Leukostasis (also called symptomatic hyperleukocytosis) is a medical emergency most commonly seen in patients with
acute myeloid leukemia. It is characterized by an extremely elevated
blast cell count and symptoms of decreased
tissue perfusion
Perfusion is the passage of fluid through the circulatory system or lymphatic system to an organ or a tissue, usually referring to the delivery of blood to a capillary bed in tissue. Perfusion is measured as the rate at which blood is delive ...
. The pathophysiology of leukostasis is not well understood, but inadequate delivery of oxygen to the body's cells is the result. Leukostasis is diagnosed when white cell plugs are seen in the
microvasculature. The most common symptoms are
dyspnea and
hypoxia
Hypoxia means a lower than normal level of oxygen, and may refer to:
Reduced or insufficient oxygen
* Hypoxia (environmental), abnormally low oxygen content of the specific environment
* Hypoxia (medical), abnormally low level of oxygen in the tis ...
, usually accompanied by visual changes, headaches, dizziness, confusion, somnolence, and coma. Prompt treatment is required since, if left untreated, it has a very high mortality rate. Treatments aim to rapidly reduce white blood cell counts while also treating the underlying disorder.
Asymptomatic hyperleukocytosis and symptomatic hyperleukocytosis (leukostasis)

Symptomatic Hyperleukocytosis (Leukostasis) is defined by a tremendously hig
blast cellcount along with symptoms of decreased tissue
perfusion
Perfusion is the passage of fluid through the circulatory system or lymphatic system to an organ or a tissue, usually referring to the delivery of blood to a capillary bed in tissue. Perfusion is measured as the rate at which blood is deliver ...
. Leukostasis is associated with people who have bone and blood disorders and is very common among people with
acute myeloid leukemia or
chronic myeloid leukemia. Leukostasis is a pathologic diagnosis that inhibits efficient flow to the
microvasculature of the body. Continued and untreated leukostasis presents
respiratory and
neurological distress simultaneously and is a medical emergency, with untreated patient mortality rates reaching a minimum of 20 and a maximum of 40 percent. A leukemia blood cell count greater than 50 x 10^9/ L (50,000 / microL) or 100 x 10^9 L / (100,000/ microL) signifies hyperleukocytosis. Symptoms of leukostasis start when blood levels of leukocytes reach over 100 x 10^9 / L (100,000 / microL). As stated before, these counts are critical and associated with
Leukemias.
Symptoms and signs
When a patient has symptomatic leukocytosis, specifically caused by a form of leukemia, it is common to find leukostasis in all their organs. The majority of the time a patient dies from neurological complications (40% of patients die due to neurological conditions) as opposed to particular organ damage. The lungs alone account for approximately 30 percent of leukostasis fatalities. All other organs combined attribute to 30 percent of deaths, with the major outliers being neurological and
respiratory failure equating to 70 percent of all death rates. Damage to the
microvasculature of the body is the primary cause of death by leukostasis. Microvasculature damage to the lungs is only second to neurological damage because the body is already experiencing hypoxic conditions, which lead to lung tissue damage as the second leading cause of fatalities.
Pulmonary signs -
Dyspnea and
hypoxia
Hypoxia means a lower than normal level of oxygen, and may refer to:
Reduced or insufficient oxygen
* Hypoxia (environmental), abnormally low oxygen content of the specific environment
* Hypoxia (medical), abnormally low level of oxygen in the tis ...
with or without diffuse interstitial or alveolar infiltrates on imaging studies.
Neurological signs - visual changes, headaches, dizziness,
tinnitus, gait instability, confusion,
somnolence, coma.
The most common symptom is the patient is usually
febrile, which is often linked with inflammation and possible infection.
Less common signs include:
myocardial ischemia / right
ventricular overload, increased
acute kidney injury,
priapism, acute limb
ischemia
Ischemia or ischaemia is a restriction in blood supply to any tissue, muscle group, or organ of the body, causing a shortage of oxygen that is needed for cellular metabolism (to keep tissue alive). Ischemia is generally caused by problems wi ...
and bowel
infarction.
Causes of asymptomatic/symptomatic hyperleukocytosis (leukostasis)
Hyperleukocytosis is very common in acutely ill patients. It occurs in response to a wide variety of conditions, including
viral
Viral means "relating to viruses" (small infectious agents).
Viral may also refer to:
Viral behavior, or virality
Memetic behavior likened that of a virus, for example:
* Viral marketing, the use of existing social networks to spread a marke ...
,
bacterial,
fungal, or
parasitic infection, cancer, hemorrhage, and exposure to certain medications.
For lung diseases such as
pneumonia and
tuberculosis, white blood cell count is crucial for the diagnosis of the disease, as leukocytosis is usually present.
Specific medications, including
corticosteroid
Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are involv ...
s,
lithium and
beta-agonists
Beta adrenergic agonists or beta agonists are medications that relax muscles of the airways, causing widening of the airways and resulting in easier breathing. They are a class of sympathomimetic agents, each acting upon the beta adrenoceptors. ...
can cause hyperleukocytosis.
Pathophysiology
The mechanism in which hyperleukocytosis or leukostasis manifests and disrupts
homeostasis is greatly associated with leukemia's but multiple other factors may cause leukocytosis. Major types of leukocytosis and their mechanisms depend on the types of leukemia that cause them.
White blood cell
White blood cells, also called leukocytes or leucocytes, are the cell (biology), cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. All white blood cells are produced and de ...
levels either rise in distinct white blood levels or in unison with others, a patient may have
neutrophilia,
lymphocytosis,
monocytosis,
eosinophilia
Eosinophilia is a condition in which the eosinophil count in the peripheral blood exceeds . Hypereosinophilia is an elevation in an individual's circulating blood eosinophil count above 1.5 x 109/ L (i.e. 1,500/μL). The hypereosinophilic syndro ...
,
basophilia or a rise in immature
blast cells.
Acute myeloid leukemia - 10 to 20 percent of patients newly diagnosed with this type leukemia have hyperleukocytosis.
Acute lymphoblastic leukemia
Acute lymphoblastic leukemia (ALL) is a cancer of the lymphoid line of blood cells characterized by the development of large numbers of immature lymphocytes. Symptoms may include feeling tired, pale skin color, fever, easy bleeding or bruisin ...
- 20 to 30 percent of patients newly diagnosed with this type of leukemia have hyperleukocytosis.
Chronic lymphocytic leukemia
Chronic lymphocytic leukemia (CLL) is a type of cancer in which the bone marrow makes too many lymphocytes (a type of white blood cell). Early on, there are typically no symptoms. Later, non-painful lymph node swelling, feeling tired, fever, nigh ...
- Exact percentage of people diagnosed with chronic
lymphocytic leukemia is unknown but a significant number also have hyperleukocytosis.
Chronic myeloid leukemia - The majority of patients with chronic myeloid leukemia usually have hyperleukocytosis.
The primary pathophysiology of leukostasis is not completely understood, but there are two possible theories.
Theory 1
Increased blood viscosity due to large leukemic blast populations which are less deformable than mature leukocytes may lead to leukostasis. The accumulation of less malleable blast products in the bloodstream accumulate within the microcirculation causing an accumulation of blockages leading to leukostasis.
Theory 2
Hypoxic events in body regions may increase the high metabolic activity of dividing
blast cells and lead to an increase in
cytokine production. The increasing levels of
cytokines within tissues may result in endothelial damage and subsequent
hemorrhage. Therefore, hypoxia, in addition to various cytokine accumulations, act in unison to further damage tissue and attract leukemic blast cells to form a triad of damage.
The combination of these theories, in addition to other events, may lead to hyperleukocytosis.
Diagnosis
White blood counts exceeding 100 x 10^9 / L (100,000 / microL) present symptoms of tissue hypoxia and may signal possible neurological and respiratory distress. Ongoing research has shown that patients have experienced hypoxia at leukocyte levels below 100 x 10^9 / L (100,000 / microL), therefore patients with leukemia need regular neurological and respiratory monitoring when leukocyte counts are approaching 100 x 10^9 / L (100,000 / microL) to decrease chances of tissue hypoxia. Acquired
biopsies are examined for damage to microvasculature, which serves as evidence of hypoxia through the identification of leukocyte blockage within the tissue. Due to the
biopsy's invasive nature and the risks associated with the procedure, it is only used when deemed necessary.
Measurements for arterial pO2 have shown to be falsely decreased in patients with hyperleukocytosis because of white blood cells ability to utilize oxygen.
Pulse oximetry should be used to more accurately assess
pO2 levels of a patient suspected to have leukocytosis. Automated blood cell counters may be inaccurate due to fragments of
blast cells being labeled on
blood smears as
platelets. The most accurate form of confirming platelet counts is by using a manual platelet count and a review of a peripheral smear. Serum potassium levels may also be artificially elevated by a release from leukemic blasts during
in vitro clotting process, therefore serum potassium levels should be monitored by
heparin
Heparin, also known as unfractionated heparin (UFH), is a medication and naturally occurring glycosaminoglycan. Since heparins depend on the activity of antithrombin, they are considered anticoagulants. Specifically it is also used in the treatm ...
ized (the addition of
heparin
Heparin, also known as unfractionated heparin (UFH), is a medication and naturally occurring glycosaminoglycan. Since heparins depend on the activity of antithrombin, they are considered anticoagulants. Specifically it is also used in the treatm ...
prevents
coagulation) plasma samples in order to obtain accurate results of potassium levels.
Disseminated intravascular coagulation
Disseminated intravascular coagulation (DIC) is a condition in which blood clots form throughout the body, blocking small blood vessels. Symptoms may include chest pain, shortness of breath, leg pain, problems speaking, or problems moving parts o ...
may occur in a significant number of patients with presentation of various degrees of
thrombin generation, followed by decreased fibrinogen and increased fibrinolysis.
Spontaneous
tumor lysis syndrome is present in approximately 10 percent of patients with leukostasis. Lab tests are used to measure the potential of elevated serum concentrations such as
uric acid,
potassium,
phosphate, and
hypocalcemia.
Disseminated intravascular coagulation
Disseminated intravascular coagulation (DIC) is a condition in which blood clots form throughout the body, blocking small blood vessels. Symptoms may include chest pain, shortness of breath, leg pain, problems speaking, or problems moving parts o ...
and spontaneous
tumor lysis syndrome can develop before and after chemotherapy treatment. Patients undergoing this type of therapy need to be closely monitored before and after, in addition to undergoing prophylactic measures to prevent possible complications.
Prevention
Since leukostasis and hyperleukostasis are associated with leukemia, preventive treatments are taken upon diagnosis.
Patients with hyperleukocytosis associated with leukemia are always considered candidates for tumor lysis syndrome prophylaxis in addition to aggressive intravenous hydration with allopurinol or
rasburicase to decrease serum uric acid levels.
Treatment
Treatment includes utilization of
prophylactic methods if the patient has been diagnosed with hyperleukocytosis. This is usually in combination with other treatments, which are dependent on the type of leukemia. Specific treatments include lysis syndrome treatment in addition to aggressive
intravenous
Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutrie ...
hydration with
allopurinol or
rasburicase to decrease serum uric acid levels.
Hematopoietic
Haematopoiesis (, from Greek , 'blood' and 'to make'; also hematopoiesis in American English; sometimes also h(a)emopoiesis) is the formation of blood cellular components. All cellular blood components are derived from haematopoietic stem cells. ...
cell transplants are critical to correct leukostasis and leukemia.
Cytoreduction is also a critical course of treatment in order to rapidly decrease white blood cell counts. Twenty to forty percent of patients diagnosed with hyperleukocytosis die within the first week of symptom presentation. Patients with the best outcome have none or limited symptoms of respiratory or neurological distress. An accumulation of these symptoms lead to decreased levels of statistical survival compared to patients diagnosed with asymptomatic hyperleukocytosis alone. Cytoreduction methods include chemotherapy, utilizing the drug
hydroxyurea (Hydroxyurea is usually used in asymptomatic hyperleukocytosis), and the less common
leukapheresis procedure. This procedure is often utilized for asymptomatic hyperleukocytosis patients who have induction chemotherapy postponed for patient-specific factors.
Variants of
chemotherapy, including
induction chemotherapy
Induction chemotherapy is the first-line treatment of cancer with a chemotherapeutic drug. The goal of induction chemotherapy is to cure the cancer. It may be contrasted with neoadjuvant therapy, with consolidation chemotherapy (intended to k ...
, are used to treat both elevated white blood cells counts while simultaneously targeting
leukemia cells in the
bone marrow
Bone marrow is a semi-solid tissue found within the spongy (also known as cancellous) portions of bones. In birds and mammals, bone marrow is the primary site of new blood cell production (or haematopoiesis). It is composed of hematopoietic ce ...
.
Prognosis
Prognosis of patients with hyperleukocytosis is dependent on the cause and type of leukemia the patient has. Patients diagnosed with asymptomatic hyperleukocytosis have significantly better survival rates than symptomatic hyperleukocytosis (leukostasis). Preventative measures and contentious monitoring of patients diagnosed with leukemia is critical in receiving treatment as early as possible to prevent and treat hyperleukocytosis.
Recent research
Recent and continuing research has shown that patients have had hypoxia at leukocyte levels below 100 x 10^9 / L (100,000 / microL), therefore patients with leukemia need regular neurological and respiratory monitoring when leukocyte counts are approaching 100 x 10^9 / L (100,000 / microL) to decrease chances of hypoxia.
Leukemia and population types are also believed to be associated with possible symptoms and may require a change in treatment.
Results of Tumor lysis/ consumption of coagulopathy in patients with acute leukemia is much more often than in patients with chronic malignant hematological diseases.
* Data retrieved for reference is 2017
Leukostasis, also known as symptomatic hyperleukocytosis, is a life-threatening complication of various
leukemias characterized by an
excess
Excess may refer to:
* Angle excess, in spherical trigonometry
* Insurance excess, similar to a deductible
* Excess, in chemistry, a reagent that is not the limiting reagent
* "Excess", a song by Tricky from the album '' Blowback''
* ''Excess'' ( ...
of
white blood cell
White blood cells, also called leukocytes or leucocytes, are the cell (biology), cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. All white blood cells are produced and de ...
s in the bloodstream. Hyperleukocytosis is arbitrarily defined as greater than 100,000 white blood cells per microliter of blood. The condition is characterized by abnormal aggregation and clumping of white blood cells in the blood vessels resulting in impaired blood flow and delivery of oxygen to the body's cells. The
brain and
lung
The lungs are the primary organs of the respiratory system in humans and most other animals, including some snails and a small number of fish. In mammals and most other vertebrates, two lungs are located near the backbone on either side of t ...
s are the two most commonly affected organs.
Leukostasis most commonly occurs with
acute myeloid leukemia.
Hyperleukocytosis/leukostasis occurs more commonly, and at lower white blood cell (WBC) counts, in acute myeloid leukemia than in
acute lymphocytic leukemia, because the cells of acute myeloid leukemia have a larger corpuscular (cell) volume than those of acute lymphocytic leukemia, and the cells of acute myeloid leukemia have more surface adhesion molecules than those of acute lymphocytic leukemia (i.e., the cancer cells in AML are "stickier").
Signs and symptoms
Individuals affected by leukostasis may present with respiratory symptoms such as
cough,
difficulty breathing,
breathing too quickly, or
inadequate levels of oxygen in the blood requiring support with a
mechanical ventilator.
Neurologic symptoms, such as
temporary confusion, blurry vision, dizziness,
ringing in the ears
Tinnitus is the perception of sound when no corresponding external sound is present. Nearly everyone experiences a faint "normal tinnitus" in a completely quiet room; but it is of concern only if it is bothersome, interferes with normal hearin ...
,
ataxia, stupor,
sleepiness,
headache
Headache is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of depression in those with severe headaches.
Headaches can occur as a result ...
s, and
coma
A coma is a deep state of prolonged unconsciousness in which a person cannot be awakened, fails to respond normally to painful stimuli, light, or sound, lacks a normal wake-sleep cycle and does not initiate voluntary actions. Coma patients exhi ...
, may be seen. Neurologic signs such as
seizures, focal neurologic deficits (e.g., weakness in one arm or leg),
swelling of the retina, retinal bleeding, and dilated blood vessels on
inspection of the back of the eye.
Rare complications of leukostasis include
renal vein thrombosis
Renal vein thrombosis (RVT) is the formation of a clot in the vein that drains blood from the kidneys, ultimately leading to a reduction in the drainage of one or both kidneys and the possible migration of the clot to other parts of the body. Firs ...
,
priapism, and acute ischemia of the leg.
Pathophysiology
The pathophysiology of leukostasis is not well understood.
Inadequate delivery of oxygen to the body's cells is thought to be the main abnormal result of leukostasis.
Proposed mechanisms for this include increased blood viscosity due to the high number of white blood cells circulating in the blood and a higher proportion of cells with a greater
mean corpuscular volume
The mean corpuscular volume, or mean cell volume (MCV), is a measure of the average volume of a red blood corpuscle (or red blood cell). The measure is obtained by multiplying a volume of blood by the proportion of blood that is cellular (the hema ...
(larger cells) with decreased deformability occupying the blood vessels.
However, certain studies have demonstrated that the blood viscosity of affected individuals is not increased due to a compensatory decrease in the number of
red blood cells sometimes resulting in
anemia and a decreased
hematocrit.
Diagnosis
The clinical signs and symptoms of leukostasis are non-specific but should be suspected in susceptible individuals with leukemia, a high white blood cell count (e.g., over 100,000), and new-onset neurologic or respiratory signs or symptoms.
Rales may be heard when
listening to the lungs with a stethoscope.
A
chest x-ray
A chest radiograph, called a chest X-ray (CXR), or chest film, is a projection radiograph of the chest used to diagnose conditions affecting the chest, its contents, and nearby structures. Chest radiographs are the most common film taken in med ...
can be normal in those with leukostasis or may demonstrate an alveolar pattern of infiltrates.
Brain imaging with
computed tomography
A computed tomography scan (CT scan; formerly called computed axial tomography scan or CAT scan) is a medical imaging technique used to obtain detailed internal images of the body. The personnel that perform CT scans are called radiographers ...
(CT) or
magnetic resonance imaging
Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to form pictures of the anatomy and the physiological processes of the body. MRI scanners use strong magnetic fields, magnetic field gradients, and radio wave ...
(MRI) is useful and can demonstrate areas of bleeding,
ischemic stroke, or masses.
Laboratory abnormalities seen in those with leukostasis include a markedly elevated white blood cell count (hyperleukocytosis) and
electrolyte
An electrolyte is a medium containing ions that is electrically conducting through the movement of those ions, but not conducting electrons. This includes most soluble salts, acids, and bases dissolved in a polar solvent, such as water. Upon dis ...
abnormalities seen with
tumor lysis syndrome such as
high concentrations of potassium,
phosphorus, and
uric acid in the blood and a low level of
calcium in the blood (due to being bound by high amounts of circulating phosphorus).
Management
It is an
acute syndrome requiring aggressive
cytoreductive modalities including
chemotherapy and/or
leukapheresis to both reduce the number of circulating leukocytes and to break apart any aggregates that have already formed. Such rapid and massive
lysis
Lysis ( ) is the breaking down of the membrane of a cell, often by viral, enzymic, or osmotic (that is, "lytic" ) mechanisms that compromise its integrity. A fluid containing the contents of lysed cells is called a ''lysate''. In molecular bio ...
of tissue poses a risk of
complications (
tumor lysis syndrome), but it is necessary to avoid a
stroke
A stroke is a medical condition in which poor blood flow to the brain causes cell death. There are two main types of stroke: ischemic, due to lack of blood flow, and hemorrhagic, due to bleeding. Both cause parts of the brain to stop functionin ...
.
Leukostasis is different from leukemic infiltration, which is a
neoplastic process where leukemic cells invade organs.
Prognosis
Leukostasis is a high-risk condition and can lead to significant complications resulting from occlusion of blood vessels, including
transient ischemic attacks and
stroke
A stroke is a medical condition in which poor blood flow to the brain causes cell death. There are two main types of stroke: ischemic, due to lack of blood flow, and hemorrhagic, due to bleeding. Both cause parts of the brain to stop functionin ...
s.
Epidemiology
The incidence and prevalence of hyperleukocytosis and leukostasis vary depending on the form of leukemia.
Hyperleukocytosis is common in
chronic myelogenous leukemia
Chronic myelogenous leukemia (CML), also known as chronic myeloid leukemia, is a cancer of the white blood cells. It is a form of leukemia characterized by the increased and unregulated growth of myeloid cells in the bone marrow and the accumulat ...
and
chronic lymphocytic leukemia
Chronic lymphocytic leukemia (CLL) is a type of cancer in which the bone marrow makes too many lymphocytes (a type of white blood cell). Early on, there are typically no symptoms. Later, non-painful lymph node swelling, feeling tired, fever, nigh ...
, but leukostasis rarely occurs.
Similarly, the incidence of hyperleukocytosis in people with
acute lymphoblastic leukemia
Acute lymphoblastic leukemia (ALL) is a cancer of the lymphoid line of blood cells characterized by the development of large numbers of immature lymphocytes. Symptoms may include feeling tired, pale skin color, fever, easy bleeding or bruisin ...
is between 10 and 30% but rarely does this progress to symptomatic leukostasis.
The incidence of hyperleukocytosis in
acute myeloid leukemia (AML) ranges between 5-20% but leukostasis is less common than hyperleukocytosis in this population; leukostasis tends to occur more often in people with AML with monocytic features.
References
{{Lymphatic disease
Blood disorders
Hematopathology
Leukemia
Oncological emergencies