This section discusses the interventions which reduce the incidence of VTE and provides generic recommendations for their use. Recommendations for specific patient groups or circumstances are made in following sections. The prophylactic effect of spinal or epidural anaesthesia is reviewed in section 7.

3.1 General measures

3.1.1 MOBILISATION AND LEG EXERCISES

Immobility increases the risk of DVT about tenfold.^46,59 A meta-analysis of RCTs of bed rest for several medical conditions found no evidence of benefit of bed rest for any condition.⁶⁶ In immobilised patients, leg exercises reduce venous stasis and should be encouraged.^1,15 Evidence level 2+,1+

Early mobilisation and leg exercises should be encouraged in patients recently immobilised.

3.1.2 HYDRATION, HAEMODILUTION AND VENESECTION

Haemoconcentration increases blood viscosity and reduces blood flow, especially in the deep veins of the leg in immobile patients.⁶⁷ Evidence level 4

Adequate hydration should be ensured in immobilised patients.

There is insufficient evidence regarding the balance of risks and benefits to support recommendations about the use of either haemodilution,^68,69 or venesection (apart from primary proliferative polycythaemia).⁷⁰

3.2 Mechanical methods

Mechanical methods of antithrombotic prophylaxis increase mean blood flow velocity in leg veins and reduce venous stasis. They include:

• graduated elastic compression stockings (GECS)
• intermittent pneumatic compression (IPC) devices
• mechanical foot pumps.

There are few trials of mechanical methods in medical patients. Unlike pharmacological methods, mechanical methods do not increase the risk of bleeding and may be preferred in patients in whom bleeding risks may outweigh the antithrombotic efficacy of pharmacological prophylaxis. Mechanical methods are contraindicated in patients at risk of ischaemic skin necrosis, e.g. those with critical limb ischaemia or severe peripheral neuropathy.^71,72 Cross-infection is a risk when devices are re-used.

Adequate precautions must be taken to prevent cross-infection when mechanical devices are re-used by subsequent patients (see manufacturer's instructions).

3.2.1 GRADUATED ELASTIC COMPRESSION STOCKINGS

A meta-analysis of RCTs of GECS in prevention of asymptomatic DVT observed that asymptomatic DVT occurred in 8.6% of active patients compared to 27% of controls (OR 0.34, 95% CI 0.25, 0.46).⁷² These results are consistent with an earlier meta-analysis,⁷³ and with historical reports of efficacy of elastic stockings in PE prophylaxis.^74,75 Evidence level 1+

GECS are effective in prophylaxis of asymptomatic DVT and symptomatic PE in surgical patients.

GECS are commercially available as both below-knee and above-knee stockings. Most controlled trials have used above-knee stockings.^{1,19,20,72,73,74} Studies comparing above-knee and below-knee stockings have been too small to determine whether or not they are equally effective.^76,77,78,79 Hence current evidence supports the preferential use of above-knee stockings unless contraindicated (e.g. thigh circumference >81 cm, incontinence). A large study of above-knee versus below-knee stockings versus no stockings in stroke patients (CLOTS) is currently in progress.

Above-knee GECS are preferred to below-knee stockings for prophylaxis of DVT.

Table 2 summarises contraindications and cautions for GECS. It has been suggested that 15-20% of patients cannot effectively wear GECS because of unusual limb size or shape.¹⁹ An educational programme for appropriate use of GECS was found to be useful in one Scottish acute trust.²⁸

Table 2: Contraindications and cautions for use of GECS

CONTRAINDICATIONS	CAUTIONS
Massive leg oedema Pulmonary oedema (e.g. heart failure) Severe peripheral arterial disease Severe peripheral neuropathy Major leg deformity Dermatitis	Select correct size Apply carefully, aligning toe hole under toe 3 Check fitting daily for change in leg circumference Do not fold down Remove daily for no more than 30 minutes

3.2.2 GECS PLUS PHARMACOLOGICAL PROPHYLAXIS OR INTERMITTENT PNEUMATIC COMPRESSION

A meta-analysis of RCTs⁷² and the preliminary results of another meta-analysis found that GECS combined with pharmacological prophylaxis or IPC increases efficacy in reducing the incidence of asymptomatic DVT in surgical patients (OR 0.24; CI 95 0.15-0.37). Evidence level 1+

A multicentre observational study of elective hip replacement patients found that the combination of GECS with pharmacological prophylaxis appeared to be more effective in reduction of asymptomatic DVT than pharmacological prophylaxis alone.⁵¹ Evidence level 2+

Increased efficacy may reflect a combined effect on venous stasis and hypercoagulability. The combined approach is currently commonly employed in Scotland,²⁹ and the rest of the UK.⁸⁰

GECS may be combined with pharmacological prophylaxis or IPC in surgical patients, to increase efficacy in reducing the incidence of DVT.

3.2.3 INTERMITTENT PNEUMATIC COMPRESSION

IPC devices periodically compress the calf and/or thigh muscles of the leg (inflation pressures 35-40 mmHg at about 10s/min),^19,20 and stimulate fibrinolysis.⁸¹ Compression devices are usually applied immediately before or during surgery and are often replaced by GECS following surgery as they can cause discomfort in the conscious patient.

Pooled analyses of trials of IPC in prevention of asymptomatic DVT after non-orthopaedic surgery showed a relative risk reduction of around 68%.²⁰ Similar results have been demonstrated following orthopaedic (mostly elective hip) surgery.²⁰ A recent observational study found that IPC reduced the risk of re-hospitalisation for symptomatic VTE after elective hip surgery.⁸² One RCT observed that the addition of IPC devices to unfractionated heparin (UFH) reduced the risk of PE following cardiac surgery from 4% to 1.5% (risk reduction 62%).⁸³ Evidence level 1+,2+

IPC devices are effective in prophylaxis of asymptomatic DVT in surgical patients.

IPC plus low dose heparin reduces the risk of symptomatic PE in cardiac surgery patients.

3.2.4 MECHANICAL FOOT PUMPS AND FOOT IMPULSE TECHNOLOGY

The A-V impulse system foot pump has been developed to provide mechanical prophylaxis in patients who are unable to weight bear and has only been used in orthopaedic surgery. RCT data suggest efficacy in prevention of asymptomatic DVT.^{84,85,86,87,88,89,90,91,92,93} There is no evidence that these devices reduce symptomatic DVT or PE. Skin necrosis has been reported and discomfort from the device can lead to poor compliance.⁹² Evidence level 1+

Mechanical foot pumps are effective in prophylaxis of asymptomatic DVT in orthopaedic surgery patients.

3.3 Antiplatelet agents (Aspirin)

3.3.1 EFFICACY AND SAFETY IN SURGICAL PATIENTS (see Table 3)

A meta-analysis of 53 RCTs of antiplatelet agents (usually aspirin) in prophylaxis of VTE in general or orthopaedic surgery reported significant reductions in risks of asymptomatic DVT (26% vs. 35%), pulmonary embolism (0.6% vs. 1.6%) and fatal PE (0.2% vs. 0.6%); with a non-significant trend to lower mortality and a significant increase in major bleeding.^3,4 These results were confirmed by a further large trial, the Pulmonary Embolism Prevention (PEP) Trial.³¹ In this study, 13,356 patients undergoing surgery for hip fracture and 4,088 patients undergoing elective hip arthroplasty were randomised to aspirin (160 mg daily, started preoperatively and continued for 35 days) or placebo; in addition to "any other thromboprophylaxis thought necessary". Patients were not screened for asymptomatic DVT. Combining the results from all trials revealed no significant reduction in total mortality (3.9% vs. 4.0%), while confirming a significant increase in major bleeding (7.7% vs. 6.2%) which was similar to the reduction in symptomatic DVT or PE (see Table 3). There was a significant reduction in fatal PE (0.2% vs. 0.6%; NNT 250). Evidence level 1++

3.3.2 EFFICACY AND SAFETY IN MEDICAL PATIENTS

The efficacy of aspirin in reduction of total cardiovascular events (myocardial infarction; MI, stroke, PE, cardiovascular death) is now clearly established in acute MI and in acute ischaemic stroke⁶ and outweighs the increased risk of bleeding (see section 8).

3.3.3 DOSE OF ASPIRIN, CONTRAINDICATIONS AND CAUTIONS

The PEP trial used aspirin 160 mg/day.³¹ The standard preparations available in the UK are 75 mg and 300 mg, hence 150 mg is recommended. Aspirin 75-300 mg/day is licensed in the UK for prevention of cardiovascular events in acute MI and in acute ischaemic stroke but not for VTE prophylaxis in surgical patients (see the SIGN guideline on antithrombotic therapy).⁶

Aspirin 150 mg/day started preoperatively and continued for 35 days is effective prophylaxis of asymptomatic and symptomatic VTE in surgical patients. Aspirin also reduces cardiovascular events in acute MI and acute ischaemic stroke.

Cautions and contraindications to aspirin are summarised in Table 4.

Table 3: Summary of meta-analyses of RCTs of antiplatelet drugs (usually aspirin) in prophylaxis of VTE in surgical patients^3,4,31

Patient group

Asymptomatic DVT

Symptomatic DVT

All PE

Fatal PE

Total Mortality

Major bleeding

Active

Control

Active

Control

Active

Control

Active

Control

Active

Control

Active

Control

Non-orthopaedic surgery

278/1434 (19.4%)

396/1459 (27.1%)

16/3408 (0.5%)

58/3419 (1.7%)

2/3408 (0.06%)

15/3419 (0.4%)

32/3408 (0.9%)

29/3419 (0.8%)

Elective orthopaedic surgery

160/427 (37.5%)

232/436 (53.2%)

23/2576 (0.9%)

39/2578 (1.5%)

1/2576 (0.04%)

4/2578 (0.15%)

9/2576 (0.35%)

13/2578 (0.5%)

Traumatic orthopaedic surgery

163/454 (35.9%)

189/444 (41.9%)

69/6679 (1.0%)

97/6677 (1.5%)

60/7183 (0.8%)

115/9171 (1.6%)

27/7183 (0.38%)

60/7171 (0.84%)

470/7183 (6.5%)

488/7171 (6.8%)

All surgery

601/2315 (26.0%)

814/2339 (34.8%)

69/6679 (1.0%)

97/6677 (1.5%)

99/13167 (0.6%)

212/13168 (1.6%)

30/14067 (0.2%)

79/13168 (0.6%)

511/13167 (3.9%)

530/13168 (4.0%)

845/10995 (7.7%)

684/11024 (6.2%)

Relative risk (95% CI)

Non-orthopaedic surgery

0.71 (0.62-0.82)

0.28(0.16-0.48)

Orthopaedic surgery

0.77 (0.69-0.86)

0.71 (0.52-0.97)

0.65 (0.50-0.85)

0.44 (0.28-0.68)

Total surgery

0.75 (0.68-0.82)

0.71 (0.52-0.97)

0.47 (0.37-0.59)

0.36 (0.23-0.54)

0.96 (0.86-1.09)

1.24 (1.12-1.37)

Table 4: Contraindications and cautions for aspirin and heparins in prophylaxis of VTE

CONTRAINDICATIONS	CAUTIONS
Uncorrected bleeding disorders, e.g. haemophilias oral anticoagulants platelet count <70x109/L Bleeding or potentially bleeding lesions oesophageal varices active peptic ulcer recent (3 months) GI or intracranial bleed intracranial aneurysm or angioma Allergy Heparin associated thrombocytopenia or thrombosis (heparin)	Asthma (aspirin) Severe liver impairment, alcoholism Severe kidney impairment Major trauma or surgery to brain, eye or spinal cord (see section 4) Spinal or epidural block (see section 7) Anaemia (Hb <10g/dl)

Aspirin is commonly used to prevent MI in the older population.⁶ Meta-analyses have shown that patients receiving aspirin combined with low dose heparins have non-significant trends to increased efficacy in VTE prevention, and to increased risk of bleeding.^3,4,31 Stopping aspirin in such patients prior to giving perioperative heparin will not reduce perioperative bleeding (because the antiplatelet effect of aspirin lasts a week) and carries the risk that aspirin may not be re-prescribed after surgery. In general therefore, perioperative low-dose heparin is not contraindicated in patients already taking aspirin.

3.4 Unfractionated and low molecular weight heparins

Unfractionated heparin (UFH) and several LMWHs (dalteparin, enoxaparin, reviparin and tinzaparin) are currently licensed in the UK for prophylaxis of VTE.^94,95,96 They vary in their manufacture, chemistry and biology, but it is not clear whether or not these characteristics affect clinical efficacy or safety equivalence.⁹⁷

For prophylaxis of VTE, heparins are usually given subcutaneously, in lower doses than are used for the treatment of established thromboembolism. In such doses, they have little effect on the activated partial thromboplastin time (APTT). LMWHs have a longer half-life than UFH, so can be given as once daily subcutaneous injections for prophylaxis, compared to 8-12 hourly for UFH. Heparin prophylaxis is usually given for at least five days (the minimum duration of prophylaxis in RCTs) or until hospital discharge if earlier. Prolonged prophylaxis may be indicated in patients with continued illness and immobility, and in orthopaedic patients (see section 5.1.3).

Post-discharge prophylaxis should be discussed with the primary care team prior to a patient's discharge from hospital.

3.4.1 EFFICACY AND SAFETY OF UFH IN SURGICAL PATIENTS

A meta-analysis of RCTs² (including a large trial³⁰) found that low-dose subcutaneous UFH significantly reduces the incidence of asymptomatic DVT, symptomatic DVT and PE, fatal PE, and total mortality. A significant increase in major bleeding (from about 4% to 6%) was also observed; however there was no increase in fatal bleeding (n=8 vs. n=6) (see Table 5). Evidence level 1++

Table 5: Summary of meta-analyses of RCTs of low-dose subcutaneous heparins in prophylaxis of VTE in surgical patients

Intervention and Group

Asymptomatic DVT

Symptomatic DVT33

Symptomatic PE

Fatal PE

Total Mortality

Major bleeding

Active

Control

Active

Control

Active

Control

Active

Control

Active

Control

Active

Control

UFH vs. control2

non-orthopaedic

373/4095 (9.1%)

813/3525 (23.1%)

72/7188 (1.0%)

173/6574 (2.6%)

14/6568 (0.2%)

40/6631 (0.6%)

214/5627 (3.8%)

260/5696 (4.6%)

400/6484 (6.2%)

229/5980 (3.8%)

elective orthopaedic

78/371 (21%)

171/368 (46.5%)

43/450 (9.6%)

42/437 (9.6%)

0/498 (0%)

8/489 (1.6%)

0/498 (0%)

8/489 (1.6%)

16/336 (4.8%)

9/322 (2.8%)

traumatic orthopaedic

73/264 (27.7%)

123/251 (49.9%)

9/241 (3.7%)

7/228 (3.1%)

5/241 (2.0%)

7/228 (3.1%)

22/241 (9.1%)

16/241 (6.6%)

4/106 (3.8%)

6/94 (6.4%)

total orthopaedic

151/635 (23.8%)

294/619 (47.5%)

52/691 (7.5%)

49/665 (7.3%)

5/739 (0.7%)

15/717 (2.1%)

22/739 (3.0%)

24/730 (3.3%)

19/543 (3.5%)

15/524 (2.8%)

Total

524/4730 (11.1%)

1107/4144 (26.7%)

33/2045 (1.6%)

122/2076 (5.9%)

124/7879 (1.6%)

202/7910 (2.8%)

19/7307 (0.3%)

55/6777 (0.8%)

236/6366 (3.7%)

284/6426 (4.4%)

419/7027 (6.0%)

244/6504 (3.8%)

LMWH vs. control98,99

non-orthopaedic

4/145 (2.8%)

17/138 (12.3%)

(see text)

2/2399 (0.08%)

4/2398 (0.17%)

9/2349 (0.38%)

20/2348 (0.85%)

123/2247 (5.5%)

48/2251 (2.1%)

orthopaedic

87/348 (25%)

169/349 (48%)

3/495 (0.6%)

6/501 (1.2%)

0/495 (0%)

3/501 (0.6%)

0/495 (1.8%)

9/501 (1.8%)

13/93 (14.0%)

7/97 (7.2%)

Total

91/493 (18.5%)

186/487 (38.2%)

2/2894 (0.07%)

7/2899 (0.24%)

18/2844 (0.6%)

29/2849 (1.0%)

136/2340 (5.8%)

55/2348 (2.3%)

UFH or LMWH vs. control2,98,99

non-orthopaedic

377/4240 (8.9%)

830/3663 (22.7%)

72/7188 (1.0%)

173/6574 (2.6%)

16/8967 (0.18%)

44/9029 (0.49%)

223/7976 (2.8%)

280/8044 (3.5%)

523/8731 (6.0%)

277/8231 (3.4%)

orthopaedic

238/983 (28.8%)

463/968 (47.8%)

55/1186 (4.6%)

55/1166 (4.7%)

5/1234 (0.4%)

18/1218 (1.5%)

31/1234 (2.5%)

33/1231 (2.7%)

32/636 (5.0%)

22/621 (3.5%)

Total

615/5223 (11.8%)

1293/4631 (27.9%)

33/2045 (1.6%)

122/2076 (5.9%)

127/8374 (1.5%)

228/7740 (2.9%)

21/10201 (0.2%)

62/10247 (0.6%)

254/9210 (2.8%)

313/9275 (3.4%)

555/9367 (5.9%)

299/8852 (3.4%)

Relative Risk (95% CI)

non-orthopaedic

0.39 (0.35-0.44)

0.38 (0.29-0.50)

0.37 (0.21-0.65)

0.80 (0.68-0.96)

1.78 (1.54-2.05)

orthopaedic

0.51 (0.45-0.58)

0.98 (0.68-1.42)

0.27 (0.10-0.74)

0.94 (0.58-1.52)

1.42 (0.84-2.42)

Total

0.42 (0.39-0.46)

0.49 (0.34-0.71)

0.52 (0.42-0.64)

0.34 (0.21-0.56)

0.82 (0.69-0.96)

1.75 (1.53-2.01)

3.4.2 EFFICACY AND SAFETY OF LMWHs IN SURGICAL PATIENTS

Meta-analyses of RCTs have shown that subcutaneous LMWHs have similar prophylactic efficacy and risk of bleeding to UFH (see Table 5).^98,99 Once UFH had been shown to significantly reduce both fatal postoperative PE and mortality,^2,30 most RCTs of LMWHs have used UFH (or other methods of prophylaxis) in the control group, rather than placebo injections or no specific prophylaxis, for ethical reasons. Evidence level 1++

Combining the results of all RCTs of UFH or LMWH versus controls (Table 5), there was a significant reduction in fatal PE which was very similar to that with aspirin prophylaxis (0.2% vs 0.6%; NNT 250). Heparin prophylaxis was more likely to increase major bleeding compared to aspirin; but unlike aspirin reduced total mortality in non-orthopaedic surgery (2.8% vs. 3.5%; NNT 150) but not in orthopaedic surgery. Evidence level 1++

3.4.3 EFFICACY AND SAFETY OF UFH AND LMWHs IN MEDICAL PATIENTS

A meta-analysis of RCTs in general medical patients⁵ showed similar reductions in asymptomatic DVT and symptomatic PE to those in surgical patients (see section 8). Evidence level 1++

Subcutaneous low dose heparin (UFH or LMWH) is effective in prophylaxis of asymptomatic and symptomatic VTE in surgical and medical patients.

3.4.4 ADMINISTRATION, DOSAGE AND COAGULATION MONITORING

Cautions and contraindications to heparin prophylaxis are summarised in Table 4 (see also section 7).

When administered for thromboprophylaxis, both UFH and LMWH are given subcutaneously. The risk of wound haematomas can be minimised by avoiding injection sites close to wounds.³⁰ The dose of UFH is 5,000 IU 8-12 hourly or 7,500 IU 12 hourly. Consult the appropriate manufacturer's data sheet for the dose of LMWH.

In general, monitoring of the anticoagulant effect of low dose UFH or LMWH is not required. As LMWHs have little effect on the APTT, plasma anti-Xa activity should be measured instead.^96,100 Monitoring of plasma APTT or anti-Xa levels should be performed:

• in high-risk pregnancy (see section 9)
• if there are complications such as haemorrhage or accidental overdose
• in patients with renal failure given higher (therapeutic) doses of LMWH.¹⁰⁰

See the SIGN guideline on antithrombotic therapy.⁶

3.4.5 MONITORING PLATELET COUNT

Clinically important heparin associated thrombocytopenia (HAT) is immune mediated and usually occurs between five and 10 days (up to 20 days) after initiation of heparin. It can occur at any dose of either UFH or LMWH. LMWH is less likely than UFH to be associated with antiplatelet antibodies. HAT should be considered in any patient whose platelet count falls by 50% or more. It may present as, or be complicated by, thrombosis.^{94, 96} Evidence level 2+

Lepirudin was shown in an RCT to be more effective than dextran.⁹⁶ Evidence level 1+

In order to detect heparin associated thrombocytopenia, a baseline platelet count should be obtained and platelet count monitored in all patients receiving heparins for five days or more.

Heparin should be stopped if thrombocytopenia develops, or if the platelet count drops by 50% or more. Possible alternative initial antithrombotics include lepirudin.96

Warfarin is a suitable alternative antithrombotic to heparin following heparin associated thrombocytopenia, once the platelet count has recovered to >100 x 109/L.96

3.4.6 MONITORING BONE DENSITY

Prolonged (over 12 weeks) use of prophylactic heparin, e.g. in pregnancy, has been associated with increased risk of osteoporosis and bone fractures.⁹⁶ Long term LMWH may carry a lower risk of bone fractures than UFH in older patients.¹⁰¹ Evidence level 2++

3.4.7 REVERSAL OF HEPARIN ANTICOAGULATION

As the half-life of UFH is short, it is usually sufficient to stop the heparin if mild bleeding occurs. If severe bleeding occurs protamine sulphate should be given.^94,96 Protamine is less effective in reversal of LMWH anticoagulation (consult manufacturer's data sheet).

3.5 Heparinoids

The heparinoid, danaparoid, is effective in prophylaxis of DVT in patients undergoing general or orthopaedic surgery.¹⁰² Provided there is no evidence of cross-reactivity, it is also effective in treatment of patients with heparin associated thrombocytopenia^94,96,103 and can be used as short-term prophylaxis in patients with a history of this condition.⁹⁴

3.6 Hirudins

Hirudins are specific and direct thrombin blockers, which unlike heparins do not require circulating antithrombin.

Desirudin administered subcutaneously has been found to be safe and superior to UFH^104,105 or to the LMWH, enoxaparin,¹⁰⁶in the prevention of asymptomatic deep vein thrombosis after total hip or knee replacement. There are no data to indicate that it is more effective in reduction of either PE or mortality. It is not presently licensed in the UK.

Lepirudin is effective in treatment of patients with VTE in patients with heparin associated thrombocytopenia.⁹⁶

3.7 Pentasaccharides

The synthetic pentasaccharide fondaparinux is a highly selective, indirect inhibitor of activated factor Xa. A meta-analysis of trials recruiting orthopaedic patients has shown that it was more effective than LMWH in reduction of asymptomatic DVT.¹⁰⁷ It was not more effective in reduction of symptomatic DVT, PE or mortality.

3.8 Oral anticoagulants

Warfarin is effective in prophylaxis of asymptomatic DVT.^19,108 However, it is not widely used for this indication in the UK^27,80 because its use requires daily monitoring by the International Normalised Ratio (INR) of the prothrombin time, and because it increases the risk of bleeding after trauma or surgery,^6,19,20 as well as after spinal or epidural anaesthesia (see section 7).

Contraindications and cautions include:⁶

• bleeding disorders (see Table 4)
• bleeding or potentially bleeding lesions (see Table 4)
• spinal or epidural anaesthesia (see section 7)
• pregnancy, due to fetal toxicity (see section 9).

In patients on long term oral anticoagulant therapy (e.g. for atrial fibrillation or heart valve disease/prosthesis) who are immobilised by illness, trauma or surgery, continuation of oral anticoagulants may be appropriate prophylaxis of VTE. However, the INR should be checked and the dose of anticoagulant adjusted according to the perceived balance of risks of thrombosis and bleeding, especially after trauma or surgery.⁶ Evidence level 4

In patients receiving long term oral anticoagulant therapy who are immobilised by illness, trauma or surgery, continuation of oral anticoagulants (target INR 2.0-2.5) may be appropriate prophylaxis.

Where the risks of bleeding during or after surgery give rise to concern, oral anticoagulant therapy may be discontinued pre-operatively provided that alternative, effective prophylaxis (e.g. the combination of UFH or LMWH with mechanical prophylaxis) is instituted once the INR is less than 2.⁶ Evidence level 4

The combination of UFH or LMWH with mechanical prophylaxis may be an effective alternative to continuing oral anticoagulants in selected surgical patients.

3.9 Dextrans

Intravenous dextrans appear less effective than heparins in prophylaxis of asymptomatic DVT, but may be equally effective in prophylaxis of PE.¹⁹ However, dextrans are not widely used in
the UK^27,80 because of cumbersome administration and adverse effects including allergic reactions (rarely anaphylaxis), bleeding, and fluid overload (especially in patients with renal or cardiac insufficiency).¹⁰⁸

Dextrans should be avoided in patients with renal or cardiac insufficiency.

Women undergoing caesarean section have been reported to suffer an anaphylactoid reaction resulting in uterine hypertonus, profound fetal distress and a high incidence of fetal death.¹⁰⁹ Thus, dextrans should be avoided peripartum.

Dextrans should be avoided peripartum.