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190 Cards in this Set
- Front
- Back
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How many new blood cells are produced each day?
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10-100 BN / day
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Where is the predominate site of hematopoiesis in the 2nd trimester of gestation?
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Liver / spleen
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Where is the primary site of hematopoiesis in the 1st trimester of gestation?
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Yolk sac
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Where is the primary site of hematopoiesis in the 1st decade of life?
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Proximal long bones
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Where is the primary site of hematopoiesis in adults?
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Axial skeleton
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Where is extramedullary hematopoiesis found?
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Liver / spleen
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What factor differentiates hematopoietic stem cells from other marrow cells?
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Stem cells express CD34 on their surface
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What organ produces thrombopoietin?
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Liver
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What organ produces erythropoietin?
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Kidneys
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What cells are found in marrow stroma that secrete hematopoietic growth factors?
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Fibroblasts, macrophages, T cells, and endothelium from the vascular supply
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What do Stem Cell Factor, FLt-Ligand and IL-3 stimulate in hematopoiesis?
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The growth/survival of progenitor cells with pluripotentiality or multipotentiality
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What family of receptors responds to CSFs?
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JAK-STAT superfamily of receptors
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Which types of leukocytes are granulocytes (PMNs)?
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Neutrophils, eosinophils, basophils
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What is another name for azurophilic granules?
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Primary granules
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What is contained in primary granules of promyelocytes?
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Lysosomes
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What do eosinophil granules contain?
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Major basic protein, for killing parasites
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What do basophil granules contain?
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Histamine, heparin for inflammatory reactions
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How long do neutrophils live?
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6-10 hours in blood, 6-10 days in marrow
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What portion of neutrophils in vasculature is circulating vs. marginated?
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50% is marginated
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What is the blue stain on the periphery of this seg, and what is it made of?
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Dohle body. Seen often with left shift, this is the remnant of rough endoplasmic reticulum
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What is a normal Absolute Neutrophil Count?
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>1500-1800
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How do you calculate absolute neutrophil count (ANC)?
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7000wbcs per mm3 X (%polys + % segs) = ANC
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Which of the following are neutropenic patients likely to present with: rubor, calor, dolor
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calor (fever) and other signs of infection at mucous membranes.
May be missing swelling and heat |
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What do chloramphenicol (antibiotic), phenytoin, carbamazapine (anticonvulsants), and chlorpromazine (antipsychotic) have in common?
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All induce neutropenia
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What is by far the greatest cause of aplastic anemia?
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Trick question: Idiopathic is >65% of cases.
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What is Fanconi anemia, and what else is associated with it?
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Congenital aplastic anemia associated with increased solid tumors and leukemias
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What are typical causes of secondary aplastic anemia?
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Ionizing radiation, benzene, organophosphates, ecstasy, drugs, non A/B/C hepatitis, Parvovirus B19
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What kind of infections would a child with Kostmann syndrome suffer from?
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Bacterial (not viral or fungal). Due to a autosomal recessive defect in neutrophil elastase, and treated with recombinant G-CSF
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How often, and for how long, does a person with cyclic neutropenia experience neutropenia?
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Every 3-4 weeks for 3-6 days at a time. Treatment is antibiotics.
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What is the leukemoid reaction, and what is a typical WBC count?
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Leukemoid reaction is an increase in leukocytes, following stress, like disease or hemorrhage.
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Why do glucocorticoids cause neutrophilia?
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Decrease neutrophil entry in tissues
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What can cause eosinophilia?
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Allergies, parasites, Hodgkin's, CML, Acute Leukemia M4-Eo.
Hypereosinophilia syndrome - responds to Gleevec |
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What can cause basophilia?
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Pretty rare, but seen in CML
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What can cause monocytosis?
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Chronic infection (endocarditis or TB), marrow-suppressive chemotherapy, followed by granulocyte recovery
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Where is erythropoietin produced?
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Peritubular cells of kidney, in response to low O2
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What causes microcytic anemias?
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Impaired globin production, from thalassemia or iron deficiency.
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What causes macrocytic anemias?
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Megaloblastic from folate/b12 deficiency.
Non megaloblastic - liver disease, hypothyroid |
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What two common states are typified by macrocytosis without pathology?
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Pregnancy, neonate
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What is a normal reticulocyte percentage of RBCs?
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.5-2%
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What should always be considered in a patient with iron-deficiency anemia?
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Occult bleed, particularly GI
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How do levels of transferrin or TIBC (iron carrier protein) and ferritin (tissue-stored iron) differ between iron-deficient and chronic disease anemics?
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In iron deficiency anemia, ferritin decreases while TIBC increases
In Chronic Disease anemia, both ferritin and TIBC is decreased. |
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What are the storage forms of iron?
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Ferritin (water soluble) and hemosiderin (water insoluble)
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In what form does iron travel in plasma?
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transferrin
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What is average daily iron intake?
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15-20 mg per day, of which about 1mg is absorbed
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What must happen to non heme inorganic iron in the gut before it can be absobed?
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Ferric iron (3+) must be reduced to ferrous iron (2+)
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Why does orange juice increase intestinal absorption of iron?
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It reduces ferric to ferrous iron, and it also complexes with iron in a more absorbable form
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Where does the transporter DMT-1 transport iron from and to?
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From the gut lumen into to the apical brush border side of enterocytes
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Where does the transporter ferroportin transport iron from and to?
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From the enterocyte into plasma (on transferrin). Also encourages iron release from macrophages
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What must happen to dietary iron to move from the enterocyte to the plasma?
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Ferrous iron (2+) must be oxidized to ferrous iron (3+) before moving from enterocyte to plasma
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What is the role of the protein transferrin?
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Binds 2 molecules of iron, carries in plasma and delivers them to bone marrow for developing RBCs
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Where are transferrin receptors found?
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Bone marrow for RBC development, tissue macrophages and enterocytes
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What is the role of ferritin, and where is it largely found?
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Storage form of iron, found everywhere, but particularly in liver, spleen, skeletal muscle, bone marrow and enterocytes
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What is the role of hemosiderin, and where is it found?
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Secondary storage form of iron (broke down ferritin), mostly in bone marrow except in pathologic states
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What is the role of HFE protein?
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Senses Fe levels along with transferrin receptor, and regulates levels of DMT (divalent metal transporter) in enterocytes
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What is the role of hepcidin?
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Inhibits ferroportin, on the basal side of enterocytes, responsible for transporting iron from cell into plasma. Also blocks iron release from macrophages
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What does HFE protein complex with to sense iron levels in gut crypts?
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HFE complexes with transferrin receptor and beta-2 microglobulin. As the cell it is in travels toward a villus tip with enterocyte shedding, it initiates transcription of more DMT-1 which imports iron into enterocyte.
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What is a normal Fe saturation level?
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30% (serum Fe/Total Iron binding capacity)
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What are the symptoms seen in an iron deficient person with Plummer-Vinson (or Paterson-Kelly) syndrome?
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Post cricoid dysphagia
Esophageal webbing/stricture Atrophic gastritis |
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What cytokine is most associated with anemia of chronic disease?
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IL-6, produced by macrophages in chronic inflammation; stimulates hepcidin production in the liver
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Apart from hepcidin's actions in the anemia of chronic disease, what changes are seen in erythropoietin that may exacerbate anemia?
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Decreased epo production, and decrease epo sensitivity in bone marrow
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How does hepcidin inhibit ferroportin's activity of importing iron from enterocyte to serum transferrin?
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Hepcidin binds to ferroportin, causing it to be internalized away from membrane of cell, and eventually degraded
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What causes hemochromatosis?
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HFE hemochromatosis: abnormal HFE impairs sensing mechanism, causes upregulation of DMT1
OR abnormal HFE blocks hepcidin production Ferroportin hemochromatosis: Deficient hepcidin-ferroportin interactions, or faulty hepcidin, cause no decrease in DMT-1 even with adequate stores Juvenile hemochromatosis: faulty hemojuvelin in liver causes deficiency of hemosiderin |
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What genetic mutations are associated with hemochromatosis?
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Mutations of the HFE gene (from crypts in gut that sense iron) on chromosome 6:
C282Y = 80% of clinical H63D, or double heterozygotes sometimes seen |
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How does hemochromatosis typically present?
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Liver function abnormalities
bronze skin Neuro: weakness and lethargy Diabetes Arthralgia Impotence EKG abnormalities |
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Hemojuvelin is required for the synthesis of what peptide?
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Hepcidin - absence of hemojuvelin causes juvenile hemochromatosis
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Describe expected values (high, low, normal) for iron deficiency anemia of:
Serum Fe Transferrin (TIBC) Transferrin sat Ferritin Hemosiderin |
Serum Fe - low
TIBC - high Transferrin sat - low Ferritin - low Hemosiderin - low |
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Describe expected values (high, low, normal) in anemia of chronic disease of:
Serum Fe Transferrin (TIBC) Transferrin sat Ferritin Hemosiderin |
Serum Fe - low
TIBC - low Transferrin sat - normal Ferritin - high Hemosiderin - high |
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Describe expected values (high, low, normal) in hemochromatosis of:
Serum Fe Transferrin (TIBC) Transferrin sat Ferritin Hemosiderin |
Serum Fe - high
TIBC - low transferrin sat - high ferritin - high hemosiderin - high |
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Describe the normal path of hemoglobin from the death of an RBC in the spleen.
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An RBC is phagocytosed at 100-120 days old by a macrophage in the RES (spleen). Globin is broken down to it's amino acids. Protoporphyrin is converted to biliverdin, then bilirubin + CO. Bilirubin circulates bound to albumin, and then is removed from circulation by liver. In liver, bilirubin is conjugated, then excreted into small intestine. C perfringens and E Coli break down conjugated bilirubin to stercobilinogen (excreted in feces) and urobilinogen (reabsorbed, filtered by kidney and excreted in urine)
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Describe the normal path of hemoglobin from the hemolysis of an RBC in circulation.
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Free hemoglobin is released from the hemolysed RBC and is immediately bound to haptoglobin. 2 hemes can bind to a haptoglobin, which circulates until it is removed by the liver. Liver conjugates bilirubin, and excretes to small intestine. C perfringens and E Coli convert to stercobilinogen and urobilinogen. Some urobilinogen is reabsorbed, filtered by kidney and excreted in urine.
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Describe the effects of hemolysis sufficient to ovewhelm free haptoglobin stores.
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Free hemoglobin circulates in plasma, is filtered by renal tubules, converted to hemosiderin and sloughed into urine. Free hemoglobin can spontaneously oxidize and be excreted as methemoglobin, or it may circulate with hemopexin or bound to albumin
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Which of the following are true of all hemolytic anemias, and which are only true of intravascular hemolytic anemia?
Reticulocytosis Increased LDH Absent haptoglobin Positive serum free hemoglobin Increased indirect bilirubin Increased urinary urobilinogen Positive urinary hemosiderin or hemoglobinuria |
All hemolytic anemia:
Increased LDH Reticulocytosis Increased ind. bilirubin Increased urinary urobilinogen Intravasc hemolysis only: Absent haptoglobin Increased urinary hemosiderin/hemoglobin Positive free hemoglobin in serum |
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How does hereditary spherocytosis progress from cause to effect?
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Cause: deficiency in any one of 5 structural proteins attaching cytoskeleton to membrane, AND spectrin (cytoskeletal fiber) deficiency leads to membrane weakness. As cells pass through spleen, chunks get torn off without RBC volume loss, leading to loss of donut shape. Spherocytes are preferentially targeted by macrophages in spleen for destruction
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What are the 3 top protein deficiencies that cause hereditary spherocytosis?
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Ankyrin/Spectrin (60%)
Band 3 (23%) Pallidin (2%) |
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What is the classic presentation for hereditary spherocytosis
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anemia, jaundice, splenomegaly, gallstones (50%)
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What events can precipitate a crisis in a patient with hereditary spherocytosis?
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transient bone marrow suppression (B19 virus), infection, megaloblastic folate depletion
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What happens to MCHC in spherocytosis?
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Increases - lost surface area increases the avg amount of hemoglobin per cell
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What is a long-term risk of performing splenectomy in a pt with hereditary spherocytosis?
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Fulminant sepsis (.73 / 1000 pt years), particularly children younger than 6
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Which variant of Glucose 6 Phosphate dehydrogenase is associated with clinically significant hemolysis in the presence of fava beans?
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G6PD Mediterranean
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What test can confirm hereditary spherocytosis?
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Osmotic fragility test: HS cells are more likely to repture in increasingly hypotonic solution
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Why is G6PD needed for red blood cell survival?
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It oxidizes NADP to NADPH, which donates a proton to glutathione. Reduced glutathione acts as a buffer for peroxides, preventing damage to hemoglobin which would eventually kill the RBC
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What immunoglobulin is implicated in warm antibody hemolysis vs. cold antibody hemolysis?
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Warm = IgG
Cold = IgM |
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What is the Coombs test?
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Used to confirm warm antibody hemolytic anemia: IgG antiserum is added to a blood sample. If the patient's RBCs are coated in IgG, the cells will clump (positive)
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What diseases are often seen with warm antibody autoimmune hemolytic anemia?
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Lymphoma, Lupus or collagen vascular disease
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Where does cold-antibody autoimmune hemolysis occur?
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IgM fixes complement, and is caught in Kupper liver cells, eventually leading to RES and intravascular destruction
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How do cold-antibody hemolysis patient present?
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With anemia sx, as well as acryocyanosis in cold weather. May be in conjuction with mycoplasma or mono infection
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Which of the following generally causes greater plasma free hemoglobin? Cold or warm antibody hemolysis?
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Cold antibody hemolysis
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What heart valve is most associated with hemolysis?
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Aortic
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Contrast hemolysis of TTP vs. hemolysis of DIC
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In DIC, strands of fibrin in arterioles shear RBCs.
In TTP, clumps of platelets in capillaries break RBCs |
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What autoimmune theory is proposed for pernicious anemia?
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Auto-antibodies directed at gastric parietal cell, intrinsic cell (preventing binding with B12 or reacting with intrinsic-B12 complex)
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What neurologic symptoms are possible in B12 deficiency?
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Loss of sensation, gait abnormalities or spasticity
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Where does B12 deficiency hemolysis take place?
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Bone marrow (intramedullary)
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How can Methylmalonate and homocysteine levels help distinguish between a B12 deficiency and Folate deficiency?
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B12 deficiency: MMA and homocysteine elevated (B12 helps metabolize both)
Folate deficiency: homocysteine elevated (folate metabolizes homocysteine) |
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How do you test for source of B12 deficiency (Schilling)?
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Give parenteral B12 to saturate binding sites in body, then radiolabeled PO B12. If radiolabeled B12 appears in urine, it was absorbed in GI tract - normal. If urine has no B12, repeat Step 1, but also give intrinsic factor. If urine has B12, intrinsic factor problem (gastrectomy?). If urine has no B12, could be a terminal ileum absorption problem.
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What patient populations are susceptible to B12 deficiency?
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Gastrectomy, bacterial overgrowth (post Billroth procedure for ulcers), D latum infection, or Crohn's disease
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Which deficiency can occur faster from normal levels? B12 of folate
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folate (months)
B12 (years) |
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Why is alcohol so bad for blood?
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Direct toxic affect on pronormoblasts
Blocks folate absorption from GI Usually reduced folate consumption, too |
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Like Crohn's disease and B12, what malabsorptive disease is associated with folate deficiency?
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Sprue (Celiac)
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If you suspect folate deficiency, should you pay more attention to an assay of serum or RBCs?
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RBCs - less sensitive to recent meals and more reflective of folate over time
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What blood type is most associated with pernicious (B12) anemia?
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A, and in northern europeans
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What organ is very commonly affected by other disorders in a patient with pernicious anemia?
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Thyroid (Hashimoto's, hypo, thyrotoxicosis)
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What does vonWillibrand factor bind?
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GpIb receptor on platelets to collagen
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What is exposed in endothelial tissue injury?
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Collagen and Tissue Factor
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What events accompany platelet activation?
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-Conformational change (sticky)
-Activate GpIIbIIIa receptor -ADP and Thromboxane A2, serotonin released |
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What does GpIIbIIIa bind?
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platelets to other platelets
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What do ADP, serotonin and TXA2 effect in platelets?
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Released when one platelet activated, encourage other platelets to activate
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How long do platelets survive in periphery?
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8-10 days
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At what platelet count can you expect spontaneous bleeds?
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<20K / mm3
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Is this typical of primary or secondary hemostasis deficiency?
Microhemorrhage, easy bruising, petechiae, heavy periods, gingival bleeding, nosebleeds |
Primary hemostasis problem
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How is idiopathic (immune) thrombocytopenia diagnosed?
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Isolated low platelets without another reason found.
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Which age group is associated with a better spontaneous remission rate of ITP?
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Children are likelier to spontaneously remit (opposite with adults)
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In a patient whose platelet count drops by 50%, is Type I or Type II HIT more likely?
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Type II - more serious
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What are IgG and IgM in HIT attaching to?
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Heparin/platelet Factor IV complex
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What are the clinical manifestations of HIT?
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Thrombosis
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What tests can you order to confirm suspicion of HIT?
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ELISA - sensitive, but not specific
Serotonin-release assay |
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What does ADAMTS13 deficiency cause?
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ADAMTS13 normally cleaves unused vWF from surface of platelets. Without cleavage, long vWF makes platelets sticky. Platelets are consumed and lead to TTP
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What is the TTP pentad?
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Fever
Thrombocytopenia Microangiopathic hemolysis(schistocytes) Renal Failure Neurologic sx |
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What is Bernard Soulier syndrome?
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Deficiency in GPIbIX, causing unstable platelet adhesion to exposed vWF
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What is Gray platelet syndrome?
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Absent alpha granules
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What is Glanzman's Thrombasthenia?
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Gp IIbIIIa deficiency, leading to unstable platelet aggregation (platelets don't stick to each other well)
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What is the bridge between aggregated platelets made of?
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GpIIbIIIa and fribrinogen
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What will thrombocytopenia or defective platelets cause?
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Primary hemostasis deficiency - easy bruising/bleeding, mucosal bleeding, prolonged bleeding from cuts
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What does platelet activation and exposed tissue factor generate?
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Activation of the coagulation cascade: secondary hemostasis
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How do you interpret an INR of 2?
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Clot takes 2x the normal time to form.
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What are the 3 steps of fibrinogen conversion to fibrin?
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1. Fibrinogen cleaved by thrombin to form fibrin monomors and fibrinopeptides
2. Fibrin monomers spontaneously form polymers connected by hydrogen bonds 3. Using thrombin, Ca, and Factor XIII, fibrin polymers are stabilized with covalent bonds |
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What cleaves fibrin?
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Plasmin, which is activated from plasminogen by tPA, itself activated by the original endothelial injury.
Limits extent of clot formation |
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What deficiencies lead to Hemophilia A and B, respectively?
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Factor VIII - Hemophilia A
Factor IX - Hemophilia B |
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What mode of inheritence do Hemophilia A and B exhibit?
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X-linked, though 30% of Hemophilia A cases are spontaneous
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What mutation accounts for almost half of hemophilia A cases?
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Inversion of Factor VIII intron at intron 22
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Which hemophilia is more common?
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Hemophilia A (5X hemophilia B)
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At what sites do hemophiliacs tend to bleed?
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Joint: Elbows/knees more than other sites
Muscle: Flexors more than extensors (iliopsoas, quads, gastroc) Post circumcision/dentistry NOT from minor scrapes and cuts |
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How is the clinical severity of hemophilia classified?
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By % of functioning Factor VIII (or IX)
Severe = <1%, Mod = 1-5%, Mild = >5% |
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What measure of coagulation is altered in Hemophilia - PT or PTT?
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PTT is elevated
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Why does von Willibrand disease cause both mucocutaneous and post operative bleeding?
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vWF is important for both platelet adhesion to endothelium, and is a carrier of Factor VIII in intrinsic pathway for stable clot formation
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What type of von Willibrand disease also causes thrombocytopenia?
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vonWillibrand disease Type IIB = thrombocytopenia
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A female patient presents with symptoms very similar to hemophilia - hemarthrosis, prolonged bleeding after dentistry. What disease would you like to test for?
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Von Willibrand disease Type IIN - defective binding to Factor VIII
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What clotting factors utilize Vitamin K in their synthesis?
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X, IV, VII, II
(1972) |
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What bleeding test abnormalities do you expect with Vit K deficiency?
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Elevated PT - Factor VII is affected first.
Eventually elevated PTT |
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What are the major sources of Vitamin K?
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Gut flora, and green vegetables
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What bleeding test abnormalities are seen in liver disease?
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Elevated PT and PTT
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What is the highlight of DIC?
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Fibrin deposition in the arterioles, which shears red cells, depletes clotting factors and causes excessive bleeding and organ failure
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What coagulopathy are AML, obstetric complications and trauma associated with?
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DIC
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What do you expect to happen to the following in DIC?
Platelets, clotting factors, fibrinogen, d-dimer, PT/PTT |
Decreased: platelets, clotting factors, fibrinogen
Increased: d-dimer, PT/PTT |
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How can you tell the difference between DIC and liver disease?
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Factor VIII will not be low in Liver disease, but will be depleted in DIC
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What is Virchow's triad, the conditions that lead to hypercoagulability?
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Slowing down of blood, hypercoagulable state (inherited or acquired), endothelial injury
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DVT is diagnosed based on clinical suspicion. What test can RULE OUT DVT?
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D-dimer. Negative rules out DVT
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Describe what differs from the normal clotting cascade in a Factor V Leiden patient?
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FVL leads to Activated Protein C (natural anticoagulant) resistance, leading to unopposed clotting
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What bleeding test abnormality would you expect in a Factor V Leiden patient?
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PTT, unless you add activated protein C to the tube
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Members of what population are likeliest to experience a Factor V Leiden-related clot?
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Caucasians, homozygous for Factor V Leiden mutation
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What is the purpose of Proteins C and S
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Protein C inactivates Factor VIIIa and Va (natural anticoagulant).
Protein S is a protein C cofactor |
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Which of the following is likeliest to experience a clot by the age of 50?
Factor V Leiden Protein C mutation Protein S mutation Antithrombin deficiency |
Antithrombin deficiency (65% of heterozygotes by age 50)
Protein S mutation (50% by age 35). FVL and ProC are 50% by 50 |
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What two deficiencies are associated with purpura fulminans?
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Protein C and Protein S deficiencies*
*Purpura fulminans after chicken pox may be due to an autoantibody against Protein S (acquired) |
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How does Antithrombin work?
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Blocks factor Xa, and thrombin
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Should a woman with Prothrombin mutation G20210A be on lifelong anticoagulation?
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No - weak clotting risk factor, like Factor V Leiden
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What bleeding test abnormalities do you expect to see with antiphospholipid antibodies (e.g., lupus)
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Increased PTT, but CLOTTING
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A 60-year-old female presents with a PE. The ER sent a hypercoagulable workup revealing low protein C activity at 22%, low protein S activity at 24%, and no presence of mutations for factor V leiden or prothrombin G20210A. Which of the following best describes the patient’s condition?
The patient has protein C deficiency The patient has protein S deficiency The patient has both protein C and S deficiencies The patient has factor V leiden deficiency There is no evidence of a hypercoagulable state |
No evidence of a hypercoag state: low levels are result, not cause of clotting
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A 20 year old female experiences leg swelling after a 18 hour airplane ride. She is found to have an extensive DVT. Her mother had a blood clot in her 20’s. What testing should be sent?
A. Factor V Leiden, PT gene mutation, Protein C and S, antithrombin, antiphospholipid antibodies B. Protein C and S and antithrombin C. Protein C and S, antithrombin, and antiphospholipid antibodies D. Factor V Leiden and PT gene mutation E. No testing for hypercoagulable states |
A. Factor V Leiden, PT gene mutation, Protein C and S, antithrombin, antiphospholipid antibodies
- STRONGLY thrombophilic, history of young clots in the family |
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A 45 year old man presents with a middle cerebral artery stroke. His father had an MI at age 45. What testing should be done?
A. Factor V Leiden, PT gene mutation, Protein C and S, antithrombin, antiphospholipid antibodies B. Factor V Leiden, PT gene mutation, Protein C and S, antithrombin C. CBC, cholesterol, antiphospholipid antibodies D. Factor V Leiden and PT gene mutation E. Protein C and S, antithrombin, and antiphospholipid antibodies |
C. CBC, cholesterol, antiphospholipid antibodies
This was an ARTERIAL clot |
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A 10 year old boy develops severe joint swelling and pain after being kicked in the knee during his first soccer game. He is found to have a hemarthrosis. He has no bleeding history. He is adopted and does not know his family history. Which statement is true?
A. This type of bleeding suggests a disorder of primary hemostasis and workup should include platelet count B. This bleeding pattern suggests mild hemophilia (factor level >5%) C. This bleeding pattern suggests severe hemophilia (factor level <1%) D. The patient’s father must have had a bleeding disorder |
B – he got kicked to bleed, and was later in life and with trauma.
Not D because it isn’t necessarily inherited |
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A 32 year old woman presents with frequent bruising. She had some delayed bleeding after having oral surgery at age 20. She has heavy menses. Which statement is true?
A. This describes a problem with primary hemostasis only. Workup for thrombocytopenia. B. This describes a problem with secondary hemostasis only. Workup for hemophilia. C. This describes a problem with primary and secondary hemostasis. Workup for vWD. D. This describes a problem with primary and secondary hemostasis. The patient may have hemophilia and thrombocytopenia. |
C – vWD involved in primary, and factor VII in secondary
Heavy menses can be either primary or secondary |
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A 50 year old man presents with an arterial clot in his left leg. Initial workup reveals platelet count of 80K and an elevated PTT. What further testing should be sent?
A. Factor VIII and IX levels B. Testing for vWD C. Lupus anticoagulant D. Anticardiolipin antibodies E. Lupus anticoagulant, anticardiolipin antibodies, and β2-glycoprotein antibodies |
E. Arterial clot, elevated PTT, associated thrombocytopenia because platelets are activated and used up. Anti-phospholipid antibody problem, test for all 3.
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A 50 year old man with chronic heavy alcohol use presents with bleeding. Which testing would be most helpful in differentiating whether he has liver disease or DIC as the cause of his bleeding?
PT and PTT Factor II, VII, IX, X Platelet count Protein C and S Factor VIII |
Factor VIII – only one not produced by liver
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How many molecules of O2 can normal hemoglobin carry?
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4 O2 molecules
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From what chromosome do the hemoglobin precursors come?
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16: alpha-like chains
11: beta-like chains |
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What are the embryonal hemoglobin (Gower 1 & 2)subunits?
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zeta (embryo alpha)
epsilon (embryo beta - Gower 1) gamma (embryo beta Gower 2) |
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What is embryonal transitional hemoglobin composed of (Portland)?
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alpha1/2 (adult alpha)
epsilon (embryo beta) |
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What is fetal hemoglobin (F)composed of?
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alpha1/2 (adult alpha)
gamma (same as embryo beta Gower) |
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What is adult hemoglobin composed of (A and A2)?
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alpha 1/2 (adult alpha)
beta/delta (adult betas) |
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What causes thalassemia
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A missing hemoglobin chain which causes the other subunit to dimerize. They precipitate in the RBC and cause hemolysis.
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What is hemoglobin Barts composed of?
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In a-thal - fetal hemoglobin composed of gamma tetramers because all 4 alpha chains knocked out.
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What is hemoglobin Constant Spring composed of?
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a-thal variant: elongated alpha chain breaks down mRNA that would otherwise produce normal alpha chains. WORSE than alpha knockout because it messes up normal production.
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How can you diagnose Hemoglobin Constant Spring?
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Hgb electropheresis - Constant Spring elongated alphas make hemoglobin bulky and they don't move as quickly as other hemoglobins.
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What is the characteristic MRI finding in Beta Thalassemia?
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Black heart on MRI - anemia causes increased iron absorption, and eventually overload
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How do you characterize thalassemia severity?
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Clinical picture: trait means you have mutation without symptoms.
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Why does deletion of all a chain genes cause death in the fetus, but deletions of all the b chain genes do not appear clinically until > 4 months of life?
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Fetuses and newborns have g chains to mop up extra a chains to maintain balance
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How can you tell the difference between thalassemia and iron deficiency anemia?
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Thal is more microcytic than Fe deficiency, and Fe deficient can make retics and extra thrombocytes
MCV/RBC count = Mentzer index. <12 = thalassmia >13 = iron deficiency anemia |
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Will a patient with a two a chain deletion and has b0 thal have MORE or LESS severe disease than b0 thal alone?
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Less severe due to less of an imbalance of a and b chains
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What is Hemoglobin Lepore composed of?
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a crossover at Chromosome 11 causes a hybrid beta-delta globin. Clinically presents as a beta-thal
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What population is hemoglobin C found in?
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Africans - worry about Hgb S compounding
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What population is hemoglobin E found in?
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SE asians - worry about alpha thalassemia compounding
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How do you identify hemoglobin C on periph smear?
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target cells on smear
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What is the hallmark of a Sickle Cell crisis?
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PAIN from venous occlusion - bone marrow or spleen, lung.
Stroke, priapism, retinopathy or renal dysfxn |
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What kind of infections are sickle cell patients susceptible to?
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encapsulated bacteria due to poor splenic fxn (normal a good spot for complement fixing)
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What hemoglobin chain is associated with sickle cell disease?
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Beta
(remember, in alpha thalassemia, Barts dies because no other alphas after embryonal stage) |
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If a baby shows on newborn screen to have sickle cell disease (FS on newborn screen), but the parents have no history of sickle cell, what do the parents have?
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Both parents are HbAS (sickle cell trait)
OR One parent is HbAS (sickle cell trait) and the other is HbA-b0 thal (b thalassemia trait) |
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What is one potential reason for lower white counts in people of African descent?
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Lower white counts probably correct for higher production induced by anemia with HbS. The combination is probably protective against malaria
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What protein is responsible for the breakdown of unbound plasmin?
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alpha-2 antiplasmin
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What inhibits tPA?
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Plasminogen activator inhibitor (PAI)
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What is responsible for the release of tPA from endothelium?
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Fibrin - it's stimulation of tPA release is a built in balance to clot formation
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What are the activators and inhibitors of plasmin?
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tPA = activator
alpha-2 antiplasmin, PAI = inhibitor |
