Hemostasis, surgical bleeding, and transfusion Flashcards
1
Q
T/F: The synthesis of prostacyclin (PGI2) and nitric oxide (NO) is largely responsible for the antiplatelet properties of the intact endothelium.
A
True; Both of these substances inhibit platelet aggregation, and NO also inhibits platelet adhesion. The vasodilation induced by NO also helps to prevent clot formation by promoting low-turbulence blood flow.
2
Q
T/F: The vasoconstriction induced by NO helps to prevent clot formation by promoting low-turbulence blood flow.
A
False; NO induces vasodilation, which does reduce turbulence.
3
Q
T/F: Platelet aggregation and adhesion are up-regulated by enzymes on the endothelial surface that degrade adenosine diphosphate (ADP).
A
False: Platelet aggregation and adhesion are prevented by enzymes on the endothelial surface that degrade adenosine diphosphate (ADP).
4
Q
T/F: The electropositive charges on endothelium and platelets physically prevent adhesion.
A
False; The electronegative charges on endothelium and platelets physically prevent adhesion.
5
Q
T/F: Endogenous heparin-like substances are present on the endothelial surface, contributing substantially to anticoagulation.
A
True
6
Q
_______________ act as cofactors for antithrombin, which inactivates thrombin and coagulation factors ___, ____, _____, and ____.
A
Glycosaminoglycans; VIIa, IXa, Xa, and XIa.
7
Q
T/F: When vessel injury occurs, endothelial cells can express tissue factor (TF) and downregulate expression of thrombomodulin, becoming procoagulant.
A
True
8
Q
T/F: Activated endothelial cells release von Willebrand factor (vWF) from the Weibel-Palade bodies, promoting platelet adhesion.
A
True
9
Q
Platelets contain _______ _________, ____________ and lysosomes, which store the majority of platelet proteins needed for the initiation of coagulation.
A
dense granules; α-granules; lysosomes
10
Q
The ____________ are the largest and most prevalent storage granules, comprising the majority of the storage capacity of platelets.
A
α-granules
11
Q
____________ contain a number of proteins involved in platelet aggregation and cohesion, including fibrinogen, factor V (FV), factor VIII (FVIII), fibronectin, vWF, platelet-derived growth factor (PDGF), and platelet factor 4.
A
α-granules
12
Q
What is “stored” in dense granules?
A
Dense granules store calcium, ADP, adenosine triphosphate (ATP), and serotonin.
13
Q
What is the strongest stimulant for the release of the contents of the dense granules?
A
Thrombin
14
Q
T/F: Platelet lysosomes contain predominantly acid hydrolases, responsible for degradation of unwanted cellular debris after complete activation of fibrin formation.
A
True
15
Q
T/F: Platelet adhesion is mediated by expression of P-selectin on the activated endothelium and by the platelet receptor GPIbα, which attaches to vWF.
A
True
16
Q
T/F: Thrombin, collagen, ADP, and thromboxane A2 promote platelet activation.
A
True
17
Q
After the platelet plug bridges the gap between endothelial cells, ___________, produced by neighboring healthy endothelial cells, prevents unwanted expansion of platelet aggregates by decreasing further ADP release.
A
prostacyclin (PGI2)
18
Q
The __________ pathway, or “contact activation” pathway, is initiated by the activation of factor ______ and subsequently factor ___ through the exposure of blood to a negatively charged surface.
A
intrinsic; factor XII (FXII); XI
19
Q
T/F: Contact proteins such as high-molecular-weight kininogen (HMWK) and prekallikrein interact with FVII to accelerate its activation.
A
False; Contact proteins such as high-molecular-weight kininogen (HMWK) and prekallikrein interact with FXII to acclerate its activation. The activation of factor VII is by TF present in fibroblasts or other tissue factor–bearing cells.
20
Q
What catalyzes the activation of factor IX by factor XIa?
A
calcium
21
Q
What catalyzes the binding of factor IXa to procoagulant VIIIa?
A
calcium
22
Q
What steps in the coagulation cascade are facilitated by calcium?
A
(intrinsic)
The activation of factor IX by factor XIa.
The binding of factor IXa to procoagulant VIIIa.
(common)
The convertion of prothrombin (factor II) to thrombin (IIa) by factor X.
The stabilization of the fibrin clot by cross-linking strands of fibrin monomer by factor XIIIa .
23
Q
The ________ pathway is initiated by the activation of factor VII by TF present in fibroblasts or other tissue factor–bearing cells.
A
extrinsic
24
Q
Which of the following is not one of the three overlapping phases of the cell-based model of coagulation?
- amplification
- fibrinolysis
- initiation
- propagation
A
fibrinolysis
25
T/F: Simultaneous activation of the fibrinolytic system with activation of coagulation is responsible for prevention of excessive fibrin deposition and restoration of nutrient blood flow to affected tissues.
True
26
Fibrinolysis, in conjunction with _____________ released by surrounding healthy endothelial cells, inhibits unwanted expansion of the fibrin clot.
prostacyclin (PGI2)
27
___________, an inactive zymogen produced primarily in the kidney and liver, is the principal component of the fibrinolytic system.
Plasminogen
28
How is plasminogen converted to plasmin?
Plasminogen activators such as tissue plasminogen activator (tPA) and urokinase plasminogen activator (uPA) convert plasminogen to plasmin.
The activation of the intrinsic pathway also activates plasminogen conversion to plasmin, through the action of kallikrein.
29
What is the role of plasmin in the fibrinolytic system?
Plasmin degrades fibrinogen and fibrin into soluble fibrin(ogen) degradation products (FDPs).
Plasmin also inactivates other members of the coagulation cascade, such as factors Va and VIIIa, and actively degrades prekallikrein and HMWK. Through these mechanisms, plasmin not only degrades fibrin(ogen) but also downregulates coagulation.
30
What are the products of fibrin(ogen) degradation?
The products of fibrinogen or fibrin degradation are the FDPs designated fragment X, fragment Y, and fragments D and E.
Plasmin degradation of cross-linked fibrin results in the D-dimer fibrin degradation product.
31
What does an increase in D-dimers indicate?
increased fibrin production (and degradation) or liver dysfunction (these fragments are removed by mononuclear phagocytes in the liver).
32
What are the principal inhibitors of coagulation (proteins that enzymatically bind with coagulation factors to form inactive complexes)?
The principal inhibitors of coagulation are antithrombin, heparin, protein C, protein S, and tissue factor pathway inhibitor (TFPI).
33
Where are platelets formed?
megakaryocytes in bone marrow and in the lungs.
34
This serine protease inhibitor is responsible for modulation of clot formation and is responsible for 70% to 80% of thrombin inhibition
in the coagulation system.
Antithrombin (AT); AT is a glycoprotein produced in the liver and in endothelial cells that binds aggressively to thrombin.
35
T/F: A stable thrombin-antithrombin (TAT) complex is removed by the reticuloendothelial system.
True
36
T/F: The cofactor heparin alters the arginine site of AT and dramatically increases its ability to interact with thrombin.
True; Heparin is a highly sulfated glycosaminoglycan, ranging in molecular weight from 3 to 30 kDa. It is produced primarily in mast cells located in the lung, liver, kidney, heart, and gastrointestinal tract. Heparin causes a conformational change in AT, which increases the activity of AT 1000-fold.
37
Where is heparin produced in the body?
It is produced primarily in mast cells located in the lung, liver, kidney, heart, and gastrointestinal tract.
38
Heparin releases ____ _____ ________ _________ from endothelial cells, thereby liberating one of the most effective inhibitors of the factor VIIa-TF complex.
tissue factor pathway inhibitor (TFPI)
39
T/F: Protein C is a vitamin C–dependent zymogen with primary inhibitory action on factors Va and VIIIa.
False; Protein C is a vitamin K–dependent zymogen with primary inhibitory action on factors Va and VIIIa.
40
Protein C is activated by __________________ complexes. This reaction is potentiated by the endothelial protein C receptor, which is located mainly in ______ vessels.
thrombomodulin-thrombin; large
41
When activated protein C is released into circulation, it associates with protein S and is able to inactivate which factors?
factors Va and VIIa.
42
T/F: Activated protein C is also profibrinolytic, since it inhibits plasminogen activator inhibitor-1 (PAI-1) and indirectly inhibits thrombin-activatable fibrinolysis inhibitor (TAFI) as a result of thrombin inhibition.
True
43
Tissue factor pathway inhibitor (TFPI) is a group of lipoprotein-bound proteins produced primarily by ________ and _____________ cells.
platelets; endothelial
44
T/F: In the presence of calcium, tissue factor pathway inhibitor (TFPI) inhibits factor VIIa-TF activation of factor X, thereby
dramatically decreasing the primary cellular initiator of coagulation.
True
45
What is the importance of calcium in the thrombomodulin–protein C–protein S pathway during the inhibition of coagulation?
In the presence of calcium, tissue factor pathway inhibitor (TFPI) inhibits factor VIIa-TF activation of factor X, thereby
dramatically decreasing the primary cellular initiator of coagulation.
46
T/F: PAI is present in endothelial cells and is stored in dense-granules of platelets.
False: plasminogen activator inhibitor (PAI) is present in endothelial cells and is stored in α-granules of platelets
47
What is the principal regulator of plasminogen?
plasminogen activator inhibitor (PAI) is the principal regulator of plasminogen through inhibitory effects on tissue plasminogen activator (tPA), which is a plasminogen activator.
48
What is the main physiologic inhibitor of plasmin?
The main physiologic inhibitor of plasmin is α-2-antiplasmin. An alternative inhibitor of plasmin, α-2-macroglobulin, may inhibit plasmin in a limited fashion, particularly if α-2-antiplasmin is overwhelmed.
49
T/F: Another inhibitor of fibrinolysis, thrombin-activatable fibrinolysis inhibitor (TAFI), is activated by thrombin, the thrombin-thrombomodulin complex, and plasmin. As a negative-feedback mechanism, plasmin can also activate TAFI.
True
50
Template bleeding time (TBT) is a platelet function test; it will be prolonged with ___________, ____________, and lack of vWF, and it may also be prolonged in cases of vasculitis.
thrombocytopenia; thrombocytopathia
51
Name 3 platelet function tests.
1. Template bleeding time (TBT)
2. platelet aggregation studies
3. platelet function analysis (PFA-100)
52
During this coagulation test platelet-poor plasma is mixed with thromboplastin and calcium, and time to clot formation is measured.
Prothrombin time
53
Prothrombin time (PT) measures the function of the _________ and __________ coagulation pathways
extrinsic and common
54
What conditions can result in a prolonged PT?
Deficiencies in FV, FVII, FX, prothrombin, and fibrinogen can result in prolonged PT.
55
Activated partial thromboplastin time (APTT) measures the function of the _________ and __________ coagulation pathways
intrinsic and common
56
The coagulation test is performed by adding an activating agent to platelet-poor plasma in a glass tube containing phospholipid emulsion and calcium.
Activated partial thromboplastin time (APTT)
57
What conditions can result in a prolonged APTT?
Deficiencies of FXII, FXI, FX, FIX, FVIII, FV, prothrombin, and fibrinogen can result in prolonged APTT.
58
T/F: Prolonged PT or APTT may be associated with body cavity bleeding, significant hematuria, or hematochezia.
True
59
This test measures the time required for whole blood to clot after contact with diatomaceous earth.
Activated clotting time (ACT)
60
Activated clotting time (ACT) simulates the _____________ and _____________ coagulation pathways.
Intrinsic and common
61
What conditions can result in a prolonged ACT?
The ACT will be prolonged with deficiencies of FVIII, FIX, prothrombin, and fibrinogen.
62
T/F: ACT is more sensitive than APTT for coagulation factor deficiencies.
False; ACT has the advantage of being a rapid, patient-side test; however, ACT is less sensitive than APTT for coagulation factor deficiencies.
63
Increased D-dimer levels indicate increased _____________ or inability to clear the products from the circulation.
fibrinolysis; The D-dimer assay is specific for plasmin degradation of fibrin, as opposed to FDPs, which indicate degradation of either fibrin or fibrinogen.
64
T/F: Severe inflammation can cause increases in coagulation, decreases in anticoagulation, and inhibition of fibrinolysis, resulting in a procoagulant state.
True
65
T/F: Endotoxin and proinflammatory cytokines can activate platelets and induce the release of vWF from endothelium.
True
66
T/F: AT and protein C have pro-inflammatory effects.
False; AT and protein C have anti-inflammatory effects.
67
What is the mechanism of action of heparin?
Heparin increases the activity of AT, thereby inhibiting thrombin and factor Xa.
68
T/F: Low-molecular-weight heparin (LMWH) has greater inhibition of FXa, dose-dependent clearance, and a longer half-life than unfractionated heparin (UFH).
True
69
T/F: In horses, administration of Low-molecular-weight heparin (LMWH) has been associated with prolonged APTT and decreased packed cell volume (PCV).
False; In horses, administration of unfractionated heparin (UFH) has been associated with prolonged APTT and decreased packed cell volume (PCV); these side effects are not seen with administration of LMWH.
70
Surgery of which of the following is not associated with significant risk for intraoperative and postoperative hemorrhage?
1. Sinuses
2. Gastrointestinal tract
3. Cranial reproductive tract
4. Spleen
Gastrointestinal tract
71
______ _______ transfusion serves to restore blood volume as well as oxygen-carrying capacity for horses that have suffered acute blood loss.
Whole blood
72
PCV may remain normal for up to _________ following acute hemorrhage because of the time required for fluid redistribution and the effects of splenic contraction.
12 hours
73
Estimation of blood loss at surgery can be used to guide the decision to transfuse, with loss of greater than ______________________ generally requiring transfusion.
30% of blood volume or approximately 12 Liters of blood from a 500 kg horse.
74
T/F: A rise in blood lactate concentration despite volume replacement with crystalloid or colloid fluids may indicate a need for blood transfusion.
True; 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.
75
T/F: Allogenic transfused red blood cells maintain a longer increase in PCV than autologous transfused red blood cells.
False; Red blood cells from allogeneic transfusions do have a much shorter half-life than autologous red cells, so transfusion should still be considered a temporary measure to restore oxygen-carrying capacity, relying on the horse’s erythropoeitic response or resolution of underlying disease to provide long-term resolution. The life span of transfused autologous RBCs after 28 days of storage is approximately 30 days, compared to a 14-day half-life for fresh, crossmatched allogeneic blood.
76
You have a 500 kg normovolemic anemic patient with a PCV of 14% and a donor with a PCV of 40%. How much whole blood is required to raise the patient's PCV to 20%?
6L of whole blood;
Blood transfusion volume = body wt x 0.08 x [(desired PCV - actual PCV)/donor PCV]
= 500kg x 0.08 x [(20 - 14)/40]
77
You have a 500 kg patient with total protein of 3.5 g/dL. How much plasma will you need to transfuse to attain a total protein of 5.0 g/dL? (assume donor has total protein of 7.0 g/dL)
4,821 mL (roughly 5 L);
Plasma transfusion volume = body wt x 45 mL/kg x [(desired TP - actual TP)/donor TP]
= 500kg x 45ml/kg x [(5.0 - 3.5)/7.0]
78
T/F: Fresh whole blood can provide platelets at concentrations high enough to treat severe thrombocytopenia.
False; Fresh whole blood can also provide platelets, though generally not in concentrations high enough to treat severe thrombocytopenia. For patients with primary thrombocytopenia or thrombocytopathia, platelet concentrates can be given. Platelet concentrates can be obtained by plateletpheresis or by centrifugation using a slow-spin technique.
79
T/F: Packed red blood cells (pRBCs) are indicated for normovolemic anemia, such as neonatal isoerythrolysis, erythropoietic failure, and chronic blood loss.
True; When pRBCs are not available, whole blood may be used for the same indications, although attention should be paid to the total volume given so that volume overload is avoided.
80
Which of the following is not an indication for a plasma transfusion?
1. hypoalbuminemia
2. clotting factor deficiency
3. neonatal failure of passive transfer
4. neonatal isoerythrolysis
neonatal isoerythrolysis constitutes a normovolemic anemia (total protein is normally unaffected and NI generally indicates adequate passive transfer) which would be more appropriately treated with whole blood or packed RBCs.
81
_________ and ______ _______ ________ contain immunoglobulins, coagulation factors (fibrinogen and factors II, VII, IX, X, XI, and XII), and cofactors (factors V and VIII), and the anticoagulant proteins _________, _________ __, and _________ __.
Fresh and fresh frozen plasma (FFP); antithrombin, protein C, and protein S
82
T/F: Colloid support is generally recommended in patients with a total protein less than 4.0 g/dL, serum albumin concentration less than 2.0 g/dL, or colloid oncotic pressure less than 14 mm Hg.
True
83
T/F: When plasma is not necessary for clotting factor replacement, a synthetic colloid such as hydroxyethyl starch (hetastarch) is preferred for volume expansion and more effective oncotic support.
True
84
__________ is a hemoglobin-based oxygen-carrying solution that is indicated for treatment of anemia.
Oxyglobin
85
The life span of transfused autologous RBCs after 28 days of storage is approximately ______, compared to a _____ half-life for fresh, crossmatched allogeneic blood.
30 days; 14-day
86
T/F: Intraoperative or posthemorrhage cell salvage is also an option for autotransfusion.
True; RBC recovery can be performed with specialized cell salvage equipment, which washes and filters collected blood, but cell salvage can also be performed with simple anticoagulation and filtration.
The technique of cell salvage is limited to cases in which the salvaged blood is not in an area of infection or malignancy, unless specialized washing and filtering equipment is used.
87
How soon after a transfusion can horses develop alloantibodies?
within 1 week of transfusion; however, a second blood transfusion may be performed safely within 2 to 3 days of the first transfusion without a blood crossmatch.
88
The major crossmatch involves mixing the ______ washed red blood cells with the ________ serum, whereas the minor crossmatch involves mixing the recipient’s _________ with the donor’s __________.
donor’s; recipient’s; red cells; serum
89
T/F: If the minor crossmatch is incompatible, but the major crossmatch is compatible, the transfusion can still be performed after washing the donor red blood cells.
True; The major crossmatch involves mixing the donor’s washed red blood cells with the recipient’s serum, whereas the minor crossmatch involves mixing the recipient’s red cells with the donor’s serum.
90
T/F: Immunoglobulins and coagulation factor activity are well-maintained for at least 1 year in fresh frozen plasma.
False; Immunoglobulins are well-maintained for at least 1 year in FFP; however, coagulation factor activity may decrease after 2 to 4 months of storage.
91
Up to ____ of RBCs lost into a body cavity (e.g., hemoperitoneum) are autotransfused back into circulation within ___ to ____ _____.
75%; 24 to 72 hours
92
T/F: In cases of severe acute blood loss, between 25% to 50% of the estimated total blood lost should be replaced by transfusion.
True; In cases of acute blood loss, PCV is often not useful for estimates of volume to be transfused since it does not accurately reflect blood loss. Instead, estimates of blood loss and evaluation of clinical parameters are used to determine the volume of blood needed. From 25% to 50% of the total blood lost should be replaced by transfusion since much of the circulating volume will be replaced by fluid shifts.
93
T/F: Volume of plasma for treatment of coagulopathy is often determined by clinical and clinicopathologic response. A starting point for treatment of coagulapathy is approximately 4 to 5 mL/kg plasma.
True
94
This hemostatic agent binds well to tissue and exerts a hemostatic effect by swelling as it is soaked with blood. It can be soaked in thrombin to help promote coagulation directly. This product can potentiate infection, and its use should be avoided in contaminated wounds. It is absorbed over a period of 4 to 6 weeks.
Purified gelatin sponges (made from purified animal gelatin)
95
______________________ is a chemically altered form of cellulose, which is particularly useful to control diffuse bleeding from broad surfaces.
Oxidized regenerated cellulose
96
What are the mechanisms of action of Surgicel (oxidized regenerated cellulose)?
Surgicel has mechanical hemostatic effects as a result of swelling from blood absorption, and it activates coagulation on the collagen surface. Surgicel also acts as a 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
97
T/F: Surgicel can be soaked in thrombin to help promote coagulation directly.
False; Gelatin sponges can be soaked in thrombin to help promote coagulation directly. Surgicel should not be soaked in thrombin, because the biologic agents will be inactivated in the low-pH environment.
98
T/F: The low pH of Surgicel may also lead to tissue inflammation and delayed wound healing.
True; The low pH may also lead to tissue inflammation and delayed wound healing, so any excess product should be removed from the surgical site.
99
How quickly is Surgicel absorbed?
Surgicel is absorbed in 7 to 14 days, although residue from the material may persist for several months to years.
100
These hemostatic agents are derived from bovine dermal collagen, and are available in fibrous (flour), sheet, and sponge forms.
Microfibrillar collagen agents (Avitene, Instat)
101
How quickly are microfibrillar collagen agents (Avitene, Instat) absorbed?
8 to 10 weeks
102
What is the mechanism of action for microfibrillar collagen agents (Avitene, Instat)?
Platelets adhere to the collagen and are activated, and the resultant platelet degranulation and aggregation lead to hemostasis. These products do not rely as much on their mechanical effect as does Gelfoam. They do bind tightly to the bleeding surface, so there is likely some mechanical blockage of injured vessels.
103
T/F: Microfibrillar collagen is an appropriate hemostatic agent for use in patients with thrombocytopenia or with contaminated wounds.
False; Microfibrillar collagen relies on platelet adherence, degranulation. and aggregation to lead to hemostasis. It can also interfere with bacterial clearance and wound healing, and it is therefore recommended that it be removed from the surgical site before closure of the wound.
104
These hemostatic agents have a porous surface that allows absorption of blood, thereby concentrating platelets and coagulation factors and reducing the time required for coagulation.
Microporous polysaccharide hemispheres (TraumaDex, chitosin)
105
T/F: Microporous polysaccharide hemispheres (TraumaDex) is absorbable and does not appear to inhibit wound healing.
True
106
_________ ____ is composed of beeswax and petroleum jelly and is used to control bleeding from bone surfaces.
Bone wax
107
What is the mechanism of action of bone wax?
Bone wax mechanically stops blood flow from vessels in bone, and it does not have any biologic hemostatic effect.
108
T/F: Bone wax is safe to use in long bone fractures and in contaminated wounds.
False; Bone wax inhibits bone healing, so it should not be used when fracture union is desired. It has also been shown to inhibit bacterial clearance from cancellous bone, and therefore it should not
be used in areas of bacterial contamination or infection.
109
T/F: Bone wax has been reported to cause adverse effects such as allergic reaction, granulomatous reaction, and embolization.
True
110
Name 5 common mechanical hemostatic agents.
1. Purified Gelatin Sponge
2. Oxidized regenerated cellulose (Surgicel)
3. Microfibrillar collagen agents (Avitene, Instat)
4. Microporous polysaccharide hemispheres (TraumaDex, chitosin)
5. Bone wax
111
T/F: Fibrin sealants do not require that the patient have normal platelets or coagulation factors.
True; Fibrin sealants replicate the last stage of coagulation and do not require that the patient have normal platelets or coagulation factors.
112
T/F: Fibrin sealants are biodegradable and have not been associated with tissue inflammation or foreign body reaction.
True
113
These products are applied directly to the tissue and promote hemostasis by adhesion and formation of a fibrin clot, reducing the size of the open bleeding defect.
Fibrin-based sealants
114
When would it be appropriate to apply topical hemostatic agents?
Topical hemostatic agents are needed for control of diffuse capillary bleeding from bone or parenchymal organs, such as liver or spleen.
