What are the classic symptoms of Anemia?
- Weakness, fatigue, and dyspnea
- Pale conjuctiva and skin
- Headache and lightheadedness
- Angina (especially with a preexisting CAD)
What are the differentiation levels based on MCV?
- Microcytic < 80 µm3
- Normocytic 80 - 100 µm3
- Macrocytic > 100 µm3
What is the definition of Anemia in men and women?
Men < 13.5 g/dL Hb (13.5 - 17.5)
Women < 12.5 g/dL Hb (12.5 - 16.0)
What are the steps of hemoglobin synthesis?
Case: Patient presents with weakness, fatigue, headache, spoonshaped nails (koilonychia), and pale conjunctiva. The patient is otherwise healthy except for celiac disease. You take a blood test to check for anemia. Which results can you most likely expect to find?
Iron deficency anemia
- Ferritin: Low
- TIBC: High (300 µg/dL)
- Serum Iron: Low (100 µg/dL)
- % Saturation: Low (33%)
What are the stages of iron deficency?
- Storrage iron depletion: Low ferritin and high TIBC
- Serum iron depletion: Low serum iron and % sat
- Normocytic anemia (fewer, but normal size)
- Microcytic anemia (smaller and fewer)
Case: Patient presents with anemia, dysphagia and a beefy-red tounge. What is the most likely syndrom?
Which chronic diseases causes anemia?
Chronic inflammation (e.g., endocarditis, autoimmune disorders) cancer.
What is the function of hepcidin which causes anemia, and what is the aim of this function?
Sequesters iron in storage sites and supress EPO. They do it to prevent bacteria from accessing crucial iron. In acute illnesses this does not cause problems, but in chronic illnesses the patients are at risk of developing anemia. (most common type in hospital)
Case: Patient presents with dyspnea, weakness, fatigue and headache. The patient is quite pale and the smear shows iron-laden mitochondria form rings around the nucleaus of erythroid precursors. What is the most common congenital cause of this anemia?
Congenital defect of aminolevulinic acid synthase which is the rate limiting step in the production of hemoglobin. This hinders the production of protoporphyrin and iron gets built up wthin the cells.
What are the aquired causes of sideroblastic anemia?
1. Alcoholism which poisions the mitochondria
2. Lead poisioning which inhibits ALAS and Ferrochelatase
3. Vitamin B6 deficency which is a required cofactor for ALAS.
What are the typical lab findings in sideroblastic anemia?
- Ferritin: High
- TIBC: Low (300 µg/dL)
- Serum Iron: High (100 µg/dL)
- % Saturation: High (33%)
Similar to hemochromatosis
Case: 35 year old Asian female presents with recurrent miscarriges. You suspect that the cause is related to a cis deletion on chromosome 16. Which illness are you suspecting?
A cis deletion is most common in Asians and is associated with an increased risk of severe anemia (hydrops fetalis) in the fetus.
Case: Patient presents with fatigue, paleness and angina. You perform electropheresis and find HbH. What is the cause of the patient's symptoms?
Alpha Thalassemia with a tripple delition.
Case: 4 month old italian infant is presenting with severe anemia, hepatosplenomegally, and a dysmorphism to the face causing a chipmunk like apparance. What is the cause of the dysmorphism?
Severe beta thalassemia
Massive erythroid hyperplasia causes expansion of hematopoesis into the skull, facial bones, liver and spleen. The infant is protected in the first few months by HbF (alpha2, gamma2)
What are the symptoms of lead poisioning?
Lead Lines on gingiva (Burton Lines)
ENcephalopathy and Erythrocyte basophilic stipling
Abdominal collic and Sideroblastic Anemia
Drops2 - wrist and foot.
What are the two major subtypes of macrocytic anemia?
Megaloblastic and non-megaloblastic anemia
What are the main causes of Megaloblastic anemia?
- Folate deficency
- Vitamin B12 deficency
- Orotic aciduria
- Diamond-Blackfan anemia
How can you differentiate between folate and B12 deficency without clinical testing?
B12 deficency presents with neurological problems, folate deficiency does not.
Case: Child presents with failure to thrive, developmental delay and megaloblastic anemia refractory to folate and B12. What is the most likely cause of the delay?
Deficiency in de novo pyrimidine synthesis
Case: Child presents with rapidly developing anemia within the first year of life, short stature, craniofacial abnormalities, and triphalangeal thumbs. Which syndrom causes this collection of symptoms?
Intrinsic defect in erythroid progenitor cells.
What are the two main differences in finding between megaloblastic and non-megaloblastic anemia?
- Hypersegmented neutrophils (megaloblastic)
- Glossitis (megaloblastic)
What are the main causes of non-megaloblastic macrocytic anemia?
Alcoholism and liver disease.
What are the main causes of folate deficency?
- drugs (e.g., methotrexate, trimethoprim, phenytoin)
- increased requirement (pregnancy, hemolytic anemia)
What are the three "Ps" of parietal cells?
- Pernicious anemia
What are the main causes of B12 deficency?
- Malabsorption, pernicious anemia, fish tapeworm, gastrectomy, and insufficient intake (rare, mostly vegans)
What are the two main causes of normacytic anemia?
Increased destruction (reticulocyte count >3) or underproduction (reticulocyte count <3)
How does one adjust the reticulocyte count?
Case: Patient presents with fatigue, weakness, lightheadedness and jaundice. He has an increased MCHC and an osmotic fragility test shows increased fragility. You perform a splenectomy to resolve the main symptoms, what type of blood cells will the patient present with after the operation?
Spherocytes are caused by a defect of the RBC cytoskeleton-membrane tethering proteins.
Case: African infant presenting with a streptococcus pneumonia infection as well as swollen hands and feet (dactylitis). She is difficult to examine as she is in so much pain she cannot lay still. You perform a metabisulfit screen which is positive. Which illness is she affected by?
Sickle Cell Disease
What is characteristic for hemoglobin C on blood smear?
Where lies the defect causing Paroxysmal Nocturnal Hemoglobinuria?
Acquired defect in myeloid stem cells results in absence of the anchoring molecule glycosylphosphatidylinositol (GPI). This molecule attatches DAF to the cell membrane. DAF protects against complement.
Why is Paroxysmal Nocturnal Hemoglobinuria mostly active at night?
The shallow breathing during sleep causes a mild respiratory acidosis which activates complement.
What is IgG and IgM mediataed Immune hemolytic anemia associated with, and what type of agglutination is characterisitc for the two types?
IgG: SLE, CLL, and drugs (penicillin and cephalosporins), Warm agglutination in the central part of the body.
IgM: Mycoplasma pneumoniae, Cold agglutination in the extremities.
What is the mechanism of damage behind G6PD deficency?
G6PD plays an important role in the neutralisation of H2O2.
what are the three most common causes of microangiopathic anemia, and what type of cells are produced?
- Microthrombi (DIC, TTP-HUS, HELLP)
- prostetic heart valves
- aortic stenosis
Why is a parovirus B19 infection dangerous in patients with a preexisting anemia causing marrow stress?
It infects progenitor red cells causing a temporarily halt in erythropoesis which leads to significant anemia in patients already under stress.
Case: Patient presents with pancytopenia, and a biopsy reveals an empty fatty marrow. What are the four main etiologies of this disease?
- Autoimmune damage
What is the myelophthisic process?
Pathologic replacement of bone marrow.