Case 10.6 – Deep Vein Thrombosis and Pulmonary Embolus

Check responsiveness, airway, breathing and circulation. Give oxygen (100% preferable) and call for ambulance.

Differential Diagnoses:

1. Acute Pulmonary Emboli
2. Pneumonia/pneumonitis
3. Although pain/presentation not typical – acute coronary syndrome

Norman is unwell. For someone who has hypertension, his BP is low and he is borderline tachycardic/tachypnoeic. This is someone who can deteriorate quickly; calling an ambulance for an urgent transfer to ED will be very appropriate.

The varied clinical presentations and non-specific nature of the physical signs can make the diagnosis of Venous thromboembolism (VTE) including DVT and PE difficult. It is often helpful to consider these questions:

• Is the clinical presentation consistent with PE?
• Does the patient have risk factors for PE? (E.g. recent surgery, hip fracture, immobility, etc.)
• Is there any alternative diagnosis that can explain the patient's presentation?

Taking a good history/examination would provide further information to exclude other causes:

• Are there any signs/symptoms of infections in the preceding days, any sick contacts?
• Are there recent risk factors for thrombosis e.g. surgery, long distance flights, immobility, injuries to lower limbs, cancer diagnoses, family history, (in female patients – pregnancy, the use of OCP)?
• Are there history of cardiovascular disease?
• Any evidence of uni-lateral swelling in lower limbs, i.e. clinical evidence of DVT

The clinical features of PE depend largely upon the size of embolism and co-morbidity. They encompass a spectrum from cardiovascular collapse to small emboli with few or no haemodynamic consequences (table 1). Further investigations would usually depend on clinical picture; however, clinical prediction scores could be of benefit to guide the best approach in these patients (diagram 1).

All patients with suspected PE should have a chest X-ray, ECG and arterial blood gas analysis. These tests may also help to exclude important differential diagnoses. D-dimer is a specific degradation product released into the circulation when cross-linked fibrin undergoes endogenous fibrinolysis. The presence of a low D-dimer has a high NPV and provides a useful screening test. However, a suggestive clinical picture in a high-risk patient must be investigated further even when the D-dimer level is normal.

The most validated clinical prediction tools for VTE are the Wells and Geneva scores. In combination with D-dimer testing, they can be used safely in outpatient clinics and ED to exclude VTE events. The pulmonary embolism rule-out criteria (PERC) score can be used similarly to exclude PE in younger patients (\<50y.o) where the estimated rate of PE is lower.

Other Confirmatory Testings

CT Pulmonary Angiography: CT pulmonary angiography (CTPA) is the preferred way of diagnosing PE. CTPA may not only exclude PE but highlight an alternative diagnosis. However, CTPA involve significant amount of radiation (therefore contra-indicated in pregnancy), and requires iodinated contrast which can result in nephrotoxicity and allergic reaction in some patients.

VQ Scan: The sensitivity and specificity of V/Q scanning is greatly increased when interpretation is informed by clinical probability. A normal V/Q scan virtually excludes PE and a low probability scan in the presence of a low clinical probability makes PE unlikely. Similarly, the presence of a high probability scan in a patient with a high clinical probability almost certainly establishes the diagnosis of PE. V/Q scans are most useful in patients with normal pulmonary architecture. However, PE often presents as an important differential in patients with pre-existing COPD or congestive cardiac failure and in these cases the majority of scans (70%) are indeterminate. This is the preferred option for scan in pregnant women and those with renal impairment.

Doppler US: Colour Doppler ultrasound of the leg veins remains the investigation of choice in patients with clinical DVT, but may also be applied to patients suspected of PE, particularly if there are clinical signs in a limb, as many will have identifiable proximal thrombus in the leg veins.

Echocardiogram: Bedside echocardiogram is extremely helpful in the differential diagnosis and assessment of acute circulatory collapse. Acute dilatation of the right heart is usually present in massive PE, and thrombus (embolism in transit) may be visible in the pulmonary trunk! Alternative diagnoses including left ventricular failure, aortic dissection and pericardial tamponade can usually be established with confidence. Echocardiography is also useful for patients who present with unexplained pulmonary hypertension.

VTE can be provoked by recent surgery. There are also recognised non-surgical transient risks and more persistent underlying factors that are associated with VTE events such as malignancy, smoking and anti-phospholipid syndrome. These should be considered especially in those patients with unprovoked VTE.

With regards to thrombophilia screening, the Australian Thrombosis Guideline recommends:

• Patients with provoked VTE by surgery should not be screened for hereditary thrombophilia
• Young patients (\<45y.o) with unprovoked VTE may be tested for some hereditary thrombophilia e.g. protein C&S deficiency or anti-thrombin deficiency
• Patients with unprovoked VTEs should have age-appropriate evaluation for malignancy

Non-surgical transient risk factors:

• Acute medical illness with immobilisation for at least 3 days
• Oestrogen therapy
• Pregnancy/post-partum
• Leg injury associated with reduced mobility for at least 3 days
• Long-haul travel

Persistent provoking risk factors:

• Active cancer
• Ongoing non-malignant condition associated with a twofold or higher increased risk of recurrent VTE after stopping anticoagulant therapy (ie, inflammatory bowel disease and other chronic inflammatory states)
• Antiphospholipid syndrome

General:

Prompt recognition and treatment is potentially life-saving. Oxygen should be given to all hypoxaemic patients in a concentration necessary to restore arterial oxygen saturation to over 90%. Opiates may be necessary to relieve pain and distress but should be used with great caution in the hypotensive patient. Diuretics and vasodilators should also be avoided; indeed, hypotension should be treated by giving intravenous fluid or plasma expander.

Anticoagulation:

Anticoagulation should be commenced immediately in patients with a high or intermediate probability of PE but can usually be safely withheld from patients with a low clinical probability pending further investigation.

The choice of anti-coagulation has changed considerably in the last decade. Whilst previously low molecular weight heparin/warfarin bridging was considered standard, many landmark trials have shown that Novel Oral Anti-coagulants (NOACs) are not inferior in efficacy, with no increased risks of bleeding compared to this approach. It is standard practice now to commence majority of VTE patients on NOACs. Rivaroxaban and Apixaban are both available on PBS.

There are certain circumstances where NOACs are not recommended (Clexane/Warfarin will be the choice for treatment):

• Pregnancy (Clexane)
• Reduced CrCl <30ml/min (Warfarin)
• Anti-phospholipid syndrome (Warfarin, although more data are supporting NOACs use for some patients with APS)

Traditionally, low molecular weight heparin (LMWH e.g. Clexane, Dalteparin) has been used for treatment in cancer related thrombosis based on the findings from CLOT trial. However, more recent data has demonstrated that NOACs such as Rivaroxaban are not inferior to LMWH for treatment of cancer related VTE, although they have been associated with increased risks of bleeding in patients with GI malignancy.

Thrombolytic therapy:

Thrombolysis appears to improve outcome when acute massive PE is accompanied by acute shock but it is not clear whether there is any advantage of thrombolysis over anti-coagulation in patients without haemodynamic instability. Patients with PE appear to have a high risk of intracranial haemorrhage and must be screened carefully for haemorrhagic risk. (Note: the dosage and treatment regime is different from that for acute myocardial infarction).

Caval filters:

Patients who experience recurrent PE despite adequate anticoagulation, or those patients in whom anticoagulation is absolutely contraindicated, may benefit from insertion of a filter in the inferior vena cava below the origin of the renal vessels. The introduction of retrievable caval filters has been useful in patients with temporary risk factors.

Other Invasive Strategies:

Pulmonary embolectomy is generally performed only in severe cases with very large PE and in patients where anticoagulation and/or thrombolytic therapy is contraindicated or has not responded adequately to standard treatments. Percutaneous thrombectomy using special catheters (Catheter directed lysis) under X-ray guidance to break up or extract the emboli is an alternative in specialised centres.

Longer term Management of VTE beyond 3-6 months:

There are increasing body of evidence in the era of NOACs that patients with moderate to high risk of recurrent thrombosis will benefit from longer-term anti-coagulation. These patients may be kept on full dose NOACs or lower dose NOACs depending on the risks.

Strong risk factors for recurrence:

• Unprovoked VTE
• Prior VTE
• PE or proximal DVT
• Persistent risk factor (eg, active cancer, antiphospholipid syndrome)
• Antithrombin, protein C or S deficiency

Moderate risk factors for recurrence:

• VTE provoked by non-surgical risk factor
• Male sex
• Elevated D-dimer level after cessation of anticoagulation

Prophylaxis options:

• Full-length graduated compression stockings
• Intermittent Pneumatic Compression devices
• Early mobilisation
• Standard LMWH or heparin
• Low dose NOACs

Early mobilisation of all patients is important to prevent DVTs. For patients with very low risk of VTE, early mobilisation may be adequate. For patients with low risk of VTE – mechanical prevention may be suitable. Patients at medium or high risk may require additional pharmacological antithrombotic measures.

Patients with moderate/high risks of VTE following surgery:

Patients in the following categories should be considered for pharmacological antithrombotic prophylaxis:

Moderate risk of VTE:

• Major surgery in patients > 40 years or with other risk factor
• Major medical illness e.g. heart failure
  • Chest infection
  • Malignancy
  • Inflammatory bowel disease

High risk of VTE:

• Hip or knee surgery
• Major abdominal or pelvic surgery for malignancy or with history of DVT or known thrombophilia