Memorandum by The Royal College of Physicians
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 underestimatedit
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."
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.
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)."
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
"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)."
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.
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.
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,
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