Emergencies in
Emergencies in
hematology
hematology
M. Zawartko, MD
M. Zawartko, MD
Department of Hematology,
Department of Hematology,
Pomeranian Medical University,
Pomeranian Medical University,
Szczecin
Szczecin
Emergencies in hematology
Emergencies in hematology
ATLS
ATLS
Hypercalcemia
Hypercalcemia
Spinal cord compression
Spinal cord compression
Superior vena cava syndrome
Superior vena cava syndrome
Leukocytostasis
Leukocytostasis
Hyperviscosity
Hyperviscosity
Pericardial effusion/tamponade
Pericardial effusion/tamponade
Intestinal obstruction
Intestinal obstruction
Urinary obstruction
Urinary obstruction
Malignant biliary obstruction
Malignant biliary obstruction
Increased intracranial pressure
Increased intracranial pressure
Neoplastic menigitis
Neoplastic menigitis
Other….
Other….
ATLS – Acute tumor lysis
ATLS – Acute tumor lysis
syndrome
syndrome
Is characterized by various combinations of:
Is characterized by various combinations of:
-
hyperuricemia;
hyperuricemia;
-
Hypergl
Hypergl
y
y
cemia;
cemia;
-
Hyperkalemia;
Hyperkalemia;
-
Hyperphosphatemia;
Hyperphosphatemia;
-
Hypocalcemia;
Hypocalcemia;
-
Lactic acidosis.
Lactic acidosis.
Is caused by the destruction of a large
Is caused by the destruction of a large
number of rapidly proliferating neoplastic
number of rapidly proliferating neoplastic
cells.
cells.
Frequently: acute renal failure develops as a
Frequently: acute renal failure develops as a
result of the syndrome.
result of the syndrome.
-Uric acid
-Glucose
-Potassium
-Phosphate
s
-Lactic acid
ATLS – Acute tumor lysis
ATLS – Acute tumor lysis
syndrome
syndrome
Most common offenders:
Leukemia
ALL & AML
Lymphoma
Aggressive or bulky
Also described in
MM, SCLC, breast, ovarian
ATLS usually occurs during or shortly (1-5 days)
ATLS usually occurs during or shortly (1-5 days)
after chemotherapy;
after chemotherapy;
In rare cases – spontaneous necrosis of
In rare cases – spontaneous necrosis of
malignancies causes ATLS – prior to chemotherapy.
malignancies causes ATLS – prior to chemotherapy.
ATLS – Acute tumor lysis
ATLS – Acute tumor lysis
syndrome
syndrome
Hyperuricemia:
Hyperuricemia:
May be present at the time of chemotherapy
May be present at the time of chemotherapy
Effective treatment kills malignant cells and
Effective treatment kills malignant cells and
leads to increased serum uric acid levels
leads to increased serum uric acid levels
from the turnover of nucleic acids.
from the turnover of nucleic acids.
Uric acid can precipitate in the tubules,
Uric acid can precipitate in the tubules,
medulla and collecting ducts of the kidney
medulla and collecting ducts of the kidney
leading to renal failure.
leading to renal failure.
Lactic acidosis and dehydratation may
Lactic acidosis and dehydratation may
contribute to the precipitation of uric acid in
contribute to the precipitation of uric acid in
the renal tubules.
the renal tubules.
ATLS – Acute tumor lysis
ATLS – Acute tumor lysis
syndrome
syndrome
Hyperphosphatemia
Hyperphosphatemia
Produces reciprocal depression in serum calcium
Produces reciprocal depression in serum calcium
Hypocalcemia – symptoms: neuromuscular irritability,
Hypocalcemia – symptoms: neuromuscular irritability,
tetany;
tetany;
Deposition of calcium phosphate in the kidney and
Deposition of calcium phosphate in the kidney and
hyperphosphatemia may cause renal failure.
hyperphosphatemia may cause renal failure.
Hyperkalemia
Hyperkalemia
-
Potassium is the principal intracellular cation and
Potassium is the principal intracellular cation and
massive destruction of malignant cells may lead to
massive destruction of malignant cells may lead to
hyperkalemia.
hyperkalemia.
-
In patients with renal failure may rapidly be life –
In patients with renal failure may rapidly be life –
threatening.
threatening.
-
Can cause ventricular arrythmias and sudden death.
Can cause ventricular arrythmias and sudden death.
ATLS – Acute tumor lysis
ATLS – Acute tumor lysis
syndrome
syndrome
The most important predictive factors:
The most important predictive factors:
-
tumor burden: hyperuricemia and high
tumor burden: hyperuricemia and high
levels of lactate dehydrogenase
levels of lactate dehydrogenase
(LDH>1500 U/l);
(LDH>1500 U/l);
-
Renal function
Renal function
Recognition & prevention are the most
Recognition & prevention are the most
important steps in the management of
important steps in the management of
this syndrome.
this syndrome.
ATLS – Acute tumor lysis
ATLS – Acute tumor lysis
syndrome
syndrome
Prophylaxis
Prophylaxis
Maintain hydratation by administration of ivf
Maintain hydratation by administration of ivf
at 3000 ml/m2 per day
at 3000 ml/m2 per day
Keep urine pH at 7,0 or greater by
Keep urine pH at 7,0 or greater by
administration of sodium bicarbonate
administration of sodium bicarbonate
Administer allopurinol at 300 mg/m2 per day
Administer allopurinol at 300 mg/m2 per day
Monitor serum chemistry.
Monitor serum chemistry.
Start chemotherapy when serum uric acid <8,0
Start chemotherapy when serum uric acid <8,0
mg/dl; serum creatinine <1,6 mg/dl; urine pH
mg/dl; serum creatinine <1,6 mg/dl; urine pH
>7,0.
>7,0.
If an urgent anticancer therapy is needed
If an urgent anticancer therapy is needed
consider dialysis.
consider dialysis.
ATLS – Acute tumor lysis
ATLS – Acute tumor lysis
syndrome
syndrome
In some cases, uric acid levels cannot be lowered sufficiently with the standard preventive
approach.
Rasburicase
can be effective in these instances.
Rasburicase
Recombinant urate oxidase enzyme
In humans, gene for this is inactivated
Converts uric acid to allantoin
Acts rapidly, decreasing uric acid levels within hours
Xanthine
Xanthine
Xanthin
e
oxidase
Uric Acid
Uric Acid
Allantoin
Allantoin
Urate Oxidase
Allopurin
ol
Hypoxanthi
Hypoxanthi
ne
ne
Xanthine
oxidase
Rasburicase
ATLS – Acute tumor lysis
ATLS – Acute tumor lysis
syndrome
syndrome
Despite aggressive
Despite aggressive
prophylaxis ATLS
prophylaxis ATLS
and/or oliguric or
and/or oliguric or
anuric renal failure
anuric renal failure
may occur;
may occur;
Dialysis is often
Dialysis is often
necessary and
necessary and
should be considered
should be considered
early in the course.
early in the course.
The prognosis is
The prognosis is
good, and renal
good, and renal
function recovers
function recovers
after the uric acid
after the uric acid
level is lowered to <
level is lowered to <
10 mg/dl.
10 mg/dl.
If:
If:
Serum K+ > 6mEq/l
Serum K+ > 6mEq/l
Serum uric acid >10
Serum uric acid >10
mg/dl
mg/dl
Serum
Serum
creatinine>10 mg/dl
creatinine>10 mg/dl
Serum
Serum
phosphate>10mg/dl
phosphate>10mg/dl
or increasing
or increasing
symptomatic
symptomatic
hypocalcemia
hypocalcemia
present
present
Treatment
Treatment
Begin
Begin
hemodialysis
hemodialysis
Hypercalcemia
Hypercalcemia is the most common life-threatening metabolic
Hypercalcemia is the most common life-threatening metabolic
disorder associated with neoplastic diseases, occurring in an
disorder associated with neoplastic diseases, occurring in an
estimated 10% to 20% of all adults with cancer. It also occurs in
estimated 10% to 20% of all adults with cancer. It also occurs in
children with cancer, but with much less frequency
children with cancer, but with much less frequency
(approximately 0.5%-1%).
(approximately 0.5%-1%).
Causes
Causes
The main causes of hypercalcemia due to cancer are an increase
The main causes of hypercalcemia due to cancer are an increase
in the amount of calcium absorbed from the bones, and an
in the amount of calcium absorbed from the bones, and an
inability of the kidneys to excrete excess calcium. Some cancer
inability of the kidneys to excrete excess calcium. Some cancer
cells secrete substances that cause calcium to be absorbed into
cells secrete substances that cause calcium to be absorbed into
the bloodstream from bones. Immobility, dehydration, anorexia,
the bloodstream from bones. Immobility, dehydration, anorexia,
nausea, and vomiting may also increase calcium levels.
nausea, and vomiting may also increase calcium levels.
Incidence
Incidence
Hypercalcemia occurs most frequently in patients with lung and
Hypercalcemia occurs most frequently in patients with lung and
breast cancer. It may also occur in patients with multiple
breast cancer. It may also occur in patients with multiple
myeloma, head and neck cancer, cancer of unknown primary
myeloma, head and neck cancer, cancer of unknown primary
origin, lymphoma, leukemia, kidney cancer, and
origin, lymphoma, leukemia, kidney cancer, and
gastrointestinal cancer.
gastrointestinal cancer.
Hypercalcemia
• History: Advanced
malignancy, especially:
multiple myeloma, breast
cancer, non-small cell lung
cancer
• Symptoms:
- Polydipsia, polyuria
- Anorexia
- Nausea, vomiting
- Lethargy, drowsiness
- Constipation, obstipation
• Signs:
- Dehydration, hypotension
- Hyporefllexia, muscle
weakness, confusion,
seizure, coma
- Ileus
• ECG
- Bradycardia
- Shortened P-R interval
- Shortened Q-T interval
- Wide T-waves
- Supraventrial and ventricular
arrhythmia
Hypercalcemia
Symptoms may
Symptoms may
be classified by the affected body
be classified by the affected body
part:
part:
Nervous system
Nervous system
Calcium plays a major role in the normal functioning of
Calcium plays a major role in the normal functioning of
the central nervous system (the brain and spinal cord).
the central nervous system (the brain and spinal cord).
Symptoms of hypercalcemia may include weakness,
Symptoms of hypercalcemia may include weakness,
loss of reflexes in the muscles, and decreased stamina.
loss of reflexes in the muscles, and decreased stamina.
Patients with central nervous system symptoms may
Patients with central nervous system symptoms may
have changes in personality, difficulty thinking or
have changes in personality, difficulty thinking or
speaking clearly, disorientation, or hallucinations.
speaking clearly, disorientation, or hallucinations.
Eventually, coma may result. Headaches can also occur,
Eventually, coma may result. Headaches can also occur,
which can be made worse by vomiting and dehydration.
which can be made worse by vomiting and dehydration.
Heart
Heart
Hypercalcemia affects normal heart rhythms and
Hypercalcemia affects normal heart rhythms and
increases sensitivity to some heart medications (such
increases sensitivity to some heart medications (such
as digoxin). As calcium levels increase, irregular
as digoxin). As calcium levels increase, irregular
heartbeats may develop, and may lead to a heart
heartbeats may develop, and may lead to a heart
attack.
attack.
Hypercalcemia
Symptoms may
Symptoms may
be classified by the affected body
be classified by the affected body
part:
part:
Gastrointestinal
Gastrointestinal
Increased stomach acid often is produced with hypercalcemia
Increased stomach acid often is produced with hypercalcemia
and may intensify loss of appetite, nausea, and vomiting.
and may intensify loss of appetite, nausea, and vomiting.
Constipation may result from the dehydration associated
Constipation may result from the dehydration associated
with hypercalcemia.
with hypercalcemia.
Kidney
Kidney
Hypercalcemia causes the kidneys to not function correctly,
Hypercalcemia causes the kidneys to not function correctly,
leading to the production of large volumes of urine. The
leading to the production of large volumes of urine. The
large amount of urine combined with less liquid intake leads
large amount of urine combined with less liquid intake leads
to symptoms of dehydration, including thirst, dry mouth,
to symptoms of dehydration, including thirst, dry mouth,
little or no sweating, and concentrated urine. Patients with
little or no sweating, and concentrated urine. Patients with
myeloma often have kidney problems due to hypercalcemia.
myeloma often have kidney problems due to hypercalcemia.
Kidney stones may result from long-term hypercalcemia.
Kidney stones may result from long-term hypercalcemia.
Bone
Bone
Hypercalcemia of cancer can result from bone metastases or
Hypercalcemia of cancer can result from bone metastases or
bone loss, and may contribute to broken bones, bone
bone loss, and may contribute to broken bones, bone
disfigurement, and pain.
disfigurement, and pain.
Hypercalcemia of Malignancy
Suspect hypercalcemia
Diagnosis
Diagnosis
-Measure blood pressure and heart rate lying and standing (if
possible)
-ECG
-Measure serum calcium, phosphate, albumin, urea, creatinine
-Correct serum calcium
Corrected Ca = measured Ca(mmol/L) + [40 - serum albumin (g/L)] x
0.027
Determine urgency of
treatment
Outpatient-based treatment
Outpatient-based treatment
-Serum calcium < 3.0 mmol/L
-Alert and oriented
-No significant nausea
-Adequate intravascular
volume
-Normal renal function
-No significant ECG
abnormality
-mild constipation
Hospital-based treatment
Hospital-based treatment
-Serum calcium > 3.0 mmol/L
-Altered level of consciousness
-Nausea or vomiting
-Intravascular volume
contraction
-Renal Dysfunction
-Significant ECG abnormality
-obstipation, ileus
Hypercalcemia of Malignancy
Treatment
(treat underlying malignancy when
(treat underlying malignancy when
possible)
possible)
General Measures
General Measures
-Avoid immobilization (if possible)
-Discontinue calcium supplements, vitamin D, cimetidine, NSAIDs,
thiazides
Hospital -based treatment
Hospital -based treatment
- Replacing fluids is the first and most
important step in treating moderate or
severe hypercalcemia.
-Use furosemide 20-40 mg IV if concerns
of volume overload
-Drugs that may help stop the
breakdown of bone include calcitonin,
plicamycin (mithramycin),
bisphosphonates (etidronate,
pamidronate, and clodronate), and
gallium nitrate.
-Steroids and phosphate may also be
used to treat hypercalcemia.
-Dialysis is used in patients with kidney
failure.
-Combinations of drugs may also be
used.
Outpatient-based
Outpatient-based
treatment
treatment
-Maintain adequate oral fluid
intake
-Correct serum phosphate
with oral supplements
-For breast cancer,
lymphomas or myelomas
give prednisone 40-100 mg
PO daily
-Arrange for urgent follow-up
with oncologist
1.
http://www.bccancer.bc.ca/HPI/Chemotherap
yProtocols/SupportiveCare/default.htm
2.Cancer: Principles and Practice of Oncology
(4th ed.) 1997: DeVita S, Hellman S,
Rosenberg S,
ed.. Vol. 2, Section 3 Metabolic
Emergencies:Hypercalcemia, pages 2486-
2493.
Superior vena cava syndrome
Superior vena cava syndrome
(SVCS)
(SVCS)
The superior vena
The superior vena
cava syndrome is
cava syndrome is
the group of
the group of
symptoms that
symptoms that
result from
result from
compression of the
compression of the
large vein (superior
large vein (superior
vena cava) that
vena cava) that
transmits blood to
transmits blood to
the heart from the
the heart from the
head, neck and
head, neck and
upper extremities.
upper extremities.
Superior vena cava
Superior vena cava
syndrome
syndrome
SVCS is the clinical manifestation of the SVC
obstruction
– External (mass effect)
– Internal (thrombus)
Etiology
Malignancy (78-85%)
- Lung (small-cell and squamous-cell histologies,
accounts for ~85% off all cases of malignant origin)
- Lymphoma =>
YOUNG ADULTS!!
YOUNG ADULTS!!
- Others (primary mediastinal germ cell, thymoma)
Infection
Thrombosis
Superior vena cava
Superior vena cava
syndrome
syndrome
Up to 60% with SVCS will not have
prior cancer diagnosis
Symptoms & signs
-
Dyspnea
-
Caugh
-
Neck & facial swelling (especially
around the eyes) (+/- plethora)
-
Venous distention
-
Other: hoarseness, tongue swelling,
headaches, nasal congestion,
epistaxis, hemopthysis, dysphagia,
pain, dizziness, syncope, and letargy.
-
Dilated veins
-
Increased number of collateral veins
covering the anterior chest wall
-
Cyanosis
-
Edema of the face, arms, and chest
-
In severe cases: proptosis, glossal
and laryngeal edema and
obtundation.
Superior vena cava
Superior vena cava
syndrome
syndrome
Chest radiographic
findings: widening of
the superior
mediastinum, most
commonly on the right
side.
However, a normal
chest radiographs is
still compatible with
the diagnosis if other
characteristic findings
are present
Superior vena cava
Superior vena cava
syndrome
syndrome
Image with CT (MRI if can’t use contrast) –
computed tomography provides the most
reliable view of the mediastinal anatomy.
Tissue diagnosis (bronchoscopy,
percutaneous needle biopsy,
mediastinoscopy, and even thoracotomy)
Superior vena cava
Superior vena cava
syndrome
syndrome
Treatment
Underlying cause:
-
Radiation therapy for SVCS caused by non – small cell lung
cancer and other metastatic solid tumors.
-
Chemotherapy for:
Small cell carcinoma of the lung
Lymphoma
-
Surgery – may provide immediate relief for patients in whom a
benign process is the cause.
-
Corticosteroids
- No benefit in patients with lung cancer
- May be useful at shrinking lymphoma masses
PROGNOSIS:
PROGNOSIS:
-
Clinical improvement - in most patients, although this
improvement may be due to the development of adequate
collateral circulation.
-
The mortality associated with SVCS does not relate to caval
obstruction, but rather to the underlying cause.
Superior vena cava
Superior vena cava
syndrome
syndrome
Recurrent SVCS occurs in 10 to 30% of patients after initial therapy;
it may be palliated with the use of intravascular self-expanding
stents;
Early stenting may be necessery in patients with severe symptoms
Relative risk associated with this procedure: the prompt increase in
venous return after stenting may precipitate heart failure and
pulmonary oedema.
1.
1.
Venogram shows
Venogram shows
almost complete
almost complete
occlusion
occlusion
of the superior vena
of the superior vena
cava
cava
with dramatic
with dramatic
collateral
collateral
drainage through the
drainage through the
left
left
superior intercostal
superior intercostal
vein.
vein.
2.
2.
A stent mounted on
A stent mounted on
a
a
balloon was deployed
balloon was deployed
in
in
the superior vena cava.
the superior vena cava.
1.
1.
2.
2.
Spinal cord compression
Spinal cord compression
Spinal cord compression develops in 1-5%
Spinal cord compression develops in 1-5%
(5-10%)
(5-10%)
of patients
of patients
with systemic cancer. It should be considered as
with systemic cancer. It should be considered as
emergency, as
emergency, as
treatment delays may result in irreversible
treatment delays may result in irreversible
paralysis and loss of bowel and bladder function
paralysis and loss of bowel and bladder function
.
.
Etiology:
Etiology:
-
Extradural metastases (95%) – ussually resuslts from tumor
Extradural metastases (95%) – ussually resuslts from tumor
involvement of the vertebral column. A tumor may
involvement of the vertebral column. A tumor may
occasionally metastasize to the epidural space without
occasionally metastasize to the epidural space without
bony involvement.
bony involvement.
-
Site of involvement: the segment most often involeved is
Site of involvement: the segment most often involeved is
the thoracic spine (70%), followed by the lumbosacral
the thoracic spine (70%), followed by the lumbosacral
(20%) and cervical spine (10%).
(20%) and cervical spine (10%).
-
Most common malignancies: lung, breast & prostate cancer,
Most common malignancies: lung, breast & prostate cancer,
multiple myeloma, lymphomas, melanoma, renal cancer
multiple myeloma, lymphomas, melanoma, renal cancer
and gastrourinary cancer.
and gastrourinary cancer.
Spinal cord compression –
Spinal cord compression –
history
history
Early symptoms are often nonspecific and include local pain or
Early symptoms are often nonspecific and include local pain or
stiffness.
stiffness.
Gradually
Gradually
worsening back pain
worsening back pain
is the classic initial feature of spinal
is the classic initial feature of spinal
cord neoplastic disease in about 90% of adult patients who are
cord neoplastic disease in about 90% of adult patients who are
affected. Pain often precedes other symptoms associated with spinal
affected. Pain often precedes other symptoms associated with spinal
cord compression by days, weeks to 2-4 months. However, once
cord compression by days, weeks to 2-4 months. However, once
symptoms other than pain appear, symptom progression may be rapid.
symptoms other than pain appear, symptom progression may be rapid.
Pain is exacerbated by movement and by coughing or sneezing.
Pain is exacerbated by movement and by coughing or sneezing.
Radicular pain in the cervical or lumbosacral areas may be unilateral or
Radicular pain in the cervical or lumbosacral areas may be unilateral or
bilateral. Radicular pain from the thoracic roots is often bilateral and is
bilateral. Radicular pain from the thoracic roots is often bilateral and is
described by patients as a feeling of tight, band-like constriction
described by patients as a feeling of tight, band-like constriction
around the thorax and abdomen.
around the thorax and abdomen.
Typical cervical radicular pain radiates down the arm; in the lumbar
Typical cervical radicular pain radiates down the arm; in the lumbar
region the radiation is down the legs.
region the radiation is down the legs.
PATIENTS WITH CANCER WHO DEVELOP BACK
PATIENTS WITH CANCER WHO DEVELOP BACK
PAIN SHOULD BE EVALUATED FOR SPINAL
PAIN SHOULD BE EVALUATED FOR SPINAL
CORD
CORD
COMPRESSION AS QUICKLY AS POSSIBLE.
COMPRESSION AS QUICKLY AS POSSIBLE.
Spinal cord compression –
Spinal cord compression –
physical
physical
The neurological signs accompanying cord compression vary
The neurological signs accompanying cord compression vary
according to:
according to:
-
the rapidity of development of compression
the rapidity of development of compression
-
the area of cord affected.
the area of cord affected.
Acute lesions often result in hypotonia and weakness.
Acute lesions often result in hypotonia and weakness.
Chronic lesions are more often associated with the classic upper
Chronic lesions are more often associated with the classic upper
motor neurone signs of hypertonia and hyper-reflexia.
motor neurone signs of hypertonia and hyper-reflexia.
The associated sensory loss is defined by the site of the lesion,
The associated sensory loss is defined by the site of the lesion,
but hyperaesthesia may be seen in the dermatome at the
but hyperaesthesia may be seen in the dermatome at the
level of the lesion.
level of the lesion.
More lateral lesions may result in a dissociative sensory loss—
More lateral lesions may result in a dissociative sensory loss—
that is, ipsilateral loss of joint position sense and
that is, ipsilateral loss of joint position sense and
proprioception with contralateral loss of pain and
proprioception with contralateral loss of pain and
temperature.
temperature.
Bladder and bowel disturbances often occur late, with the
Bladder and bowel disturbances often occur late, with the
exception of the cauda equina compression syndrome, in
exception of the cauda equina compression syndrome, in
which they are an early feature.
which they are an early feature.
Spinal cord compression
Spinal cord compression
If cord compression is
If cord compression is
suspected the patient
suspected the patient
should be investigated with
should be investigated with
plain spinal radiography,
plain spinal radiography,
which may show evidence
which may show evidence
of lytic lesions (as, for
of lytic lesions (as, for
example, in myeloma).
example, in myeloma).
The definitive investigation
The definitive investigation
is magnetic resonance
is magnetic resonance
imaging to delineate the
imaging to delineate the
level of the lesion and to
level of the lesion and to
help plan further treatment
help plan further treatment
(MRI is to be done in first
(MRI is to be done in first
24 hours)
24 hours)
Spinal Cord Compression
Clinical suspicion:
back pain
back pain
, weakness, motor/sensory
loss,
increased tone, hyperreflexia, loss of sphincter tone
Suspicious for
myelopathy
Symptomatic
treatment
Corticosteroids
10
10
-
-
100 mg bolus
100 mg bolus
,
then 4 mg
qid
Assess pain control
Need for foley
catheter
Review recent bone
scan if available
Radiation oncology
consult
MRI scan
MRI scan
Spinal cord
Spinal cord
compressio
compressio
n present
n present
on MRI
on MRI
scan?
scan?
Urgent radiation oncology
evaluation
Consider neurosurgical
consult for:
- Previously radiated area
- No previous history of
cancer
(for tissue diagnosis)
- Spinal instability or bony
compression of spinal cord
- Radioresistant tumors
(renal, melanoma)
- Neurologic deterioration on
radiation
Yes
No
Yes
No
Reassess patient
Consider other
pathology for spinal
cord dysfunction
Spinal Cord Compression
Radiation therapy plus
Radiation therapy plus
glucocorticoids is generally the initial
glucocorticoids is generally the initial
treatment of choice.
treatment of choice.
Up to 75% of patients treated when
Up to 75% of patients treated when
still ambulatory remain ambulatory,
still ambulatory remain ambulatory,
but only 10% of patients with
but only 10% of patients with
paraplegia recover walking capacity.
paraplegia recover walking capacity.
Hyperviscosity Syndrome
Hyperviscosity Syndrome
Refers to the clinical sequelae of increased blood
Refers to the clinical sequelae of increased blood
viscosity. Increased serum viscosity usually results
viscosity. Increased serum viscosity usually results
from increased circulating serum immunoglobulins and
from increased circulating serum immunoglobulins and
can be seen in Waldenström macroglobulinemia and
can be seen in Waldenström macroglobulinemia and
multiple myeloma.
multiple myeloma.
Is associated most commonly with plasma cell
Is associated most commonly with plasma cell
dyscrasias and is due to the large size of the excess
dyscrasias and is due to the large size of the excess
immunoglobulin M (IgM) paraproteins in these
immunoglobulin M (IgM) paraproteins in these
disorders. Waldenström macroglobulinemia is the most
disorders. Waldenström macroglobulinemia is the most
common cause. Rarely, the disease can occur in
common cause. Rarely, the disease can occur in
multiple myeloma (especially with myeloma proteins
multiple myeloma (especially with myeloma proteins
of the IgA and IgG types) or connective tissue
of the IgA and IgG types) or connective tissue
diseases.
diseases.
Clinical presentation of the syndrome:
Clinical presentation of the syndrome:
-
mucous membrane bleeding,
mucous membrane bleeding,
-
retinopathy,
retinopathy,
-
neurologic symptoms.
neurologic symptoms.
Hyperviscosity Syndrome
Hyperviscosity Syndrome
History:
History:
Tendency to bleed is the most common symptom of
Tendency to bleed is the most common symptom of
hyperviscosity syndrome.
hyperviscosity syndrome.
►
►
Spontaneous gum bleeding
Spontaneous gum bleeding
►
►
Epistaxis
Epistaxis
►
►
Rectal bleeding
Rectal bleeding
►
►
Menorrhagia
Menorrhagia
►
►
Persistent bleeding after minor procedures
Persistent bleeding after minor procedures
Visual changes range from blurred vision to vision loss.
Visual changes range from blurred vision to vision loss.
Neurologic manifestations are frequent and varied. The
Neurologic manifestations are frequent and varied. The
neurologic symptoms of hyperviscosity have been
neurologic symptoms of hyperviscosity have been
referred to as the Bing-Neal syndrome.
referred to as the Bing-Neal syndrome.
–
Vertigo
Vertigo
–
Hearing loss
Hearing loss
–
Paresthesias
Paresthesias
–
Ataxia
Ataxia
–
Headaches
Headaches
–
Seizures
Seizures
–
Somnolence progressing to stupor and coma
Somnolence progressing to stupor and coma
Other manifestations may include heart failure,
Other manifestations may include heart failure,
fatigue, and anorexia.
fatigue, and anorexia.
Hyperviscosity Syndrome
Hyperviscosity Syndrome
Physical:
Physical:
Physical findings are
Physical findings are
related to the 3 major organ systems
related to the 3 major organ systems
involved.
involved.
Bruises, epistaxis, or gum bleeding
Bruises, epistaxis, or gum bleeding
may be noted.
may be noted.
Ophthalmic examination may reveal
Ophthalmic examination may reveal
decreased visual acuity, dilated
decreased visual acuity, dilated
retinal veins, sausage-linked retinal
retinal veins, sausage-linked retinal
veins, or retinal hemorrhages.
veins, or retinal hemorrhages.
Neurological examination may reveal
Neurological examination may reveal
various findings, including
various findings, including
diminished mental status, confusion,
diminished mental status, confusion,
ataxia, or nystagmus.
ataxia, or nystagmus.
Hyperviscosity Syndrome
Hyperviscosity Syndrome
Lab Studies:
Lab Studies:
Serum viscosity.
Serum viscosity.
–
Serum viscosity is
Serum viscosity is
diagnostic in evaluating
diagnostic in evaluating
hyperviscosity syndrome.
hyperviscosity syndrome.
–
The reference range is 1.4-
The reference range is 1.4-
1.8 units.
1.8 units.
–
Symptoms usually are not
Symptoms usually are not
seen before the viscosity
seen before the viscosity
reaches 4 units, and
reaches 4 units, and
hyperviscosity syndrome
hyperviscosity syndrome
usually presents with a
usually presents with a
serum viscosity greater
serum viscosity greater
than 5 units.
than 5 units.
P
P
eripheral blood smear.
eripheral blood smear.
Rouleaux formation
Rouleaux formation
is
is
often present with
often present with
increased serum viscosity.
increased serum viscosity.
Total protein level;
Total protein level;
IgG, IgA,
IgG, IgA,
IgM
IgM
serum
serum
levels.
levels.
Hyperviscosity Syndrome
Hyperviscosity Syndrome
Plasmapheresis is the treatment of
Plasmapheresis is the treatment of
choice for hyperviscosity syndrome.
choice for hyperviscosity syndrome.
–
As plasmapheresis removes the
As plasmapheresis removes the
circulating paraproteins, the serum
circulating paraproteins, the serum
viscosity decreases and symptoms
viscosity decreases and symptoms
improve.
improve.
–
While arranging for plasmapheresis,
While arranging for plasmapheresis,
treat hemorrhage, CHF, and metabolic
treat hemorrhage, CHF, and metabolic
imbalances with standard therapies.
imbalances with standard therapies.
Hyperviscosity Syndrome
Hyperviscosity Syndrome
Blood viscosity is a function of the
Blood viscosity is a function of the
concentration and composition of its
concentration and composition of its
components. A marked increase in plasma
components. A marked increase in plasma
proteins (for example, monoclonal
proteins (for example, monoclonal
immunoglobulin in myeloma) or cellular
immunoglobulin in myeloma) or cellular
constituents (for example, white blood cells
constituents (for example, white blood cells
in acute leukemia) will raise the overall
in acute leukemia) will raise the overall
blood viscosity.
blood viscosity.
Blood viscosity is increased also in:
Blood viscosity is increased also in:
- Polycythaemia
- Polycythaemia
- High white cell count (hyperleucocytosis)
- High white cell count (hyperleucocytosis)
Hyperleukocytosis
Hyperleukocytosis
Definition: peripheral leukocyte count greater
Definition: peripheral leukocyte count greater
than 100,000/mm3 (100 G/L).
than 100,000/mm3 (100 G/L).
Hyperleukocytosis is present at diagnosis in 5-
Hyperleukocytosis is present at diagnosis in 5-
13% of patients with AML, 10-30% of patients
13% of patients with AML, 10-30% of patients
with ALL, and nearly all adults with
with ALL, and nearly all adults with
CML
CML
.
.
Respiratory complications are a more
Respiratory complications are a more
prominent feature of elevated leukocyte counts
prominent feature of elevated leukocyte counts
in patients with AML.
in patients with AML.
Hemorrhagic complications and death rates
Hemorrhagic complications and death rates
significantly increase when peripheral
significantly increase when peripheral
leukocyte counts are greater than
leukocyte counts are greater than
100,000/mm3 in the context of AML and
100,000/mm3 in the context of AML and
greater than 300,000-400,000/mm3 in the
greater than 300,000-400,000/mm3 in the
context of ALL.
context of ALL.
Leucocytostasis c
Leucocytostasis can also occur in CLL when WBC >
400,000/mm3.
Hyperleukocytosis
Hyperleukocytosis
Physical findings result
Physical findings result
from the increased
from the increased
viscosity associated with
viscosity associated with
blast cell aggregates and
blast cell aggregates and
thrombi in combination
thrombi in combination
with damage to vessels
with damage to vessels
and secondary
and secondary
hemorrhage. Resultant
hemorrhage. Resultant
clinical findings primarily
clinical findings primarily
include respiratory and
include respiratory and
neurologic signs.
neurologic signs.
Respiratory signs:
Respiratory signs:
-
dyspnea
dyspnea
-
hypoxia.
hypoxia.
Neurologic signs:
Neurologic signs:
-
focal deficit,
focal deficit,
-
ataxia,
ataxia,
-
agitation,
agitation,
-
confusion,
confusion,
-
delirium,
delirium,
-
stupor.
stupor.
Other signs include:
Other signs include:
-
plethora,
plethora,
-
cyanosis,
cyanosis,
-
papilledema, and retinal
papilledema, and retinal
artery or retinal vein
artery or retinal vein
distension.
distension.
Hyperleukocytosis
Hyperleukocytosis
Specific antileukemic therapy is the treatment of choice
Specific antileukemic therapy is the treatment of choice
for decreasing the peripheral leukocyte count.
for decreasing the peripheral leukocyte count.
In the absence of definitive antileukemic therapy,
In the absence of definitive antileukemic therapy,
leukophoresis may be considered;
leukophoresis may be considered;
The goal of the therapies is to decrease blood viscosity
The goal of the therapies is to decrease blood viscosity
and the metabolic risks associated with a large tumor
and the metabolic risks associated with a large tumor
burden.
burden.
L
L
eukophoresis may be considered if a delay is expected
eukophoresis may be considered if a delay is expected
in initiating specific antileukemic therapy and leukocyte
in initiating specific antileukemic therapy and leukocyte
counts are greater than 100,000/mm3 in patients with
counts are greater than 100,000/mm3 in patients with
A
A
M
M
L or 300,000-400,000/mm3 in patients with ALL.
L or 300,000-400,000/mm3 in patients with ALL.
PRBC transfusions increase the viscosity of blood
PRBC transfusions increase the viscosity of blood
and should be avoided, if possible, in the context
and should be avoided, if possible, in the context
of hyperleukocytosis.
of hyperleukocytosis.
Platelet transfusions do not significantly change
Platelet transfusions do not significantly change
the viscosity of circulating blood, and platelets
the viscosity of circulating blood, and platelets
may be transfused safely if indicated.
may be transfused safely if indicated.
Leukoreduction Apheresis
Leukoreduction Apheresis
(LRA)
(LRA)
The process of removing
The process of removing
unwanted WBC or blasts
unwanted WBC or blasts
from the circulation
from the circulation
The procedure is indicated
The procedure is indicated
for the rapid correction of
for the rapid correction of
hyperleukocytosis
hyperleukocytosis
.
.
One procedure generally
One procedure generally
removes between 20-80%
removes between 20-80%
of WBC by processing 7-10
of WBC by processing 7-10
liters of blood
liters of blood
Indications for LRA
Indications for LRA
:
:
-
-
Hyperleukocytosis
Hyperleukocytosis
WBC/Blast layer
WBC/Blast layer
Blast cell