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I. Importance of the Subject




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I. Importance of the Subject:

Anemia is the clinic and hematological syndrome described by decrease of haemoglobin level and erythrocytes in unit of blood volume. The prevalence of anemia in population studies of healthy nonpregnant people depends on the Hb concentration chosen for the lower limit of normal values. By World Health Organization criteria in the United States, approximately 4% of men and 8% of women have values lower than those cited. The prevalence of anemia in Canada and northern Europe is believed to be similar to that in the United States. In underprivileged countries, limited studies of purportedly healthy subjects show the prevalence of anemia to be 2-5 times greater than that in the United States. Although geographic diseases, such as sickle cell anemia, thalassemia, malaria, hookworm, and chronic infections, are responsible for a portion of the increase, nutritional factors with iron deficiency and, to a lesser extent, folic acid deficiency play major roles in the increased prevalence of anemia. Populations with little meat in the diet have a high incidence of iron deficiency anemia because heme iron is better absorbed from food than inorganic iron. The anemic syndrome could be a sign of many other diseases: lymphoproliferative, endocrine, rheumatological, chronic renal failure, pneumonias, chronic active hepatitises etc. Process of diagnostics is difficult and demands attraction of specialist in various fields of medicine.

If the importance of the subject has been understood, proceed to studying the learning objectives.


^ II. Learning Objectives

Key objective: to develop skills in making a differential diagnosis of diseases with anemia, and planning a patient management.

Specific Objectives

Pre-Practice Knowledge and Skills

To gain knowledge of and develop skills in:

1. Identifying basic syndromes in anemias.

1. Selecting the data from the complaints and case history findings showing the presence of anemia (Explained in the Propaedeutics and Therapy Course).

2. Making up an individual diagnostic chart and interpreting the obtained findings in anemias.

2. Determining the necessary amount and sequence of investigative methods (Explained in the Physiology and Pathophysiology Course and Propaedeutics and Therapy Course).

3. Making a differential diagnosis of anemias.

3. Applying medications of pharmacotherapy and other methods of treatment (Explained in the Pharmacology Course).

4. Explaining the principles of anemic patient management.

The information necessary for reviewing and revising the basic knowledge and skills can be found in the following references:


  1. Arthur C. Guyton, John E. Textbook of Medical Physiology (Textbook Binding). - Hall W.B. Saunders Company; 10th edition. – 2000.

  2. Aaron B. Caughey, Nancy Palmer, Christie Del Castillo, and Dana Tuttle. Pathophysiology: Hematology and Oncology. -Blueprints Notes & Cases Series. - 2003.

  3. Propedeutics of internal diseases. Edited by V.H.Vasilenko, and A. Grebenev.-Moscow: medicine, 2006.

  4. Drew Provan, Charles R.J. Singer, Trevor Baglin, John Lilleyman. Oxford Handbook of Clinical Hematology. New York, 2004.


Pre-Practice Knowledge and Skills Test Questions


Q1. In complete blood count was found the cells having spherical or slightly oval biconcave form without nucleus. Average diameter of cells was 7,5-8,3 microns, average volume cells 80-100 microns, an osmotic resistance of cells - the beginning 0,44 %, the end - 0,32 %. What cells have been found?

А) normal erythrocytes;

B) megaloblasts;

C) microspherocytes;

D) sickle-cells;

Д) target cells.


Q2. In the complete blood count: erythrocytes 2,5x1012/l, haemoglobin - 81 g/l, color index of blood- 0,8, reticulocytes - 0 %, mean corpuscular volume 65 microns. Which anemia is it?

А) microcytic, hypochromatic, aregenerative;

B) macrocytic, hyperchromatic, aregenerative;

C) macrocytic, hypochromatic, hyperregenerative;

D) microcytic, hyperchromatic, normoregenerative;

E) normocytic, hypochromatic, hyporegenerative.


Q3. Results of analysis of patient D., 38 years old: in complete blood count: erythrocytes-1,2x1012/l, haemoglobin - 58 g/l, color index of blood - 0,9 reticulocytes-10 %, white blood cells -4,0x109/l, basophilocytes -1, eosinophils - 1 %, bond neutrophils - 6 %, segmentonuclear leukocytes - 54 %, lymphocytes-36 %, monocytes-2 %, thrombocytes-25x109/l, ESR-15 mm/hour; in biochemical blood analysis: total bilirubin-98,6 mkmol/l, indirect - 86,6 mkmol/l, direct-12 mkmol/l. What changes are found?

А) anemia, reticulocytosis, hyperbilirubinemia;

B) anemia, leukopenia, normal bilirubin level;

C) hyporegenerative anemia, lymphocytosis, hyperbilirubinemia;

D) anemia, leukocytosis, hyperbilirubinemia;

E) all parameters are normal.


Q4. On examination of patient С., 66 years old, hospitalized because of serious anemia, were found icteritiousness of scleras, atrophy of lingual papillas; symmetric paresthesias, gait disorder; splenomegaly. On gastroscopy: atrophic gastritis with achlorhydria. In the complete blood count macrocytosis was revealed. Which of the following is necessary for diagnosis?

А) a sternal puncture;

B) ultrasound of abdomen;

C) lumbar puncture;

D) upper gastrointestinal endoscopy;

E) chest roentgenography.

Q5. Patient К., 35 years old, was admitted to the hospital with complaints of weakness, palpitation and a short wind at exertion. She marked inverted gustatory sensation: wish for eating a chalk, clay. On examination: paleness, xeroderma, koilonychia, systolic murmur on the heart apex. The liver and spleen are not palpated. In complete blood count: erythrocytes-2,2x1012/l, haemoglobin - 65 g/l, color index of blood - 0,7 reticulocytes-0,5 %, white blood cells -5,4x109/l, basophilocytes -0, eosinophils - 1 %, bond neutrophils - 5%, segmentonuclear leukocytes - 52%, lymphocytes-38%, monocytes-5%, ESR-18 mm/hour, anisocytosis, poikilocytosis of erythrocytes. serum level of Fе - 7 mkmol/l, total bilirubin-17,3 mkmol/l. Which of the following is necessary for treatment of this patient?

А) iron preparations;

B) vitamin B12;

C) fresh frozen plasma;

D) red cells;

E) β-adrenoblockers.


Key Answer 1

Correct answer is А) - in this question the form, the sizes, and parameters of an osmotic resistance of cells is typical for normal erythrocytes of a peripheric blood.


Key Answer 1

Correct answer is А) - this anemia is microcytic because mean corpuscular volume <80 microns, hypochromatic because color index of blood <0,82, aregeneratiry ecause of reticulocytes level=0.


^ IV. Theory Topics on the Subject

To reach the learning objectives it is essential to master the following theory issues:

  1. Methods of clinical, laboratory and instrumental diagnostics of anemic syndrome.

  2. Differential diagnostics of anemic syndrome.

  3. Classification of anemias.

  4. Management of the patients affected by anemia.


The information necessary for mastering the theory issues may be found in the following references:


  1. Hematology. American Society of Hematology. Education Program Book. 2001.

  2. Michael Harvey. Haematology Handbook. Haematology Unit, Liverpool Hospital. 2001.

  3. Alan Rosenwald. Practical Diagnosis of Hematologic Disorders, Fourth Edition. – 2006. - P.168-197.

  4. Chris Cheson Clinical Laboratory Hematology.- Delphi Publishers. – 2007. –P. 54-109.

  5. A Flow Chart “Anemia” (see Appendix 1).

  6. Lecture notes on hospital therapy.

  7. Diagnostic Algorithm of anemic syndrome (see Appendix 2).

  8. Classification of Anemias (see Appendix 4).


Then, proceed to solving some test questions and checking test question 5 with the key answers.


Q1. In complete blood count of patient D.: erythrocytes-2,9x1012/l, haemoglobin - 75 g/l, color index of blood - 1,1, white blood cells -3,4x109/l, basophilocytes -0, eosinophils - 1 %, bond neutrophils - 4%, segmentonuclear leukocytes - 58%, lymphocytes-32%, monocytes-5%, thrombocytes-200x109/l, ESR-10 mm/hour, Howell-Jolly bodies, Cabot rings. On examination – symptoms of funicular myelosis. What complaints are typical for this syndrome?

А) short wind, palpitation, weakness;

B) shedding of hair, fragility of nails, xeroderma;

C) jaundice, heaviness in left and right hypochondrium;

D) nausea, diarrhea, burning sensation in tongue;

E) symmetric paresthesia, gait disorder.


Q2. The patient was admitted to hematological department with complaints of shedding of hair, fragility of nails, koilonychias, desire hunger for chalk, inhale odor nuisance. Symptoms of what syndrome are this complaints?

А) sideropenic;

B) hemolytic;

C) funicular myelosis;

D) toxic;

E) allergic.


Q3. Patient B., 50 years old, was admitted to hematological department with complaints of weakness, short wind, palpitation. On examination: skin and mucous were pale, with an icteric shade. The spleen was + 3 sm. In complete blood count: erythrocytes-2,9x1012/l, haemoglobin - 75 g/l, color index of blood - 1,0, reticulocytes-30%o, white blood cells -5,4x109/l, basophilocytes -0, eosinophils - 1 %, bond neutrophils - 4%, segmentonuclear leukocytes - 58%, lymphocytes-32%, monocytes-5%, thrombocytes-200x109/l, ESR-10 mm/hour, positive direct Cumbs’ test. Serum level of Fе - 20 mkmol/l, total bilirubin-42,0 mkmol/l, indirect - 30 mkmol/l, direct - 12 mkmol/l. Which of the following is the most probable diagnosis?

А) iron deficiency anemia;

B) aplastic anemia;

C) chronic myelosis;

D) chronic lymphoid leucosis;

E) autoimmune hemolytic anemia;


Q4. In complete blood count of patient N., 29 years old: erythrocytes-1,9x1012/l, haemoglobin - 53 g/l, color index of blood - 0,9, reticulocytes-0%o, white blood cells -2,0x109/l, basophilocytes -0, eosinophils - 1 %, bond neutrophils - 0%, segmentonuclear leukocytes - 15%, lymphocytes-80%, monocytes-4%, thrombocytes-25x109/l, ESR-45 mm/hour. In resulrs of trephine biopsy - replacement of red bone marrow by yellow bone marrow. Which of the following is the most probable diagnosis?

А)chronic lymphoid leucosis;

B) hemolytic anemia;

C) iron deficiency anemia;

D) pernicious anemia;

E) aplastic anemia.


Q5. For patient D., suffering from autoimmune hemolytic anemia, therapy by glucocorticoids wasn’t effective. What is you tactic for this case?

А) transplantation of bone marrow;

B) treatment by erythropoietin;

C) treatment by iron supplementations;

D) treatment by anabolic steroids;

E) splenectomy.


Key Answer 5

The correct answer is E) - splenectomy is recommended to the patients suffering from autoimmune hemolytic anemia for whom treatment by glucocorticoids was noneffective or in case of relapse of a hemolysis after a end of treatment.


^ Teaching Guidelines for Practice Activities on Anemias


At the beginning of the class, the instructor gives a test to check and correct the pre-practice level of knowledge. Then, the students start to see patients under the instructor’s supervision after which the students give an analysis of the practice patients and the instructor checks the mastering of the practice topics. A final test is provided to strengthen the knowledge gained. At the end of the class, the instructor reviews the students’ self-learning activity, considers and corrects the students’ typical mistakes with a subsequent improvement of knowledge and skills.

Appendix 1
Flow Chart of «Аnemias»


Anemia



^

Complaints and on examination


1. General weakness, short wind, dizziness. On examination: pallor, tachycardia, systolic murmur on the heart apex.

2. Dysgeusia, smell sense and swallowing disorder. On examination: atrophy of lingual papillas, cheilitis, xeroderma, shedding of hair, fragility of nails.

3. Sensitivity disorders.

4. Jaundice, hepatosplenomegaly.

5. Bleeding sickness, hemorrhagic rash.

  1. Fever, bacterial, fungal, viral infections






Significant syndromes









1.Аnemic

2.Sideropenic

3.Neurological (funicular myelosis)

4.Hemolytic

5.Hemorrhagic

6.Syndrome of infectious complications





Additional investigation findings




^



Instrumental


Laboratory






Complete blood count, urine analysis, biochemical blood analysis (bilirubin, transaminases), level of iron, iron-binding capacity of blood, osmotic resistance of erythrocytes.




Sternal puncture, trephine biopsy ultrasound of abdomen, roentgenography of gastrointestinal tract, gastric acidity investigation







^ Differential diagnosis by a diagnostic algorithm: iron deficiency anemia, pernicious anemia, aplastic anemia, hemolytic anemia









Patient Management



pharmacotherapy



nonpharmacotherapy






  1. iron deficiency anemia – iron supplementation

  2. pernicious anemia – vitamin В-12

  3. autoimmune hemolytic anemia – corticosteroids, splenectomy

  4. aplastic anemia – bone marrow transplantation, thymoglobulin, cyclosporine A, corticosteroids

^

elimination of anemia cause


Appendix 2

Etiologic classification of anemias


1. Posthemorrhagic anemias

2. Hemopoietic disorders:

а) Iron deficiency anemias;

b) porphyrins synthesis disorders;

c) pernicious anemias;

d) deficiency of proteins, amino acids etc.;

e) hypo-and aplastic.

^ 3. Hemolytic anemias:

а) hereditary vs. acquired

b) immune vs. non-immune

c) extravascular vs. intravascular.


Appendix 3


Diagnostic Algorithm For "Anemia"

List of Nosological Units


  1. Iron deficiency anemia

  2. Pernicious anemia

  3. Hemolytic anemia

  4. Aplastic anemia





Anemia


Decrease of serum iron level




yes

no


1

megaloblastic normoblasts in bone marrow


no


2

yes

Increase of indirect bilirubin level, positive Cumbs’ test


yes

no


3

Replacement of red bone marrow by yellow bone marrow in results of trephine biopsy


yes


4

Appendix 4

^ Normal parameters of a blood


Complete blood count

Erythrocytes: M - 4,0 - 5,1х1012/l

F - 3,7 - 4,7х1012/l

Haemoglobin: M - 130 - 164 g/l

F - 115 - 145 g/l

Color index of blood - 0,82-1,05

Reticulocytes - 0,2-1,2 %

Thrombocytes - 170 - 400х109/l

Leucocytes - 4,0 - 9,0х109/l

Basophils - 0-1 %

Eosinocytes - 1-5 %

Bond neutrophils - 1 - 6 %

segmentonuclear leukocytes - 45 - 70 %

Lymphocytes - 18 - 40 %

Monocytes - 2 - 9 %

ESR M - 2-10 mm / hour

F - 4-16 mm / hour

Hematocrit of M - 40 - 48 %

F - 36 - 42 %


^ Parameters of iron metabolism


Serum level of Iron - 9,0 - 31,3 mkmol/l

Total iron-binding capacity - 30,6 - 84,6 mkmol/l

Level of ferritin

M - 106 ±21,5 mkg / l

F - 65 ± 18,6 mkg / l


mean corpuscular volume 80-100 microns

Osmotic resistance the beginning 0,44 %

the end of 0,32 %


At the end of the practice class, you shall take a final test, and with this aim in mind, pay attention to the following example tests.


^ Final Test Questions

Q1. Patient D., 49 years old, was admitted to hematologic department with complaints on a short wind, general weakness, dysphagia, a fragility of nails and hair. On examination: paleness, xeroderma, angular stomatitis, koilonychias. In history duodenal ulcer and hemorrhoids. In complete blood count: erythrocytes-2,7x1012/l, haemoglobin - 80 g/l, color index of blood - 0,7 reticulocytes-0,5 %, white blood cells -5,0x109/l, basophilocytes -1, eosinophils - 2 %, bond neutrophils - 3 %, segmentonuclear leukocytes - 50 %, lymphocytes-40 %, monocytes-5 %, ESR-12 mm/hour; Serum level of iron - 9,5 mkmol/l, total bilirubin - 20 mkmol/l, direct - 8 mkmol/l, indirect - 12 mkmol/l. Bone marrow - normal. Which of the following is the most probable diagnosis?

А) iron deficiency anemia;

B) pernicious anemia;

C) hemolytic anemia;

D) thalassemia;

E) aplastic anemia.


Q2. Patient К., 29 years old, accumulator worker, was admitted to hospital with complaints of weakness in hands, pane in nerves, acute pains in stomach. On examination: paleness of skin with an sallow shade, narrow lilac strip on the margin of gums. In complete blood count: erythrocytes-1,6x1012/l, haemoglobin - 56 g/l, color index of blood - 0,7, reticulocytes-8%o, white blood cells -8,0x109/l, basophilocytes -0, eosinophils - 5 %, bond neutrophils - 9%, segmentonuclear leukocytes - 65%, basophilic punctuation of neutrophils, lymphocytes-19%, monocytes-2%, ESR-15 mm/hour.

Serum level of iron - 16 mkmol/l. Which of the following is the most probable diagnosis?

А) iron deficiency anemia;

В) lead anemia;

С) aplastic anemia;

D) hemorrhagic vasculitis;

Е) pernicious anemia.


Q3. Patient К., 42 years old, was admitted to hospital in a serious condition with complaints of general weakness, fever, short wind, relapsing, nasal, uterine bleedings, ecchymoses on the skin. On examination: dull percussion note under the right lung, weak vesicular respiration, crepitation. In common blood count erythrocytes-1,6x1012/l, haemoglobin - 46 g/l, color index of blood - 0,9 reticulocytes-0 %, thrombocytes-30x109/l white blood cells -1,5x109/l, basophilocytes -0%, eosinophils - 1 %, bond neutrophils - 0%, segmentonuclear leukocytes - 16%, lymphocytes-79%, monocytes-5 %, ESR-38 mm/hour; in results of histological study of bone marrow there was hypocellularity of specimen, replacement of red bone marrow by yellow. Which of the following is the most probable diagnosis?

А) pernicious anemia;

В) aplastic anemia;

С) Werlhof's disease;

D) hemolytic anemia;

Е) acute leucosis.


Q4. Patient Z., 21 years old, was admitted to the hospital with complaints of general weakness, short wind, fever, purpura, ecchymoses on the skin. On examination: necrotic tonsillitis, purpura on the skin, enlargement of liver and spleen. In common blood count erythrocytes-1,9x1012/l, haemoglobin - 71 g/l, color index of blood - 0,7, thrombocytes-30x109/l, white blood cells -300,0x109/l, basophilocytes -0%, eosinophils - 1 %, bond neutrophils - 2%, segmentonuclear leukocytes - 31%, lymphocytes-18%, monocytes-2 %, blast cells-46%, ESR-30 mm/hour. Serum level of iron-16,2 mkmol/l, total bilirubin - 18,7 mkmol/l, direct - 10,7 mkmol/l, indirect - 8 mkmol/l Which of the following is the most probable type of anemia?

А) metaplastic;

В) pernicious;

С) aplastic;

D) hemolytic;

Е) iron deficiency.


Q 5. Patient К., 50 years old, was admitted to the hospital with complaints of pain in tongue, sensitivity disorder, dyspepsia. On examination: paleness with icteric shade, an atrophy of lingual papillas, spleen +2 sm. In common blood count erythrocytes-3,1x1012/l, haemoglobin – 96 g/l, color index of blood - 1,2, thrombocytes-150x109/l, white blood cells -3,5x109/l, macrocytosis, Howell-Jolly bodies, Cabot rings. Serum iron-20 mkmol/l. In bone marrow megaloblasts were found. Which of the following is the most probable diagnosis?

А) hereditary spherocytosis;

В) iron deficiency anemia;

С) aplastic anemia;

D) acute leucosis;

Е) pernicious anemia.


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