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Thrombosis is an ugly thought;
Dicumarol and heparin,
Statistics show, prevent most ills
Like thrombus of the coronary, infarction of the heart
And tests are made so many times
That arms turn blue and blood runs thin
DAVID LITTMAN, ‘THE GOOD OLD DAYS’, N ENGL J MED, 1965
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A thrombus is defined as a clot formed in the circulation from the constituents of the blood, whereas emboli are fragments of thrombus that break off and block vessels downstream. Almost half of adult deaths in Western countries are due to thrombosis of coronary or cerebral arteries, or to pulmonary embolism.1 A thrombus is the result of a cascade of events involving platelets, RBCs, coagulation factors and the vessel wall.
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Conditions predisposing to thrombosis:
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Thrombophilia refers to a disorder of haemostasis in the form of a primary coagulopathy leading to a tendency to thrombosis. This should be considered in patients with major unprecipitated venous thromboembolism with or without a strong family history of venous thrombosis. Several causes can be tested, both inherited and acquired:
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inherited:
– factor V Leiden gene mutation (activated protein C resistance)
– prothrombin gene mutation
– protein C deficiency
– protein S deficiency
– antithrombin deficiency
acquired:
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The above factors can all be measured in the laboratory with specific genetic tests, coagulation or antibody-based tests. Other acquired causes (regarded as risk factors) include malignancy, oral contraceptives, HRT, immobilisation, obesity, smoking, pregnancy and major surgery. Most DVTs do not require investigation for an underlying cause, but consideration should be given to screening patients who have had an unprovoked DVT. Refer to a haematologist if thrombophilia is proven or suspected. Of particular interest is factor V Leiden, which occurs in about 4% of Caucasians; the relative risk of venous thrombosis is increased three to seven times in heterozygotes and 80 times in homozygotes.2
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Indications for investigation
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Recurrent or unusual thrombosis
Arterial thrombosis <30 years
Skin necrosis, especially on warfarin
Recurrent fetal loss
Familial thromboembolism
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Venous thromboembolism
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A feature of venous thrombosis is that it develops in normal vessels, with key factors being stasis and increased coagulability, including thrombophilia. The classic example is deep venous thrombosis of the leg veins. Another poorly recognised thrombosis is axillosubclavian venous thrombosis, which is associated with pulmonary embolism in 30% of cases.3
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Other sites of deep vein thrombosis are the pelvic/ovarian veins, which should be suspected in a person at risk with pelvic pain and swollen upper thighs, mesenteric venous thrombosis and cerebral sinus thrombosis, which are usually due to thrombophilia.
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Deep venous thrombosis
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Past history is very important.
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Family history
Thrombophilia
History of previous thromboembolism
Drugs (e.g. OCP, tamoxifen, HRT)
Malignancy (watch idiopathic DVT)
Increasing age; age >40
Varicose veins
Significant illness, esp. heart failure and cancer
Other chronic illness
Recent surgery
Major/orthopaedic surgery
Immobility
Long flights
Pregnancy/puerperium
Obesity
Dehydration
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There is an up to 20% association with pulmonary emboli, of which 30% may be fatal. DVT may be asymptomatic, but usually causes tenderness in the calf. DVT may present with painless unilateral leg swelling. Because of the potentially serious consequences from untreated thromboembolism, it is essential to objectively confirm or exclude clinically suspected disease.
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Examine both legs. Look for:
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Don’t test Homan’s sign (pain on sharp dorsiflexion of foot) as it may dislodge a thrombus.
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Duplex ultrasound: accurate for above-knee thrombosis; improving for distal calf
Should be repeated in 1 week if initial test normal
Contrast venography: reserved if ultrasound doubtful
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MRI appears to be very accurate for DVT, but is not yet available generally.
The plasma D-dimer can help to ‘rule out’ thrombosis. Where the clinical probability of venous thrombosis is low, a normal D-dimer effectively excludes the diagnosis. However, where clinical probability is high, appropriate imaging with Doppler ultrasound or a lung scan should be performed. A raised D-dimer is non-specific and does not help with diagnosis.
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Provide education and counselling. Admit to hospital (usually 5–7 days)—can treat as an outpatient. Drugs used in the treatment of thromboembolism are summarised in general format in TABLE 131.1.
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Collect blood for APTT, international normalised ratio (INR) and platelet count
Check renal function
LMW heparin e.g. enoxaparin or dalteparin
or
unfractionated heparin (UFH) 330 U/kg, SC loading dose then 250 U/kg bd SC (or monitor with APTT)
or
UFH 5000 U bolus IV then infusion in N saline (12 500 U over 12 hours)
or
fondaparinux SC, according to weight e.g. 50–100 kg: 7.5 mg SC daily
Oral anticoagulant (warfarin) for 3 months (or 6 months if unprovoked)
commence on day 1 or 2, usually 5 mg nocte for 2 nights and then according to INR monitoring (max. 30 mg in 3 days)
Do not give aspirin
Mobilisation within the limits of pain, tenderness and swelling
Class II graded compression stocking to affected leg in proximal DVT associated with significant swelling. The stocking may be above or below the knee depending on the extent of the swelling.
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Long term: complete resolution 50–80% at 6 months and almost 100% by 12 months.
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Early ambulation
LMW heparin or new anticoagulants for orthopaedic (for 14–35 days) or other high-risk surgery (for 1 week or until fully mobile) See TABLE 131.1
Graded pressure elastic stockings
Physiotherapy
Pneumatic compression (especially in high-risk patients where heparin is contraindicated)
Electrical calf muscle stimulation during surgery
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Prolonged travel/immobilisation
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Keep hydrated—ample water.
Avoid or restrict alcohol and coffee.
Exercises—3–4 minutes per hour (e.g. walking, calf contraction—e.g. foot pumps, see FIG. 131.1, ankle circles, knee lifts).
Injections—LMWH just prior to flying and on arrival for those at high risk. Use a prophylactic dose (e.g. enoxaparin 40 mg or dalteparin 5000 U—both SC injections twice daily).
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Refer to CHAPTER 40 for more detail on the clinical features and management of pulmonary embolism. CT pulmonary angiography is very specific and appears to be as sensitive as V/Q scanning for embolism, and is currently the preferred first-line investigation. The basis of treatment is LMW heparin and warfarin, as for DVT.
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Arterial thromboembolism
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The common serious manifestations of this are myocardial infarction, stroke, occlusion of the arterial system of the lower limbs and ‘eye’ embolism (e.g. central retinal artery thrombosis). Emboli originate from the left side of the heart, the carotid arteries or the iliac arteries. Atrial fibrillation is an important predisposing factor.
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Preventing systemic embolism in atrial fibrillation6
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Atrial fibrillation (AF) accounts for about 15% of ischaemic strokes caused by systemic embolism of cardiac thrombi. This risk gradually increases with age. Use of warfarin or DOAC reduces the annual incidence of stroke during AF from 4.5% to 1.4%—a risk reduction of almost 70%. The decision to use it or an antiplatelet agent is a difficult one and should be made in consultation with a cardiologist. Although aspirin reduces stroke rate by about 20% in patients with AF when compared with no treatment, it has half the effectiveness of warfarin/DOACs and is less able to prevent severe strokes. As a general rule, all patients with AF should start on warfarin or an appropriate DOAC unless <65 years old or have a major contraindication to its use. It is not indicated in patients with lone AF who are less than 60 years of age with no risk factors. If using warfarin, start with a low dose (e.g. 2–4 mg) and maintain an INR of 2–3 with regular checks. Anticoagulant therapy is also required to prevent embolism after cardioversion.