ANEMIA & COAGULOPATHIES Flashcards
anemia definition
decrease in red cell mass
- women hgb <11.5; hct<36%
- men hgb <12.5; hct<40%
decreases O2 carrying capacity
arterial oxygen content equation
CaO2 = (hgb*1.39)SaO2 + PaO2(0.003)
- hgb has biggest effect
compensatory mechanisms of anemia
- decreased blood viscosity
- decreased SVR (a function of vascular tone & blood viscosity)
- increased CO (increased SV & HR)
- tissue redistribution of blood to organs w/ high extraction ratios (myocardium, brain, kidneys – pallor occurs)
- EPO renal secretion
- oxyhemoglobin R shift (increased 2,3-DPG –> increases P50)
oxyhemoglobin dissociation curve: P50; P90
P50 = 27mmHg P90 = 60mmHg
R shift oxyhemoglobin dissociation curve
represents reduced affinity of Hgb for O2
things that indicate increased metabolic rate:
- increased temp
- increased [H+] (acidosis)
- increased 2,3 DPG
- sickle cell anemia
L shift oxyhemoglobin dissociation curve
represents increased affinity of Hgb for O2
things that indicate decreased metabolic rate
- decreased temp
- decreased [H+] (alkalosis)
- decreased 2,3 DPG
- CO
- abnormal Hgb (metHgb, etc.)
Bohr effect
increasing CO2 concentrations in the tissues facilitates release of O2
(and thus the pick up of CO2)
Haldane effect
oxygenation of the blood in the lungs facilitates the RBC release of CO2
basic anesthesia management of anemia
- determine underlying disease
- determine “state” of anemia for that patient
- don’t disrupt compensatory mechanisms (don’t decrease CO or L shift oxyhgb curve)
- maximize O2 delivery
- tx blood loss as necessary
in the compensated anemic patient, are rates of induction w/ volatiles changed?
NO
- less soluble in anemia = faster induction
- high CO in anemia = slower induction
considerations when thinking of transfusing
- Hgb (almost always if <6g/dl, consider b/n 6-10) **no transfusion trigger
- risks/benefits
- coexisting dz (ie CAD - keep hgb>7)
- anticipated EBL
goals of transfusion therapy
- increase oxygen carrying capacity
2. correct a coagulation disorder
risks of RBC transfusion
- hep B/C, HIV, infections
- longer ICU/hospital LOS
- transfusion related acute lung injury
- hemolytic transfusion rxns
- higher mortality rates
EBL & replacement generalities
<15% of total blood volume = no replacement therapy
15-30% loss = replace 3:1 w/ crystalloids
> 30% loss = RBC transfusion to replace O2 carrying capacity
> 50% loss = massive transfusion = add FFP & platelets to the RBC replacement @ 1:1:1
normal adult blood volume
men = 75mL/kg women = 65mL/kg
allowable blood loss
ABL = [EBV*(hct - allowable hct)] / hct
what is the effect of 1U PRBC
increases hgb 1g/dL
increases hct 2-3%
1U has a hct of 70%
s/s associated w/ acute blood loss
tachycardia
orthostatic hypotension
CVP change
w/ 40% acute blood loss, additional s/s:
- tachypnea
- oliguria
- acidosis
- restlessness
- diaphoresis
- EKG ischemia
MASKED BY ANESTHESIA
hct changes w/ acute blood loss
takes 3 days to plateau, may not be reflective of current status
- decreases in hct >1%/24hrs can only be explained by blood loss/hemolysis
anesthetic management of acute blood loss
- monitoring = invasive?, F/C
- induction = ketamine/etomidate
- maintenance = may have to avoid volatiles & just use scopolamine, benzos, opioids
- keep warm
- watch surgical field for blood loss, oozing, non-clotting blood, listen to suction, ask.
- restore intravascular volume = crystalloids, colloids, blood products
labs to monitor w/ acute blood loss
coags CBC (h/h, platelets) fibrinogen Ca++, K+ (RBC have citrate, binds Ca++; K+ leak occurs) ABGs (met acidosis = hypovolemia)
definition of massive transfusion
>10U of PRBC in 24hrs -same as- replacement of at least 1 blood volume in 24hrs -same as- replacement of 50% blood volume in 6hrs
consequences of massive transfusion
- hypothermia (use fluid warmer!)
- volume overload
- dilutional coagulopathy (no clotting factors in PRBC)
- 2,3 DPG decrease (none in PRBC)
- hyperkalemia (K+ leak)
- citrate toxicity
- PRBC contains glucose –> converted to lactate –> acidosis
iron deficiency anemia
ineffective erythropoiesis
- microcytic, hypochromic anemia
usually infants/small children
adults = reflects depletion of iron stores 2/2 chronic blood loss (GIB, menstruation, CA)
tx = iron; postpone elective surgery x4 weeks if severe to allow for correction
pernicious anemia
B12 deficiency = impaired DNA synthesis
- macrocytic anemia
- 2/2 EtOH, poor diet, malabsorptive syndromes, whip-its
can also lead to degeneration of lateral & posterior spinal columns = symmetrical paresthesia, unsteady gait
**thick, large, smooth tongue
anesthetic management of pernicious anemia
- AIRWAY management & plan B
- maintain adequate O2
- avoid N2O
- transfusion if necessary
- consider avoiding regional if paresthesia present
hemolytic anemia
accelerated destruction (hemolysis) of erythrocytes
- increased levels of unconjugated bilirubin
- increased LDH
- immature RBCs
EX:
- hereditary spherocytosis (impaired RBC structure)
- paroxysmal nocturnal hemoglobinuria (impaired RBC structure)
- G6PD deficiency (RBC metabolism disorder)
- pyruvate kinase deficiency (RBC metabolism disorder)
hereditary spherocytosis
autosomal dominant
most common hereditary hemolytic anemia in US
- severity ranges
- risk of hemolytic crisis w/ infections
s/s = splenomegaly & fatigue, gallstones, jaundice
anesthetic management of hereditary spherocytosis
depends on severity & if hemolytic exacerbation is present
- avoid infections
- cardiopulmonary bypass & mechanical valves may = excessive hemolysis
paroxysmal nocturnal hemoglobinuria
complement activated RBC hemolysis
- 20s-80s
- abnormalities/reduction in RBC membrane protein
- life expectancy after diagnosis = 10yrs
- result of CO2 retention & subsequent acidosis (OSA)
anesthetic management of paroxysmal nocturnal hemoglobinuria
- avoid respiratory depressants (acidosis)
- avoid hypoxemia, hypoperfusion, hypercarbia (acidosis)
- maintain hydration
- DVT prophylaxis (high risk 2/2 complement activation)
G6PD deficiency (glucose-6-phosphate dehydrogenase)
phosphogluconate oxidative metabolic pathway
- normally counteracts environmental oxidants & prevents globin denaturation
- w/ deficiency, oxidative stress = RBC membrane damage & hemolysis
what is the most common RBC enzymatic disorder?
G6PD deficiency
classes of G6PD deficiency
class I = chronic hemolytic anemia to Class V & VI = mild/no hemolysis
what aggravates preexisting G6PD (ie causes more hemolysis)?
oxidative drugs
infection
fava beans
anesthetic management of G6PD deficiency
depends on severity & acuity of anemia
- avoid risk of hemolysis
- avoid oxidative drugs (NSAIDs, quinolones, sulfa drugs, N2O, NO)
- avoid drugs that depress G6PD (iso, sevo, diazepam)
- avoid methylene blue & metHgb causing drugs (methylene blue = life threatening rxn) (lidocaine?, prilocaine, silver nitrate)
- avoid/aggressively treat conditions that cause oxidative stress (hypothermia, acidosis, hyperglycemia, infections)
what is the most common enzyme defect that results in congenital hemolytic anemia?
pyruvate kinase deficiency
what is more prevalent, G6PD or pyruvate kinase deficiency? which has more hemolysis?
G6PD more prevalent; pyruvate kinase is more hemolytic
what is pyruvate kinase deficiency?
accumulation of 2,3-DPG = oxyhgb R shift.
high incidence of hemolysis in the spleen = splenomegaly (improved w/ splenectomy)
- life threatening hemolytic anemia @ birth; chronic jaundice, gall stones
what are some types of acquired hemolytic anemia?
- immune induced (sensitization of RBCs, disease or drug-induced)
- infection induced (ie malaria)
periop considerations w/ hemolytic anemia
- increased risk of tissue hypoxia
- h/o splenectomy = increased infection risk
- increased DVT risk 2/2 coag cascade activation
- often on EPO preop
- consider transfusion if acute hgb drop <8 or chronic <6
- PREOP HYDRATION, possibly preop transfusion
- caution w/ methylene blue admin
what is sickle cell disease?
homozygous inherited disorder of hgb S mutation = defective beta globulin chain (valine substitute for glutamic acid) in 78-90% of hgb
- extreme states of deoxygenation –> Hgb aggregation & sickled shape cell
- this can occlude small vessels (impairs O2 delivery)
- higher rate of hemolysis; average RBC lifespan 10-20 days
complications of sickle cell disease
- severe hemolytic anemia = end organ damage
- splenic infarction by 10s = infection
- renal = painless hematuria & loss of concentrating ability = CRF by 30-40s
- pulmonary damage 2/2 chronic persistent inflammation
- neuro = ischemia & hemorrhagic strokes
- vaso-occlusive crises (episodic bone & joint pain associated w/ illness, stress, dehydration)
what is sickle cell crisis
life threatening, acute episode of hgb sickling in response to low O2 states
- ischemia/infarctions of oragns
- pain, stroke, liver/renal failure, splenic sequesteration, PE
- ACS
- PAIN
what is acute chest syndrome as associated w/ sickle cell crisis? tx?
can be fatal (typically 2-3 days postop)
- PNA like; new pulmonary infiltrate w/ one complete lung segment
- pulm vasc occlusion
- pleuritic chest px, dyspnea, fever, acute pulm HTN
TX
- transfusion/exchange transfusion
- O2, N2O (pulm vasodilation)
- abx; inhaled bronchodilators
- aggressive px management
sickle cell trait - what is it and what are the implications for anesthetic management?
heterozygous “carriers” of sickle cell disease
- genotype AS
- 40% of hgb S; 60% hgb A (normal)
- usually no anemia/symptoms, need no tx; 5% have some minor symptoms
- don’t require preop transfusions
sickle cell disease: what are some factors that put these pts at high risk for periop complications?
- advanced age
- frequent sickling episodes; severe episodes
- evidence of end-organ damage
- concurrent infection
w/ sickle cell pts, avoid all situations that lead to:
- HYPOXEMIA/ACIDOSIS
- HYPOVOLEMIA
- STASIS
preop management of the patient w/ sickle cell disease
- supplemental O2
- preop hydration x12hrs
- caution w/ premeds that cause resp depression (acidosis risk)
- regional for px control (although caution w/ stasis & hypotension –> compensatory vasoconstriction)
- pain management
- avoid infections
- avoid tourniquets
- keep pt warm
- maintain high CO
- take care w/ positioning to avoid stasis
what is thalassemia major?
inability to form either alpha (a-thalassemia) or beta (b-thalassemia) globulin chains of hgb
- deficit in O2 carrying capacity prompts high, defective RBC release –> aggregation & precipitation formation
- severe anemia, often require repeated transfusions
hallmarks of thalassemia major
- ineffective erythropoiesis
- hemolytic anemia
- hypochromia w/ microcytosis
complications of thalassemia major
- extramedullary hematopoiesis (bone marrow hyperplasia, stunted growth, osteoporosis, hepatomegaly) –> large max/frontal bones
- hemolytic anemia (splenomegaly, CHF, dyspnea, orthopnea)
- transfusion therapy (iron overload = cirrhosis, RHF)
- increased infection risk w/ splenectomy
- arrhythmias
- spinal cord compression
major organs (and implications) affected by iron overload
- pituitary = impaired growth, infertility
- thyroid = hypoparathyroidism
- heart = cardiomyopathy, cardiac failure
- liver = hepatic cirrhosis
- pancreas = DM
- gonads = hypogonadism
what is thalassemia minor?
heterozygous trait for either alpha or beta globulin gene mutation
= mild anemia, normal RBC count
anesthetic considerations of the patient w/ thalassemia major
- hemodynamic: CHF (+/- arrhythmias) common w/ severe anemia, low cardiac reserve, may want to avoid cardiac depressants
- hepatosplenomegaly (splenectomy? infection); coagulopathies (+/- regional)
- airway (maxillary overgrowth?)
- consider complications of iron loading from chronic transfusions
what is methemoglobinemia?
when iron in Hgb is oxidized from ferrous (+2) to ferric (+3)
what are the oxygen delivery implications w/ methemoglobinemia?
oxyhemoglobin dissociation curve is markedly shifted to the L = decreased O2 delivery to tissues
what are normal methgb levels? what levels cause issues?
normal = <1% <30% = no compromise to tissue oxygenation 30-50% = symptoms of O2 deprivation >50% = coma & death
what causes methgb?
- globulin chain mutations that favor hgb M formation (usually asymptomatic)
- mutations impairing the methgb reductase system (methgb levels <25%)
- toxic exposure to substances that oxidize normal hgb faster than reductase systems can convert back (infants at greater risk; LA, nitrates, NO)
anesthetic management of methgb
- AVOID toxic levels of methgb-causing meds, especially in infants, hgb M, & G6PD deficiency
- pulse ox is unreliable (typically reads 85% whether it’s higher or lower)
- tx of toxic methgb:
- avoid tissue hypoxia & further L shift of oxyhgb
- O2
- 1-2mg/kg methylene blue 1% over 3-5mins; repeat after 30mins
- art line
- correct acidosis
- monitor EKG for ischemia
what is aplastic anemia
bone marrow failures characterized by destruction of rapidly growing cells
causes:
- genetic disorders (fanconi)
- drugs
- radiation
- infectious process (viral hepatitis, epstein-barr, HIV, rubella, TB)
drugs associated w/ bone marrow damage & subsequent aplastic anemia
- abx
- antidepressants (TCAs, lithium)
- antiepileptics
- anti-inflammatory
- antidysrhythmics
- antithyroidal
- diuretics
- antihypertensives (captopril)
- antiuricemics
- antimalarials
- hypoglycemics
- platelet inhibitors (ticlid)
- tranquilizers
anesthetic considerations w/ aplastic anemia
- immunosuppressive therapy (stress dose)
- reverse isolation
- prophylactic abx
- hemorrhage risk
- LV dysfunction 2/2 hyperdynamic CO
- coexisting congenital abnormalities
- difficulty w/ cross matching blood products after multiple transfusions
anesthetic management of aplastic anemia
- preinduction/induction
- consider pretransfusion
- avoid nasal intubation, possibility of airway hemorrhage w/ DVL
- regional depends on coags
- labile hemodynamic response to induction - maintenance
- hyperoxia depresses bone marrow, use PEEP instead of increased FiO2
- avoid nitrous (bone marrow suprression)
- maintain normothermia - postop
- oxygenate
- monitor coag status
what is polycythemia
expanded RBC mass & increased hct
- increases O2 carrying capacity BUT increases viscosity –> net decreased tissue perfusion
causes of polycythemia
- reduction in plasma volume (dehydration)
- production of excess RBC (polycythemia vera)
- chronic hypoxia (pulmonary dz, low CO, extreme obesity w/ hypoventilation, high altitudes)
- increased EPO (renal dz, EPO secreting tumor)
at what hct level does polycythemia cause problems? how to treat?
hct >55%
tx = phlebotomy
4 steps of coagulation
- vascular spasm (TxA2)
- primary hemostasis (platelet plug) (adhere to vWF, activate, release ADP/TxA2 to activate other platelets)
- secondary hemostasis (fibrin mesh formation) (extrinsic or intrinsic pathway)
- fibrinolysis (plasminogen via tPA –> plasmin; breaks down fibrin)
extrinsic pathway of coagulation cascade
when cascade is initiated outside of intravascular space; fast (12 seconds)
factors = III, VII
PT/INR
intrinsic pathway of coagulation cascade
when cascade is initiated inside of intravascular space; slow (6mins)
factors = VII, IX, XI, XII
PTT/ACT
factors involved in final common pathway
I, II, V, X, XIII
what is factor IV
calcium
essential in all pathways
how does heparin work
increases action of antithrombin III
- -> inhibition of intrinsic pathway (measure via PTT/ACT
- -> also works on common pathway via inhibition of activated factor X
how does coumadin work
inhibits vitamin K factors (blocks extrinsic pathway (measure via PT/INR)
–> also inhibits intrinsic & common pathways
vitamin K dependent coagulation factors
II, VII, IX, X
protein C & S
what does FFP contain
all coagulation factors, no platelets
what does cyroprecipitate contain
fraction of plasma that precipitates once FFP is thawed
high concentrations of VIII, XIII, vWF, & fibrinogen
what is desmopressin
synthetic ADH
stimulates the release of endogenous vWF & increases factor VIII activity
what is hemophilia A
X-linked congenital factor VIII deficiency
what is the different between mild, moderate, and severe hemophilia A
severe = <1% of normal VIII levels (childhood diagnosis)
moderate = 1-5% of normal VIII levels; less problems than severe, but still increased risk of bleeding w/ surgery/trauma
mild = 6-30% of normal VIII levels; often undiagnosed until adulthood; increased bleeding w/ major surgery
anesthetic management of hemophilia A
bring factor VIII levels near 100% normal for surgery
- infusion of factor VIII concentrate, 50-60U/kg
- E1/2t factor VIII = 12hrs; thus may need to repeat
- continue therapy x2 weeks to avoid postop bleeding
- FFP, cryoprecipitate
- desmopressin (0.3mcg/kg IV for mild hemophilia A)
what is hemophilia B
congenital factor IX deficiency
what is the difference between mild, moderate, and severe hemophilia B
mild = factor IX levels 5-40%
moderate = factor IX levels 1-5%
severe = factor IX levels <1%; associated w/ severe bleeding
significantly prolonged PTT/normal PT
what are the lab findings in hemophilia A & hemophilia B?
B = prolonged PTT/normal PT
A = prolonged PTT/normal PT
anesthetic management of hemophilia B
- recombinant/purified factor IX to treat mild bleeding or as prophylaxis (100U/kg)
- E1/2t = 18-24hrs, may need to repeat dose
- increased risk of thromboembolic complications
- FFP
what is von willebrand’s disease?
most common inherited disorder of platelet function
different types, problem w/ either quantity or quality of vWF
type 1 = quantitative defect; desmopressin will work
type 2 = qualitative defect
type 3 = virtual absence of vWF b/c endothelium lacks vWF; desmopressin has no effect
clinical findings in patients w/ von willebrand’s disease
mucus membrane bleeding = epistaxis, easy bruising, gingival bleeding, GIB
- type 3 = bleeding in muscles & joints
- menorrhagia
labs
- normal platelet count
- prolonged PTT
what is normal beleeding time?
3-10mins
anesthetic management of von willebrand’s disease
- avoid nasal intubation/nasal trumpet insertion
- DDAVP therapy for mild bleeding or minor surgery
- – 0.3mcg/kg IV diluted in 30-50mL saline, infused over 10-20mins to minimize side effects
- — 300mcg intranasal; 100microL of 1.5mg/mL solution to each nostril
- cryo is more reliable for severe bleeding or surgical prophylaxis
list the blood products that you could give to hemophilia A, B, and von willebrand’s diseaes
hem A = factor VIII, FFP, cryo, DDAVP
hem B = factor IX, FFP
vW = cryo, DDAVP
drugs that induce platelet dysfunction or inhibition
- ASA (irreversible inhibition of COX–> decreased TxA2)
- NSAIDS (reversible COX inhibition)
- abx (PCN, cephalosporins –> interfere w/ platelet adhesion, activation, aggregation
- volume expanders (dextran, hydroxyethyl starch >2L)
patient factors that can induce platelet dysfunction
- hypothermia (<35)
- acidosis (<7.3)
- uremia
- liver disease
what is thrombocytopenia, what are s/s
low platelet count
s/s
- petechial rash
- nose bleeds
- easy bruising
- GIB
what is normal platelet count & lifespan
150,000-450,000
lifespan 9-10 days
what do you need the patient’s platelets to be for surgery
> 50,000
20,000-30,000 ok for minor surgery
100,000 for neurosurgery
how much does one 6 pack of platelets increase the patient’s platelet count by?
50,000
what is the most common cause of intraoperative coagulopathy?
dilutional thrombocytopenia & dilution of pro-coagulants
what are some reasons a patient could have acquired defects in platelet production?
- radiation
- chemotherapy
- exposure to toxins
- drugs (thiazides, alcohol, estrogen)
- malignancies
- viral hepatitis
- vitamin B12 or folate deficiencies
what is DIC
disseminated intravascular coagulation
- excessive deposition of fibrin/impaired fibrin degradation
- -> platelet consumption
what is DIC associated with
- sepsis
- trauma
- CA
- obstetric complications
- vascular disorders
- immunologic disorders
clinical symptoms of DIC
consequence of thrombosis & bleeding
- micro emboli accumulation in various systems = organ damage + impaired functioning
diagnosis of DIC
no single lab test can establish or rule out the diagnosis
- rapid decrease in platelet count <50,000
- prolonged PT, PTT
- elevated FDP (D-dimer)
- low plasma [ ] of factor VIII
- decreased fibrinogen levels
treatment of DIC
management of underlying clinical disorder that triggered the coagulation process
- transfuse platelets, FFP, cryo, RBCs if indicated
- heparin gtt
- hemodynamic/respiratory support
reasons for vitamin K deficiency
- malnutrition
- GI malabsorption
- abx induced elimination of normal intestinal flora
- liver disease/obstructive jaundic
lab results in vitamin K deficiency
prolonged PT
normal PTT
treatment of vitamin K deficiency
vitamin K (6-24hrs for full effect)
FFP for active bleeding
tests: what is normal bleeding time & what is it testing?
3-10 minutes
platelet function
tests: what is normal PT and what is it testing?
10-12 seconds
VII, III (X, V, II, fibrinogen)
tests: what is normal PTT & what is it testing?
25-35seconds
VIII, IX, XI, XII (X, V, II, fibrinogen)
tests: what is normal ACT & what is it testing?
90-120secs
VIII, IX, XI, XII
- specifically used to monitor the action of heparin
tests: what is normal thrombin time & what is it testing?
9-11 seconds
fibrinolysis, prolonged w/ low levels of fibrinogen
tests: what is normal fibrinogen level?
160-350
what are causes of hypercoagulability disorders?
congenital disorders acquired - malignancies - pregnancy - oral contraception - nephrotic syndrome - SLE
anesthetic considerations of hypercoagulability disorders
- early ambulation
- SubQ heparin
- TEDs
- ASA
- vena caval filter
- hydration
who is possibly on long term anticoagulant therapy?
- recurrent DVT
- hereditary hypercoaguable states
- CA
- mechanical heart valves
- afib
periop management of patients on warfarin
hold x5 days preop
- measure INR 1 day preop & if INR >1.8, give 1mg vitamin K subQ
- emergent reversal = 5-8mL/kg FFP
if high risk
- bridge w/ heparin 3 days after stopping coumadin
- turn off heparin 6hrs prior to surgery
- ok when INR <1.5
heparin reversal
protamine
long term anticoagulation and regional anesthesia
- can develop spinal hematoma/hemorrhage
- stop LMWH 24hrs prior
- ASA/NSAIDS: regional may be ok on their own
- stop plavix 7 days prior
- heparin: regional may be ok
- stop coumadin 7-10 days prior (INR <1.5)
