Heme Flashcards
How to eval and treat hemolytic anemia from G6PD def
What is G6PD def
enzymatic d/o that inhibits regeneration of glutathione in RBC making them more suceptible to oxidative damage reduced lifespan of RBC
Workup: Hct, increased reticulocyte count, unconjugatedbilirubin, peripheral smear (heinz body), urinalysis (hemosiderin, urobilinogen), haptoglobin decreased
Eliminate precipitating factors: hypoxia, acidosis, hypothermia, hyperglycemia, infection/stress, fava beans,
drugs: methylene blue, nitrofuranotin, chloramphenicol, high dose ASA, hydralazine, procanamdie, SNP
Avoid drugs that induce metemoglobinemia (methemoglobin produces significant volume of oxidizing agents: lido, benzocaine, prilocaine, SNP
administer fluid & mannitol (maintain UOP and free radical scavanging properties
transfusion if necessary
Antimalarial drugs: primaquine, pamaquine, chloroquine
Sulfonamides: sulfanilamide, sulfamethoxazole mafenide, thiazolesulfone, dapsone
Methylene blue, toluidine blue
Drugs causing methemoglobinemia: benzocaine, lidocaine, articaine, prilocaine
Certain analgesics: aspirin,
nitrofurantoin
What is DIC?
cause
What labs would confirm
tx
differentiate bwteen liver dz and DIC
Disseminated intravascular coagulopathy-uncontrolled thrombosis and fibrinolysis (overerwhelming its inhibitors AT3 and alpla 2 antiplasmin)–>depletion of factors and plts, micro and large vessel thrombosis
cause
instrinisc pathway: endothelial damage:immune complex, bacteria/virus, vasculitis, sepsis (lead to activation factor 12)
Extrinsic; release TF from AFE/abruption/fetall death, adenocarcinoma, HUS, trauma/burns
dx: defects must be detected in all 3 pathways of hemostasis:
1) low plt 2)elevated PT PTT 3), decreased AT3 levels, low fibrinogen <100, elevated D-dimer=FSP (result of plasmin degradation of crosslinked fibrin)
tx
- treat cause
2) . FFP (replace factors, AT 3 and alpha 2 antiplasmin ) cryo (replace fibrinogen), plts
3) heparin for clots?
4) activated protein C? inhibits thrombin formation via 5a and 8a inhibition, also antiinflammatory agent - TXA contraindicated
- DIC precipitous decline in fibrinogen and plt
what is TRALI, pathophy
dx criteria
tx
Transfusion related acute lung injury-more common w plasma components
path: donor leukocyte antibodies lead to activation of neutrophils on pulm vascular endothelim –>endothelial damage capillary leakage
1. acute onset hypoxemia Pa02/Fi02<300, SP02<90%
2. pulm edema on CXR (b/l chest infiltreates) within 6 hrs of transfusion
3. absence of cardiac failure or fluid overload (PCWP<18)
tx: stop transfusion from this donor, support vent (low TV) No diuretics
TACO vs TRALI
- signs:
TRALI: normal-low BP, fever, transient leukopenia, +leukocyte antibody testing
TACO: HTN, JVD, edema
- fluid status
TRALI: normo-hypovolemic
TACO: hypervolemic–>diuretic
- cardiac fxn
TRALI: normal TACO: impaired, elevated BNP
Pathophys of SSD
when does polymerization occur
Hct goal
hemoglobinopaty in which mutation of chromosome 11 for beta chain. In presence of decreased oxygen tension, HBs polymerize an RBC take on deformed SS shape. Prone to hemolysis 15 days vs 120, microvascular occlusion of capillaries, ischemic end organ injury
PaO2 50 (PaO2 venous 40 75% sat), process also time dependent
Hct at least 30% and HBS <30-40% (leukoreduced)
COnsideration for SS pts
Preop: determine dz and severity
adequate hydration and pain control
Hct 40% and Hb SS<30% via simple or exchange transfusion
Intraop
avoid conditions that promote sickling-hypoxia, hypo/hyperthermia, hypovolemia, hypotension, acisosis, shivering
no tourniquet
SS head to toe
CNS: cerebral thrombosis, painful/vasoocclusive crises, deficits from stoke/seizures
Cardiac: CHFfrom chronic hypoxia, hemochromatosis, MI,
pulm: increased intrapulm shunting, ACS
GI: nonconjugated hyper bili from hemolysis, bile cholelithaisis,
renal: meduallary infarcts leading to isothenuria
Heme: splenic infarcts, aspetic necrosis, osteo, infection (asplenic), aplastic anemia(Parovovirus/folate decreased rbc production+ reduced life span (20 vs 120 days)–>profound anemia), transfusion, anemia
Endocrine: hemachromatosis-DI, hepatomegaly, adrenal insufficiency, hypothyroidism, hypopara
Goals w SSD
ACS tx
avoid hypoxia, hypercarbia, acidosis, anemia, hypotension
normothermia
ACS 1) oxygen, broncodilators, IS, chest physio 2) abx atypical and encapsuled org 3) pain control 4)correct anemia w simple transfusion or exchange
SS crises
- painful/vasoocculsive
- aplastic: infection or folate def
- sequestration in spleen
- hemolytic
ACS\
Conditons that promote sickling
anything that causes RBC hypoxia or lowerHg O2 affinity (Rightward shift)
- hypoxemia, hypotension, hypovolemia,
- hyperviscosity, vasoconstriction, hypothermia
- acidosis, fever, increased 2,3,DPG, shivering
leukocyte reduced blood benefits
- reduce risk HLA and RBC allooimmunization, limit plt refractoriness
- CMV transmission
- febril non hemolytic transfusion rxn
- may limit immune suppression
infectious risk associated with immunomodulation (TRIM)
Need to transfuse but no T&S
give type O RH neg blood- they have no A B D antigens on their surface. Switch to type specific when it become available. No longer throught that more than 10 units of O neg will result in significant amount of anti A and anti B antibodies tha will lead to incompatibility when pt own blood type is transfused. More of a concern w whole blood as contains significant amount of plasma whereas RBC do not
difference between type and screen and type and cross
T&S: typed for ABO and Rh antigens; mixes recipient plasma with pannel of commercial RBCs antigens to detect presence of known antibodies
T&C: mix recipient plasma with donor RBC to detect incompatbility
risk of hemolytic rxn
2/1000 type specific
6/10k T&S
5/10K for T&C
cell saver contraindications and relative
reduce risk how
absolute; mocrobial contamination of field, cancer surgery high risk of direct tumor manipulation and rupture
relative
hemoglobinopathy: SS thalassemia
- contamination:
- drugs not meant for systemic use-cholhexadine
- clotting agents–>activate systemic coagulation
- methy methacrylate–>hemodynamic changes
- urine–>bacteremia
- bowel contents–>bactermia
- amniotic fluid–>DIC
- pheo–>retransfusion of catecholamines
- malignancy
many concerns minimal if processed, washed, admin through leukodepletion feliter
Pharmacological agents
Clotting agents (Avitene, Surgicel, Gelfoam, etc.)
Irrigating solutions (betadine, antibiotics meant for topical use)
Methylmethacrylate
Contaminants
Urine
Bone chips
Fat
Bowel contents
Infection
Amniotic fluid
Malignancy
Haematological disorders
Sickle cell disease
Thalassaemia
Miscellaneous
Carbon monoxide (electrocautery smoke)
Catecholamines (phaeochromocytoma)
Oxymetazoline (Afrin)
Papaverine
Risks of cell salvage
- hemolysis/nephrotoxicity (high levelsof free hemoglobin)
- contamination (urine, amniotic fluid, fat bacteria, cancer cells)
- coagulopathy: hemodilution, contamination w procoagulants (activated coagulation factors)
- gas embolism if infusion bag in circuit w pt
unwashed more likely to contain debris and activated clotting factors
post esophagectomy complications
neuro: phrenic, vagal, larngeal nerve injury
cardiac: arrythmia, hypotension
pulm: aspiration, PNA, BPF, PE, ARDS (10-24%)
GI; anastomatic leak/dehis, complications of TPN
pathogenesis of acute porphyria
signs of attack
an enzyme in the heme bisynthetic pathway is deficient, resulting in overprodion of porphyrins. heme is the most abundant form for porhyrin used to make Hgb and cytoP450 proteins. production controlled by ALA synthestase
neuro: AMS, seziure, muscle weakness (peripheral neuropathy), cranial nerve dysfunctiom
cards: autonomic neuropathy-hemodynamic instability (HTN tachy),
resp: resp failure (bulbar paralysis)
GI: N/V abdominal pain
endocrine; electrolyte disburbances Low K, soidum calcium
How to reduce risk of porphyric crisis?
- minimize fasting (10% glucose in saline as source cards), dehydration, stress (anxiolytic), infection
- avoid drugs that could trigger crisis: barbituates (methohexital, penytoin), diazapam, ketorolac, etomidate?,
hydralazine, nefidipine
How to treat porphyric crisis
dscontinue any tiggering drugs
IV hydration w dextrose
hematin to inhibit ALA synthetase
neuro: if seziure/anxiety/pain control give midaz-not phenytoin /pain meds
resp: ensure oxygenation and ventilation
cards: control tachycardia HTN w BB
GI: N/V antiemetic, hydration, carb (10% dextrose)
refractory: admin hematin- suppressed ALA synthetase activitiy and thus productin prophyrin
PE for prophria
neuro: neuropathy, cranial nerve dysfuncton (bulbar), muscle weaknes (can be at risk of aspiration and resp weakness)
cards: autonomic NS instability (tachy and HTN), fluid imbalance
electrolytes imbalance
post op bleeding. What labs to order.
CBC, PT PTT INR, fibrinogen, Fibrin degradation products
etiology of uremic plt dysfxn
tx
- decreased VWF formation and release
- increased NO and prostacylin
- uremia induced anemia-decreased viscocity-decresed plt interaction w endothelail surfaces
tx.
DDAVP, cryo, plt
EPO for anemia
fastest most effective: remove uremic acid-hemodialysis
Thinks to consider when debating transfusion
- severity of anemia
- risk of excessive/ongoing blood loss
- comorbidites- CAD CHF
role of platlets in coagulation
secondary hemostasis
primary hemostasis-plt plug formation
- adhesion to subendothelial collagen via GP1b binding vwF
- activation shape change, expose GP2b/2a R that binds to fibinogen, degranulation
- alpha granules: PF4, fibrinognen/fibonectin, factor 5,8,vwf
- dense granules: ADP/ATP, calcium, serotonin - aggregation via GP2b/3a allowing plt-plt binding via fibrinogen
formation of fibrin clot via instrinstic and extrinsic pathway
- extrinisc 7a/TF–>10–>2–>1
- instrinisc: 11–>9/8–>10 (12
thrombin: activates 1, 13, 5,8, and factor 11 of instrinsic pathway
What factors are not made in liver
TF (3)
4 (calcium)
8:vwF (endothelium)
How is coagulation regulation
how is fibrinolysis regulatied
various inhibitors
primary
- normal endothelium, production No and prostaglidin
secondary
- AT3 inibits: 12a 11a 9a 10a
- Protein C s inhibit 5,8,
- tissue factor pathway inhibitor inhibits TF/7a complex
secondary
- PAI inhibits TPA
- alpha 2 antiplasmin consume plasmin
- thrombi activated fibrinolytic inhibitor prevents plasminogen activation
how is TEG measured
values
measures visoelastic changes via elasticity changes as detected by a piston in a slowly rotating cuvette
- R-time to initial clot formation (measures intrinsitic pathway
- K time from R to 20mm deflection
- alpha angle: measures rate of clot formation
- MA: max amplitude, measures clot strength
- A 60; amplitude at 60 min, measures clot retraction
Examples of aquired quantitative and qualiatitive plt d/o
Aquired:
autoimmume (ITP, drug induced)
blood dilution
CPB
DIC
splenic sequestration
Qualitative
hypothermia, hydroxyethyl starch, uremia, CBP, liver dz
thrombocytopenia, when to transfuse
depends on cause and expected response to transfusion, any ongoing coaguopathy, and type surgery
- ITP transfusion wont have prolonged effect
- minor surgery no signs of coagulopathy no need if 50k
- major surgery plt should be around 70-100k
- minor should have 50k
- 20K at risk for sponateous bleeding
Evaluate a bleeding d/o
H: ask about epistaxis, rectal bleeding, menorrhagia, hematuria, hemoptypsis,
NSAID ASA use
excessive bleeding w trauma, surgery, dental extraction, prior transfusion
P: look for petechiae and echymoses, arthrici changesn, signs liver dz or splenomegaly
Causes of elevated PTT
- hemophilia A-factor 8 (sex linked recessive)-joint bleeding most common & hemophilia B (9(
- VWD
- heparin, coumadin
- liver dysfxn
- vit K def
- lupus anticoagulant
anesthetic considerations for hemophilia A
why not FFP or cryo
what if ptt doesnt improve w factor 8 C
-Preop: determine severity via H&P and factor 8 level. activity of 50-100% required for surgery (DDAVP or factor 8::C 1-2 hrs bf incision
Intaop: avoid regional, careful positioning
postop: monitor for bleeding, half dose of factor 8C may need to be readmin every 12 hr
- decreased volume and infectious risk (crypo pooled from several donors
- antibody to/inhibiotr to factor 8 may be present
most common coagulopathy
Should DDAVP used
tx
VWD-most have minimal to no sx (easy brusing, epistxsis. PT and PTT usually normal
PTT usually only decreased in severe cases in which depletion of VWF leads to decrease in factor 8 (carried by VWF)
- Not all pts have clinical coagualopthy
- Response different depending on type
1: quantitiative defect
2. 2b contraindicated thrombosis and thrombocyopenia may result
3. complete deficiency
tx
- DDAVP 1 hr preop to cause endothelial release
- Humate P-factor 8C concentrate also contains vWF and preferred over cryo, pasturized –>viral inactivation
- ineffective try cryo: infectious risk
- FFP: volume (20cc/kg) +infectious risk (
-
How does liver failure cause coagulopathy
- decreased synthesis of clotting factors
- failure to clear activated clotting factors, plasminogen activators
- splenic sequestration in liver
Role vit K on coagulation
Who is at risk of vit K def
best test
- cofactor that catalyes the attachment of a carboxyl group to factors 2,7,9,10 protein C and S,
- malabs,oral abx, poor diet, coumadin, neonate
- PT since factor 7 has shortest half life and will be effected first
Why does hypothermia cause coagulopathy
- plt sequestration in liver and spleen
- plt dysfunction from impaired plt thromboxane A2
- Interference with factor activity
- release of thromboplastins
Aquired factor def causes
- liver dz: failure to synthesis
- vit K def
dilutional
fibrinolysis: CBP, hypothesmia, prostate surgery (urokinase), TPA
hypothermia
heparin
RBC processing
How long pRBC good for? plt
- 500cc whole blood centrifuged to give 250 cc RBC (hct 70%) resuspended to volume 350 6C
- RBC supernanent spun down to yeiled 70cc plt, stored at 24C
- FFPremaining supernanent frozen (to avoid inactivation of 8 and 5)
- cryo: collect gelantinous precipitate collected during slow thawing FFP
- in CPDA 35 days ADSOL 42 days, plt 5
-Risks of homologous/allogenic blood
Blood product modification
hemolytic transfusion rxn, transmitted dz (Hep c B, HIV HTLV), alloimmunization, immunosupression
- leukodepletion: prevent febrile rxn and alloimmunization
- irradiation: to prevent graft vs host
- CMV neg: for premature neonates, seroneg pregnant, immunocompromised
- washing- remove Iga
Transfusion indications
- RBCs: improve oxygen carrying capacity, symptomatic anemia
- plt:treat coaglopathy associated w thrombocyopenia/pathia
1. <100 and diffuse microvascular bleeding (+/-CBP_
2. < 50K ad impending surgery or invasive procedure
3. <20K in nonbleeding pt at risk for spontaneous bleeding - FFP:
1. bleeding associated w factor def (hemophilia, DIC, ), - TTP, AT3 def
- hemodilution
PT/PTT>1.5x normal in pt going to surgery or invasice procedure
reversal warfarin prior to emergency surgery and no time for vit K
diffuse microvascular bleeding
-cryp: hemophilia A, VWD, fibrinogen def (8 VWF, fibinogen, fibronectin 13)
No blood for pt w rare blood type, what to do
H1 & H2 blocker steriods
type specific blood if available, if not, type O-
o- risk of hemolytic trasfusion rxn 1-2/1000
6/10k ts
5/10 tc
Cause of acute hemolytic transfusion rxn
signs under GETA
tx
different from delayed
- ABO incompatble blood
- hypotension, tachycardia, fever, diffuse oozung (DIC) RF, ***hemoglobinuria if often only apparent sign***
- stop transfusion
- ABC-tx hypotension, fluid pressors
- limit renal injury: mannitol lasix, bicarb (prevents tubular hemoglobin precipitation)
- r/o couagulopathy
- confirm diagnosis; retyped donor and recpipeint and crossmatcg, coombs, low haptoglobin,hemoglobinuria and hemoglobinemia, increased serum bili
- acute are intravascular complement mediated whil delayed are mediated extravascular via RES (jaudice anemia fever)
Transfusion reactions (GAIN FAT)
- febrile: host antibodies against donor neutrophils (most common)
- anaphylaxiss: IgA to IgA def pt (wash RBC)
- TRALI: fever hypoxia pulm edema , antileukocyte antibodies against host leukocytes in the lung
- graft vs host: donor lymphocytes attacking host (irradiation or leukocyte depltion filter
- in immunocompromised: improved renal graf surivival and decrease reoccurance of crohns; increased tumor reoccurance and post op infection
- alloimmunization
- hemolytic
What is massive transfusion
complications
transfuison of 1-2 x the blood volume over 24 hr
coagulopathy (hemodilution)
hypothermia, acidosis/alkalosis, hyperK, hypocalcemia
volume overload, transfusion reaction
Indications of DDAVP (3 causes)
SE:
- Hemophilia A: works better when factor levels >5%
- Type 1 and 2a VWD
- uremia
- hypotension, flushing, ADH relese and hyponatremia
limitations of DDAVP
treatment for type 1 (not 2 or 3)
LIMITED DURATion of 6-12 hr
tachyphalaxisis
-type of blood that can be transfused depending on comptabiltiy
platelets do not need ABO but rh compatible for child bearing females (no Rh antigens, but ABO on surface, hemolysis rare)
FFP needs to be ABO but not rh
How does heparin work
- dose for CPB
- dose promatmine
- neg charged binds to AT3 and enhances its activity (inhibit 9,10,11)
- 300-400U/kg, ACT 400-480 (PTT unable to quantify larger doses)
- 1mg/100U
How does ANH work (Acute normovolemic hemodilution)
contraindications
blood loss minimized by reducing the blood likely to be shed during the procedure.
Leads to decreased viscosity and increased CO. maintain adequate oxygen deliver: decreased Hct but increased CO
-Blood flow is increased to vital organs, or organs that have higher oxygen extraction ratios
Anemia –>increase 2,3-DPG, –>facilitates oxygen extraction by tissues.
- Anemia Hbg <11 Hct<33
- Impaired renal fxn-pt may no be able to excrete fluid load
- conditions that make increased CO undesireable- AS
- signficant pulm dz: oxygen delivery to tissues may be inadequate in setting of pulm and decreased oxygen content associated with ANH
5 preexisiting coagulopathy
- severe CAD, Cerebrovascular dz
mechanism of HIT
-heparin binds to plt causing agglutination
anti-heparin IgG binds to complexes of PF4 and heparin
can consider plasmapheresis of antiheparin IgG
Protamine rxn
- histamine release from mast cells
- anaphylasis IgE in pt w prior protamin exposure (NPH PZI), fish allergy, vasectomy
3, anaphylactoid: IgG mediated
- PHTN: heparin protamin complexes result in release of thromboxane A2 from pulm macrophages
- A/C
mechanism of aminocaproic acid/TXA
-antifibinolytics: bind to lysine binding sites of plasminogen preventing to the conversion of plasminogen to plasmin and attachment to fibrinogen
SE: thrombosis (CI in DIC)
contraindication to neuraxial
refusal
coagulopathy
infection at site
critical preload and afterload dependence
How to reduce need for homologous transfusion
CI induced hypotension
- use lowest transfusion trigger that still provides adeuquate oxygen delivery: depends on coexisting dz, chronicity of anemia, and rapidity of anticipated loses. 7-9 usually acceptable for healthy pt, 10 for significant CAD
- intraop salvaging
- employ techniques that minimize blood loss: induced hypotension, isovolemic hemodilution, phamacology (NO, SNP, alpha blocks, BB, CCB)
- severe anemia, hypotension or dz w inadewuate end organ perfusion (CAD, CVD) - drugs tthat reduce transfusion: DDAVP, antifinrinolytics
How does body compensate for anemia
- increase CO: decrease viscosity (decreased afterload, increase venois return and preload-starling)
2, increase O2 extraction: increase 2,3, DPG
What is met Hbg
What causes it
dx
tx
- excess of oxidized Fe3+ ferric hemoglobin-which has decreased ability to bind to Oxygen and results in left shift of oxy hemoboglobin curve
- oxidizing agents- sulfonimides, nitrates, NO, SNP, benzocaine, prilocaine, G6PD def (inadequate reduced glutathione production which protects Hgb from oxidation)- def of enzyme responsible for oxidizing hemglobin
dx; cynaosis, sx tissue hypoxia (H/A dizziness), pulse ox 88
tx: mtheylene blue
Plan for case expecting massive blood loss
- 2 large bore IV + central introducer
- rapid infusers + blood warmers
- Blood products in room
- cell salvage
- antifibrinolytics
- ANH
