Literature Review Flashcards
Fresh frozen plasma components
Separated from whole blood and frozen w/in 8 hours
Coagulation factors
Antithrombin
Fibrinogen
Albumi
Alpha-macroglobulins
Stored for up to 1 year when frozen at -20 to -30
evidence it can be refrozen w/in 1 hour of thawing and retain its hemostatic protein activity
Frozen plasma definition and components
Plasma that is separated from whole blood but not frozen w/in 8 hours or that has been frozen w/in 8 hours but stored for more than 1 year up to 4 years.
Factors: II, VII, IX, X and albumin
Define TRALI and 2 subsets
Transfusion-associated acute lung injury
(1) antibody mediated (transfusion of human leukocyte or neutrophil antibodies and subsequent reaction)
(2) non antibody mediated (accumulation of pro inflammatory mediators during storage of blood products)
Describe the classic coagulation pathway
Intrinsic - 12, 11, 9, 8 (localized w/in the blood)
initiated through contact activation of factor XII on negatively charged surfaces
Extrinsic - includes TF and VIIa (localized outside of the blood)
Common - 10, 5, 2, 1 (Factor 10 leads to the activation of prothrombin (II) –> thrombin (IIa) –> fibrinogen (I) –> fibrin (Ia)
Describe the cell-based coagulation system
= coagulation occurs in distinct and overlapping phases and requires 2 main cell types: (1) TF-bearing cell (2) platelet.
3 phase: Initiation, amplification, and propagation
Describe the initiation phase of the cell-based coagulation system
Injury occurs and blood is exposed to a TF-bearing cell, causing VII to become activated –> results in the production of a small amount of IXa and thrombin that diffuses from the surface of the TF-bearing cell to the platelet.
Describe the amplification phase of the cell-based coagulation system.
The small amount of thrombin from the initiation phase activates platelets, releasing vWF and leading to the generation of activated forms of factors (V, VIII, and XI).
Describe the propagation phase of the cell-based coagulation system.
Enzymes activated during earlier phases assemble on the procoagulant surface of the activated platelet to form intrinsic tense, which leads to factor Xa generation on the platelet surface and a burst of thrombin generation directly on the platelet that results in fibrin formation.
Define INR
International normalized ratio
= Patient PT / mean normal PT
Normal = 0.8 to 1.2, with > 1.5 suggestive of hypocoagulability
How is a pro inflammatory state procoagulant?
Inflammation results in pro inflammatory cytokine release, leads to activation of mononuclear cells and endothelial cells.
–> cells produce TF, which initiates coagulation.
+ downregulation of proteins and endothelial cell disruption causes impairment of anticoagulant mechanisms (antithrombin, proteins C, S and TFPI)
Mechanism of antithrombin?
Inhibits thrombin and factor Xa
Mechanism of activated protein C and S
Degrades cofactors Va and VIIIa
Mechanism of TFPI
forms a complex with factors Xa and VIIIa to inhibit coagulation induced by TF
List the chemical components of hydroxyethyl starch
Molecular weight C2/C6 ratio Raw material Concentration MS
What makes up hydroxyethyl starch?
Maize and potato starches
What are the components of maize and potato in HES?
Maize- 95% amylopectin
Potato - 80% amylopectin and 20% amylose
What are the properties of hetastarch compared to vetstarch?
Hetastarch: Concentration 6%, Mw/MS: 600/0.7; maize; 0.9% NaCl; C2:C6 ratio 5:1
Vetstarch: 6%, Mw/MS: 130/0.5; maize, 0.9% NaCl; C2:C6 9:1
What is the difference in the 1-3 generations of HES?
1st generation MW > 400
2nd generation: MW 200-400
3rd generation: Mw < 200
*moderateion 3rd generation molecules are characterized by a lower Mw with a narrower range in an attempt to reduce adverse effects and improve pharmacokinetics.
Describe the C2/C6 ratio
Natural amylopectin is chemically modified by hydroxyethylation at the glucose subunits C2, C3, or C6 to increase solubility and inhibit degradation by alpha amylase. Average number of hydroxyethyl residues per glucose subunit defines the MS, which higher substitution associated with delayed enzymatic degradation.
Define the glycocalyx
Web of membrane bound proteoglycans and glycoproteins that carry a negatively charged side chains, which covers the entire endothelial surface.
How does hypervolemia affect the glycocalyx?
Leads to degradation of the glycocalyx. w/ acute hypervoleumia atrial natriuretic peptide is secreted which causes rapid shedding of the glycalyx with subsequent increase in permeability.
Is HES anti-inflammatory or pro-inflammatory?
Anti-inflammatory
Decrease in activity of inflammatory cells (decreased activation, migration, adhesion of leukocytes)
What molecules effect plasma COP?
Albumin (mainly), globulin, fibrinogen
Does hypoalbuminemia cause both peripheral and pulmonary edema?
Causes peripheral rather than pulmonary edema
Side effects of HES?
Coagulopathies Acute kidney injury Tissue accumulation Anaphylactic reactions Prutitis
Why is albumin better at generating an improved effect on COP compared to hetastarch?
Albumin is believed to hook into the glycocalyx
it’s likely that maintaining an adequate intravascular volume is not really a matter of an adequate COP, rather the health of the glycocalyz
What is the COP paradox?
The ability of albumin (and other colloids) to “seal” the vascular endothelium and reduce extravasation independent of its effect on COP
Mechanism of coagulopathy with HES?
(1) dilutional coagulopathy (decreased [ ] of f VIII/vWF complex
(2) coating of platelets with HES –> decreased expression and activation of the surface receptor GPIIb IIIa, which binds vWF and fibrinogen and plays a key role in platelet adhesion and aggregation
(3) reduced clot firmness due to decreased interaction between activated factor XIII and fibrin
How does the C2/C6 ratio affect HES degradation?
High C2/C6 ratio and high MW will delay enzymatic degradation
increase intravascular HES accumulation and result in increased coagulation impairment and plasma viscosity
Define osmotic nephrosis
Histomorphological pattern w/ vacuolization and swelling of the renal proximal tubular epithelial cells (distal tubules and collecting ducts are usually not affected)
How is HES degradaded?
alpha amylase degardes
lost in the urine
Old/new definitions of sepsis?
Old sepsis = SIRS + bacteria
New sepsis = includes tissue hypo perfusion
Septic shock = septic patients with circulatory failure despite adequate volume resuscitation
What are the recommended choices of vasopressors with septic shock?
Norepinephrine recommended first
**can add epinephrine as an additional agent
Vasopression can be added to reduce NE dose used or to aid in increasing BP to target; but not to be used as the initial vasopressor
Dopamine is not recommended except in highly selected circumstances
Alpha-adrenergic agonists MOA
Increase vascular tone
May decrease CO and regional blood flow
Beta-adrenergic agonists MOA
Maintain CO via positive inotropic and chronotropic effects
also have deleterious effects such as increased cellular metabolism and immunosuppression
Vasopressin MOA
Synthesized in the hypothalamus and transported to the pituitary gland for storage.
Released in response to a decrease in blood pressure, decreased intravascular volume, increased osmolality.
Causes constriction of vascular smooth muscle by directly activating the V1 receptors, which leads to an increase in intracellular calcium via the phosphatidylinositol-bisphosphonate cascade.
List the subtype vasopressin receptors - location and function
V1 (G protein coupled) - vascular smooth muscle, platelet, liver myometrium, kidney, brain. Causes vasoconstriction, platelet aggregation, glycogenolysis, uterine contraction, efferent arteriolar constriction.
V2 (G protein coupled, cAMP) - kidney collecting ducts and vascular endothelium –> insertion of aquoporin-2 channels and release of vWF and factor VIII
V3 (G protein-coupled) - located in the brain. Fx,: stress adaption, cognitive function, regulation of social behavior .
What is the MOA that vasopressin uses to cause constriction of vascular smooth muscle
Directly activates V1 receptors
Leads to an increase in intracellular calcium via the phosphatidylinositol-bisphosphonate cascade.
Results of the VASST trial (vasopressin and septic shock trial)
Vasopressin might have decreased mortality when compared to NE in septic shock patients.
Low-dose vasopressin plus corticosteroid therapy significantly improved 28-day mortality compared to NE plus corticosteroid therapy.
How is D-lactate formed?
Glyoxalase pathway
-OR-
produced by commensal bacteria in th mammalian gastrointestinal tract and absorbed into circulation
Describe glycolysis
Biochemical cascade, by which one 6-carbon glucose molecule is broken down into two 3-carbon molecules of pyruvate, 2 molecules of ATP, and 2 molecules of NADPH
Pyruvate is transported into the mitochondrion - undergoes decarboxylation to produce acetyl-CoA (irreversible).
Acetyl-CoA then proceeds through the TCA cycle to produce CO2, NADH, and FADH2
When glycolysis, the TCA cycle, and the ETC are combined the oxidation of one molecule of glucose produces about 36 molecules of ATP
What effect does lactate have in regards to the Stewart physicochemical approach?
Lactate is a strong anion and has acidifying effects in manner similar to chloride
Increase in lactate causes a decrease in SID
and decreasing SID results in a proportionate increase in H+ and therefore acidosis (in accordance w/ the law of electroneutrality)
What does the quantitative approach say about acid-base?
For ever 1 mmol/L increase in lactate, SBE will decrease by 1 unit
What is the most reliable place to measure tissue oxygen saturation?
Sartorius
What is total hemoglobin index?
Indicator of signal strength and is reported as a unites number between 1 and 99
THI is NOT a measurement of blood hemoglobin - it measures the amount of intravascular hemoglobin, intramuscular myoglobin, melanin, a nd mitochondrial cytochrome c oxidase
