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What are the formed elements of blood?
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What percentage of blood does plasma make up?
55%
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What percentage of blood do RBCs make up?
45%
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What is the buffy coat?
Layer of Leukocytes and platelets in between plasma and erythrocytes in uncoagulated blood
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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
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What is plasma made of?
- Dissolved elements
- Proteins
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Where are plasma proteins formed?
In the liver
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What is the most abundant solute in plasma?
Plasma proteins
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What are the major types of plasma proteins?
- Albumins
- Globulins
- Fibrinogen
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What are the three types of globulin plasma proteins?
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What is the function of gamma globulins?
Antibodies
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What is the function of alpha globulins?
Steroid and bilirubin transport
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What is the function of beta globulins?
Iron and copper transport
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What is the lifespan of a RBC?
~120 days
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What percentage of blood is made up of WBCs?
1%
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What is the difference between a macrophage and a monocyte?
Monocytes circulate in blood and macrophages are found in tissues
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Where are blood cells formed?
- Adult: bone marrow (some in liver/spleen)
- Fetus: blood vessels, liver, spleen
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Which bones contain marrow that will produce blood cells?
Flat bones of pelvis, ribs, sternum and vertebral bodies
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What are cytokines?
Signaling molecules released by cell that acts on another cell
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What do cytokines do?
Stimulate proliferation, differentiation and functional activation in bone marrow
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What does it mean when there are many mature blood cells?
Equilibrium, no pathologic processes
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What does it mean when there are many immature blood cells?
Mature cells are being lost somehow.
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What are Segs?
Mature neutrophils
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What are Bands?
Immature neutrophils
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What is erythrocyte sedimentation rate?
The rate erythrocytes fall out of solution
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What does a high erythrocyte sedimentation rate indicate?
- Infection
- Inflammatory disease
- Blood cancer
- Metastasized cancer
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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
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What is the lifespan of a platelet?
8-9 days
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What is the lifespan of an RBC?
~120 days
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Which cytokine controls the production of platelets?
Thrombopoietin
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What are non-cellular, cytoplasmic fragments of megakaryocytes have no DNA, no Nucleus and cannot reproduce?
Platelets
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What promotes platelet adhesion?
- Thromboxane A2 (TXA2)
- Plasma Proteins
- vonWillebrand factor
- ADP
- Calcium
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How long does vessel spasm last?
~1 minute
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What initiates vessel spasm?
Endothelial injury
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What effect does prostacyclin have?
Relaxes vessel endothelium and inhibits platelet aggregation
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What do platelets release that promotes vasoconstriction and spasm?
Thromboxane A2
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What inhibits platelet adhesion?
Prostacyclin
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What is activation of the arachidonic acid pathway?
Platelets release TXA2 and ADP
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What causes platelets to aggregate?
Thromboxane A2
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What contributes to platelet plug stabilization?
TXA2, ADP, Thrombin and Fibrin
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Why is fibrin important?
It stabilizes the clot
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Where does the intrinsic pathway begin?
Blood
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Where does the extrinsic pathway begin?
Trauma to tissues/vessels and release of a tissue factor
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What are the terminal steps of the coagulation cascade?
- Activation of Factor X
- Conversion of prothrombin to thrombin
- Thrombin converts fibrinogen to fibrin
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What is fibrinolysis?
Clot dissolution
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What is fibrinolysis regulated by?
Thrombin and plasminogen activations
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What is the function of plasmin?
It digests fibrin
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How long is plasmin’s half-life and why?
Very short to keep the effect local
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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
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What is the major purpose of clot retraction?
Bring the edges of the broken vessel closer together
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What are the two types of thrombosis?
- Increased platelet function
- Accelerated Activity of coagulation
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What conditions are associated with increased platelet function?
- atherosclerosis
- Diabetes mellitus
- Smoking
- Increased lipids/cholesterol
- Increased platelets
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What conditions are associated with accelerated activity of coagulation?
- Pregnancy
- Oral birth control
- Postoperative
- Immobility
- CHF
- Malignant dx
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What are three situations that increase probability of venous thrombosis and what is it called?
- Virchow’s Triad
- Stasis of blood
- Increased blood coagulability
- Vessel wall injury
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What is the function of all treatments for venous thrombosis?
Increased venous flow
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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)
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When are anticoagulants used?
- For DVT
- For patients with a likelihood or history of thrombotic stroke
- For patients with hypercoagulability syndrome
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What is heparin?
Polysaccharide made in our bodies that binds and activates antithrombin III
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What happens when antithrombin III is activated?
It prevents the activation of factor X
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What does heparin do?
Directly prevent the conversion of prothrombin to thrombin
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Why can’t heparin be given PO?
Stomach acid destroys it
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What is aPTT?
Activated Partial Thromboplastin Time
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Why is it important to know aPTT?
It can indicate if there are factor deficiencies
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What is a healthy aPTT?
1.5 to 2 times the normal value
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Can heparin be given during pregnancy?
Yes
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How do heparin and aPTT related?
aPTT determines how much heparin is administered
- What is PT?
- Prothrombin Time
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What is INR?
International Normalized Ratio
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What does the INR do?
Adjusts the PT ratio to a value that takes into account the variability of lab reagents
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What is a target INR for basic blood-thinning needs?
2.0 to 3.0
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What is a target INR for high risk of clot formation?
2.5 to 3.5
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What is the treatment for heparin overdose?
Stop infusion until the aPTT returns to the target level
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What is fractionated heparin?
Low molecular weight heparin
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Why is fractionated heparin used?
- It is safer
- Doesn’t cause thrombocytopenia so monitoring not necessary
- Can be given by caregiver at home
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How does fractionated heparin work?
Inhibits Factor X, but not thrombin
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What is Warfarin’s MOA?
Inhibits the synthesis of particular clotting factors (II, VII, IX, and X) by inhibiting vitamin K binding.
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What is the route of administration for Warfarin?
PO
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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
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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
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What are two examples of platelet drugs?
Plavix and Ticlid
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What is the effect of Plavix and Ticlid?
Cause irreversible inactivation of platelet aggregation
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What is the MOA of Plavix and Ticlid?
Inhibit platelet aggregation
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What is TTP?
Thrombocytopenic Thrombolytic purpura
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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
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What tests are used to monitor patients taking plavix and ticlid?
CBC with differential for neutrophil count
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Which drug is active as taken, Plavix or Ticlid?
Ticlid
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Which drug is a prodrug, Plavix or Ticlid?
Plavix
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What is the MOA of Glycoprotein Receptor Antagonists?
Reversible blockade of platelet glycoprotein IIb/IIIa receptors, therefore inhibit the final step in aggregation
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What are glycoprotein receptor antagonists used for?
To prevent ischemic events in patients with acute coronary syndromes, short-term
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What is the big benefit of using glycoprotein protein receptor antagonists over Ticlid or Plavix?
It is reversible
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What is the action of thrombolytic drugs?
Activate plasminogen to plasmin, which degrades fibrin and dissolve clot
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What are the indications/uses for tPA?
Embolisms and MIs
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How can plasminogen activators be given?
Itra-arterially into clotted vessel or by IV
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What are three causes of bleeding disorders?
- Dysfunctional platelets or platelet action
- Deficiency of Coagulation Factors
- Poor Vascular Integrity
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What is petechia?
Pinpoint hemorrhage
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What are the symptoms of thrombocytopenia?
- Severe decrease in platelet count (10K-15K/ml)
- Bleeding in small vessels
- Petechia, purpura
- Bleeding from nose/GI tract
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How do leukemia, HIV, radiation and chemotherapy cause platelet defects?
- Decrease platelet counts
- Decrease platelet production in bone marrow
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Where are 1/3 of platelets reserved in the body?
Spleen
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What causes splenomegaly and what are the effects?
Cirrhosis, portal hypertension and lymphomas, cause increased pooling of platelets in the spleen
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What is the end result of ITP and why?
Fewer platelets because antibodies are produced against platelets.
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What is the difference between thrombocytopenia and thrombocytopathia?
- Penia = fewer
- Pathia = impaired function
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What are two causes of thrombocytopathia?
- Inherited disorders of adhesion
- Acquired defects
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What are three types of coagulation defects?
- Defects in synthesis of factors
- Inherited coagulation defects
- Increased consumption of factors
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Which clotting factors are synthesized in the liver?
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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
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What causes Hemophilia A?
A decrease in Factor VIII
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When is Hemophilia A diagnosed and how?
- In childhood by severe and spontaneous bleeding
- In adults through severe bleeding with mild trauma
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What causes Von Willebrand’s disease (VWF)?
A decrease in platelet adhesion due to decreased VW factor
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When is Von Willebrand’s Disease diagnosed?
Usually in adulthood
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What are two genetic diseases that cause coagulation defects?
- Hemophilia A
- Von Willebrand’s Disease
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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)
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What are the other conditions that can occur with DIC?
- OB complications
- Cancer
- Infections
- Shock
- Trauma
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What is the treatment for methemoglobin and carboxyhemoglobin?
100% O2 gas
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What are 3 hemoglobin oxidation scenarios?
- HbO2 (desirable)
- Methemoglobin (low O2 affinity)
- Carboxyhemoglobin (low O2 affinity)
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What causes methemoglobin?
Chemicals, nitrates and smoking
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What causes carboxyhemoglobin?
Carbon monoxide
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What will an iron deficiency do to Hb?
Decrease hemoglobin in RBCs
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What does serum ferritin measure?
Level of iron in liver and circulation
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Where does most of the iron reside in the body?
Complexed to heme in hemoglobin (80%)
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What is the rate of RBC destruction?
1% per day
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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
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How long does it take for a reticulocyte to mature to an RBC?
1-3 days
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How long does it take for a stem cell to mature to a reticulocyte?
1 week
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What organ drives RBC production?
Kidney
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What is the function of erythropoietin?
Erythropoiesis
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What does Hct measure?
Percent of RBCs in 100 ml of blood
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What does MCV measure?
Size of RBCs
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What does MCHC measure?
Color of RBC
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What does hypochromic indicate?
Decrease in Hb concentration
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What are some causes of anemia?
- Excessive blood loss
- Destruction of RBCs
- Decrease in RBC production
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What is defined as anemia?
Abnormally low number of RBCs or hemoglobin (or both)
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What is hemolytic anemia caused by?
Destruction of RBCs and Iron retention
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Where does destruction of RBCs occur in hemolytic anemia?
Intravascularly or in spleen
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What causes hemolytic anemia?
- Intrinsic: defect in cell membrane
- Extrinsic: thing that destroy RBC (toxins, Abys, trauma, etc…)
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What are signs and symptoms of hemolytic anemia?
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What is the etiology of Sickle Cell Anemia?
Abnormal substitution of one amino acid in Hb molecule
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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
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What can chronic sickle cell anemia lead to?
CVA, splenomegaly
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What can cause acquired hemolytic anemia?
- Exogenous factors that destroy RBCs (drugs, chemicals, infection toxins)
- Mechanical factors (heart valves, pumps)
- Immune system (antibodies)
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What causes microcytic hypochromic anemia?
Iron deficiency
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What causes megaloblastic normochromic anemia?
- Folic acid deficiency
- Vitamin B12 deficiency
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What causes pernicious anemia?
Altered absorption of B12
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What causes aplastic anemia?
Decrease in production of RBCs due to decreased number or function or bone marrow stem cells or radiation/chemotherapy
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Why does renal failure cause anemia?
Decreased erythropoietin production
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What is pharmacologic erythropoietin?
Epoetin alfa (recombinant protein)
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Why is darbepoetin preferred over epoetin alfa?
It can be given less frequently
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Why is it important to monitor hematocrit and maintain iron levels when taking pharmacologic erythropoietin?
To make sure healthy RBCs are being produced
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How is erythropoietin administered?
SubQ and sometimes IV
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What is the target hematocrit when administering erythropoietin?
36%
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What is leucopenia?
Decrease in the absolute number of WBCs (neutrophils mostly)
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What causes neutropenia?
- Decrease in production by bone marrow
- Peripheral destruction
- Shift from circulatory system to peripheral tissues
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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
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What does G-CSF do?
Promotes proliferation/maturation of granulocyte precursors
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In what circumstance will G-CSF not work?
If the bone marrow has completely failed or if the bone marrow is functioning maximally
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What is Filgrastim?
Recombinant protein with short half-life G-CSF drug
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What is pegfilgrastim?
Filgrastim encased in protective substance
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What is febrile neutropenia a serious complication of?
Chemotherapy
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Why does bone pain occur with treatment of leucopenia?
Because of the bone marrow expansion
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How is Filgrastim administered?
Daily IV or with SubQ injections
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How is Pegfilgrastim administered?
One SubQ injection
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What does increase in neutrophils indicate when treating leucopenia?
Decreased infection
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What is a platelet’s stem cell?
Megakaryocyte stem cell
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Which cells do not come from myeloid stem cells?
T cells and B cells
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What is the neutrophil’s stem cell?
Granulocyte stem cell
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What is the erythrocyte’s precursor?
Reticulocyte
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What is the macrophage’s precursor?
Monocyte
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What is the monocyte’s precursor?
monoblast
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