RED BLOOD CELL ABNORMALITIES(APPROACH TO THE DIAGNOSIS OF ANEMIA)

ANEMIAReduction below normal in the concentration of hemoglobin or RBC’s in the bloodAnemia is not a diagnosis in itself, but merely an objective sign of disease.

First step in its diagnosis is detection of its presence.

3 FUNCTIONAL CATEGORIES OF THE ANEMIAS

• Disorders of Proliferation

• Disorders in Erythrocyte Maturation

• Disorders due Primarily to Erythrocyte Destruction or Red Cell Loss

SUBJECTIVE DATA Severity of the anemia Rapidity of onset Patient’s age and CV statuso capacity of the CV & pulmonary system to compensate for the anemia Associated manifestations of the underlying disorder

- Endocrine disorder- Renal disorder- Hepatic disorder

• Onset & Duration of symptoms insiduous or acute

• Previous prescription for hematinics & response

• Medication history• Occupation, household customs &

hobbies• Symptoms of hemolysis

jaundice, changes in urine color• Symptoms of blood loss

melena, hematochezia, epigastirc pain

• Obstetric & Gynecologic history # of pads/day duration # of pregnancies, abortions - interval

• Concomitant bleeding manifestations• Dietary history• Fever, Weight loss

I. Cardiac Signs

• Hemic murmurs: mid or holosystolic often in the pulmonic or apical area, due to increased blood flow and turbulence

• Gallop rhythms

• Tachycardia/Cardiomegaly

• Strong peripheral pulses with wide pulse pressure

II. Integumentary Manifestations

• Pallor: <8 to 10 mg/dL hemoglobinAffected by: - state of vasoconstriction/vasodilatation - degree & nature of pigmentation - nature & fluid content of the subcutaneous

tissuesMost constantly detected in: - mucous membranes of the mouth, pharynx,

conjunctivae, lips - nailbeds

* Areas where vessels are close to the skin surface

• Dry, Shriveled skin• Thinning, loss of luster, premature graying of hair• Brittle, lackluster nails, spooning

III. Neuromuscular Signs

• Headache

• Vertigo

• Tinnitus

• Faintness

• Retinal hemorrhage

• Paresthesias

• Scotomas

• Lack of mental concentration

• Drowsiness

• Restlessness

IV. GI Manifestations

• Glossitis

• Atrophy of the papillae of the tongue

• Dysphagia

• Oral ulcers

• Gingival hyperplasia

• Hepatosplenomegaly

V. Sternal Tenderness Lymphadenopathy

Even the most expert clinical appraisal does not supplant accurate measurement of the blood for the detection, quantification and characterization of anemia.

Changes in Normal Hemoglobin/Hematocrit Values with Age and Pregnancy• Age/Sex Hemoglobin g/dl Hematocrit %

At birth 17 52Childhood 12 36Adolescence 13 40Adult man 16(+2) 47(+6)Adult woman 13(+2) 40(+6)(menstruating)Adult woman 14(+2) 42(+6)(postmenopausal)During pregnancy 12(+2) 37(+6)

Red Cell Indices

• Index Normal ValueMean Cell Volume(MCV): (hematocrit x 10)/(red cell ct. x 106) 90 + 8 fL

Mean Cell Hemoglobin (MCH): (hemoglobin x 10)/ (red cell ct. x 106) 30 + 3 pg

Mean Cell Hemoglobin Concentration: (hemoglobin x 10)/ hematocrit, 33 + 2% or MCH/MCV

VI. Genitourinary Signs• Slight proteinuria• Changes in urine color

Always rule out primary disease of the GUT.

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Even the most expert clinical appraisal does not supplant accurate measurement of the blood for the detection, quantification and characterization of anemia.

Objective Data

Laboratory tests: I. Red cell count- hgb, hct, reticulocyte count, RBC indices II. White Blood cell count- diff’l, nuclear segmentation of neutros III. Platelet count IV.Peripheral smear morphology V. Iron Studies VI. Bone marrow examination

RETICULOCYTE COUNT

• Normal Value: 0.5 – 1.5% (old) 5 – 15 x 10-3 (SI)

Correction: Patient’s Hct x Reticulocyte count % = corrected 45

reticulocyte

Corrected Reticulocyte = RPI 2

WHITE BLOOD CELL COUNT

• Normal Value: 4.5 – 10.0 x 10 9/L Percentage Absolute No.

Bands 0-0.05 0-0.7Segmenters 0.50-0.70 1.8-7.0Lymphocytes 0.20-0.40 1.0-4.8Monocytes 0-0.07 0-0.80Eosinophils 0-0.05 0-0.45Basophils 0-0.01 0-0.20

Normal Peripheral Smear

Normal bone marrow (LPO)

Normal bone marrow (HPO)

ASSESSMENT (Possible Cause of Anemia)

CLASSIFICATION OF ANEMIAS BASED ON ETIOLOGY Increased Blood Loss

Acute and Chronic Hemorrhage Excessive Blood Destruction ((Hemolysis)

A. Congenital 1. Red Cell Morphologic Defects (e.g. Congenital Spherocytosis) 2. Hemoglobinopathies (e.g. Thalassemias) 3. Enzyme Defects (e.g. G6PD Deficiency)

B. Acquired 1. Immune Disorders

(e.g. LE)2. Non-Immune Disorders (e.g. Infections, Allergy, etc.)

Marrow production defectsa. Hematinic deficiencies – iron, Vit.

B12, Folic Acidb. Infiltrative Diseases – Leukemias,

lymphomas, Cancerc. Aplasiad. Miscellaneous – Endocrine, Renal,

Infections

CASE STUDIES

• Case 1 Mr. Santos, 48 years old farmer consulted

because of progressive weakness and pallor. No jaundice nor hepatosplenomegaly on P.E. Petechiae noted on both L.E.’s CBC Result: Hb: 7 gm/dl Hct: 21 WBC: 4,000

lymph: 48% segs: 52% Platelet count: 80,000 Reticulocyte Count:5 x 10-3

Bone Marrow: FATTY MARROW

APLASTIC ANEMIA

• A type of hypoproliferative anemia characterized by pancytopenia with marrow hypocellularity

• Etiology:1. Primary

a. CongenitalFanconi’s Anemia

b. Idiopathic 2. Secondary

a. Radiationb. Drugs and Chemical

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Regular effectsIdiosyncratic effects

c. Virusesd. Immune diseasese. PNHf. Pregnancy

Pathogenesis: Depletion of hematopoietic cells by an agent or

event that kills stem cells Suppression of proliferation and maturation of stem

cells by an immunologic or lymphocyte mediated mechanism

Clinical Features: - symptoms related to decrease RBC, WBC, platelets

- Physical exam: lymphadenopathy and splenomegaly not typical

- Laboratories: Pancytopenia, decrease reticulocyte count

Bone marrow: fatty marrow

Management Options: Transfusion support Bone marrow transplantation Immunosuppression with anti-thymocyte globulin,

with or without steroids Androgen stimulation

• Case 2 J.K., 35 year old housewife complains of progressive

easy fatigability of about 3 months duration. Review of System: (-) epigastric pain

(-) hematochezia nor melena

menses – 28 days cycle, 7 days duration, 3 days profuse flow consuming 5-6 fully soaked pads/day

(-) bruises/ecchymoses

P.E. Pale, no jaundice (-) hepatosplenomegaly

Laboratory results:

CBC: Hb: 60g/L WBC: 6 x 109/L Hct: .21 seg: 70%

MCV: 80fL lymph: 25% MCH: 25 pg eos: 3% MCHC: 28% mono: 2%

platelets: adequate Reticulocyte count: 1.5 x 10-3

Peripheral smear: HYPOCHROMIC

Iron studies:Ferritin: 8ug/LIron: 10 (N.V.9 - 27 umol/L)TIBC: 60 (N.V. 54 – 64 umol/L)Percent Saturation: 17%

IRON DEFICIENCY ANEMIA

• Most common cause of anemia worldwide

• Iron is absorbed primarily in the duodenumand upper jejunum

• Picture : causes of iron anemia

• Case 3

Mrs. Cruz, 75 year old female consulted because of progressive weakness and loss of balance. She also complains of numbness and tingling sensation in all extremities. She has no gastrointestinal complaints.

- not a diabetic but is hypertensive- prefers to eat vegetables and fish

because of poor dentition

P.E. Patient is pale with smooth, red tongue. No organomegaly noted

Laboratory ResultsCBC: Hb: 80 g/L WBC: 9 x 109/L

Hct: .26 seg: 74% MCV: 102fL lymph: 20% MCH: 36 pg eos: 2% MCHC: 38% mono: 4%

platelets: adequate

Peripheral Smear: Macrocytes

MEGALOBLASTIC ANEMIA

- disorder caused by impaired DNA synthesis

- Cell primarily affected: blood cells GI epithelial cells

- slowed nuclear cell division with normal progression of cytoplasmic maturation

Megaloblastosis

Folate sources: mainly fruits and vegetables Cobalamin sources: meat & dairy foods

Cause: B12 or/& Folate Deficiency

Clinical Manifestations: Anemia with slight icteresia

GI manifestations – glossitis, smooth, beefy red tongue, malabsorption3. Neurologic manifestations (Cobalamin) - subacute

combined degeneration of CNSperipheral neuropathy – numbness,

weakness, ataxia, paresthesia, disturbances of mentation

• Management:1. Treatment of underlying problem2. Replacement therapy

oral folic acidparenteral B12

• Case 4 Mrs. Santos, 50 year old male was referred for

evaluation of anemia. She begun to experience easy fatigability about 5 weeks PTC. She also noticed passage of highly colored urine.(+) weight loss of about 5 lbs in the last 2 months(+) febrile episodes

• P.E. icteric sclerae (+) cervical lymphadenopathy

(-) hepatomegaly(+) splenomegaly

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CBC: Hb: 70 g/L WBC: 13x 109/L Hct: .21 seg: 80%

MCV: 98fL lymph: 20% MCH: 35pg MCHC: 36%

platelets: adequate

Reticulocyte count: 80 x 10-3/LPeripheral smear: spherocytesOther tests:

Direct Coombs: +++Peripheral Smear: SPHEROCYTES

IMMUNE HEMOLYSISWarm-antibody Immunohemolytic Anemia

- induced by IgG or IgM Abs reacting specifically on antigens on RBC membraneDiagnosis: (+) Coomb’s test

Management:SteroidsSplenectomyImmunosuppresants

• Case 5JA, 18 year old male consulted because of

recurrent jaundice and pallor. Jaundice was first noted when he was 4 years old.

No history of blood transfusions.Family history is positive for another sibling with

similar problem.

P.E. Icteric scleraemoderate splenomegaly

CBC: Hb: 81 g/L Hct: .30

WBC: 11.5 x 109/Lseg: 75%lymph: 24%eos: 1%

platelets: adequate Reticulocyte count: 60 x 10-3/L Peripheral smear: (+) spherocytes

HEREDITARY SPHEROCYTOSIS

- inherited RBC membrane abnormality – autosomal dominant pattern of inheritance

- Characterized by spherical RBC due to a molecular defect in one of the proteins of the cytoskeleton of the RBC membrane

ankrinProtein 3Spectrin

Clinical Manifestations:anemiajaundicecholelithiasis

Diagnosis: spherocytes on smearreticulocytosis(-) Coomb’s test(+) Osmotic fragility test

Management:

Splenectormy – for moderate to severe hemolysis

Folic Acid supplementationAPPROACH TO THE BLEEDING PATIENT

SCREENING HISTORY

• A history taken to evaluate hemostasis should answer these questions:

• Has the patient experienced abnormal bleeding or bruising? If so, are symptoms recently acquired or do they date back to childhood?

• Is there a history of an acquired disorder that would impair hemostasis? E.g., chronic liver disease, SLE, uremia or a hematologic malignancy.

• Is the patient taking a drug that could interfere with hemostasis?

• Have other members of the family bled abnormally?In questioning a parent about significant bleeding in a small child, one should ask specifically about:

• Bleeding from umbilical stump

• Bleeding after circumcision

• Bleeding from cuts in mouth

• Frequency & size of hematomas of scalp

• Extent of bruising from minor trauma, eg. Falls from swings or bicycles or down steps

• Nosebleeds that stop w/in mins, even if frequent, suggest that hemostasis is N. Prolonged nosebleeds requiring medical intervention arouse suspicion of impaired hemostasis. In assessing bleeding history of an adult patient, one evaluates:

• Abnormal bruising, ask specific questions:

• How often do you notice a new bruise on your body?• Do you develop bruises larger than a 1in dm without remembering how you got the bruise? If so, how big was the largest of these bruises?• Do you notice bruises after injections?

• Excessive bleeding from small cuts

• Bleeding after previous surgery

• Bleeding after dental extractions. Bleeding that lasts >24h after extraction of a permanent tooth or that starts again after 3-4 days is suggestive of a hemostatic abnormality.

DRUGS THAT INTERFERE WITH HEMOSTASIS

• Aspirin, clopidogrel, dipyridamole

• Drugs that interfere with blood coagulation: heparin, oral anticoagulants, (?) herbal medications

PHYSICAL EXAMINATION

• Bleeding into skin and soft tissues

• Petechiae: characteristic of vessel & platelet problem. Usually pinhead size but maybe bigger. Characteristically develops 7 regress in crops. Most conspicuous in areas of increased venous pressure.

Must be distinguised from small telangiectsias & angiomas

• Ecchymoses, hematomas: large superficial hematomas maybe seen in coagulation disorders.

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• Palpable purpuras may be seen in vasculitis

• Hemarthorses – bleeding into synovial joints and virtually diagnostic of a severe hereditary coagulation disorder. May develop without discoloration or other external evidence of bleeding.

• Traumatic bleeding Response to trauma is an excellent “screening test” for

the presence of hereditary hemorrhagic disorder. A history of surgical procedures or significant injury w/o abnormal bleeding is equally good evidence against presence of such disorder.

• Miscellaneous bleeding manifestations

spontaneous bleeding from body orificesmenorrhagia melena

metrorrhagia epistaxishematuria gingival bleedinghematemesis hemoptysis

Bleeding into serous cavities & internal fascial spacesretroperitoneal spacepsoas sheathCNSretina

CLINICAL DISTINCTION BETWEEN DISORDERS OF VESSELS & PLATELETS & DISORDERS OF BLOOD COAGULATION

FINDINGS COAG D/O PLT OR VESSEL D/O

Petechiae Rare Characteristic

Deep dissecting hematomas

Characteristic Rare

Superficial ecchymoses

Common, usually large & solitary

Characteristic, usually small &

multipleHemarthrosis Characteristic Rare

Delayed bleeding common Rare

Bleeding from sup. cuts & scratches

minimal Persistent, often profuse

Sex of patient 80-90% of hereditary forms

M

Relatively more common in F

(+) family hx common rare

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