Venous thromboembolism: Prophylactic and therapeutic practice guideline
B F JacobsonI; S LouwI; H BüllerII; M MerIII; P R de JongIV; P RowjiV; E SchapkaitzI; D AdlerVI; A BeetonVII; H-C HsuVIII; P WesselsIX; S HaasX, on behalf of the Southern African Society of Thrombosis and Haemostasis
IMB ChB, FRCS (Glasg), MMed (Haematol), FCPath (SA), PhD (Med). Department of Molecular Medicine and Haematology, University of the Witwatersrand and National Health Laboratory Services, Johannesburg, South Africa
IMB BCh, FCPath (Haem), MMed (Haem). Department of Molecular Medicine and Haematology, University of the Witwatersrand and National Health Laboratory Services, Johannesburg, South Africa
IMB BCh, FCPath (Haem), MMed (Haem). Department of Molecular Medicine and Haematology, University of the Witwatersrand and National Health Laboratory Services, Johannesburg, South Africa
IIMD, PhD. Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands ]]>
IIIMB BCh, Dip PEC (SA), FCP (SA), MMed (Int Med) Pulmonol, Cert Crit Care (SA), FRCP (Lond), FCCP, PhD. Department of Medicine, Division of Pulmonology and Critical Care, Charlotte Maxeke Johannesburg Academic Hospital and University of the Witwatersrand, Johannesburg, South Africa
IVFRCOG, FCOG, MMed. Department of Obstetrics and Gynaecology, University of Cape Town, and Chris Barnard Memorial Hospital, Cape Town, South Africa
VIBSc (Med), MB BCh, FCP (SA). Faculty of Consulting Physicians, South Africa
VIIMB BCh, DA (SA), FFA (SA). Wits Donald Gordon Medical Centre, Johannesburg, South Africa
VIIIMB BCh, FCP (SA). Milpark Hospital, Johannesburg, and Executive Member, South African Renal Consortium, South Africa
IXMB ChB, MMed (Haematol), Cert Clin Haematol (CMSA). Consultant, Ampath Laboratories, and Consultant, Department of Medical Oncology, University of Pretoria, South Africa
XMD. Technical University of Munich, Germany
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ABSTRACT
BACKGROUND: Pharmacological prophylactic anticoagulation in many countries, including South Africa, is under-prescribed. This has resulted in unacceptable rates of morbidity and mortality.
METHOD: The Southern African Society of Thrombosis and Haemostasis held a meeting to update the previous guideline and review new literature including guidelines from other societies. The following specialties were represented on the committees: anaesthetics, cardiology, clinical haematology, critical care, obstetrics and gynaecology, haematopathology, internal medicine, neurology, orthopaedic surgery and pulmonology. A draft document was presented at the meeting, which was then revised by consensus agreement. To avoid local bias, the guideline was adjudicated by recognised international external experts.
RESULTS AND CONCLUSION: A concise, practical updated guideline for thromboprophylaxis and treatment in medical and surgical patients has been produced for South African conditions. It is hoped that this guideline will continue to improve anticoagulation practice in this country, which we believe will directly benefit patient outcomes.
1. Prophylactic anticoagulation
This guideline reflects current best practice. However, every patient should still be assessed on merit, with individualisation of therapy where indicated. Special attention is needed in geriatric and obese patients, those with renal dysfunction and those with concomitant medical disorders. Drug recommendations are based on Medicines
Control Council (MCC) registration at the time of publication, unless otherwise indicated.
]]> 1.1 Medical patients[1-7]1.1.1 Background
In the absence of anticoagulation, the risk of deep-vein thrombosis (DVT) in medically ill patients is comparable to that in moderate-risk surgical patients (10 - 20%). Although the clinical significance of asymptomatic distal DVT is debatable, pulmonary embolism (PE) is the commonest preventable cause of death in hospital patients, contributing to 10% of all hospital deaths. Three-quarters of these deaths occur in medically ill patients. The efficacy of heparins in preventing venous thromboembolism (VTE) in medically ill patients is now well established. However, their use is associated with a modestly increased risk of major bleeding episodes, and this should be balanced against the thrombotic risk.
1.1.2 Risk assessment
Risk assessment is essential, and treatment needs to be individualised. Refer to Appendix I for further information.
1.1.3 Recommendations for prophylaxis in medically ill patients NOTE: Aspirin offers only weak VTE prophylaxis when compared with other agents used for prophylaxis such as low-molecular-weight heparin (LMWH).
The recommended prophylactic doses for LMWH and unfractionated heparins are as follows:
OR
NOTE: Prophylaxis is not required for patients who are mobile, i.e. when more active than sitting in a chair and walking to the bathroom.
In patients at high risk of bleeding, the use of mechanical prophylaxis such as graduated compression stockings or intermittent pneumatic compression (IPC) should be considered as an alternative if the risk of thrombosis is high.
1.1.4 Monitoring
See 'General recommendations', section 1.2.6.
]]> 1.2 Surgical patients[8-14] 1.2.1 BackgroundRefer to comments in sections 1.1.1 and 1.1.2 regarding background and risk assessment. VTE is an important cause of morbidity and mortality in surgical patients. However, the relative risk of developing VTE varies, and some measure of risk assessment is required for appropriate selection of prophylaxis. This guideline attempts to simplify risk assessment models, which are often too complicated for routine use.
Both patient-related and procedure-related risk factors should be considered when assessing an individual's risk of developing VTE.
1.2.1.1 Patient-related risk factors
1.2.1.2 Procedure-related risk factors
1.2.2 Recommendations for prophylaxis in surgical patients NOTE: Aspirin offers only weak VTE prophylaxis when compared with other agents used for prophylaxis such as LMWH.
1.2.2.1 Low-risk procedures (minor surgery) with no patient-related risk factors
OR
OR
Prophylaxis can be given 12 hours before surgery. Postoperative administration is acceptable, and then once daily thereafter (see 'Timing of prophylaxis', section 1.2.3).
IPC devices may be acceptable alternatives, particularly if minor bleeding is likely to be harmful or other factors suggest an increased bleeding risk. If feasible and practical, IPC devices can therefore be utilised, although at most only modest evidence exists as to their benefit.
1.2.2.3 Higher-risk procedures (major surgery) with additional patient-related risk factors OR very high-risk procedures (orthopaedic or trauma surgery)
OR
OR
OR
OR
In this group of patients, use of additional mechanical devices such as IPC devices should be considered.
1.2.3 Timing of prophylaxis
NOTE: This is extremely controversial.
1.2.4 Duration of prophylaxis
1.2.5 Special circumstances
1.2.5.1 Recommendations with reference to centroneuroaxial blockade (spinal and epidural anaesthesia) in the setting of prophylactic doses
• Neurological monitoring is mandatory for a minimum of 12 hours and ideally for 72 hours after neuroaxial blockade in association with anticoagulation.
• Extreme caution should be exercised in patients on other haemostatically active agents such as aspirin and non-steroidal anti-inflammatory agents.
• LMWH:
• Fondaparinux:
• NOACs, rivaroxaban and dabigatran:
1.2.5.2 Recommendations with reference to thromboprophylaxis in pregnancy and gynaecological surgery
]]> There are no drugs registered for this indication in pregnancy; these are therefore off-label recommendations. (All other recommendations in this guideline are as per registered indications/'on-label'.)Refer to Appendix I for VTE risk factor assessment.
• Thromboprophylaxis during pregnancy and after caesarean section (CS):
• NOACs (rivaroxaban and dabigatran) should not be used in pregnancy, as the molecules are small and cross the placenta, and should also be avoided while the mother is breastfeeding.
• Thromboprophylaxis following gynaecological surgery:
1.2.5.3 Recommendation for the treatment of acute cerebral venous thrombosis[15-17]
• There is general consensus that anticoagulation with unfractionated heparin or LMWH is appropriate and sufficient treatment, provided meningitis has been excluded.
• There is insufficient evidence to support the routine use of local or systemic thrombolysis.
• The presence of venous infarction is not a contraindication to anticoagulation.
1.2.6 General recommendations
1.2.6.1. Monitoring of patients on LMWH
• The patient's platelet count should be checked on initiation of LMWH, after 5 days, and regularly thereafter while on therapy.
• Anticoagulant activity is measured using an anti-Xa activity assay:
• Target levels for anti-Xa:
• No routine laboratory monitoring is required.
• Measuring the drug effect may be useful in:
• Suggested assays to measure drug activity of NOACs:
• Routine coagulation assays may also be affected by the NOACs, with dabigatran prolonging the partial thromboplastin time and rivaroxaban affecting the INR.
1.2.6.3. Switching between anticoagulation modalities[13,17,18]
Recommendations when switching between standard anticoagulation modalities and NOACs are presented in Table 2.
]]> 1.2.6.4. Management of bleeding patients[10,12,13,17-20]• Do not use thromboprophylaxis if there is severe bleeding.
• Discontinue LMWH as well as any other haemostatically active agents that may contribute to haemorrhage.
• Supportive care including transfusion of blood products.
• LMWH:
2. Treatment of VTE
2.1 Initiation of anticoagulation[2,3]
LMWH offers definite advantages over UFH, because not only is the dosing convenient but there is generally no need to monitor patients. This allows for outpatient management for certain patients. It may also result in a reduced risk of recurrence of VTE. LMWH should be used as follows:
OR
OR
The above drugs should be given for at least 5 days.
The NOACs were not registered for the treatment of VTE at the time of publication of this guideline.
2.2 Duration of oral anticoagulation[9,13,20]
The duration of treatment needs to be individualised according to the patient's thromboembolic risk level, and only basic recommendations are given.
2.3 Venocaval filters[2]
Venacaval filters are indicated in the following situations:
2.4 Catheter-directed thrombolysis[2]
Catheter-directed thrombolysis may be indicated only in centres with the necessary expertise for selected young patients with a large clot burden in ileo-femoral thrombosis.
2.5 Thrombophilia screening[21]
The presence of an underlying hereditary thrombophilic state does not alter initial management, and thrombophilia screening should be delayed until 2 weeks after discontinuation of therapy because the results are altered by the acute event and by anticoagulant therapy.
2.6 Outpatient management[12,22]
Management of VTE in the outpatient setting is safe and cost-effective provided that:
2.7 Management of non-therapeutic INRs[12,22]
This should be individualised according to bleeding risk. General guidelines are as follows:
• INR >5 and <10, no significant bleeding:
• omit warfarin
• Significant life-threatening bleeding:
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Corresponding author: S Louw (susan.louw@nhls.ac.za)
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