Ch.4 Hemostasis, Surgical Bleeding, Transfusions Flashcards
Absorption time of CoSeal (polyethylene glycol hydrogel)
30 days
To what extent does CoSeal (polyethylene glycol hydrogel) swell
Up to 4 times its volume
How does polyethylene glycol hydrogel (CoSeal) act
Polymerizes to form hydrogel acting directly as a barrier to blood flow.
Advantages of fibrin sealants
1- Do not require patient to have adequate platelets or coag factors
2- Biodegradable
3 - Have not been associated with tissue inflammation or FB rxn
How do fibrin sealants work
Replicate last stage of coagulation
Tisseel contains what
Thrombin and fibrinogen
Flowseal is an example of
A thrombin product
Disadvantages of bone wax
1- Non-absorbable
2 - Inhibits bacterial clearance
3 - Inhibits bone healing
4 - Allergic rxns
5 - Granulomatous rxns
6 - Embolization
Biologic hemostatic effect of bone wax?
None - mechanical
Advantages of polysaccharide hemostatic agents (TraumaDex, Arista)
Do not inhibit wound healing
What polysaccharide is used in hemostatic dressings such as HemCon
Chitosan
Absorption time for TraumaDex, Arista (polysaccharide hemostatic agents)
24-48hrs
Mechanism of hemostasis of polysaccharide hemostatic agents
Have a porous surface which allows absorption of blood - concentrating platelets, coag factors and reduces time for coag.
TraumaDex and Arista are examples of?
Polysaccharide hemostatic agents
Absorption time of microfibrillar collagen hemostatic agents
Should be removed from surgical site before closure of wound
Disadvantages of microfibrillar collagen hemostatic agents
(Avtene, Instat)
1-Allergic reactions - related to bovine origin
2-Interfere with bacterial clearance and wound healing
On which patients are microfibrillar collagen hemostatic agents (Avtene, Instat) less effective?
Patients with thrombocytopenia.
How do microfibrillar collagen hemostatic agents (Atvene, Instat) act?
1-Bind tightly to the bleeding surface - mechanical blockage.
2-Platelets adhere to the collagen and are activated the resultaning platelet degranulation and aggregation leads to hemostasis.
Absorption time of microfibrillar collagen hemostatic agents
8-10 weeks
Absorption time of surgicel (oxidized regenerated cellulose)
7-14 days however residue may persist for several months to years.
Disadvantages of using surgicel (oxidized regenerated cellulose)
1-Can’t be soaked in thrombin - the biologic agents will be inactivated in the low pH
2-Low pH may lead to tissue inflammation and delayed wound healing.
Advantage of Surgicel (Oxidized regenerated cellulose) over gelatin sponge?
Low ph confers antibacterial properties so can be used in contaminated areas.
How does oxidized regenerated cellulose (Surgical) elicit its hemostatic effects?
1-Swelling from blood absorption,
2-Activates coagulation on the collagen surface,
3-Caustic hemostatic agent due to low ph
Absorption time of gelatin sponge
4-6 weeks
Contraindication of gelatin sponges
Not to be used in contaminated wounds - can potentiate infection
How does a purified gelatin sponge exert its hemostatic effect?
Swelling as it is soaked with blood.
Can be soaked in thrombin to help promote coagulation directly.
Proposed activity of Yunnan baiyao
Activates platelets and enhances expression of surface glycoproteins on platelets.
Haemostatic dose of formalin
10-100ml of 10% formalin in 1L isotonic saline
Dose of Tranexamic acid
5-25mg/kg
How are conjugated estrogens believed to contribute to hemostasis
Enhance platelet activity and decrease antithrombin activity
How are conjugated estrogens believed to contribute to hemostasis
Enhance platelet activity and decrease antithrombin activity
Dose of Aminocaproic acid
10-40mg/kg IV q6 diluted in 1L Saline administered slowly
or
3.5mg/kg/min for 15mins then 0.25mg/kg/min at CRI
How does aminocaproic acid work?
Lysine derivative - inhibits fibrinolysis by
1 - binding plasminogen activators and
2 - enhancing antiplasmin activity.
Half-life of transfused RBC of fresh crossmatched allogenic blood?
20 days
Life-span of transfused RBC of autologous blood stored for 28 days?
30 days
What % blood loss do we estimate for a horse in shock?
30%
Formula for acute blood loss volume
BW(Kg) x 0.08 x 0.30
Formula for blood transfusion
BW(Kg) x 0.08 x <(Desired PCV - Actual PCV)/Donor PCV>
What can hypocalcemia be a sign of regarding blood transfusion?
Citrate toxicity
How to treat signs of anaphylaxis in horses receiving transfusion?
Epinephrine 0.01 to 0.02 ml/kg IV of 1:1000 solution (0.1mg/ml),
Mild rxn tx w NSAID or antihistamine
If no reaction is seen in the first 20 mins of WB transfusion the rate can be increased to?
5ml/kg/hr for normovolemic and up to 20-40ml/kg/hr in hypovolemic horses
What is the rate of adverse reactions to WB transfusion?
16% with 2% (1/44) having a fatal reaction
At what rate should blood be transfused?
0.3ml/kg over the first 10-20mins
How many ml/kg body weight of plasma is advisable for treating a coagulopathy?
4-5ml/kgBw
What % of blood lost into a body cavity is auto-transfused back into circulation?
75% in 24-72 hours
What % of blood lost should be replaced y transfusion?
25-50%
For how long can USDA licensed equine plasma products be stored?
1 year
How many litres of plasmapheresis can be performed on a donor?
4-11L every 30 days
When transfusing blood from the dam to an NI foal how should the blood be prepared?
Wash RBC
At what temp should blood be stored?
4*C
For how long is blood that has been stored in saline-adenine-glucose-mannitol suitable for transfusion?
35 days
What is the % RBC survival of stored blood at 28 days?
73%
For how long can whole blood be stored in citrate-phosphate-dextrose-adenine (CPDA)-1 bags?
3 weeks
What ratio of 3.2% sodium citrate is used as an anticoagulant in blood collected for immediate transfusion
1:9 anti-cog : blood
Cons of using glass bottles to collect blood?
Inactivates platelets and damages RBCs
At what % blood collection from a donor is volume replacement with crystalloid fluids recommended?
15%
What % of its’ total blood volume can a healthy horse donate?
20% every 30 days
Transfused RBC from cross-matched incompatible blood have a half life of?
4.7 days
Transfused RBC from fresh autologous blood have a half life of?
50 days
Transfused RBC from a cross-matched compatible donor have a half life of?
20 days
If the minor cross-match is incompatible but the major is can the transfusion be performed?
Yes after washing the donor RBCs
Rapid agglutination method tests what?
Detects RBC antigens Ca and Aa
What does the minor cross-match involve?
Mixing recip RBC with the donor serum
What does the major cross-match involve?
Mixing the donor’s washed RBCs with the recip’s serum
What can be added to the reaction mixture to detect hemolytic reactions?
Rabbit complement
How long after an initial blood transfusion of unmatched blood is it safe to perform a second one?
Within 2-3 days
How soon after a transfusion can horses develop alloantibodies?
1 week
The ideal blood donor should be..
Gelding,
young,
healthy
>500kg,
vaccinated inc rhino, tet, etc
Lack Aa Qq alloantigens
How many recognized equine blood groups?
8
Action of plasmin in fibrinolysis?
Degrades fibrin and fibrinogen into soluble F degradation products,
inactivates FVa and FVIIIa and
degrades prekallikrein and HMWK
Plasminogen activators such as what convert plasminogen to plasmin.
tPA (tissue plasminogen activator) and
uPA (urokinase plasminogen activator) &
Kallikrenin
Where is plasminogen produced?
Kidney and liver
What is the principle component of the fibrinolytic system?
Plasminogen an inactive zymogen
What is the primary mechanism of clot dissolution?
Activation of the fibrinolytic system
Function of Thrombin in amplification process?
Cleaved vWF/FVIII allowing vWF to stimulate platelet adhesion.
What constitutes the amplification of coagulation?
Adherence, activation and aggregation of platelets along with the accumulation of activated co-factors
What does the TF-FVIIa complex activate?
FX and FIX
What is the primary initiator of coagulation?
Tissue Factor TF
What are the 3 phases of physiologic hemostasis?
Initiation, amplification and propagation
How does FXIIIa stabilize the clot?
Cross-linking strands of fibrin monomer in the presence of Ca2+
In the final step of clot formation FIIa converts what?
Fibrinogen to fibrin
FX in the presence of of activated FVa, Ca2+ and a platelet phospholipid converts what?
prothrombin(FII) to thrombin (IIa)
The extrinsic pathway starts with the activation of?
FVII by TF present in fibroblasts or other TF bearing cells
The common coag pathway is marked by the activation of?
FX
What procoagulant does FIX bind to in the presence of Ca2+?
VIIIa
FXIa activates FIX in the presence of?
Ca2+
What contact proteins interact with FXII to accelerate its activation?
High molecular weight Kininogen (HMWK) and Prekallikrein.
The intrinsic pathway is initiated by?
Activation of Factor XII and subsequently XI on the surface of activated platelets
How does prostacyclin prevent unwanted expansion of platelet aggregates?
Decreases ADP release
Platelet activation Is promoted by?
Thrombin,
collagen,
ADP,
Thromboxane A2
How is platelet adhesion mediated?
P-selectin and platelet receptor GPIb𝜶 which attaches to vWF.
What is responsible for degradation of unwanted cellular debris after complete activation of fibrin formation?
Acid hydrolayses in platelet lysosomes
What stores the majority of platelet proteins needed for the initiation of coagulation?
𝜶 Granules, Dense granules and lysosomes
What is the strongest stimulant for release of contents from dense granules?
Thrombin
Function of Ca2+ in hemostasis?
Cofactor in platelet-phospholipid interactions
What do dense granules store?
Ca2+,
ADP,
Adenosine triphosphate and
serotonin.
What proteins do 𝜶 granules contain?
1- Fibrinogen,
2- Factor V,
3- Factor VIII,
4- Fibronectin,
5- vWF,
6- Platelet derived growth factor,
7- Platelet factor 4.
What are the largest and most prevalent storage granules in platelets?
Alpha 𝜶
What does local vasoconstriction, platelet activation, adhesion and aggregation lead to the formation of?
A temporary platelet plug
From what are von Willebrand factor released?
Weibel-Palade bodies
How do endothelial cells react to vessel injury?
Express TF and
downregulate expression of thrombomodulin, becoming procoagulant.
Release von Willebrand factor promoting platelet adhesion.
Immediate response of the blood vessel to injury is?
Vasoconstriction
What does AT (Antithrombin) inactivate?
Thrombin and coag factors 7a, 9a,10a and 11a
How do enzymes on the endothelial surface prevent clotting?
Prevent platelet agg and adhesion by degrading ADP Adenosine Diphosphate
What’s the action of of prostacyclin and nitric oxide (NO) on clotting?
Inhibit platelet aggregation. NO also inhibits platelet adhesion and causes vasodilation causing low turbulence flow.
What is responsible for antiplatelet properties of the endothelium?
Prostacyclin and nitric oxide
What are the fragments produced as FDPs
Fragments X, Y, D and E
Plasmin degradation of the cross-linked fibrin results in
D Dimer degradation product
The principle inhibitors of coagulation are
AT
Heparin
Protein C
Protein S
TFPI
What is responsible for 70-80% of thrombin inhibition in the coagulation system
AT
Where is heparin produced
Mast cells in lungs, liver, kidney, heart and GI
How does Heparin affect AT
Conformation change increasing AT activity 1000 fold
What do D-Dimer result from
Degradation of fibrin
What do FDPs indicate
Degredation of either fibrin or fibrinogen
How to measure D-Dimers
Latex agglutination
Latex emnhanced turbidimetric immunoassay
What does increased D-Dimers indicate
Increased fibrinolysis
or
Inability to clear the products from circulation
How to test for DIC
Platelet count - thrombocytopenia
Clotting time - Prolonged PT/APTT
Fibrinogen conc = Decreased
D-dimer conc = incresed
FDP = increased
Protein C activity in inflammation
DECREASES
How to treat DIC
Treat primary disease
Fresh frozen plasma - will provide AT
Polymixin B
NSAIDs
Heparin
What forms of heparin are used in DIC treatment, why?
Use the Low molecular-weight heparin - 4.5kDa
- Greater inhibition of FXa
- Longer half life than UFH
- Dose dependent clearance
Unfractioned heparin (15kDA) associated with
- Prolonged APTT and decreased PCV
Heparin regimen for LMWH vs UFH Heparin in DIC
LMWH 4.5 kDa
Dalteparin: 50-100 units/kg SQ q24
Enoxaparin: 40-80 units/kg (0.35mg/kg) SQ q24
UFH 15kDa
Heparin Ca2+: 150IU/kg SQ once
then
125IU/kg SQ q12 for 3 days
then
100IU/kg SQ q12
(Use 40-80iu/kg if sodium heparin)
What are the principle inhibitors of coagulation
AT
Heparin
Protein C
Protein S
TFPI
Deficiencies in what can result in prolonged PT
FV
FVII
FX
Prothrombin
Fibrinogen
Extrinsic and common pathways
How is prothrombin time measured
Plasma mixed with thromboplastin and Ca2+
Time to clot measured
Increase by 20% = abnormal
TBT will be prolonged in what conditions
Thrombocytopenia
Thrombocytopathia
Lack of WVF
Tests of primary hemostasis
Platelet count <100,000/ul
TBT
PFA-100
What pathway/s does Activated Partial Thromboplastin Time measure (factors)
Intrinsic and common
5, 7, 9 , 10, 11 prothrombin, fibrinogen
How is an activated partial thromboplastin time test performed
Activating agent
plasma
glass tube
phospholipid emulsion
Ca2+
How is the activated clotting time test performed and what does it measure
Time for whole blood to clot after contact with diatomaceous earth
Stimulating intrinsic and common pathways
Blood collected in tube containing diatomaceous earth and is incubated at 37*C
ACT prolonged with deficincies in 7 and 9, prothrombin and fibrinogen
Rapid patient side test
How is AT measured
Chromogenic assay
How is protein c measured
Chromogenic assay
A PCV below what usually requires a blood transfusion
<20%
Blood loss in surgery greater than what usually requires a blood transfusion
> 30%
What oxygen extraction ratio indicates need for blood transfusion
> 40-50%
What PCV is an indication for pRBC transfusion
<10-12%
What cases might benefit from pRBC transfusion
Normovolemic anaemia
Isoerythrolysis NI
Erythropoietic failure
Chronic blood loss
Plasma frozen >8 hours after collection has decreased what
Considered frozen not fresh frozen
Reduced F8 and 5
FFP should be started at what rate
4ml/kg
What can be added to detection mixtures to detect hemolytic rxns
Rabbit compliment
If the minor crossmatch is incompatible but major is compatible
Ok to do transfusion but with washed donor cells
Why should glass not be used to collect
Inactivates platelets
Hemolysis
What anticoagulant should be used to collect blood which will be used immediately
3.2% sodium citrate 1:9 anticoag:blood
RBC stored in saline-adenine-glucose-mannitol solution can be transfused up to how many days after collection
35
How often can plasmapherisis be performed in a donor
4-11L every 30 days
What % of blood lost should be replaced by transfion
25-50%
Blood should be delivered at what rate
0.3ml/kg over 10-20mins
