Essential Thrombocythemia

ET

Essential thrombocythemia, also known as essential thrombocytosis or primary thrombocytosis, is a rare, chronic myeloproliferative disorder.

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Essential Thrombocythaemia

Essential Thrombocythaemia, CC BY-SA 4.0

Presentation

In about two thirds of the individuals, the disease does not cause any symptoms and is diagnosed incidentally on routine blood tests. In patients with symptomatic disease the signs and symptoms vary among different individuals. The most common manifestations are abnormal bleeding or thrombosis.

Bleeding tendency may manifest in the form of:

Bleeding from respiratory tract.
Bleeding from gastrointestinal tract.
Bleeding from urinary tract.
Bleeding from gums.
Epistaxis.
Early bruising.

Thrombi may form anywhere in the body including the heart and intestine, thus compromising their blood supply. Thrombosis occurring in small vessels mainly causes numbness and abnormal burning sensations of hands and feet [5] [6].

Other signs and symptoms of clotting include:

Changes in speech and orientation causing confusion.
Seizures.
Shortness of breath.
Nausea.
Discomfort in arms, legs, back, neck, jaw or abdomen.

In high risk cases clotting in the brain may result in stroke. In pregnant females, blood clots in the placenta may cause problems in the fetal growth and development or may lead to termination of pregnancy. All the females with essential thrombocythemia who use oral contraceptive pills are at a higher risk of developing thrombosis.

Hematological

Easy Bruising

About one-third of patients with ET will demonstrate no symptoms at all, but many will experience easy bruising or bleeding with little or no injury.[uihc.org]
Symptoms include dizziness, easy bruising, headache, bloody stools, numbness of the hands or feet, ulcers on the toes or fingers, nosebleeds, prolonged bleeding after surgery or tooth removal, and bleeding from the gums, gastrointestinal and/or urinary[amarillo.com]
Blood vessel disturbances or bleeding can result in: Headache Vision disturbances or silent migraines Dizziness or lightheadedness Coldness or blueness of fingers or toes Burning, redness, and pain in the hands and feet Easy bruising, nosebleeds or heavy[hopkinsmedicine.org]
bruising and nosebleeds Bleeding from the gastrointestinal tract, respiratory system, urinary tract, or skin Bleeding from the gums Prolonged bleeding from surgical procedures or tooth removal Most of the time, ET is found through blood tests done for[medlineplus.gov]

Immune System

Splenomegaly

And the clinical characteristics of ET patients, such as WBC counts, hemoglobin level, splenomegaly and thrombosis, were influenced by JAK2V617F mutation burden.[ncbi.nlm.nih.gov]
[…] erythroid hyperplasia, atypical megas Panmyelosis, atypical tightly clustered megas Megas Erythroid dysplasia, ring sideroblasts, megas Erythroid hypoplasia, small megas Marrow Fibrosis Varies in spent phase in fibrotic phase Minimal Varies Minimal Splenomegaly[surgpathcriteria.stanford.edu]
Polycythemia Vera (PV) and essential thrombocythemia (ET) are myeloproliferative neoplasms respectively characterized by erythrocytosis and thrombocytosis; other disease features include leukocytosis, splenomegaly, thrombosis, bleeding, microcirculatory[ncbi.nlm.nih.gov]
The primary endpoint for PV was overall response rate (ORR), defined as the proportion of patients with hematocrit 45%, white blood cell count 10 109/L, platelet count 400 109/L, and resolution of palpable splenomegaly, each lasting 4 weeks.[ncbi.nlm.nih.gov]
The 2016 revised WHO criteria for the diagnosis of pre-fibrotic/early primary myelofibrosis (pre-PMF) require at least one of the following four borderline expressed minor clinical criteria: anemia, leukocytosis, elevated lactate dehydrogenase and splenomegaly[ncbi.nlm.nih.gov]

Respiratoric

Dyspnea

A 52-year-old African American male with ET presented with chest pain, shortness of breath, and dyspnea on exertion. His ET was managed with hydroxyurea 1500 mg by mouth twice a day and anagrelide 1 mg by mouth 3 times a day.[ncbi.nlm.nih.gov]
Three patients experienced serious AEs (7.7%), with 1 considered related to momelotinib (dyspnea). Peripheral neuropathy occurred in 7 (17.9%) patients (4 PV, 3 ET).[ncbi.nlm.nih.gov]
Adverse events: The most common adverse reactions are headache, palpitations, diarrhea, asthenia, edema, nausea, abdominal pain, dizziness, pain, dyspnea, cough, flatulence, vomiting, fever, peripheral edema, rash, chest pain, anorexia, tachycardia, malaise[oatext.com]

Hemoptysis

Other superficial bleeding manifestations of ET include mucosal hemorrhage, such as epistaxis, hemoptysis, gingival oozing or bleeding from the gastrointestinal or genitourinary tracts.[cancertherapyadvisor.com]

Liver, Gall & Pancreas

Hepatomegaly

PHYSICAL EXAMINATION • Unremarkable • 40-50% present with splenomegaly • 20% present with hepatomegaly 12.[slideshare.net]
In some cases the liver may also be enlarged (hepatomegaly). Other symptoms include weight loss and generalised itching. Blood clots (thrombosis) and bleeding Thrombosis is a major complication of essential thrombocythaemia.[leukaemia.org.au]
Approximately 40-50% of patients present with splenomegaly; 20% present with hepatomegaly. Causes The etiology and predisposing factors for the development of essential thrombocytosis (primary thrombocythemia) remain unclear.[emedicine.medscape.com]
Slight hepatomegaly is seen in about 20% of cases. Lymphadenopathy is not characteristic. Examination of the peripheral blood smear typically shows both an increased number of platelets and giant sized platelets.[cancertherapyadvisor.com]

Hepatosplenomegaly

Ultrasound scan An ultra sound scan can be used to assess hepatosplenomegaly, which can then provide an indication of how far the disease has progressed.[aoporphan.com]

Urogenital

Hematuria

[…] disturbances is erythromelalgia, consisting of congestion, redness and burning pain to ischemia and gangrene of the distal portions of toes and fingers. 15 The most frequent bleeding events are hemorrhages from the gastrointestinal tract followed by hematuria[nature.com]

Neurologic

Headache

Case A 32-year-old woman, 4 weeks postpartum, presented to the ED with a chief complaint of headache, which she stated had become worse over the past 4 days. The headache was gradual-onset, bioccipital, and pressure-like.[mdedge.com]
Causes - Hemorrhagic thrombocythemia (Essential Thrombocythemia) * Anemia * Central nervous system ischemia * Coughing up blood * Deep vein thrombosis * Dizziness * Enlarged spleen * Headache * Increased platelets * Melena * Menorrhagia * Nosebleed *[checkorphan.org]
Diagnosing Essential Thrombocythemia Essential thrombocythemia is often spotted during a routine blood exam in persons who either have no symptoms or vague, nonspecific symptoms (such as fatigue or a headache).[verywell.com]
Side effects can include headaches and palpitations (a fast heartbeat). Some research studies suggest it may increase the risk of developing myelofibrosis.[macmillan.org.uk]
Side effects are common, especially headache and tachycardia, but usually subside or disappear within a few weeks. Around 20 % of patients stop ANA therapy due to side effects or insufficient response.[ncbi.nlm.nih.gov]

Stroke

Stroke in a tertiary hospital in Saudi Arabia: a study of 372 cases. Eur Neurol . 1991 ; 31 : 251 -256. Bogousslavsky J, Van Melle G, Regli F. The Lausanne Stroke Registry: analysis of 1,000 consecutive patients with first stroke.[stroke.ahajournals.org]
Ischemic stroke is one of the most serious complications of ET. The risk factors for thrombotic/ischemic events in patients with ET include age ( 60 years) and previous vascular events.[ncbi.nlm.nih.gov]
The abnormal blood clotting of essential thrombocythemia can lead to a variety of potentially serious complications, including: Stroke. A clot that blocks blood flow to your brain can cause a stroke.[mayoclinic.org]
Symptoms Symptoms of blood clots may include any of the following: Headache (most common) Tingling, coldness, or blueness in the hands and feet Feeling dizzy or lightheaded Vision problems Mini- strokes ( transient ischemic attacks ) or stroke If bleeding[ufhealth.org]
Abnormal blood clotting can also occur, leading to stroke, heart attack, and unusual clots in the blood vessels of the abdomen.[my.clevelandclinic.org]

Dizziness

Causes - Hemorrhagic thrombocythemia (Essential Thrombocythemia) * Anemia * Central nervous system ischemia * Coughing up blood * Deep vein thrombosis * Dizziness * Enlarged spleen * Headache * Increased platelets * Melena * Menorrhagia * Nosebleed *[checkorphan.org]
A total of 31 (79.5%) patients experienced momelotinib-related adverse events (AEs), the most frequent being headache (23.1%), dizziness (18.0%), somnolence (15.4%), nausea (15.4%), and fatigue (15.4%).[ncbi.nlm.nih.gov]
In the central nervous system, it manifests itself in the guise of functional disturbances such as repetitive sight and speech disorders, dizziness, balance difficulties, paralysis and even seizures.[aoporphan.com]
Symptoms include dizziness, easy bruising, headache, bloody stools, numbness of the hands or feet, ulcers on the toes or fingers, nosebleeds, prolonged bleeding after surgery or tooth removal, and bleeding from the gums, gastrointestinal and/or urinary[amarillo.com]

Tingling

This occurs in around half of the patients and is noticeable in the fingers and toes through a reddening of the skin, which is accompanied by swelling (erythromelalgia) and a burning and tingling sensation.[aoporphan.com]
Corresponding ICD-10 Codes D47.3 Essential (hemorrhagic) thrombocythemia Corresponding ICD-10-CM Codes (U.S. only) D47.3 Essential (hemorrhagic) thrombocythemia (effective October 01, 2015) Signs and Symptoms Bleeding from mucosa l surfaces Burning or tingling[seer.cancer.gov]
Symptoms, when they do occur, commonly include: Thrombosis Abnormal bleeding Headaches Tingling in the extremities Pain in the extremities Peripheral Blood Findings The platelet count is greater than 600 x 10 9 /L, frequently 1,000 - 5,000 x 10 9 /L.[labce.com]
Some patients with essential thrombocythemia develop erythromelalgia, causing pain, swelling, and redness of the hands and feet, as well as numbness and tingling. Next: Diagnosis and Tests Cleveland Clinic is a non-profit academic medical center.[my.clevelandclinic.org]

Paresthesia

Symptoms and signs may include weakness, headaches, paresthesias, bleeding, splenomegaly, and erythromelalgia with digital ischemia.[msdmanuals.com]
Some patients with ET are asymptomatic, while others may experience microcirculatory disturbances or vasomotor events: headaches, visual disturbances, lightheadedness, atypical chest pain, distal paresthesias, erythromelalgia, and other symptoms of transient[orpha.net]
Patients also report paresthesias and episodic transient ischemic attacks; transient neurologic symptoms include the following: Unsteadiness Dysarthria Dysphoria Vertigo Dizziness Migraine Syncope Scotoma Seizures Thrombosis of large veins and arteries[emedicine.medscape.com]
Patients may have complaints of dizziness, light-headed, paresthesia, visual changes, or headaches. Patients may also have findings of bleeding, or alternately thrombosis. B. History Part 2: Prevalence. 2 Females: 1 Males.[clinicaladvisor.com]

Entire body system

Pain

They include: Headache Dizziness or lightheadedness Chest pain Fainting Temporary vision changes Numbness or tingling of the hands and feet Redness, throbbing and burning pain in the hands and feet (erythromelalgia) Less commonly, essential thrombocythemia[mayoclinic.org]
An 82-year-old woman who had a history of essential thrombocythemia presented with ocular pain, bleeding, and decreased visual acuity of the left eye.[ncbi.nlm.nih.gov]
Resources - Hemorrhagic thrombocythemia (Essential Thrombocythemia) Call your health care provider: * If unexplained or prolonged bleeding occurs * If chest pain, leg pain, confusion, weakness, numbness, or other new symptoms develop[checkorphan.org]
A 52-year-old African American male with ET presented with chest pain, shortness of breath, and dyspnea on exertion. His ET was managed with hydroxyurea 1500 mg by mouth twice a day and anagrelide 1 mg by mouth 3 times a day.[ncbi.nlm.nih.gov]
Symptoms of ET include: Headache Dizziness or light-headedness Chest pain Weakness Fainting Vision changes that eventually go away Numbness or tingling in the hands and feet Redness, throbbing, and burning pain in the hands and feet Mildly enlarged spleen[voicesofmpn.com]

Weakness

Symptoms and signs may include weakness, headaches, paresthesias, bleeding, splenomegaly, and erythromelalgia with digital ischemia.[msdmanuals.com]
Resources - Hemorrhagic thrombocythemia (Essential Thrombocythemia) Call your health care provider: * If unexplained or prolonged bleeding occurs * If chest pain, leg pain, confusion, weakness, numbness, or other new symptoms develop[checkorphan.org]
They include: Headache Dizziness or lightheadedness Chest pain Weakness Fainting Temporary vision changes Numbness or tingling of the hands and feet Redness, throbbing and burning pain in the hands and feet (erythromelalgia) Mildly enlarged spleen Less[medicalmarijuana.com]
Symptoms of ET include: Headache Dizziness or light-headedness Chest pain Weakness Fainting Vision changes that eventually go away Numbness or tingling in the hands and feet Redness, throbbing, and burning pain in the hands and feet Mildly enlarged spleen[voicesofmpn.com]

Fever

[…] and marrow fibrosis grade 2 - 3 (on 0 - 3 scale) Additional criteria (2 required) : anemia or decrease in Hb by 2 gm/dL from the baseline level; leukoerythroblastic peripheral blood; splenomegaly; rise in LDH levels; constituitional symptoms including fever[pathologyoutlines.com]
[…] gastrointestinal (GI) tract, skin, eyes, gums or urinary tract abdominal discomfort or feeling of fullness if the spleen or liver is enlarged tingling in the hands and feet sweating itchiness slightly higher than normal temperature (called a low-grade fever[cancer.ca]
She denied head injury, fever, chills, nausea, vomiting, neck pain, visual changes, focal weakness, or numbness. Her past medical history was significant for essential thrombocytosis (ET) with three prior spontaneous abortions.[mdedge.com]
Lossos IS, Matzner Y (1995) Hydroxyurea-induced fever: case report and review of the literature. Ann Pharmacother 29:132–133 PubMed Google Scholar 49. Braester A, Quitt M (2000) Hydroxyurea as a cause of drug fever.[link.springer.com]
Other symptoms include sweating, low-grade fever, and pruritus. Pregnancy complications are as follows [22] : Spontaneous abortions increase Placental infarctions may occur, resulting in intrauterine growth retardation and fetal death.[emedicine.medscape.com]

Gangrene

If left untreated, erythromelalgia usually leads to painful acrocyanosis and gangrene of one or more toes or tips of the finger[ 4 - 12 ].[wjgnet.com]
Aspirin in low doses can be used to control microvascular symptoms such as redness and pain in the fingers and toes, insufficient blood flow (ischemia), infections in the limbs (gangrene), strokes, syncopes, instability or visual disturbances. [4] [10[rarediseases.info.nih.gov]
Microvascular occlusion of the toes and fingers causes digital pain; gangrene; or erythromelalgia , which is is characterized by burning pain and dusky extremity congestion The pain increases with exposure to heat and improves with cold; a single dose[emedicine.medscape.com]
Painful vascular insufficiency may progress to frank gangrene and necrosis of the digits unless treatment is promptly instituted.[medtextfree.wordpress.com]
Definitions and statistical analysis Thrombotic events included arterial events (thrombotic strokes, transient ischemic attacks, and digital gangrene) and venous thrombosis (pulmonary embolism, deep venous thrombosis, retinal venous thrombosis, and portal[jamanetwork.com]

Burning Pain

Symptoms of ET include: Headache Dizziness or light-headedness Chest pain Weakness Fainting Vision changes that eventually go away Numbness or tingling in the hands and feet Redness, throbbing, and burning pain in the hands and feet Mildly enlarged spleen[voicesofmpn.com]
They include: Headache Dizziness or lightheadedness Chest pain Fainting Temporary vision changes Numbness or tingling of the hands and feet Redness, throbbing and burning pain in the hands and feet (erythromelalgia) Less commonly, essential thrombocythemia[mayoclinic.org]
They include: Headache Dizziness or lightheadedness Chest pain Weakness Fainting Temporary vision changes Numbness or tingling of the hands and feet Redness, throbbing and burning pain in the hands and feet (erythromelalgia) Mildly enlarged spleen Less[medicalmarijuana.com]
Others may experience symptoms such as: Heart attack or stroke Persistent or repeated headaches Bruising and bleeding, including nosebleeds or heavy periods Burning pain, redness in hands or feet Gastrointestinal bleeding or blood in the urine Bleeding[mpnvoice.org.uk]
Microvascular occlusion of the toes and fingers causes digital pain; gangrene; or erythromelalgia , which is is characterized by burning pain and dusky extremity congestion The pain increases with exposure to heat and improves with cold; a single dose[emedicine.medscape.com]

Gastrointestinal

Nausea

A total of 31 (79.5%) patients experienced momelotinib-related adverse events (AEs), the most frequent being headache (23.1%), dizziness (18.0%), somnolence (15.4%), nausea (15.4%), and fatigue (15.4%).[ncbi.nlm.nih.gov]
Most common treatment-emergent adverse events were diarrhea (55.3%) and nausea (42.1%), a majority of which were of grade 1 severity. Best response of clinical improvement was achieved by 29% of myelofibrosis patients.[ncbi.nlm.nih.gov]
Nausea. Discomfort in arms, legs, back, neck, jaw or abdomen. In high risk cases clotting in the brain may result in stroke.[symptoma.com]
She denied head injury, fever, chills, nausea, vomiting, neck pain, visual changes, focal weakness, or numbness. Her past medical history was significant for essential thrombocytosis (ET) with three prior spontaneous abortions.[mdedge.com]
., deep vein thrombosis or pulmonary embolism ), headache, nausea, vomiting, abdominal pain, visual disturbances, dizziness, fainting , and numbness in the extremities; the most common signs are increased white blood cell count , reduced red blood cell[en.wikipedia.org]

Abdominal Pain

., deep vein thrombosis or pulmonary embolism ), headache, nausea, vomiting, abdominal pain, visual disturbances, dizziness, fainting , and numbness in the extremities; the most common signs are increased white blood cell count , reduced red blood cell[en.wikipedia.org]
Adverse events: The most common adverse reactions are headache, palpitations, diarrhea, asthenia, edema, nausea, abdominal pain, dizziness, pain, dyspnea, cough, flatulence, vomiting, fever, peripheral edema, rash, chest pain, anorexia, tachycardia, malaise[oatext.com]
As the disease progresses, many patients develop abdominal pain secondary to organomegaly.[clevelandclinicmeded.com]

Melena

Symptoms - Hemorrhagic thrombocythemia (Essential Thrombocythemia) The list of signs and symptoms mentioned in various sources for Hemorrhagic thrombocythemia includes the 18 symptoms listed below: * Spontaneous bleeding * Coughing up blood * Melena *[checkorphan.org]
A history of gastrointestinal blood loss (melena and/or hematemesis) or biological evidence in favor of chronic occult blood loss may be evidenced at diagnosis. Secondary bleeding, eventually life-threatening can also occur after trauma or surgery.[ojrd.biomedcentral.com]

Blood in Stool

The patients may complain of nose bleeds, blood in stools, early bruising, prolonged bleeding from cuts or other injuries, burning or tingling sensations in palms and soles of the hands and feet respectively.[symptoma.com]

Jaw & Teeth

Bleeding Gums

This may appear as nosebleeds, bleeding gums or bruising. Rarely, essential thrombocythemia may progress to these potentially life-threatening diseases: Acute myelogenous leukemia.[mayoclinic.org]
Some people notice frequent or severe nose bleeds or bleeding gums and some women may have unusually heavy menstrual periods. In pregnancy, uncontrolled essential thrombocythaemia can reduce the blood supply to the placenta or foetus.[leukaemia.org.au]
Monitor clinically for signs of bleeding, bleeding gums, DVT, erthromelalgia. Patients with reactive thrombocytosis, even with platelets 1000 x10 9 /L, will not usually experience vasomotor symptoms or significant bleeding or thrombosis. C.[clinicaladvisor.com]

Cardiovascular

Thrombosis

To better predict the occurrence of thrombotic events, an International Prognostic Score for Thrombosis in Essential Thrombocythemia (IPSET-thrombosis) has recently been proposed.[ncbi.nlm.nih.gov]
In ET, risk stratification includes four categories: very low risk (age 60 years, no thrombosis history, JAK2/MPL un-mutated), low risk (age 60 years, no thrombosis history, JAK2/MPL mutated), intermediate risk (age 60 years, no thrombosis history, JAK2[ncbi.nlm.nih.gov]
The role of antiplatelet therapy as primary prophylaxis of thrombosis in low-risk essential thrombocythemia has not been studied in randomized clinical trials.[ncbi.nlm.nih.gov]
We currently consider three major risk factors for thrombosis (history of thrombosis, JAK2/MPL mutations, and advanced age), in order to group ET patients into four risk categories: "very low risk" (absence of all three risk factors); "low risk" (presence[ncbi.nlm.nih.gov]
The objective of this study was to better define the effect of JAK2V617F mutant allele burden on clinical phenotypes in Chinese patients, especially thrombosis.[ncbi.nlm.nih.gov]

Musculoskeletal

Leg Pain

Resources - Hemorrhagic thrombocythemia (Essential Thrombocythemia) Call your health care provider: * If unexplained or prolonged bleeding occurs * If chest pain, leg pain, confusion, weakness, numbness, or other new symptoms develop[checkorphan.org]
You notice chest pain , leg pain , confusion , weakness , numbness , or other new symptoms. Images References Hoffman R, Kremyanskaya M, Najfeld V, Mascarenhas J. Essential thrombocythemia.[ufhealth.org]
pain or swelling in arms or legs shortness of breath chest pain increased coughing (possibly with blood) Follow-Up Care and Prognosis ET requires regular appointments with your doctor.[uihc.org]
pains Coldness or blueness of fingers or toes Vision disturbances or silent migraines Diagnostic tests If your haematologist suspects you have ET, he or she may suggest some of the following tests: Full blood count (blood test): The full blood count[mpnvoice.org.uk]

Neck Pain

She denied head injury, fever, chills, nausea, vomiting, neck pain, visual changes, focal weakness, or numbness. Her past medical history was significant for essential thrombocytosis (ET) with three prior spontaneous abortions.[mdedge.com]

Back Pain

pain, pruritus and dyspepsia.[oatext.com]

Eyes

Scotoma

Patients also report paresthesias and episodic transient ischemic attacks; transient neurologic symptoms include the following: Unsteadiness Dysarthria Dysphoria Vertigo Dizziness Migraine Syncope Scotoma Seizures Thrombosis of large veins and arteries[emedicine.medscape.com]
The MIAs in these 10 JAK2 V617F mutated MPN patients ranged from attacks of transient blindness, diplopia and scotomas to migraine-like attacks followed by throbbing headaches, nausea, vomiting or even seizures.[wjgnet.com]
How I manage patients with ET Low-dose aspirin In ET, aspirin, 100 mg daily, has been found to control microvascular symptoms, such as erythromelalgia, and transient neurological and ocular disturbances including dysarthria, hemiparesis, scintillating scotomas[nature.com]
[…] feature of ET and other MPNs affects patients’ quality of life and is multifactorial in etiology. 23-25 Vasomotor symptoms, including headaches, erythromelalgia, acroparesthesias, livedo reticularis, transient ischemic attacks, peripheral ischemia, scotomas[hematologyandoncology.net]

Skin

Pruritus

We currently do not recommend treatment with ruxolutinib or other JAK2 inhibitors in PV or ET, unless in the presence of severe and protracted pruritus or marked splenomegaly that is not responding to the aforementioned drugs.[ncbi.nlm.nih.gov]
[…] clustered megas Megas Erythroid dysplasia, ring sideroblasts, megas Erythroid hypoplasia, small megas Marrow Fibrosis Varies in spent phase in fibrotic phase Minimal Varies Minimal Splenomegaly Absent Clinical/Other B symptoms Hypertension, thrombosis, pruritus[surgpathcriteria.stanford.edu]
Other symptoms include sweating, low-grade fever, and pruritus. Pregnancy complications are as follows [22] : Spontaneous abortions increase Placental infarctions may occur, resulting in intrauterine growth retardation and fetal death.[emedicine.medscape.com]
[…] adverse reactions are headache, palpitations, diarrhea, asthenia, edema, nausea, abdominal pain, dizziness, pain, dyspnea, cough, flatulence, vomiting, fever, peripheral edema, rash, chest pain, anorexia, tachycardia, malaise, paresthesia, back pain, pruritus[oatext.com]
Parameters examined for possible association included age, sex, risk category, 16 , 17 karyotype, thrombosis history, leukocyte count, hemoglobin level, platelet count, palpable splenomegaly, pruritus, and microvascular symptoms.[bloodadvances.org]

Night Sweats

sweats, 10% weight loss in 6 months Microscopic (histologic) images Images hosted on PathOut server: Peripheral blood: Clusters of large platelets (platelet count is 1700K) Images hosted on other servers: Bone marrow smear: Increased megakaryocytes Molecular[pathologyoutlines.com]
In one large internet-based survey of 304 patients with ET, 72% reported fatigue, and 40% or more reported itching, night sweats and bone pain.[healio.com]
Systemic symptoms such as weight loss, fevers and night sweats are unusual in ET; their occurrence should raise the suspicion of an alternative diagnosis. The physical exam in most patients with ET is normal.[cancertherapyadvisor.com]
Palpable spleens were resolved in three out of four subjects and reductions in patient-reported symptom scores for pruritus, night sweats and bone pain were observed.[nature.com]

Purpura

(hemorrhagic) thrombocythemia ( D47.3 ) hemorrhagic thrombocythemia ( D47.3 ) purpura fulminans ( D65 ) thrombotic thrombocytopenic purpura ( M31.1 ) Waldenström hypergammaglobulinemic purpura ( D89.0 ) ICD-10-CM Diagnosis Code D69 Purpura and other[icd10data.com]
Note that in patients with idiopathic thrombocytopenic purpura (ITP) younger megakaryocytes are also commonly seen but patients have thrombocytopenia rather than thrombocytosis. [ESSENTIAL THROMBOCYTHEMIA].[pathpedia.com]
The remaining disorders consisted of polycythemia vera (2), smoker’s polycythemia (1), thrombotic thrombocytopenic purpura (1), familial protein C deficiency (1), IgA myeloma (1), acute leukemia (1), and Waldenström’s macroglobulinemia (1).[stroke.ahajournals.org]
Bierling P, Divine M, Farcet JP, Wallet P, Duedari N: Persistent remission of adult chronic autoimmune thrombocytopenic purpura after treatment with high-dose intravenous immunoglobulin. Am J Haematol 25:271, 1987. 37.[medtextfree.wordpress.com]

Petechiae

The following symptoms require prompt attention: Bleeding Symptoms easy bruising bleeding for no apparent reason unusually heavy or prolonged bleeding nose or gum bleeding bleeding of mucous membrane petechiae , or tiny areas of pinpoint bleeding on the[uihc.org]
Petechiae are never seen. A history of gastrointestinal blood loss (melena and/or hematemesis) or biological evidence in favor of chronic occult blood loss may be evidenced at diagnosis.[ojrd.biomedcentral.com]

Face, Head & Neck

Epistaxis

Epistaxis. Early bruising. Thrombi may form anywhere in the body including the heart and intestine, thus compromising their blood supply. Thrombosis occurring in small vessels mainly causes numbness and abnormal burning sensations of hands and feet.[symptoma.com]
Other superficial bleeding manifestations of ET include mucosal hemorrhage, such as epistaxis, hemoptysis, gingival oozing or bleeding from the gastrointestinal or genitourinary tracts.[cancertherapyadvisor.com]
The other four patients, who were in the control group (median age, 61 years; range, 61 to 82), had bleeding times ranging from 3.5 to 5 minutes at enrollment and had a total of three mild episodes of epistaxis and one minor gastrointestinal hemorrhage[nejm.org]

Workup

Most of the cases of essential thrombocythemia are diagnosed during routine blood tests. In patients with the signs and symptoms of platelet dysfunction or thrombocytosis, the diagnosis of primary thrombocythemia is established after ruling out all the causes of these abnormalities.

In order to confirm the diagnosis, a number of different tests are required. These include the following [7].

Complete blood count: The blood count will show increased numbers of platelets greater than 600,000 per micro liter of blood.
Blood smear: Blood smear will show abnormally large or clumped platelets.
Genetic testing: This is done to look for JAK2 kinase mutation.
Bone marrow aspiration: This will show abnormal megakaryocytes.
Bone marrow biopsy: Bone marrow biopsy is required to confirm the results of bone marrow aspiration.

Ultrasound

Enlargement of the Liver

This progressive disorder results in bone marrow scarring, leading to severe anemia and enlargement of your liver and spleen.[mayoclinic.org]

Serum

Thrombocytosis

] , thrombocythemia essential , Thrombocytosis;essential , essential thrombocythaemia , thrombocytosis essential , Thrombocytoses, Primary , Thrombocytosis, Primary , Primary Thrombocytoses , Primary Thrombocythemia , Essential thrombocytosis (disorder[fpnotebook.com]
Doctors don’t know what causes essential thrombocytosis, but some people with essential thrombocytosis have a change, or mutation, in the JAK2 (Janus kinase 2) gene. What causes this gene mutation is not known.[cancer.ca]
What is thrombocytosis? Thrombocytosis is a condition in which there is an excessive number of platelets in the blood. Platelets are blood cells in plasma that stop bleeding by sticking together to form a clot.[my.clevelandclinic.org]
"Thrombocytosis". N Engl J Med. vol. 350. 2004. pp. 1211-9. [Concise review with special emphasis on differentiating various forms of thrombocytosis.] Skoda, RC. "Thrombocytosis". Hematology Am Soc Hematol Educ Program.. 2009. pp. 156-67.[cancertherapyadvisor.com]

Platelet Aggregation Abnormal

Other laboratory findings in ET include: Normal or slightly increased thrombopoeitin Usually normal prothrombin time (PT) and activated partial thromboplastin time (aPTT) Platelet aggregation: abnormal with adenosine diphosphate, epinephrine, and collagen[labce.com]
aggregation abnormalities in patients are variable.[medtextfree.wordpress.com]
Although platelet aggregation abnormalities exist in most patients, these abnormalities do not appear to correlate with the risk of bleeding or thrombosis.[clevelandclinicmeded.com]

Treatment

Most of the patients with primary thrombocythemia do not need any treatment.

In individuals who are at a higher risk of developing thrombosis or abnormal bleeding, the mainstay of treatment is to lower the platelet count [8]. The most widely used drugs for this purpose are hydroxyurea, interferon-alpha or anagrelide along with low doses of aspirin. These medications are to be taken for whole life [9].

In pregnant and lactating patients, hydroxyurea and anagrelide are contraindicated. These females are monitored closely throughout pregnancy to detect any blood clots. After parturition, these patients receive injections of low molecular weight heparin daily for several weeks as during this time they are more prone to develop thrombosis.

In rare cases with life threatening complications, platelet count can be rapidly reduced by removing platelets directly from blood in a procedure referred to as platelet apheresis.

Prognosis

The outlook for the disease may vary from one patient to another. Most of the patients, if diagnosed and treated properly, may have a normal life span [10].

In a small number of people, complications from bleeding or blood clotting may arise. Rarely, the disease may have the following complications:

Etiology

There is no definite cause of essential thrombocythemia or other myeloproliferative disorders; however, certain gene mutations in the JAK2 kinase, a member of the Janus-kinase family of genes, have been found in half of the patients with this disorder [3] [4].

Epidemiology

Essential thrombocythemia is not a very common disease. The annual incidence rate of essential thrombocythemia is about 2 to 3 per 100, 000 individuals.

The average age at diagnosis is around 40 to 50 years, although it may occur in females below 40 years of age [1]. Very rarely, it can also occur in children and young adults [2].

Sex distribution

Age distribution

Pathophysiology

The bone marrow contains stem cells that develop into different blood cell lineages. Platelets are produced from large cells called megakaryocytes. The normal platelet count ranges from 150,000 to 300,000 per microliter of blood. The main function of platelets is to help in hemostasis by forming a platelet plug at the site of bleeding.

In essential thrombocythemia, there is an increase in the number of platelets in the blood. Besides, these extra platelets do not function normally. In about 50 percent of the patients, this abnormality occurs due to a mutation in the JAK2 kinase which renders the megakaryocytes excessively sensitive to stimulation by the growth factors.

These abnormally functioning thrombocytes may cause episodes of bleeding from different sites in the body or they may cause the formation of blood clots restricting blood flow to the vital organs.

Prevention

There are no guidelines for prevention of essential thrombocythemia.

Summary

Essential thrombocythemia or essential thrombocytosis (ET) is an uncommon chronic hematologic disorder in which megakaryocytes in the bone marrow produce excessive platelets (thrombocytes) without any known cause. It is also known as primary thrombocythemia (PT).

Essential thrombocythemia is one of the four components of a group of conditions called myeloproliferative disorders; the other three members of this group being chronic myelogenous leukemia, polycythemia vera and primary myelofibrosis.

It is primarily a disease of platelets but rarely other cell lineages such as red blood cells and white blood cells are also produced excessively. Essential thrombocythemia mostly occurs in people of the age of 40 to 50 years.

Most common presentations include abnormal bleeding (from the respiratory system, gastrointestinal system and skin), thrombosis, headache, dizziness and abnormal sensations in hands and feet.

The condition needs no treatment if it is symptomless; however, in case of symptomatic disease, platelet-lowering drugs are used along with small doses of aspirin to control thrombotic events.

In patients with proper treatment, the life expectancy is the same as that of a person who is not suffering from this condition.

Patient Information

Essential thrombocythemia is a rare, slowly progressive disease of blood in which a large number of abnormal platelets are produced. These platelets cause abnormal blood clotting or bleeding episodes in the persons suffering from this disorder.

The patients may complain of nose bleeds, blood in stools, early bruising, prolonged bleeding from cuts or other injuries, burning or tingling sensations in palms and soles of the hands and feet respectively.

In some cases, blood clots in large vessels may result in brain stroke or heart attack. In pregnant females, this condition may cause miscarriages.

The disease is treated with medicines which lower the number of platelets and the overall prognosis is good with a normal life expectancy.

References

Article

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Montanaro M, Latagliata R, Cedrone M, et al. Thrombosis and survival in essential thrombocythemia: A regional study of 1144 patients. American journal of hematology. Jan 31 2014.

Symptoms

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Essential Thrombocythemia

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