Low-Molecular-Weight Heparin versus Low-Dose Unfractionated Heparin as Prophylaxis
Several studies have been found which examined LMWH alone or compared different dosages or types of LMWHs.
Author Year; Country |
Methods | Outcome |
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Spinal Cord Injury Thromboprophylaxis Investigators (2003a) |
Population: Mean age=40.6 yr (unfractionated heparin (UFH)-intermittent pneumatic compression (IPC) group), mean age=38.5 yr (Enoxaparin group); Gender: males=79.6% (UFH-IPC group), males=89.7% (Enoxaparin group); Level of injury: not specified; Severity of injury: (AIS) A-D. Chronicity: All individuals were studied beginning within 72 hr of sustaining injury and monitored for approximately 2 weeks during acute treatment (mean=13.4 days for UFH-IPC group, mean=14 days for Enoxaparin group). Intervention: Individuals were assigned to receive either low-dose UFH (5000 IU subcutaneously every 8 hr) plus IPC (used at least 22hr/day), or only Enoxaparin (30 mg subcutaneously every 12 hr). Outcome Measures: Incidence of deep vein thrombosis (DVT), pulmonary embolism (PE), and major bleeding. Method of Diagnosis: Doppler ultrasonography, venography, ventilation-perfusion lung scanning, spiral computed tomographic scanning, and pulmonary angiography. |
Timing of DVT onset: DVT/PE screening/data collection was performed at the end of the 2-week acute treatment phase or within 2 days of the last dose of acute-phase medication. Incidence of DVT:
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Green et al. 1990; USA |
Population: Mean age=31 yr (LDUH group), mean age=28 yr (LMWH group); Gender: males=4, females=17 (LDUH group), males=3, females=17 (LMWH group); Level of injury: cervical-lumbar; Severity of injury: not specified. Chronicity: All individuals were studied beginning within 72 hr of sustaining injury and monitored for 8 weeks. Intervention: Individuals were randomly assigned to receive either low dose unfractionated heparin (LDUH) (5000 IU) subcutaneously every 8 hr or low molecular unfractionated heparin (LMWH) (Logiparin, 3500 anti-Xa units) subcutaneously once daily. Outcome Measures: Incidence of deep vein thrombosis (DVT), pulmonary embolism (PE), and major bleeding. Method of Diagnosis: Impedance plethysmography, Doppler flow measurements and duplex ultrasonography. |
Timing of DVT onset: DVT events occurred on days 4, 7, and 32 after admission; PE events occurred on days 21 and 38 after admission. Incidence of DVT:
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Arnold et al. 2010; USA |
Population: Acute SCI individuals were a subset of the study population (n=24); no further information was provided. Chronicity: Individuals studied were admitted after>72 hr post injury. Intervention: Retrospective review of individuals who received either 5000 U low dose unfractionated heparin (LDUH) three times a day or low molecular unfractionated heparin (LMWH) (Enoxaparin, 30 mg twice daily or 40 mg once daily). Outcome Measures: Incidence of deep vein thrombosis (DVT) or pulmonary embolism (PE). Method of Diagnosis: Duplex ultrasonography. |
Timing of DVT onset: Not indicated. Incidence of DVT:
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Worley et al. 2008; Canada |
Population: Mean age=46yr (LDUH group), mean age=38 yr (LMWH group); Gender: males=40, females=7 (LDUH group), males=39, females=4 (LMWH group); Level of injury: cervical-sacral; Severity of injury: tetraplegia=35, paraplegia=12, (AIS) A-D. Chronicity: Individuals studied were under acute care following acute SCI. No other information was provided. Intervention: Individuals reviewed received either 5000 U low molecular unfractionated heparin (LMWH) (Dalteparin) subcutaneously daily or 5000 U low dose unfractionated heparin (LDUH) subcutaneously twice daily. Outcome Measures: Incidence of deep vein thrombosis (DVT) or pulmonary embolism (PE). Method of Diagnosis: Compression ultrasonography, ventilation-perfusion lung scanning, computed tomography, and pulmonary angiography. |
Timing of DVT onset: Not indicated. Incidence of DVT:
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Spinal Cord Injury Thromboprophylaxis Investigators (2003b); USA |
Population: Mean age=34 yr (unfractionated heparin (UFH) group), mean age=30.5 yr (Enoxaparin group); Gender: males=78.3% (UFH group), males=89.8% (Enoxaparin group); Level of injury: not specified; Severity of injury: (AIS) A-D. Chronicity: All individuals were studied from 2-8 weeks following injury (in continuation of study 2003a, above). Intervention: Continuation of study 2003a (above): Individuals previously receiving unfractionated heparin (UFH) continued on this regimen (5000 IU subcutaneously every 8 hr), but intermittent pneumatic compression (IPC) was discontinued. Those previously receiving Enoxaparin continued this regimen, but at a dose of 40mg once daily (instead of 30 mg twice daily). Outcome Measures: Incidence of deep vein thrombosis (DVT) or pulmonary embolism (PE). Method of Diagnosis: Doppler ultrasonography, venography, ventilation-perfusion lung scanning, spiral computed tomographic scanning, and pulmonary angiography. |
Timing of DVT onset: DVT/PE screening/data collection was performed at the end of the 6-week rehabilitation treatment phase (8 weeks following injury). Incidence of DVT:
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Thumbikat et al. 2002; UK |
Population: Age range=10-60 yr (27 individuals were over 60); Gender: males=129, females=44; Level of injury: cervical-lumbar; Severity of injury: not specified. Chronicity: Individuals in the heparin group commenced treatment “soon after admission,” and individuals in the Enoxaparin group received treatment on the day of admission. Individuals were studied beginning within an average of 12 days following injury (range 0-80). Average period of anticoagulation was 57 days for individuals in the heparin group and 52 days for individuals in the Enoxaparin group. Intervention: Individuals received either a combination of heparin 5000 IU twice daily followed by warfarin, or only Enoxaparin 20 mg (n=40) or 40 mg (n=32). Outcome Measures: Incidence of deep vein thrombosis (DVT) or pulmonary embolism (PE) and other complications. Method of Diagnosis: Doppler ultrasonography and ventilation-perfusion scanning. |
Timing of DVT onset: Peak incidences of VTE occurred at 20-30 and 90-100 days following injury for both groups studied. Incidence of DVT:
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Green et al. 1994; USA |
Population: No demographical information was provided. Chronicity: Individuals were studied beginning within 72 hr post injury and monitored for 8 weeks. Intervention: All individuals received low molecular unfractionated heparin (LMWH) (Logiparin) at a dose of 3500 anti-Xa U subcutaneously once daily, beginning within 72 hr of injury for 8 weeks. Outcome Measures: Incidence of deep vein thrombosis (DVT), pulmonary embolism (PE), and bleeding in these 48 individuals combined with 20 individuals receiving LMWH in the study by Green et al., 1990 (above) were compared to previously studied individuals treated with standard heparin. Method of Diagnosis: Impedance plethysmography Doppler flow measurements and duplex ultrasonography. |
Timing of DVT onset: DVT screening was done at the conclusion of the 8 week timeframe post injury. Incidence of DVT:
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Author Year; Country Research Design Total Sample Size AMSTAR Score |
Methods | Outcome |
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Arnold et al. 2017; USA |
Method: A comprehensive literature search was conducted to identify randomized controlled trials (RCT) evaluating the efficacy and safety of antithrombotic strategies. The strength of evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system.
Databases: MEDLINE; Cochrane Collaboration Library.
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Question one:
Question two:
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Question five:
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Fehlings et al. 2017; Canada Clinical Practice Guideline |
Method: A comprehensive literature search was conducted to address key questions relating to thromboprophylaxis in SCI. The strength of evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system.
Databases: Not reported.
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Chen & Wang, 2013; China Review of published articles up to February 2013 N = 18 AMSTAR = 9 |
Method: Comprehensive literature search of randomized controlled trials (RCT), quasi-RCTs, cohort studies, case control studies, and cross-sectional studies of individuals with acute SCI receiving heparin to prevent the risk venous thromboembolism (VTE) and major bleeding.
Databases: MEDLINE.
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Discussion
Several studies have examined the thromboprophylactic effectiveness of LMWH compared to that of LDUH on the incidence of DVT and PE in the acute phase (<3 months) of SCI. Two studies evaluated the efficacy of Logiparin compared to LDUH. One RCT by Green et al. (1990) included individuals who were within 72 hours of sustaining SCI, and who were randomly assigned to receive 5000 IU LDUH every 8 hours or 3500 anti-Xa U Logiparin once daily. Significantly more individuals receiving LDUH (24%) developed DVT/PE compared to individuals receiving LMWH (0%, p=0.02). Green et al. (1994) studied 48 individuals who were given 3500 anti-Xa U Logiparin once daily for 8 weeks, beginning within 72 hours of injury. These individuals, combined with 20 individuals receiving the same regimen in the previously mentioned study (1990), were compared to individuals receiving LDUH (also from the previously mentioned study by Green et al. (1990)). Although not significant, a trend was reported in terms of fewer thrombotic events occurring for LMWH, which compared favourably to LDUH for VTE prophylaxis.
Several studies evaluated the efficacy of Enoxaparin compared to LDUH. In a case control study, Arnold et al. (2010) retrospectively reviewed individuals who were admitted greater than 72 hours post-SCI, and who received either 5000 U LDUH three times a day or Enoxaparin (30 mg twice daily or 40 mg once daily). A significant difference between groups in incidence of DVT was not observed (p=0.357). Thumbikat et al. (2002) also conducted a case control study in which individuals were studied, on average, 12 days post-injury. Participants received either 5000 IU LDUH twice daily, or 20 or 40 mg Enoxaparin. The authors reported that 13% of individuals receiving LDUH and 18% of individuals receiving Enoxaparin developed VTE, with peak incidences occurring at 20 to 30 days and 90 to 100 days following injury for both groups overall; however, no statistical analyses were reported.
In an RCT by the Spinal Cord Injury Thromboprophylaxis Investigators (2003a), individuals were randomly assigned to receive either 5000 IU LDUH every 8 hours along with IPC, or 40 mg of Enoxaparin every 12 hours without IPC. All individuals studied had sustained an SCI within 72 hours, were monitored for approximately two weeks, and were screened for DVT/PE. In individuals receiving LDUH, the incidence of DVT was 44.9%, which was not significantly different from 60.3% of individuals receiving Enoxaparin (p=0.11). The incidence of PE was significantly higher (18.4%) in individuals receiving LDUH compared to Enoxaparin (5.2%, p=0.03). Further to the previous study, the Spinal Cord Injury Thromboprophylaxis Investigators (2003b) investigated the effect of 6 more weeks of pharmacological prophylaxis following the initial 2-week protocol. Individuals previously receiving 5000 IU LDUH every 8 hours continued to do so, but without concurrent IPC. Individuals previously receiving Enoxaparin continued this regimen, but at a dose of 40 mg once daily. Screening for DVT and PE was performed at the conclusion of the additional 6-week protocol. In individuals receiving LDUH, the incidence of DVT was 18.3% which was not significantly different from 6.8% of individuals receiving Enoxaparin (p=0.067). The incidence of PE was also not significantly different between groups (3.3% and 1.7% of individuals receiving LDUH and Enoxaparin, respectively, p=0.576).
Finally, a case control by Worley et al. (2008) evaluated the efficacy of Dalteparin compared to LDUH. Individuals in acute care (time post-injury otherwise not specified) were retrospectively reviewed; individuals received either 5000 U LDUH twice daily or 5000 U Dalteparin daily. No significant difference in DVT incidence was found between the groups (p=0.7054).
A systematic review by Chen and Wang (2013) examining 18 studies with 2578 individuals compared the effect of different pharmacological VTE prophylactic options. It was concluded that LMWH is similar to LDUH in VTE prevention but has less bleeding complications. There was no difference in VTE prophylaxis using various types and/or doses of LMWH, including enoxaparin, tinzaparin, and dalteparin. Despite the conflicting results presented by Chen and Wang (2013), there is still strong evidence based on five studies that LMWH is more effective than LDUH.
Conclusions
There is level 1b evidence (from one RCT: Green et al. 1990) that Logiparin (low molecular weight heparin) is more effective than low-dose unfractionated heparin as prophylaxis for venous thromboembolism in acute SCI individuals.
There is level 1b evidence (from one RCT: Spinal Cord Injury Thromboprophylaxis Investigators 2003a) that Enoxaparin (low molecular weight heparin) is more effective than low-dose unfractionated heparin as prophylaxis for pulmonary emboli in acute SCI.
There is level 1b evidence (from one RCT: Spinal Cord Injury Thromboprophylaxis Investigators 2003a; one prospective controlled trial: Spinal Cord Injury Thromboprophylaxis Investigators 2003b; and two case controls: Arnold et al. 2010; Thumbikat et al. 2002) that Enoxaparin (low molecular weight heparin) is equally as effective as low-dose unfractionated heparin as prophylaxis for deep venous thrombosis in acute SCI.
There is level 3 evidence (from one case control: Worley et al. 2008) that Dalteparin (low molecular weight heparin) is equally as effective as low-dose unfractionated heparin as prophylaxis for venous thromboembolism in acute SCI individuals.