Chapter 4 - Hemostasis, surgical bleeding, transfusion Flashcards
What is the primary function of physiological hemostasis?
Control of bleeding related to surgery and trauma
What does healthy endothelium primarily prevent?
Inappropriate clot formation
What are prostacyclin and nitric oxide(NO) responsible for in the endothelium?
Endothelial cells produce this secretions in high Inhibiting platelet aggregation in the vessels
NO= vasodilation to prevent clot adhesion
when theres is a cut NO and PG decreases and secrete endothelin instead to contract = vasoconstriction
How does the endothelium prevent platelet aggregation?
NOxide produces vasodilation
Electronegative charges on endothelium and platelets prevent adhesion
Endogenous heparin like substances on endothelial surface prevent coagulation
What is the immediate response of a blood vessel to injury?
Vasoconstriction
What role do platelets play in primary hemostasis?
- Activating,
- adhering,
- and aggregating at injury sites
What is the strongest stimulant for platelet degranulation?
Thrombin
Which coagulation pathway is primarily responsible for initiating coagulation?
Extrinsic pathway
What does the cell-based model of coagulation emphasize?
The interconnectedness of the coagulation pathways
What is the principal inhibitor of coagulation mentioned in the text
Antithrombin (AT)
Gycosaminoglycans act as cofactors for what?
antithrombin (AT), which inactivates thrombin and
coagulation factors VIIa (FVIIa), IXa (FIXa), Xa (FXa), and XIa
(FXIa).
What is the main role of platelets in secondary hemostasis?
Activating to provide binding sites for coagulation factors
What triggers the amplification phase in the cell-based model of coagulation?
Formation of small amounts of thrombin
How does heparin enhance the activity of antithrombin?
By binding to it and causing a conformational change
injuried endothelial cells release a factor important for intrinsic pathway what is it?
von Willebrand factor (vWF)
α-granules, are inside the platelets are are the house for proteins that contribute in platelet aggregation and cohesion, including (name them)
fibrinogen,
factor V (FV),
factor VIII (FVIII),
fibronectin,
vWF,
platelet-derived growth factor,
and platelet factor 4.
Dense granules store ionized calcium (Ca2+), a common cofactor in platelet–phospholipid interactions, as well as ADP, adenosine
triphosphate, and serotoni
Who stimulates α-granules to release proteins?
Thrombin
hemostasis has two phases name them
primary and secondary hemostasis
what happens to blood flow when large vessel disruption occurs
With large-vessel disruption, blood flow becomes quite turbulent, resulting in large platelet aggregates coating the exposed endothelium.
To form a stable fibrin clot a secondary hemostasis has to occur that is divided into
intrinsic
extrinsic
common pathways
why intrisic is called intrinsic?
because factors are found inside the blood
why extrinsic is called extrinsic?
because factors are found outside the blood
Endamaged endothelial cells will release Von Willebrand’s factor that will get contact with PLT + GP1B+VW = activated platelet. But who says to the organism to not do too much coagulation?
the unaffected endothelial cells tell them to calm down by sending prostaglandings and NO
what are the products produced by platelets?
ADP, vWF, Ca2+, serotoninm, thromboxane
Extrinsic pathway describe how it starts
Injuried cells of endothelial layer have factor III in them
Factor VII floatting in the blood is active VIIa taht binds to TF (formed by activated platelets that along with Ca2+ cleave the factor X and form Xa
Common pathway Product - Final - Xa will activate with Va and calcium ion as cofactor to form prohromb complex that will activate thrombin (IIa) taht along with calcium will activate platelets and 3 cofactors that will lead to formation of Fibrinogen (Final) soluble in blood that with Ia will give fibrin that precipitates out of plasma and tight platelets to each other that along with XIIIa and Ca2+ will reinforce the fibrin mesh
Intrinsic pathway describe how it starts
Negatively charged phophates of the activated platelet or subendothelial collagen injuried will activate factor XII - XIIa - XI that will give XIa with calcium and gives IX - into IXa that along with VIII and Calcium will activate X into Xa (common pathway) and VIII is dependent of Von Willebrand factor to keep himself in blood circulation
XIII along with calcium helps fibrin form crosslinks
which factors need calcium as cofactor for activation?
Factors II, VII, VIII, IX, X, XI, XIII
Physiologic hemostasis occurs in three overlapping phases name them
initiation, amplification, and propagation
Initiation happen how and when?
Iniation starts with trauma in the vessel and the cells realse TF that will activate the **Factor VII that is in circulation blood. Factor VII + TF + Ca = cleave factor X **that will give Xa.The membrane of Xa will combine with FVa to produce small amounts of thrombin
What triggers the amplification phase in the cell-based model of coagulation?
Formation of small amounts of thrombin (factor IIa)
Amplification describe the process
Amplification of coagulation occurs when the platelet is activated bt cofactors
FV is inside α-granules of the platelet and during platelet activation the FV moves to the surface of the platelet and gets activated by thrombin and FXa
Thrombine (released by FII) cleaves vWF/FVIII to stimulate the platelets adhesion
Describe the process of propagation
Coagulation complexes assemble on the activated platelet surface and the resulting generation of large amounts of thrombin leads to the propagation of the coagulation process
FIXa and FVIIIa combine and activate FX on the platelet surface
FXa and FVa combine to forma the prothrombinase complex that will produce thrombin
Fibrinolysis is responsible for what?
This is the primary mechanism of clot dissolution and is responsible for prevention of excessive fibrin deposition and restoration of nutrient blood flow to affected tissues
thrombin-activatable fibrinolysis inhibitor (TAFI), is activated by
thrombin
what is one the most important product for coagulation? name the functions
since thrombin is so crucial for coagulation it is the main target of the anticoagulation protein named
What is the main molecule of fibrinolysis system?
Plasminogen
Where is plasminogen produced?
an inactive zymogen produced primarily in the kidney and liver
tPA and urokinase plasminogen activator (uPA) convert plasminogen to plasmin.
intrinsic pathway induces action of_________ that will activate palsminogen to converse into plasmin
kallikrein
What is the function of plasminogen?
Plasmin degrades fibrinogen and fibrin into soluble fibrin(ogen) degradation products (FDPs) and inactivates other members of the coagulation cascade
Name the products of fibronogen or fibrin degration
FDPs designated fragment X, fragment Y, and fragments D and E.
What does it mean if the FDPs D-dimers or fibrin are high in circulation?
This can be interpreted either as being the result of a thrombogenic process or as the patient being in a hypercoagulable state.
What is the primary mechanism of clot dissolution?
Fibrinolysis
What does a prolonged activated partial thromboplastin time (APTT) indicate?
Deficiency in intrinsic and common coagulation pathways
What factor is associated with inherited coagulopathies in horses?
Factor XI
What is an initial response in treating disseminated intravascular coagulation (DIC)?
administering fresh frozen plasma
What is the primary mechanism of action of heparin in treating DIC?
Inhibiting thrombin and factor Xa
Which lab test is used to diagnose DIC?
D-dimer concentration
What does an increase in fibrin degradation products (FDPs) indicate?
Hyperfibrinolysis or increased clot formation
what are the principal inhibitors of coagulation?
AT, heparin, protein C, protein S, and TFPI (Table 4-1).
TFPI is a group of lipoprotein-bound proteins produced primarily by platelets and endothelial cells. Heparin enhances the release of TFPI into the circulation
what is protein C?
Protein C is a vitamin K–dependent zymogen with primary inhibitory action on FVa and FVIIIa.
who is responsible for 70 to 80% inhibition of thrombin formation?
Anti - Thrombin (AT) and also neutralizes
FXIIa, FXIa, FXa, and FIX
AT-heparin complex inactivates which factor?
FVIIa
What type of molecule is heparin?
heparin is a glycosaminoglycan that is produced by mast cells in lungs, liver, kidney, heart and GI tract
What does the heparin do beside decreasing thrombin?
decreases thrombin-generated fibrin formation significantly. Heparin also releases TFPI from endothelial cells, thereby liberating one of the most effective inhibitors of the FVIIa-TF complex.
TFPI released by endothelial cells along with calcium will inhibit what?
FVIIa-TF activation of FX thereby dramatically decreasing the primary cellular initiator of coagulation.
PAI-1 is the main regulator of? where is it stored?
PAI-1 regulates plasminogen and is stored in α-granules of platelets.
2 coagulation blood tests
PT (play tenis outdoor extrinsic and common patway)
PTT (play table tenis indoors intrinsic and common patway)
what does it mean PT and APTT?
prothrombin time (PT)
activated partial thromboplastin time (APTT)
what clinical signs lead to suspected defects in primary hemostasis?
mucosal bleeding, petechiation, ecchymoses, and epistaxis.
what is the normal platelet count for horses?
150,000 to 250,000 platelets/μL range.
bellow 100 000 is abnormal
How do you perfom PTT test?
The test is performed by adding an activating agent to platelet-poor plasma in a glass tube containing phospholipid emulsion and Ca2+.
How do you test PT?
Platelet-poor plasma is mixed with thromboplastin and Ca2+, and time to clot formation is measured. Deficiencies in FV, FVII, FX, prothrombin, and fibrinogen can result in prolonged PT
what factors can be missing in PTT test?
Deficiencies of FXI, FX, FIX, FVIII, FV, prothrombin, and fibrinogen can result in prolonged APTT.
are PT and PTT adequate to ID early stages of hypercoagulability or disseminated intravascular coagulation?
no, they are not sensitive
AT can be decreased in which probems and increased in which?
decrease in AT levels may occur through consumption in states of increased thrombin formation; through protein loss, such as nephropathies or enteropathies; or through failure of adequate production.
AT levels may be increased with some acute inflammatory conditions.
How are fibrin(ogen) degradation products measured?
FDPs are produced by the proteolytic degradation of fibrin(ogen) by plasmin
most commonly measured anticoagulant.
Antithrombin (AT)
What are teh reasons for FDP increment in coagulation profile?
FDP are cleaned by mononuclear cells and and if an accumulation of DFP exist there is a failure of the MPS and can be the result of local or systemic hyperfibrinolysis, and it may be indicative of a dramatic increase in clot formation.
possible ranges for FDPs: 0 to 10 μg/mL, 10 to 20 μg/mL, 20 to 40 μg/mL, or greater than 40 μg/mL, with FDPs greater than ___ μg/mL considered abnormal.
possible ranges for FDPs: 0 to 10 μg/mL, 10 to 20 μg/mL, 20 to 40 μg/mL, or greater than 40 μg/mL, with FDPs greater than 10 μg/mL considered abnormal.
High or low levels of fibrinogen are related to DIC?
low levels potentially related to DIC,
Increased D-dimer levels indicate what at the level of fibrinolysis?
D-dimer is an epitope resulting from the plasmin degradation of fibrin
Increased D-dimer levels indicate increased fibrinolysis or inability to clear the products from the circulation
which drugs have been associated with thrombocytopenia?
sulfonamides,
penicillin,
phenylbutazone,
ibuprofen,
estrogens,
antihistamines
What are the methods of measurement of fibrinogen?
- heat precipitation method,
- von Clauss technique,
- or automated photometric detection
Endotoxin and proinflammatory cytokines can also activate platelets and induce the release of
vWF from endothelium
how do you diagnose DIC?
includes determination of the
- platelet count (thrombocytopenia),
- clotting times (prolonged PT and APTT),
- fibrinogen concentration (decreased),
- D-dimer concentration,
- or FDPs (increased)
Name pathologies in the horse linked with DIC
colon volvulus
Neonatal foals with sepsis (not in shock)
What is the treatment of DIC?
Since DIC is not a primary disease, there is no specific treatment that will effectively reverse the process of coagulopathy
Prevention and treatment of endotoxemia, including treatment with fresh frozen plasma (FFP), polymyxin B, and nonsteroidal antiinflammatory drugs, are reasonable strategies for prevention of DIC
heparin
why the low molecular weight heparin is better used in horses than UFH?
LMWH has greater inhibition of FXa, dose-dependent clearance, and a longer half-life than UFH
UFH has been associated with prolonged APTT and decreased packed cell volume (PCV), whereas these side effects are not seen with administration of LMWH.
what are the two heparins available what size they havE?
Low-molecular-weight heparin (LMWH) has an average molecular weight of 4.5 kDa
15 kDa for unfractionated heparin (UFH).
Which surgeries represent challenges for bleeding cotnrol?
paranasal sinuses, cranial reproductive tract, spleen, and any areas of invasive tumor removal
give examples of LMWH
dalteparin 50 to 100 units/kg SQ q24h; enoxaparin 40 to 80 units/kg (0.35 mg/kg) SQ q24h.
what are the parameters measured for transfusion?
physical examination
Serial monitoring of PCV
and total solids (TS) as the horse is rehydrated with intravenous fluids will give an indication of the extent of blood loss.
A rise in blood lactate concentration despite volume replacement with crystalloid or colloid fluids may indicate continued tissue hypoxia and a need for blood transfusion
what is the PCV value to which if below the transfusion has to be considered?
<20%
Plasma transfusion is indicated in which cases?
treatment of clotting factor deficiency, hypoalbuminemia, and failure of transfer of passive immunity in neonates.
If plasma is not frozen within 8 hours of collection it is reduced in which factor?
FVIII and FV levels
what are the two alloantigens that the ideal donor should lack?
Aa and Qa alloantigens
what is the starting dose for fresh plasma
starting dose 4mL/kg of FFP
Donor should be tested and vaccinated to which disease?
Donor horses should be up to date on vaccinations, including
rhinopneumonitis,
tetanus,
eastern and western equine encephalomyelitis,
rabies,
and West Nile virus.
Donors should be tested annually for equine infectious anemia
The ideal equine blood donor is a healthy, young gelding weighing at least ___ kgs
500 kgs
What horses are not suitable for being donors
Horses that have received blood or plasma transfusions and mares that have had foals are not suitable as donors because they have a higher risk of carrying RBC alloantibodies
Why are mares that have had foals not suitable as blood donors?
Higher risk of carrying RBC alloantibodies
Which RBC antigen is not present in horses and can cause issues when using donkeys or mules as donors?
“Donkey factor”
What is recommended before a second blood transfusion in horses?
Blood typing and crossmatching
What is the purpose of the major crossmatch in transfusion?
Mix donor’s RBCs with recipient’s serum
What is a key consideration when choosing the blood type of a donor horse?
The horse’s breed
What should be monitored during blood collection from a donor horse?
Heart rate, respiratory rate, and attitude
How often can a healthy horse donate approximately 20% of its total blood volume?
Every 30 days
What is the ideal anticoagulant for blood collected for immediate transfusion?
3.2% sodium citrate
For how long can equine blood be stored in CPDA-1 bags?
At least 3 weeks
What is the recommended volume of blood to treat a horse with normovolemic or chronic anemia based on?
The target PCV
What is the purpose of using an in-line filter during blood and plasma product transfusion?
To remove small clots and fibrin
When is volume replacement with intravenous crystalloid fluids recommended during blood donation?
When collecting 15% or greater blood volume
What type of bags are used for blood collection?
Plastic bags
Why are glass bottles not preferred for blood collection?
They inactivate platelets and damage RBCs
For how long can equine blood be stored in saline-adenine-glucose-mannitol solution?
Up to 35 days
What is the recommended treatment for mild transfusion reactions such as urticaria, fever, and tachypnea?
Administration of NSAID or antihistamine
What is the main systemic treatment for acute hemorrhage?
Fluid therapy and blood transfusion
Horses can develop alloantibodies within _____week(s) of transfusion,
Horses can develop alloantibodies within 1 week of transfusion,
Is it safe to do a second blood transfusion within 2 to 3 days of the first?
second blood transfusion may be performed safely within 2 to 3 days of the first transfusion without a blood crossmatch.
Major crossmatch
Real blood donor with serum recipient
Minor crossmatch
recipient RBC with donor’s serum
Blood flow may be improved by placing 10 or 12 gauche catheter in which direction?
Blood flow may be improved by placing the catheter opposite the venous blood flow (catheter directed toward the head).
Can you do blood transfer with minor crossmatach incompatible but major crossmatch compatible?
yes after washing donor RBC
The volume of blood to be transfused depends on 3 things name them
estimated blood loss
estimated total blood volume
donor PCV
Volumes of plasma for treatment of hypoproteinemia can be estimated by
total protein (TP) or albumin concentrations
75% of RBCs lost into a body cavity (e.g., hemoperitoneum) are autotransfused back into circulation within
24 to 72 hours
What is the advised rate that the blood should be given in the beginning?
0.3 mL/kg over the first 10 to 20 minutes, while monitoring the heart rate, body temperature, and respiratory rate
what are the signs that should be monitored during the blood transfusion?
signs of muscle fasciculation, piloerection, and urticaria.
% of WB transfusion reaction and fatal anaphylatic reation?
16% and 2% have fatal anaphylatic reaction
Initial dose is 0.3 mL/kg over the first 10 to 20 minutes and if no reaction you can increase to
5 mL/kg/hr normovolemic horses
20 to 40 mL/kg/hr hypovolemic horses
in case of anaphylatic shock what can you give and what dosage?
epinephrine (0.01 to 0.02 mL/kg intravenously [IV]
If you want to use autologous RBC when should you consider the collection?
2 weeks prior the planned surgery
what adjunctive treatments can you give in acute hemorrhage beside fluidotherapy and blood transfusion?
Aminocaproic acid is a lysine derivative that inhibits fibrinolysis by binding plasminogen activators and enhancing antiplasmin activity
what is aminocaproic acid and what is the dosage
Aminocaproic acid is a lysine derivative that inhibits fibrinolysis by binding plasminogen activators and enhancing antiplasmin activity.
Dosage 10 to 40 mg/kg IV diluted in 1L NaCl fiven slowly
what is the dosage of tranexamic acid?
5 to 25mg/kg IV
Foramlin has been proposed to
enhance endothelial and platelet activation
dosage of formalin
10 a 100 mL of 10% formalin in 1L-isotonic saline
Gelatin sponge (Gelfoam) is made from
purified animal gelatin
what are the surgical hemostasis techniques
mechanical
thermal
chemical
physical hemostasis
Gelatin sponges (Gelfoam) can be soaked in _____ to help promote coagulation directly
Gelatin sponges can be soaked in thrombin to help promote coagulation directly
Purified gelatin sponge (Gelfoam) is absorved in how much time ?
4 to 6 weeks
Oxidized regenerated cellulose (surgicel) is a chemically altered form of cellulose activates coagulation on the
collagen surface
Oxidized regenerated cellulose (surgicel) act as caustic hemostatic agent because of its __________ (low/high) pH
Oxidized regenerated cellulose act as caustic hemostatic agent because of its low pH
The low pH additionally confers antibacterial properties and therefore is preferred over gelatin foam for use in contaminated areas
Oxidized regenerated cellulose (surgicel) proprieties of the low pH
The low pH additionally confers antibacterial properties and therefore is preferred over gelatin foam for use in contaminated areas
the low pH also leads also to tissue inflammation and delayed wound healing so excess should be removed
Oxidized regenerated cellulose (surgicel) absorption time
7-14 days
Microfibrillar collagen agents (Avitene, Instat) are derived from
bovine dermal collagen and are available in sheet and foam
Microfibrillar collagen agents (Avitene, Instat) mechanism of work
Microfibrillar collagen agents do not swell, and they do not rely as much on their mechanical effect as does Gelfoam. The product does bind tightly to the bleeding surface, so there is likely some mechanical blockage of injured vessels
Microfibrillar collagen agents (Avitene, Instat) absorption time
8 to 10 weeks
chitosan is what?
type of polysaccharide, chitosan, is present in hemostatic dressings designed to control bleeding from traumatized extremities (HemCon Bandage)
Bone wax is composed of and the function is
beeswax and petroleum jelly and, as its name suggests, is used to control bleeding from bone surfaces.
can bone wax be used in fractures?
No, bone wax is nonabsorbable and inhibits bone healing, so it should not be used on fracture surfaces
bone wax disadvantages
inhibit bacterial clearance from cancellous bone, and therefore it should not be used in areas of bacterial contamination or infection.
Causes adverse effects such as allerfic and granulamatous reactions
thrombin productsis available in which type of products?
actively promotes coagulation by converting fibrinogen to fibrin and activating platelets
powder
Fibrin sealants replicate last stage of coagulation are biodegradable and contain what?
Fibrin glues (Tisseel) contain thrombin and fibrinogen, which are combined at the time of application through a dual-chamber syringe
needs contact with blood to form fibrin clot
Polyethylene glycol hydrogel (CoSeal) polymerizes forms what? a foam? a gel?
forms a hydrogel that acts as direct barrier to blood flow in high pressure vascular areas
absorbed in 30 days
