Select Committee on Health Minutes of Evidence


Memorandum by The Royal College of Physicians (VT 15)

THE PROBLEM

  1.  Thrombosis in the veins usually occurs in the deep veins of the lower limb or pelvis (deep vein thrombosis, DVT). The main danger is that a clot can break free (embolise), and be carried in the blood stream into the right atrium of the heart. From there it will usually pass with the blood into the right ventricle of the heart and then out of the heart in the pulmonary artery. As the pulmonary arterial system divides into smaller vessels the clot will come to rest and block the flow of blood through the lungs. This is called a pulmonary embolism (PE) and a large PE can be fatal. DVT and PE are collectively referred to as venous thromboembolism (VTE).

  2.  The incidence of DVT is approximately 100 per 100,000 and for PE 50 per 100,000. The risk factors are increasing age, surgery and trauma, immobilisation and paresis, malignancy, and changes in the blood (the inherited thrombophilias and antiphospholipid antibodies). In women they would also include pregnancy and the puerperium, the combined oral contraceptive pill and hormone replacement therapy.

  3.  Most hospitalised patients have risk factors for VTE and DVT is common in hospitalised patients. The condition is often at first clinically silent but symptomatic DVT and PE are common in patients who do not receive prophylaxis. The in-hospital case-fatality rate of VTE is often underestimated—it is 12%1. Approximately 10% of hospital deaths may be due to PE2, 3. Investigating and treating symptomatic patients is costly. Patients are at increased risk of future VTE and may develop post-thrombotic syndrome. Post thrombotic syndrome is chronic pain, swelling, and occasional ulceration of the skin of the leg and it occurs in up to one third of patients who have a DVT4, 5. It can occur early or have a latency of up to 10 years, the cumulative frequency has been estimated as 23% at two years and 28% at five years4.

  4.  Thromboprophylaxis is highly effective and cost effective. PE is the most common preventable cause of hospital death. The Agency for Healthcare Research and Quality has published a report entitled "Making Health Care Safer: a Critical Analysis of Patient Safety Practices"6. This systematic review ranked 79 patient safety interventions based on the strength of the evidence supporting more widespread implementation of these procedures. The highest ranked safety practice was the "appropriate use of prophylaxis to prevent VTE in patients at risk."

DO WE NEED GUIDELINES?

  5.  No, we already have them. I think the best are the ACCP guidelines7 available at http://www.chestjournal.org/cgi/content/full/126/3 suppl/338S. These have just been updated and are evidenced based with 794 references.

WHAT DO THE GUIDELINES RECOMMEND?

  6.  A summary of the ACCP advice is:

    "For moderate-risk general surgery patients, we recommend prophylaxis with low-dose unfractionated heparin (LDUH) (5,000 U bid) or low-molecular-weight heparin (LMWH) (< 3,400 U once daily) (both Grade IA). For higher risk general surgery patients, we recommend thromboprophylaxis with LDUH (5,000 U tid) or LMWH (> 3,400 U daily) (both Grade IA). For high-risk general surgery patients with multiple risk factors, we recommend combining pharmacologic methods (LDUH three times daily or LMWH, > 3,400 U daily) with the use of graduated compression stockings and/or intermittent pneumatic compression devices (Grade 1C). We recommend that thromboprophylaxis be used in all patients undergoing major gynecologic surgery (Grade IA) or major, open urologic procedures, and we recommend prophylaxis with LDUH two times or three times daily (Grade IA). For patients undergoing elective total hip or knee arthroplasty, we recommend one of the following three anticoagulant agents: LMWH, fondaparinux, or adjusted-dose vitamin K antagonist (VKA) (international normalized ratio (1NR) target, 2.5; range, 2.0 to 3.0) (all Grade IA). For patients undergoing hip fracture surgery (HFS), we recommend the routine use of fondaparinux (Grade IA), LMWH (Grade 1C), VKA (target 1NR, 2.5; range, 2.0 to 3.0) (Grade 2B), or LDUH (Grade 113). We recommend that patients undergoing hip or knee arthroplasty, or HFS receive thromboprophylaxis for at least 10 days (Grade lA). We recommend that all trauma patients with at least one risk factor for VTE receive thromboprophylaxis (Grade 1A). We recommend, on admission to the intensive care unit, all patients be assessed for their risk of VTE. Accordingly, most patients should receive thromboprophylaxis (Grade IA)."

THE ADVICE FOR MEDICAL PATIENTS

  7.  70 to 80% of fatal PEs occur in non-surgical patients. Hospitalised medical patients account for one quarter of all VTE in the population 8. LDUH and LMWH lower the risk of VTE by at least 50% in medical patients. The advice for medical patients is:

    "In acutely ill medical patients who have been admitted to the hospital with congestive heart failure or severe respiratory disease, or who are confined to bed and have one or more additional risk factors, including active cancer, previous VTE, sepsis, acute neurological disease, or inflammatory bowel disease, we recommend prophylaxis with LDUH (Grade 1A) or LMWH (Grade IA)."

WHY IS PROPHYLAXIS NOT GIVEN PROPERLY?

  8.  Many doctors believe that the incidence of VTE has declined in recent years. They frequently site retrospective surveys of their own experience. It may be true that VTE has declined recently due to more widespread use of prophylaxis as well as improved operative and peri-operative management but the rate is still high. The low post-mortem rate in the UK means that many cases of fatal PE will not be known.

  9.  Another reason for not giving prophylaxis is the perceived risk of bleeding. However, abundant data from meta-analyses and placebo-controlled, blinded, randomized clinical trials have demonstrated little or no increase in the rates of clinically important bleeding with LDUH or LMWH. In practice bleeding may be mistakenly attributed to prophylaxis whilst its benefit (say a reduction in fatal PE from 0.7 to 0.2%) may not be appreciated by the individual practitioner.

  10.  Finally it should be emphasised that although the SIGN guidelines9 consider aspirin a reasonable prophylactic agent, the ACCP guidelines specifically state that "we recommend against the use of aspirin alone as thromboprophylaxis for any patient group (Grade 1A)". The oft quoted PEP trial10 supporting aspirin has been heavily criticised, eg11.

WHAT DO WE NEED TO DO?

  11.  We have excellent guidelines but need to ensure they are implemented.

  12.  Every patient admitted to hospital should have their risk of VTE assessed. All clinical areas should have protocols for VTE prophylaxis based on authoritative guidelines. It should be clearly recorded either that the patient does not require prophylaxis or if they do the regimen should be recorded in the notes and implemented.

References:

  1.  Anderson, F J, et al, A population-based perspective of the hospital incidence and case fatality rates of deep vein thrombosis and pulmonary embolism. The Worcester DVT Study. Arch Intern Med, 1991. 151(5): p p933-8.

  2.  Lindblad, B, A Eriksson, and D Bergqvist, Autopsy-verified pulmonary embolism in a surgical department: analysis of the period from 1951 to 1988. Br J Surg, 1991. 78(7): p 849-52.

  3.  Stein, P D and J W Henry, Prevalence of acute pulmonary embolism among patients in a general hospital and at autopsy. Chest, 1995. 108(4): p 978-81.

  4.  Prandoni, P, et al, The long-term clinical course of acute deep venous thrombosis [see comments]. Ann Intern Med, 1996. 125(1): p pl-7.

  5.  Prandoni, P, et al, Which is the outcome of the post-thrombotic syndrome? [letter]. Thromb Haemost, 1999. 82(4): p p1358.

  6.  Shojania, K G, et al, Making health care safer: a critical analysis of patient safety practices. Evid Rep Technol Assess (Sunup), 2001(43): p i-x, 1-668.

  7.  Geerts, W H, et al, Prevention of venous thromboembolism: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest, 2004. 126(3 Suppl): p 338S-400S.

  8.  Heit, J A, et al, Relative impact of risk factors for deep vein thrombosis and pulmonary embolism: a population-based study. Arch Intern Med, 2002. 162(11): p 1245-8.

  9.  Prophylaxis of Venous Thromboembolism. SIGN Publication No 62 ISBN 1899893 03 2www.sign.ac.uk/guidelines/fulltext/62/index.html, 2002.

10.  Prevention of pulmonary embolism and deep vein thrombosis with low dose aspirin: Pulmonary Embolism Prevention (PEP) trial. Lancet, 2000.355(9212): p 1295-302.

11.  Cohen, A and D Quinlan, PEP trial. Pulmonary Embolism Prevention. Lancet, 2000. 356(9225): p 247; author reply 250-1.





 
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