Part 27 Flashcards
2 steps of coagulation and their details
1) Formation of platelet plug from aggregation and bridge formation and glycoprotein IIb/IIIa activation on thrombocytes
2) fibrin production from fibrinogen bound to the 2b/3a receptors (coagulation, intrinsic with all the factors present in the vascular system activated when blood makes contact with collagen exposed as a result of trauma to vessel wallor extrinsic with thromboplastin (tissue factor) from outside the vasculature being required to work)
The intrinsic and extrinsic clotting pathways converge at factor ____, this functions to ____ to ____ also known as ___ and ____
X, which converts prothrombin to thrombin (factor 2 to factor 2a)
Thrombosis is a disease involving…
Pathogenic functioning of hemostatic mechanisms
3 major classes of drug therapy for thromboembolic disorders and their action
- anticoagulants (disrupt coagulation cascade, suppressing fibrin production)
- antiplatelet drugs (inhibit platelet aggregation)
- thrombolytic drugs (promote lysis of fibrin acting like plasmin, causing clot dissolution)
Anticoagulants are more effective in preventing ___ while antiplatelets are more effective in preventing ____
venous thrombosis, arterial thrombosis
All agents that affect hemostasis affect…
…bleeding risk, must assess mucous membranes for internal bleeding when on these drugs
Warfarin drug class, mechanism of action
- Anticoagulant,
- inhibits synthesis of clotting factors including factor X and thrombin as a vitamin K antagonist
Heparin and dabigatrin drug class, mechanism of action
- Anticoagulant
- inhibit clotting factor activity either Xa or thrombin
Unfractionated heparin definition
Injected heparin that activates antithrombin
Heparin activity on antithrombin
Binds to antithrombin and thrombin siultaneously, forming a ternary complex needed for thrombin inactivation
Heparin acts within ____ time range
minutes of IV administration
Heparin therapuetic uses (2)
- preferred anticoagulant for pregnancy
- preferred agent during PE, stroke, DVT, and MI
Heparin ADR’s (4)
- Hemmorrhaging in about 10% of patients
- Spinal/epidural hematoma
- heparin induced thrombocytopenia
- cross contamination from animal source resulting in allergic rxn
Overdosage of heparin can be treated with…
…protamine sulfate
Laboratory test for heparin monitoring is….
….activated partial thromboplastin time (APTT)
APTT normal value range
24-33 seconds
Low molecular weight heparin advantages (3)
- can be given on fixed dose schedule
- doesn’t require APTT monitoring
- As effective of standard heparin
Enoxaprin (lovenox) drug class, indications, administration
- low molecular weight heparin
- approved for prevention of DVT flollwoing surgery, treatment of DVT and PE
- administered via SC
Warfarin (coumadin and Jantoven) drug class
Vit K antagonist anticoagulatn
Warfarin (coumadin and Jantoven) mech of action
Inhibit vit K epixide reductaes complex 1 needed to convert vit K to active form, which then decreases production of active vit K dependent clotting factors (II, VII, IX, X)
Warfarin (coumadin and Jantoven) doesn’t affect ___. As a result it takes ____ to see response
clotting factors that are already made, several days
After discontinuation of warfarin (coumadin and Jantoven), how long does coagulation remain inhibited?
2-5 days because of long half life of warfarin
Warfarin (coumadin and Jantoven) therapeutic uses
- Prevent venous thrombosis and PE
- prevention of thrombosis during atrial fibrilation
Prothrombin time (PT)/INR
Most common test for evaluating warfarin therapy performed by adding a thromboplastin reagent and calcium to citrated plastma and measuring time required for clot to form, have to use INR to standardize reporting of prothrombin time by taking into account relative differences in sensitivity of tissue thromboplastin
When dosage of warfarin (coumadin and Jantoven) is changed, it takes ___ for INR to reflect the effects of the new dose
36 hours
Kcentra definition (oh lawdy its a doozy)
A 4 factor prothrombin complex concentrate for reversal of warfarin anticoagulation
Direct thrombin inhibitors definition and how do they differ from heparins?
Inhibit thrombin directly opposed to heparins that act thru antithrombin
Dabigatran etexilate (pradaxa) drug class
Direct thrombin inhibitor
Dabigatran etexilate (pradaxa) advantages over warfarin (4)
- rapid onset
- no need to monitor anticoaguation
- lower risks of major bleeds
- few food drug interactions
Dabigatran etexilate (pradaxa) mechanism of action
Synthetic, nonpeptide, reversible direct thrombin inhibitor, therefore preventing conversion of fibriongen to fibrin, prevents activation of factor XIII, preventing conversion of soluble fibrinogen to insoluble fibrin
Rivaroxaban (Xarelto) function
Act as a direct factor Xa inhibitor indirectly preventing formation of thrombin
Apixaban (Eliquis)function
A direct factor Xa inhibitor indirectly preventing formation of thrombin
3 groups of antiplatelet drugs which is strongest?
- aspirin
- GP IIb/IIIa receptor antagonists (strongest)
- P2Y ADP receptor antagonists
Once a clotting cascade begins, it has a…
…domino effect where it is self sustaining and self reinforcing
4 vitamin K dependant coagulation factors
II, VII, IX, X
Antithrombin III function, what drug is it very involved with?
Inactivates clotting factors by forming a complex with them preventing widespread coagulation beyond the site of vessel injury, intimately involved with heparin
Plasmin function, what 2 things activates it?
Removal of clot through disolving fibrin after activation from precursor state plasminogen, activated by thrombin and tPA
Fondaparinux sodium (Arixta) drug class, therapeutic uses
- antithrombin identical anticoagulant
- Enhance antithrombin activity to help prevent DVT
Heparin to warfarin administration
Often desirable as warfarin is oral and can allow for discharge, because of delay btwn warfarin administration and antithrombolytic effect, have to overlap approx 4 days and only discontinue heparin when INR is adequate for condition to be treated
Warfarin effect on pregnancy
Teratogenic effect and can cause fetal malformation
Aspirin (ASA) mech of action
Causes irreversible inhibition of cyclooxygenase enzyme preventing synthesis of thromboxane A2 to promote aggregation and vascular smooth muscle to promote constriction
Clopidogrel (plavix) drug class, mech of action, ADR’s
- Oral antiplatelet
- irreversibly blocks p2y adp receptors and subsequet activation of glycoprotein iib/iiia complex and aggregation of platelets
- well tolerated but can cause thrombotic thrombocytopenic purpura
Thrombotic thrombocytopenic purpura
Rare autoimmune blood clotting disorder that blocks o2 flow to vital organs
Ticagrelor (Brilinta) mech of action and unique fact
-Reversible P2Y ADP receptor antagonist that wears off faster than clopidogrel
Alteplase (activase) function
Bio identical to tPA used to convert plasminogen to plasmin to digest fibrin as a thrombolytic
General function of all leukocytes
Destroy or neutralize invading bacteria, fungi, or viruses
From a multipotential hematopoietic stem cell (hemocytoblast), what are the 2 offspring it can develop into
- common myeloid progenitor
- common lymphoid progenitor
From a common lymphoid progenitor, what 3 cells can arise from it?
- Natural killer cell
- T lymphocyte
- B lymphocyte
From a common myeloid progenitor, what 4 cell types can arise from it?
- megakaryocyte
- erythroblast
- mast cell
- myeloblast
From a myeloblast, what4 cell types can arise from it?
- basophil
- neutrophil
- eosinophil
- monocyte
List the 4 phagocytes
- neutrophils
- monocytes (eventually macrophages and dendritic cells)
- mast cells
- B lymphocytes
Chemotaxis
Movement of an organism in response to chemical stimuli
3 steps of neutrophil recruitment
- Margination (adherence to vessel wall)
- Diapedesis (sliding out of vessel)
- chemotaxis (follow the signals to the source)
Walling off effect
Refers to clotting factors that block off areas where fluid has leaked to keep the pathogen from spreading to the rest of the body
What cell type causes the body to produce IgE?
Basophils
Langerhan cells of the skin are also known as ___
Histiocytes (macrophages)
Granuloma
Capsuled “giant cell” formed from alveolar macrophages creating calcifications in the lungs that often appear as tubercles
What surface molecule do natural killer cells recognize?
MHC to distinguish infected and tumor cells from normal and uninfected cells
Common reasons for leukocytosis (5)
Infection Inflammation Hereditary Malignancy Allergies
Common reasons for Leukopenia (3)
- Aplastic anemia or bone marrow suppression
- chemotherapy
- HIV/AIDS
Left shift or bandemia definition
Appearance of high numbers of immature wbc’s in blood recognized by presents of “bands” on their surface, indicates wbc’s being released before they have time to mature sometimes indicating serious bacterial infection or blood loss
Blood antigen definition
Groups of over 700 known Proteins, lipoproteins and carbohydrates that sit on the surface of RBC membranes with certain ones often being based on genetic expression of the individual, to which an antibody response can be mounted against
Most blood antigens are ____ genetically
Co dominant (if the gene is present, the antigen will be expressed - think AB blood type)
Naturally occurring antibodies/alloantibodies
Exceptions to the antibody formation rule that exposure to an antigen via pregnancy or transfusion is required to form an antibody, these can be formed from food or other object exposure over a life time
Most common example of alloantibodies, what is the most common example of problematic alloantibodies?
ABO antibodies, Rh antibodies
What type of hypersensitivity reaction is a blood transfusion hemolytic response?
A type 2
Bombay type
An hh genotype resulting in lack of an H substance on RBC, very rare and result in only being able to receive blood from their own as they have a hemolytic reaction to H type
H substance
A carbohydrate chain present on almost all human’s RBC unless they are rare hh type, allows for binding of A and B enzymes for blood typage
If you are type O blood, you form antibodies against…
….The A and B antigens
Group O cells are considered a universal ___, while group O plasma is considered a universal ____
Donor, recipient
Group AB cells are considered a universal ___, while group AB plasma is considerred a universal ___
Recipient, donor
Most Rh antibodies are produced by direct stimulation by these 2 mechanisms
1) pregnancy
2) transfusion
The antigen most efficient at eliciting an immune response is the antigen designated ___, a major antigen of the ___ system
D, Rh
Rarest ABO and Rh genetic setup
AB, Rh neg
Because antiD is a ___ antibody, it is of concern during ___
IgG, pregnancy crossing the placenta and causing hemolysis of fetal RBC’s
Rhogam mech of action
- Immunize every Rh neg mom at 28 weeks pregnant (it lasts 12 weeks, so to term) with an then at birth get another immunization of it
- This allows the anti-D antibody to destroy fetal cells that have leaked into mom’s circulation without crossing placenta and before mom mounts her own antigenic response
- If amniocentesis occurs at 16 weeks then rhogam is given at 16 weeks and then 12 weeks later again and then at delivery again (3 times, unless baby and mom are Rh neg)
During pregancy, what Rh type do you always assume the fetus is?
Rh positive
Rhogam should be given even in the case of…
…miscarriage, stillbirth, natural or elective abortion
Direct coomb’s test
A test for hemolytic anemia that checks for antibodies attached to the surface of red blood cells such as on a new born
Indirect coombs test
A test for hemolytic anemia that checks for antibodies floating in serum, such as on a mother
Protocol for a woman given rhogam is to…
why?
….carry a card that identifies this in case of an emergency
-because she will appear Rh positive even though she may be Rh negative
Hemoglobin structure, how many o2 molecules can it carry?
4 chains a1 and 2, b1 and 2, each with a heme group containing an iron atom, it can carry 4 o2 molecules
Hgb A vs Hgb F vs Hgb AS vs Hgb SS
- A is 90% of normal human hemoglobin
- F is fetal hemoglobin that has a higher carrying capacity than HgbA useful for fetal development, it drops drastically 3 months after birth
- AS is sickle cell trait
- SS is sickle cell disease
A patient with acute active hemorrhage will have a ___ H&H
normal, serum and RBC’s are being lost together
Thrombocytes are derived from this organ, while clotting factors are derived from this organ
Bone marrow, liver
Name the 4 red cell indices
1) Mean corpuscular volume
2) Mean corpuscular hemoglobin
3) mean corpuscular hemoglobin conc.
4) red cell distribution width
Mean corpuscular volume (MCV) function and reference range
Determines presence of macrocytic or microcytic anemia by measuring the avg size of an RBC, reference range being 80-100fL
Common causes of macrocytosis (2)
- folate or B12 deficiency
- acoholism or liver disease
Common causes of microcytosis (2)
- Chronic iron deficiency
- blood loss
Mean corpuscular hemoglobin (MCH) function
Measures the weight of hemoglobin in avg RBC, correlates very closely with MCV andis redundant
Mean corpuscular hemoglobin concentration (MCHC) function
Avg conc of hemoglobin in the average RBC, correlates with degree of chromasia (redness of RBC)
Anisocytosis
Presence of RBC’s with varying sizes
Polkiocytosis
Presence of RBC’s with varying shapes
Red cell distribution width (RDW) function
Measure of variation in RBC size, with deficiency anemias tending to have higher RDW’s
Reticulocyte count function, what do we want to see it look like on an anemic patient?
A measure of reticulocytes in the blood, indicative of functioning bone marrow
-If patient is anemic want to see high count to indicate bone marrow is working to replenish
Serum ferritin test function, what is it most sensitive test for?
A measure of the intracellular protein that stores iron in the body to be mobilized in times of need, most sensitive test for iron deficiency
Total Iron Binding Capacity test function, what does increased and decreased values indicate?
TIBC measures the blood capacity to bind iron with transferrin, if increased indicative of iron deficiency anemia, if normal or decreased could indicate hemolytic anemia or pernicious anemia
Haptoglobin test function and what does a decrease or increase indicate?
Measures a blood glycoprotein that binds free hemoglobin, increased indicates inflammation or infection, decreased indicates hemolysis because the majority of it is bound to the free heme iron (it indirectly is measuring heme iron this way)
Reticulocyte appearance under smear
Slightly larger than mature RBC and contain cytoplasmic remnants of RNA that stains blue
A mean corpuscular volume (MCV) must be taken with consideration of presence of these 2 pathologies
Macro and microcytic anemias (avg out to normal appearing volume)
Target, spherocyte, schistocyte, acanthocyte, echinocyte definitions
Target - dark center light colored ring dark periphery
Spherocytes - thickened rounded, microcytic hyperchromatic
Schistocytes - irregular RBC fragments
Acanthocytes - multiple spike like projections
Echinocytes - multiple smaller spiked projections
Anemia of chronic disease (ACD) definition
Most common type of normocytic anemia, derived from autoimmune disorders, cancer, CKD, lliver disease, or other infections
Anemia of renal disease often has ___ cells appear on a smear
Burr
4 sources of pathophysiology of normocytic and hemolytic anemia and some examples
1) decreased RBC production (autoimmune, cancer, renal failure, aplastic bone marrow)
2) destruction or loss of RBC’s (bleeding, hemolysis)
3) uncompensated increase in plasma volume (overhydration, pregnancy)
4) mixed micro/macrocytic anemia (look for elevated RDW because MCV gonna be normal!)
Iron is metabolized to ___
Bilirubin
Unconjugated bilirubin nickname and definition
AKA indirect, goes to liver
Conjugated bilirubin nickname and defintion
AKA direct bilirubin, occurs in the liver
Very high levels of bilirubin can harm the brain, in a disease state called
Kernicterus
Sickle cell crisis
Acute painful attack of the back abodmen and joints that results in fever, dehydration and pulmonary distress due to sickling cells claudicating
G6PD deficiency definition
An enzyme that protects the RBC from oxidative damage, a deficiency in G6PD can result in hemolysis in sudden episodic periods despite normal health between episodes
3 triggers for G6PD deficiency episode
Sulfonamides
febrile illness
Fava beans
G6PD deficiency appearance on peripheral smear
Heinz bodies (small blue dots) of denatured hemoglobin in the cells and bite cells due to macrophages removing heinz bodies
Sickle cell mutations are a result of…
…mutations on the B chain of the 6th amino acid
Hemoglobin transports these 3 compounds
- O2
- CO2
- NO (vasodilator)
Hemoglobinopathies definition
Genetic defects that result in abnormal structure of one of the globin chains of hemoglobin
Thalassemias definition
Reduced or absent production of one or more globin chains in hemoglobin molecule (e.g. Beta thalassemia)
Sickle cell trait definition
A benign condition in which an individual has one of the sickle cell genes, they live a normal life but can rarely have sickling under extreme conditions (such as sports) and thus should be accommodated appropriately
The biconcave shape of RBC allow for it to ___, sickle cells cannot and thus results in ____
pass thru capillaries, ischemia or claudication
Sickle cell pathophysiology
Molecule is less soluble, B molecule binds other B molecules creating chains of HgB and changing the shape to a sickle
Sickle cell rarely affects patients below 4 months of age because…
….they use hemoglobin F
Estimated age of death in sickle cell patients
42-48 years
Priapism or stroke in young individuals might indicate…
…sickle cell disease
Hydroxyurea use in sickle cell disease pain management
It reactivates fetal hemoglobin production which has higher affinity for O2 helping alleviate frequency of pain episodes from sickle cell
Dactylitis and what disease is it a hallmark of?
Sausage digits, occurs in children less than 7 years in the phalanges of hands and feet causing swelling, infarction causees premature fusion shortening affected digits, its a hallmark of sickle cell disease
Pulmonary fat embolism definition
When fat from bone marrow gets into circulataion and becomes and emboli, can be fatal pulmonary emboli similar to a clot
Aplastic crisis definition
Transient arrest of erythropoiesis in patients with sickle cell, abrupt reduction in hemoglobin conc. most often seen in children following infection with Human parvovirus B19 (fifth’s disease, think of the slapped cheek), results in a large infarct of portion of bone marrow
Avascular necrosis of bone definition
Seen most often in femoral heads or humeral heads in both appendages, causes intense pain till infarct kills tissue then feel better, tissue becomes weak and collapses
Acute chest syndrome definition and what is it the leading cause of in sickle cell patients?
- Appearance of infiltrate with pulmonary symptoms in patient with sickel cell anemia,
- leading cause of death
Only sickle cell cure available
Hematopoietic stem cell transplant from match, and destruction of patient’s current bone marrow
What disease started the blood borne pathogens standard? What is the disease that is most likely to be transmitted via needle stick?
- HIV
- hepC
