Leukostasis (also called symptomatic hyperleukocytosis) is a medical emergency most commonly seen in patients with
acute myeloid leukemia
Acute myeloid leukemia (AML) is a cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal cells that build up in the bone marrow and blood and interfere with normal blood cell production. Symptoms may inclu ...
. It is characterized by an extremely elevated
blast cell
In cell biology, a precursor cell, also called a blast cell or simply blast, is a partially differentiated cell, usually referred to as a unipotent cell that has lost most of its stem cell properties. A precursor cell is also known as a proge ...
count and symptoms of decreased
tissue perfusion. 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 microcirculation is the circulation of the blood in the smallest blood vessels, the microvessels of the microvasculature present within organ tissues. The microvessels include terminal arterioles, metarterioles, capillaries, and venules. ...
. The most common symptoms are
dyspnea
Shortness of breath (SOB), also medically known as dyspnea (in AmE) or dyspnoea (in BrE), is an uncomfortable feeling of not being able to breathe well enough. The American Thoracic Society defines it as "a subjective experience of breathing di ...
and
hypoxia, 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)
![1916 Leukocyte Key](https://upload.wikimedia.org/wikipedia/commons/8/81/1916_Leukocyte_Key.jpg)
Symptomatic Hyperleukocytosis (Leukostasis) is defined by a tremendously hig
blast cellcount along with symptoms of decreased tissue
perfusion. Leukostasis is associated with people who have bone and blood disorders and is very common among people with
acute myeloid leukemia
Acute myeloid leukemia (AML) is a cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal cells that build up in the bone marrow and blood and interfere with normal blood cell production. Symptoms may inclu ...
or
chronic myeloid 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 accumulati ...
. Leukostasis is a pathologic diagnosis that inhibits efficient flow to the
microvasculature
The microcirculation is the circulation of the blood in the smallest blood vessels, the microvessels of the microvasculature present within organ tissues. The microvessels include terminal arterioles, metarterioles, capillaries, and venules. ...
of the body. Continued and untreated leukostasis presents
respiratory
The respiratory system (also respiratory apparatus, ventilatory system) is a biological system consisting of specific organs and structures used for gas exchange in animals and plants. The anatomy and physiology that make this happen varies gre ...
and
neurological
Neurology (from el, νεῦρον (neûron), "string, nerve" and the suffix -logia, "study of") is the branch of medicine dealing with the diagnosis and treatment of all categories of conditions and disease involving the brain, the spinal c ...
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
Leukemia
Leukemia ( also spelled leukaemia and pronounced ) is a group of blood cancers that usually begin in the bone marrow and result in high numbers of abnormal blood cells. These blood cells are not fully developed and are called ''blasts'' or ...
s.
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
Respiratory failure results from inadequate gas exchange by the respiratory system, meaning that the arterial oxygen, carbon dioxide, or both cannot be kept at normal levels. A drop in the oxygen carried in the blood is known as hypoxemia; a rise ...
equating to 70 percent of all death rates. Damage to the
microvasculature
The microcirculation is the circulation of the blood in the smallest blood vessels, the microvessels of the microvasculature present within organ tissues. The microvessels include terminal arterioles, metarterioles, capillaries, and venules. ...
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
Shortness of breath (SOB), also medically known as dyspnea (in AmE) or dyspnoea (in BrE), is an uncomfortable feeling of not being able to breathe well enough. The American Thoracic Society defines it as "a subjective experience of breathing di ...
and
hypoxia with or without diffuse interstitial or alveolar infiltrates on imaging studies.
Neurological signs - visual changes, headaches, dizziness,
tinnitus
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 ...
, gait instability, confusion,
somnolence
Somnolence (alternatively sleepiness or drowsiness) is a state of strong desire for sleep, or sleeping for unusually long periods (compare hypersomnia). It has distinct meanings and causes. It can refer to the usual state preceding falling asleep ...
, coma.
The most common symptom is the patient is usually
febrile
Fever, also referred to as pyrexia, is defined as having a temperature above the normal range due to an increase in the body's temperature set point. There is not a single agreed-upon upper limit for normal temperature with sources using val ...
, which is often linked with inflammation and possible infection.
Less common signs include:
myocardial ischemia
Coronary artery disease (CAD), also called coronary heart disease (CHD), ischemic heart disease (IHD), myocardial ischemia, or simply heart disease, involves the reduction of blood flow to the heart muscle due to build-up of atherosclerotic pla ...
/ right
ventricular overload, increased
acute kidney injury
Acute kidney injury (AKI), previously called acute renal failure (ARF), is a sudden decrease in kidney function that develops within 7 days, as shown by an increase in serum creatinine or a decrease in urine output, or both.
Causes of AKI are c ...
,
priapism
Priapism is a condition in which a penis remains erect for hours in the absence of stimulation or after stimulation has ended. There are three types: ischemic (low-flow), nonischemic (high-flow), and recurrent ischemic (intermittent). Most cases ...
, acute limb
ischemia and bowel
infarction
Infarction is tissue death ( necrosis) due to inadequate blood supply to the affected area. It may be caused by artery blockages, rupture, mechanical compression, or vasoconstriction. The resulting lesion is referred to as an infarct
(from th ...
.
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,
bacterial
Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were amon ...
,
fungal
A fungus ( : fungi or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and molds, as well as the more familiar mushrooms. These organisms are classified as a kingdom, separately from th ...
, or
parasitic infection
A parasitic disease, also known as parasitosis, is an infectious disease caused by parasites. Parasites are organisms which derive sustenance from its host while causing it harm. The study of parasites and parasitic diseases is known as parasitolo ...
, cancer, hemorrhage, and exposure to certain medications.
For lung diseases such as
pneumonia
Pneumonia is an inflammatory condition of the lung primarily affecting the small air sacs known as alveoli. Symptoms typically include some combination of productive or dry cough, chest pain, fever, and difficulty breathing. The severi ...
and
tuberculosis
Tuberculosis (TB) is an infectious disease usually caused by '' Mycobacterium tuberculosis'' (MTB) bacteria. Tuberculosis generally affects the lungs, but it can also affect other parts of the body. Most infections show no symptoms, i ...
, white blood cell count is crucial for the diagnosis of the disease, as leukocytosis is usually present.
Specific medications, including
corticosteroids,
lithium
Lithium (from el, λίθος, lithos, lit=stone) is a chemical element with the symbol Li and atomic number 3. It is a soft, silvery-white alkali metal. Under standard conditions, it is the least dense metal and the least dense solid ...
and
beta-agonists can cause hyperleukocytosis.
Pathophysiology
The mechanism in which hyperleukocytosis or leukostasis manifests and disrupts
homeostasis
In biology, homeostasis (British also homoeostasis) (/hɒmɪə(ʊ)ˈsteɪsɪs/) is the state of steady internal, physical, and chemical conditions maintained by living systems. This is the condition of optimal functioning for the organism and ...
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 levels either rise in distinct white blood levels or in unison with others, a patient may have
neutrophilia
Neutrophilia (also called neutrophil leukocytosis or occasionally neutrocytosis) is leukocytosis of neutrophils, that is, a high number of neutrophils in the blood. Because neutrophils are the main type of granulocytes, mentions of granulocytosi ...
,
lymphocytosis
Lymphocytosis is an increase in the number or proportion of lymphocytes in the blood. Absolute lymphocytosis is the condition where there is an increase in the lymphocyte count beyond the normal range while relative lymphocytosis refers to the cond ...
,
monocytosis
Monocytosis is an increase in the number of monocytes circulating in the blood. Monocytes are white blood cells that give rise to macrophages and dendritic cells in the immune system.
In humans, monocytosis occurs when there is a sustained rise i ...
,
eosinophilia,
basophilia
Basophilia is the condition of having greater than 200 basophils/μL in the venous blood.
Basophils are the least numerous of the myelogenous cells, and it is rare for their numbers to be abnormally high without changes to other blood components. ...
or a rise in immature
blast cells
In cell biology, a precursor cell, also called a blast cell or simply blast, is a partially differentiated cell, usually referred to as a unipotent cell that has lost most of its stem cell properties. A precursor cell is also known as a pro ...
.
Acute myeloid leukemia
Acute myeloid leukemia (AML) is a cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal cells that build up in the bone marrow and blood and interfere with normal blood cell production. Symptoms may inclu ...
- 10 to 20 percent of patients newly diagnosed with this type leukemia have hyperleukocytosis.
Acute lymphoblastic leukemia - 20 to 30 percent of patients newly diagnosed with this type of leukemia have hyperleukocytosis.
Chronic lymphocytic leukemia - Exact percentage of people diagnosed with chronic
lymphocytic leukemia is unknown but a significant number also have hyperleukocytosis.
Chronic myeloid 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 accumulati ...
- 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
In cell biology, a precursor cell, also called a blast cell or simply blast, is a partially differentiated cell, usually referred to as a unipotent cell that has lost most of its stem cell properties. A precursor cell is also known as a pro ...
and lead to an increase in
cytokine
Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in autocrin ...
production. The increasing levels of
cytokine
Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in autocrin ...
s within tissues may result in endothelial damage and subsequent
hemorrhage
Bleeding, hemorrhage, haemorrhage or blood loss, is blood escaping from the circulatory system from damaged blood vessels. Bleeding can occur internally, or externally either through a natural opening such as the mouth, nose, ear, urethra, v ...
. 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
A biopsy is a medical test commonly performed by a surgeon, interventional radiologist, or an interventional cardiologist. The process involves extraction of sample cells or tissues for examination to determine the presence or extent of a dise ...
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
A biopsy is a medical test commonly performed by a surgeon, interventional radiologist, or an interventional cardiologist. The process involves extraction of sample cells or tissues for examination to determine the presence or extent of a dise ...
'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
Pulse oximetry is a noninvasive method for monitoring a person's oxygen saturation. Peripheral oxygen saturation (SpO2) readings are typically within 2% accuracy (within 4% accuracy in 95% of cases) of the more accurate (and invasive) reading o ...
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
In cell biology, a precursor cell, also called a blast cell or simply blast, is a partially differentiated cell, usually referred to as a unipotent cell that has lost most of its stem cell properties. A precursor cell is also known as a pro ...
being labeled on
blood smears as
platelet
Platelets, also called thrombocytes (from Greek θρόμβος, "clot" and κύτος, "cell"), are a component of blood whose function (along with the coagulation factors) is to react to bleeding from blood vessel injury by clumping, thereby i ...
s. 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
''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called " test-tube experiments", these studies in biology ...
clotting process, therefore serum potassium levels should be monitored by
heparinized (the addition of
heparin prevents
coagulation
Coagulation, also known as clotting, is the process by which blood changes from a liquid to a gel, forming a blood clot. It potentially results in hemostasis, the cessation of blood loss from a damaged vessel, followed by repair. The mechanis ...
) plasma samples in order to obtain accurate results of potassium levels.
Disseminated intravascular coagulation may occur in a significant number of patients with presentation of various degrees of
thrombin
Thrombin (, ''fibrinogenase'', ''thrombase'', ''thrombofort'', ''topical'', ''thrombin-C'', ''tropostasin'', ''activated blood-coagulation factor II'', ''blood-coagulation factor IIa'', ''factor IIa'', ''E thrombin'', ''beta-thrombin'', ''gamma- ...
generation, followed by decreased fibrinogen and increased fibrinolysis.
Spontaneous
tumor lysis syndrome
Tumor lysis syndrome (TLS) is a group of metabolic abnormalities that can occur as a complication from the treatment of cancer, where large amounts of tumor cells are killed off ( lysed) from the treatment, releasing their contents into the blood ...
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
Uric acid is a heterocyclic compound of carbon, nitrogen, oxygen, and hydrogen with the formula C5H4N4O3. It forms ions and salts known as urates and acid urates, such as ammonium acid urate. Uric acid is a product of the metabolic breakdown ...
,
potassium
Potassium is the chemical element with the symbol K (from Neo-Latin ''kalium'') and atomic number19. Potassium is a silvery-white metal that is soft enough to be cut with a knife with little force. Potassium metal reacts rapidly with atmosph ...
,
phosphate
In chemistry, a phosphate is an anion, salt, functional group or ester derived from a phosphoric acid. It most commonly means orthophosphate, a derivative of orthophosphoric acid .
The phosphate or orthophosphate ion is derived from phosph ...
, and
hypocalcemia
Hypocalcemia is a medical condition characterized by low calcium levels in the blood serum. The normal range of blood calcium is typically between 2.1–2.6 mmol/L (8.8–10.7 mg/dL, 4.3–5.2 mEq/L) while levels less than 2.1 mm ...
.
Disseminated intravascular coagulation and spontaneous
tumor lysis syndrome
Tumor lysis syndrome (TLS) is a group of metabolic abnormalities that can occur as a complication from the treatment of cancer, where large amounts of tumor cells are killed off ( lysed) from the treatment, releasing their contents into the blood ...
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
Rasburicase (trade names Elitek in the US and Fasturtec in the EU) is a medication that helps to clear uric acid from the blood. It is a recombinant version of urate oxidase, an enzyme that metabolizes uric acid to allantoin. Urate oxidase is kn ...
to decrease serum uric acid levels.
Treatment
Treatment includes utilization of
prophylactic
Preventive healthcare, or prophylaxis, consists of measures taken for the purposes of disease prevention.Hugh R. Leavell and E. Gurney Clark as "the science and art of preventing disease, prolonging life, and promoting physical and mental hea ...
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 hydration with
allopurinol
Allopurinol is a medication used to decrease high blood uric acid levels. It is specifically used to prevent gout, prevent specific types of kidney stones and for the high uric acid levels that can occur with chemotherapy. It is taken by mouth ...
or
rasburicase
Rasburicase (trade names Elitek in the US and Fasturtec in the EU) is a medication that helps to clear uric acid from the blood. It is a recombinant version of urate oxidase, an enzyme that metabolizes uric acid to allantoin. Urate oxidase is kn ...
to decrease serum uric acid levels.
Hematopoietic cell transplants are critical to correct leukostasis and leukemia.
Cytoreduction
Debulking is the reduction of as much of the bulk (volume) of a tumour without the intention of a complete eradication. It is usually achieved by surgical removal. When performed for curative intent, it is a different procedure, which is called sur ...
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
Hydroxycarbamide, also known as hydroxyurea, is a medication used in sickle-cell disease, essential thrombocythemia, chronic myelogenous leukemia, polycythemia vera, and cervical cancer. In sickle-cell disease it increases fetal hemoglobin and d ...
(Hydroxyurea is usually used in asymptomatic hyperleukocytosis), and the less common
leukapheresis
Leukapheresis () is a laboratory procedure in which white blood cells are separated from a sample of blood. It is a specific type of apheresis, the more general term for separating out one particular constituent of blood and returning the remain ...
procedure. This procedure is often utilized for asymptomatic hyperleukocytosis patients who have induction chemotherapy postponed for patient-specific factors.
Variants of
chemotherapy
Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs ( chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemothe ...
, 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
Neoadjuvant therapy is the administration of t ...
, are used to treat both elevated white blood cells counts while simultaneously targeting
leukemia
Leukemia ( also spelled leukaemia and pronounced ) is a group of blood cancers that usually begin in the bone marrow and result in high numbers of abnormal blood cells. These blood cells are not fully developed and are called ''blasts'' or ...
cells in the
bone marrow.
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
leukemia
Leukemia ( also spelled leukaemia and pronounced ) is a group of blood cancers that usually begin in the bone marrow and result in high numbers of abnormal blood cells. These blood cells are not fully developed and are called ''blasts'' or ...
s characterized by an
excess of
white blood cells 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
A brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as vision. It is the most complex organ in a ve ...
and
lungs are the two most commonly affected organs.
Leukostasis most commonly occurs with
acute myeloid leukemia
Acute myeloid leukemia (AML) is a cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal cells that build up in the bone marrow and blood and interfere with normal blood cell production. Symptoms may inclu ...
.
Hyperleukocytosis/leukostasis occurs more commonly, and at lower white blood cell (WBC) counts, in acute myeloid leukemia than in
acute lymphocytic 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 ...
, 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
A cough is a sudden expulsion of air through the large breathing passages that can help clear them of fluids, irritants, foreign particles and microbes. As a protective reflex, coughing can be repetitive with the cough reflex following three ph ...
,
difficulty breathing,
breathing too quickly, or
inadequate levels of oxygen in the blood requiring support with a
mechanical ventilator
A ventilator is a piece of medical technology that provides mechanical ventilation by moving breathable air into and out of the lungs, to deliver breaths to a patient who is physically unable to breathe, or breathing insufficiently. Ventilators ...
.
Neurologic symptoms, such as
temporary confusion, blurry vision, dizziness,
ringing in the ears,
ataxia
Ataxia is a neurological sign consisting of lack of voluntary coordination of muscle movements that can include gait abnormality, speech changes, and abnormalities in eye movements. Ataxia is a clinical manifestation indicating dysfunction of ...
, stupor,
sleepiness
Somnolence (alternatively sleepiness or drowsiness) is a state of strong desire for sleep, or sleeping for unusually long periods (compare hypersomnia). It has distinct meanings and causes. It can refer to the usual state preceding falling asleep ...
,
headaches, and
coma, may be seen. Neurologic signs such as
seizure
An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much of the body with l ...
s, 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,
priapism
Priapism is a condition in which a penis remains erect for hours in the absence of stimulation or after stimulation has ended. There are three types: ischemic (low-flow), nonischemic (high-flow), and recurrent ischemic (intermittent). Most cases ...
, 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 (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 cell
Red blood cells (RBCs), also referred to as red cells, red blood corpuscles (in humans or other animals not having nucleus in red blood cells), haematids, erythroid cells or erythrocytes (from Greek ''erythros'' for "red" and ''kytos'' for "holl ...
s sometimes resulting in
anemia
Anemia or anaemia (British English) is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. When anemia comes on slowly, t ...
and a decreased
hematocrit
The hematocrit () (Ht or HCT), also known by several other names, is the volume percentage (vol%) of red blood cells (RBCs) in blood, measured as part of a blood test. The measurement depends on the number and size of red blood cells. It is norm ...
.
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 can be normal in those with leukostasis or may demonstrate an alveolar pattern of infiltrates.
Brain imaging with
computed tomography (CT) or
magnetic resonance imaging (MRI) is useful and can demonstrate areas of bleeding,
ischemic 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 funct ...
, or masses.
Laboratory abnormalities seen in those with leukostasis include a markedly elevated white blood cell count (hyperleukocytosis) and
electrolyte abnormalities seen with
tumor lysis syndrome
Tumor lysis syndrome (TLS) is a group of metabolic abnormalities that can occur as a complication from the treatment of cancer, where large amounts of tumor cells are killed off ( lysed) from the treatment, releasing their contents into the blood ...
such as
high concentrations of potassium,
phosphorus
Phosphorus is a chemical element with the symbol P and atomic number 15. Elemental phosphorus exists in two major forms, white phosphorus and red phosphorus, but because it is highly reactive, phosphorus is never found as a free element on Ear ...
, and
uric acid
Uric acid is a heterocyclic compound of carbon, nitrogen, oxygen, and hydrogen with the formula C5H4N4O3. It forms ions and salts known as urates and acid urates, such as ammonium acid urate. Uric acid is a product of the metabolic breakdown ...
in the blood and a low level of
calcium
Calcium is a chemical element with the symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar t ...
in the blood (due to being bound by high amounts of circulating phosphorus).
Management
It is an
acute
Acute may refer to:
Science and technology
* Acute angle
** Acute triangle
** Acute, a leaf shape in the glossary of leaf morphology
* Acute (medicine), a disease that it is of short duration and of recent onset.
** Acute toxicity, the adverse eff ...
syndrome requiring aggressive
cytoreductive modalities including
chemotherapy
Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs ( chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemothe ...
and/or
leukapheresis
Leukapheresis () is a laboratory procedure in which white blood cells are separated from a sample of blood. It is a specific type of apheresis, the more general term for separating out one particular constituent of blood and returning the remain ...
to both reduce the number of circulating leukocytes and to break apart any aggregates that have already formed. Such rapid and massive
lysis of tissue poses a risk of
complications (
tumor lysis syndrome
Tumor lysis syndrome (TLS) is a group of metabolic abnormalities that can occur as a complication from the treatment of cancer, where large amounts of tumor cells are killed off ( lysed) from the treatment, releasing their contents into the blood ...
), but it is necessary to avoid a
stroke.
Leukostasis is different from leukemic infiltration, which is a
neoplastic
A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...
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
A transient ischemic attack (TIA), commonly known as a mini-stroke, is a minor stroke whose noticeable symptoms usually end in less than an hour. TIA causes the same symptoms associated with strokes, such as weakness or numbness on one side of ...
and
strokes.
Epidemiology
The incidence and prevalence of hyperleukocytosis and leukostasis vary depending on the form of leukemia.
Hyperleukocytosis is common in
chronic myelogenous leukemia and
chronic lymphocytic leukemia, but leukostasis rarely occurs.
Similarly, the incidence of hyperleukocytosis in people with
acute lymphoblastic leukemia is between 10 and 30% but rarely does this progress to symptomatic leukostasis.
The incidence of hyperleukocytosis in
acute myeloid leukemia
Acute myeloid leukemia (AML) is a cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal cells that build up in the bone marrow and blood and interfere with normal blood cell production. Symptoms may inclu ...
(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