Anemias, Thrombotic Disorders, Bleeding Disorders Flashcards
What is the definition of anemia?
A reduction in circulating RBC mass.
Name six clinical manifestations of anemia.
- Weakness
- Fatigue
- Dyspnea
- Pale conjunctiva and skin
- Headache, lightheadedness
- Angina, especially when there is pre-existing CAD
What serum Hb value is the cutoff for anemic/not anemic in males and females, respectively?
Anemia is Hb < 13.5g/dL in males and < 12.5g/dL in females
What values correspond to normal MCV?
80-100 fL
What is the differential for macrocytic anemias?
- B12 deficiency
- Folate deficiency
- Orotic aciduria
- Alcoholism
- Liver disease
- Drugs (ex. 5-FU)
Other than measuring serum folate and B12 levels, how can you figure out which is deficient in a person with a macrocytic anemia?
Serum homocysteine and methylmalonic acid levels. If both are elevated, the patient has a B12 deficiency. If only homocysteine is elevated, the patient has a folate deficiency.
What would you see on a blood smear in a patient with megaloblastic anemia?
- Macroovalocytes
2. Hypersegmented neutrophils (>5 lobes)
What is megaloblastic anemia?
A macrocytic anemia caused by either B12 or folate deficiency.
Characterized by macroovalocytes and hypersegmented neutrophils on blood smear, as well as megaloblastic changes in rapidly-dividing cells like GI epithelial cells.
Where along the GI tract is folate absorbed?
Jejunum
In what foods are folate found?
Green vegetables, fruits
Your patient is anemic and a blood smear shows macrocytosis. On physical exam you note glossitis. What diagnosis does this exam finding support?
This supports a B12 or folate deficiency anemia (megaloblastic anemia)
Methotrexate inhibits _________ (an enzyme) and can potentially cause _______ deficiency.
inhibits DHF reductase, can cause folate deficiency
Does the body store much folate? How long does it take to develop a folate deficiency if one suddenly stops eating foods containing folate?
Folate stores are minimal; folate deficiency can develop within months
Describe the process of absorption of B12 in the GI tract.
- B12 binds to haptocorrin/R-binder/transcobalamin, which is made by salivary glands
- In the duodenum, pancreatic enzymes cause dissociation of B12-haptocorrin
- B12 attaches to intrinsic factor
- In the distal ileum, B12-IF binds to cubilin receptors on epithelial cells –> endocytosis
- B12 is released into the blood and binds to transcobalamin/haptocorrin, which is the transport protein for B12 in the blood –> liver (principal storage site for B12)
What foods are B12 found in?
Fish, meat, dairy
Does the body store much B12? How long does it take to develop a B12 deficiency if one suddenly stops eating foods containing B12?
Liver stores a lot of B12 so it takes years to develop B12 deficiency
What is pernicious anemia?
Autoimmune destruction of gastric parietal cells (that make acid and intrinsic factor) –> B12 deficiency
Your anemic patient has lower extremity weakness and hyperreflexive achilles and patellar reflexes. What is possibly going on?
Subacute combined degeneration of the spinal cord from build-up of methylmalonic acid (from B12 deficiency)
Vegans can potentially develop a _____ deficiency due to not ingesting much of it.
B12
In general, anything that disrupts synthesis of ___________ can cause a microcytic anemia.
hemoglobin
What is the differential diagnosis for microcytic anemias?
- Iron deficiency
- Anemia of chronic disease
- Sideroblastic anemia
- Thalassemias
In the early stages of iron deficiency, which lab value would most likely be low: serum iron, TIBC, % saturation, or serum ferritin?
Serum ferritin, because this measures intracellular iron stores, and this is what decreases first
Your anemic patient has mildly low serum iron levels and % iron saturation, but has normal-sized RBCs on blood smear. What is an explanation for this?
Early iron deficiency anemia can cause a normocytic anemia. This is when the bone marrow is simply making fewer RBCs, but they’re normal in morphology.
Other than the six general clinical manifestations of anemia, name two more findings that would be suggestive of iron-deficiency anemia.
- Koilonychia
2. Pica
Describe the pathophysiology of anemia of chronic disease.
Inflammation –> IL-6 upregulation –> upregulation of hepcidin –> endocytosis and degradation of ferroportin –> iron is locked in cells –> microcytic, hypochromic anemia
Hepcidin also suppresses EPO production
What is the treatment for iron-deficiency anemia?
Supplemental iron (oral ferrous sulfate)
What is the most common mutation responsible for hereditary hemochromatosis?
HFE gene mutation
Describe the pathophysiology of hereditary hemochromatosis.
Mutated hepcidin –> uncontrolled uptake and release of iron –> iron overload
You see a patient with a chief complaint of impotence. It is in the middle of winter and the patient is very tan. He also has a laterally displaced cardiac apex and a systolic murmur radiating to the back. What is the treatment for the likely disease this person has?
Hereditary hemochromatosis –> iron overload –> hemosiderin deposition in skin (tan skin) and in myocardium –> congestive HF
Treatment is regular phlebotomies
What syndrome is characterized by the triad of iron-deficiency anemia, dysphagia from esophageal web, and glossitis?
Plummer-Vinson syndrome
Ring sideroblasts are erythroblasts with excess iron inside ________ (an organelle) that stain strongly with prussian blue stain. What is the congenital (inherited) defect that can cause this? How can one acquire this?
This is sideroblastic anemia, a problem with protoporphyrin synthesis.
Iron builds up inside mitochondria in erythroblasts.
Congenital cause: ALA-synthase mutation (1st, rate-limiting step in porphyrin synthesis)
Acquired: toxins: lead poisoning (denatures ALA-DH and ferrochetalase), ethanol, chloramphenicol, isoniazid, B6 deficiency (ALA-S needs it)
Describe the expected lab values one would see in sideroblastic anemia.
It is an iron-overloaded state…
increased ferritin, decreased TIBC, increased serum iron, increased % saturation
What is the differential Dx for normocytic anemias w/ fragments and/or schistocytes on a blood smear?
- Paroxysmal nocturnal dyspnea
- G6PD deficiency
- Immune hemolytic anemia
- TTP
- HUS
- DIC
- Prosthetic heart valves/aortic stenosis
- Malaria
Describe the pathogenesis of paroxysmal nocturnal hemoglobinuria (PNH).
Acquired defect of the GPI in the myeloid stem cell –> DAF (CD55) and MIRL (CD59) can’t attach to RBC surface –> CD55 can’t degrade C3b and CD59 can’t prevent MAC formation –> red cell lysis at night when there is respiratory acidosis (which increases complement activity) from hypoventilation –> hemoglobinuria