a brief review on anemia & its clinical management

Int. J. Pharm. Res. Sci., 2014, 02(1), 37-41. www.ijprsonline.com ISSN: 2348 –0882==========================================================================

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A Brief Review on Anemia & Its Clinical ManagementBabita Gautam*, Arunbala, Anshubala, Ajay kumar, Chetan kr Dubey , Shalini Tripathi.

*Department of Pharmacy, Rameshwaram Institute of Technology and Management Lucknow, UPTUEmail- [email protected]

----------------------------------------------------------------------------------------------------------------------------------Abstract:A reduction of hemoglobin concentration in bloodis termed as anemia. Especially women’s aresuffering from anemia due to loss of blood inmenstrual cycle, poor nutrition foods and inpostpartum females and different types of diseasesin humans which causes anemia. To treat thisthere is no specific medicine is available exceptiron tablets though they are not safe and maycause serious health problems. That’s why in thisparticular review article I will emphasis on thenaturally occurring products which may bebeneficial in anemia.

Keywords: Hemoglobin, anemia and its types,causes, diagnosis and treatments.

IntroductionAnemia is a medical condition in which the redblood cells or hemoglobin is less than normal. Thenormal level of hemoglobin is generally differentin males and females. For men, anemia istypically defined as hemoglobin level is less than13.5gm/100 ml and in women less than 12gm/100 ml. [1] Anemia causes serious problemsdue to loss of blood in the body by variousreasons. In the tropics, due to endemicity ofmalaria, between 10-20 % of the populationpresents less than 10gm/dl of hemoglobin.Hemoglobin is a main part of RBC which bindsoxygen and oxyhemoglobin. If there is less orabnormal RBCs in your blood, it is the reason thatyour body will not get enough oxygen. Womenand people with chronic disease are at increasedrisk of anemia. Anemia occurs when you don’t

have enough RBC or when yours RBC do notwork properly [2]

Symptoms: In case of anemia followingsymptoms are appear-Fatigue, Weakness, Shortness of breath, Lightheadedness, Palpitations, Decrease energy,Looking pale, Dizziness, Heart attack, Rapid heartrate, Low blood pressure, Rapid breathingCauses: Following are the causes which maycause anemia-External bleeding, Chronic disease, Pregnancy,Bleeding disorders, Infections, Hereditaryconditions, Jaundice, Imbalance nutrition.Types of anemia: Anemia has various types,some of which are named below-Sickle cell anemia, A plastic anemia, Thalassemia,Bone marrow related anemia, Hemolytic anemia,Pernicious anemia, Anemia from active bleeding,Iron deficiency anemia, Anemia of chronicdisease, Anemia related to kidney disease,Anemia related to pregnancy.Anemia Treatment

approachesReference

Hemolyticanemia

In case of thisanemia, Special bloodtransfusions

[3]

Perniciousanemia

ThisTreatment involves ashot of vitamin B12once a month

[4]

Sickle cellanemia

Drugs, likeAnalgesic , opiods

[5]

Thalassemia Deferoxamine,deferasirox,deferiprone

[6]


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approachesReference

Hemolyticanemia


[3]

Perniciousanemia


[4]

Sickle cellanemia


[5]


[6]


37








approachesReference

Hemolyticanemia


[3]

Perniciousanemia


[4]

Sickle cellanemia


[5]


[6]


38

Alcoholism Diazepam,disulfuram,

[7]

Irondeficiencyanemia

Iron sulfate [8]

Aplasticanemia

hematopoietic stemcell transplantationCombination

[9]

Table.1 (various types of anemia and its treatmentapproaches)

Sickle cell anemia:Sickle cell anemia is caused by an autosomalrecessive inherited disorder which results ashemolysis. The genetic abnormality is due tosubstitution of the amino acid valine for glutamicacid at the sixth position on the beta globulinchain and was first described over one hundredyrs ago [10]. Hemoglobin S, the hemoglobin that isproduced as a result of this defeat, is ahemoglobin tetramer (alpha 2/ beta S2) that ispoorly soluble and polymerizes whendeoxygenated. [11] Over all the incidence of sicklecell disease exceeds that of most other seriousgenetic disorder including cystic fibrosis andhemophilia [12].Sign and symptoms: Sickle cell anemia hassymptoms like-Shortness of breath, Dizziness, Headaches,Coldness of hand and feet, Paler than normal skinor mucous membranes (the tissue that lines yournose, mouth, and other organs and body cavities),Jaundice (a yellowish color of the skin or whitesof the eyes).

Figure.1.normal RBCs [13]

Figure.2 sickle shapedRBCs

Treatment:Folic acid and penicillin:Children born with sickle-cell disease willundergo close observation by the pediatrician andwill require management by a hematologist toassure they remain healthy. These patients willtake a 1 mg dose of folic acid daily for life. Frombirth to five years of age, they will also have totake penicillin daily due to the immature immunesystem that makes them more prone to earlychildhood illnesses [14].Analgesics:Painful crises are treated symptomatically withanalgesics; pain management requires opioidadministration at regular intervals until the crisishas settled. For milder crises, subgroups ofpatients manage on NSAIDs (such as diclofenacor naproxen). For more severe crises, mostpatients require inpatient management forintravenous opioids; patient-controlled analgesia(PCA) devices are commonly used in this setting.Diphenhydramine is also an effective agent that isfrequently prescribed by doctors in order to helpcontrol any itching associated with the use ofopioids [15].

Blood transfusions: Blood transfusions are oftenused in the management of sickle cell disease inacute cases and to prevent complications by


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decreasing the number of red blood cells (RBC)that can sickle by adding normal red blood cells[16]

Hemolytic anemia:Glucose-6-phosphate dehydrogenase (G-6-PD)deficiency is an X-linked disorder, in this type ofanemia there is rupture blood cells in blood streamwhich leads to acute hemolytic anemia.

Although many G-6-PD variants have beendescribed, susceptibility to some drugs has beenmainly confined to the G-6-PD Mediterraneanvariant largely found in Sardinia. Its incidence inthe North is different from that of the South [17]

Many patients who are already anemic, they alsohave jaundice. Splenomegaly, reticulocytosis andincreased osmotic fragility of RBCs. [18]

Symptoms: following symptoms are observed-

Feeling grumpy, Weakness, Headaches, Brittlenails, Blue color to the whitish of eye, Pale skincolor, Shortness of breath

Important test for hemolytic anemia: [19]

Absolute reticulocyte count- The reticulocytecount is used to estimate the degree of effectiveerythropoiesis, which can be reported as absolutereticulocyte count or as a reticulocyte percentage.

Coombs test- Used for the autoimmunehemolytic anemia, and a condition of a low countRBC immune system lysis or breaking of RBCmembranes causing RBC destruction.

Coombs test, indirect - it's mostly for prenatalpregnant women, It detects antibodies againstRBCs that are present unbound in the patient'sserum.

Donath-landsteiner test-- The Donath-Landsteiner test is used for detecting harmfulantibodies related to a rare disorder calledparoxysmal cold hemoglobinuria. The antibodiesform and destroy red blood cells when the body isexposed to cold temperatures [20].

Platelet count- This test measures the number ofplatelets in blood. It is used to evaluate bleedingdisorders [21] this test may be used when disorderscaused by low blood platelets such asthrombocytopenia are suspected

Serum LDH- The LDH level is measured in orderto check for tissue damage, especially to the heart,liver, kidney, skeletal muscle, brain, and lungs —all of which elevates the normally low LDH levelin the blood.

Hemosiderin in the urine- This test detectshemosiderin in urine. Hemosiderin is a pigmentformed when hemoglobin breaks down. This testis used to evaluate and manage disordersinvolving the destruction of red blood cells [21]

Febrile of cold agglutinins- Agglutinins areantibodies that cause the red blood cells to clumptogether Cold agglutinins are active at coldtemperatures. Febrile (warm) agglutinins areactive at normal body temperatures. This articlediscusses the blood test used to measure the levelof these antibodies in the blood.

Treatment: [22]

Blood transfusion may be needed. Hemolyticanemia caused by an overactive immune systemdrugs that suppress the immune system may beused. When blood is destroyed at a fast pace thebody may need extra folic acid and ironsupplements to replace what is being lost.

Pernicious anemia:

Pernicious anemia is a type of vitamin B12deficiency anemia. The body needs vitamin B12to make red blood cells. You get this vitamin fromeating foods such as meat, poultry, shellfish, eggs,and dairy products. A special protein, calledintrinsic factor, helps your intestines absorbvitamin B12. This protein is released by cells inthe stomach. When the stomach does not makeenough intrinsic factor, the intestine cannotproperly absorb vitamin B12 [23]


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Symptoms: There are following symptoms ofpernicious anemia- Diarrhea or constipation.Fatigue, lack of energy, or light-headedness whenstanding up or with exertion , Loss of appetite ,Pale skin , Problems concentrating , Shortness ofbreath, mostly during exercise , Confusion ,Depression, Loss of balance .

Anemia in pregnancy:According to WHO, anemia in pregnancy isdefined as hemoglobin level is less than 11 g/dland hematocrit level is less than 33% at any stageof pregnancy [26]. Anemia of pregnancy affectswomen of low socioeconomic status. According toWHO 52% of pregnant women from undevelopedor developed countries area anemic as comparedwith 20% from industrialized nation [24].The riskof anemia in pregnancy increases with progressionof pregnancy by CDC criteria among low incomepregnant women in the US 8% are anemic in thefirst trimester ,12% in the second & 34% in thethird [25] . Hydremia of pregnancy was firstproposed by German & French physician in the1830s formally demonstrated in 1934 byDieckmann & Degner [26].Folate deficiency ishistorical regarded as the second most commoncause of anemia of pregnancy after iron deficiency& B12 dificiency is more prevalent. In studies,from India, Turkey, Africa, Newfoundland, &Venezuela 10% to 100% of pregnant women havea folate deficiency where as 30% to 100% havevit. B12 deficiency. The prevalence of folate or vitb12 deficiency increased with gestation [27].

Thalassemia:

Thalassemia can cause significant complications,including pneumonia, iron overload, bonedeformities and cardiovascular illness. Howeverthis same inherited disease of red blood cells mayconfer a degree of protection against malaria,

which is or was prevalent in the regions where thetrait is common. This selective survival advantageon carriers (known as heterozygous advantage)may be responsible for perpetuating the mutationin populations. In that respect, the variousthalassemias resemble another genetic disorderaffecting hemoglobin, sickle-cell disease. [28]

Alpha (α) thalassemias

The α thalassemias involve the genes HBA1[29].

And HBA2[30]. inherited in a Mendelian recessive

fashion. There are two gene locii and so fouralleles.

Beta (β) thalassemiasBeta thalassemias are due to mutations in theHBB gene on chromosome 11[31] also inherited inan autosomal-recessive fashion.Aplastic anemia:Aplastic anemia is a term which defined asdestruction of bone marrow to produce RBC.Aplastic anemia is rare disease but approx. 2000patient diagnosed in America in every year [32].Two mechanisms have been suggested for bonemarrow failure. The first mechanism is directhematopoietic injury by chemicals (e.g. benzene).The second mechanism, supported by clinicalobservations and laboratory studies, is immune-mediated suppression of marrow cells [33].

Figure. 3 Abnormal celFigure. 4 Normal cells [34]

(Fig no 3 Showing Abnormal shape of RBCs dueto bone marrow Suppression)


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Pathophysiology of aplastic anemia:

Figure 4. Immune destruction ofhematopoiesis [35].

Antigen representing cells (APCs) trigger T-cellto activate and proliferate. A transcription factorwhich binds to the interferon-y promoters’ siteand induce gene expression and reduce genetranscription [36]. Patient with aplastic anemiashows constitutive T-bet expression and low SAPlevels, TNF-a and IFN-y up regulate other T-cellcellular receptor and also the FAS receptorIncreased production of interleukin-2 leads topolyclonal expansion of T- cell. Activation of fasligand leads to apoptosis of target cell whichinhibit the transcription of cellular genes and entryinto the cell cycle [37]. INF-y is a potent inducer ofmany cellular genes and NOS (nitric oxidesynthase) and production of toxic gas and NO [38].The processes ultimately lead to reduced cellcycling and cell death by apoptosis.Iron deficiency anemia:

Iron-deficiency anemia (or iron-deficiencyanaemia) is a common anemia (low red blood cellor hemoglobin levels) caused by insufficientdietary intake and absorption of iron, or iron lossfrom bleeding which can be from a variety ofsources such as intestinal, uterine or from the

Urinary tract. Iron deficiency causesapproximately half of all anemia cases worldwide,and affects women more often than men. Worldestimates of iron deficiency occurrence aresomewhat vague, but the true number probablyexceeds one billion people [39]. The mostsignificant cause of iron-deficiency anemia isparasitic worms: hookworms, whipworms, androundworms. Worms cause intestinal bleeding,which is not always noticeable in faeces, and isespecially damaging to growing children. [40]

Malaria, hookworms and vitamin A deficiencycontribute to anemia during pregnancy in mostunderdeveloped countries [40].

Diagnosis, cause and treatment of anemia [41] :In the below table different types of anemia,description, causes, and their diagnosis andtreatments are described.


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Type ofanemia

Description Diagnosis Causes Treatments

Aplasticanemia

Bone marrow fails toproduce differenttype of blood cells

Bleeding inmucousmembranes,gingivitis, andshortness ofbreath.

Known causes arehereditary conditions(fanconi’s anemia),HIV virus, hepatitis,rheumatoid arthritis.

Transfusion, bonemarrow or stem celltransplantation,immunosuppressantdrugs

Thalassemia Irregular productionof hemoglobin thereare two types ofthallesemia i.e majorand minor

Affect equallymales andfemales, bothtypes ofthalassemia arefound in anarea of northernAfrica andsouthernEurope.

Thalassemia major ismore common infamilies whointermarry

Transfusions to supplyenough red blood cellsto achieve moderateanemia and avoid ironoverload are standardapproaches forthalassemia major.

Hemolyticanemia

Prematuredestruction of RBC’s

Consideredwhen there ismarkedincrease in redblood cellsproduction bybone marrow.

Causes associated withdisorders such assystemic lupuserythematosus,lymphoma, andparoxysmal nocturnalhemoglobinuria. Othercauses are highexposure to certainmetals or chemicals.

Corticosteroids forautoimmune anemia,immunosuppressivedrugs may be used.Transfusion is used inmany cases.

Sickle cellanemia

Inherited type ofanemia, sickle-shaped RBC hasimpaired abilitytosqueezethroughvessels. Shortlifespan of RBC (10-20 days)

Joint and bonepain, infections,and heartfailure canoccur.

Disease and genetictrait occurs primarilyin people of Africandescent and peoplefrom India andMediterranean regions.

Measures to avoidcycling and controlpain. Includinghydration, hydroxyurea,NSAIDs and narcoticanalgesics. Bonemarrow transplantation


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Sideroblasticanemia

Group of anemiacaused by impairedability of bonemarrow to produceRBC’S

Symptoms ofanemia arejaundice,enlarged liverand spleen,fever,headache, lossof appetite,vomiting, andleg sores.

Caused by excessivealcohol use, certainmedications, includingchloramphenicol, orother disorders,including some cancersand rheumatoidarthritis. Morecommon in the elderly

Deferoxamine, andFolate , pyridoxine areused,

Table. 2Herbal treatment for anemia [42]: Herbalmedicines are the oldest remedies known tomankind. The demand for herbal products isgrowing exponentially throughout the worldbecause herbal drugs having no side effects ascompare to other drugs and major pharmaceuticalcompanies are currently conducting extensiveresearch on plant materials for their potentialmedicinal value some herbal drugs are givenbelow.Table. 3

Homeopathic treatment for anemia [43]:Homeopathic treatments are used since ancienttime in India and other countries. It is popularbecause of its availability, cheap in cost andmostly due to fewer side effects. Few drugs andtheir contribution is mentioned in the below table.4

Oral iron supplements:

There are two forms of supplemental iron: ferrousand ferric. Ferrous iron is better absorbed and isthe preferred form of iron tablets. Ferrous iron isavailable in three forms: ferrous fumarate, ferroussulfate, and ferrous gluconate. A 325 mg ironsupplement contains the following amounts ofelemental iron depending on the type of iron-Ferrous fumarate. 108 mg of elemental iron,Ferrous sulfate 65 mg of elemental iron, Ferrousgluconate ,35 mg of elemental iron.

Dosage: Depending on the severity of youranemia, as well as your age and weight, yourdoctor will recommend a dosage of 60 - 200 mgof elemental iron per day. This means taking oneiron pill 2 - 3 time during the day.

Side Effects and Safety: Common side effects ofiron supplements include- Constipation and

Herbaldrugs

Work

Ash gourd Ash gourd can prevent the risk ofanemia by checking the amount ofblood lost from the lungs, nose andif there are piles

Celery Celery has a high quantity of ironand magnesium content. Iron is acomponent of Heme, whichnecessary for the production ofhemoglobin in the blood

Chicory Chicory is an effective tonic for theblood

Fenugreek Its leaves are helpful in building thevolume of blood in the body

Onion Onion has rich iron content. Henceonion is the most effective remedyfor anemia


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diarrhea are very common, Nausea andvomiting, Black stools are normal when takingiron tablets.Supplements:A healthy diet, rich in iron, must be consumed.Whole grain cereals, legumes and pulses aregood sources of iron. Anemia that is causeddue to deficiency of vitamins can be avoidedby a proper intake of vitamins in the diet.Consult a diet chart for better guidance.Pregnant women can take multivitamin pillsand other nutritional supplements at the adviceof the doctor. Beetroot is also very goodsource of iron intake.

Conclusion:This review contains different type of anemia-sickle cell anemia, hemolytic anemia,pernicious anemia, iron deficiency anemia,aplastic anemia and Thalassemia and the waysby which they cause, diagnose, and treated.Acknowledgment:We would like to thank the University forproviding the resources to carry on ourresearch and our teachers and friends for theirsupport.

Table. 4: Few drugs and their contribution

Drugs Works

Ferrumetallicum It’s a great homeopathic remedy but itwill not cure every case of anemia

Pulsatilla it’s the great antidote to iron and henceis indicated in the anemic conditionproduced by large or continued dosesof it

Calcareacarbonica Use in anemic and debilited condition

Arsenicum Being a direct poison to the RBC takesfirst rank in case of pernicious anemiaor anemia due to a material of toxicinfluence

Helonias An excellent remedy in anemia andchlorosis it suits especially anemiafrom prolonged hemorrhage in women

Secale This remedy produces a progressivegeneral anemia it shown by the peculiarcachexia of anemia, pale, bloodlessjaundiced color

Natrummuriaticum This is one of the best remedies inanemic conditions there is paleness andinspite of the fact that the patient eatswell, there is emaciation


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a brief review on anemia & its clinical management

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