As we observe yet another World Sickle Cell Disease Day which falls today, and Haematologists are raising awareness that globally, sickle cell disease (SCD) is one of the most common haemoglobinopathy and is considered a public health problem in many countries, our paper today will bring to the table an equally important and serious condition closely linked to SCD – namely Thrombosis, which all those with Sickle Cell disease (SCD) are at greater risk than the general population and which can leave lasting adverse impacts on their health even lead to early mortality.
To get more insights into this condition, The Sunday Observer asked Consultant Hemotologist, Head of Hematology unit, National Hospital, Colombo, Dr Bhaddika Jayaratne, in an online interview to tell our readers what Thrombosis is, its related health issues, how it is caused and how it could be controlled using simple low-cost guidelines.
Excerpts
Q: Although today is World Sickle Cell Day,(SCD) we would like you to discuss a subject that is closely linked to SCD, namely Thrombosis, about which many of us are still in the dark including those with suspected symptoms of the disease. So tell us what exactly is Thrombosis?
A. The simplest way to describe Thrombosis is that it is a local coagulation or clotting of blood within a part of circulatory system or vasculature
Q: Are there different types of Thrombosis?
A. Thrombosis can occur in the veins or arteries. On some occasions it can occur in both arteries and veins at the same time. Thrombosis also occurs in capillaries the minute vasculature and in arterio-venous fistula made surgically as a part of management in patients with kidney disease.
Thrombosis is also categorised according to whether it is provoked or unprovoked. This is helpful in the long term management.
Q: What causes it?
A. A Thrombus can be formed due to a damage to the innermost layer of the vessel wall which is called the endothelium that initiates formation of a platelet plug which propagates into a Thrombus while the composition of circulating blood is within normal limits. When there is a clot formed inside the lumen of an artery the blood flow gets partially obliterated and results in tissue hypoxia or if there is a complete obstruction to blood flow, tissue ischemia.
Thrombus can also form due to changes in composition of the plasma and cellular components of blood. Formation of a thrombus is evident when there is increase of coagulation proteins or reduced levels of certain thrombolytic proteins in plasma. Clonal or reactive platelet disorders with increased platelet counts and increase of red cell mass in erythrocytic disorders can cause Thrombosis due to changes of the cellular component of blood.
Q: What are the risk factors of developing Thrombosis?
A. There are some physiological risk factors identified to develop Thrombosis such as advanced age, pregnancy, immobilisation commonly travelling long distances and use of estrogen containing contraceptives or hormone therapy. Others at high risk of developing Thrombosis are : Patients who have undergone surgery as well as Trauma and bedridden patients .
Q: What about patients with underlying pre-conditions that have already affected their immune system.
A. Obesity, smoking, diabetes, atherosclerosis and hypertension are well known predisposing conditions that could lead to developing Thrombosis. In addition, infections, autoimmune diseases including vasculitis, malignancies and malnutrition are also conditions with high risk for Thrombosis. I should add that there are also several acquired hematological diseases identified with Thrombotic risk factors. For example , there is a strong Thrombotic risk in Antiphospholipid syndrome (APLS). Paroxysmal nocturnal hemoglobinuria (PNH) and presence of Janus Kines mutation are known for high risk of Thrombosis. Presence of sickle cells in blood is also a risk factor for Thrombosis.
Q: Can Thrombosis develop at any age? Age –wise and gender wise who are most likely to develop it? Why ? And at which age are they most at risk ?
A. Thrombosis occurs at any age from infancy to old age and both males and females are affected. There is an influence of predisposing factors on different age groups. Thrombosis due to inherited thrombophilia factors can be manifested at a younger age. Advancing age is itself a risk factor for Thrombosis. Diabetes, atherosclerosis, hyper-cholesteremia, hypertension and malignancy associated Thrombosis are commoner in the middle and old age including the working age group. Estrogen containing contraceptives and pregnancy are associated with reproductive age group of females
Q: Incidence of DVT in Sri Lanka ?
A. There are about 450 to 500 patients per year who register for Thrombophilia screening tests at the hematology unit, National hospital Colombo, with a history of unprovoked arterial and venous Thrombosis.
Q: What organs are most affected by Thrombosis? How?
A. Thrombosis of coronary arteries results in acute coronary syndrome from unstable angina to myocardial infarction. Thrombosis of arteries of the brain results in minute infarcts to large hemorrhagic infarcts. Distal digital or limb necrosis is a result of Thrombosis of arteries to digits or limbs. Similarly, any other organ such as spleen, lungs, kidneys, bowels can undergo local ischemia and necrosis due to Thrombosis of the appropriate arteries.
Q: You referred to Venous Thrombosis. What is it? What are the common sites of Venous Thrombosis?
A. When it is mainly in the deep veins of lower limbs it is called Deep Vein Thrombosis (DVT) and DVT usually follows Pulmonary Embolism. ( PE) Venous Thrombosis in internal jugular, brachial, portal, splenic and mesenteric veins are less common. Cerebral venous sinus Thrombosis can be associated with cerebral infections, malignancies, malnutrition in children and any other haematological risk factors for Thrombosis. Superficial venous Thrombosis is usually associated with infection and ends up relatively uncomplicated to treatment.
Q: What are the symptoms of Thrombosis to look out for?
A. Symptoms of arterial Thrombosis are mainly due to lack of blood supply to the appropriate area of tissue. Severe left sided chest pain radiating along the arm or neck, sweating, fainting etc. are symptoms of coronary artery Thrombosis. Arterial Thrombosis in the brain can vary from a stroke to loss of memory and headache. Thrombosis of arteries supplying other organs can lead to severe pain in the location where the organ is.
DVT of lower limbs manifest swelling, pain, warmth, redness and difficulty in walking at the acute stage and patients experience sudden onset of shortness of breath and chest pain when they develop pulmonary embolism (PE). There is a possibility of sudden death due to a large pulmonary embolism.
Patients with portal vein Thrombosis complain of upper abdominal pain, splenomegaly and upper gastrointestinal bleeding. Constant headache and loss of consciousness are symptoms of cerebral venous sinus Thrombosis.
Q: Are patients with Sickle Cell Disease more at risk of Thrombosis than others?
A. Patients with sickle cell disease carry higher risk for arterial Thrombosis than venous and they can present with stroke or digital ischemia.
Q: How do you treat Thrombosis?
A. The mainstay of treatment of arterial Thrombosis is antiplatelet therapy. In certain instances, the option of revascularization is considered in the acute setting. The mainstay of treating venous Thrombosis is anticoagulation. And the anticoagulation is mandatory during the first three months of the acute stage. Long term anticoagulation is recommended for patients with Thrombosis due to a persistent provoking factor or in the absence of a provoking factor. If the anticoagulation by means of drugs is contraindicated insertion of an inferior vena cava filter (IVC filter) can be considered.
Q: Is the treatment method for SCD and Thrombosis the same?
A. The treatment approach for patients with sickle cell disease and Thrombosis is different. Both primary and secondary prevention of Thrombosis is based on reducing the burden of haemoglobin S, by exchange transfusions or using hydroxyurea.
Q: Are these drugs available in Sri Lanka?
A. Anticoagulation is available in oral formulation or parenteral forms. In Sri Lanka the commonly used oral anticoagulant is warfarin which is a vitamin K antagonist however regular monitoring of INR (blood test) is necessary for safe use of the drug. Direct acting oral anticoagulants (DOAC) are available in the Sri Lankan market which do not need regular monitoring but are expensive.
Q: Screening? How are patients screened?
A. The thrombophilia screening tests are done at one point of the management of Thrombosis for patients on long term anticoagulation with an episode of unprovoked Thrombosis. This group of tests can be used as a guidance to modern anticoagulation therapy in the setting of long-term management.
Q: Can you prevent Thrombosis? If so, how? Are there simple rules to follow?
A. Prevention of arterial Thrombosis is mainly based on dietary and lifestyle adjustment with control of diabetes, obesity, hypertension, cholesterol levels and quitting smoking. Regular exercises are part of the lifestyle adjustment. Prevention of venous Thrombosis is similar to lifestyle adjustment in prevention of arterial Thrombosis.
It is better to seek medical or haematological advice before using hormonal contraceptives, distance and air travelling in those who have single or multiple risk factors and early mobilisation of patients following surgery. Those who already have Thrombosis should wear pressure gradient stockings and maintain prompt and proper hydration. It is important to follow the same precautionary measures by those who have a family history of Thrombosis.
Q: What about pregnant women ? Are those with risk factors screened ?
A. As pregnancy is a known risk for Thrombosis every pregnant woman has to undergo personal thrombotic risk factor assessment at their obstetric follow up and plan thrombo-prophylactic measures if necessary.
Q: Although air pollution is linked to an elevated risk of cardiovascular diseases, such as myocardial infarction and heart failure, the association between air pollution and risk of venous Thrombosis remains controversial. Your comments ?
A. Ultrafine gaseous particulate matter pollutants entering the bloodstream via lungs can cause acute coronary Thrombosis. This problem is related to urban living, particularly road traffic associated with air pollution with microelements of heavy metals.
Q: So how do you prevent exposure to this polluted air ?
A: Preventing particulate matter entering deep into the lungs can be reduced and avoided by wearing masks particularly KN95 masks. This would significantly prevent sudden death of young people due to heart attacks.
Q: Where are patients screened for Thrombophilia in Sri Lanka? How? Who does the screening?
A. Thrombophilia screening is done at the haematology unit of National hospital that caters island wide. Patients who develop symptoms of arterial or venous Thrombosis need hospital admission at the initial stage of acute management. They can be treated by haematology, cardiology, neurology and vascular surgery team’s appropriately.
Q: Do you have a word of advice for our readers on minimising or preventing risks of developing Thrombosis.?
A. Thrombosis of any type can be a life threatening and debilitating disease condition. Practising a healthy lifestyle including consuming a nutritional dietary pattern with more weight on vegetables and fruits as well as prompt and proper hydration are important.
Strict adherence to healthy personal habits, living a life free of unnecessary stress and breathing unpolluted air are equally important for a long and healthy life out of Thrombosis.