The Hematologic System
Red Blood Cells
Essential
substances are required to produce normal RBCs:
Iron
• For ages 22-65, you get all the iron you
need from recycling of RBCs by the spleen
• It is almost impossible to get iron-deficiency
anemia in the US for ages 22-65; if it occurs, it is probably actually due to
losing blood.
• Need to increase dietary iron in those <
22 years old and during pregnancy (to be able to grow)
·
Mild
anemia may be asymptomatic and should be suspected in infants, women of
menstruation age, and pregnant women.
B12
• get from diet (animal protein) and Brewer’s
yeast
• at risk: vegetarians, elderly
• Vitamin B12 deficiency - similar to ALS, MS
• stored in liver - would take 5-7 years to
become deficient (use in micrograms, store in milligram). Thus, it is not an acute type of
anemia.
Folic
acid
• stored in bone marrow
• we store 40 days
worth
• folic acid anemia
is an acute type of anemia
• needed for development of neural tube
(defects such as spina bifida due to lack of folic
acid occurring in the first 28 days of gestation)
Amino
acids
- recycled by spleen
Erythropoietin (Epogen)
• hormone produced
by kidneys
• patients with
chronic infection, chronic inflammatory conditions, or cancer produce interleukin-I (IL-I), a potent
suppressor of erythropoietin, resulting in “anemia of chronic disease”
• athletes get Epogen
in black market ($25,000/year); use to pump up RBC’s ---> 75-80 Hct ---> sludge in cerebral arteries ---> stroke at
age 20
Thyroid
• screen TSH at age 35
• hypothyroidism: female:male 8:1
(18:1 in elderly female)
• hypothyroidism
---> anemia (Sx: increased cholesterol)
• hypothyroidism
---> decreased BMR ---> decreased RBC production
• Most
common cause of high cholesterol in women = low TSH
Normal
RBC count: 4.5-6.0 million (women closer to 4.5, men
closer to 6.0)
This is due to men being composed of
more muscle, which needs RBCs for oxygenation.
Women, on the other hand, have more fat and less muscle, so do not require as many RBCs.
Hgb
(14) and Hct (42) should NOT be different in elderly
Erythropoiesis: formation and
maturation of RBCs
Stage of RBC
maturation include:
·
erythroblast
(in bone marrow, has nucleus)
·
pronormoblast
·
normoblast
·
reticulocyte (no nucleus; in
peripheral blood)
·
erythrocyte
(mature RBC)
Should
not have any nucleated RBCs in peripheral blood (on lab report, “Nucleated
RBCs” should be “0” because they are removed by the spleen). If no spleen, may have a few nucleated RBCs.
Nucleated
RBCs are seen in:
• sickle cell anemia
• thalassemia
• bone marrow
problems
• leukemias
retic count = rate at which
bone marrow produces RBCs
reticulocytes are immature precursors; 2% of total
RBCs
Case
examples:
·
14
year old female with anemia: retic count = 0.1% with anemia
Diagnosis? underproduction
anemia (Iron-deficiency anemia from diet)
(Note: For iron-deficient patients: check retic count
at least 7 days after starting iron)
·
22
year old female with anemia: retic count = 16%
Diagnosis? breakdown of RBC? (hemolytic)
overdestruction
of RBC
? bleeding
When
estrogen levels are highest, body cells look foreign ---> autoimmune disease
(RA, SLE, sickle cell, thalassemia)
In
sickle cell trait, RBC’s last 40 days compared to the normal of 109 days. It is OK for sickle cell patients to have a
high retic count.
RBC
Morphology
(RBC indices)
**
MCV (mean cell volume) = 80-96
(MCH, mean cell hemoglobin, does
corresponding changes = 28-33)
(MCHC
is usually a useless index)
RBC
indices used to diagnose anemia, a condition characterized by a
reduction in RBCs, which in turn decreases the oxygen-carrying capacity of the
blood. Hypoxia produces fatigue, among
other problems.
Anemia
is not in itself a disease, but a principal manifestation of many abnormal
conditions, such as:
·
deficiency
states caused by a dietary lack of iron, vitamin B12, and folic acid
·
hereditary
disorders of RBCs
·
disorders
involving the hematopoietic tissues (bone marrow damage or a hyperactive
spleen)
·
bleeding
from the GI tract or any organ secondary to cancer or trauma
·
a
family history of anemia is common, especial in certain racial and ethnic
groups
Etiology: Major causes of anemia are:
·
excessive
blood loss
·
deficiencies
and abnormalities of RBC production
·
excessive
destruction of RBCs
Remember
the normals of MCV (80-96) and MCH (28-33) for the
following case studies:
a. RBC of
3 million, MCV of 65 and MCH of 22
• MCV is decreased, or small, so microcytic
• MCH is decreased, so pale, or hypochromic
• with microcytic, hypochromic anemia,
S/S include being tired, palpitations, SOB
• 9 out of 10 are iron-deficient: assess for vaginal and GI bleeding, use of
NSAIDs, exercising too much (marathon runners and weight lifters get muscle
tears), drinking a lot of tea (can’t absorb iron)
• 1 out of 10 are due to other causes such as
thalassemia (Mediterranean background), lead
poisoning (on smear will see basophilia and
stippling, or blue dots on the RBCs).
• Those at risk for lead poisoning include
children, plumbers, painters, policemen, those drinking moonshine (made in
radiators), elderly
• Lead compounds with calcium and is stored
in the bone. Many current elderly ate
lead as children, which was stored in their bones. The lead is now coming out of the bone as
they lose their calcium
b. RBC of
3 million, MCV of 120 and MCH of 40
• MCV is increased, so large, or macrocytic
• MCH is increased, so “hyperpigmented”,
or polychromic
• Note:
alcoholics have MCV of 100-110
·
**
Alcohol abuse can be associated with direct marrow toxicity, vitamin
deficiency, and upper GI blood loss and is a common cause of a mixed microcytic and macrocytic anemia.
• With MCV > or = to 120, cause is Vitamin
B12 or Folic acid deficiency.
• The deficiency may be due to being a “tea
and toaster”, having a gastrectomy > 6 years ago, malabsorption in the small bowel due to Crohn’s
or celiac sprue, tapeworm, or being on a drug for at
least 40 days which inhibits folic acid.
• Drugs which inhibit folic acid include methotrexate for rheumatoid arthritis, Septra/Bactrim, phenytoin (Dilantin).
c. RBC of 3 million, MCV of 88 and MCH of 30
• MCV and MCH are both normal, so normocytic, normochromic
• But the RBC’s are low
• Causes:
anemia of chronic disease, hypothyroidism, cancer
Anemia
of chronic disease
– caused by chronic infection/inflammation or malignancy (decreased RBC
lifespan, failure of compensatory erythropoiesis,
disturbance of the iron cycle); RBCs more vulnerable to phagocytosis.
Other
important lab tests: serum iron, iron
binding capacity, ferritin.
serum ferritin:
best measure of iron stores (2X higher in males)
Too
high of iron level --> oxidation --> damaged artery wall --> increased
risk of placing cholesterol in walls --> increased risk of coronary artery
disease
(ASA
after MI --> small amount of bleeding --> decreased iron level -->
decreased CAD risk)
Hemoglobin A1C
(glycosylated hemoglobin)
• Normal is < 6
• Indicates blood sugar level over a 3 month period
(RBC lifespan is 109 days. Glucose
attaches and cannot unattach)
• Urine sugars are useless: urine output today is what the blood sugar
was 4 days ago. (only
good for ketone check in Type 1 diabetic)
• 5-8 weeks after treatment change, should
start to see improvement (decrease) in Hgb A1C
Polycythemia – an increase
in both the number of circulating erythrocytes (many number as high as 8-12
million/mm3) and the concentration of Hgb within the blood (rises to
18-25 g/100 ml)
Three
types of polycythemia:
1.
Polycythemia vera – classified as
a myeloproliferative disorder (meaning overgrowth of
bone marrow). Usually develops in middle
age, particularly among Jewish men.
a.
Possibly
a form of malignancy similar to leukemia and is often considered a premalignant
condition.
b.
3
major hallmarks of the condition
i.
relentless,
unrestrained production of erythrocytes
ii.
production
of excessive myelocytes (WBCs within the bone marrow)
iii.
overproduction
of platelets
c.
Clinical
manifestations: increase in blood
viscosity, increase in total blood volume (may be 2-3 times normal), severe
blood congestion of all tissues and organs, resulting in many symptoms
d.
Diagnosis: RBC count, Hgb, Hct,
and platelet count are increased, ABGs are normal, hyperplastic
bone marrow, serum uric acid 3-4X normal
e.
Management
(goals are to reduce blood volume and viscosity and reduce bone marrow
activity)
i.
Phlebotomy
(500-2000 ml blood until Hct reaches 45%)
ii.
Myelosuppressive agents
(radioactive phosphorus, chlorambucil, busulfan, hydroxyurea)
iii.
Radiation
therapy (to decrease production of RBCs in the marrow)
f.
Mortality
(prognosis depends on age at diagnosis, treatment used, and complications)
i.
30%
die of thrombotic complications
ii.
10-15%
die from hemorrhage
iii.
15%
die from either myelogenous leukemia or myelogibrosis accompanied by pancytopenia
2.
Secondary polycythemia: When the body’s demand for oxygen increases
for any reason, the bone marrow must produce more RBCs in order to prevent
tissue hypoxia. This compensatory
response to tissue hypoxia is called secondary polycythemia
a. Causes: chronic lung disease (particularly emphysema), congenital heart disease, and prolonged exposure to altitudes of 10,000 feet or more
b.
Symptoms
and lab findings same as those with polycythemia vera, except the WBC and platelet counts are normal and splenic enlargement is absent
c.
Management: treat the underlying disease or condition
causing hypoxia
3.
Relative polycythemia: Whenever the body loses plasma without losing
RBCs, the concentration of RBCs increases relative to the amount of plasma
remaining in the vascular system.
a. Causes are fluid loss and dehydration as a result of not enough fluid intake, diarrhea, vomiting, burns, and excessive administration of diuretics.
b.
Management: reestablishment of fluid and electrolyte
balance
Hemolytic
disease of newborn (HDN)
·
Can
occur only if antigens on fetal erythrocytes differ from antigens on maternal
erythrocytes
·
Maternal-fetal
incompatibility exists if mother and fetus differ in ABO blood type or if the fetus
is Rh-positive and the mother is Rh-negative
·
Incidence:
ABO incompatibility occurs in 20-25% of all pregnancies, but only one in
10 cases results in HDN. Rh incompatibility occurs in <10% of pregnancies and
rarely causes HDN in the first incompatible fetus (usually erythrocytes from
the first incompatible fetus released when the placenta detaches at birth,
cause the mother’s immune system to produce antibodies that affect the fetuses
of subsequent incompatible pregnancies).
·
Pathophysiology: HDN results if:
o
the
mother’s blood contains pre-formed antibodies against fetal erythrocytes or
produces them on exposure to fetal erythrocytes
o
sufficient
amounts of antibody (usually IgG) cross the placenta
and enter fetal blood, and
o
IgG binds with sufficient numbers of
fetal erythrocytes to cause widespread antibody-mediated hemolysis
and splenic removal
·
Clinical manifestations: If mild HDN:
appear healthy or slightly pale with slight enlargement of the liver or
spleen.
·
Pronounced
pallor, splenomegaly, and hepatomegaly
indicate severe anemia, which predisposes the neonate to cardiovascular failure
and shock.
·
Because
the maternal antibodies remain in the neonate’s circulatory system after birth,
erythrocyte destruction can continue.
This causes hyperbilirubinemia and icterus neonatorum
(neonatal jaundice) shortly after birth.
·
Without
replacement transfusions, in which the child receives Rh-negative erythrocytes,
the bilirubin is deposited in the brain, a condition
termed kerniterus. This produces cerebral damage and usually
causes death. Infants who do not die may
have mental retardation, cerebral palsy, or high-frequency deafness.
·
Prevention/Diagnosis: Coombs’ test
o
indirect Coombs measures antibody in the
mother’s circulation and indicates if the fetus is at risk for HDN
o
direct Coombs measures
antibody already bound to the surfaces of fetal erythrocytes and is used
primarily to confirm the diagnosis of antibody-mediated HDN.
·
Treatment:
prevention through immunoprophylaxis
o
If
an Rh-negative woman is given Rh immune globulin (RhoGAM) within 72 hours of exposure to Rh-positive
erythrocytes, she will not produce antibody against the D antigen and the next
Rh-positive baby will be protected. (The
mother must be given Rh immune globulin injections
after the birth of each Rh-positive baby and with any abortion.)
·
Treatment:
exchange transfusions in which the neonate’s blood is replaced with new
Rh-positive blood that is not contaminated with anti-Rh
antibodies (done within 24 hours after birth).
Phototherapy also is used to reduce the toxic effect of unconjugated bilirubin.
Sickle
cell disease: a group of disorders characterized by the
presence of an abnormal form of hemoglobin:
hemoglobin S (Hb S) within the
erythrocytes.
·
Hb S is formed by a genetic mutation
in which one amino acid (valine) replaces another (glutamic acid)
·
Hb S reacts to deoxygenation
and dehydration by solidifying and stretching the erythrocyte into an elongated
sickle shape.
·
Sickle
cell disease is an inherited, autosomal
recessive disorder that is expressed as sickle cell anemia, sickle cell-thalassemia disease, or sickle cell-hemoglobin C disease,
depending on the mode of inheritance.
·
Sickle cell anemia, a homozygous form (inherits HB
S from both parents), is the most severe.
·
Sickle cell-thalassemia and sickle
cell-Hb C disease are heterozygous forms in which
the child simultaneously inherits another type of abnormal hemoglobin from one
parent (and Hb S from the other parent).
·
Sickle cell trait, in which the child inherits Hb S from one parent and normal hemoglobin (Hb A) from the other, is a heterozygous
carrier state that rarely have clinical manifestations. (Because the
child has 50% Hb S, clinical manifestations occur
only with extreme stress.).
·
Incidence:
in persons with origins in equatorial countries, particularly central
Africa, the Near East, the Mediterranean area, and parts of India.
·
Incidence:
In US, most common in African Americans, 1:4000-1:5000 live births. In the general population, the risk of two
African-American parents having a child with sickle cell anemia is 0.7%. Sickle cell trait occurs in 7-13% of African
Americans.
·
Clinical Manifestations: When sickling
occurs, the general manifestations of hemolytic anemia—pallor, fatigue,
jaundice, and irritability—sometimes are accompanied by acute manifestations
called crises.
·
4
types of crises:
o
vaso-occlusive
(thrombotic) crisis
(vasospasm causes “log-jam” of blood)
o
aplastic crisis (In sickle cell
anemia, erythrocyte survival is only 10-20 days. Despite the increased need for new
erythrocytes, erythropoiesis is diminished, resulting
in profound anemia)
o
sequestration crisis (large amounts
of blood become acutely pooled in the liver and spleen (seen only in the young
child)
o
hyperhemolytic crisis
·
Treatment:
supportive care aimed at preventing consequences of anemia and avoiding
crises. Avoid fever, infection,
acidosis, dehydration, constricting clothes, and exposure to cold. Bone marrow transplant.
·
Acute
infection of B-lymphocytes (B-cells)
·
Most
common virus is the Epstein-Barr virus (EBV).
Others = CMV and other viruses and the bacterium Toxoplasma
gondii)
·
Can
be thought of as “it would have been a lymphoma, but it stopped short”
·
Usually
affects young adults between the ages of 15 and 30 (“kissing disease”)
·
Unaffected
B cells produce antibodies against the virus, and T cells assist the B cell
response of attacking the virus directly.
The proliferation of clones of B and T cells and removal of dead and
damaged leukocytes are largely responsible for the swelling of lymphoid tissues
(lymph nodes, spleen, tonsils, and occasionally, liver).
·
Sore
throat and fever, two of the earlier manifestations of infectious mono, are
caused by inflammation at the site of viral entry (and initial infection), the
mouth and throat.
·
Incubation
period: 30-50 days
·
S/S: headache, malaise, and fatigue during the
first 3-5 days that continue for 7-20 days.
Temperature for 7-10 days, sore throat, enlargement and tenderness of
the cervical lymph nodes.
·
Sore throat is the most common symptom. It appears in the first week and is usually
accompanied by hyperplasia of the pharyngeal lymphoid tissue with inflammation
and edema, as well as exudative tonsillitis.
·
Lymph node enlargement is the predominant clinical
manifestation of infectious mono.
Enlargement occurs gradually, most commonly in the anterior and
posterior cervical chains, and generalized lymph node enlargement also may
develop. Splenomegaly
occurs in about ˝ of affected individuals.
·
Usually
self-limiting, and recovery occurs in a few weeks. Treatment consists of rest and alleviation of
symptoms and analgesics.
·
Lab
findings: increase in lymphocyte and monocyte counts, with 10-20% atypical forms. During the first week of infection, the WBC
count may be normal or slightly low, secondary to mild neutropenia. After the first week, the WBC count
(predominantly lymphocytes and monocytes) increases
to 10,000 to 20,000 and persists at this level from 4-8 weeks. Platelet counts are low (<140,000)
·
Serologic
tests are necessary to diagnose infection by EBV. A Monospot
agglutination test is performed to show the presence of heterophilic
antibodies associated with infection by EBV.
(Heterophilic antibodies are a heterogeneous
group of antibodies that are agglutinins against sheep RBCs).
Leukemia: a malignant disease of the blood and
blood-forming organs causing an accumulation of dysfunctional cells and a loss
of cell division regulation
·
Two
major forms: acute and chronic: classified by predominant cell type and the
rate at which the affected individual develops clinical symptoms
·
Acute leukemia is characterized by
undifferentiated or immature cells, usually a blast cell. The onset of disease is abrupt and rapid. Disease progression results in a short
survival time.
·
In
chronic leukemia the predominant cell is mature in appearance but does
not function normally. The onset of
disease is gradual and the prolonged clinical course results sin a relatively
longer survival time.
·
Acute
types: ANLL (acute nonlymphoblastic
leukemia) founds in adults, ALL (acute lymphoblastic leukemia) most common in
children, and AEL (acute erythroleukemia)
·
Chronic
types: CML (chronic myelocytic
leukemia) and CLL (chronic lymphocytic leukemia) seen in adults
·
Mortality
rate for the US is about 7 per 100,000 individuals (high in Japan due to atomic
bombs)
·
Strikes
both sexes and all ages. Incidence rises
steeply, however, beyond age 50
·
5-year
survival rate is 35%, partly because of the poor survival of those with ANLL
·
Chemotherapy
has helped increase the 4-year survival rate for people with ALL from 4% in the
1960s to 73% in the 1990s
·
S/S: fatigue caused by anemia, bleeding resulting
from thrombocytopenia, fever caused by infection, weight loss, bone pain,
elevated uric acid, liver, spleen, and lymph node enlargement
·
Dx:
blood tests, bone marrow biopsy
·
Treatment: chemotherapy is treatment of choice
·
Controversial
are immunotherapy agents that induce differentiation of immature granulocytes,
and marrow transplants.
·
Chronic
leukemia cells are well differentiated and can be readily identified.
·
S/S: Advances slowly and surreptitiously, without
warning. Symptoms, when they do appear,
include splenomegaly, extreme fatigue, weight loss,
night sweats, and low-grade fever.
·
Incidence: of CML is approximately 1 per 100,000 people
·
CML
= a group of diseases called myeloproliferative
disorders, along with polycythemia vera, primary thrombocytosis, and
idiopathic myelofibrosis
·
Presence
of the Philadelphia chromosome is a diagnostic marker of CML
·
The
acute effects of CML resemble those of acute leukemia, but with more prominent
and painful splenomegaly.
·
CLL
predominately involves malignant transformation of B-cells (although T cell CLL
occurs less commonly). The B cells fail
to mature into plasma cells that synthesize immunoglobulin.
·
A
possible mechanism responsible for CLL of B cells is a deficiency of normal
helper T cells with an increase in suppressor T cells.
·
Treatment
for CML: bone marrow transplantation,
biologic response modifiers, and combination chemotherapy (but does not prolong
the average survival time)
Malignant
Lymphomas: tumors of primary lymphoid tissue (thymus and
bone marrow) or secondary tissue (lymph nodes, spleen, tonsils, and intestinal
lymphoid tissue).
·
The
major subdivisions of malignant lymphomas are Hodgkin disease and non-Hodgkin
lymphoma.
·
Hodgkin disease is a clonal
disorder: distinctive abnormal
chromosomes are present
·
An
inhibitor in the serum and spleen of individuals with Hodgkin disease
selectively binds to T cells and interferes with their function.
·
More
popular theory of how the disease spreads is the contiguity theory,
which suggests that Hodgkin disease spreads by the movement of existing tumor
cells through lymphatic routes.
·
Role
of EBV: Higher-than-normal antibody
titers to the Epstein-Barr virus are reported in individuals with Hodgkin
disease.
·
S/S: initial sign is usually an enlarged painless
mass, lump, or swelling in the neck. May
have intermittent evening fever, weakness, malaise, weight loss, anemia
(especially in the elderly)
·
Most
commonly affected lymph nodes in Hodgkin disease: cervical, axillary, inguinal, and
retroperitoneal (mesenteric, epitrochlear, bronchial,
and popliteal nodes are rarely involved).
·
Dx:
CXR, lymphangiography, and biopsy; presence of Sternberg-Reed cells
·
Treatment: radiotherapy and chemotherapy
·
Cause
of lymph node enlargement and cancerous transformation in non-Hodgkin lymphoma
is unknown.
·
Immunosuppressed persons have a
greater incidence of non-Hodgkin lymphoma, suggesting an immune mechanism. In contrast to Hodgkin disease, T cell
function is minimally affected. B cell abnormalities,
such as impaired and decreased antibody production, are more common in
non-Hodgkin lymphoma than in Hodgkin disease.
·
Increasing
frequency in persons with AIDS with extremely poor prognosis
·
S/S: The cervical, axillary, inguinal, and femoral
chains are the most frequent sites of lymph nodes enlargement (painless). CBC initially is normal…abnormalities not
seen until the disease is advanced. Pancytopenia (decreased RBC, WBC, and platelet counts),
when present, indicates hypersplenism or extensive
replacement of bone marrow by lymphoma.
·
Treatment: chemotherapy, radiation, bone marrow
transplantation
Platelets
have no nucleus.
For
cancer patients receiving platelets, the HLA antigens on the platelet surface
membrane need to be matched.
Normal
platelet count: 150,000 - 450,000
(depends on lab)
thrombocytopenia: platelet count < 100,000
Symptoms when < 50,000
3
types of problems:
1. Underproduction (bone marrow suppression)
due to:
• chemotherapy
• alcohol
• Tagamet
• viruses
2. Overdestruction
due to:
• ITP
• autoimmune problem
• viruses
• HELLP syndrome (Hemolysis (--> anemia), Elevated Liver enzymes, Low Platelets); seen with preeclampsia --> DIC
• heparin-induced
thrombocytopenia
3. Overutilization due to DIC caused by:
• complication of
pregnancy (#1 abruptio placentae,
#2 amniotic fluid embolism)
• sepsis
• multiple trauma
• snakebites
• cancer
Heparin-induced
thrombocytopenia
(“white clot syndrome”):
• Increased risk with high molecular weight
(MW) heparin
• Can even occur with heparin locks
• If on beef or pork heparin, check platelets
daily.
• Heparin should be discontinued within 5
days of starting
• After 7 days, it stimulates the immune
system to form heparin antibodies (autoimmune problem) ---> “white clots” in
arteries which can lead to multiple amputations
• Problems occur when platelets < 100,000
• Does not occur with Coumadin
Symptoms
of low platelet count:
• superficial
bleeding (mucous membranes, petechiae, purpura, oozing around tubes)
• prolonged
menstrual period
• coffee ground
emesis
• nosebleeds
(bilateral if not due to nose picking)
It
takes 7-10 days to reverse the effects of ASA.
It also takes time to reverse the effects of NSAIDs (for long-acting
preparations, takes at least 7 days).
Coagulation
cascade:
Left
side (extrinsic pathway) is initiated by damage outside the blood vessel (in
the tissue)
* factor
VII is: - dependent on Vitamin K
- inhibited
by Coumadin
- measured
by PT/INR
INR (International
Normalized Ratio)
• standardizes tests among hospitals, labs,
and offices
• normal is 2-3 when
on Coumadin (= 1.3-1.6 PT)
• Exceptions:
normal needs to be higher for those with artificial heart valves
Coumadin is very
sensitive to drugs (>77 drug interactions on Epocrates!):
- Decreases Coumadin level: phenobarbital,
black licorice
- Increases Coumadin level: Septra
Major
increase in intake of Vitamin K-containing foods (green, leafy vegetables) can
mess up PT/INR (test is also affected by Questran, enteral feedings, and Metamucil)
Right
side of cascade (intrinsic pathway) is initiated by damage within the blood
vessel
Heparin
blocks the intrinsic cascade
- monitor with PTT/aPTT
Fibrinogen:
• increased by
estrogen, birth control pills, and smoking
• BUT estrogen-replacement therapy (p.o.) DOESN’T increase fibrinogen (unless the patient had
had clots while on estrogen-containing BCPs)
DON’T
put female smoker on estrogen BCPs (use Norplant, Depo-Provera, progestin)
OR If smoker < 35 years old, give < 35 mg.
estrogen pills.