Week 1 Flashcards
Match the following RBC morphologies with its associated condition (hint: it may be helpful to write this down on scratch paper to compare to the answer)
- Central pallor
- Target cell
- Acanthocyte (long projections)
- Burr cell
- Schistocytes
- Spherocytes
- Bite/ Blister cells
- Chronic liver disease
- Liver disease and thalassemia
- Kidney disease
- Iron deficiency anemia (also in thalassemia)
- Microangiopathic hemolysis
- Heinz body hemolysis
- Immune-mediated hemolysis
Answer:
- Central pallor – iron deficiency anemia (also in thalassemia)
- Target cell – liver disease and thalassemia (can also be seen in sickle cell, although sickled cells are the hallmark)
- Acanthocyte (long projections) – chronic liver disease
- Burr cell – kidney disease
- Schistocytes – microangiopathic hemolysis (due to small clots shearing RBCs)
- Spherocytes – immune-mediated hemolysis
- Bite/ Blister cells – heinz body hemolysis (G-6-PD deficiency, unstable hemoglobin, oxidant drugs)
Explanation:
Central pallor occurs with iron deficiency due to the decreased production of hemoglobin. Target cells occurs when there is an excess of membrane area compared to cell volume. Therefore when viewed in cross section there appears to be a bleb of membrane at the center of a red blood cell when there is less hemoglobinin the cytoplasm (this can be seen in liver disease and beta-thalassemia).. Bite/Blister cells occur when oxidative stress precipitates hemoglobin as Heinz bodies, which get removed by splenic macrophages (they effectively take a bite of the cell). Schistocytes occur when red blood cells are sheared most frequently as they pass through microthrombi in capillaries. Spherocytes occur when splenic macrophages consume portions of the red blood cell membrane due to antibodies coating their surface (as in immune mediated anemias) or there is an abnormal membrane structure due to a membrane protein defect (as in hereditary spherocytosis).
Lecture: 240b Intro to CBC
Learning Objective: 3. Recognize variations in red cell morphology and the associated underlying clinical conditions (MKS 1b, 1d)
Name 3 possible presenting symptoms of anemia.
Answer: headache, tachycardia, palmar pallor, dyspnea on exertion
Explanation: Anemia is reduced number of red blood cells. When red blood cell number declines, so does oxygen delivery to tissues. The body will compensate by pumping the blood faster, resulting in tachycardia. Because of this compromised oxygen distribution, when the body is challenged (ie when getting up quickly), it is unable to compensate for the challenge, resulting in dyspnea on exertion and headaches. Palmar (and conjunctival) pallor quickly reveal the low number of circulating red blood cells in the bloodstream.
Lecture: 241b Approach to Anemias
Learning Objective: 3. Identify
Which of the following are derived from a Lymphoid Blast (aka Common Lymphoid Progenitor)?
- Red Blood Cells
- Platelets
- Macrophages
- T Cells
Answer: D. T Cells
Explanation: Hematopoietic stem cells differentiate into either a common lymphoid progenitor (lymphoid blast) or common myeloid progenitor (myeloid blast). Note how many different types of cells come from the common myeloid progenitor: red blood cells, platelets, macrophages, granulocytes. On the other hand, the common lymphoid progenitor develops into either B cells or T cells.
Lecture: 242b Stem cells and Erythropoiesis
Learning Objective: 1. Describe the defining characteristics of hematopoietic stem cells including differences with embryonic stem cells. MKS1a
A 14 year old patient comes in with fever, back pain, and what they describe as “dark urine.” They recently were prescribed Trimethoprim-sulfamethoxazole for bronchitis. On blood smear, you see bite cells. What is the most likely diagnosis?
- G6PD deficiency
- Sickle cell anemia
- Hereditary spherocytosis
Answer: A. G6PD deficiency
Explanation: G6PD is an enzyme that helps generate NADPH which can help reduce reactive oxygen species. Without the enzyme, cells are more susceptible to oxidative stress. Anything that worsens that oxidative stress (sulfa drugs, infection, or fava beans) can trigger an episode of hemolysis that presents with fever, back pain, and dark colored urine. Bite cells form due to the precipitation of hemoglobin as Heinz bodies in the presence of reactive oxygen species. Splenic macrophage will ‘bite’ out the Heinz bodies, forming bite cells.
Lecture: 243b Congenital Hemolytic Anemia and Sickle Cell Disease
Learning Objective: 3. Describe the pathophysiologic mechanisms, epidemiology and clinical findings associated with the most common inherited disorders of the RBC membrane (spherocytosis, ovalocytosis) and metabolic pathways (G6PD deficiency, PK deficiency) (MKS, 1b, 1d, 1f)
Which of the following statements about autoimmune hemolytic anemia (AIHA) is most accurate?
- Warm Antibody AIHA is extravascular hemolysis caused by IgG coating the RBC, inducing consumption in the spleen. Cold Antibody AIHA is intravascular hemolysis caused by IgM binding the red blood cell and stimulating complement.
- Warm Antibody AIHA is intravascular hemolysis caused by IgG coating the RBC, inducing consumption in the spleen. Cold Antibody AIHA is extravascular hemolysis caused by IgM binding the red blood cell and stimulating complement.
- Warm Antibody AIHA is extravascular hemolysis caused by IgM binding the red blood cell and stimulating complement. Cold Antibody AIHA is intravascular hemolysis caused by IgG coating the RBC, inducing consumption in the spleen.
Answer: A. Warm Antibody AIHA is extravascular hemolysis caused by IgG coating the RBC, inducing consumption in the spleen. Cold Antibody AIHA is intravascular hemolysis caused by IgM binding the red blood cell and stimulating complement.
Explanation: Extravascular hemolysis refers to hemolysis that occurs in the spleen. When IgG coats a red blood cell, it results in cell lysis by splenic macrophages,seen in Warm Antibody AIHA. Warm AIHA can be primary or secondary (associated with lymphoma, autoimmune disorders, infections, or tumors). Intravascular hemolysis refers to hemolysis that occurs in the blood vessels. When IgM binds red blood cells, complement can become activated and result in lysis of the red blood cells, as in Cold Antibody AIHA. It is named Cold Antibody AIHA because the antibodies are typically reactive at temperatures cooler than body temperature. The antibody coated red blood cells will agglutinate at cooler temperatures also. Cold Antibody AIHA can be primary or secondary (associated with Mycoplasma, Mononucleosis, or lymphoma).
Lecture: 244b Acquired Hemolytic Anemias
Learning Objective: 2. Describe the pathologic mechanism of immune-mediated red blood cell hemolysis. (MKS-1b)
: Do you expect the following lab parameters to be increased or decreased in iron deficiency anemia?
- Iron
- Ferritin
- Hepcidin
What about for anemia of chronic disease (due to inflammation)?
- Iron
- Ferritin
- Hepcidin
- ESR/CRP
Answer and explanation:
Iron deficiency anemia
Low iron (iron is depleted either due to losing too much iron in an active bleed or not getting enough iron due to diet or malabsorption). Serum iron is not a reflection of iron stores, and a recent ingestion of iron in the diet can transiently raise serum iron levels, even if the total body stores of iron (ferritin) are low.
Low ferritin (ferritin represents iron stores and eventually gets depleted, and if low is the most sensitive measure of body iron stores
Iron deficiency anemia downregulates hepcidin production, in order to make sure the iron channel is open, and that iron is available
Anemia of chronic disease
Low iron When inflammation occurs, it is an innate and evolutionary response to hide iron. (the body thinks its fighting an infection and will purposely reduce available iron to impair bacterial survival.). Low iron occurs because hepcidin increases, binds ferroportin, and degrades the iron channel
High Ferritin (the body reduces available iron by producing hepcidin which will sequester iron for storage. The body is getting plenty of iron but its getting put away in storage in the form of ferritin; ferritin also increases because it is an acute phase reactant)
High hepcidin—inflammation triggers hepcidin production, which limits iron availability, as above
High ESR and CRP (these acute phase reactants are indicators of inflammation)
Lecture: 245b Iron and Anemia of Chronic Disease
Learning Objective: 3. Describe the clinical, laboratory manifestations, and treatment of iron deficiency anemia—MKS 1b, 1d, 1e
Describe the expected findings for the following parameters in B12 deficiency vs folate deficiency.
- Homocysteine
- Methylmalonyl-CoA
- Neurologic Symptoms
Answer: B12 deficiency will have high homocysteine and high methylmalonyl-CoA with neurologic symptoms (dementia, personality change, loss of vibration/position sense and parasthesias of hands and feet). Folate deficiency will have high homocysteine, normal methylmalonyl-CoA, and no neurologic symptoms (except for the possibility of neural tube defects in pregnant patients).
Explanation: Folate donates a methyl group to tetrahydrofolate reductase, which is then passed on to B12, which transfers the methyl group from homocysteine to make methionine. This is why there is high homocysteine in both B12 and folate deficiency. B12 is involved in a peripheral pathway and helps to convert methylmalonic acid into succinyl-CoA. That’s where there is high methylmalonyl-CoA in only B12 deficiency. Build up of methylmalonyl-CoA in myelin of the spinal cord is also what leads to the neuro symptoms only seen in B12 deficiency. This whole pathway makes DNA precursors. Without DNA precursors, red blood cells make 1 less division since there is not enough material to divide, resulting in larger (megaloblastic/macrocytic) red blood cells.
Lecture: 246b Megaloblastic Anemias
Learning Objective: 2. Describe the metabolism and absorption of vitamin B12 and folic acid metabolism, and accordingly, associated disease states that lead to deficiency states (MKS 1a,1b, 1d)
Match the presentation to the genetic defect of these variations of thalassemia.
- 1 alpha-chain gene deleted
- 2 alpha-chain genes deleted
- 3 alpha-chain genes deleted
- 4 alpha-chain genes deleted
- 1 gene with diminished beta-chain production
- 2 genes with no beta-chain production
- Asymptomatic, microcytosis
- Severe anemia, HbH production (beta4)
- Hydrops fetalis, HbBarts (alpha4)
- Asymptomatic with increased RBC count, microcytosis
- Severe anemia a few months after birth, with massive erythroid hyperplasia and dependence on transfusions
- Mile anemia with increased RBC count
Answer:
- 1 alpha-chain gene deleted – asymptomatic, microcytosis
- 2 alpha-chain genes deleted – Mild anemia with increased RBC count
- 3 alpha-chain genes deleted – Severe anemia, HbH production (beta4)
- 4 alpha-chain genes deleted – Hydrops fetalis, HbBart’s (gamma4)
- 1 gene with diminished beta-chain production – Asymptomatic with increased RBC count, microcytosis
- 2 genes with no beta-chain production – severe anemia a few months after birth, with massive erythroid hyperplasia and dependence on transfusions
Explanation: There are 3 types of normal hemoglobin: Fetal hemoglobin (HbF) made of 2 alpha chains and 2 gamma chains (alpha2gamma2). Adult hemoglobin (HbA) made of 2 alpha chains and 2 beta chains (alpha2beta2). And Hemoglobin A2 made of 2 alpha chains and 2 delta chains (alpha2delta2). Alpha thalassemia is due to disruption in the genes for alpha chain expression and Beta thalassemia is due to disruption in the genes for beta chain expression. There are 4 genes for alpha chain expression so alpha thalassemia severity will vary based on the number of disrupted genes. When 3 alpha-chain genes are deleted, the produced beta chains will form tetramers (HbH) that will damage red blood cells. When all 4 alpha-chains are deleted, the gamma chain from fetal hemoglobin will form tetramers that damage red blood cells. There are 2 genes for beta chain expression, but 2 possible variants of the gene: one that leads to reduced production of the beta chain and one that leads to no production of the beta chain. Having 1 gene with diminished beta-chain production and the other chain normal leads to Beta Thalassemia Minor (and is asymptomatic with increased RBC count). Having both genes with no production of the beta-chain leads to the most severe form of the disease and is called Beta Thalassemia Major.
Lecture: 247b Thalassemia
Learning Objective: 2. Explain how the pathophysiology in thalassemia results in the clinical manifestations of thalassemia.(MKS 1d, 1b)
Question: How do you distinguish a clotting factor deficiency disorder from a clotting factor inhibitor?
Answer and explanation: A mixing study: Mix patient plasma with normal plasma. If there is a deficiency, mixing will correct the PT or PTT, as the normal plasma contents will compensate for the deficiency. If there is an inhibitor, mixing will NOT correct the PT or PTT as the inhibitor from the patient plasma will inhibit the clotting factors in the normal plasma.
Lecture: 248b Coag and Inherited Bleeding
Learning Objective: 3. Describe the laboratory tests which can be performed to evaluate a patient for a bleeding disorder. (MKS-1d)
: Fill in the blank in the description below for the formation of a platelet plug.
Endothelial injury will reveal subendothelial collagen at the site of injury. ______ lines subendothelial collagen. Von Willebrand factor will bind _____ on the platelet. This interaction with collagen will initiate increased intracellular_____, which leads to platelet release of_____, which will upregulate the fibrinogen receptor, and platelet release of _____, which will induce expression of GIIbIIIa on the platelet. ___ will bind GpIIbIIIa on one platelet and the fibrinogen receptor on another platelet, forming a fibrinogen crosslink, which will eventually lead to the platelet plug as more fibrinogen crosslinks form.
Answer: Endothelial injury will reveal subendothelial collagen at the site of injury. Von Willebrand factor lines subendothelial collagen. Von Willebrand factor will bind GpIb on the platelet. This interaction with collagen will initiate increased intracellular calcium, which leads to platelet release of thromboxane A2, which will upregulate the fibrinogen receptor and recruit other platelets, and platelet release of ADP, which will induce expression of GPIIbIIIa on the platelet. Fibrinogen will bind GPIIbIIIa on two platelets forming a fibrinogen crosslink, which will eventually lead to the platelet plug as more fibrinogen crosslinks form.
Lecture: 249b Platelet Function and Formation
Learning Objective: 3. The student will be able to explain the major features of platelet function and how platelets contribute to hemostasis. (MKS 1a)
You are following a patient after a major surgery. The patient was given heparin for DVT prophylaxis. On day 7 post-op, you look at the patient’s CBC and see a 50% reduction in platelet count. What’s the most likely diagnosis?
Answer: Heparin Induced Thrombocytopenia
Explanation: Heparin Induced Thrombocytopenia is due to an antibody against heparin-platelet factor 4 complex after a patient is given heparin (unfractionated or Low molecular weight). To treat, you’ll stop all heparin and treat with direct thrombin inhibitors instead of heparin.
Lecture: 250b Thrombocytopenias
Learning Objective: Describe the pathophysiology, presentation, and treatment of heparin-induced thrombocytopenia (MKS 1b,1d,1e)
For a standard dose and average size patient, what change should you see on CBC for that given parameter?
- 1 dose packed RBC (300 mL per dose) = _____ rise in HgB/dL
- 300 mL plateletpheresis donor = ____ K/uL rise immediately in platelets
- Cryoprecipitate (2 g fibrinogen) = ____ mg/dL rise in fibrinogen
Answer:
- 1 dose packed RBC (300 mL per dose) = 1g rise in HgB/dL
- 300 mL plateletpheresis donor = 25-30 k/uL rise immediately in platelets
- Cryoprecipitate (2 g fibrinogen) = 65 mg/dL rise in fibrinogen
Lecture: 251b Blood Transfusion Indications
Learning Objective: 2. Summarize the contents of and expected responses to transfusions of platelets, plasma, and cryoprecipitate (MKS1e).
Match the mechanism underlying each of the following blood transfusion reactions.
- Allergic reaction
- Febrile reaction
- Transfusion-Associated Circulatory Overload (TACO)
- Acute Hemolytic reaction
- Transfusion Related Acute Lung Injury (TRALI)
- Sepsis
- Transfusion Associated Graft vs Host Disease
- Donor lymphocytes attack patient’s organs (usually patient’s immune system will clear these lymphocytes)
- Bacteria in blood bag
- Patient IgE to plasma components
- Patient IgG to donor RBC’s
- Patient antibody to WBC’s in blood bag
- Increased intravascular volume
- Donor antibodies to patient WBC’s due to donor multiparity
Answer:
- Allergic reaction – Patient IgE to plasma components
- Febrile reaction – Patient antibody to WBC’s in blood product
- Transfusion-Associated Circulatory Overload (TACO) – Increased intravascular volume
- Acute Hemolytic reaction – Patient IgG to donor RBC’s
- Transfusion Related Acute Lung Injury (TRALI) – Donor antibodies to patient WBC’s due to donor multiparity
- Sepsis – Bacteria in blood product
- Transfusion Associated Graft vs Host Disease – Donor lymphocytes attack patient’s organs particularly in immunocompromised patients (usually patient’s immune system will clear these lymphocytes)
Lecture: 252b Blood Transfusions – Compatibility and Complications
Learning Objective: 3. Identify transfusion reactions for indicated therapeutic and preventive measures (MK&S 1d, 1e).
