Hematology I Flashcards
The intima (the inner layer)
it is made up primarily of endothelial cells. The smooth endothelial lining physically repels the blood components away from the vessel wall, preventing activation of the clotting mechanism.
The second layer of the vessel wall
extremely thrombogenic and very active.
contains:
Collagen, a potent and important stimulus for platelet attachment to the injured vessel wall
Fibronectin, which facilitates the anchoring of fibrin during the formation of a hemostatic plug.
The third layer, the adventitia/externa
, participates in the control of blood flow by influencing the vessel’s degree of contraction.
Platelets
Platelets are round and disklike and circulate freely within the blood.
Platelets are constantly working to “patch” thousands of minute vascular injuries that occur in perpetuity. Approximately 7.1 × 103are used each day.
Where are platelets formed?
They are formed in the bone marrow from megakaryocytes, maintain a concentration count of approximately 150,000 to 300,000/mm3
how long do platelets live?
8-12 days
how do platelets flow?
The platelets flow along the vessel surface. Because they are smaller than some other constituents in fluid blood (e.g., RBCs, WBCs), they tend to be pushed aside, strategically positioned near the vessel-wall surface where they can then “react” in the event of injury.
Platelet function
Platelets are largely inactive unless they become activated as a result of vascular trauma. Adequate hemostasis is not possible in the absence of an adequate quality or quantity of activated platelets. Platelets work in conjunction with plasma proteins of the coagulation cascade to build a stable clot when injury to the vascular integrity occurs.
traditional description of clot formation in the response to injury
adherence of the platelet to the injured vessel wall and the response of the clotting cascade to form a stable clot and stop the progress of bleeding
What happens immediately after injury?
The vessel wall immediately contracts to cause a tamponade, decreasing blood flow.
3 phases of formation of primary plug
adhesion, activation, and aggregation
adhesion stage
vWF mobilizes from within the endothelial cells and emerges from the endothelial lining. Glycoprotein Ib (GpIb) receptors emerge from the surface of the platelet. The purpose of GpIb is to attach to vWF and attract platelets to the endothelial lining; vWF makes platelets “sticky” and allows them to adhere to the site of injury
Activation stage
platelet then undergoes a conformational transformation as it becomes activated under the influence of TF (a cofactor of the extrinsic clotting pathway)
aggregation phase
platelets form a mound whose only goal is to seal and heal the site of injury within the blood vessel.
Cofactors
Most cofactors are enzymes, with some exceptions (e.g., factors V and VIII).
The coagulation factors circulate as inactive cofactors until they are activated to assist in the process of coagulation.
Activation of cofactors results from either tissue or organ damage and sets in motion a process that terminates in stabilization of hemorrhagic conditions in the absence of pathology.
where is von wildebrand factor synthesized
endothelial cells
factors dependent on Vit K?
2, 7, 9,10
describe the intrinsic coagulation pathway
damage to vessel (internal) –> factor XII –> Factor XIIa –> Factor XI –> Factor XIa –> Factor IX –> Factor IXa; Factor IXa and Factor VIII come into the common pathway
describe the extrinsic coagulation pathway
external tissue damage causes conversion of Factor VII to factor VIIa, that along with tissue factor enter the common pathway
Thrombin (Factor IIa) assists in activating what factors? and influences recruitment of ______________ to the injured area w/ coagulation
I, V, VIII, XIII; platelets
T/F: most coagulation proteins are synthesized in the spleen
false; liver
which clotting factors are vitamin K dependent for utilization?
II, VII, IX, and X
which factor of the clotting cascade is required to ensure the platelet plug will hold, d/t it helping to form a cross linked mesh within the platelet plug
XIII
with the H&P what important questions would you ask directly related to issues with bleeding?
- do you experience any unusual bleeding or bruising (gums, nose bleeds, stools)
- hx of previous bleeding with dental procedures?
- repeated spontaneous bleeding episodes or excess bleeding after trauma?
- hx of bleeding more than anticipated in surgery?
- Family hx of bleeding tendencies/d/o?
H&P related to bleeding
1.important questions to ask r/t bleeding
2. do you see any physical signs of bleeding? bruising/petechiae
3. do they have any disorders of malnutrition, liver insufficiency, or possible vitamin D deficiency
4. pre-existing inherited coagulation d/o
5. preoperative use of medications that may influence bleeding/clotting
why would you be concerned about bleeding in a patient with: liver disease, cirrhosis, or absorption issues?
it would impair vitamin K synthesis and therefore the synthesis of vitamin K dependent clotting factors: II, VII, IX, X
anticoagulation medications
heparins and heparin derivatives
coumadin and derivatives
direct thrombin inhibitors
procoagulation medictions
vitamin K
antiplatelet meds
NSAIDs
ASA
persantine
thienopyridine
antifibrinolytic medications
amicar
transexamic acid
nonherbal dietary (vitamins) medications that can disrupt or influence coagulation
Vitamin K and E
Coenzyme Q10
Zinc
Omega 3 fatty acids
Herbals that can influence coagulation
garlic
ginger
ginko
feverfew
fishoil
flaxseed oil
black cohosh
cranberry
what are the most frequently assessed tests related to bleeding d/o?
Pt and aPTT
What do PT and APTT measure?
platelet function: adhesion and aggregation
T/F: modest prolonged bleeding time (PT and aPTT) does not predict surgical bleeding
true
what meds can alter bleeding time
NSAIDs and ASA
T/F: a normal platelet count inadvertently means they are functioning correctly
false; only tells how many are in plasma does not give information on fx
normal plt count
150,000 - 300,000
plt count is used to evaluate what
pts with petechiae , unexplained spontaneous bleeding, and to monitor thrombocytopenia
what is the primary role/fx of plt
maintain vascular integrity
aggregate when plug is needed to stop bleeing
help initiate clotting cascade
thrombocytopenia is defined as
< 150,000
surgical risk for bleeding would be when plts are < ___________
50,000
at what plt count is a pt at risk for spontaneous bleeding
< 20,000
normal PT
12-14 seconds
PT will be prolonged with d/o of the ______________ and ____________ pathways
extrinisic; common
coumadin and derivatives will alter which diagnostic bleeding time lab value
PT
normal INR
0.8-1.2
where do you want a pts INR before they go to surgery
1.2
normal aPTT
25-32 seconds
aPTT will be prolonged in disorders of the _____________ and ____________ pathways
intrinsic and common
aPTT is altered by what meds
heparin and LMWH
we use aPTT to monitor anticoagulation with _______________ therapy
heparin
we do not see evidence of prolonged PT or aPTT until it is decreased by ___________%
30
normal activating clot time (ACT)
90-150seconds
for cardiac surgery you would like to see an ACT of >
> 400sec
what is a TEG
measures the process of clot formation over time
what is the benefit of a TEG
allows you to evaluate platelet reactions, coagulation, and fibrinolysis over time
results of a TEG provide an indication of
clot strength
plt number and fx
intrinsic pathway defects
thrombin formation
rate of fibrinolysis
____________________ is used to guide blood product administration
TEG
T/F: you can use TEG to determine disorders in any coagulation pathway
false; INTRINSIC only
_________________ is a protein synthesized by endothelial cells and megakaryocites
von willebrand factor
what is von willebrand disease
failure to synthesize or secrete vWF or an accelerated clearance of vWF.
rare
may be inherited or acquired
sx range from mild to severe
when would you consider someone to have vWD?
when vWF is <30% of normal
which category of vWB would you have no evidence of regular/spontaneous bleeding, but bleeding may be likely after a surgery or trauma
mild
which category of vWB would you have spontaneous bleeding which can be relentless
severe
what is the most common inherited subtype of vWB
type 1 mild
acquired vWD is associated with…..
malignancy
autoimmune disorders
hypothyroidism
pt presents with mucocutaneous bleeding, and no clinical family hx of bleeding, but has hypothyroidism. What would you be concerned with
acquired vWD
what is the tx of vWD?
DDAVP
Tranexamic acid (Txa)
Factor VIII/vWF concentrate or cryoprecipitate
what is the drug of choice in tx’ing vWD
DDAVP
if you do not have Factor VIII/vWF concentrate in an acute bleeding situation in pt with vWD, what can you use?
cryoprecipitate
what do you give in an acute bleeding situation in a patient with vWD?
Factor VIII/vWF concentrate or cryopreciptate
avoid all antiplatelet drugs
___________________ is a x-linked hematologic recessive d/o characterized by unpredictable bleeding patterns
hemophilia
T/F: hemophilia affects males almost exclusively
true
hemophilia A is a deficiency of factor ___________, and B is a deficiency of factor _____________
VIII; IX
people with this bleeding disease often exhibit spontaneous bleeding, muscle hematomas, and joint pain leading to progressive arthropathy and orthopedic surgical intervention d/t severely decreased range of motion
hemophilia
mild hemophila A has factor VIII levels about _____________% to normal
5-30
moderate hemophilia A has factor VIII levels of ______________% to normal
1-5
moderate hemophilia A has factor VIII levels of ______________% to normal
<1
which category of hemophilia A is most common
severe
what is referred to as Christmas disease
hemophilia B (factor IX def)
T/F: hemophilia A and B are clinically indistinguishable from one another
true
considerations if pt comes in for surgery with hx of hemophilia
- hematology consult
- detailed coagulation profile
- detailed factor replacement plan prior to day of surgery
- plan for how to monitor levels in the perioperative period
tx for hemophilia A
cryoprecipitate
DDAVP
TXA and amicar
Factor VIIa
tx for hemophilia B
FFP
TXA amicar
Factor VIIa
________________ is a hemostatic agent of last resort for pts with hemophila A and B
Factor VIIa
_____________ reduces the efficacy of Factor VIIa (used to tx hemophilia A/B)
acidosis
T/F: DDAVP is a treatment for hemophilia A and B
false; no value in the tx of hemophilia B. used in Hemophila A
_______________ plays a central role in the development of DIC
tissue factor
primary cause of acute DIC
sepsis
what plays a role in the development of chronic DIC
tumors and large aortic aneurysms
how do you dx DIC
clinical presentation with laboratory tests such as: plt, aPTT, PT, fibrinogen, antithrombin, D-dimer
how do you Tx DIC
- ID and tx underlying cause
- hemodynamic support if needed
- blood products
- heparin
when would you use heparin in the tx of DIC
for DIC manifested by thrombosis or acrocyanosis and without active bleeding
what blood products could you give in the tx of DIC with active bleeding or high risk for bleeding
FFP
plts
cryoprecipitate and Antithrombin III
what is the most commonly inherited thrombophilia ?
factor V leiden
this is an autosomal dominant mutation that causes activated protein C resistance
Factor V leiden
how do you manage factor V leiden thrombophilia
antithrombotic therapy
anemia is described as a hgb [ ] of less than ______ in women and _____ in men
12; 13
what is THE most important adverse effect with anemias
reduction in arterial O2 concentration and potential decreased delivery to tissues.
H&P for anemia
general appearance
functional capcity
do they have fatigue
hx of blood transfusion?
bone pain?
splenectomy?
Dx testing for anemia
CBC
Iron and TIBC
type and screen/type and cross
_________________ is an autosomal recessive disorder for abnormal hgb, Hgb S
sickle cell anemia
if heterozygous for the autosomal recessive hgb S you have ______________; if homozygous you have __________________
sickle cell trait
sickle cell disease
which is more common heterozygous Hgb S (sickle cell trait) or homozygous Hgb S (Sickle cell disease)
heterozygous; sickle cell train ~ 10% of AA
those with sickle cell trait (heterozygous) you may not see sickling until PaO2 is ___________, but with sickle cell disease (homozygous) you may see it with a PaO2 of ________________
20-30; 30-40
triggers for sickle cell crisis
hypoxemia
hypothermia
infection
dehydration
venous stasis
acidosis
S/Sx of sickle cell crisis
chronic hemolytic anemia
intermittent vaso-occlusion
severe pain
end organ damage
what is the most common surgical procedure those with Sickle cell disease have to have? and why?
cholecystectomy; for gall stones d/t rapid breakdown of sickled RBCs –> increased bilirubin
how do you manage sickle cell
adequate hydration
PRBC transfusion
avoid hypoxemia
maintain normothermia
maintain normal acid base balance
adequate perioperative pain managemetn
caution with vaso-occlusive devices (tourniqutes)
for pt with sickle cell coming in for surgery; when would you consider giving PRBC peroperatively?
for young pts that are low to mod risk
to decreased Hgb S level to < 30-50%
for those that PRBC will not cause hgb to become > 10-11
this is a group of x-linked disorders resulting in RBC hemolysis when exposed to oxidative stress; is d/t a deficiency in _______________________
glucose-6 phosphate dehydrogenase
this disorder can present in african, middle eastern, mediterranean, and asian populations. may have severe newborn jaundice, acute hemolytic episodes throughout life, but most are asymptomatic throughout life. what is this?
glucose-6-phosphate dehydrogenase deficiency
in glucose-6-phosphate dehydrogenase deficiency, what oxidative stressors could lead to RBC hemolysis
infection
hypothermia
fava beans
meds: antimalarials, sulfonamides, nitrofurantoin, ciprofloxin, methylene blue, antipyretic analgesics
_______________ decribes an abnormally high Hct
polycythemia
what is the polycythemia that is due to reduction in plasma volume without an increase in red cell mass?
relative polycythemia
fasting would cause what type of polycythemia
relative polycythemia; reduction in plasma volume without increase in red cell mass
in polycythemia a HCT of > 55-60% causes what?
- increases whole body viscosity which affects blood flow esp in small vessels and cerebral circulation
- increase risk for thrombosis arterial and venous
thrombocytopenia is defined as a plt count less than _____________________
150,000
what are the causes of thrombocytopenia?
- decreased production: bone marrow, folate deficiency, and/or malignancy
- sequestration - liver and spleen diseases
- increased destruction: sepsis, DIC, ITP, TTP
T/F: risk of bleeding is inversely related to plt count
true
Generally, you can go to surgery if plt is greater than ______________
50,000
what is heparin induced thrombocytopenia?
immune response to heparin where plts are destroyed to > 50% decrease in plt count from baseline or plt < 100,000 from normal baseline count
complications of HIT
severe thrombosis which can lead to amputation and/or death
this HIT type occurs 1-4 days after start of heparin therapy
Type I HIT
HIT type I is __________________ mediated and type II is ________________ mediated
non-immune; immune
T/F: with HIT type I the thrombocytopenia will resolve spontaneously even with continued administration of heparin
true
T/F: HIT type I is associated with increased risk of thrombosis and serious complications
false
which type of HIT has an onset 5-14 days after the start of heparin therapy, and has severe thrombocytopenia affiliated with thrombosis and severe complications
HIT type II
Hit type __________ induces a clinically relevant hypercoagulable state with clotting and thrombus formation
II
which type of HIT does not resolve spontaneously, and requires the heparin therapy to be stopped to resolve?
type II
how do you diagnose HIT
thrombocytopenia
cutaneous abnormalities and tachyphylaxis after heparin administration
tx of HIT
- consult hematology
- stop heparin even prior to confirmatory lab tests
- administer direct thrombin inhibitors: Argatroban or lepirudin
- treat complications of thrombus formation
what is the leading cause of morbidity and mortality after orthopedic surgery
thromboembolic events
what ortho surgeries are the highest risk for thromboembolic events?
Total hip arthroplasty
total knee arthorplasty
pelvic fractures
Triad etiology behind thromboembolic events
triad: venous stasis, hypercoagulability, and vascular trauma
for total hip/knee patients should recieve LMWH when?
either > 12 hours preop or > 12 hours post op
those undergoing a major orthopedic surgery esp for total hip or total knee should recieve what post op prophylactic therapy to reduce risk of thromboembolic event?
LMWH or compression device for minimum of 10-14 days
postop prevention of DVT
early mobilization or ambulation
compression stockings
intermittent pneumatic compression (SCD)
ASA should be d/c’d how many days prior to surgery
7
ASA is antiplatelet which works by inhibiting _________________, and is ________________
cox-1; irreversible
NSAIDs are antiplatelets which inhibit __________________, but is _______________
Cox-1 or 2; reversible
how do you reverse NSAIDs?
platelets
most Cox-1 inhibitors (NSAIDs) should be d/c’d how many days prior to surgery
3
T/F: selective Cox-2 inhibitors are okay to continue up until the day of surgery
true
how many days before surgery should Thienopyridine derivative (antiplt) meds like plavix and ticlid be d/c’d?
7-10 days prior
Abciximab (Eliquis) should be d/c’d ______________ before surgery
48-72 hours
Low-molecular weight heparin should be d/c’d ______________ before surgery
12-24 hours
how do you reverse LMWH and heparin?
protamine sulfate
heparin should be d/c’d _______________ before surgery
6 hours
how do you reverse coumadin (warfarin)
vitamin K
FFP
Factor VII
warfarin (coumadin) should be d/c’d __________________ before surgery
5 days
INR < ____________ okay for most surgery’s, but for those where blood loss can be a good issue want the INR at least ______________
1.5; 1.2
if a patient is on coumadin, but they have 3+ risk factors for thromboembolus, how should you proceed before surgery?
bridge them to heparin or LMWH; coumadin must be stopped 5 days prior to surgery but heparin only 6 hours and LMWH only 12-24
what would be considered risk factors for thromboembolism
Afib
CHF
rheumatic heart disease
TIA
DM
HTN
> 75 years of age
mechanical heart valves.
what medications that we give in anesthesia account for the largest number of type 1 hypersensitivity reactions?
NMB
list the NMB from most likely to cause type 1 hypersensitivity reaction to the least likely
succ > vec > roc > pancuronium > Cisatracurium
what mediates a type I hypersensitivity reaction?
IgE
sx of type I hypersensitivity reaction
mild cutaneous sx
bronchospasm
cardiopulmonary collapse and death
T/F: 60-70% of anesthesia related reactions are IgE mediated
true
algorithm of intraoperative anaphylaxis treatment
- d/c triggering agent, put in trendelenburg, give 100% FiO2
- Epi
- NS or LR 10-30 ml/kg
- secondary treatment meds: vaso, albuterol, BB, benadryl, or hydrocortisone
Grade II anaphylaxis you administer what dose of epi?
10 -20 mcg SC/IM, IV
Grade III anaphylaxis you administer what dose of epi?
100-200 mcg SC/IV/IM q1-2 min; 1-4 mcg/min
Grade IV anaphylaxis you administer what dose of epi
1 mg IV, repeat as needed: 0.05-0.1 mcg/min
in the secondary treatment phase of the intraoperative anaphylaxis algorithim, if the pt is unresponsive to epi, you should give what?
vasopressin 2-10 units IV
secondary tx of intraoperative anaphylaxis if pt is still having bronchospasms what should you administer?
albuterol/ipratropium inhalants, or terbutaline SC
secondary tx of intraoperative anaphylaxis that we think could be due to a preoperative beta blocker, we would give
glucagon 1-5 mg IV q5 min
secondary treatment of intraoperative anaphylaxis d/t continued airway edema, you would give
hydrocortisone 100-250 mg IV
if you have an intraoperative anaphylactic event, post resuscitation, how should you proceed?
- trend serum tryptase for 120 min
- 24 hour monitoring for recurrence
- notify family/pt of rxn
- referral to allergist
factors that play a contributing role to the perioperative immune system dysfunction
- surgery
- blood transfusions
- hyperglycemia
- hypothermia
- general anesthesia
- opioids
Surgical site infection is defined as….
an infection at or near surgical incision within 30 days of the procedure or within 1 year after implantation of prosthetic device
which part of the immune system is activated during surgery?
innate
d/t immunosuppression affiliated with surgery and anesthesia, what can occur postoperatively?
surgical site infection/sepsis
tumor metastasis
T/F: surgical excision of a tumor may stimulate proliferation and metastasis of tumor cells
true
which anesthetic meds actually reduces cancer recurrence and metastasis?
- local anesthetics
- ASA
- NSAIDs
which anesthetic meds promote cancer progression and reduce long term survival
opoids
T/F: pts given 80% oxygen postoperatively have a shorter cancer free survival period
true
which anesthesic meds have no effect on cancer survival
NO and dexmethasone
T/F: you should avoid volatile anesthetic agents in cancer surgery d/t reproliferation and metastasis of cancer cells
false; insufficient evidence to avoid these in surgery
anesthesia management of the immunocompromised pt
- strict aseptic technique and maximum barrier precautions
- general or regional anesthesia or combined technique
- prophylactic abx administered 30 min prior to incision
- active warming measures to avoid hypothermia
- perioperative hyperglycemia must be avoided
- leukocyte poor and irridated blood products should be used when transfusion is unavoidable
- postoperative multimodal pain management.
