Emergencies in haematology

Emergencies in hematology



ATLS



Hypercalcemia



Spinal cord compression



Superior vena cava syndrome



Leukocytostasis



Hyperviscosity



Pericardial effusion/tamponade



Intestinal obstruction



Urinary obstruction



Malignant biliary obstruction



Increased intracranial pressure



Neoplastic menigitis



Other….

ATLS – Acute tumor lysis

syndrome



Is characterized by various combinations of:

hyperuricemia;

Hypergl

cemia;

Hyperkalemia;

Hyperphosphatemia;

Hypocalcemia;

Lactic acidosis.



Is caused by the destruction of a large

number of rapidly proliferating neoplastic

cells.



Frequently: acute renal failure develops as a

result of the syndrome.

-Uric acid
-Glucose
-Potassium
-Phosphate

s
-Lactic acid

ATLS – Acute tumor lysis

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)

after chemotherapy;



In rare cases – spontaneous necrosis of

malignancies causes ATLS – prior to chemotherapy.

ATLS – Acute tumor lysis

syndrome

Hyperuricemia:



May be present at the time of chemotherapy



Effective treatment kills malignant cells and

leads to increased serum uric acid levels

from the turnover of nucleic acids.



Uric acid can precipitate in the tubules,

medulla and collecting ducts of the kidney

leading to renal failure.



Lactic acidosis and dehydratation may

contribute to the precipitation of uric acid in

the renal tubules.

ATLS – Acute tumor lysis

syndrome

Hyperphosphatemia



Produces reciprocal depression in serum calcium



Hypocalcemia – symptoms: neuromuscular irritability,

tetany;



Deposition of calcium phosphate in the kidney and

hyperphosphatemia may cause renal failure.

Hyperkalemia

Potassium is the principal intracellular cation and

massive destruction of malignant cells may lead to

hyperkalemia.

In patients with renal failure may rapidly be life –

threatening.

Can cause ventricular arrythmias and sudden death.

ATLS – Acute tumor lysis

syndrome



The most important predictive factors:

tumor burden: hyperuricemia and high

levels of lactate dehydrogenase

(LDH>1500 U/l);

Renal function



Recognition & prevention are the most

important steps in the management of

this syndrome.

ATLS – Acute tumor lysis

syndrome

Prophylaxis



Maintain hydratation by administration of ivf

at 3000 ml/m2 per day



Keep urine pH at 7,0 or greater by

administration of sodium bicarbonate



Administer allopurinol at 300 mg/m2 per day



Monitor serum chemistry.

Start chemotherapy when serum uric acid <8,0

mg/dl; serum creatinine <1,6 mg/dl; urine pH

>7,0.

If an urgent anticancer therapy is needed

consider dialysis.

ATLS – Acute tumor lysis

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

Xanthin
e
oxidase

Uric Acid

Allantoin

Urate Oxidase

Allopurin
ol

Hypoxanthi

Xanthine
oxidase

Rasburicase

ATLS – Acute tumor lysis

syndrome



Despite aggressive

prophylaxis ATLS

and/or oliguric or

anuric renal failure

may occur;



Dialysis is often

necessary and

should be considered

early in the course.



The prognosis is

good, and renal

function recovers

after the uric acid

level is lowered to <

10 mg/dl.

If:



Serum K+ > 6mEq/l



Serum uric acid >10

mg/dl



Serum

creatinine>10 mg/dl



Serum

phosphate>10mg/dl

or increasing

symptomatic

hypocalcemia

present



Treatment

Begin

hemodialysis

Hypercalcemia



Hypercalcemia is the most common life-threatening metabolic

disorder associated with neoplastic diseases, occurring in an

estimated 10% to 20% of all adults with cancer. It also occurs in

children with cancer, but with much less frequency

(approximately 0.5%-1%).



Causes

The main causes of hypercalcemia due to cancer are an increase

in the amount of calcium absorbed from the bones, and an

inability of the kidneys to excrete excess calcium. Some cancer

cells secrete substances that cause calcium to be absorbed into

the bloodstream from bones. Immobility, dehydration, anorexia,

nausea, and vomiting may also increase calcium levels.



Incidence

Hypercalcemia occurs most frequently in patients with lung and

breast cancer. It may also occur in patients with multiple

myeloma, head and neck cancer, cancer of unknown primary

origin, lymphoma, leukemia, kidney cancer, and

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

be classified by the affected body

part:



Nervous system



Calcium plays a major role in the normal functioning of

the central nervous system (the brain and spinal cord).

Symptoms of hypercalcemia may include weakness,

loss of reflexes in the muscles, and decreased stamina.

Patients with central nervous system symptoms may

have changes in personality, difficulty thinking or

speaking clearly, disorientation, or hallucinations.

Eventually, coma may result. Headaches can also occur,

which can be made worse by vomiting and dehydration.



Heart



Hypercalcemia affects normal heart rhythms and

increases sensitivity to some heart medications (such

as digoxin). As calcium levels increase, irregular

heartbeats may develop, and may lead to a heart

attack.

Hypercalcemia

Symptoms may

be classified by the affected body

part:



Gastrointestinal

Increased stomach acid often is produced with hypercalcemia

and may intensify loss of appetite, nausea, and vomiting.

Constipation may result from the dehydration associated

with hypercalcemia.



Kidney

Hypercalcemia causes the kidneys to not function correctly,

leading to the production of large volumes of urine. The

large amount of urine combined with less liquid intake leads

to symptoms of dehydration, including thirst, dry mouth,

little or no sweating, and concentrated urine. Patients with

myeloma often have kidney problems due to hypercalcemia.

Kidney stones may result from long-term hypercalcemia.



Bone

Hypercalcemia of cancer can result from bone metastases or

bone loss, and may contribute to broken bones, bone

disfigurement, and pain.

Hypercalcemia of Malignancy

Suspect hypercalcemia

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

possible)

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

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

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

(SVCS)



The superior vena

cava syndrome is

the group of

symptoms that

result from

compression of the

large vein (superior

vena cava) that

transmits blood to

the heart from the

head, neck and

upper extremities.

Superior vena cava

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!!

- Others (primary mediastinal germ cell, thymoma)



Infection



Thrombosis

Superior vena cava

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

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

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:

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

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.

Venogram shows

almost complete

occlusion

of the superior vena

cava

with dramatic

collateral

drainage through the

left

superior intercostal

vein.

A stent mounted on

balloon was deployed

the superior vena cava.

Spinal cord compression

Spinal cord compression develops in 1-5%

(5-10%)

of patients

with systemic cancer. It should be considered as

emergency, as

treatment delays may result in irreversible

paralysis and loss of bowel and bladder function

Etiology:

Extradural metastases (95%) – ussually resuslts from tumor

involvement of the vertebral column. A tumor may

occasionally metastasize to the epidural space without

bony involvement.

Site of involvement: the segment most often involeved is

the thoracic spine (70%), followed by the lumbosacral

(20%) and cervical spine (10%).

Most common malignancies: lung, breast & prostate cancer,

multiple myeloma, lymphomas, melanoma, renal cancer

and gastrourinary cancer.

Spinal cord compression –

history



Early symptoms are often nonspecific and include local pain or

stiffness.



Gradually

worsening back pain

is the classic initial feature of spinal

cord neoplastic disease in about 90% of adult patients who are

affected. Pain often precedes other symptoms associated with spinal

cord compression by days, weeks to 2-4 months. However, once

symptoms other than pain appear, symptom progression may be rapid.



Pain is exacerbated by movement and by coughing or sneezing.



Radicular pain in the cervical or lumbosacral areas may be unilateral or

bilateral. Radicular pain from the thoracic roots is often bilateral and is

described by patients as a feeling of tight, band-like constriction

around the thorax and abdomen.



Typical cervical radicular pain radiates down the arm; in the lumbar

region the radiation is down the legs.

PATIENTS WITH CANCER WHO DEVELOP BACK

PAIN SHOULD BE EVALUATED FOR SPINAL

CORD

COMPRESSION AS QUICKLY AS POSSIBLE.

Spinal cord compression –

physical

The neurological signs accompanying cord compression vary

according to:

the rapidity of development of compression

the area of cord affected.

Acute lesions often result in hypotonia and weakness.

Chronic lesions are more often associated with the classic upper

motor neurone signs of hypertonia and hyper-reflexia.

The associated sensory loss is defined by the site of the lesion,

but hyperaesthesia may be seen in the dermatome at the

level of the lesion.

More lateral lesions may result in a dissociative sensory loss—

that is, ipsilateral loss of joint position sense and

proprioception with contralateral loss of pain and

temperature.

Bladder and bowel disturbances often occur late, with the

exception of the cauda equina compression syndrome, in

which they are an early feature.

Spinal cord compression



If cord compression is

suspected the patient

should be investigated with

plain spinal radiography,

which may show evidence

of lytic lesions (as, for

example, in myeloma).



The definitive investigation

is magnetic resonance

imaging to delineate the

level of the lesion and to

help plan further treatment

(MRI is to be done in first

24 hours)

Spinal Cord Compression

Clinical suspicion:

back pain

, weakness, motor/sensory

loss,

increased tone, hyperreflexia, loss of sphincter tone

Suspicious for
myelopathy

Symptomatic
treatment

Corticosteroids

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

Spinal cord

compressio

n present

on MRI

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

Reassess patient
Consider other
pathology for spinal
cord dysfunction

Spinal Cord Compression



Radiation therapy plus

glucocorticoids is generally the initial

treatment of choice.



Up to 75% of patients treated when

still ambulatory remain ambulatory,

but only 10% of patients with

paraplegia recover walking capacity.

Hyperviscosity Syndrome

Refers to the clinical sequelae of increased blood

viscosity. Increased serum viscosity usually results

from increased circulating serum immunoglobulins and

can be seen in Waldenström macroglobulinemia and

multiple myeloma.



Is associated most commonly with plasma cell

dyscrasias and is due to the large size of the excess

immunoglobulin M (IgM) paraproteins in these

disorders. Waldenström macroglobulinemia is the most

common cause. Rarely, the disease can occur in

multiple myeloma (especially with myeloma proteins

of the IgA and IgG types) or connective tissue

diseases.



Clinical presentation of the syndrome:

mucous membrane bleeding,

retinopathy,

neurologic symptoms.

Hyperviscosity Syndrome

History:



Tendency to bleed is the most common symptom of

hyperviscosity syndrome.

►

Spontaneous gum bleeding

►

Epistaxis

►

Rectal bleeding

►

Menorrhagia

►

Persistent bleeding after minor procedures



Visual changes range from blurred vision to vision loss.



Neurologic manifestations are frequent and varied. The

neurologic symptoms of hyperviscosity have been

referred to as the Bing-Neal syndrome.

–

Vertigo

–

Hearing loss

–

Paresthesias

–

Ataxia

–

Headaches

–

Seizures

–

Somnolence progressing to stupor and coma



Other manifestations may include heart failure,

fatigue, and anorexia.

Hyperviscosity Syndrome



Physical:

Physical findings are

related to the 3 major organ systems

involved.



Bruises, epistaxis, or gum bleeding

may be noted.



Ophthalmic examination may reveal

decreased visual acuity, dilated

retinal veins, sausage-linked retinal

veins, or retinal hemorrhages.



Neurological examination may reveal

various findings, including

diminished mental status, confusion,

ataxia, or nystagmus.

Hyperviscosity Syndrome

Lab Studies:



Serum viscosity.

–

Serum viscosity is

diagnostic in evaluating

hyperviscosity syndrome.

–

The reference range is 1.4-

1.8 units.

–

Symptoms usually are not

seen before the viscosity

reaches 4 units, and

hyperviscosity syndrome

usually presents with a

serum viscosity greater

than 5 units.



eripheral blood smear.

Rouleaux formation

often present with

increased serum viscosity.



Total protein level;

IgG, IgA,

IgM

serum

levels.

Hyperviscosity Syndrome



Plasmapheresis is the treatment of

choice for hyperviscosity syndrome.

–

As plasmapheresis removes the

circulating paraproteins, the serum

viscosity decreases and symptoms

improve.

–

While arranging for plasmapheresis,

treat hemorrhage, CHF, and metabolic

imbalances with standard therapies.

Hyperviscosity Syndrome



Blood viscosity is a function of the

concentration and composition of its

components. A marked increase in plasma

proteins (for example, monoclonal

immunoglobulin in myeloma) or cellular

constituents (for example, white blood cells

in acute leukemia) will raise the overall

blood viscosity.



Blood viscosity is increased also in:

- Polycythaemia

- High white cell count (hyperleucocytosis)

Hyperleukocytosis



Definition: peripheral leukocyte count greater

than 100,000/mm3 (100 G/L).



Hyperleukocytosis is present at diagnosis in 5-

13% of patients with AML, 10-30% of patients

with ALL, and nearly all adults with

CML



Respiratory complications are a more

prominent feature of elevated leukocyte counts

in patients with AML.



Hemorrhagic complications and death rates

significantly increase when peripheral

leukocyte counts are greater than

100,000/mm3 in the context of AML and

greater than 300,000-400,000/mm3 in the

context of ALL.



Leucocytostasis c

Leucocytostasis can also occur in CLL when WBC >

400,000/mm3.

Hyperleukocytosis



Physical findings result

from the increased

viscosity associated with

blast cell aggregates and

thrombi in combination

with damage to vessels

and secondary

hemorrhage. Resultant

clinical findings primarily

include respiratory and

neurologic signs.



Respiratory signs:

dyspnea

hypoxia.

Neurologic signs:

focal deficit,

ataxia,

agitation,

confusion,

delirium,

stupor.

Other signs include:

plethora,

cyanosis,

papilledema, and retinal

artery or retinal vein

distension.

Hyperleukocytosis



Specific antileukemic therapy is the treatment of choice

for decreasing the peripheral leukocyte count.



In the absence of definitive antileukemic therapy,

leukophoresis may be considered;



The goal of the therapies is to decrease blood viscosity

and the metabolic risks associated with a large tumor

burden.



eukophoresis may be considered if a delay is expected

in initiating specific antileukemic therapy and leukocyte

counts are greater than 100,000/mm3 in patients with

L or 300,000-400,000/mm3 in patients with ALL.

PRBC transfusions increase the viscosity of blood

and should be avoided, if possible, in the context

of hyperleukocytosis.

Platelet transfusions do not significantly change

the viscosity of circulating blood, and platelets

may be transfused safely if indicated.

Leukoreduction Apheresis

(LRA)



The process of removing

unwanted WBC or blasts

from the circulation



The procedure is indicated

for the rapid correction of

hyperleukocytosis



One procedure generally

removes between 20-80%

of WBC by processing 7-10

liters of blood



Indications for LRA

Hyperleukocytosis

WBC/Blast layer

Blast cell

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