Anemia
Definition: Anemia is a disorder of the red blood cell. Anemia is present when there is a decreased level of hemoglobin in the blood-below the reference level for the age, sex and pregnancy state of the individual.
Symptoms:
Depends on acuteness and severity of anemia. Symptoms can occur when anemia is chronic, however most patients are asymptomatic. Symptoms which relate to the underlying cause include non-specific complaints such as fatigue, headache, faintness, dyspnea, palpitations, intermittent claudication, tinnitus.
Physical exam findings:
General: pallor of mucus membranes, signs of hyperdynamic circulation (tachycardia,
bounding pulse, cardiomegaly, and systolic flow murmur), heart failure, orthostatic hypotension
Specific: koilonychia (ridging and spoon shape nails in iron deficiency anemia), jaundice
(hemolytic anemia), bone deformities (thalassemia), leg ulcers (sickle cell disease), splenomegaly, petechaie/purpura (bleeding disorder), glossitis (iron, folate, vitamin B12 deficiencies), neurologic abnormalities (vitamin B12 deficiency)
Classification of Etiologies:
| Decreased production | Increased destruction or loss |
| Nutritional deficiencies -iron deficiency -vitamin B12 deficiency -folate deficiency Bone marrow suppression -Infections: HIV, tuberculosis, malaria, schistosomiasis, hepatitis, parvovirus -Drugs: Isoniazid, chloramphenicol, alcohol, zidovudine, 5-FU, hydroxyurea -Chronic disease: renal and liver disease, rheumatologic diseases, hypothyroidism -Pure red cell aplasia Hemoglobinopathies -Thalassemias | Blood loss -acute or chronic GI bleeding -menstrual bleeding -trauma Hemolysis -Malaria -G6PD deficiency -Microangiopathic hemolytic anemia: TTP, HUS, DIC, eclampsia, HELLP -Hereditary spherocytosis -Autoimmune hemolytic anemia -Sickle cell disease -Paroxysmal nocturnal hemoglobinuria -Hypersplenism |
Laboratory Findings
Red cell values: vary according to age, sex, pregnancy state
-normal hemoglobin in men 13-18 g/dl normal MCV 76-96
-normal hemoglobin in women 11.5 -16.5 normal MCV 76-96
Leukocyte and platelet counts: distinguish isolated anemia from pancytopenia. The white blood count increase in hemolytic anemia, infections, and leukemias. Platelets may be increased in chronic inflammation and post sickle cell crisis
Reticulocyte count: Increases with the severity of the anemia, as in chronic hemolysis. A lower reticulocyte level in the face of anemia suggests: impaired bone marrow function, deficiency of iron, vitamin b12 or folate; lack of erythropoietin (renal failure); ineffective erythropoiesis
Iron studies: help distinguish between different types of microcytic anemia
Blood smear: very useful in pointing towards specific types of anemia. See below for findings.
Classification of anemia by size
Microcytic anemia
-Iron deficiency anemia: most common worldwide. Clinically: brittle nails, atrophy of papillae of tongue, brittle hair. Etiology: poor diet, chronic blood loss (schistosomiasis, worms, GI loss from esophageal varices, peptic ulcer). Diagnosis: MCV < 80, blood smear shows hypochromic red cells, pencil shaped (poikilocytosis), target cells. Treatment: iron replacement ferrous sulfate 200 mg tds
-Anemia of chronic disease: associated with chronic inflammatory or malignant disease. Etiologies: infectious (TB, lung abscess, pneumonia, endocaritis) or non-infectious (rheumatoid arthritis, lupus), malignancy. Clinical features: normocytic anemia, reduced serum iron and TIBC, normal or raised ferritin. Treatment is treat underlying cause.
-Thalassemia: heterogeneous group of genetic disorders which result from a reduced rate of synthesis of alpha (4 chains) or beta chains (2 chains) of hemoglobin. Changes in normal ratio results in each of the disorders. Thalassemia minor: often asymptomatic. Beta thalassemia major: autosomal recessive, presents with hepatosplenomegaly, bone expansion, infections. Diagnosis; severe hypochromic microcytic anemia with raised reticulocyte count, target cells
Normocytic Anemia:
-Anemia of chronic disease: see above
-Hypothyroidism: treatment is thyroid replacement
-Acute blood loss: can be normocytic before iron stores are reduced
-Pure red cell aplasia: destructive antibodies or lymphocytes leading to ineffective erythropoiesis. Associated with thymoma and parvovirus. Diagnosis: lack of erythroid precursors on bone marrow biopsy. Treatment: supportive care
Macrocytic Anemia:
-Vitamin B12 deficiency: Etiologies include malnutrition (alcoholics, vegetarians), pernicious anemia, decreased absorption (celiac sprue, Crohn’s disease), increased competition (fish tapeworm, intestinal bacterial overgrowth). Clinical features neurologic changes (numbness, paresthesias, decreased vibratory and positional sense, ataxia). Smear shows hypersegmented neutrophils. Treatment: replacement of B12
-Folate deficiency: Etiologies include malnutrition (alcoholics, elderly), decreased absorption (sprue), impaired metabolism (methotrexate, trimethoprim, antimalarials). Treatment: folate repletion
Hemolytic Anemia:
-See table for etiologies
-Due to red cell destruction and increased red cell turnover. Bone marrow is able to compensate 5 times the normal rate.
-Clinical features: jaundice, hepatosplenomegaly, dark urine.
-Labs: increased reticulocyte count, indirect hyperbilirubinemia, shistocytes on blood smear
-Treatment: treatment underlying cause of hemolysis
***Sickle cell disease: a severe hemolytic anemia caused by inheritance of a point-mutated gene. The mutation results in a Glu-Val amino acid substitution in position 6 of the Beta globin chain of the hemoglobin molecule and formation of HbS. When deoxygenated, the HbS molecules polymerize into long fibers and cause the red blood cells to sickle.
-Clinical features: severe anemia causes crises. Typically hemoglobin levels are 6-8
g/dl, reticulocytes 10-20%. Often get painful swelling of hands and feet. Shortness of breath, chest pain with infiltrate on chest xray is called acute chest syndrome
-Crises: painful vascular-occlusive crises precipitated by infection, dehydration, deoxygenation. Infarcts may occur in bone.
-Complications of sickle cell include renal failure, bone necrosis, infections (Salmonella osteomyelitis), splenomegaly.
-Laboratory findings: hemoglobin levels of 6-8 g/l, sickle cells on blood smear.
-Management: avoid precipitating factors. Give folic acid, improve hygiene. Give malaria prophylaxis. In sickle cell crisis: give IV fluids with normal saline, give antibiotics for signs of infections. Obtain urine dipstick, chest xray and FBP. Give oxygen and transfuse blood for severe anemia.
Approach to Anemia
-Obtain a thorough history: menstrual history, bleeding tendencies, hematuria, rectal bleeding, melena. Consider colonoscopy/endoscopy, urinalysis/ urine cytology for hematuria, pelvic ultrasound for fibroids.
-Check FBP, MCV, peripheral blood smear
-Determine underlying cause of anemia
-If hemodynamically unstable or very symptomatic, transfuse packed red blood cells
-Treat underlying cause of anemia
Reticulocyte Index*<2 (decreased production) Microcytic (MCV<80) Provisional Diagnosis: Iron deficiency Anemia •Look for sources of slow bleeding** •Treat with ferrous sulfate 200mg TDS for 4-8 weeks. •If Hgb increases and reticulocytosis on blood film, continue with iron supplementation for 3 months. •If no improvement, consider thalassemia. Normocytic (MCV 80-100) Provisional diagnosis: Anemia of Chronic Disease •Treat underlying disease and obtain rapid test and serum creatinine for possible chronic renal failure. •If pt has no chronic disease, treat with Vitamin B12, Folate and Iron for possible early iron, vitamin B12 and folate deficiencies. . Macrocytic (MCV>100) Provisional Diagnosis: Vitamin B12/Folate deficiency •Treat with Vitamin B12 and Folic Acid. •Recheck Hgb in 4-8 weeks. •If no improvement, check liver function tests, thyroid function tests and schilling’s test. Reticuloycte Index*>2 (increased destruction or loss) MPS positive: Treat malaria. Pancytopenia (Low Hgb, Low WBC <4.5 and Low platelets <150,000) •Rapid Test; HIV may cause pancytopenia •Review medications •Bone marrow biopsy Schistocytes on Peripheral Smear Concern for hemolysis. Examine patient for jaundice and splenomegaly. •Sickling Test •G6PD deficiency (check in 4-8 weeks when patient is healthy) •Hypersplenism: Tropical splenomegaly syndrome, splenic sequestratioon •Autoimmune hemolytic anemia •TTP •DIC/Sepsis
Case 1
40 year old male with history of portal hypertension comes into the hospital with complaints of fatigue and general body weakness for over 6 months. He denies fevers or chills. He does complain of mild epigastric pain after eating for months. A few months ago, he did have black stool but that resolved. On physical exam T 36.4 HR 70 BP 120/70. Pertinent findings are pale conjunctiva, tenderness in the epigastric region with no guarding or rebound, no hepatosplenomegaly, brittle nails and brown stool on rectal exam.
1. What is your differential diagnosis for the general body weakness?
-anemia, chronic viral infection, malignancy
2. What would you like to do next?
-check FBP, malaria test, peripheral blood smear
-consider abdominal ultrasound to evaluate portal hypertension further
-consider endoscopy for history of melena
The FBP shows WBC 6, Hgb 7 and platelets of 300,000. MCV is 60. Malaria smear is negative. His blood smear shows microcytic cells.
3. What type of anemia is this patient presenting with?
-microcytic anemia
4. What is the likely etiology for anemia?
-iron deficiency from chronic blood loss
-patient may have esophageal or gastric varices secondary to portal hypertension
5. What is the treatment?
-treat with ferrous sulfate 200 mg TDS
-consider endoscopy and banding if esophageal varices are present
Case 2
65 year old male with history of hypertension presents with fatigue and lower extremity numbness. His wife also tells you that he has fallen several times over the past 6 months and that his gait has become abnormal. He denies fever, headaches, visual changes and muscle weakness. On physical exam, T 36.8 HR 75 BP 120/80. No orthostasis. Neuro exam is pertinent for normal cranial nerves, normal power, decreased sensation to light touch in lower legs bilaterally, decreased vibratory and positional sense in feet and ataxic gait.
1. What is your differential diagnosis?
-Vitamin B12 deficiency, primary CNS lesion such as stroke or tumor either in brain or spinal cord, peripheral neuropathy secondary to diabetes, myopathy, other peripheral neuropathies
2. What would you like to do next?
-check FBP, peripheral blood smear, RBG
-if unrevealing, consider CT scan of head
The FBP shows WBC 5 Hgb 6.8 Platelets 250,000. MCV is 115. His blood smear shows macrocytic erythrocytes and hypersegmented neutrophils. RBG is 6.5.
3. What type of anemia is this patient presenting with?
-macrocytic anemia
4. What is the likely etiology for anemia?
-vitamin B12 deficiency
5. What is the treatment and prognosis?
-give 1 mg of vitamin B12 IM, start vitamin B12 and folate repletion by mouth
-neurologic abnormalities are usually reversible if treated within 6 months
Case 3
16 year old female with no known medical history presents with bilateral knee and ankle pain for 1 day. She recently started a new job selling fruits and vegetables and has been outside in the sun all day. She denies fevers or chills. Upon further questioning, she reveals that she has drunk very little water over the past few days. In addition, she has had joint pains on and off several times throughout her life. On physical exam, T 37.1 HR 95 BP 115/70. Pertinent findings include pale conjunctiva, mild scleral icterus, regular rate with a 2/6 systolic ejection murmur heard at the left upper sternal border, clear lungs and mild bilateral ankle and knee swelling without warmth or erythema. There is tenderness with motion of the knees and ankles.
1. What is your differential diagnosis?
-sickle cell disease, hemolytic anemia, gout, rheumatoid arthritis
2. What would you like to do next?
-check FBP, ESR, peripheral blood smear, AST, ALT, bilirubin, orthostatics
Her FBP shows WBC 9 Hgb 6 Platelets 500,000. Her ESR is 50. Blood smear shows sickle-shaped RBCs and Howell-Jolly bodies. AST and ALT are normal. Total bilirubin is elevated to 5.
4. What type of anemia is this?
-hemolytic anemia – evidence is scleral icterus and elevated bilirubin
5. What is the most likely diagnosis?
-sickle cell disease with pain crisis likely secondary to dehydration
6. What is the treatment?
-IV fluids
-pain control with opiates (avoid NSAIDs with dehydration)
-give folic acid
-check CXR to rule out acute chest syndrome
-continue to periodically check FBP and peripheral smear
-transfuse if anemia becomes more severe
-if becomes febrile, search for source of infection and treat with antibiotics
