Red Blood Cell Abnormalities

RED BLOOD CELL ABNORMALITIES (APPROACH TO THE DIAGNOSIS OF ANEMIA) ANEMIA Reduction below normal in the concentration of hemoglobin or RBC’s in the blood Anemia 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 status o 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

* 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 52 Childhood 12 36 Adolescence 13 40 Adult 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)

•Gallop rhythms •Tachycardia/Cardiomegaly •Strong peripheral pulses with wide pulse pressure

Red Cell Indices

II. Integumentary Manifestations

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

•Pallor: <8 to 10 mg/dL hemoglobin Affected by: - state of vasoconstriction/vasodilatation - degree & nature of pigmentation - nature & fluid content of the subcutaneous tissues Most constantly detected in: - mucous membranes of the mouth, pharynx, conjunctivae, lips - nailbeds

•Index

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

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

30 + 3 pg 33 + 2%

VI. Genitourinary Signs • Slight proteinuria • Changes in urine color Always rule out primary disease of the GUT. 1

Even the most expert clinical appraisal does not supplant accurate measurement of the blood for the detection, quantification and characterization of anemia. Normal bone marrow (HPO)

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

ASSESSMENT (Possible Cause of Anemia)

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

No. Bands Segmenters 7.0 Lymphocytes Monocytes 0.80 Eosinophils 0.45 Basophils

0-0.05

Absolute 0-0.7

0.50-0.70 0.20-0.40

0-0.01

Normal Peripheral Smear

1.81.0-4.8

0-0.07

0-

0-0.05

00-0.20

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 defects a. Hematinic deficiencies – iron, Vit. B12, Folic Acid b. Infiltrative Diseases – Leukemias, lymphomas, Cancer c. Aplasia d. Miscellaneous – Endocrine, Renal, Infections

CASE STUDIES

•Case 1

Normal bone marrow (LPO)

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: 2

1. Primary a. Congenital Fanconi’s Anemia b. Idiopathic 2. Secondary a. Radiation b. Drugs and Chemical Regular effects Idiosyncratic effects c. Viruses d. Immune diseases e. PNH f. 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: MCV: 80fL lymph: 25% MCH: 25 pg eos: MCHC: 28% mono: platelets: adequate Reticulocyte count: 1.5 x 10-3

70% 3% 2%

•Most common cause of anemia worldwide •Iron is absorbed primarily in the duodenum and 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 Results CBC: 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, malabsorption 3. Neurologic manifestations (Cobalamin) - subacute combined degeneration of CNS peripheral neuropathy – numbness, weakness, ataxia, paresthesia, disturbances of mentation

•Management: 1. Treatment of underlying problem 2. Replacement therapy oral folic acid parenteral B12

Peripheral smear: HYPOCHROMIC Iron studies: Ferritin: 8ug/L Iron: 10 (N.V.9 - 27 umol/L) TIBC: 60 (N.V. 54 – 64 umol/L) Percent Saturation: 17% IRON DEFICIENCY ANEMIA

•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

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•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/L Peripheral smear: spherocytes Other tests: Direct Coombs: +++ Peripheral Smear: SPHEROCYTES

IMMUNE HEMOLYSIS Warm-antibody Immunohemolytic Anemia

-induced by IgG or IgM Abs reacting specifically on

Splenectormy – for moderate to severe hemolysis Folic Acid supplementation APPROACH 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?

antigens on RBC membrane Diagnosis: (+) Coomb’s test

•Have other members of the family bled abnormally?

Management: Steroids Splenectomy Immunosuppresants

•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

•Case 5 JA, 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 sclerae moderate splenomegaly CBC: Hb: 81 g/L Hct: .30 WBC: 11.5 x 109/L seg: 75% lymph: 24% eos: 1% platelets: adequate Reticulocyte count: 60 x 10-3/L Peripheral smear: (+) spherocytes HEREDITARY SPHEROCYTOSIS

In questioning a parent about significant bleeding in a small child, one should ask specifically about:

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

dominant pattern of inheritance

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

-Characterized by spherical RBC due to a molecular defect

DRUGS THAT INTERFERE WITH HEMOSTASIS

-inherited RBC membrane abnormality – autosomal in one of the proteins of the cytoskeleton of the RBC membrane ankrin Protein 3 Spectrin Clinical Manifestations: anemia jaundice cholelithiasis Diagnosis: spherocytes on smear reticulocytosis (-) Coomb’s test (+) Osmotic fragility test Management:

•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. •Palpable purpuras may be seen in vasculitis

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•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 orifices menorrhagia melena metrorrhagia epistaxis hematuria gingival bleeding hematemesis hemoptysis Bleeding into serous cavities & internal fascial spaces retroperitoneal space psoas sheath CNS retina 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

Hemarthrosis

Characteristic

Characteristic, usually small & multiple Rare

Delayed bleeding

common

Rare

Bleeding from sup. cuts & scratches Sex of patient

minimal

Persistent, often profuse

80-90% of hereditary forms M common

Relatively more common in F

(+) family hx

rare

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