Download Hematologic Disorders

Hematologic Disorders
I.
Hematopoeisis
a. The process by which formed elements in the blood are produced
b. Begins with stem cell and differentiates based on hormonal influence or body need
II. Eurythropoesis
a. EPO – Eurythropoetin is the regulatory hormone required for creation of red blood cells
and without which cells would undergo apoptosis (programmed cell death)
b. Produced and released largely in the kidney
c. Stimulus for its production is low O2
d. Low O2 can cause anemia, hypoxemia, but rarely impairs blood flow to kidney.
e. Red cell production can only occur with the stimulus of EPO and adequate nutrients,
especially iron.
III. Red Blood Cell Disorders
a. Anemia – Decreased RBCs
i. Definition:
1. Hct of less than 36% in women, Hb of less than 11.5 g/dl
2. Hct of less than 40% in men, Hb of less than 12.5 g/dl
3. Characterized by decreased tissue O2 delivery
4. A small decrease in Hb can equal a big decrease in O2 carrying capacity
ii. Clinical manifestations:
1. Blood loss – acute blood loss results in hypovolemia, hypoxemia,
tachycardia, shortness of breath with rapid progression to shock or
circulatory collapse
a. Vascular instability appears with losses of 10-15% of total blood
volume.
2. Slower blood loss over months allows for compensatory mechanisms
a. Compensation for decreased CaO2 shifts O2 dissociation curve
to the right
b. Increased CO and RR
c. Increased 2,3 DPG – principally responsible for maintaining O2
carrying capacity in the face of anemia
d. Plasma volume expansion by pulling fluid from interstitium
e. Redistribution of blood to vital organs
f. Kidneys sense poor O2 and release erythropoetin
iii. Anesthetic Implications
1. If we think the patient is hypovolemic and we give lots of fluids, we are
diluting their hemoglobim even further.
2. Since their curve is shifted to the right, when we induce we
hyperventilate them we make them more acidotic and shift their curve
to the right. When we put them on the vent and give them too big
breaths we can overshoot and make them alkylotic
iv. Types of anemia – Morphology - three main classifications
1. Normocytic, Normochromic
a. RBCs are normal size, shape and Hb
b. Causes include acute blood loss, chronic disease
c. This is the type of anemia seen in chronic disease
d. People develop this mostly due to lack of erythropoietin
v.
vi.
vii.
viii.
2. Macrocytic, normochromic
a. RBCs are enlarged but Hg [] is normal
b. Can see in B12 or folic acid deficiency or both
c. Megaloblastic anemias are secondary to malnutrition,
malabsorption
i. This type is seen in alcoholics and in pregnant women
where demand is higher.
3. Microcytic hypochromic
a. Small cells that contain less than normal Hb
b. Seen in iron deficiency anemia and thalassemia
Types of Anemia – etiology
1. Increased RBC loss
a. Eg. Bleeding
i. Destruction of RBC or Hemolysis due to a defect
(intrinsic) or altered environment (extrinsic)
ii. Intrinsic – Sickle Cell, Thalassemia
iii. Extrinsic- incompatible blood transfusion
2. Decreased or defective RBC formation
a. Includes bone marrow malignancies
b. Chronic diseases involving kidney and liver or lack of B12,
intrinsic factor and folic acid
Types of Anemia – Functional classification
1. Marrow production defects (hyperproliferation)
a. Accounts for 75% of all anemia cases.
b. Results from marrow damage, iron deficiency, inadequate EPO
stimulation
c. Red cell maturation defects - Two types
i. Nuclear defects
1. Folate deficiency
2. B12 deficiency
3. Drug damage (methotrexate)
ii. Cytoplasmic defects
1. Severe iron deficiency
2. Defects in globin synthesis
3. Acquired abnormalities
4. Drug toxicity, alcohol abuse, and lead poisoning
are common causes of this condition
2. Decreased cell survival rate
Blood Loss/Hemolysis
1. In acute blood loss, our marrow can’t produce enough reticulocytes .
Chronic losses will increase reticulocytes.
2. Large chronic losses such as GI peptic ulcer or heavy menstruation
would present more like iron deficiency so we need to be aware that it
could be chronic bleeding instead.
Iron Deficiency Anemia
1. Smaller than normal and fragmented RBCs
2. Microcytic and hypochromic cells
3. Treatment
a.
b.
c.
d.
Iron administered orally if GI is normal
Transfusion is questionable depending on Hb [] and need
In cardiac disease we’d want them at Hb 10
Maximize O2 delivery and reduce demand
i. Decreased tissue O2 requirements may accompany
depressant effects of anesthetic drugs and
hypothermia, offsetting the decreases in tissue oxygen
delivery although this is unpredictable.
e. Normovolemic hemodilution
f. Cell saver
g. Effects on anesthetic agents
i. Volatile anesthetics may be less soluble in the plasma of
anemic patients, thereby accelerating the increase in
arterial partial pressure of agents. Although this would
lead one to believe that induction would be hastened,
the effect of increased CO in anemic patients makes this
unlikely.
ix. Anemia of Chronic Disease
1. Caused by disease, infection, cancer, AIDS, ETOH Liver disease
(cirrhosis), renal failure (lowered EPO release) Diabetes Mellitus
2. RBCs have normal appearance
3. Release of iron is blocked
4. Iron replacement treatment is not effective
x. Aplastic Anemia
1. Disorder of stem cell in marrow produces insufficient number of RBCs
2. Cells are normocytic and normochromic
3. Most common cause is cancer chemo drugs and radiation (but there are
lots of other causes including SLE –lupus)
4. Treatment – responds to Stopping the offending drug and supportive
transfusions
5. Management of anesthesia
a. Give corticosteroids, RBC transfusions prior to induction
b. avoid N2o b/c it has bone marrow suppression side effects
c. Maintain adequate PP of O2 (greater than 60)
d. Avoid decreases in CO
e. Be careful during induction because they can arrest if we lower
their CO
f. Careful with intubating b/c it can cause bleeding.
xi. Megaloblastic Anemia
1. marocytic normochromic – large cells
2. Most often due to folic acid or B12 deficiency resulting in disordered
DNA synthesis
3. folic acid deficiency is the most common of the vitamin deficiencies
4. Caused by malabsorption, malnutrition, intestinal disease, cancer
5. Complications:
a. Peripheral neuropathy, memory impairment
b. Liver dysfunction
6. Treatment
xii.
a. Oral B12 or folic acid
7. Anesthetic Management
a. Maintain O2 deliver
b. presence of neurologic changes may detract from using regional
or peripheral nerve blocks b/c of parathesias
c. Questionalbe to use Use of N2O, antiepileptics, barbiturates b/c
they can cause impariment of folic acid absorption in intestine
Thalassemia
1. Microcytic hypochromic
2. inherited disorders characterized by decreased rates of synthesis or
failure to synthesize structurally normal Hb.
3. No treatment is available for anemia due to thalassemia other than RBC
transfusion
4. Three types:
a. B-Thalassemia Major
i. Markedly reduced or no Beta chains
ii. Extra alpha chains create toxic bodies that kill
erythroblasts
iii. Overgrowth of the maxillae can make visualization of
the glottis difficult during DL
b. B-Thalassemia Minor
i. partial deficiency of B-chains
ii. Most of them are asymptomatic but are recognized due
to the presence of hypochromic, microcytic blood
picture that does not respond to iron
c. Treatment of B-Thalassemia
i. Diagnosis made during childhood
ii. Many patients require chronic hypertransfusion therapy
so that erythropoiesis is suppressed
iii. Splenectomy is required if the annual transfusion
requirement (volume of RBCs / kg/ year) increases by
>50%.
iv. Folic acid supplements may be useful.
v. Vaccination with Pneumovax in anticipation of eventual
splenectomy is advised.
vi. Early endocrine evaluation is required for glucose
intolerance, thyroid dysfunction and other endocrine
deficiencies which may result from iron overload.
d. Alpha –Thalassemia
i. lack of production of alpha chains of HbA
ii. Two main clinical syndromes
1. Hb-Barts - No physiologically useful hemoglobin
is produced beyond the embryonic stage. This
is incompatible with life and results in
intrauterine death between 28 and 34 weeks
iii. HbH disease - characterized by lifelong anemia of
variable severity, with splenomegaly. The disease is
unstable and precipitates in the red cell, forming
inclusions that are removed by the spleen
xiii. Sickle Cell Disease
1. The defect in structure occurs in the globin fraction of Hb
2. inherited disorder that ranges in severit
3. autosomal recessive genetic disorder in which an individual inherits the
sickle Hb from both parents
4. major rearrangement of Hb molecule when deoxygenation occurs
5. RBC then elongate and become rigid and crescent or sickle shaped
6. vaso-occlusion is the single most important pathophysiologic process
that results in most of the acute complications of sickle cell disease
7. Crises are exacerbated by hypoxia, infection or dehydration, may mimic
other acute illnesses, and last from a few hours to several days.
8. The incidence of the crises decreases with increasing age
9. Initiating conditions:
a. Hypoxia, hypothermia, dehydration, acidosis
10. Manifestations:
a. Hemolytic anemia
b. Painful crises
c. Microinfarction
d. Acute chest syndrome
e. The more crises they have, the lower their survival
11. Anesthesia
a. Increasing Hct to 30% is effective in decreasing post op
complication
b. Limit irritating conditions – preoxing, bag after meds to avoid
acidosis
i. Maintain hydration
ii. Avoid acidosis
iii. Maintain oxygenation
iv. Proper positioning – to avoid pooling of blood
c. Regional is advocated over general
d. Epidural and spinal can cause vasoconstriction and decreased
PaO2 in non-blocked areas
e. Hydroxyurea (10-30 mg/kg/day) – a big advance in therapy
f. Pain management: Untreated pain can also trigger crisis.
xiv. Hereditary Spherocytosis
1. abnormalities of RBC membranes that permit sodium, followed by
water, to enter RBCs at an increased rate
2. swollen, spherical cells cannot be compressed and are vulnerable to
rupture with even slight compression as they pass through the spleen
3. Manifestations:
a. Anemia, reticulocytosis and mild jaundice
b. Cholelithiasis secondary to chronic Hemolysis
4. Treatment
a. splenectomy if the anemia is severe. This procedure greatly
decreases hemolysis, returning RBC survival to 80% of normal
xv. Paroxysmal Nocturnal Hemoglobinuria
xvi.
xvii.
xviii.
xix.
xx.
xxi.
1. Sensitivity of RBC to lytic actions of complement proteins
2. Hypercarbia / acidosis activates it
3. Thrombotic episodes linked to direct activation of platelets Predisposition for venous thrombosis
4. Anesthetic Treatment –
a. Preoperative hydration and treatment of sepsis are
recommended to reduce the risk of thrombotic episodes
b. Post-op anticoagulation is preferably with coumadin as use of
heparin in low doses may activate complement pathways.
Glucose-6-Phosphate Dehydrogenase Deficiency
1. most common inherited RBC enzyme disorder – predominantly in males
2. Chronic hemolytic anemia is the most common clinical manifestation
3. Drug induced lysis – drugs that form peroxides are triggers
a. non opioid analgeiscs, sulfa, metheylene blue, nitroprusside
4. Severe hemolysis can lead to DIC – they clot and bleed at the same
time. Dessimated intervascular coagulation - DIC mortality is 70-80%.
5.
Pyruvate kinase deficiency
1. RBC membranes are highly permeable to K+ and prone to rupture (but
true mechanism of hemolysis is not completely understood)
2. Splenectomy does not prevent hemolysis but decrease the rate
3. Use of SUX has not been associated with hyperkalemia
Immune hemolytic anemia
1.
Dyshemoglobinemias
1. Methemoglobinemia
a. Ferric form of Iron unable to bind O2
b. O2Hb curve shifted to the left
c. red absorbance characteristics- SPO2 reads 85%
2. Treatment is methylene blue 1mg/kg every hour
3. Caution in patients with G-6-PD deficiency. If methylene blue is
contraindicated, only moderate doses of ascorbic acid (300 to 1000
mg/day orally in divided doses) should be given
4. Sulfahemoglobinemia
a. Drug induced
b. sulfhemoglobin is incapable of transporting oxygen and carbon
dioxide.
c. O2 curve shifted to right
d. No treatment – not reversible
Myeloproliferative Disorders
1. Stem cell disorders that are manifested by proliferation of
erythropoiesis, granulopoiesis and megakaryocytes in marrow
2. Types:
a. Polycythemia rubra vera
b. Essential thrombocythemia
c. Leukemia
d. Myelofibrosis
Polycythemia
1. an increased number of circulating RBCs reflected as an increased Hct
and elevated Hb concentration
2. Increased whole blood viscosity and volume
3. Primary Polycythemia
a. Myeloproliferative disorder where stem cell is abnormal
b. Progressive disease of middle age
c. Plasma is normal, vasodilation to accommodate RBC volume
d. Pt has red complexion
e. Predisposed to thrombosis and hemorrhage
f. Initial treatment is phlebotomy – removal of 500cc of blood 1-2
times a week until normal crit is obtained.
4. Secondary polycythemia
a. the volume of circulating plasma is decreased but the total
volume of circulating RBCs is normal.
b. most likely cause is dehydration.
c. Hemoconcentration, Renal dysfunction
5. Relative Polycythemia - “Smoker’s polycythemia”
a. most often occurs in middle-aged, obese, hypertensive men
who have a chronic history of smoking.
b. Increased production of RBCs most likely reflects a response to
chronic decreases in the patient’s PaO2 to less than 60 mmHg
c. smokers plug up their alveoli. They are hypoxic. So they release
more EPO and get more red blood cells
b. White Blood Cell Disorders
i. Neutrophilia
1. Increased nuetrophils following infection
2. Neutrophilia also occurs following stresses, such as severe violent
exercise or injection with epi.
3. This is why in OR and surgeon says give decadron (steroid) we need to
tell PACU nurse so they’ll know the white count could be elevated
ii. Neutropenia
1. decrease in the absolute neutrophil count
2. Older folks, marrow can’t be ramped up for infection, so they’ll
decrease their white count b/c marrow can’t produce enough to help in
an imune reaction.
3. Can also see in aplastic anemia.
iii. Leukemia – 4 Types
1. Acute Nonlymphocytotic Leukemia (ANLL) or Acute Myeloid Luekemia
(AML)
2. Acute Lymphoblastic (ALL)
3. Chronic Granulocytic Leukemia – presents most frequently in middle
age
4. Chronic lymphocytic leukemia
iv. Lymphoma
1. malignancies of the lymphatic system of unknown etiology
2. Non-hodgkin’s lymphomas
3. Hodgkin’s disease is a lymphoma that is predominant in young adults
18-35.
4. Anesthesia - we’ll see them take masses in abdomen and chest. Not a
lot of anesthetic complications
v. Multiple Myeloma
1. Plasma cell dyscrasias are a group of disorders manifested by a
proliferation of plasma cells in the bone marrow or peripheral blood or
both
2. Cause bone marrow suppression
3. Anemia
4. Thrombocytopenia
5. Leukopenia
6. Altered immune function
7. Hemostatic manifestation