrocyte status in disease. For example, anemia shows a low value; polycythemia, a high value. Neonatal Polycythemia on a CBC. Testing for EPO EPO Glycoprotein hormone, secreted chiefly by the kidney in the adult and the liver in the fetus, that acts on erythroid stem cells of the bone marrow to stimulate proliferation and differentiation. Erythrocytes: Histology is indicated next (unless evaluation points to volume depletion Volume depletion Volume status is a balance between water and solutes, the majority of which is Na. Volume depletion refers to a loss of both water and Na, whereas dehydration refers only to a loss of water. Volume depletion can be caused by GI losses, renal losses, bleeding, poor oral Na intake, or third spacing of fluids. Volume Depletion and Dehydration alone).^[8]

Initial evaluation^[14]

• Repeat CBC (especially if volume contraction is evident)
• Electrolytes Electrolytes Electrolytes are mineral salts that dissolve in water and dissociate into charged particles called ions, which can be either be positively (cations) or negatively (anions) charged. Electrolytes are distributed in the extracellular and intracellular compartments in different concentrations. Electrolytes are essential for various basic life-sustaining functions. Electrolytes, renal and hepatic function, urinalysis Urinalysis Examination of urine by chemical, physical, or microscopic means. Routine urinalysis usually includes performing chemical screening tests, determining specific gravity, observing any unusual color or odor, screening for bacteriuria, and examining the sediment microscopically. Urinary Tract Infections (UTIs) in Children:
  • Detect underlying liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy and/or kidney disease, which can lead to erythrocytosis
  • BUN/creatinine can help indicate volume status Volume Status ACES and RUSH: Resuscitation Ultrasound Protocols.
• Pulse oximetry
• EPO EPO Glycoprotein hormone, secreted chiefly by the kidney in the adult and the liver in the fetus, that acts on erythroid stem cells of the bone marrow to stimulate proliferation and differentiation. Erythrocytes: Histology

Rule out secondary causes of polycythemia Polycythemia An increase in the total red cell mass of the blood. Renal Cell Carcinoma (high EPO EPO Glycoprotein hormone, secreted chiefly by the kidney in the adult and the liver in the fetus, that acts on erythroid stem cells of the bone marrow to stimulate proliferation and differentiation. Erythrocytes: Histology levels)^[14]

• High altitude
• Chronic hypoxia Hypoxia Sub-optimal oxygen levels in the ambient air of living organisms. Ischemic Cell Damage:
  • Evaluate for chronic cardiopulmonary disease.
  • Arterial oxygen saturation Oxygen Saturation Basic Procedures < 92% leads to erythrocytosis.
•  Paraneoplastic syndrome ( renal cell carcinoma Renal cell carcinoma Renal cell carcinoma (RCC) is a tumor that arises from the lining of the renal tubular system within the renal cortex. Renal cell carcinoma is responsible for 80%-85% of all primary renal neoplasms. Most RCCs arise sporadically, but smoking, hypertension, and obesity are linked to its development. Renal Cell Carcinoma)
• Other underlying conditions leading to ↑ hemoglobin and hematocrit Hematocrit The volume of packed red blood cells in a blood specimen. The volume is measured by centrifugation in a tube with graduated markings, or with automated blood cell counters. It is an indicator of erythrocyte status in disease. For example, anemia shows a low value; polycythemia, a high value. Neonatal Polycythemia (with raised EPO EPO Glycoprotein hormone, secreted chiefly by the kidney in the adult and the liver in the fetus, that acts on erythroid stem cells of the bone marrow to stimulate proliferation and differentiation. Erythrocytes: Histology), such as parathyroid Parathyroid The parathyroid glands are 2 pairs of small endocrine glands found in close proximity to the thyroid gland. The superior parathyroid glands are lodged within the parenchyma of the upper poles of the right and left thyroid lobes; the inferior parathyroid glands are close to the inferior tips or poles of the lobes. Parathyroid Glands: Anatomy tumor Tumor Inflammation, cerebellar hemangioma Hemangioma A vascular anomaly due to proliferation of blood vessels that forms a tumor-like mass. The common types involve capillaries and veins. It can occur anywhere in the body but is most frequently noticed in the skin and subcutaneous tissue. Imaging of the Liver and Biliary Tract, pheochromocytoma Pheochromocytoma Pheochromocytoma is a catecholamine-secreting tumor derived from chromaffin cells. The majority of tumors originate in the adrenal medulla, but they may also arise from sympathetic ganglia (also referred to as paraganglioma). Symptoms are associated with excessive catecholamine production and commonly include hypertension, tachycardia, headache, and sweating. Pheochromocytoma

Laboratory findings for primary PV Primary Pv Polycythemia Vera^[1,7,13,14]

• CBC and chemistry:
  • Increased:
    • Hemoglobin and hematocrit Hematocrit The volume of packed red blood cells in a blood specimen. The volume is measured by centrifugation in a tube with graduated markings, or with automated blood cell counters. It is an indicator of erythrocyte status in disease. For example, anemia shows a low value; polycythemia, a high value. Neonatal Polycythemia
    • Leukocytes Leukocytes White blood cells. These include granular leukocytes (basophils; eosinophils; and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). White Myeloid Cells: Histology
    • Platelets Platelets Platelets are small cell fragments involved in hemostasis. Thrombopoiesis takes place primarily in the bone marrow through a series of cell differentiation and is influenced by several cytokines. Platelets are formed after fragmentation of the megakaryocyte cytoplasm. Platelets: Histology 
    • Uric acid Uric acid An oxidation product, via xanthine oxidase, of oxypurines such as xanthine and hypoxanthine. It is the final oxidation product of purine catabolism in humans and primates, whereas in most other mammals urate oxidase further oxidizes it to allantoin. Nephrolithiasis and B₁₂ (not needed for diagnosis)
    • LDH LDH Osteosarcoma
  • Decreased:
    • MCV
    • Iron Iron A metallic element with atomic symbol fe, atomic number 26, and atomic weight 55. 85. It is an essential constituent of hemoglobins; cytochromes; and iron-binding proteins. It plays a role in cellular redox reactions and in the transport of oxygen. Trace Elements
    • EPO EPO Glycoprotein hormone, secreted chiefly by the kidney in the adult and the liver in the fetus, that acts on erythroid stem cells of the bone marrow to stimulate proliferation and differentiation. Erythrocytes: Histology
• Peripheral smear: Findings depend on the stage at the time of diagnosis.
  • Erythrocytosis (excess RBCs RBCs Erythrocytes, or red blood cells (RBCs), are the most abundant cells in the blood. While erythrocytes in the fetus are initially produced in the yolk sac then the liver, the bone marrow eventually becomes the main site of production. Erythrocytes: Histology)
  • Dacryocytes (teardrop-shaped RBCs RBCs Erythrocytes, or red blood cells (RBCs), are the most abundant cells in the blood. While erythrocytes in the fetus are initially produced in the yolk sac then the liver, the bone marrow eventually becomes the main site of production. Erythrocytes: Histology)
  • Poikilocytosis (abnormally shaped RBCs RBCs Erythrocytes, or red blood cells (RBCs), are the most abundant cells in the blood. While erythrocytes in the fetus are initially produced in the yolk sac then the liver, the bone marrow eventually becomes the main site of production. Erythrocytes: Histology)
  • Circulating nucleated RBCs RBCs Erythrocytes, or red blood cells (RBCs), are the most abundant cells in the blood. While erythrocytes in the fetus are initially produced in the yolk sac then the liver, the bone marrow eventually becomes the main site of production. Erythrocytes: Histology
  • Hypochromia and microcytosis in the case of iron Iron A metallic element with atomic symbol fe, atomic number 26, and atomic weight 55. 85. It is an essential constituent of hemoglobins; cytochromes; and iron-binding proteins. It plays a role in cellular redox reactions and in the transport of oxygen. Trace Elements deficiency
  • Thrombocytosis
  • Leukocytosis Leukocytosis A transient increase in the number of leukocytes in a body fluid. West Nile Virus in the absence of fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever or infection
• Testing for JAK2, CALR, and LNK mutations (done sequentially)
  • Testing for JAK2 V617F:
    • Stage 1 Stage 1 Trypanosoma brucei/African trypanosomiasis investigation in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with clinical features of PV PV Polycythemia vera (PV) is a chronic myeloproliferative neoplasm characterized by the overproduction of rbcs. In addition, the wbc and platelet counts are also increased, which differentiate pv from erythrocytosis seen with chronic hypoxia and other chronic conditions. Polycythemia Vera 
    • Confirms diagnosis in majority of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with PV PV Polycythemia vera (PV) is a chronic myeloproliferative neoplasm characterized by the overproduction of rbcs. In addition, the wbc and platelet counts are also increased, which differentiate pv from erythrocytosis seen with chronic hypoxia and other chronic conditions. Polycythemia Vera
  • Testing for JAK2 exon 12 mutation Mutation Genetic mutations are errors in DNA that can cause protein misfolding and dysfunction. There are various types of mutations, including chromosomal, point, frameshift, and expansion mutations. Types of Mutations:
    • Obtained if with sustained elevated hemoglobin and hematocrit Hematocrit The volume of packed red blood cells in a blood specimen. The volume is measured by centrifugation in a tube with graduated markings, or with automated blood cell counters. It is an indicator of erythrocyte status in disease. For example, anemia shows a low value; polycythemia, a high value. Neonatal Polycythemia, subnormal EPO EPO Glycoprotein hormone, secreted chiefly by the kidney in the adult and the liver in the fetus, that acts on erythroid stem cells of the bone marrow to stimulate proliferation and differentiation. Erythrocytes: Histology, but JAK2 V617F–negative
    • Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship are often younger and have higher hemoglobin and lower white blood cell (WBC) and platelet counts Platelet counts The number of platelets per unit volume in a sample of venous blood. Coagulation Studies.
• Bone marrow Bone marrow The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. Bone Marrow: Composition and Hematopoiesis biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma:
  • No bone marrow Bone marrow The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. Bone Marrow: Composition and Hematopoiesis findings absolutely differentiate PV PV Polycythemia vera (PV) is a chronic myeloproliferative neoplasm characterized by the overproduction of rbcs. In addition, the wbc and platelet counts are also increased, which differentiate pv from erythrocytosis seen with chronic hypoxia and other chronic conditions. Polycythemia Vera from other disorders of erythrocytosis.
  • Increased cellularity (versus fibrosis Fibrosis Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. Bronchiolitis Obliterans)
  • Typically shows panmyelosis (prominent erythroid, granulocytic, and megakaryocytic proliferation)
  • Large and clumped megakaryocytes
  • Occasional increase in reticulin fibers

World Health Organization diagnostic criteria^[10]

A diagnosis of PV PV Polycythemia vera (PV) is a chronic myeloproliferative neoplasm characterized by the overproduction of rbcs. In addition, the wbc and platelet counts are also increased, which differentiate pv from erythrocytosis seen with chronic hypoxia and other chronic conditions. Polycythemia Vera is made with the presence of either: 

• 3 major criteria
• 1st 2 major criteria and the minor criterion

Major criteria:

• Laboratory testing:
  • Hemoglobin > 16.5 g/dL in men, > 16.0 g/dL in women, OR 
  • Hematocrit Hematocrit The volume of packed red blood cells in a blood specimen. The volume is measured by centrifugation in a tube with graduated markings, or with automated blood cell counters. It is an indicator of erythrocyte status in disease. For example, anemia shows a low value; polycythemia, a high value. Neonatal Polycythemia > 49 % in men, > 48 % in women, OR
  • Increased red cell mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast (> 25 % above mean normal predicted value)
• Bone marrow Bone marrow The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. Bone Marrow: Composition and Hematopoiesis biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma: prominent erythroid, granulocytic, and megakaryocytic proliferation (panmyelosis) with pleomorphic Pleomorphic Bacteroides, mature megakaryocytes
• JAK2 V617F or JAK2 exon 12 mutation Mutation Genetic mutations are errors in DNA that can cause protein misfolding and dysfunction. There are various types of mutations, including chromosomal, point, frameshift, and expansion mutations. Types of Mutations

Minor criterion: 

• EPO EPO Glycoprotein hormone, secreted chiefly by the kidney in the adult and the liver in the fetus, that acts on erythroid stem cells of the bone marrow to stimulate proliferation and differentiation. Erythrocytes: Histology level < normal reference range (helps differentiate from causes of secondary erythrocytosis, such as smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases, sleep apnea Sleep apnea Repeated cessation of breathing for > 10 seconds during sleep and results in sleep interruption, fatigue, and daytime sleepiness. Obstructive Sleep Apnea, exogenous testosterone Testosterone A potent androgenic steroid and major product secreted by the leydig cells of the testis. Its production is stimulated by luteinizing hormone from the pituitary gland. In turn, testosterone exerts feedback control of the pituitary LH and FSH secretion. Depending on the tissues, testosterone can be further converted to dihydrotestosterone or estradiol. Androgens and Antiandrogens)

Management and Prognosis

The goals of treatment are to reduce symptoms, prevent thrombosis Thrombosis Formation and development of a thrombus or blood clot in the blood vessel. Epidemic Typhus, and improve quality Quality Activities and programs intended to assure or improve the quality of care in either a defined medical setting or a program. The concept includes the assessment or evaluation of the quality of care; identification of problems or shortcomings in the delivery of care; designing activities to overcome these deficiencies; and follow-up monitoring to ensure effectiveness of corrective steps. Quality Measurement and Improvement of life and survival by decreasing leukemic transformation Transformation Change brought about to an organism’s genetic composition by unidirectional transfer (transfection; transduction, genetic; conjugation, genetic, etc.) and incorporation of foreign DNA into prokaryotic or eukaryotic cells by recombination of part or all of that DNA into the cell’s genome. Bacteriology and progression to myelofibrosis. The following is based on US, UK, and European guidelines.

General management^[5,9,11,13]

• All patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship:
  • Phlebotomy Phlebotomy The techniques used to draw blood from a vein for diagnostic purposes or for treatment of certain blood disorders such as erythrocytosis, hemochromatosis, polycythemia vera, and porphyria cutanea tarda. Hereditary Hemochromatosis to reduce hematocrit Hematocrit The volume of packed red blood cells in a blood specimen. The volume is measured by centrifugation in a tube with graduated markings, or with automated blood cell counters. It is an indicator of erythrocyte status in disease. For example, anemia shows a low value; polycythemia, a high value. Neonatal Polycythemia to < 45%
  • Low-dose aspirin Aspirin The prototypical analgesic used in the treatment of mild to moderate pain. It has anti-inflammatory and antipyretic properties and acts as an inhibitor of cyclooxygenase which results in the inhibition of the biosynthesis of prostaglandins. Aspirin also inhibits platelet aggregation and is used in the prevention of arterial and venous thrombosis. Nonsteroidal Antiinflammatory Drugs (NSAIDs) 81 mg daily (unless contraindicated) to reduce symptoms of microvascular events
    • In patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with platelets Platelets Platelets are small cell fragments involved in hemostasis. Thrombopoiesis takes place primarily in the bone marrow through a series of cell differentiation and is influenced by several cytokines. Platelets are formed after fragmentation of the megakaryocyte cytoplasm. Platelets: Histology > 1 million/µL, test for acquired von Willebrand syndrome (aVWS).
    • Those with aVWS should not receive aspirin Aspirin The prototypical analgesic used in the treatment of mild to moderate pain. It has anti-inflammatory and antipyretic properties and acts as an inhibitor of cyclooxygenase which results in the inhibition of the biosynthesis of prostaglandins. Aspirin also inhibits platelet aggregation and is used in the prevention of arterial and venous thrombosis. Nonsteroidal Antiinflammatory Drugs (NSAIDs), as they are at risk for aspirin-associated bleeding.
  • Smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases cessation (if applicable)
  • Address other modifiable atherosclerotic cardiovascular disease risk factors (e.g., diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus, hyperlipidemia, hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension, obesity Obesity Obesity is a condition associated with excess body weight, specifically with the deposition of excessive adipose tissue. Obesity is considered a global epidemic. Major influences come from the western diet and sedentary lifestyles, but the exact mechanisms likely include a mixture of genetic and environmental factors. Obesity)
• Approach:
  • Low-risk patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship ( patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship ≤ 60 years old and with no history of thrombosis Thrombosis Formation and development of a thrombus or blood clot in the blood vessel. Epidemic Typhus) are treated with phlebotomy Phlebotomy The techniques used to draw blood from a vein for diagnostic purposes or for treatment of certain blood disorders such as erythrocytosis, hemochromatosis, polycythemia vera, and porphyria cutanea tarda. Hereditary Hemochromatosis and aspirin Aspirin The prototypical analgesic used in the treatment of mild to moderate pain. It has anti-inflammatory and antipyretic properties and acts as an inhibitor of cyclooxygenase which results in the inhibition of the biosynthesis of prostaglandins. Aspirin also inhibits platelet aggregation and is used in the prevention of arterial and venous thrombosis. Nonsteroidal Antiinflammatory Drugs (NSAIDs).
  • High-risk patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship ( patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship > 60 years old and with history of thrombosis Thrombosis Formation and development of a thrombus or blood clot in the blood vessel. Epidemic Typhus) are recommended to also have cytoreductive therapy in addition to phlebotomy Phlebotomy The techniques used to draw blood from a vein for diagnostic purposes or for treatment of certain blood disorders such as erythrocytosis, hemochromatosis, polycythemia vera, and porphyria cutanea tarda. Hereditary Hemochromatosis and aspirin Aspirin The prototypical analgesic used in the treatment of mild to moderate pain. It has anti-inflammatory and antipyretic properties and acts as an inhibitor of cyclooxygenase which results in the inhibition of the biosynthesis of prostaglandins. Aspirin also inhibits platelet aggregation and is used in the prevention of arterial and venous thrombosis. Nonsteroidal Antiinflammatory Drugs (NSAIDs).

Cytoreductive agents^[5,9,11,14]

Hydroxyurea Hydroxyurea An antineoplastic agent that inhibits DNA synthesis through the inhibition of ribonucleoside diphosphate reductase. Antimetabolite Chemotherapy ( hydroxycarbamide Hydroxycarbamide An antineoplastic agent that inhibits DNA synthesis through the inhibition of ribonucleoside diphosphate reductase. Antimetabolite Chemotherapy in UK):

• 1st-line cytoreductive agent
• Dosing:
  • Initial: 500 mg twice daily 
  • Titrate to hematocrit Hematocrit The volume of packed red blood cells in a blood specimen. The volume is measured by centrifugation in a tube with graduated markings, or with automated blood cell counters. It is an indicator of erythrocyte status in disease. For example, anemia shows a low value; polycythemia, a high value. Neonatal Polycythemia target

Interferons Interferons Interferon (IFN) is a cytokine with antiviral properties (it interferes with viral infections) and various roles in immunoregulation. The different types are type I IFN (IFN-ɑ and IFN-β), type II IFN (IFN-ɣ), and type III IFN (IFN-ƛ). Interferons:^[8]

• Restore normal RBC counts; effect may persist after discontinuing.
• Decreases JAK2 V617F allele Allele Variant forms of the same gene, occupying the same locus on homologous chromosomes, and governing the variants in production of the same gene product. Basic Terms of Genetics burden → improved myelofibrosis-free survival rate compared to hydroxyurea Hydroxyurea An antineoplastic agent that inhibits DNA synthesis through the inhibition of ribonucleoside diphosphate reductase. Antimetabolite Chemotherapy or phlebotomy Phlebotomy The techniques used to draw blood from a vein for diagnostic purposes or for treatment of certain blood disorders such as erythrocytosis, hemochromatosis, polycythemia vera, and porphyria cutanea tarda. Hereditary Hemochromatosis
• May lower the rate of disease progression to myelofibrosis or leukemia
• Used in younger patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship (< 40 years) or those who may become pregnant, who require further therapy beyond phlebotomy Phlebotomy The techniques used to draw blood from a vein for diagnostic purposes or for treatment of certain blood disorders such as erythrocytosis, hemochromatosis, polycythemia vera, and porphyria cutanea tarda. Hereditary Hemochromatosis
• Options:
  • Ropeginterferon alfa-2b (brand name Besremi):
    • Initially 100 mcg SC every 2 weeks
    • Increase dose every 2 weeks until Hct < 45%, platelets Platelets Platelets are small cell fragments involved in hemostasis. Thrombopoiesis takes place primarily in the bone marrow through a series of cell differentiation and is influenced by several cytokines. Platelets are formed after fragmentation of the megakaryocyte cytoplasm. Platelets: Histology < 400,000/µL, and leukocytes Leukocytes White blood cells. These include granular leukocytes (basophils; eosinophils; and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). White Myeloid Cells: Histology < 10,000/µL (maximum dose, 500 µg/dose)
  • Peginterferon alfa-2a (brand name Pegasys):
    • 90 µg SC once weekly
    • Adjust based on response.

Ruxolitinib Ruxolitinib Targeted and Other Nontraditional Antineoplastic Therapy (JAK2 inhibitor):

• Only for patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with severe pruritus Pruritus An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. Atopic Dermatitis (Eczema), symptomatic splenomegaly Splenomegaly Splenomegaly is pathologic enlargement of the spleen that is attributable to numerous causes, including infections, hemoglobinopathies, infiltrative processes, and outflow obstruction of the portal vein. Splenomegaly, or myelofibrosis that fails to respond to hydroxyurea Hydroxyurea An antineoplastic agent that inhibits DNA synthesis through the inhibition of ribonucleoside diphosphate reductase. Antimetabolite Chemotherapy
• Dosing:
  • 10 mg orally twice daily for 4 weeks
  • If needed, titrate by increasing dose in increments of 5 mg twice daily (no more frequently than every 2 weeks) to a maximum of 25 mg twice daily.

Busulfan Busulfan An alkylating agent having a selective immunosuppressive effect on bone marrow. It has been used in the palliative treatment of chronic myeloid leukemia, but although symptomatic relief is provided, no permanent remission is brought about. According to the fourth annual report on carcinogens, busulfan is listed as a known carcinogen. Bronchiolitis Obliterans:

• Alkylating agent Alkylating Agent Alkylating agents are cell cycle-independent antineoplastic drugs that work primarily by binding alkyl groups to various parts of DNA. The overall action produces cross-linking of DNA, leading to inhibition of DNA replication and DNA damage. Alkylating Agents and Platinum associated with cytopenia, pulmonary fibrosis Fibrosis Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. Bronchiolitis Obliterans, marrow aplasia Aplasia Cranial Nerve Palsies
• Reserved for older patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship (> 60 years old) who have PV PV Polycythemia vera (PV) is a chronic myeloproliferative neoplasm characterized by the overproduction of rbcs. In addition, the wbc and platelet counts are also increased, which differentiate pv from erythrocytosis seen with chronic hypoxia and other chronic conditions. Polycythemia Vera that has not responded to hydroxyurea Hydroxyurea An antineoplastic agent that inhibits DNA synthesis through the inhibition of ribonucleoside diphosphate reductase. Antimetabolite Chemotherapy and/or interferon
• Initial dose is 2–4 mg a day.

Prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas and complications^[11]

• Thrombosis Thrombosis Formation and development of a thrombus or blood clot in the blood vessel. Epidemic Typhus is the most common cause of morbidity Morbidity The proportion of patients with a particular disease during a given year per given unit of population. Measures of Health Status and death, followed by the complications of myelofibrosis and leukemic transformation Transformation Change brought about to an organism’s genetic composition by unidirectional transfer (transfection; transduction, genetic; conjugation, genetic, etc.) and incorporation of foreign DNA into prokaryotic or eukaryotic cells by recombination of part or all of that DNA into the cell’s genome. Bacteriology.
• About 10%–30% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship progress to a syndrome compatible with primary myelofibrosis Primary myelofibrosis Primary myelofibrosis (PMF) is a myeloproliferative neoplasm characterized by chronic myeloproliferation with nonclonal fibroblastic deposition, resulting in bone marrow fibrosis. The abnormality stems from genetic mutations of the hematopoietic stem cells (typically, JAK2 mutation). Primary symptoms are anemia and extramedullary hematopoiesis,. Primary Myelofibrosis but with better survival.
• Leukemic transformation Transformation Change brought about to an organism’s genetic composition by unidirectional transfer (transfection; transduction, genetic; conjugation, genetic, etc.) and incorporation of foreign DNA into prokaryotic or eukaryotic cells by recombination of part or all of that DNA into the cell’s genome. Bacteriology from PV PV Polycythemia vera (PV) is a chronic myeloproliferative neoplasm characterized by the overproduction of rbcs. In addition, the wbc and platelet counts are also increased, which differentiate pv from erythrocytosis seen with chronic hypoxia and other chronic conditions. Polycythemia Vera occurs in about 2% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship at 10 years to about 8% at 20 years.^[12,13]

Differential Diagnosis

• Secondary polycythemia Secondary Polycythemia Polycythemia Vera: an increase in RBCs RBCs Erythrocytes, or red blood cells (RBCs), are the most abundant cells in the blood. While erythrocytes in the fetus are initially produced in the yolk sac then the liver, the bone marrow eventually becomes the main site of production. Erythrocytes: Histology due to chronic hypoxemia Hypoxemia Neonatal Respiratory Distress Syndrome, familial erythrocythemia, paraneoplastic syndromes Paraneoplastic syndromes Paraneoplastic syndromes are a heterogeneous group of disorders caused by an abnormal immune response to a neoplasm. The substances produced are not due to the direct effect of the tumor, such as metastasis, mass effect, or invasion. Antibodies, hormones, cytokines, and other substances are generated and affect multiple organ systems. Paraneoplastic Syndromes, or relative polycythemia Polycythemia An increase in the total red cell mass of the blood. Renal Cell Carcinoma due to contraction of plasma Plasma The residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation. Transfusion Products volume as seen with dehydration Dehydration The condition that results from excessive loss of water from a living organism. Volume Depletion and Dehydration.
• Essential thrombocytosis (primary thrombocythemia): a nonreactive, chronic myeloproliferative disorder in which excessive proliferation of megakaryocytes and platelets Platelets Platelets are small cell fragments involved in hemostasis. Thrombopoiesis takes place primarily in the bone marrow through a series of cell differentiation and is influenced by several cytokines. Platelets are formed after fragmentation of the megakaryocyte cytoplasm. Platelets: Histology is seen. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship are largely asymptomatic but may develop thrombosis Thrombosis Formation and development of a thrombus or blood clot in the blood vessel. Epidemic Typhus and bleeding.
• Chronic myeloid leukemia Chronic myeloid leukemia Chronic myeloid leukemia is a malignant proliferation of the granulocytic cell line characterized by a fairly normal differentiation. The underlying genetic abnormality is the Philadelphia chromosome, an abbreviated chromosome 22, resulting from reciprocal (9;22)(q34;q11) translocation. Chronic Myeloid Leukemia: a myeloproliferative disorder characterized by an increase in WBCs, including an increased number of granulocytes Granulocytes Leukocytes with abundant granules in the cytoplasm. They are divided into three groups according to the staining properties of the granules: neutrophilic, eosinophilic, and basophilic. Mature granulocytes are the neutrophils; eosinophils; and basophils. White Myeloid Cells: Histology and their immature precursors. Blast cells are also seen occasionally. 
• Primary myelofibrosis Primary myelofibrosis Primary myelofibrosis (PMF) is a myeloproliferative neoplasm characterized by chronic myeloproliferation with nonclonal fibroblastic deposition, resulting in bone marrow fibrosis. The abnormality stems from genetic mutations of the hematopoietic stem cells (typically, JAK2 mutation). Primary symptoms are anemia and extramedullary hematopoiesis,. Primary Myelofibrosis: a clonal disorder arising from the neoplastic transformation Transformation Change brought about to an organism’s genetic composition by unidirectional transfer (transfection; transduction, genetic; conjugation, genetic, etc.) and incorporation of foreign DNA into prokaryotic or eukaryotic cells by recombination of part or all of that DNA into the cell’s genome. Bacteriology of early hematopoietic stem cells Hematopoietic stem cells Progenitor cells from which all blood cells derived. They are found primarily in the bone marrow and also in small numbers in the peripheral blood. Bone Marrow: Composition and Hematopoiesis. Primary myelofibrosis Primary myelofibrosis Primary myelofibrosis (PMF) is a myeloproliferative neoplasm characterized by chronic myeloproliferation with nonclonal fibroblastic deposition, resulting in bone marrow fibrosis. The abnormality stems from genetic mutations of the hematopoietic stem cells (typically, JAK2 mutation). Primary symptoms are anemia and extramedullary hematopoiesis,. Primary Myelofibrosis is characterized by anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types, bone marrow fibrosis Bone Marrow Fibrosis Primary Myelofibrosis, extramedullary hematopoiesis Extramedullary Hematopoiesis Primary Myelofibrosis, leukoerythroblastosis, teardrop-shaped RBCs RBCs Erythrocytes, or red blood cells (RBCs), are the most abundant cells in the blood. While erythrocytes in the fetus are initially produced in the yolk sac then the liver, the bone marrow eventually becomes the main site of production. Erythrocytes: Histology, and hepatosplenomegaly Hepatosplenomegaly Cytomegalovirus.
• EPO EPO Glycoprotein hormone, secreted chiefly by the kidney in the adult and the liver in the fetus, that acts on erythroid stem cells of the bone marrow to stimulate proliferation and differentiation. Erythrocytes: Histology receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors mutations: a rare familial disorder that can mimic the basic findings of PV PV Polycythemia vera (PV) is a chronic myeloproliferative neoplasm characterized by the overproduction of rbcs. In addition, the wbc and platelet counts are also increased, which differentiate pv from erythrocytosis seen with chronic hypoxia and other chronic conditions. Polycythemia Vera (elevated hemoglobin and hematocrit Hematocrit The volume of packed red blood cells in a blood specimen. The volume is measured by centrifugation in a tube with graduated markings, or with automated blood cell counters. It is an indicator of erythrocyte status in disease. For example, anemia shows a low value; polycythemia, a high value. Neonatal Polycythemia with low serum EPO EPO Glycoprotein hormone, secreted chiefly by the kidney in the adult and the liver in the fetus, that acts on erythroid stem cells of the bone marrow to stimulate proliferation and differentiation. Erythrocytes: Histology). A positive family history Family History Adult Health Maintenance, early age at disease onset, and the lack of PV-associated clinical findings can help distinguish EPO EPO Glycoprotein hormone, secreted chiefly by the kidney in the adult and the liver in the fetus, that acts on erythroid stem cells of the bone marrow to stimulate proliferation and differentiation. Erythrocytes: Histology receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors mutations from primary PV Primary Pv Polycythemia Vera.