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Table 12.32 Unfractionated Heparin or LMWH versus Placebo for DVT Prevention

Author

Year

Country

Research Design

PEDro

Sample Size

 

Methods

 

Outcome

Phelan et al.

(2012)

USA

Pilot Study-RCT

PEDro=8

N=62

 

Population: TBI; Intervention Group (n=34): Mean Age=40.7 yr; Gender: Male=22, Female=12. Control Group (n=28): Mean Age=42.6 yr; Gender: Male=16, Female=12.

Treatment: The intervention group received enoxaparin (30 mg, 2x/day) within 24-96 hr after injury, whereas the control group received a placebo.

Outcome Measure: Radiographic worsening of TBI, VTE, and extracranial hemorrhagic complications.

1.        1 DVT occurred in the control group; however, no mention of DVT occurrence was made for the intervention group.

2.        No clinical TBI progressions were found.

Hachem et al.

(2018)

Canada

PCT

N=64

Population: TBI; Gender: Male=45, Female=19. Mean Age=44yr; Mean GCS=5.

Intervention: Prospective evaluation of patients who received enoxaparin within 3 days of admission (Early group), after 3 days (Late group), and no enoxaparin (No treatment group). All patients were provided Thombo-Embolic Deterrent stockings. Doppler ultrasounds (DUS) 7 days (+/- 3d) post admission were used to evaluate DVTs, in addition to care and investigations ordered by the treating clinicians.

Outcome Measure: VTE events, intracranial hemorrhage (ICH) progression, DUS

1.        Progression of ICH after initiation of enoxaparin was similar between the early (0%) and late (7%) groups.

2.        VTE incidence was not significantly different between the early (10%) and late (16%) groups (p=0.99).

Seifi et al.

(2018)

USA

Case Control

N=155

 

Population: TBI; Gender: Male=119, Female=36. Mean Age=41.6yr.

Intervention: Retrospective review of patients who received chemical thromboprophylaxis or inferior vena cava (IVC) filter for prevention of VTE. Only patients with clinical suspicion of PE had diagnostic investigations, there was no surveillance for PE.

Outcome Measure: Incidence of PE

 

1.        33 patients did not receive chemical thromboprophylaxis.

2.        60 patients received an IVC filter.

3.        4 patients developed a clinically significant PE. They were all in the group of patients that received chemical thromboprophylaxis. None had an IVC filter prior to developing a PE.

4.        There was no significant difference between incidence of PE between patients that received chemical thromboprophylaxis and those who did not (p=0.58).

Byrne et al.

(2016)

USA

Case Control

N=3634

Population: ABI; Median Age=43 yr; Gender: Male=2798, Female=836; Median Time Post Injury=84 hr; Median GCS=3.

Treatment: Participants were included in retrospective analysis after having received either unfractionated heparin (UFH) or low molecular weight heparin (LMWH) as either early prophylaxis (<72 hr) or late prophylaxis (>72 hr) for VTE.

Outcome Measure: Risk of DVT, PE, late neurosurgical intervention and mortality; abbreviate head injury scale (AIS) and incidence of ischemic (ICH) stroke.

1.        PE occurred in 1.7% of participants, and DVT in 6.5%.

2.        Early prophylaxis was associated with lower odds of PE (OR=0.48) and DVT (OR=0.51) than late prophylaxis.

3.        There was no significant difference in risk of late neurosurgical intervention or death between early and late prophylaxis.

4.        LMWH was associated with lower odds of VTE (OR=0.6) and mortality (OR=0.59) than UFH.

5.        Late prophylaxis group had significantly higher AIS score, ICH incidence, and early neurosurgical intervention rate than early prophylaxis group.

6.        The late group most commonly received LWMH and early group most commonly received UFH.

Daley et al.

(2015)

USA

Case Control

N=271

 

Population: TBI; Intervention Group (n=45): Mean Age=42 yr; Gender: Male=38, Female=7; Mean GCS=10. Control Group (n=226): Mean Age=47 yr; Gender: Male=173, Female=53; Mean GCS=10.

Treatment: Participants were categorized based on exposure (intervention) or lack of exposure (control) to enoxaparin during the acute phase after undergoing an emergency craniotomy, post-TBI.

Outcome Measure: Rate of DVT and PE, days on ventilation (DOV), length of stay (LOS), mortality rate.

1.        No significant differences between groups (intervention and control) were found in terms of rate of DVT (2% vs 3%, p=0.87) and PE (0% vs 1%, p=0.99), as well as LOS and DOV.

2.        The intervention group had a significantly lower rate of mortality in hospital compared to the control group (4% vs 24%, p=0.01).

Kim et al.

(2014)

USA

Case Control

N=75

Population: TBI; Mean Age=44 yr; Gender: Male=59, Female=16; Mean GCS=4.

Treatment: Participants received heparin prophylaxis at early (<3 days, n=22), intermediate (3-5 days, n=34), or late (>5 days, n=19) time intervals post injury.

Outcome Measure: Rate of DVT, PE, and morality, number of ventilator and Intensive care unit (ICU) days, Glasgow Coma Scale (GCS), Abbreviated Injury Scale (AIS), Injury Severity Score , Marshall CT), neurological improvement.

1.        There was no significant difference between groups in mean rates of DVT, PE, or mortality; mean days on ventilator or in ICU; or mean scores on GCS, AIS, or Marshall CT.

2.        There was a significant difference in mean ISS score between the early and intermediate groups (28 vs 35, p=0.02) and between the early and late groups (28 vs 36, p=0.007).

3.        There was a significant difference in cumulative neurological improvement between the early and late groups (p<0.05), with greater improvement the early group.

Lin et al.

(2013)

USA

Case Series

N=3812

Population: TBI, Abbreviated Injury Severity Scale>3.

Treatment: Patient records were reviewed. Participants were grouped based on intervention without the heparin prophylaxis protocol (n=1970) and treatment after the implementation of a heparin prophylaxis protocol (n=1842).

Outcome Measure: Rate of DVT and PE.

1.        Rate of DVT was 0.97% without the protocol and 1.21% with the heparin prophylaxis protocol.

2.        A single patient had PE in each group.

 

Farooqui et al.

(2013)

USA

Case Control

N=236

Population: TBI; Gender: Male=146, Female=90. Group A (n=107): Mean Age=53.3 yr. Group B (n=129): Mean Age=57.4 yr.

Treatment: Group A had no routine administration of chemoprophylaxis and Group B received either Lovenox (30 mg, 2x/day) or Heparin (5000U, 3x/day) 24 hr after stable CT.

Outcome Measure: Rate of DVT and PE.

1.        DVT rate was higher in group A than group B (5.6% vs 0%, p=0.008).

2.        PE rate was 3.74% in group A and 0.78% in group B (p=0.18).

3.        Progression of intracranial hemorrhage did not differ significantly between groups (p=0.33).

Kwiatt et al.

(2012)

USA

Case Control

N=1215

Population: TBI; Gender: Male=836, Female=379. Control Group (n=995): Mean Age=52.9 yr; Mean GCS=11.4. LMWH Group (n=220): Mean Age=46.2 yr; Mean GCS=8.

Treatment: Retrospective comparison of patients who received LMWH for VTE prophylaxis and those who did not.

Outcome Measure: Progression of intracranial hemorrhage.

1.        Patients receiving LMWH were significantly older and had more severe injuries (p<0.001) than those who did not.

2.        LMWH compared to the control had greater hemorrhage progression (42% vs 24%, p<0.001).

3.        For those receiving LMWH, when it was initiated did not impact the rate of hemorrhage progression.

4.        The LMWH compared to the control group had a greater number of VTE episodes (9.1% vs 3.1%, p<0.001).

Praeger et al.

(2012)

Australia

Observational

N=36

 

Population: TBI; Mean age=40.3 yr; Gender: Male=28, Female=8; Mean GCS=8.

Treatment: Thromboprophylaxis included compression stockings and compression devices, and/or LMWH.

Outcome Measure: Rate of DVT and PE assessed with compression ultrasound.

1.        The rate of DVT was 6%, PE was 6%, and total VTE was 11%.

2.        Among individuals with severe TBI the rates of DVT, PE, and total VTE were 10%, 10% and 19%, respectively.

Minshall et al.

(2011)

USA

Case Series

N=386

Population: TBI; Gender: Male=293, Female=93.

Treatment: Chart review of patients receiving LMWH (30 mg, 2x/day; n=158), unfractionated heparin (UFH; 5000 IU 3x/day; n=171) or sequential compression devices alone (n=57).

Outcome Measure: Rate of DVT, PE, and intracranial hemorrhage complications.

1.        Mortality in the sequential compression devices alone group was higher (47%) compared to the LMWH (5%) and UFH (16%) groups.

2.        Those in the UFH group had a significantly higher rate of DVT and PE than those in the LMWH group (p<0.05).

3.        5% of those in the LMWH group and 12% in the UFH group had progression of their intracranial hemorrhage, compared to 25% in the untreated group.

Koehler et al.

(2011)

USA

Cohort

N=669

 

Population: TBI; Gender: Male=487, Female=182. Early Group (n=268): Mean Age=39.8 yr. Late Group (n=401): Mean Age=40.2 yr.

Treatment: Enoxaparin (30 mg 2x/day) was administered to all patients. The early group received the VTE prophylaxis within 0-72 hr and the late group at 73 hr or later.

Outcome Measure: Incidence of DVT and PE.

1.        Those in the early group compared to the late group spent significantly fewer days on a ventilator (p<0.001), fewer days in ICU (p<0.002) and hospital (p<0.004).

2.        Intracranial hemorrhage progression for the early vs late groups was 9.38% vs 17.41% (p<0.001) before prophylaxis and 1.46% vs 1.54% after (p=0.912).

3.        The proportion of DVTs and PEs were not significantly different (p=0.117 and p=0.49, respectively).

Scudday et al.

(2011)

USA

Case Series

N=812

Population: TBI; Gender: Male=560, Female=252. Intervention Group (n=402): Mean Age=45.2 yr. Control Group (n=410): Mean Age=51.5 yr.

Treatment: Retrospective review comparing patients that received chemical thromboprophylaxis (91% Heparin, 9% Enoxaparin) to an untreated control group.

Outcome Measure: Incidence of VTE.

1.        A lower incidence of VTE was found in the treated group compared to the untreated group (1% vs 3%, p=0.019).

Salottolo et al.

(2011)

USA

Case Series

N=480

 

Population: TBI; Mean Age=53 yr; Gender: Male=296, Female=184; Mean GCS=12.2.

Treatment: Retrospective review of patients considered for thrombus prophylaxis (lovenox 30 mg 2x/day or heparin 5000 U, 2x/day), timing of administration, and whether or not the intervention was interrupted.

Outcome Measure: Development of VTE or DVT.

1.        53.1% of patients received pharmacological thromboprophylaxis (PTP); median time to start was 3d and it was continuous in 73.7%.

2.        Medications began <72 hr post injury in 108 patients and >72 hr post injury in 147.

3.        The no PTP group had 4 DVTs and 2 PEs compared to the PTP group which had 8 DVTs and 3 PEs.

4.        Neither the administration of these medications (p=0.29) or the timing of administration (p=0.26) had any effect on the development of VTE.

Norwood et al.

(2008)

USA

Case Series

N=525

 

Population: TBI; Mean Age=39.6 yr; Gender: Male=387, Female=138; Abbreviated Injury Scale ≥2; Mean Time Post-Injury=36.2 hr.

Treatment: Patients were given Enoxaparin sodium (30 mg, 2x/day).

Outcome Measure: Incidence of DVT and PE, mortality rates.

1.        4.0% of patients died.

2.        Of 151 patients that underwent a lower extremity venous Doppler ultrasound, 6 patients were diagnosed with a DVT.

3.        No patients within the study group were diagnosed with a PE.

Kurtoglu et al.

(2004)

Turkey

PCT

N=120

Population: TBI=103, Other=17; Median Age=37.1yr; Gender: Male=47, Female=73.

Intervention: Patients admitted to the Intensive Care Unit (ICU) were allocated to receive either Intermittent Pneumatic Compression devices (IPC; n=60) placed below the knee or Low-Molecular-Weight Heparin (LMWH) (n=60) (40 mg/day, enoxaparin sodium) for VTE prophylaxis.

Outcome Measure: Rate of DVT, PE and mortality.

1.        In the IPC group, there were 4 (6.6%) and 2 (3.3%) cases of DVT and PE, respectively.

2.        In the LMWH group, there were 3 (5%) and 4 (6.6%) cases of DVT and PE, respectively.

3.        Overall, 7 (11.6%) and 8 (13.3%) patients died in the IPC and the LMWH group, respectively.

4.        There were no significant differences between groups in rates of DVT (p=0.04), PE (p=0.07), or mortality (p=0.08).

Kleindienst et al.

(2003)

USA

Case Series

N=940

 

Population: Head Injury=344, Elective Surgery (tumors)=294, Intracranial Hemorrhage (ICH)=302; Mean Age=57.3 yr.

Treatment: A retrospective review of patients either receiving 18 mg/d of Certoparin-sodium (3000 U anti-factor Xa) for prophylaxis on the evening prior to elective neurosurgery (ES) and within 24 hr after surgery, or admission whenever a CT showed an absence of a progressive haematoma.

Outcome Measure: Incidence of bleeding complications, VTE events, and morbidity/mortality rates.

1.        155 patients were excluded due to coagulation abnormalities or significant bleeding.

2.        Intracranial bleeding was found in 1.5% of the total sample.

3.        The incidence of VTE and PE was 0.2% and 0.1% of patients respectively, with no associated mortality.

4.        No heparin induced thrombocytopenia was observed.

Norwood et al.

(2002)

USA

Pre-Post

N=150

 

Population: Traumatic Intracranial Hemorrhagic injuries (IHI); Mean Age=39.5 yr; Mean GCS=10.

Treatment: Patients received Enaxoparin-sodium (30 mg, 2x/day) beginning 24 hr after initial evaluation.

Outcome Measure: Incidence of DVT or PE, Progression of IHI, mortality, Glasgow Outcome Scale (GOS).

1.        At discharge (n=106), 2% of patients had a DVT and no PE

2.        23% of patients had CT progression of IHI pre-treatment. Rate of progression of IHI significantly decreased after initiation of the intervention (p=0.002).

3.        Study group mortality was 7%.

4.        On the GOS, the majority (76%) of patients showed good recovery.

Kim et al.

(2002)

USA

Cohort

N=64

Population: ABI; Gender: Male=49, Female=15. Early Group (n=47): Mean Age=37.7 yr; Mean GCS=9.1. Late Group (n=17): Mean Age=44 yr; Mean GCS=9.4.

Treatment: Retrospective review of patients who received unfractionated heparin (UFH) within 72 hr of admission (Early Group) and those who received it after the third day (Late Group).

Outcome Measure: VTE events, bleeding complications.

1.     There was no increase in intracranial bleeding or deterioration on neurological examination due to UFH administration.

2.     There was no statistical difference in VTE events between groups.