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Low Molecular Weight Heparin as Prophylaxis

Five studies have been found which examined LMWH alone, or compared different dosages or types of LMWHs.

Table 9. Evaluating Physical Methods for the Prevention of DVT

Author Year

Country

Research Design

PEDro Score

Sample Size

 

 

Methods

 

 

 

Outcomes

Becker et al., (1987)

USA

RCT

PEDro=6

N=15

 

Population: Age range=17-75yr; Gender: males=11, females=3; Severity of injury: complete/incomplete.

Chronicity: Acute.

Intervention: Rotating treatment tables.

Outcome Measures: Impedance blood plethysmography.

1.     4/5 control individuals and only 1/10 treated individuals developed positive fibrinogen leg scans.
Matsumoto et al., (2015)

Japan

Observational

N=29

Population: Mean Age: 63.2yr; Gender: males=25, females=4; Injury etiology: High fall (n=11, 38%), Fall at ground level (n=8, 28%), Motor Vehicle Accident (n=4, 14%), Sports (n=3, 10%), Low fall (n=2, 7%), Stairs (n=1, 3%); Severity of Injury: American Spinal Injury Association Impairment Scale (AIS) A=9, AIS B=2, AIS C=8, AIS D=10; Level of Injury: C3-4=11, C5-8=8, T1-12=6, L1-4=4.

Chronicity:<24 hr post SCI.

Intervention: All individuals were monitored for the development of deep venous thrombosis (DVT) after surgery and after they had received Intermittent pneumatic compression (IPC) with a calf pump and elastic stockings. The pump was attached throughout the day for at least 2wk after surgery and the elastic stockings were utilised after a median of 3 days post-surgery. Assessments were conducted 1, 3, 7, 14, and 28 days post-surgery.

Outcome Measures: Development of deep venous thrombosis (DVT), D-Dimer levels.

1.      DVT developed in 12 individuals (41.4%), all of which were located distal to the popliteal vein.

2.      The median length of time from surgery to detection of DVT was 7.5 days.

3.      Seven of the 12 individuals (58.3%) with DVT were classified as AIS A, one classified as AIS B (8.3%), three classified as AIS C (25.0%), and one classified as AIS D (8.3%).

4.      Mean D-Dimer level in individuals who developed DVT was 14.6+13.5ug-ml but this was not significantly different compared to individuals who did not developed DVT (p>0.05) at all assessment time-points except for 7 days after surgery (p=0.028).

5.      Cutoff D-Dimer levels according to the receiver operator characteristic curve did not differ significantly between individuals who developed DVT and those who did not except for 3 days after surgery (p=0.0287).

Chung et al., (2011)

Korea

Pre-Post

N=37

Population: Mean age=53 yr; Gender: Males=26, females=11; Level of injury: cervical-lumbar; Severity of injury: American Spinal Injury Association Impairment Scale (AIS) A-D.

Chronicity: All individuals were studied beginning within 1 week of injury.

Intervention: Only routine mechanical prophylaxis was administered to all individuals in the form of gradient elastic stockings (GES), external sequential pneumatic compression, and early ambulation.

Outcome Measures: Incidence of deep vein thrombosis (DVT) or pulmonary embolism (PE).

Method of Diagnosis: Doppler ultrasonography.

Timing of DVT onset: Routine checks for DVT were performed every 2 weeks beginning usually within 1 week of injury. 27% of individuals developed DVT within 7 days after injury, 8% developed DVT within 2-3 weeks after injury, and 8% developed DVT>1 month after injury.

Incidence of DVT:

1.     43% of individuals developed DVT.

2.     2 individuals (5%) developed a PE.

3.     Incidence of DVT in individuals in the present study was higher when compared to studies using pharmacological forms of prophylaxis.

Maxwell et al., (2002)

USA

Case Series

N=111

 

Population: Mean age=37.5 yr; Gender: males=81%, females=19%; Level of injury: not specified; Severity of injury: paraplegia=41.4%, tetraplegia=58.6%.

Chronicity: Individuals were hospitalized and monitored for an average of 23 ± 20 days following injury.

Intervention: Retrospective review of individuals using sequential compression devices alone or in combination with 5000 IU low dose unfractionated heparin (LDUH) subcutaneously every 12 hr or low molecular unfractionated heparin (LMWH) (Enoxaparin) 30 mg subcutaneously every 12 hr.

Outcome Measures: Incidence of deep vein thrombosis (DVT) or pulmonary embolism (PE).

Method of Diagnosis: Venous duplex ultrasonography.

Timing of DVT onset: Screening for DVT was performed on average 2.3 times during each admission. No other information was provided.

Incidence of DVT:

1.     The overall incidence rate for DVT and PE in SCI individuals was 9.0% and 1.8%, respectively, which was not significantly different.

2.     The incidence of DVT and PE in individuals using compression only was 7.1% and 2.4%, respectively.

Winemiller et al., (1999)

USA

Case Series

N=285

Population: Mean age=26 yr (VTE), mean age=25 yr (no VTE); Gender: males=88% (VTE), males=72% (no VTE); Level of injury: cervical-lumbar/sacral; Severity of injury: Frankel scores: A-B.

Chronicity: All individuals were studied for the initial 6 week duration following injury.

Intervention: Retrospective review of individuals who were administered antithrombotic prophylaxis (sequential compression devices (SCD)/gradient elastic stockings (GES)) or unfractionated heparin (UFH)) for 42 days-6 weeks after injury.

Outcome Measures: Incidence of deep vein thrombosis (DVT) or pulmonary embolism (PE).

Method of Diagnosis: Fibrinogen scans, impedance plethysmography, Doppler studies, venograms, and ventilation-perfusion scanning.

Timing of DVT onset: DVT/PE first detected at a median of 14.5 days after injury. 63% of initial DVT/PE events occurred within the first 3 weeks.

Incidence of DVT:

1.     Overall Incidence of DVT/PE was 19.6%.

2.     Multivariate analysis showed that SCD and GES were associated with a reduced risk of venous thromboembolism.

3.     The risk reduction for heparin compared to SCD/GES was not significant (p=0.06 (95% CI, 0.05-1.08) for the first 14 days, p=0.13 for anytime); SCD/GES and heparin seemed to each be effective.

4.     SCD/GES should be continued after 2 weeks post injury.

CHRONIC
 

Nash et al., (2000)

USA

RCT

PEDro=8

N=20

Population: Mean age=27.9yr; Gender: males=20; Level of injury: tetraplegic=20; Chronicity: 2mo-17yr post SCI.

Intervention: Individuals were randomized into one of two groups: 1) Slow sequential pneumatic compression devices (SCD)-15sec compression, 45sec relaxation at 35 mmHg (ankle), 30 mmHg (calf) or 20 mmHh (thigh); or 2) intermittent pulsatile compression (IPC-2sec compression, 18sec relaxation at 160mmHg.

Outcome Measures: Venous flow/min (VFM); average venous velocity (AVV); maximum venous velocity (MVV); for bilateral popliteal and femoral veins at rest (baseline) and during compression.

1.      Popliteal vein: no differences between devices.

2.      Femoral vein: increase in VFM and MVV during IPC versus SCD (p<0.05).

3.      Rest versus compression: VFM, AVV and MVV, all increased during compression (p<0.001).

Table 10. Prophylactic Vena Cava Insertion in Individuals with Traumatic SCI

Author Year

Country

PEDro Score

Research Design

Sample Size

MethodsOutcomes
Roberts & Young (2010)

USA

Case Series

N=45

Population: Mean age=39.7 yr; Gender: males=37, females=8; Level of injury: cervical; Severity of injury: injury severity score (ISS)>20 (mean score=34.2).

Chronicity: Filters were placed in all individuals within 72 hr of admission.

Intervention: Placement of a prophylactic inferior vena cava (IVC) filter. Individuals were placed on prophylactic anticoagulant therapy 1 week after injury (Lovenox or Heparin).

Outcome Measures: Incidence of pulmonary embolism (PE) and complications related to insertion.

Method of Diagnosis: Not indicated.

Timing of DVT onset: Not indicated.

Incidence of PE:

1.     No individuals sustained a PE.

2.     No complications related to IVC filter insertion were observed.

3.     IVC filters are suggested as safe and perhaps add preventative value against thrombotic complications.

 

 

Gorman et al., (2009)

USA

Case Control

N=112

Population: Mean age=37.1 yr (inferior vena cava (IVC) filter), Mean age=48.1 yr (no filter); Gender: males=96% (IVC filter), males=69% (no filter); Level of injury: C3-L3; Severity of injury: not specified.

Chronicity: Individuals either received or did not receive an IVC filter during their acute hospitalization before admission to the rehabilitation centres. No other information was provided.

Intervention: Retrospective review of SCI individuals who had received a prophylactic IVC filter, compared to those that had not. All individuals were also treated with another form of prophylaxis, “usually low molecular unfractionated heparin (LMWH) and compression stockings.”

Outcome Measures: Incidence of deep vein thrombosis (DVT).

Method of Diagnosis: Clinical examination and duplex ultrasonography.

Timing of DVT onset: Average length of stay for individuals was 39 days (IVC filter) and 27 days (no filter) after acute hospitalization. No information was provided specifying when screening was performed.

Incidence of DVT:

1.     Individuals without IVC filter had fewer DVTs than those with an IVC filter (5.2% and 20.4% respectively, p=0.021).

2.     IVC filter placement resulted in significantly increased risk of DVT development.

 

 

 

Kinney et al., (1996)

USA

Case Control

N=11

Population: Mean age=33.8 yr; Gender: males=100% (SCI group); Level of injury: cervical; Severity of injury: not specified.

Chronicity: The mean acute hospitalization after injury was 27.5 days (SCI group). Timing of filter insertion was not described.

Intervention: Retrospective review of SCI individuals who received prophylactic inferior vena cava (IVC) filters, compared to non-SCI individuals (historical controls) who received the filter.

Outcome Measures: Incidence of pulmonary embolism (PE).

Method of Diagnosis: Computed tomography and ventilation-perfusion lung scanning.

Timing of PE onset: No information was provided specifying when screening was performed.

Incidence of PE:

1.     The SCI population had an 18.2% incidence rate of PE, which was higher compared to rates in historical controls.

Rogers et al., (1995)

USA

Pre-Post

N=63

Population: Mean age=38.9 yr; Gender: males=73%, females=27%; Level of injury: not specified; Severity of injury: not specified.

Chronicity: The mean time from admission to filter insertion was 4.3 days.

Intervention: A subset of high-risk trauma individuals (SCI=25) received prophylactic vena cava filter (VCF) insertion. Forms of standard prophylaxis were contraindicated.

Outcome Measures: Incidence of deep vein thrombosis (DVT) or pulmonary embolism (PE).

Method of Diagnosis: Impedance plethysmography, venous duplex ultrasonography, ventilation-perfusion scanning, and pulmonary angiography.

Timing of DVT onset: Screening was done within 48 hr of filter insertion and on a weekly basis afterwards until death/discharge. No other information specifying timing of DVT onset was described.

Incidence of DVT:

1.     3 individuals developed DVT.

2.     No individuals developed PE.

 

Wilson et al., (1994)

USA

Pre-Post

N=15

Population: Mean age=31.4 yr; Gender: males=12, females=3; Level of injury: cervical-lumbar; Severity of injury: injury severity score (ISS)>20.

Chronicity: Individuals were hospitalized for a median of 22 days. Timing of filter insertion was done “as soon as clinically feasible.”

Intervention: Prophylactic inferior vena cava (IVC) filter insertion. All individuals also received either low-dose subcutaneous heparin or venous compression devices while hospitalized. These individuals were compared to historic controls who did not receive filters.

Outcome Measures: Incidence of deep vein thrombosis (DVT) or pulmonary embolism (PE).

Method of Diagnosis: Impedance plethysmography and venous duplex ultrasonography.

Timing of DVT/PE onset: No PE was observed in up to 24 mo of follow-up.

Incidence of DVT:

1.     No individuals developed DVT during acute hospitalization.

2.     No individuals developed PE after filter insertion.

 

 

Balshi et al., 1989

USA

Case Series

N=13

Population: Age range=17-48yr; Gender: males=11, females=2; Severity of Injury: quadriplegia.

Chronicity: 2 weeks-4 yr post SCI.

Intervention: Prophylactic Greenfield inferior vena cava (IVC) filter insertion.

Outcome Measures: Incidence of deep venous thrombosis (DVT) or pulmonary embolism (PE).

1.     Twelve individuals experienced a DVT while one had a PE.

2.     Two individuals experienced recurrent DVT.

3.     Distal migration of the filter occurred in two individuals.

Jarrell et al., (1983)

USA

Case Series

N=21

 

Population: Not clear.

Chronicity: Acute.

Intervention: Prophylactic Greenfield inferior vena cava (IVC) filter insertion.

Outcome Measures: Incidence of pulmonary embolism (PE).

1.     There was one PE-related fatality.

2.     There was no other instance of suspected or proved PE after insertion of the filter.

3.     Follow-up revealed two instances of thrombosis.

 

Discussion

In examining the LMWH enoxaparin, Harris et al. (1996) performed a case series with 105 subjects (66 with SCI). All patients received 30 mg of enoxaparin s/c q12h beginning at the time of admission. Patients scheduled for surgery withheld anticoagulation therapy on the morning of the operation, resumed 24 hours later, and continued until the patients’ discharge. No patient developed clinical or ultrasound evidence of a DVT.

The optimal dose of enoxaparin has not been established to date. Hebbeler et al. (2004) compared two dosing regimens of enoxaparin (40 mg daily or 30 mg twice daily) among 129 acute SCI patients. Symptomatic thromboembolism did not differ between the two groups with DVT occurring in only one patient in each group. Furthermore, there was no difference in bleeding complications between the two groups.

Since there are many new LMWHs available, studies have compared their efficacy. One RCT (Chiou-Tan et al. 2001) and one case control study (Slavik et al. 2007) compared acute SCI patients who received enoxaparin (30-40 mg s/c q12h) to those who received dalteparin (2000-5000 IU s/c daily). There were no significant group differences between the two groups in terms of incidence and location of DVTs or bleeding complications. A third study by Marciniak et al. (2012) compared enoxaparin to two different doses of tinzaparin (4500 IU and 3500 IU). After controlling for multiple variables they reported no differences in DVT incidence between the LMWHs.

One systematic review evaluated the ideal time for initiating DVT treatment with LMWH. Christie et al. (2011) concluded that LMWH prophylaxis for DVT should be administered within 72 hours post SCI. However, this conclusion should be interpreted with caution, as it was based on a single, small (N=5) systematic review.

Conclusion

There is level 4 evidence (from one case control study; Hebbeler et al. 2004) that 40 mg daily enoxaparin is no more effective than 30 mg twice daily enoxaparin in reducing the incidence of deep venous thrombosis or bleeding complications when used prophylactically.

There is level 1b evidence (from one RCT and one case control study; Chiou-Tan et al. 2003; Slavik et al. 2007) that enoxaparin is no more effective than dalteparin in reducing the risk of deep venous thrombosis or bleeding complications although enoxaparin is more expensive.

There is level 3 evidence (from one case control study; Marciniak et al. 2012) that enoxaparin is no more effective than tinzaparin in reducing the risk of deep venous thrombosis or bleeding complications.

There appears to be no difference between enoxaparin and dalteparin, or enoxaparin and tinzaparin, in reducing the risk of venous thrombosis post-SCI.