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hemostasis hematopoiesis anemia coagulation
NURS 501 Hematopoiesis lecture
What are the formed elements of blood?
What percentage of blood does plasma make up?
What percentage of blood do RBCs make up?
What is the buffy coat?
Layer of Leukocytes and platelets in between plasma and erythrocytes in uncoagulated blood
What are the functions of plasma?
Prevent blood loss
Carry RBCs that transport gases
Aid in body defenses
Transport nutrients, waste products, hormones
Facilitate exchange of body heat
What is plasma made of?
Where are plasma proteins formed?
In the liver
What is the most abundant solute in plasma?
What are the major types of plasma proteins?
What are the three types of globulin plasma proteins?
What is the function of gamma globulins?
What is the function of alpha globulins?
Steroid and bilirubin transport
What is the function of beta globulins?
Iron and copper transport
What is the lifespan of a RBC?
What percentage of blood is made up of WBCs?
What is the difference between a macrophage and a monocyte?
Monocytes circulate in blood and macrophages are found in tissues
Where are blood cells formed?
: bone marrow (some in liver/spleen)
: blood vessels, liver, spleen
Which bones contain marrow that will produce blood cells?
Flat bones of pelvis, ribs, sternum and vertebral bodies
What are cytokines?
Signaling molecules released by cell that acts on another cell
What do cytokines do?
Stimulate proliferation, differentiation and functional activation in bone marrow
What does it mean when there are many mature blood cells?
Equilibrium, no pathologic processes
What does it mean when there are many immature blood cells?
Mature cells are being lost somehow.
What are Segs?
What are Bands?
What is erythrocyte sedimentation rate?
The rate erythrocytes fall out of solution
What does a high erythrocyte sedimentation rate indicate?
What are the five steps of hemostasis?
1. Vessel spasm
2. Platelet plug formation
3. Formation of insoluble fibrin clot (coagulation cascade)
4. Clot retraction
5. Clot dissolution
What is the lifespan of a platelet?
What is the lifespan of an RBC?
Which cytokine controls the production of platelets?
What are non-cellular, cytoplasmic fragments of megakaryocytes have no DNA, no Nucleus and cannot reproduce?
What promotes platelet adhesion?
Thromboxane A2 (TXA2)
How long does vessel spasm last?
What initiates vessel spasm?
What effect does prostacyclin have?
Relaxes vessel endothelium and inhibits platelet aggregation
What do platelets release that promotes vasoconstriction and spasm?
What inhibits platelet adhesion?
What is activation of the arachidonic acid pathway?
Platelets release TXA2 and ADP
What causes platelets to aggregate?
What contributes to platelet plug stabilization?
TXA2, ADP, Thrombin and Fibrin
Why is fibrin important?
It stabilizes the clot
Where does the intrinsic pathway begin?
Where does the extrinsic pathway begin?
Trauma to tissues/vessels and release of a tissue factor
What are the terminal steps of the coagulation cascade?
Activation of Factor X
Conversion of prothrombin to thrombin
Thrombin converts fibrinogen to fibrin
What is fibrinolysis?
What is fibrinolysis regulated by?
Thrombin and plasminogen activations
What is the function of plasmin?
It digests fibrin
How long is plasmin’s half-life and why?
Very short to keep the effect local
Why do platelets contract and squeeze the serum from the clot and what stage of hemostasis does this occur?
Drying increases stability of the clot during clot retraction
What is the major purpose of clot retraction?
Bring the edges of the broken vessel closer together
What are the two types of thrombosis?
Increased platelet function
Accelerated Activity of coagulation
What conditions are associated with increased platelet function?
What conditions are associated with accelerated activity of coagulation?
Oral birth control
What are three situations that increase probability of venous thrombosis and what is it called?
Stasis of blood
Increased blood coagulability
Vessel wall injury
What is the function of all treatments for venous thrombosis?
Increased venous flow
What kinds of patients are likely to have thrombotic stroke?
Had a transient ischemic attack (TIA)
Previous thrombotic stroke
Likely to have clot formation in left heart (atrial fibrillation/heart valves)
When are anticoagulants used?
For patients with a likelihood or history of thrombotic stroke
For patients with hypercoagulability syndrome
What is heparin?
Polysaccharide made in our bodies that binds and activates antithrombin III
What happens when antithrombin III is activated?
It prevents the activation of factor X
What does heparin do?
Directly prevent the conversion of prothrombin to thrombin
Why can’t heparin be given PO?
Stomach acid destroys it
What is aPTT?
Activated Partial Thromboplastin Time
Why is it important to know aPTT?
It can indicate if there are factor deficiencies
What is a healthy aPTT?
1.5 to 2 times the normal value
Can heparin be given during pregnancy?
How do heparin and aPTT related?
aPTT determines how much heparin is administered
What is PT?
What is INR?
International Normalized Ratio
What does the INR do?
Adjusts the PT ratio to a value that takes into account the variability of lab reagents
What is a target INR for basic blood-thinning needs?
2.0 to 3.0
What is a target INR for high risk of clot formation?
2.5 to 3.5
What is the treatment for heparin overdose?
Stop infusion until the aPTT returns to the target level
What is fractionated heparin?
Low molecular weight heparin
Why is fractionated heparin used?
It is safer
Doesn’t cause thrombocytopenia so monitoring not necessary
Can be given by caregiver at home
How does fractionated heparin work?
Inhibits Factor X, but not thrombin
What is Warfarin’s MOA?
Inhibits the synthesis of particular clotting factors (II, VII, IX, and X) by inhibiting vitamin K binding.
What is the route of administration for Warfarin?
Why is heparin continued when warfarin is started?
Because warfarin has no effect on clotting factors that are already circulating, so they must be given time to leave the system
What will effect the action of warfarin?
Foods rich in vitamin K will inhibit warfarin, if Vitamin K is deficient warfarin will be too effective
What are two examples of platelet drugs?
Plavix and Ticlid
What is the effect of Plavix and Ticlid?
Cause irreversible inactivation of platelet aggregation
What is the MOA of Plavix and Ticlid?
Inhibit platelet aggregation
What is TTP?
Thrombocytopenic Thrombolytic purpura
What drug is used as prophylaxis with 81 mg aspirin for atherosclerotic events or patients who are at risk for stroke or MI?
Plavix and Ticlid
What tests are used to monitor patients taking plavix and ticlid?
CBC with differential for neutrophil count
Which drug is active as taken, Plavix or Ticlid?
Which drug is a prodrug, Plavix or Ticlid?
What is the MOA of Glycoprotein Receptor Antagonists?
Reversible blockade of platelet glycoprotein IIb/IIIa receptors, therefore inhibit the final step in aggregation
What are glycoprotein receptor antagonists used for?
To prevent ischemic events in patients with acute coronary syndromes, short-term
What is the big benefit of using glycoprotein protein receptor antagonists over Ticlid or Plavix?
It is reversible
What is the action of thrombolytic drugs?
Activate plasminogen to plasmin, which degrades fibrin and dissolve clot
What are the indications/uses for tPA?
Embolisms and MIs
How can plasminogen activators be given?
Itra-arterially into clotted vessel or by IV
What are three causes of bleeding disorders?
Dysfunctional platelets or platelet action
Deficiency of Coagulation Factors
Poor Vascular Integrity
What is purpura?
What is petechia?
What are the symptoms of thrombocytopenia?
Severe decrease in platelet count (10K-15K/ml)
Bleeding in small vessels
Bleeding from nose/GI tract
How do leukemia, HIV, radiation and chemotherapy cause platelet defects?
Decrease platelet counts
Decrease platelet production in bone marrow
Where are 1/3 of platelets reserved in the body?
What causes splenomegaly and what are the effects?
Cirrhosis, portal hypertension and lymphomas, cause increased pooling of platelets in the spleen
What is the end result of ITP and why?
Fewer platelets because antibodies are produced against platelets.
What is the difference between thrombocytopenia and thrombocytopathia?
Penia = fewer
Pathia = impaired function
What are two causes of thrombocytopathia?
Inherited disorders of adhesion
What are three types of coagulation defects?
Defects in synthesis of factors
Inherited coagulation defects
Increased consumption of factors
Which clotting factors are synthesized in the liver?
Why do patients with liver problems have increased risk of defective clotting factors?
Because vitamin K is required for normal clotting activity and vitamin K needs bile salts to be absorbed from the intestines
What causes Hemophilia A?
A decrease in Factor VIII
When is Hemophilia A diagnosed and how?
In childhood by severe and spontaneous bleeding
In adults through severe bleeding with mild trauma
What causes Von Willebrand’s disease (VWF)?
A decrease in platelet adhesion due to decreased VW factor
When is Von Willebrand’s Disease diagnosed?
Usually in adulthood
What are two genetic diseases that cause coagulation defects?
Von Willebrand’s Disease
What secondary disorder that is a paradox of widespread coagulation and bleeding involves systemic formation of fibrin, excessive clot formation and consumption of clotting factors?
Disseminated Intravenous Coagulation (DIC)
What are the other conditions that can occur with DIC?
What is the treatment for methemoglobin and carboxyhemoglobin?
100% O2 gas
What are 3 hemoglobin oxidation scenarios?
Methemoglobin (low O2 affinity)
Carboxyhemoglobin (low O2 affinity)
What causes methemoglobin?
Chemicals, nitrates and smoking
What causes carboxyhemoglobin?
What will an iron deficiency do to Hb?
Decrease hemoglobin in RBCs
What does serum ferritin measure?
Level of iron in liver and circulation
Where does most of the iron reside in the body?
Complexed to heme in hemoglobin (80%)
What is the rate of RBC destruction?
1% per day
What happens to the components of hemoglobin when the RBCs are destroyed in the spleen, liver, bone marrow and lymph?
Amino acids and iron are recycled
Heme is converted to billirubin and excreted
How long does it take for a reticulocyte to mature to an RBC?
How long does it take for a stem cell to mature to a reticulocyte?
What organ drives RBC production?
What is the function of erythropoietin?
What does Hct measure?
Percent of RBCs in 100 ml of blood
What does MCV measure?
Size of RBCs
What does MCHC measure?
Color of RBC
What does hypochromic indicate?
Decrease in Hb concentration
What are some causes of anemia?
Excessive blood loss
Destruction of RBCs
Decrease in RBC production
What is defined as anemia?
Abnormally low number of RBCs or hemoglobin (or both)
What is hemolytic anemia caused by?
Destruction of RBCs and Iron retention
Where does destruction of RBCs occur in hemolytic anemia?
Intravascularly or in spleen
What causes hemolytic anemia?
: defect in cell membrane
: thing that destroy RBC (toxins, Abys, trauma, etc…)
What are signs and symptoms of hemolytic anemia?
What is the etiology of Sickle Cell Anemia?
Abnormal substitution of one amino acid in Hb molecule
How does sickle cell anemia lead to sickle cell crisis?
Sickle cells are hyperadhesive and obstruct flow in circulation, leading to increased cell destruction from hypoxia
What can chronic sickle cell anemia lead to?
What can cause acquired hemolytic anemia?
Exogenous factors that destroy RBCs (drugs, chemicals, infection toxins)
Mechanical factors (heart valves, pumps)
Immune system (antibodies)
What causes microcytic hypochromic anemia?
What causes megaloblastic normochromic anemia?
Folic acid deficiency
Vitamin B12 deficiency
What causes pernicious anemia?
Altered absorption of B12
What causes aplastic anemia?
Decrease in production of RBCs due to decreased number or function or bone marrow stem cells or radiation/chemotherapy
Why does renal failure cause anemia?
Decreased erythropoietin production
What is pharmacologic erythropoietin?
Epoetin alfa (recombinant protein)
Why is darbepoetin preferred over epoetin alfa?
It can be given less frequently
Why is it important to monitor hematocrit and maintain iron levels when taking pharmacologic erythropoietin?
To make sure healthy RBCs are being produced
How is erythropoietin administered?
SubQ and sometimes IV
What is the target hematocrit when administering erythropoietin?
What is leucopenia?
Decrease in the absolute number of WBCs (neutrophils mostly)
What causes neutropenia?
Decrease in production by bone marrow
Shift from circulatory system to peripheral tissues
What conditions can lead to neutropenia?
Complication of procedures
Diseases that interfere with blood cell formation
Infections which drain neutrophils from blood faster than they can be replaced
What does G-CSF do?
Promotes proliferation/maturation of granulocyte precursors
In what circumstance will G-CSF not work?
If the bone marrow has completely failed or if the bone marrow is functioning maximally
What is Filgrastim?
Recombinant protein with short half-life G-CSF drug
What is pegfilgrastim?
Filgrastim encased in protective substance
What is febrile neutropenia a serious complication of?
What are 2 G-CSF drugs?
Why does bone pain occur with treatment of leucopenia?
Because of the bone marrow expansion
How is Filgrastim administered?
Daily IV or with SubQ injections
How is Pegfilgrastim administered?
One SubQ injection
What does increase in neutrophils indicate when treating leucopenia?
What is a platelet’s stem cell?
Megakaryocyte stem cell
Which cells do not come from myeloid stem cells?
T cells and B cells
What is the neutrophil’s stem cell?
Granulocyte stem cell
What is the erythrocyte’s precursor?
What is the macrophage’s precursor?
What is the monocyte’s precursor?