H E M A T O L O G Y
C L I N I C
Essential thrombocythaemia Introduction In normal health, the bone marrow makes different kinds of blood cells to keep us healthy. It makes white cells to fight infection, red cells to carry oxygen around the body and platelets to help our blood clot if we are injured. The myeloproliferative neoplasms (MPN) are blood disorders where too many blood cells are produced (Figure 1). Essential thrombocythaemia (ET) is an MPN where too many platelets are made (Figure 2). It is called ‘essential’ to indicate that is a primary bone marrow disorder and not secondary to another problem. It is a rare disorder occurring in around 2 per 100 000 people and is more common in those over 60 years old. In a few patients, it can progress to more serious problems such as myelofibrosis where the bone marrow becomes scarred and its normal function severely impaired, or develop into a form of leukaemia.
Cause Not everything is known about the cause of ET, but over the past few years our understanding has greatly improved. It has been shown that people with this condition often have genetic changes or mutations in genes that are involved in producing blood cells. These mutations are neither inherited nor passed on to our children but are events that happen in cells during our lives. Around 90% of those with ET have a mutation in either a gene called JAK2, MPL or calreticulin. These mutations mean than more and more cells are produced. As ET is characterized by uncontrolled cell growth, it is classified as a neoplasm (meaning new growth), and so is technically a form of blood cancer although it shares more features with benign conditions than malignant ones. It is likely that in the future, we will develop greater understanding of other genetic mutations found in MPNs which may help to develop new treatments
Symptoms and signs Around half of people with ET do not have any symptoms, but when they do these symptoms can be wide ranging often including fatigue and headaches. The most serious symptoms are due to blood clots being formed inappropriately due to the increased number of platelets. These blood clots can result in blockages to arteries and veins
© W. S. Maney & Son Ltd 2015 DOI 10.1179/1024533215Z.000000000349
causing heart attacks, strokes, deep vein thrombosis and clots on the lungs (pulmonary embolism). Around one in five patients present with a blood clot and the primary aim of treatment is to avoid this. Other common symptoms occur when ‘sticky’ platelets make the blood thick and prevent it flowing as easily this can be experienced as tiredness, headaches, visual disturbances and itch or burning feelings in the hands and feet. Some people can experience night sweats or bone pain. Around a third of people with ET have an enlarged spleen. Occasionally, if the platelet count is very high people can experience bleeding problems as clotting factors in the blood are absorbed by the excess platelets and so do not work properly.
Tests 1. blood count and film (blood examined under a microscope); 2. ESR/CRP (markers or inflammation); 3. autoimmune screen and Ferritin (a marker of iron stores) to exclude secondary causes of high platelets; 4. genetic tests for JAK2, MPL and calreticulin mutations – a blood test; 5. bone marrow aspirate and trephine- to confirm the diagnosis and exclude other haematological causes of high platelets and 6. sometimes a chest X-ray or ultrasound of the abdomen to look for other causes of high platelets or an enlarged spleen.
Treatment options The aim of treatment in ET is to prevent complications such as blood clots or bleeding from occurring. The best strategy to use is dependent on each individual’s risk factors. Risk factors that put people at a higher risk for complications include 1. 2. 3. 4.
age over 60 years a previous history of a clot (arterial or venous) very high-platelet counts (greater than 1500) cardiovascular risk factors such as high cholesterol, diabetes or high blood pressure
High-risk patients (who have at least one of the factors above) are generally treated with ‘cytoreductive therapy’ which is treatment to actually lower the platelet counts.
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Figure 1
The myeloproliferative neoplasms
C L I N I C
hydroxycarbamide if used over a long period may be associated with an increased risk of transformation to acute leukaemia. In truth, it is not known if this association is true or not, but this drug is often avoided in younger patients for this reason. Anagrelide is a tablet that reduces the bone marrows ability to produce platelets. It can be associated with headaches, fluid retention, diarrhoea and palpitations. There is a need to monitor cardiac status for patients taking this drug. It may increase the chance of changes in the bone that may develop into myelofibrosis Interferon, alpha-interferon, is a protein that naturally occurs in our bodies in response to infection and can effectively reduce platelet counts. However, it has to be given by injection under the skin and is often not as well tolerated as other treatments due to side effects which include flu-like symptoms, headaches, muscle aches and depression. It can safely be given in pregnancy. Newer agents on the horizon include JAK 2 inhibitors which are showing promising results in clinical trials
Outlook
Figure 2
A blood film showing different types of blood cells
Low-risk patients usually have aspirin which reduces the ability of platelets to stick together but will not lower the platelet count on its own. All the patients should make sure to keep vascular risk factors under control, for example, by keeping their weight under control and not smoking.
Cytoreductive therapies Hydroxycarbamide is the most common treatment and a mild tablet form of chemotherapy. It causes only minimal side effects such as nausea, constipation or diarrhoea and sometimes ulcers of the mouth or skin. It can lower resistance to infection and there is controversial evidence that
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Generally, the survival for people with ET is near normal and is mainly affected by disease-related complications such as blood clots. The rate of transformation into myelofibrosis, which carries a poorer prognosis, is low – being less than 1% of patients a year while the rate of transformation into acute leukaemia is even more rare. This means that these risks, while small, slightly increase over time which is another reason why your doctor will continue to monitor you closely even if things appear very stable.
Additional resources www.mpnvoice.org.uk www.leukaemiacare.org.uk www.macmillan.org.uk
George Double, Claire Harrison Department of Haematology, Guys and St Thomas’ NHS Foundation Trust, London, UK Correspondence to: Claire Harrison, Department of Haematology, Guys and St Thomas’ NHS Foundation Trust, London, UK, Email claire.harri [email protected]
C L I N I C
Essential thrombocythaemia Introduction In normal health, the bone marrow makes different kinds of blood cells to keep us healthy. It makes white cells to fight infection, red cells to carry oxygen around the body and platelets to help our blood clot if we are injured. The myeloproliferative neoplasms (MPN) are blood disorders where too many blood cells are produced (Figure 1). Essential thrombocythaemia (ET) is an MPN where too many platelets are made (Figure 2). It is called ‘essential’ to indicate that is a primary bone marrow disorder and not secondary to another problem. It is a rare disorder occurring in around 2 per 100 000 people and is more common in those over 60 years old. In a few patients, it can progress to more serious problems such as myelofibrosis where the bone marrow becomes scarred and its normal function severely impaired, or develop into a form of leukaemia.
Cause Not everything is known about the cause of ET, but over the past few years our understanding has greatly improved. It has been shown that people with this condition often have genetic changes or mutations in genes that are involved in producing blood cells. These mutations are neither inherited nor passed on to our children but are events that happen in cells during our lives. Around 90% of those with ET have a mutation in either a gene called JAK2, MPL or calreticulin. These mutations mean than more and more cells are produced. As ET is characterized by uncontrolled cell growth, it is classified as a neoplasm (meaning new growth), and so is technically a form of blood cancer although it shares more features with benign conditions than malignant ones. It is likely that in the future, we will develop greater understanding of other genetic mutations found in MPNs which may help to develop new treatments
Symptoms and signs Around half of people with ET do not have any symptoms, but when they do these symptoms can be wide ranging often including fatigue and headaches. The most serious symptoms are due to blood clots being formed inappropriately due to the increased number of platelets. These blood clots can result in blockages to arteries and veins
© W. S. Maney & Son Ltd 2015 DOI 10.1179/1024533215Z.000000000349
causing heart attacks, strokes, deep vein thrombosis and clots on the lungs (pulmonary embolism). Around one in five patients present with a blood clot and the primary aim of treatment is to avoid this. Other common symptoms occur when ‘sticky’ platelets make the blood thick and prevent it flowing as easily this can be experienced as tiredness, headaches, visual disturbances and itch or burning feelings in the hands and feet. Some people can experience night sweats or bone pain. Around a third of people with ET have an enlarged spleen. Occasionally, if the platelet count is very high people can experience bleeding problems as clotting factors in the blood are absorbed by the excess platelets and so do not work properly.
Tests 1. blood count and film (blood examined under a microscope); 2. ESR/CRP (markers or inflammation); 3. autoimmune screen and Ferritin (a marker of iron stores) to exclude secondary causes of high platelets; 4. genetic tests for JAK2, MPL and calreticulin mutations – a blood test; 5. bone marrow aspirate and trephine- to confirm the diagnosis and exclude other haematological causes of high platelets and 6. sometimes a chest X-ray or ultrasound of the abdomen to look for other causes of high platelets or an enlarged spleen.
Treatment options The aim of treatment in ET is to prevent complications such as blood clots or bleeding from occurring. The best strategy to use is dependent on each individual’s risk factors. Risk factors that put people at a higher risk for complications include 1. 2. 3. 4.
age over 60 years a previous history of a clot (arterial or venous) very high-platelet counts (greater than 1500) cardiovascular risk factors such as high cholesterol, diabetes or high blood pressure
High-risk patients (who have at least one of the factors above) are generally treated with ‘cytoreductive therapy’ which is treatment to actually lower the platelet counts.
Hematology
2015
VOL.
20
NO.
2
119
H E M A T O L O G Y
Figure 1
The myeloproliferative neoplasms
C L I N I C
hydroxycarbamide if used over a long period may be associated with an increased risk of transformation to acute leukaemia. In truth, it is not known if this association is true or not, but this drug is often avoided in younger patients for this reason. Anagrelide is a tablet that reduces the bone marrows ability to produce platelets. It can be associated with headaches, fluid retention, diarrhoea and palpitations. There is a need to monitor cardiac status for patients taking this drug. It may increase the chance of changes in the bone that may develop into myelofibrosis Interferon, alpha-interferon, is a protein that naturally occurs in our bodies in response to infection and can effectively reduce platelet counts. However, it has to be given by injection under the skin and is often not as well tolerated as other treatments due to side effects which include flu-like symptoms, headaches, muscle aches and depression. It can safely be given in pregnancy. Newer agents on the horizon include JAK 2 inhibitors which are showing promising results in clinical trials
Outlook
Figure 2
A blood film showing different types of blood cells
Low-risk patients usually have aspirin which reduces the ability of platelets to stick together but will not lower the platelet count on its own. All the patients should make sure to keep vascular risk factors under control, for example, by keeping their weight under control and not smoking.
Cytoreductive therapies Hydroxycarbamide is the most common treatment and a mild tablet form of chemotherapy. It causes only minimal side effects such as nausea, constipation or diarrhoea and sometimes ulcers of the mouth or skin. It can lower resistance to infection and there is controversial evidence that
120
Hematology
2015
VOL.
20
NO.
2
Generally, the survival for people with ET is near normal and is mainly affected by disease-related complications such as blood clots. The rate of transformation into myelofibrosis, which carries a poorer prognosis, is low – being less than 1% of patients a year while the rate of transformation into acute leukaemia is even more rare. This means that these risks, while small, slightly increase over time which is another reason why your doctor will continue to monitor you closely even if things appear very stable.
Additional resources www.mpnvoice.org.uk www.leukaemiacare.org.uk www.macmillan.org.uk
George Double, Claire Harrison Department of Haematology, Guys and St Thomas’ NHS Foundation Trust, London, UK Correspondence to: Claire Harrison, Department of Haematology, Guys and St Thomas’ NHS Foundation Trust, London, UK, Email claire.harri [email protected]
