IRON DEFICIENCY ANEMIA IN ADULTS by mikesanye

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									                        National Clinical Protocol “Iron Deficiency Anemia in Adults”, Chisinau 2008




      MINISTERUL                                   MINISTRY OF HEALTH
      SĂNĂTĂŢII                                          OF THE
AL REPUBLICII MOLDOVA                             REPUBLIC OF MOLDOVA




             IRON-DEFICIENCY ANEMIA
                    IN ADULTS



                   National Clinical Protocol




                            Chisinau
                            July 2008
                                                                        National Clinical Protocol “Iron Deficiency Anemia in adults”, Chisinau, July 2008



CONTENTS
    Abbreviations used in the document............................................................................................................................................. 3

FOREWORD.................................................................................................................................................................................. 3

A. INTRODUCTION ..................................................................................................................................................................... 3
   A.1. Diagnosis ............................................................................................................................................................................ 3
   A.2. Disease code (CIM 10) ........................................................................................................................................................ 3
   A.3. Users ................................................................................................................................................................................... 3
   A.4. Protocol goals ...................................................................................................................................................................... 3
   A.5. Date of protocol development............................................................................................................................................... 4
   A.6. Date of next revision ............................................................................................................................................................ 4
   A.7. List and contact information of authors and persons participating in the protocol development ............................................... 4
   A.8. Definitions used in the document.......................................................................................................................................... 5
   A.9. Epidemiologic information................................................................................................................................................... 5

B. GENERAL PART...................................................................................................................................................................... 6
   B.1. Level of primary health care facilities ................................................................................................................................... 6
   B.2. Specialized consultative level ............................................................................................................................................... 7
   (internist – district and municipal levels/hematologist – republican level) ..................................................................................... 7
   B.3. Stationary level .................................................................................................................................................................... 9

C.1. MANAGEMENT ANGORITHMS....................................................................................................................................... 11
   C 1.1. Diagnostic algorithm in iron deficiency anemia................................................................................................................ 11
   C 1.2. Treatment algorithm in iron deficiency anemia................................................................................................................. 12

C.2. DESCRIPTION OF METHODS, TECHNIQUES AND PROCEDURES............................................................................ 13
   C.2.1. Classification .................................................................................................................................................................. 13
   C.2.2. Risk factors ..................................................................................................................................................................... 13
   C.2.3. Prophylaxis ..................................................................................................................................................................... 13
      C.2.3.1. Primary prophylaxis ................................................................................................................................................ 13
      C.2.3.2. Secondary prophylaxis............................................................................................................................................. 13
   C.2.4. Screening ........................................................................................................................................................................ 14
   C.2.5. IDA patient management ................................................................................................................................................. 14
      C.2.5.1.Anamnesis................................................................................................................................................................ 14
      C.2.5.2.Physical examination (objective data) ....................................................................................................................... 15
      C.2.5.3.Paraclinical investigations........................................................................................................................................ 15
      C.2.5.4. Differential diagnosis .............................................................................................................................................. 16
      C.2.5.5. Hospitalization criteria............................................................................................................................................ 17
      C.2.5.6. Treatment................................................................................................................................................................ 17
      C.2.5.7. Evolution and prediction.......................................................................................................................................... 17
      C.2.5.8. Patient follow-up ..................................................................................................................................................... 17
   C.2.6. Emergencies.................................................................................................................................................................... 18
   C.2.7. Complications ................................................................................................................................................................. 18

D. HUMAN RESOURCES AND MATERIALS NECESSARY FOR THE OBSERVANCE OF THE PROTOCOL................. 19
   D.1. Primary health care facilities .............................................................................................................................................. 19
   D.2. Consultative-diagnostic units and facilities.......................................................................................................................... 19
   D.3. General profile units of district and municipal hospitals....................................................................................................... 20
   D.4. Hematological Center of IMSP Oncology Institute.............................................................................................................. 20

E. INDICATORS FOR PROTOCOL IMPLEMENTATION MONITORING........................................................................... 22

APPENDICES.............................................................................................................................................................................. 23
  Appendix 1 Guide for the patient with iron deficiency anemia ..................................................................................................... 23
  Appendix 2. Recommendations to implement in IDA infected patient treatment management........................................................ 25

REFERENCES............................................................................................................................................................................. 26




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                                               National Clinical Protocol “Iron Deficiency Anemia in Adults”, Chisinau 2008




ABBREVIATIONS USED IN THE DOCUMENT
      IDA                                       Iron-deficiency anemia
      Hb                                        hemoglobin



FOREWORD
This protocol was developed by the working group of the Ministry of Health of the Republic of
Moldova (MoH), formed of representatives of the Hematology and Oncology Chair of the State
University of Medicine and Pharmacy “N. Testemitanu”, in co-operation with Moldova Governance
Threshold Country Program, an initiative funded by the Millennium Challenge Corporation (MCC)
and managed by the United States Agency for International Development (USAID).

This national protocol was developed in accordance with the existing international guidelines on
iron-deficiency anemia in adults and will serve as basis for the development of facility clinical
protocols, to be adapted to the medical resources of each facility in the current year. Upon MoH
recommendation, additional forms may be used to monitor the facility clinical protocols, which are
not included in the national clinical protocol.


A. INTRODUCTION

A.1. Diagnosis: Iron-deficiency anemia in adults
Examples of clinical diagnosis:
1. Iron-deficiency anemia

A.2. Disease code (CIM 10): D.50
A.3. Users:
     Family Doctor Offices (family doctors and family doctor nurses);
     Health Centers (family doctors and family doctor nurses);
     Family Doctor Centers (family doctors and family doctor nurses);
     District Consultative Centers (internists);
     Territorial medical associations (family doctors, internists);
     Internal disease units of district, regional and republican hospitals (internists);
     The Hematology Center of the Oncology Institute (hematologists)
Note: If necessary, this protocol can be also used by other specialists.

A.4. Protocol goals:
    1. Increase the percentage of persons included in the risk group of developing IDA who would
       benefit from preventive treatment with bivalent iron compounds.
    2. Improve the diagnosing of iron-deficiency anemia.
                                     National Clinical Protocol “Iron Deficiency Anemia in adults”, Chisinau, July 2008



3. Improve the iron-deficiency anemia treatment.
4. Decrease IDA recurrence by secondary prophylaxis with bivalent iron compounds.
A.5. Date of protocol development: July 2008

A.6. Date of next revision: July 2010

A.7. List and contact information of authors and persons participating in the
protocol development:

               Name                                          Position
 Dr. Ion Corcimaru, Corresponding    Head of Hematology and Oncology Chair, State Medical
 Member of Moldova Science           University of Medicine and Pharmacy “Nicolae
 Academy, PhD, university            Testemitanu”, main hematologist of the Ministry of
 professor                           Health
 Dr. Maria Robu, M.D., university    University lecturer, Hematology and Oncology Chair,
 lecturer                            State Medical University of Medicine and Pharmacy
                                     “Nicolae Testemitanu”
 Dr. Larisa Mustata, M.D.,           University lecturer, Hematology and Oncology Chair,
 university lecturer                 State Medical University of Medicine and Pharmacy
                                     “Nicolae Testemitanu”
 Dr. Elena Maximenco, MPH            Local Public Health Specialist, Moldova Governance
                                     Threshold Country Program


The protocol was discussed, approved and countersigned by:
          Name (agency)                                      Name and signature
 Hematology and Oncology Chair,
 State Medical University of
 Medicine and Pharmacy “Nicolae
 Testemitanu”
 Society of Hematologists and
 Transfusiologists of the Republic
 of Moldova
 Association of Family Doctors of
 the Republic of Moldova
 Hematology and Oncology
 Specialized Scientific Methodical
 Committee
 Drug Agency
 Expert Council of the Ministry of
 Health
 National Council of Health
 Evaluation and Accreditation
 National Health Insurance
 Company




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                                      National Clinical Protocol “Iron Deficiency Anemia in adults”, Chisinau, July 2008




A.8. Definitions used in the document
Iron-deficiency anemia – is part of anemia group characterized by an impaired formation of red
cells in which the hemoglobin synthesis is deficient as a result of a decrease in the total iron body
stores.
Recommended – something that is not compulsory. The doctor will make a separate decision for
each case.

A.9. Epidemiologic information
Iron-deficiency anemia is the most frequent type of anemia, and one of the most spread human
diseases. It represents approx. 80-85% [1, 2] of all anemia types.
Iron-deficiency anemia is developed in all age groups, but it is most frequently found in children and
women of childbearing potential [5, 8, 9]. Iron deficiency anemia is registered in 8-15% of women of
childbearing potential, an iron deficiency being identified in every third woman [1, 2].
According to World Health Organization data, iron deficiency affects 30% of world population,
approximately 1.3 billion inhabitants [5]. Iron deficiency is identified in about one third of
population [9]. In the USA, where there is sufficient iron in food, the food is enriched with iron, and
iron additives are largely used, iron deficiency anemia is also a problem. For instance, 24% of young
girls are registered with iron store depletion, and 42% - with suboptimal iron status [5].
About 50-60% of pregnant women suffer from iron-deficiency anemia, and iron deficiency is found
in 70% of pregnant women. By the end of the pregnancy, practically all women are tested positive
with latent iron deficiency [7, 10].
Iron-deficiency anemia is frequent in all countries and indicates a significant increase in morbidity in
the socially and economically less developed countries.
Therefore, a great part of population suffers from iron-deficiency anemia.




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                                National Clinical Protocol “Iron Deficiency Anemia in adults”, Chisinau, July 2008




                                B. GENERAL PART

                     B.1. Level of primary health care facilities
         Description                     Rationale                                     Steps
1. Prophylaxis
1.1. Primary prophylaxis      Administration of bivalent        Mandatory:
                              iron compounds to risk groups  Oral administration of
                              prevents IDA development           bivalent iron compounds: 1
                              [5,6]                              pill 2-3 times per week to
                                                                 persons in the risk group
                                                                 (Boxes 2, 3)
1.2. Secondary prophylaxis    Administration of bivalent        Mandatory:
                              iron compounds to persons         Oral administration of
                              treated for iron-deficiency        bivalent iron compounds: 1
                              anemia, in whom the cause of       pill 2-3 times per week
                              iron deficit persists, allows to   (Box 4)
                              prevent IDA recurrence [1,5]
1.3. Screening                Early identification of iron      Mandatory:
                              deficient patients allows         The following tests shall be
                              preventing IDA development.        conducted in the risk group
                              Serum ferritin is the index        population:
                              allowing the early                Full blood count with
                              identification of iron             thrombocytes and
                              deficiency in the body [3,4,6]     reticulocytes
                                                                Serum iron
                                                                Serum ferritin (when
                                                                 possible)
2. Diagnosis
2.1. Suspicion and            Anamnesis allows suspecting              Mandatory:
confirmation of IDA diagnosis IDA in persons with                      Anamnesis (Boxes 8, 9)
                              symptoms of anemic and                   Physical examination (Box
                              sideropenic syndrome.                     10)
                                                                       Paraclinical investigations
                              Sideropenic syndrome is only              (Box 11)
                              specific for IDA.                         Full blood count with
                                                                          thrombocytes and
                              Full blood count allows to                  reticulocytes
                              determine the hypochrome                  Serum iron content
                              anemia                                    Ferritin content (when
                                                                          possible)
                              Serum iron – latent iron                  Investigations to
                              deficiency                                  determine IDA cause
                                                                          (together with specialists:
                              Ferritin – prelatent iron                   internist, endoscopist,
                              deficiency                                  radiologist, gynecologist,
                                                                          etc.)
                                                                       Differential       diagnosis

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                                National Clinical Protocol “Iron Deficiency Anemia in adults”, Chisinau, July 2008



                                                                           (Boxes 12, 13)
2.2. Decision on specialist                                               Recommendation for
consultation and/or                                                        hematologist consultation
hospitalization                                                            to patients with difficulties
                                                                           of diagnosis
                                                                          Evaluation of
                                                                           hospitalization criteria (Box
                                                                           14)
3. Treatment
3.1. Drug treatment           IDA treatment consists in                Mandatory:
                              normalization of hemoglobin              Oral administration of
                              content, red cells number and             bivalent iron compounds: 1
                              recovery of iron storage in               pill twice a day, 30-40
                              tissues [1,5]                             minutes before meal, with
                                                                        100 ml of water or juice
                                                                        until the normalization of
                                                                        hemoglobin content and
                                                                        red cells number, to be
                                                                        continued for another 6
                                                                        months (Box 15)
4. Follow-up                                                           Mandatory:
                                                                       Full blood count, serum
                                                                        iron, (ferritin – when
                                                                        possible) every 6 months
                                                                        for the next 2-3 years (Box
                                                                        16)

                          B.2. Specialized consultative level
    (internist – district and municipal levels/hematologist – republican level)
         Description                     Rationale                                     Steps
1. Prophylaxis
1.1. Primary prophylaxis      Administration of bivalent        Recommended:
                              iron compounds to risk groups  Oral administration of
                              prevents development of iron-       bivalent iron compounds: 1
                              deficiency anemia [5,6]             pill 2-3 times per week to
                                                                  persons in the risk group
                                                                  (Boxes 2, 3)
1.2. Secondary prophylaxis    Administration of bivalent        Mandatory:
                              iron compounds to persons         Oral administration of
                              treated for iron-deficiency         bivalent iron compounds: 1
                              anemia, in whom the cause of        pill 2-3 times per week
                              iron deficit persists, allows to    (Box 4)
                              prevent the IDA recurrence
                              [1,5]
1.3. Screening                Early identification of iron      Mandatory:
                              deficient patients allows         The following tests shall be
                              preventing IDA development.         conducted in the risk group
                              Serum ferritin is the index         population:
                              allowing early identification
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                                National Clinical Protocol “Iron Deficiency Anemia in adults”, Chisinau, July 2008



                              of iron deficiency in the body            Full blood count with
                              [3,4,6]                                    thrombocytes and
                                                                         reticulocytes
                                                                        Serum iron content
                                                                       Ferritin content (when
                                                                        possible)
2. Diagnosis
2.1. IDA diagnosis            Anamnesis allows suspecting              Mandatory:
confirmation                  IDA in persons with                      Anamnesis (Boxes 8, 9)
                              symptoms of anemic and                   Physical examination (Box
                              sideropenic syndrome.                      10)
                                                                       Paraclinical investigations
                              Sideropenic syndrome is only               (Box 11)
                              specific for IDA.                         Full blood count with
                                                                           thrombocytes and
                              Complete blood count allows                  reticulocytes
                              determining hypochrome                    Serum iron content
                              anemia                                    Ferritin content (when
                                                                           possible)
                              Serum iron – latent iron                  Investigation for IDA
                              deficiency                                   cause determination
                                                                       Differential         diagnosis
                              Ferritin – prelatent iron                  (Boxes 12, 13)
                              deficiency                              Recommended:
                                                                       Additional special
                                                                         investigations (indicated by
                                                                         hematologists)
                                                                         (Box 11)
2.2. Decision on specialist                                            Recommendation for
consultation and/or                                                      hematologist consultation
hospitalization                                                          to patients with difficulties
                                                                         of diagnosis
                                                                       Consultation of other
                                                                         specialists, if needed
                                                                       Evaluation of
                                                                         hospitalization criteria (Box
                                                                         14)
3. Treatment
3.1. Drug treatment           IDA treatment consists in                Mandatory:
                              normalization of hemoglobin              Oral administration of
                              content, red cell number and              bivalent iron compounds: 1
                              recovery of iron storage in               pill twice a day, 30-40
                              tissues [1,5]                             minutes before meal, with
                                                                        100 ml of water or juice
                                                                        until the normalization of
                                                                        hemoglobin content and
                                                                        red cells number, to be
                                                                        continued for another 6
                                                                        months (Box 15)

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                             National Clinical Protocol “Iron Deficiency Anemia in adults”, Chisinau, July 2008




                             B.3. Stationary level
         Description                  Rationale                                  Steps
1. Hospitalization                                                  Hospitalization criteria in
                                                                    general therapy units
                                                                    (district, municipal):
                                                                    Patients with severe disease
                                                                       forms, who need
                                                                       investigations to determine
                                                                       the IDA cause which
                                                                       cannot be performed in
                                                                       ambulatory conditions
                                                                    Elderly patients with
                                                                       hemoglobin content less
                                                                       than 70 g/l with coexisting
                                                                       severe illnesses.
                                                                    Hematology units
                                                                    (republican level)
                                                                    Cases when it is not
                                                                       possible to establish IDA
                                                                       diagnosis at district or
                                                                       municipal level
                                                                    Patients with impaired iron
                                                                       absorption and increased
                                                                       digestive intolerance to
                                                                       iron-containing
                                                                       preparations, who need
                                                                       treatment with iron
                                                                       preparations for parenteral
                                                                       use (Box 14)
2. Diagnosis
2.1. Confirmation of IDA   Early identification of iron    Mandatory:
diagnosis                  deficient patients allows       Anamnesis (Boxes 8, 9)
                           preventing IDA development.  Physical examination (Box
                           Serum ferritin is the index       10)
                           allowing early identification   Paraclinical investigations
                           of iron deficiency in the body    (Box 11)
                           [3,4,6]                          For IDA confirmation
                                                            For IDA cause
                                                               determination
                                                           Differential        diagnosis
                                                             (Boxes 12, 13)
                                                          Recommended:
                                                           Recommended
                                                             investigations
                                                           Additional special
                                                             investigations (indicated by
                                                             hematologists) (Box 11)

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                                  National Clinical Protocol “Iron Deficiency Anemia in adults”, Chisinau, July 2008



                                                                            Consultation of other
                                                                             specialists, if needed
3. Treatment
3.1. Drug treatment             IDA treatment consists in        Mandatory
                                normalization of hemoglobin      Oral administration of
                                content, red cell number and       bivalent iron compounds :
                                recovery of iron storage in        1 pill twice a day 30-40
                                tissues [1,5]                      minutes before meal, with
                                                                   100 ml water or juice
                                                                   during 2-3 weeks, and
                                                                   further the treatment will
                                                                   be continued in ambulatory
                                                                   conditions
                                                                 Transfusion of
                                                                   concentrated suspensions
                                                                   of red blood cells, washed
                                                                   according to vital
                                                                   indications (precoma,
                                                                   anemic coma, hemoglobin
                                                                   content less than 70 g/l in
                                                                   old patients with coexisting
                                                                   severe illnesses)
                                                                 Iron compounds for
                                                                   parenteral use
                                                                   (Box 15)
4. Discharge with referral to   On discharge, a further patient The mandatory excerpt shall
primary level for treatment     management algorithm has to include:
continuation and follow-up      be developed and                  Exact detailed diagnosis;
                                recommended to the family         Results of investigations
                                doctor.                           Performed treatment;
                                                                  Clear recommendations
                                                                    for the patient;
                                                                  Recommendations for the
                                                                    family doctor.




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                                      National Clinical Protocol “Iron Deficiency Anemia in adults”, Chisinau, July 2008




C.1. MANAGEMENT ANGORITHMS

C 1.1. Diagnostic algorithm in iron-deficiency anemia

                                          I. Suspecting IDA
Anemia syndrome (general weakness, dizziness, exertional dyspnea, palpitations, pale skin,
tachycardia, etc.)
Sideropenic syndrome (dry skin; cracked heels; fragile, easily breaking and stratified nails; brittle
hair; hair loss; dry mouth; angular stomatitis; taste and smell perversion, etc.)



                                        II. IDA confirmation
1   Full blood test with thrombocytes and reticulocytes (anemia, hypochromia, microcytosis)
2   Serum iron (decreased)
3   Serum ferritin (decreased)


                                    III. IDA cause determination
1   Anamnesis (iron deficiency, increased iron needs, increased iron loss, impaired iron absorption)
2   Fecal occult blood test
3   Fecal test for helminth eggs
4   Radioscopic examination of the stomach with passage to small bowel
5   Irrigoscopy
6   Rectoromanoscopy
7   Fibrogastroduodenoscopy
8   Fibrocolonoscopy
9   Gynecologist consultation (for women)




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                                    National Clinical Protocol “Iron Deficiency Anemia in adults”, Chisinau, July 2008




C 1.2. Treatment algorithm in iron-deficiency anemia

                     Goal                                               Treatment method
          Normalize the hemoglobin                       Oral administration of bivalent iron
Stage 1   content and number of red                      compounds (sorbifer durules, ferrous chloride
                                                         etc.): 1 pill twice a day, 30-40 minutes before
          cells
                                                         meal, with 100 ml water or juice




Stage 2                Goal                                            Treatment method
          Recover iron stores in tissues                  Further administration of bivalent iron
          (ferritin normalization)                        compounds in the same curative dose for 4-6
                                                          months (until ferritin is normalized).


                                                                      Secondary prophylaxis
                                                          If the cause of iron deficiency cannot be
Stage 3               Goal                                eliminated (cause of iron deficiency
          Eliminate the cause of iron                     persists), a bivalent iron compound shall be
          deficiency (when possible)                      administrated: 1 pill 2-3 times a week, as
                                                          long as the etiologic factor persists.




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                                        National Clinical Protocol “Iron Deficiency Anemia in adults”, Chisinau, July 2008




C.2. DESCRIPTION OF METHODS, TECHNIQUES AND PROCEDURES
C.2.1. Classification
Box 1. IDA classification according to the degree of anemia
   Ist degree – hemoglobin content 91-110 g/l
   IInd degree – hemoglobin content 71-90 g/l
   IIIrd degree – hemoglobin content < 71 g/l

Table 1. IDA classification according to evolution stages of iron deficiency
  Iron deficiency stage       Serum ferritin           Serum iron            Hemoglobin content
                                   level
Prelatent deficiency         Decreased            Normal                    Normal
Latent deficiency              Significantly             Decreased                        Normal
                               decreased
Iron-deficiency anemia         Seriously                 Decreased                        Low (anemia)
                               decreased


C.2.2. Risk factors
Box 2. Risk factors
   Iron deficiency in consumed food
   Increased iron need in the body (pregnancy and lactation period, teenage period)
   Gastrointestinal bleeding (duodenal and gastric ulcers, hiatus hernia, erosive gastritis, polyposis,
    ulcerative colitis, stomach or colon cancer, hemorrhoids, etc.)
   Menorrhagias, metrorrhagias
   Systematic blood donation
   Haemostatic impairment
   Impaired iron absorption (extended small bowel resection in the proximal region, malabsorption
    syndrome, chronic enteritis, hypotransferrinemia.

C.2.3. Prophylaxis
C.2.3.1. Primary prophylaxis
 Box 3. Primary prophylaxis
 Oral administration of bivalent iron compounds: 1 pill 2-3 times per week to persons in the risk
   group, as long as the cause of iron deficit persists.
 Administration of bivalent iron compounds, 1 pill twice a day, to pregnant women starting with
   the 10-12th week of pregnancy during the entire pregnancy period and 6 lactation months.

C.2.3.2. Secondary prophylaxis
 Box 4. Secondary prophylaxis
 If the chronic hemorrhage source is not eliminated after the IDA treatment, bivalent iron
   compounds (1 pill 2-3 times a week) shall be administered by oral route as long as the cause of
   iron deficiency development persists.


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                                        National Clinical Protocol “Iron Deficiency Anemia in adults”, Chisinau, July 2008



C.2.4. Screening
Box 5. Risk group to develop iron deficiency
   Teenagers (their accelerated growth requires larger iron stores, incorrect and deficient diet, as well
    as blood losses in girls during menstruation)
 Pregnant women
 Women with polymenorrhea and metrorrhagias
 Persons with ulcer disease
 Persons with stomach and small bowel proximal sector resection
 Persons suffering from chronic enteritis
 Persons suffering from chronic colitis
 Persons suffering from polyposis
 Persons suffering from hiatus hernia
 Persons suffering from hemorrhoids
 Note: A full blood count, serum iron and serum ferritin shall be carried out every 6 months, except
 for pregnant women, whose full blood test and ferritin shall be carried out every 3 months.

C.2.5. Management of patients with IDA
Box 6. Objectives of diagnosing procedures in IDA
   Confirmation of anemia
   Evaluation
   Assessment of prelatent iron deficiency
   Determination of latent iron deficiency

Box 7. Diagnosis procedures in IDA
   Anamnestic
   Clinical examination
   Full blood count + thrombocytes + reticulocytes, with red cells morphology assessment
   Serum iron determination
   Ferritin investigation
   Mandatory investigation of risk factors (appendix no.1)

C.2.5.1.Anamnesis
Box 8. Issues to be examined when IDA is suspected
   Clinical signs of anemia syndrome are identified (weakness, fatigue, exertional dyspnea,
    dizziness, palpitations)
   Clinical signs of sideropenic syndrome are identified (dry skin, fragile nails, cracked heels,
    angular stomatitis, sideropenic dysphagia, taste and smell perversion called “pica chlorotica” –
    patients have the urge to eat chalk, ground, raw meat, dough, salt, burned wood, etc., they prefer
    gas and acetone smell.

Box 9. Recommendations for IDA cause assessment
   Determine the diet type (vegetarian diet and mostly consisting in dairy products)
   In teenage period – growing rhythm, in girls – polymenorrhea
   Exclude gastrointestinal bleedings (black-colored stool, blood stripes in stool)

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                                        National Clinical Protocol “Iron Deficiency Anemia in adults”, Chisinau, July 2008



   In women – meno- metrorrhagias, number of pregnancies and interval between them
   Determine hemostatic disorders (nasal, gingival hemorrhage, etc.)
   Specify the type of surgical intervention (stomach resection according to Billroth II method,
    gastrectomy, extended proximal small bowel resection).

C.2.5.2.Physical examination (objective data)
Box 10. Objective data in IDA
   Clinical signs of anemia syndrome (pale skin, tachycardia, systolic murmur in the apex)
   Clinical signs of sideropenic syndrome (dry skin, fragile nails, stratified nails, with possible
    longitudinal stripes. Brittle hair. Angular stomatitis. Cracked heels).


C.2.5.3.Paraclinical investigations
Box 11. Investigations in IDA
 Investigations for IDA confirmation (mandatory investigations)
 Full peripheral blood count with reticulocytes and thrombocytes
 Serum iron content
 Ferritin content (it is currently performed only in the Republican Diagnosing Center)

 Investigations for IDA cause determination (mandatory investigations)
 Fecal occult blood test
 Fecal test for helminth eggs
 Radioscopic examination of the stomach with passage to small bowel
 Irrigoscopy
 Fibrogastroduodenoscopy
 Fibrocolonoscopy
 Rectoromanoscopy
 Gynecologist consultation (for women)

 Recommended investigations
 Complete urinalysis
 Urea, creatinine, bilirubin, transaminases, glycemia
 Blood type and Rh-factor in cases with indications for hemotransfusion
 HIV/AIDS test before hemotransfusion, when the latter is prescribed
 Determine the antigens for B and C hepatitis before hemotransfusion, when the latter is prescribed

 Special additional investigations (for hematologists)
 Iron absorption
 Bone marrow puncture (if necessary)
 Bone marrow trepanobiopsy (if necessary)
 Ham’s test (when needed)
 Urinalysis for hemosiderin (if necessary)




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                                      National Clinical Protocol “Iron Deficiency Anemia in adults”, Chisinau, July 2008




The full blood count allows determining anemia. A decrease in hemoglobin and red cells is
registered. A special importance is given to morphological study of red cells on the blood smear.
Microcytosis and erythrocytes hypochromia are identified.
Serum iron allows diagnosing iron deficiency in its latent stage. Serum iron is decreased (normal
values 12.5-30.4 μmol/l). A correct blood collection is extremely important when determining serum
iron. First of all, specially prepared test tubes must be used. Otherwise, the test tubes washed with
ordinary distilled water contain iron traces, which elevate the serum iron level. Second, the patient
scheduled for a serum iron test shall not take iron compounds for at least 5 days prior to the test.
Ferritin content in serum allows early diagnosis of prelatent iron deficiency (normal values 25-250
µg/l).

C.2.5.4. Differential diagnosis
Box 12. IDA differential diagnosis in comparison with other anemia types, characterized by red
cell hypochromia
   Marchiafava-Micheli syndrome (atypical forms)
   Thalassemia
   Sideroacrestic anemia
   Anemia caused by chronic diseases

Box 13. Key issues in differential diagnosis
 Marchiafava-Micheli syndrome
   Patients with Marchiafava-Micheli develop iron deficiency syndrome, triggered by
     haemoglobinuria
   Serum iron level is decreased, temporarily increasing during hemolytic crises
   Signs of intravascular hemolysis, hemoglobinemia, haemoglobinuria, hemosiderinuria,
     indirect bilirubinemia, reticulocytosis
   Positive Ham’s test and saccharose test

 Thalassemia
   Red cells are hypochromic, and due to this fact most of them have a haemoglobinized point,
     and are called “target cells”
   Serum iron content is increased
   Hemolysis syndrome is present
   Hemoglobin electrophoresis confirms the diagnosis of thalassemia

 Sideroacrestic anemia
    In sideroacrestic anemia iron ions are not used, but stored in tissues and organs, developing a
      hemosiderosis
    Serum iron level is increased
    Serum ferritin is increased
    Bone marrow increases the sideroblast score

 Anemia caused by chronic diseases
   Are triggered by iron redistribution in the body. Iron is stored in tissues (by different
     mechanisms) as ferritin and hemosiderin, leaving the erythropoiesis without iron ions.
   Presence of a infectious process

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                                       National Clinical Protocol “Iron Deficiency Anemia in adults”, Chisinau, July 2008



     Increased ferritin in serum


C.2.5.5. Hospitalization criteria
Box 14. Hospitalization criteria for patients with IDA
   Hemoglobin content lower than 70 g/l (IIIrd degree anemia) in persons over 60 years old
   Hemoglobin content lower than 70 g/l in patients with simultaneous serious diseases of cardiovascular,
    respiratory, etc. systems.
   Disturbed absorption, increased intolerance to orally administrated iron compounds (will be
    hospitalized only in Hematological Center)
   Difficulties in establishing the diagnosis

C.2.5.6. Treatment
Box 15. Drug treatment principles for IDA
   IDA treatment principles in ambulatory and secondary health care facilities are identical
   IDA treatment objective is to normalize hemoglobin and red cell number; replenish the iron stores in
    tissues (ferritin normalization).
   The following orally administered compounds containing bivalent iron in pills are recommended:
    sorbifer durulex, ferrous sulfate, ferric chloride, administered as one pill twice a day 30-40 minutes
    before meal with 100 ml water or juice (not recommended with tea, coffee, milk, because these inhibit
    iron absorption) until hemoglobin level is normalized. After hemoglobin normalization the treatment
    will be prolonged with the same dose for another 4-6 months (until ferritin is normalized)
   If the cause of iron deficiency persists (hiatus hernia, ulcerative colitis, menorrhagias, hemorrhoids,
    etc.), the administration of an iron compound (2-3 pills per week) is recommended as long as the
    physiologic factor persists.
   Iron compounds for parenteral use are only needed in exceptional cases: increased digestive
    intolerance to orally administered iron compounds, impaired iron absorption. They are only
    administered on hematologist’s recommendations and in hematological secondary health care facility
    because of the possible severe complications. In case of absolute necessity, Ferrum-Lek shall be
    prescribed: 5 ml for intravenous administration or 2 ml for intramuscular injections, a total of 15
    injections, to be administered daily or once in two days.

C.2.5.7. Evolution and prognosis
Evolution and prognosis are favorable - cured (complete recovery).


C.2.5.8. Patient follow-up
Box 16. Follow-up of patients with IDA
   Patients’ follow-up by the family doctor
   Full blood count, serum iron test (ferritin – when possible)to be performed every 6 months in the first
    2-3 years




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                                       National Clinical Protocol “Iron Deficiency Anemia in adults”, Chisinau, July 2008



C.2.6. Emergencies
Box 17. Emergencies in IDA
   Anemic coma. As treatment, a transfusion of washed red cells concentrate will be performed.
   Anemic precoma. As treatment, a transfusion of washed red cells concentrate will be performed.
   Hemoglobin level is below 50 g/l in older patients with coexisting severe illnesses. As treatment, a
    transfusion of washed red cells concentrate will be performed

C.2.7. Complications

Box 18. IDA complications
   Gastric mucosal atrophy
In pregnant women
   Preterm births
   Birth of a dead foetus
   Hypotonia and uterus contractile failure with hypotonic hemorrhages during birth
   Formation of low iron stores in the future baby.




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                                 National Clinical Protocol “Iron Deficiency Anemia in adults”, Chisinau, July 2008




D. HUMAN RESOURCES AND MATERIALS NECESSARY FOR THE
OBSERVANCE OF THE PROTOCOL
                    Health professionals:
                    Family doctor
                    Family doctor’s nurse
                    Laboratory doctor and medical college graduate laboratory assistant
                    Equipment:
                    fundoscope
                    tonometer
D.1. Primary        Standard clinical laboratory for hemogram identification
health care         Biochemical laboratory for serum iron, ferritin identification (when possible)
facilities          Drugs:
                    Bivalent iron compounds for internal administration
                    sorbifer durulex
                    ferric chloride
                    ferric sulfate, etc.
                    Health professionals:
                    internist
                    laboratory doctor in clinical and biochemical laboratory
                    endoscopist
                    radiologist
                    gynecologist
                    nurses
                    medical college graduate laboratory assistant in the clinical and biochemical
                       laboratory
                    Equipment:
D.2.                fundoscope
Consultative-       tonometer
diagnostic units    X-ray office
and facilities      Standard clinical laboratory for hemogram identification
                    Biochemical laboratory for serum iron, ferritin (when possible), and
                       biochemical indexes identification
                    endoscopic office (fibrogastroscope, fibrocolonoscope, rectoromanoscope)
                    Drugs:
                    Bivalent iron compounds for internal administration
                    sorbifer durulex
                    ferric chloride
                    ferric sulfate, etc.




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                                 National Clinical Protocol “Iron Deficiency Anemia in adults”, Chisinau, July 2008



                    Health professionals:
                    internist
                    clinical and biochemistry laboratory doctor
                    radiologist
                    endoscopist
                    gynecologist
                    nurses
                    medical college graduate laboratory assistant in the clinical and biochemical
                       laboratories
D.3. General        Equipment: tools or access for examinations and procedures:
profile units of    fundoscope
district and        tonometer
municipal           X-ray office
hospitals           Standard clinical laboratory for hemogram identification
                    Biochemical laboratory for serum iron, ferritin (when possible), and
                       biochemical indexes identification
                    endoscopic office (fibrogastroscope, fibrocolonoscope, rectoromanoscope)
                    Drugs:
                    Bivalent iron compounds for internal administration
                    sorbifer durulex
                    ferric chloride
                    ferric sulfate, etc.
                   Washed erythrocytes concentrate (in emergencies)
                    Health professionals:
D.4.                hematologists
Hematological       laboratory doctors, hematologists
Center of the       laboratory doctors, biochemists
Oncology            radiologists
Institute           endoscopists
                    gynecologists
                    nurses
                    medical college graduate laboratory assistants in hematology laboratory
                    medical college graduate laboratory assistants in the clinical and
                       biochemical laboratories
                    specialists in functional diagnosis
                    Equipment: tools or access for examinations and procedures:
                    sterna puncture needle
                    trepanobiopsy needle
                    tonometer
                    fundoscope
                    electrocardiograph
                    ultrasonograph
                    rectoromanoscope
                    X-ray office
                    Endoscopy office
                    hematology laboratory
                    Drugs:
                    Bivalent iron compounds in pills

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              National Clinical Protocol “Iron Deficiency Anemia in adults”, Chisinau, July 2008



 sorbifer durulex
 ferric chloride
 ferric sulfate, etc.
Iron compounds for intravenous or intramuscular injections
 Ferrum-Lek etc.
Washed erythrocytes concentrate (in emergencies)




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                                     National Clinical Protocol “Iron Deficiency Anemia in adults”, Chisinau, July 2008




E. INDICATORS FOR PROTOCOL IMPLEMENTATION MONITORING
No                          Assessment of goal                  Method of indicator calculation
       Protocol goal
                                achievement                   Numerator               Denominator
1.   To increase           1.1. Percentage of           Number of                Total number of
     percentage of         persons/patients at risk     persons/patients at risk persons/patients at risk
     persons included in   of developing IDA,           of developing IDA,       of developing IDA,
     the risk group of     who received                 who received             followed up by the
     developing IDA,       prophylactic treatment       prophylactic treatment family doctor during
     who benefit from      with bivalent iron           with bivalent iron       the last year
     prophylactic          compounds                    compounds during the
     treatment with                                     last year X 100
     bivalent iron
     compounds
2.   To improve the        2.1. Percentage of           1.1. Number of                  Total number of
     diagnosing of         persons/patients at risk     persons/patients in the         persons/patients at risk
     patients with IDA     of developing IDA            risk group of                   of developing IDA,
                           who underwent an             developing IDA, who             followed up by the
                           IDA screening during         underwent an IDA                family doctor during
                           one year according to        screening during the            the last year
                           the recommendations          last year, according to
                           set forth in the             the recommendations
                           National Clinical            set forth in the
                           Protocol “IDA in             National Clinical
                           adults”                      Protocol “IDA in
                                                        adults”
3.   To improve the        3.1. Percentage of           Number of patients              Total number of
     treatment of          patients with IDA,           with IDA, receiving             patients with IDA,
     patients with IDA     who received                 bivalent iron                   treated by the family
                           treatment with               compounds treatment             doctor during the last
                           bivalent iron                for 4-6 months after            year
                           compounds for 4-6            Hb normalization
                           months after Hb              (until iron stores
                           normalization (until         replenishment in the
                           iron stores                  tissues (Ferritin))
                           replenishment in the         during the last year X
                           tissues (Ferritin))          100
4    To decrease IDA       4.1 Percentage of            Number of patients              Total number of
     recurrences by        patients with IDA,           with IDA, whose iron            patients with IDA, in
     secondary             whose iron deficiency        deficiency trigger              which the cause of
     prophylaxis with      trigger persists and         persists and who                iron deficiency
     bivalent iron         who received                 received prophylactic           persists and who were
     compounds             prophylactic treatment       treatment with                  followed up by the
                           with bivalent iron           bivalent iron                   family doctor during
                           compounds                    compounds during the            the last year
                                                        last year X 100




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                                       National Clinical Protocol “Iron Deficiency Anemia in adults”, Chisinau, July 2008




APPENDICES
Appendix 1 Guide for the patient with iron deficiency anemia
                                   Iron deficiency anemia in adults

Contents
Your health care
Iron-deficiency anemia
Iron-deficiency anemia diagnosis
Iron-deficiency anemia treatment

Introduction
This guideline is about the care and treatment of people with iron-deficiency anemia in the Health
Sector in the Republic of Moldova. It explains guidance for people with iron-deficiency anemia but it
may also be useful for their families or for anyone with an interest in the condition.

The guideline aims to help you better understand the care and treatment options that should be
available in the Health Sector.


The advice in the patient guideline covers:
    how physicians should find out whether someone has iron-deficiency anemia
    how the causes of iron deficit in the body can influence the evolution of iron-deficiency
       anemia
    prescription of medicines for the treatment of iron-deficiency anemia
the follow-up of patients with community-acquired pneumonia.
Your health care
Your treatment and care must be complete. You have the right to be informed of the treatment and
make decisions together with your health care professionals. To help with this, your health care team
should give you information you can understand and that is relevant to your circumstances. All
health care professionals should treat you with respect, sensitivity and understanding, and explain
iron-deficiency anemia and the treatments for it simply and clearly.

Iron deficiency anemia
Iron-deficiency anemia is a disease characterized by hemoglobin synthesis deficiency, triggered by
decrease in the total body iron stores. Iron-deficiency anemia is the most frequent type of anemia,
being one of the most spread human diseases. Iron-deficiency anemia is developed in all age groups,
but most frequently in children and in women of childbearing potential. Iron-deficiency anemia is
frequent in all countries, with a significantly increased morbidity index in the socially and
economically less developed countries.

Causes of iron deficiency in the body:
1. Insufficient iron in food

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                                       National Clinical Protocol “Iron Deficiency Anemia in adults”, Chisinau, July 2008



     Vegetarian diet and diet mostly based on dairy products
     Poor quality of food in less developed countries
2. Increased iron need
     teenage period
     pregnancy and lactation
3. Increased iron losses
     gastrointestinal bleeding
     heavy menstrual bleeding and genital tract bleeding
     systematic blood donation
     hemostatic disorders
4. Iron absorption disorder
     extended small bowel resection in proximal part
     malabsorption syndrome
     chronic enteritis
It is very important to identify the causes of iron deficiency, because they represent the basis of the
patient analysis plan for identifying causes in each separate case. The elimination of the etiological
factor and a specific treatment contribute to a complete recovery. At the same time, in order to avoid
the development of iron deficiency in persons from the risk group, a prophylaxis shall be conducted.

Iron-deficiency anemia manifestations
Iron deficiency anemia manifests itself by two clinical syndromes: anemia and sideropenic.
   1. Anemia syndrome is characterized by general weakness, fatigue, dizziness, exertional
      dyspnea, palpitations, pale skin, and tachycardia.
   2. Sideropenic syndrome (characteristic only for iron-deficiency anemia): dry skin, cracked
      heels. Nails are fragile, brittle, stratified, with longitudinal stripes. Brittle hair, hair loss. Dry
      mouth. Angular stomatitis is often developed. In some cases, deglutition is painful; the bolus
      is swallowed with difficulty, feeling of “lump in the throat”. Discomfort in the abdomen and
      murmur. Taste and smell perversion is characteristic. Patients have the urge to eat chalk,
      ground, raw meat, dough, raw pasta, salt, burned wood, etc. They prefer gas and acetone
      smell.
Iron-deficiency anemia diagnosis is established based on the anamnesis and clinical manifestations,
and is confirmed by a laboratory test: full blood count with thrombocytes and reticulocytes, serum
iron, serum ferritin. The investigation plan must also include all the tests performed to identify the
causes of iron deficiency development.
Upon receiving the investigation and test results, your physician must discuss these results with you
and explain you the treatment algorithm.

Treatment
Bivalent iron compounds are prescribed (sorbifer durulex or ferrous chloride (hemofer)) by oral
route, 1 pill twice a day, 30-40 minutes before meal, with 100 ml water or juice until hemoglobin and
red cell number are normalized, and foe another 4-6 months (until ferritin is normalized). If the cause
of iron deficiency persists, a bivalent iron compound, 1 pill 2-3 times per week, shall be taken as
long as the etiological factor persists.
Adverse effects can be dyspeptic disorders: nausea, vomiting, diarrhea or constipation, epigastric
pain.


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                                     National Clinical Protocol “Iron Deficiency Anemia in adults”, Chisinau, July 2008



Appendix 2. Recommendations to be implemented in the management of patients
with IDA
1. We regard as necessary the mandatory performance of serum ferritin test for prelatent iron
   deficiency, by family doctors, internists and hematologists. The serum ferritin test is currently
   performed only in Republican Center of Medical Diagnosis.
2. We regard as necessary to provide bivalent iron compounds (sorbifer durulex, ferrous chloride) to
   all patients with IDA.




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                                    National Clinical Protocol “Iron Deficiency Anemia in adults”, Chisinau, July 2008




REFERENCES

1.  Corcimaru I.T. Anemia fierodeficitară // Anemiile (“Iron-deficiency anemia”), 2003; 17-54
2.  Corcimaru I.T., Musteaţă L.Z., Robu M.V. Diagnosticul diferenţial şi tratamentul anemiilor
    (Recomandări metodice) (“Differential diagnosis and anemia treatment” (Methodical
    recommendations)). – Chisinau, 1997.
3. Health Care Guideline for patients and families: Preventive services for children and
    adolescents. Institute for Clinical System Improvement. October 2007.
4. Identification, diagnosis, and management of anemia in adult ambulatory patients treated by
    primary care physicians: evidence-based and consensus recommendations. National Anemia
    Action Council - Private Nonprofit Research Organization. 2006 Feb. 11 pages. NGC:005320
5. Munteanu N. Anemia feriprivă. Tratat de Medicină Internă. Hematologie, partea I (edited by
    Radu Păun) (“Iron-deficiency anemia. Treatise on Internal Medicine. Hematology, 1st Part”)
    Editura medicală. Bucuresti, 1997. – p. 579-604.
6. Screening for iron deficiency anemia - including iron supplementation for children and pregnant
    women. United States Preventive Services Task Force - Independent Expert Panel. 1996 (revised
    2006). 12 pages. NGC:004965
7. Бахрамеева С.Н., Денисова С.Н., Хотимченко С.Н., Алексеева И.А. Латентная форма
    железодефицитной анемии беременных женщин и состояние здоровья их детей //
    Рос.вестник перинатология и педиатрия, 1996, 41(3), 26-30.
8. Бокарев И.Н., Кабаева Е.В., Пасхина О.Е. Лечение и профилактика железодефицитной
    анемии в амбулаторной практике // Тер.архив, 1998. – № 4. – с. 70-74.
9. Идельсон Л.И., Воробьев П.А. Железодефицитные анемии. Руководство по гематологии,
    том 3 (под редакцией А.И.Воробьова). Издательство «Ньюдиамед» Москва. 2005, c. 171-
    190.
10. Шехтман М.М. Железодефицитная анемия и беременность. Клиническая лекция //
    Гинекология.- 2000.- том 2.- № 6.- с. 1-13.




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