Most cases of VTE are triggered by causes other than surgery and most fatal PE occur in medical patients.^{7,12,13,46,47,48,49} Despite this high risk in medical patients, there are a smaller number of medical patients in randomised trials compared with the number of surgical patients. In recent years, meta-analyses in myocardial infarction,⁴³ stroke^161,162 and other medical patients⁵ have clarified the benefits and risks of prophylaxis in these patients.

8.1 ACUTE MYOCARDIAL INFARCTION

Prior to the introduction of routine antithrombotic therapy (aspirin, thrombolysis, anticoagulants) patients with acute myocardial infarction had a risk of asymptomatic DVT of about 24%, and a risk of clinical PE of 2.6-9.4%.^19,43 The risk increases with age and in the presence of heart failure.¹⁶³

8.1.1 ANTIPLATELET DRUGS (ASPIRIN) AND THROMBOLYTIC THERAPY

Current evidence-based guidelines endorse the routine use of aspirin (and thrombolytic therapy) in selected patients in clinically suspected evolving acute myocardial infarction, because both interventions reduce mortality. Aspirin also reduces the rates of reinfarction and stroke. The following recommendations are taken from the SIGN guideline on antithrombotic therapy:⁶ Evidence level 1++

It is strongly recommended that all patients with clinically suspected evolving acute MI who are not already receiving aspirin should be given aspirin (150-300 mg).

It is strongly recommended that all patients with clinically suspected evolving acute MI should be considered for thrombolytic therapy.

8.1.2 ANTICOAGULANTS

A meta-analysis of randomised trials of anticoagulants in acute myocardial infarction⁴³ showed that routine intravenous or subcutaneous heparin reduced the risk of DVT (asymptomatic or symptomatic), PE and mortality. In the absence of aspirin, anticoagulant therapy reduced mortality by 25%, representing 34 fewer deaths per 1,000. It also reduced PE by 49%, representing 18 fewer PE per 1,000.⁴³ However in the presence of aspirin, high dose heparin reduced mortality by only 6%, representing five fewer deaths per 1,000, and PE by 25%, representing one fewer PE per 1,000. High-dose heparin was associated with an excess of three major bleeds per 1,000.⁴³ Evidence level 1++

The SIGN guideline on antithrombotic therapy⁶ recommends the following:

Heparin should not be used routinely in addition to aspirin in acute MI, but reserved for patients at increased thromboembolic risk (and for certain patients undergoing thrombolysis).

Patients with acute, established MI at increased risk of systemic or pulmonary thromboembolism due to: large anterior Q-wave infarction severe left ventricular dysfunction congestive heart failure history of systemic or pulmonary embolism or thrombophilia echocardiographic evidence of mural thrombus persistent atrial fibrillation prolonged immobilisation marked obesity should be considered for anticoagulation with full-dose heparin (target APTT ratio 2.0, range 1.5-2.5) followed (if indicated by continuing risk) with warfarin (target INR 2.5, range 2.0-3.0) for up to three months, depending upon the physician's estimate of the risk: benefit ratio in the individual patient.

In other patients with acute MI, and in patients as defined above in whom the bleeding risks of full-dose anticoagulation are judged to outweigh the benefits, prophylaxis of VTE with low-dose subcutaneous heparin (7,500 IU 12-hourly) for seven days or until ambulant, should be considered.

8.1.3 GENERAL MEASURES

Early mobilisation appears to reduce mortality in acute myocardial infarction.⁶⁶

8.1.4 MECHANICAL PROPHYLAXIS

In a small RCT of 80 patients with acute MI, all of whom received aspirin, the incidence of asymptomatic DVT was significantly reduced in the stockinged leg compared with the other (control) leg.¹⁶⁴ Taken in conjunction with good evidence for the efficacy of compression stockings in prevention of asymptomatic DVT and PE in surgical patients,^72,73 there is evidence to support the use of compression stockings in patients with MI. Evidence level 1+

Compression stockings may be considered in patients with acute MI who are at increased risk of VTE, especially when heparin prophylaxis is contraindicated.

8.2 Acute stroke

Asymptomatic DVT occurs in up to 50% of patients with acute hemiplegic stroke, most often in immobile patients with paralysis of a leg. However, clinically apparent DVT or PE probably occurs in fewer than 5%. Autopsy series have identified PE in a large proportion of patients, and PE may account for up to 25% of early deaths.¹⁶⁵ See also SIGN guideline on Stroke Rehabilitation (currently under review).¹⁶⁶

8.2.1 GENERAL MEASURES

Early mobilisation and hydration should, in theory, reduce the risk of thrombosis, although no studies have been performed to evaluate the impact of these interventions on VTE. There is evidence from one RCT that early intravenous fluids improve stroke outcome,¹⁶⁷ perhaps by maintaining homeostasis.¹⁶⁸ A meta-analysis of RCTs of haemodilution showed that VTE was reduced, despite overall lack of benefit.¹⁶⁹

Patients with stroke should be mobilised as early as practicable and measures taken to ensure good hydration.

8.2.2 MECHANICAL PROPHYLAXIS

In small trials of patients with acute stroke, the incidence of asymptomatic DVT was significantly reduced by GECS.¹⁷⁰ Taken in conjunction with good evidence for the efficacy of compression stockings in prevention of asymptomatic DVT and PE in surgical patients,^72,73 they may therefore be effective in VTE reduction after stroke, although no large RCTs have evaluated their use in this context. Evidence level 1+

Selected use of graduated compression stockings may be justified for some high risk patients.

Compression stockings are preferred for patients with haemorrhagic stroke.

There is no evidence that intermittent pneumatic compression is effective in stroke patients, although it is effective in patients undergoing neurosurgery.¹⁷¹

8.2.3 ANTIPLATELET DRUGS (ASPIRIN)

Eight trials involving 41,325 patients were included in a systematic review of the effect of aspirin on clinical outcome after acute stroke.¹⁷² Two trials testing aspirin 160 to 300 mg once daily started within 48 hours of onset contributed 98% of the data. The maximum follow-up was six months. With treatment, there was a significant decrease in death or dependency at the end of follow-up. This corresponds to an additional 13 patients alive and independent at the end of follow-up for every 1,000 patients treated. Evidence level 1++

The systematic review included two trials which reported on the effect of aspirin on DVT in patients with acute stroke.¹⁷² Only 35 of 136 patients developed symptomatic or asymptomatic DVT during the treatment period; 29% of those allocated to control and 24% of those allocated to treatment: a non-significant 22% reduction in odds, but potentially of clinical significance since it represents the avoidance of about 40 DVTs per 1,000 patients treated.¹⁷² Reliable data are available for the effects of aspirin on PE (over 40,000 patients). Aspirin significantly reduced pulmonary embolism from 0.5% in controls to 0.3% in treated patients, an odds reduction of 29%, i.e. avoiding PE in two patients for every 1,000 treated. This effect is similar to that in meta-analyses of surgical patients.^3,31 Under-ascertainment of events in both groups may mean that the absolute benefit has been underestimated; if the true rate of pulmonary embolism were 2% in the control group, and the same proportional reduction were applied, then aspirin might avoid PE in seven per 1,000 patients. Evidence level 2+,1++

Early treatment with aspirin (initially 150-300 mg/day) is recommended in acute ischaemic stroke, starting as soon as intracranial haemorrhage is excluded by CT or MR brain scanning, for risk reduction in death and cardiovascular events, including DVT and PE.

Aspirin can be given by nasogastric tube or rectally (using 300mg suppositories) for those who are unable to swallow.

8.2.4 HEPARINS

Systematic reviews of RCTs of low dose subcutaneous heparins (including heparinoids and LMWHs) have shown that heparin reduces the risk of asymptomatic DVT after stroke.^160,161 It is less certain whether clinically apparent DVT is prevented by such regimens. Any benefit in terms of prevention of DVT, PE and early recurrence of ischaemic stroke is offset by an increase in haemorrhagic complications.^160,161,172 Routine heparin use in the first two weeks after a presumed ischaemic stroke has not been associated with any net reduction in the proportion of patients who are dead or dependent at six months.^160,161 The bleeding risk with UFH and LMWH is dose-related. Since there is no evidence of greater net benefit from higher dose regimens, if heparins are to be used after stroke, low dose regimens should be selected,^160,161 and LMWH may be preferred due to a lower risk of bleeding in medical patients.⁵ Evidence level 1++

UFH (e.g. 5,000 IU subcutaneously twice a day) or a LMWH may be considered in patients with ischaemic stroke who are judged to be at higher than average risk of VTE (e.g. history of previous VTE, known thrombophilia or active cancer) and lower than average risk of haemorrhagic complications.

8.3 Other medical patients

Autopsy studies have highlighted the contribution of PE to deaths in other groups of immobilised patients in medical wards.^5,12,13 Most trials of prophylaxis have been performed in patients with heart failure, respiratory failure, or infections (e.g. chest infections). Patients immobilised in intensive care units, or for diabetic coma, cancer, inflammatory bowel disease or nephrotic syndrome should also be considered for prophylaxis.

8.3.1 HEPARINS

A recent meta-analysis of seven trials of heparin versus control and eight trials of LMWH versus UFH observed a 56% decrease in asymptomatic DVT, and a 51% decrease in clinical PE with heparins.⁵ The reduction in mortality was not statistically significant and the risk of major bleeding was higher. LMWH was similarly effective to UFH in reducing the risks of DVT, PE and mortality; but had a 55% lower risk of major bleeding.⁵ These data are supported by a recent controlled trial of two doses of a LMWH in which the benefit was maintained at three month follow-up.¹⁷⁴ Evidence level 1++

In general medical patients who are immobilised in hospital due to acute illness, especially those with heart failure, respiratory failure infections, diabetic coma, inflammatory bowel disease, nephrotic syndrome, or in intensive care, prophylaxis of VTE with low doseUFH or LMWH should be considered. LMWH carries a lower risk of bleeding.

8.3.2 MECHANICAL METHODS

No trials were identified. In medical patients at risk of VTE, graduated compression stockings may be considered (especially if heparin prophylaxis is contraindicated), extrapolating from a meta-analysis of trials in all groups of patients, including medical patients with acute myocardial infarction.¹⁶⁴ Evidence level 1+

In general medical patients at significant risk of VTE in whom heparin prophylaxis is contraindicated, GECS may be considered.

8.4 Cancer patients

As discussed in section 2, patients with cancer have an increased risk of VTE, including central venous line thrombosis and chemotherapy-induced thrombosis. As noted above, immobilised cancer patients in medical or surgical wards should be considered for prophylaxis. The SIGN guideline on antithrombotic therapy⁶ includes the following additional recommendations:

Minidose warfarin (1 mg/day, no INR monitoring) is recommended for prophylaxis of thrombosis in cancer patients with central venous catheters.

Low-dose warfarin (target INR 1.6, range 1.3-1.9) is recommended for prophylaxis of thrombosis during chemotherapy in stage IV breast cancer.

8.5 Patients receiving antipsychotic drugs

There is recent evidence that patients receiving antipsychotic drugs may have an increased risk of VTE,¹⁷⁵ possibly due to immobility.¹⁷⁶ It may be prudent to avoid strict bedrest and to encourage exercise in such patients, and to educate patients and carers about this potential risk.¹⁷⁶

Patients receiving antitpsychotic drugs may have an increased risk of VTE: education on risk and mobility is encouraged.