A Review on Novel Approaches for Cure, Diagnosis, Treatment and Future Direction in Polycythemia

Ankita Damahe, Khilendra Kumar Sahu, Antra Sahu, Chunesh kumar, Devki Markande, Nilesh kumar, Janvi NilMarkar,

doi:10.5281/zenodo.14852627

Review Paper | Open Access
Volume 02 | Issue 02 | Article Id IJSRT/250302022

A Review on Novel Approaches for Cure, Diagnosis, Treatment and Future Direction in Polycythemia
Ankita Damahe* Khilendra Kumar Sahu Antra Sahu Chunesh kumar Devki Markande Nilesh kumar Janvi NilMarkar
Apollo College of Pharmacy Anjora ,Durg 491001 ,(C.G) , India

Abstract

An excess of red blood cells in the body is known as polycythemia. The blood becomes thicker due to the additional cells, which raises the risk of blood clots and other health problems. There are various causes of polycythemia, and each one has a unique course of treatment. Discover more about polycythemia's causes, symptoms, and available treatments in this article. An rise in hemoglobin or hematocrit levels over the standard values is known as polycythemia. The majority of its causes are linked to the development of hyper viscosity, and the majority of cases are classified as primary or secondary polycythemia (SP). The underlying disease of the former, often referred to as polycythemia vera (PV), affects the bone marrow itself, whereas the latter is typified by an overabundance of stimulation of cell creation in the normal bone marrow. This study included patients who were diagnosed with PV or SP after undergoing additional testing at our hospital from January 2020 to December 2023 after polycythemia was discovered. The 2016 WHO criteria (hemoglobin > 16.5 mg/L for men and >16.0 mg/L for women, and/or hematocrit > 49% for men and >48% for women) were followed in determining the laboratory thresholds used to diagnose polycythemia. A case of PV exacerbated by cardiac hypertrophy is presented in this paper. It provides a full summary of the patient's long-term follow-up and a detailed account of their experience using antihypertensive medication. With an emphasis on clinical case studies, a thorough literature analysis was also carried out to look into any potential connections between PV and the risk of cardiovascular disease. The goal is to offer fresh viewpoints and understandings for evaluating cardiovascular risk and predicting prognosis in MPN patients. These findings have important ramifications for future clinical care guidelines in addition to improving our understanding of the relationship between PV and cardiovascular disease

Keywords

Polycythamia; Hypertension,Thrombosis; Cardiomyopathy Hypertrophic,Choroidal Thickness; Hematocrit; Restricted Blood Flow

Introduction

Polycythemia or erythrocytosis, refers to an increase in the absolute amount of red blood cells (RBCs) in the body. In practice, this is reflected as an increase in hemoglobin levels, or hematocrit, above what is considered physiological for a particular age and sex. Normal red blood cell volume usually does not exceed 36 ml/kg in men and 32 ml/kg in women. Reference ranges for normal hemoglobin and hematocrit levels vary by altitude, ethnicity, and country^.[1]However, for reference, the hemoglobin and hematocrit of a healthy adult male are 16 g/dL +/- 2 g/dL and 47% +/- 6%, respectively. The hemoglobin and hematocrit of an adult menstruating woman are typically 13 g/dL +/- 2 g/dL and 40% +/- 6%, respectively. Polycythemia in neonates is defined as a central venous hematocrit greater than 65% or a hemoglobin value greater than 22 g/dL^.[2] Polycythemia vera is a subtype of polycythemia. Often colloquially referred to simply as “polycythemia,” it is an acquired myeloproliferative disorder with a Philadelphia chromosome negative pattern^{. [3]} This condition may be associated with overproduction of all three cell lineages, but with a marked predilection for red blood cells. The clinical significance of polycythemia, regardless of cause, is the associated risk of thrombotic events due to increased blood viscosity. Furthermore, polycythemia vera may lead to leukemia progression, which also necessitates the implementation of additional therapeutic strategies^[4]. Laboratory evaluations such as serum erythropoietin levels and genetic analysis may assist in determining the cause of polycythemia when the physical examination and medical history do not indicate a probable reason. Mild polycythemia typically does not present any symptoms. The management of polycythemia is variable and generally focuses on addressing its underlying cause. Treatment for primary polycythemia (refer to polycythemia vera) may include procedures like phlebotomy, antiplatelet medications to decrease the risk of blood clots, and other cytoreductive therapies to lower the production of red blood cells in the bone marrow. Laboratory research, such as the level of erythroopoettin in serum and genetic testing, can help clarify the cause of polycology if the patient's physical examination and history do not clarify the cause^.[5] Soft vegetation itself is often asymptomatic.The treatment of polyconomics varies, and usually includes the main causes of the main cause^.[6]Treatment of primary hyperhidrosis (see VERA polycacoritis) In order to reduce the risk of blood tricks to reduce the amount of red blood cells generated in the bone marrow, to reduce the risk of blood tricks and anticroat therapy may be included ^[7].

CLASSIFICATION

Spurious polycythemia

This occurs due to a decrease in the volume of red blood cells, rather than an actual increase in their mass. The reasons include:Severe dehydration due to isolated fluid loss: May be accompanied by severe diarrhea and vomiting. Heisbock syndrome: Common in obese and hypertensive men. Smoking, alcohol [abuse and the use of diuretics contribute to this.[4]

True Polycythemia

Additional stratification by serum erythropoietin (EPO) levels as follows:

1.Low serum EPO levels (primary polycythemia) Polycythemia veraPrimary familial and congenital polycythemia ^[52]

2.High serum EPO level (secondary polycythemia) High altitude Respiratory disorders: chronic obstructive pulmonary disease (COPD), Pickwick syndrome, uncontrolled asthma, Cyanotic heart disease with right-to-left shunts Renal disorders: renal cysts, renal cancer, renal artery stenosis, Bartter syndrome, focal sclerosing glomerulonephritis, Elevated carboxyhemoglobin: commonly seen in smokers, people working on cars in enclosed spaces, or people working in boiler rooms^[51] Hemoglobinopathies: high hemoglobins affinity such as Hb Yakima, methemoglobinemia EPO-secreting tumors: sources include hepatomas, uterine leiomyomas, and cerebellar hemangiomas Iatrogenic causes: including administration of erythropoietin analogues, anabolic steroids, and testosterone replacement therapy Neonatal polycythemia^{. [48][35]}

Etiology

The etiology of the disease process appears to be neoplastic proliferation.There is a signaling defect leading to an abnormal response to growth factors, and the abnormal clonal line interferes with normal lineage proliferation.The JAK2 (Janus kinase 2) gene, involved in intracellular signaling, is mutated in 90% of polycythemia vera (PV) cases. Cytogenetic studies have shown that hematopoietic progenitor cells in approximately 34% of PV patients have abnormal karyotypes. At the time of diagnosis, 20% of patients have cytogenetic abnormalities, and this figure rises to more than 80% in patients with more than 10 years of available follow-up^[8]

Epidemiology

Polycythemia vera (PV) can affect all ethnicities without sexual predisposition, but occurs slightly more often in men than women^.[9] It can occur at any age, but the average age at diagnosis is 60 years^[10]PV affects 0.6-1.6 people per million in the United States.The incidence is lower in Japan than in the United States and Europe^.[11]

Pathophysiology

The bone marrow of patients with polycythemia vera (PV) contains normal stem cells and contains abnormal clonal stem cells that suppress normal stem cell growth and maturation.The cause of panmyelosis is unregulated neoplastic proliferation.JAK2 kinase mutation likely leads to the signaling derangements resulting in PV.A valine to phenylalanine substitution at position 617 of the JAK2 gene, or JAK2V617F, leads to constitutively active cytokine receptors^.[12] ^[37]This mutation is observed in over 90% of patients with PV and 50% to 60% of primary myelofibrosis, and 50% of essential thrombocythemia^{.[13][14][35]} This process leads to increased production of red blood cells and platelets with associated complications of thrombosis and bleeding.

Treatment and Management

There is no cure for polycythemia vera (PV).The goal of treatment is to relieve symptoms and reduce the risk of complications, such as thrombosis, bleeding, and hematologic changes.Currently, there is no treatment to prevent progression to myelofibrosis or acute leukemia/myelodysplastic syndrome, but there are known medications that may increase this risk and should be avoided^.[15]

Novel polycythemia vera therapies under investigation and clinical trial

Table 1

Level of Study Author	Target	Mechanism of action
Phase 2 Ongoing	Iron Metabolism Pathway Apoptosis	Hepcidin mimetic MDM2 inhibitor
Phase 1 Ongoing	Erythroid Lineage Differentiation	Phosphoinositide 3-kinase (PI3 K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway
Phase 2	Genetic transcription Genetic transcription	Histone deacetylase inhibitor, 3in combination with hydroxyurea Monotherapy Histone deacetylase inhibitor
Phase 1	Genetic transcription Apoptosis	Monotherapy Histone deacetylase inhibitor, MDM2 inhibitor
Animal Study	Iron Metabolism Pathway	Minihepcidin-small molecule
In-vitro	Genetic transcription Genetic transcription Erythroid Lineage Differentiation Erythroid lineage proliferation through cytokines	Histone deacetylase inhibitor,, in combination with hydroxyurea Monotherapy Histone deacetylase inhibitor, Phosphoinositide 3-kinase (PI3 K)/protein kinase B, (Akt)/mammalian target of rapamycin (mTOR) pathway Insulin receptor substrate 1/2 small molecule inhibitor

Medical treatment

Patients under 60 with no history of thrombotic events are considered low risk and recommended treatment is as follows:

Phlebotomy: Aim for a hematocrit of less than 45%.Each unit (500 ml) of blood phlebotomized is expected to reduce the hematocrit of an average-sized adult by 3%. Men can tolerate a maximum withdrawal of 1.5-2 units per week, while women, the elderly, those weighing less than 50 kg, or those with cardiovascular disease can only tolerate a withdrawal of 0.5 units per week.The purpose of pulse pipe incision is to intentionally induce iron deficiency.This is to limit the abilities of the bone marrow of red blood cells to some extent.Therefore, patients do not take iron supplements^[29]Compared to objective hematrits, vascular patients with less than 45 % have a significant less than 45 % of cardiovascular and thrombosis events^.[16] If there is no contraindications, a low -dose aspirin (40 mg for 100 mg), if there is no contraindications, it is necessary to reduce thrombosis risk.[19] Patients with platelets exceeding 1 million /microliters should not be placed in aspirin because they may be more risky for bleeding due to phytowil brand's acquired diseases^.[17][36]Treats aspirin's intractable symptoms.

Optimize cardiovascular health, including weight loss, exercise, smoking cessation, and blood pressure control.Patients over 60 years of age and/or those with a history of thrombosis are considered at higher risk.For high-risk patients, cytoreductive therapy is recommended in addition to phlebotomy and aspirin.The first-line treatment is hydroxyurea (HU) due to its safety profile, cost, and effectiveness^.[18] ^[49]The initial dosage is 15 mg per kg of actual body weight per day, given in two divided doses per day. The goal is to reduce platelets to 100,000 to 400,000 / MicrolyTra without excessive neutropenia and anemia.The dosage should not be regulated more often by once a week, because to achieve the therapeutic effect, it takes three to five days.For patients who do not respond to or cannot tolerate hydroxyurea therapy, pegylated interferon or busulfan may be tried. Other alternatives include ruxolitinib, anagrelide, pipobroman, and radioactive phosphorus^.[18][19]

Blood withdrawals

The most common treatment for polycythemia vera is having frequent blood withdrawals, using a needle in a vein (phlebotomy).It\'s the same procedure used for donating blood.This decreases your blood volume and reduces the number of excess blood cells.The frequency of blood tests depends on the severity of the condition^.[30]

Treatment of itching

If you are bothered by itching, your doctor may prescribe medications such as antihistamines to reduce the discomfort or recommend ultraviolet light therapy.Drugs called selective serotonin reuptake inhibitors (SSRIs), commonly used to treat depression, have helped reduce itching in clinical trials. Examples of selective serotonin reuptake inhibitors (SSRIs) include paroxetine (Brisdell, Paxil, Pexeva, and others) or fluoxetine (Prozac, Sarafem, Selfemra, and others)^[31].

Drugs that reduce the number of red blood cells

If phlebotomy alone is not enough, your doctor may recommend medications that can reduce the number of red blood cells in your bloodstream. Here are some examples:

• Hydroxylura (Droxia, Hydrea)

• Interferon alpha-2b (Intron A)

• Ruxolitinib (Jakafi)

• Busulfan (Busulfex, Myleran)^[32]

Heart medications

Your doctor will also likely prescribe medications to control risk factors for heart and blood vessel disease, including high blood pressure, diabetes and abnormal cholesterol.Your doctor may recommend that you take a low dose of aspirin to reduce your risk of blood clots. Low-dose aspirin may also help reduce burning pain in your feet or hands^[33]

Self-care

If you've been diagnosed with polycythemia vera, there are steps you can take to feel better.Try:

• Exercise. Moderate exercise, such as walking, gets the blood flowing. This helps reduce the risk of blood clots.Stretching and exercising your legs and ankles can also improve circulation.

• Avoid tobacco.Smoking can cause your blood vessels to narrow, increasing your risk of heart attack or stroke due to blood clots.

• Avoid low-oxygen environments.Life in highlands, skiing or mountain climbing in the mountains still reduce the level of oxygen in the blood.

• Be kind to your skin -Swim with cold water to reduce itching and stroke the skin using a soft cleansing agent. Adding a starch such as cornstarch to the bathtub may help.

Avoid hot baths, hot whirlpools, and hot showers or baths.

Don't hurt your skin, as it can damage the skin and increase the risk of infection.

Use lotion to wet your skin.

• Avoid extreme temperatures. Poor circulation increases the risk of injury from hot and cold temperatures.

Always wear warm clothing during cold weather, especially your arms and legs. In hot weather, protect yourself from the sun and drink plenty of fluids.

• Watch for ulcers. Poor circulation can make it difficult for ulcers to heal, especially on the hands and feet.Check your feet regularly and tell your doctor about pain^.[34][35]

Heart medications

Your doctor will also prescribe medications to control risk factors for heart and vascular disease, such as high blood pressure, diabetes, and abnormal cholesterol. Your doctor may recommend taking low-dose aspirin to reduce the risk of blood clots.Low-dose aspirin may also help reduce burning pain in the feet and hands.[33]

Surgical Treatment

Splenectomy may be appropriate in cases of painful splenomegaly and recurrent splenic infarction.BUDD-CHIARI syndrome or venous liver drainage is a surgical intervention such as the intravenous intravenous intraorphitho (TIPS), Porto-Chabal Shunt, Shunt Cabal Star, Caval / Caval Midarterial Shint, or Sage Shunt Sage Sage.A potential complication that requires the potential complications required] [21]
Differential diagnoses to consider include

Rare mutations in the erythropoietin (EPO) receptor can mimic the cardinal symptoms of PV, such as increased red blood cell mass and decreased EPO, but the mechanism is not EPO-independent but rather a hypersensitive EPO receptor mechanism. [23][24] Isolated granulocytosis can occur as a result of an infection or leukemic reaction.Only plateletosis may be the result of bleeding or iron deficiency.

Essential thrombocythemia

Chronic myeloid leukemia

Myeloid metaplasia of unknown origin

Chronic myeloid leukemia

Primary myelofibrosis

Secondary polycythemia^[22][23][24]

Future direction

Polycythemia vera (PV) is a condition in which the bone marrow is overworked and produces too many red blood cells, white blood cells, and platelets, which can put you at risk for life-threatening blood clots, bleeding, and some types of blood cancer.Therefore, frequent visits to a hematologist and close monitoring and treatment are important to reduce these risks.Treatment options include phlebotomy, daily aspirin, and certain bone marrow suppressant drugs^{[25,26,27,28]}

CONCLUSION

These reviews explore the potential and future directions of various treatments to treat or prevent polycythemia or erythrocytosis and its symptoms. It provides a full summary of the patient's long-term follow-up and a detailed account of their experience using antihypertensive medication. With an emphasis on clinical case studies, a thorough literature analysis was also carried out to look into any potential connections between PV and the risk of cardiovascular disease. The goal is to offer fresh viewpoints and understandings for evaluating cardiovascular risk and predicting prognosis in MPN patients. These findings have important ramifications for future clinical care guidelines in addition to improving our understanding of the relationship between PV and cardiovascular disease.In summary, NLR, PLR, and SII showed remarkable ability to distinguish PV from MS. The diagnostic efficacy of these three parameters in recognizing PV was improved when used in combination with EPO.EPO and SII, and SII alone, have been shown to be the most useful biomarkers for the diagnosis of PV.These results indicate that these biomarkers, especially SII, may serve as additional criteria in the diagnosis of PV.We believe that further studies are warranted to explore the diagnostic improvements achieved by combining SII (and other inflammatory markers) with EPO levels in patients with erythrocytosis, which may be important in facilitating the early diagnosis of PV

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