Blood and Anemia Flashcards
What are the two main components of blood?
Plasma (55%)
Cells (45%)
What cells are in the blood?
RBC
WBC
Granulocytes (Neutro., Eosino., Baso., Mono., Lympho.,)
What are the sites of hematopoiesis during different life stages?
Fetus: Yolk sac, Bones, liver, spleen
Child: Most bones have red marrow
Adult: Fewer bones have red marrow (Skull, ribcage, sternum, vertebrae, and pelvis)
Where are red marrow sample taken from in adults?
The pelvis
What causes progenitor cells to mature into a specific mature cell?
Due to a unique mix/set of growth factors
8 major hematopoietic lineages are generated my multi potential stem cells
What causes initiation of the intrinsic pathway?
Vessel damage and exposure to vWBF
Factor 12 —> Factor 12a (which stimulates Factor 11—> Factor 11a), This activates Factor 9 —> Factor 9a (which stimulates Factor 10 —> Factor 10a
Factor 9a and 10a are directly inhibited by Warfarin
Xa inhibiting DOACs and Heparin inhibit Factor 10a
What causes the initiation of the extrinsic pathway of clotting?
Caused by trauma
This stimulates conversion of Factor 7 into Factor 7a, which in turn activates Factor 10 into Factor 10a.
Following this point, both intrinsic and extrinsic pathways have shared clotting factors
Activated Factor 10 (Xa), activated Factor 2 into Factor 2A, which in turn activates fibrinogen into fibrin. Fibrin is turned into a fibrin clot after interacting with Factor 13a (XIIIa)
What is the mechanism of Warfarin?
It blocks the Vitamin K dependent process of producing factors II (prothrombin), VII, IX, and X. INR monitoring is essential
What is the mechanism of action for DOACs?
These drugs are Factor 10a (Xa) inhibitors
ex. Apixaban, Edoxaban, and rivaroxaban
What is the mechanism of action for Heparin?
It binds to and activates antithrombin, inactivating Factor Xa and IIa
Often used in acute DVT and MI management
What is the mechanism of action of LMWH?
Similar to heparin, except they have less anti-factor IIa activity vs. anti-factor Xa
Ex. Enoxaparin
What is different about Dabigatran vs. other DOACs in terms of mechanism of action?
Dabigatran is a direct thrombin inhibitor
What is the mechanism of action for Aspirin?
It is an anti platelet drug and it prevents platelets from aggregating.
What is the utility in using a PPI in patients on DOACs + antiplatelet coaguation drugs?
PPIs can limit stomach acidity, effectively reducing the number and severity of potential GI bleeds
What is the primary function of erythrocytes?
They are suited for their primary function (transport of oxygen from the lungs into peripheral tissue
What is anemia?
Anemia is a reduction of hemoglobin in the blood to below-normal levels
Usual definition: less than 13g/dL in males and less than 11.5g/dL in females
What is the common clotting factor where the two pathways converge?
Activation of Factor 10 (X)
What is teh function of thrombin?
Generates fibrin monomers which polymerize to give structural integrity to the clot
How are clots broken down?
Healing endothelium releases tPA which activates plasmin. Plasmin lyses the clot
Do different people have different affinity for oxygen in their hemoglobin?
Yes, namely fetuses and newborns have a type of hemoglobin that has higher affinity to oxygen than adult hemoglobin
What are some causes of anemia?
Low production
Destruction
Bleeding
What is the etiology of anemia?
Appearance of abnormal hemoglobin: abnormal hematopoeisis
Reduced number of RBCs: Decreased hematopoiesis
Structural abnormalities of RBCs: Abnormal hematopoiesis
Anemia may also be a consequence of increased loss or destruction of RBCs
What can cause decreased hematopoiesis?
Aplastic anemia (bone marrow failure)
Myelophthistic anemia secondary to bone marrow replacement with tumour cells
Leukemia
Deficiency disorders (Fe, Viamin B12, proteins)
What can cause abnormal hematopoiesis?
Genetic hemoglobinopathies (sickle cell, thalassemia)
Structural protein defects
What can cause increased loss or destruction of RBCs?
Bleeding (GI bleeds especially concerning to drug therapy)
Immune hemolytic anemia
Hypersplenism (enlarged spleen + anemia
Is RBC shape relevant to function?
Yes, due to internal abnormalities the shape of RBCs can be altered. This altered shape usually reduces function
What is normocytic, normochromic anemia?
Known as “dilutional anemia”
Acute IV infusion increases blood volume rapidly, effectively reducing hemoglobin concentration. This is temporary and is not a sign of RBC dysfunction
What is microcytic, hypochromic anemia?
These patients have RBCs that are small, pale, and are iron difficient
What is macrocytic, normochromic anemia?
These RBCs are large, but normal cells. These cells are Vitamin B12 deficient (likely pernicious anemia)
What are some examples of anemias characterized by abnormal RBC shapes?
Elliptocytosis, spherocytosis, and sickle cell anemia
Most of these are due to genetic diseases
What are some notable symptoms of anemia?
Pale skin and weakness
Yellow Eyes (seen in hemolytic anemia, causing buildup of bilirubin)
Rapid heart rate (Low hemoglobin O2 carrying capacity, is compensated by pumping more blood)
Fatigue (this symptoms is not exclusive to anemia)
Describe Iron Deficiency Anemia
It is the most common form of anemia
Fe deficiency is due to the following:
Increased loss of Fe (chronic bleeding)
Inadequate Fe intake or absorption
Increased Fe requirements (Newborns build adult hemoglobin, muscle growth, menstruation, pregnancy)
Should everyone take an iron supplement to avoid iron deficiency?
No, iron is oxidizing and is toxic at high concentrations
Only those who have a need for supplementation should use iron supplements
What is folic acid?
Folic acid (Vitmain B9), works with Vitamin B12 and Vitmain C in protein and DNA metabolism, and int the formation of red and white blood cells
What are some factors that can cause folate deficiency?
Diseases in which folic acid is not well absorbed (Celiac or Crohn’s)
Heavy drinkers
Overcooked food (eliminates nutrients)
Hemolytic anemia or kidney dialysis
What does leukocytosis mean?
Abnormally high levels of leukocytes
What does Neutropenia mean?
Not enough WBCs
What does lymphocytosis mean?
Abnormally high amounts of lymphocytes
What is lymphopenia?
Not enough lymphocytes
What is Neutrophillia?
Abnormally high amounts of neutrophils (WBC)
When does neutrophillia occur?
Increased marrow activity (Bacterial infections, acute systemic inflammation, leukemia)
Release from Marrow Pool (Stress, corticosteroids, endotoxin exposure)
Demmargination into blood (Bacterial infections, hypoxemia, stress, corticosteroids)
When does neutropenia occur?
Decreased Marrow Activity (Drugs, Radiation exposure, Megaloblastic anemia, marrow replacement by tumour)
Decreased Neutrophil Survival (Sepsis, Viral infection, immune destruction due to drugs)
What can cause lymphocytosis?
Medium to large, atypical lymphocytes predominant (Viral infections, Active immune response, Toxoplasmosis)
Small, mature lymphocytes predominant (Chronic infections, autoimmune diseases, Metabolic diseases, lymphoma with circulating cells)
What drugs and conditions can cause lymphopenia?
AIDS
Corticosteroid therapy
Toxic drugs
Cushing syndrome
What are some characteristics of macrocytic anemia?
Abnormal nuclear maturation or a high fraction of young, large red cells (reticulocytes)
What are some characteristics of normocytic anemia?
Decreased numbers of red cell precursors in the marrow
LOw levels of erythropoietin (caused by CKD) and can affect availability of iron in the marrow
What are some characteristics of microcytic anemia?
Abnormalities in hemoglobin production, either in number of hemoglobin molecules per cell or cell type
Can be caused by things like iron deficiency or thalassemias (reduced hemoglobin production due to genetic factors)
