Approach to Anemia: An Interactive Discussion
Mark M. Udden, MDChief, Benign HematologyBaylor College of Medicine
DisclosuresI didnt do it.
You didnt see me.
You have no evidence.
Consultant for NovartisCo-Investigator for sameFree meals from Injectafer
people
Bart Simpson
Objectives: Develop an Approach
to evaluation of microcytic anemia anemia
to evaluation of microcytic anemia
to evaluation of iron deficiency
to anemia of chronic disorders
to anemia of renal disease
After the Hx and PE:
Peripheral Blood Smear Reticulocyte Count
Patient 1
A 25-year-old woman presents with weakness, fatigue, and pallor. She reports that she has had heavy periods for most of her adult life and that she has three children, the youngest of which is 10 months old.Her CBC shows a Hct of 28 %, with an MCV of 72 fL, and a platelet count of 540,000. The WBC is normal.
Iron Deficiency Anemia History
BleedingPicaRestless LegsSubtle neurologic dysfunctionDysphagia
Physical ExamPainless stomatitisSpoon nailsBlue Sclera?Telangiectasia
Peripheral Blood Smear in Fe Deficeincy
Peripheral Blood Smear in Fe Deficeincy
Forms of Pica Reported in Association with Iron Deficiency
Pagophagia Ice Geophagia Clay, dirt Amylophagia Starch Geomelophagia Potatoes Gooberphagia Peanuts
Unnamed Forms of Pica
Ash Baking Powder Card Board Paper Venetian Blind Dust Wood, Toothpicks
Nail Changes in Fe Deficiency
Spooning!
Plummer Vincent: Esophageal Web
Iron Studies in Fe Deficiency
Low SI, high TIBC; low % sat Low ferritin How high can the ferritin be? Two other causes of a low ferritin
HypothyroidismVitamin C deficiency
Causes of Iron Deficiency Nutritional
infants women of child
bearing years Blood loss
uterine (menorrhagia, fibroids)
vWF disease GI bleeding
Helicobacter pylori
IBD HHT
Trauma Frequent blood
donation
Malabsorption Gastric bypass postgastrectomy sprue
Loss as hemosiderin valve hemolysis PNH
Pulmonary hemosiderosis
Unusual causes of iron deficiency
PresenterPresentation NotesWhen you can liver forever, what do you live for?
Bella Lugosi on the left and Bella Swan played by Kristen Stewart.Film buffs know Bella Lugosi. See the movie Ed Wood (Johnny Depp), a biopic about the worst movie director of all time. Martin Landau is a wonderful Bella Lugosi in that movie.
http://www.imdb.com/media/rm2266076160/tt1099212http://www.imdb.com/media/rm2266076160/tt1099212
More Vampires
PresenterPresentation NotesMaila Nurmi (Vampira) and Martin Landau (as Bella Lugosi in the movie Ed Wood).
Treatment of Iron Deficiency
Use cheap FeSO4, 325 mg TID Keep away from Children Ascorbic acid may help absorption
Follow Hematocrit, ferritin
Iron Refractory Iron Deficiency Anemia (IRIDA)
Endoscopic evaluation often fails to identify a cause of iron deficiency anemia Capsule studies have been informative AVM in the elderly arent always detected
Some patients will not respond to oral iron even if complianttoo much iron is being lost Menstrual loses IBD, HHT, Cancer
Patient has something else: Thalassemia
Poor Mans Iron Absorption Test
Patient Fasts Overnight AM baseline serum iron Give 100 mg of elemental iron PO as liquid
FeSO4 Draw serum iron at one and two hours Typical basal iron is
IRIDA
Celiac Disease Anti TTG (tissue transglutaminase)
Autoimmune gastritis Achlorhydria, anti Parietal cell and Intrinsic
factor antibodies and PA H. Pylori
Relationship to autoimmune gastritis Hereditary IRIDArara avis
PresenterPresentation NotesTTG ab are IGA and may not be present in IgA deficient individuals, Anti endomysial abs, seronegative mild celiac disease HLA DQ2/DQ8Exlude ACD with CRPChronic renal failure PPI, GI bleeding due to drugs
IV Iron
IBD HHT Menorrhagia Pregnancy Roux en Y
Sleeves/stapling ? Ordinary iron deficiency and intolerance to
oral iron
Patient 2
A 40 year old man presents after having been told that he was anemic after routine tests for an insurance physical exam. He has no history of bleeding and has enjoyed good health. He is a runner who puts in 20 miles per week and has done a marathon in the last year. He believes that his mother was anemic. His CBC: HCT 32 with MCV of 70 fL. WBC and platelet count are normal.
Alpha Thalassemia
Diagnosis of exclusion Normal iron studies Normal Hb electrophoresis Common in Black Americans Hypochromic microcytic anemia
(mild) Normal RDW
New Methylene Blue Stain in Hemoglobin H disease
Alpha ThalassemiasPOPULATION GENOTYPE CLINCAL
PRESENTATIONAfrican 0+/++ Silent
0+/0+ ThalassemiaMinor
Asia, Near East 00/++ ThalassemiaMinor
00/0+ Hemoglobin H
00/00 Hydrops Fetalis
POPULATION
GENOTYPE
CLINCAL PRESENTATION
African
0+/++
Silent
0+/0+
Thalassemia Minor
Asia, Near East
00/++
Thalassemia Minor
00/0+
Hemoglobin H
00/00
Hydrops Fetalis
Beta Thalassemia Minor
Seen in all groups, common in Mediterranean
Hypo/micro, fine basophilic stippling, targeting, normal RDW
May have minimally enlarged spleen Normal iron studies, Hb electrophoresis:
A2> 3.5 %; F variably increased Genetic Counseling
Thalassemic Hemoglobinopathies
Hemoglobin E traitHigh frequency in SE Asia
Viet NamCambodia
Microcytic E-Beta thalassemia
Thalassemia major Thalassemia intermedia
Patient 3
A 55-year-old woman presents with a long history of rheumatoid arthritis. For the past two weeks she has had a flare with pain in the hands. Her Hematocrit is 30 %, her MCV is 83 fL, and the WBC and platelet counts are normal. On exam she has swollen tender MCP joints.
IL-6 up regulates production of hepcidin in the liverHepciden interacts with iron transporter ferroportin 1 which is then internalized and destroyediron not able to get out of macrophages
Weiss G and Goodnough L. N Engl J Med 2005;352:1011-1023
Pathophysiological Mechanisms Underlying Anemia of Chronic Disease
PresenterPresentation NotesFigure 1. Pathophysiological Mechanisms Underlying Anemia of Chronic Disease.
In Panel A, the invasion of microorganisms, the emergence of malignant cells, or autoimmune dysregulation leads to activation of T cells (CD3+) and monocytes. These cells induce immune effector mechanisms, thereby producing cytokines such as interferon-{gamma} (from T cells) and tumor necrosis factor {alpha} (TNF-{alpha}), interleukin-1, interleukin-6, and interleukin-10 (from monocytes or macrophages). In Panel B, interleukin-6 and lipopolysaccharide stimulate the hepatic expression of the acute-phase protein hepcidin, which inhibits duodenal absorption of iron. In Panel C, interferon-{gamma}, lipopolysaccharide, or both increase the expression of divalent metal transporter 1 on macrophages and stimulate the uptake of ferrous iron (Fe2+). The antiinflammatory cytokine interleukin-10 up-regulates transferrin receptor expression and increases transferrin-receptor-mediated uptake of transferrin-bound iron into monocytes. In addition, activated macrophages phagocytose and degrade senescent erythrocytes for the recycling of iron, a process that is further induced by TNF-{alpha} through damaging of erythrocyte membranes and stimulation of phagocytosis. Interferon-{gamma} and lipopolysaccharide down-regulate the expression of the macrophage iron transporter ferroportin 1, thus inhibiting iron export from macrophages, a process that is also affected by hepcidin. At the same time, TNF-{alpha}, interleukin-1, interleukin-6, and interleukin-10 induce ferritin expression and stimulate the storage and retention of iron within macrophages. In summary, these mechanisms lead to a decreased iron concentration in the circulation and thus to a limited availability of iron for erythroid cells. In Panel D, TNF-{alpha} and interferon-{gamma} inhibit the production of erythropoietin in the kidney. In Panel E, TNF-{alpha}, interferon-{gamma}, and interleukin-1 directly inhibit the differentiation and proliferation of erythroid progenitor cells. In addition, the limited availability of iron and the decreased biologic activity of erythropoietin lead to inhibition of erythropoiesis and the development of anemia. Plus signs represent stimulation, and minus signs inhibition.
Anemia of Chronic Disorders
Hypo/micro or normochromic anemiaLow serum iron (< 60 ug/dL) and
TIBC, Low % saturation Ferritin (>50 ng/mL) Normal RDW Bone marrow shows adequate iron
stores, but no incorporation into precursors
Conditions Associated with Anemia of Chronic Disorders
Acute or Chronic Infection 32 Inflammatory Disease 5 Malignant Disease 17 Renal Insufficiency 14 Other 22
Other In ACD
ETOH liver disease (5) CHF (5) DVT (3) COPD/no apparent infection (2) Myocardial Ischemia (2) Multiple Diagnoses (2) Brittle DM (1) Hypothyroidism (1)
Patient 4
60 year old woman with history of DM for 18 years. Has early retinopathy. Urine study shows microalbuminuria.
Hb is 10.5, MCV is 88 fl, reticulocyte count 1.2 %
GFR estimated is 65 ml/min Iron studies are normal, B12 and folate
are normal
Heme Work Up
Peripheral blood smear normal Thyroid Function Tests normal SPEP and kappa/lambda are
normal Erythropoietin level ordered Testosterone level ordered when
patient is a man
Anemia and DM
Anemia is a common complication of DM and correlates with renal failure
Rate of anemia is higher in patients with Diabetic nephropathy than in non diabetic renal disease with similar levels of renal impairment.
Failure to increase EPO in response to decrease in Hb due to damage to the tubulointerstium.
Patient 5
A 65-year-old black man, a retired minister, presents with anemia. He is diabetic but has done well on a diet. He is referred to you for evaluation of mild anemia: Hct 28 %, MCV 110, and folate, B12, and iron studies are normal. His physical exam is unremarkable, he has no splenomegaly.
Sideroblastic Anemia
Dual Population of RBCs Pseudo Pelger Huet WBC in
Myelodysplastic Increased serum iron, and increased %
Sat High Ferritin Presence of Ringed Sideroblasts TX: Pyridoxine, Transfusions
Differential Diagnosis of Sideroblastic Anemia
Hereditary X-linked Autosomal Recessive Mitochondrial
Pearsons Pancreatic Syndrome Abcb7 deficiency and ataxia
ALA synthase deficiency Acquired
Myelodysplasia V617F JAK2 mutation: Sideroblastic anemia and thrombocytosis Toxins: Alcohol, Lead Drugs: INH, PZA, cycloserine, chloramphenicol Copper Deficiency, Zinc overload, Hypothermia
Causes of Microcytic Anemia
Iron Deficiency Thalassemia Minor Anemia of Chronic Disease Sideroblastic Anemia
IRON STUDIESTEST IRON
DEFICIENCYACD
SERUM IRON LOW LOW
TIBC HIGH LOW
% SAT LOW LOW
FERRITIN 50
TEST
IRON DEFICIENCY
ACD
SERUM IRON
LOW
LOW
TIBC
HIGH
LOW
% SAT
LOW
LOW
FERRITIN
50
Use of Ferritin Alone
5070 ng/ml ACD A rule of thumb: If hemoglobin is 10 or
less and ferritin is less than 50there is a component of iron deficiency.
Rudyard Kipling
Gold is for the mistress, silver for the maid.Copper for the craftsman cunning at his trade.Good! said the Baron, sitting in his hall.But IronCold Ironis master of them all.
PresenterPresentation NotesTime cover in 1926 Canadian Engineers are given an iron ring as part of their graduation ceremony devised by RK
Approach to Anemia: An Interactive DiscussionDisclosuresObjectives: Develop an ApproachAfter the Hx and PE:Patient 1Iron Deficiency AnemiaPeripheral Blood Smear in Fe DeficeincyPeripheral Blood Smear in Fe DeficeincyForms of Pica Reported in Association with Iron DeficiencyUnnamed Forms of PicaSlide Number 11Slide Number 12Slide Number 13Iron Studies in Fe DeficiencyCauses of Iron DeficiencySlide Number 16More VampiresTreatment of Iron DeficiencyIron Refractory Iron Deficiency Anemia (IRIDA)Poor Mans Iron Absorption TestIRIDAIV IronPatient 2Slide Number 24Slide Number 25Alpha ThalassemiaSlide Number 27Alpha ThalassemiasBeta Thalassemia MinorThalassemic HemoglobinopathiesPatient 3Slide Number 32Slide Number 33Anemia of Chronic DisordersConditions Associated with Anemia of Chronic DisordersOther In ACDPatient 4Heme Work UpAnemia and DMPatient 5Slide Number 41Slide Number 42Sideroblastic AnemiaDifferential Diagnosis of Sideroblastic AnemiaSlide Number 45Slide Number 46Slide Number 47Causes of Microcytic AnemiaIRON STUDIESSlide Number 50Use of Ferritin Alone Rudyard Kipling