Movatterモバイル変換


[0]ホーム

URL:


Jump to content
WikipediaThe Free Encyclopedia
Search

Leukostasis

From Wikipedia, the free encyclopedia
Human disease
It has been suggested that this article besplit into articles titledAsymptomatic hyperleukocytosis andsymptomatic hyperleukocytosis. (Discuss)(September 2020)

Leukostasis (also called symptomatic hyperleukocytosis) is a medical emergency most commonly seen in patients withacute myeloid leukemia. It is characterized by an extremely elevatedblast cell count and symptoms of decreasedtissue 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 themicrovasculature. The most common symptoms aredyspnea andhypoxia, 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)

[edit]
Leukocytes

Symptomatic Hyperleukocytosis (Leukostasis) is defined by a tremendously highblast cell count along with symptoms of decreased tissueperfusion. Leukostasis is associated with people who have bone and blood disorders and is very common among people withacute myeloid leukemia orchronic myeloid leukemia. Leukostasis is a pathologic diagnosis that inhibits efficient flow to themicrovasculature of the body. Continued and untreated leukostasis presentsrespiratory andneurological 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 withLeukemias.[1]

Symptoms and signs

[edit]

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 andrespiratory failure equating to 70 percent of all death rates. Damage to themicrovasculature 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.[2]

Pulmonary signs -Dyspnea andhypoxia 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 usuallyfebrile, which is often linked with inflammation and possible infection.

Less common signs include:myocardial ischemia / rightventricular overload, increasedacute kidney injury,priapism, acute limbischemia and bowelinfarction.

Causes of asymptomatic/symptomatic hyperleukocytosis (leukostasis)

[edit]
Causes of leukocytosis
Neutrophilic
leukocytosis
(neutrophilia)
Eosinophilic
leukocytosis
(eosinophilia)
Basophilic
leukocytosis
Basophilia
(rare)[3]
Monocytosis
Lymphocytosis

Hyperleukocytosis is very common in acutely ill patients. It occurs in response to a wide variety of conditions, includingviral,bacterial,fungal, orparasitic infection, cancer, hemorrhage, and exposure to certain medications.

For lung diseases such aspneumonia andtuberculosis, white blood cell count is crucial for the diagnosis of the disease, as leukocytosis is usually present.

Specific medications, includingcorticosteroids,lithium andbeta-agonists can cause hyperleukocytosis.[4]

Pathophysiology

[edit]

The mechanism in which hyperleukocytosis or leukostasis manifests and disruptshomeostasis 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 haveneutrophilia,lymphocytosis,monocytosis,eosinophilia,basophilia or a rise in immatureblast cells.[2]

Acute myeloid leukemia - 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 chroniclymphocytic 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

[edit]

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.[citation needed]

Theory 2

[edit]

Hypoxic events in body regions may increase the high metabolic activity of dividingblast cells and lead to an increase incytokine production. The increasing levels ofcytokines within tissues may result in endothelial damage and subsequenthemorrhage. 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.[citation needed]

The combination of these theories, in addition to other events, may lead to hyperleukocytosis.

Diagnosis

[edit]

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.

Acquiredbiopsies are examined for damage to microvasculature, which serves as evidence of hypoxia through the identification of leukocyte blockage within the tissue. Due to thebiopsy's invasive nature and the risks associated with the procedure, it is only used when deemed necessary.[2]

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 assesspO2 levels of a patient suspected to have leukocytosis. Automated blood cell counters may be inaccurate due to fragments ofblast cells being labeled onblood smears asplatelets. 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 duringin vitro clotting process, therefore serum potassium levels should be monitored byheparinized (the addition ofheparin preventscoagulation) 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 ofthrombin generation, followed by decreased fibrinogen and increased fibrinolysis.[citation needed]

Spontaneoustumor 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 asuric acid,potassium,phosphate, andhypocalcemia.

Disseminated intravascular coagulation and spontaneoustumor 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

[edit]

Since leukostasis and hyperleukostasis are associated with leukemia, preventive treatments are taken upon diagnosis.[2]

Patients with hyperleukocytosis associated with leukemia are always considered candidates for tumor lysis syndrome prophylaxis in addition to aggressive intravenous hydration with allopurinol orrasburicase to decrease serum uric acid levels.

Treatment

[edit]

Treatment includes utilization ofprophylactic 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 aggressiveintravenous hydration withallopurinol orrasburicase to decrease serum uric acid levels.[2]

Hematopoietic 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 drughydroxyurea (Hydroxyurea is usually used in asymptomatic hyperleukocytosis), and the less commonleukapheresis procedure. This procedure is often utilized for asymptomatic hyperleukocytosis patients who have induction chemotherapy postponed for patient-specific factors.[citation needed]

Variants ofchemotherapy, includinginduction chemotherapy, are used to treat both elevated white blood cells counts while simultaneously targetingleukemia cells in thebone marrow.[citation needed]

Prognosis

[edit]

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.[citation needed]

Recent research

[edit]

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.[2]

Leukemia and population types are also believed to be associated with possible symptoms and may require a change in treatment.[2]

Results of Tumor lysis/ consumption of coagulopathy in patients with acute leukemia is much more often than in patients with chronic malignant hematological diseases.[5]

  • Data retrieved for reference is 2017

Leukostasis, also known assymptomatic hyperleukocytosis, is a life-threatening complication of variousleukemias characterized by anexcess ofwhite 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. Thebrain andlungs are the two most commonly affected organs.[6] Leukostasis most commonly occurs withacute myeloid leukemia.

Hyperleukocytosis/leukostasis occurs more commonly, and at lower white blood cell (WBC) counts, in acute myeloid leukemia than inacute 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

[edit]

Individuals affected by leukostasis may present with respiratory symptoms such ascough,difficulty breathing,breathing too quickly, orinadequate levels of oxygen in the blood requiring support with amechanical ventilator.[6][7] Neurologic symptoms, such astemporary confusion, blurry vision, dizziness,ringing in the ears,ataxia, stupor,sleepiness,headaches, andcoma, may be seen. Neurologic signs such asseizures, focal neurologic deficits (e.g., weakness in one arm or leg),swelling of the retina, retinal bleeding, and dilated blood vessels oninspection of the back of the eye.[7] Rare complications of leukostasis includerenal vein thrombosis,priapism, and acute ischemia of the leg.[6]

Pathophysiology

[edit]

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.[7] 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 greatermean corpuscular volume (larger cells) with decreased deformability occupying the blood vessels.[6] However, certain studies have demonstrated that the blood viscosity of affected individuals is not increased due to a compensatory decrease in the number ofred blood cells sometimes resulting inanemia and a decreasedhematocrit.[7]

Diagnosis

[edit]

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 whenlistening to the lungs with a stethoscope.[6]

Achest x-ray can be normal in those with leukostasis or may demonstrate an alveolar pattern of infiltrates.[7] Brain imaging withcomputed tomography (CT) ormagnetic resonance imaging (MRI) is useful and can demonstrate areas of bleeding,ischemic stroke, or masses.[7]

Laboratory abnormalities seen in those with leukostasis include a markedly elevated white blood cell count (hyperleukocytosis) andelectrolyte abnormalities seen withtumor lysis syndrome such ashigh concentrations of potassium,phosphorus, anduric acid in the blood and a low level ofcalcium in the blood (due to being bound by high amounts of circulating phosphorus).[7]

Management

[edit]

It is anacute syndrome requiring aggressivecytoreductivemodalities includingchemotherapy and/orleukapheresis to both reduce the number of circulating leukocytes and to break apart any aggregates that have already formed. Such rapid and massivelysis of tissue poses a risk ofcomplications (tumor lysis syndrome), but it is necessary to avoid astroke.

Leukostasis is different from leukemic infiltration, which is aneoplastic process where leukemic cells invade organs.[8]

Prognosis

[edit]

Leukostasis is a high-risk condition and can lead to significant complications resulting from occlusion of blood vessels, includingtransient ischemic attacks andstrokes.

Epidemiology

[edit]

The incidence and prevalence of hyperleukocytosis and leukostasis vary depending on the form of leukemia.[7] Hyperleukocytosis is common inchronic myelogenous leukemia andchronic lymphocytic leukemia, but leukostasis rarely occurs.[7] Similarly, the incidence of hyperleukocytosis in people withacute lymphoblastic leukemia is between 10 and 30% but rarely does this progress to symptomatic leukostasis.[7] The incidence of hyperleukocytosis inacute 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.[7]

References

[edit]
  1. ^Schiffer, Charles, MD."Hyperleukocytosis and Leukostasis".UpToDate. Retrieved11 November 2017.{{cite web}}: CS1 maint: multiple names: authors list (link)
  2. ^abcdefg"Hyperleukocytosis and leukostasis in hematologic malignancies".www.uptodate.com. Retrieved2017-12-12.
  3. ^abcdefghijklmnopqrstuvwxyzaaabacadaeTable 12-6 in:Mitchell, Richard Sheppard; Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson (2007),Robbins Basic Pathology, Philadelphia: Saunders,ISBN 978-1-4160-2973-1 8th edition.
  4. ^Leukocytosis: Basics of Clinical Assessment,American Family Physician. November 2000.
  5. ^Schellongowski, P.; Staudinger, T. (September 2013). "[Leukostasis and tumor lysis: important complications of hyperleukocytosis]".Der Internist.54 (9):1051–1060.doi:10.1007/s00108-013-3260-5.ISSN 1432-1289.PMID 23943008.
  6. ^abcdeGanzel, C; Becker, J; Mintz, PD; Lazarus, HM; Rowe, JM (May 2012). "Hyperleukocytosis, leukostasis and leukapheresis: practice management".Blood Reviews.26 (3):117–22.doi:10.1016/j.blre.2012.01.003.PMID 22364832.
  7. ^abcdefghijkAli, AM; Mirrakhimov, AE; Abboud, CN; Cashen, AF (June 2016)."Leukostasis in adult acute hyperleukocytic leukemia: a clinician's digest".Hematological Oncology.34 (2):69–78.doi:10.1002/hon.2292.PMID 27018197.
  8. ^"Leukostasis".Medical Subject Headings, 2009–2009-02-13. 1995-06-01.
Diseases ofmonocytes andgranulocytes
Monocytes andmacrophages
-cytosis:
-penia:
Granulocytes
-cytosis:
-penia:
Disorder of phagocytosis
Chemotaxis anddegranulation
Respiratory burst
Lymphatic disease: organ and vessel diseases
Thymus
Spleen
Lymph node
Lymphatic vessels
Retrieved from "https://en.wikipedia.org/w/index.php?title=Leukostasis&oldid=1258607993"
Categories:
Hidden categories:

[8]ページ先頭

©2009-2025 Movatter.jp