Key Points

Deep venous thrombosis is common in spinal cord injured patients not receiving
prophylaxis.

5,000 units subcutaneously every 12 hours of unfractionated heparin does not appear
to prevent venous thrombosis post SCI while higher adjusted doses are more
effective.

Low molecular weight heparin reduces the risk of venous thromboembolism post SCI
more effectively than standard or unfractionated heparin prophylaxis with fewer
bleeding complications.

There appears to be no difference between Enoxaparin and Dalteparin in reducing the

risk of venous thrombosis post SCI.

Mechanical compression may reduce the incidence of venous thromboembolism post

SCI.

The use of rotating treatment tables reduces the incidence of venous thrombo-
embolism post SCI.

A combined regimen of pneumatic compression, pressure stockings and low-dose

heparin given prophylactically may reduce the incidence of venous thrombosis and
the effect is better in early post SCI.

Inferior vena cava filters significantly reduce the risk of pulmonary emboli in high-risk
SCI patients.

Enoxaparin subcutaneously can be considered as an alternative to intravenous

Heparin for acute DVTs post SCI although more research needs to be done.
 Table of Contents
1.0 Introduction ............................................................................................................. 1
2.0 Incidence of Venous Thromboembolism Post SCI............................................... 1
3.0 Diagnosis of Venous Thromboembolism Post SCI .............................................. 2
3.1 Deep Venous Thrombosis ................................................................................................ 2
3.1.1 Clinical Presentation of DVT ...................................................................................... 2
3.1.2 Venous Ultrasound .................................................................................................... 2
3.1.3 Venography ............................................................................................................... 3
3.1.4 D-Dimer Assay .......................................................................................................... 3
3.1.5 Diagnosis of DVT ...................................................................................................... 3
3.2 Pulmonary Embolism ....................................................................................................... 4
3.2.1 Clinical Presentation of Pulmonary Embolus ............................................................. 4
3.2.2 Ventilation/Perfusion (V/Q) Scanning......................................................................... 4
3.2.3 Pulmonary Angiography ............................................................................................ 4
3.2.4 Spiral CT Scan .......................................................................................................... 5
3.2.5 Right Bundle Branch Block ........................................................................................ 5
4.0 Prophylaxis of Venous Thromboembolism Post SCI ........................................... 5
4.1 Pharmacological Agents for DVT Prophylaxis .................................................................. 5
4.1.1 Unfractionated Heparin as Prophylaxis for Venous Thromboembolism Post SCI ....... 5
4.1.2 Low Molecular Weight Heparin (LMWH) as Prophylaxis Post SCI ............................. 8
4.1.3 LMWH vs. UFH as Prophylaxis for Venous Thromboembolism Post SCI .................. 8
4.1.5 LMWH as a Prophylaxis of Venous Thrombosis .......................................................12
5.0 Prevention of DVT through Mechanical Methods ............................................... 15
6.0 Vena Cava Filtration .............................................................................................. 20
7.0 Treatment of Acute Venous Thromboembolism in SCI ..................................... 24
8.0 Summary ................................................................................................................ 25

This review has been prepared based on the scientific and professional information available in 2009. The SCIRE
information (print, CD or web site www.scireproject.com) is provided for informational and educational purposes only.
If you have or suspect you have a health problem, you should consult your health care provider. The SCIRE editors,
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from the use or misuse of this material.

Teasell RW, Mehta S, Loh E, Hsieh JTC, Janzen S, Eng JJ, Krassioukov A (2012). Venous Thromboembolism
Following Spinal Cord Injury. In Eng JJ, Teasell RW, Miller WC, Wolfe DL, Townson AF, Hsieh JTC, Connolly SJ,
Mehta S, Boily K, editors. Spinal Cord Injury Rehabilitation Evidence. Version 4.0.

www.scireproject.com
 Venous Thromboembolism
Following Spinal Cord Injury
1.0 Introduction
Deep venous thrombosis (DVT) and subsequent pulmonary embolism (PE) remain a significant
cause of morbidity and mortality in spinal cord injured (SCI) patient. The incidence of DVT has
been reported by various authors to range between 9% to 100% during the acute stage of SCI,
with most occurring in the first 2 weeks post-injury, sometimes leading to a pulmonary embolism
which remains a common cause of death (Tribe 1963; Walsh & Tribe 1965; Watson 1968;
Stover et al. 1983; Winchelli et al. 1996; Aito et al. 2000; Chiou-Tan et al. 2003).

2.0 Incidence of Venous Thromboembolism Post SCI

The incidence of DVT in patients with acute SCI has been reported to be very high, more than
50% in early prospective studies (Joffe 1975; Todd et al. 1976; Brach et al. 1977; Rossi et al.
1980; Becker et al. 1987) with the incidence of fatal PE estimated to be as high as 2% in
paraplegics (Joffe 1975). The prevalence of DVT in acute SCI has been found to range from
14% to 100% (Chiou-Tan et al. 2003) or 9% to 90% (Aito et al. 2000). Chiou-Tan et al. (2003)
have noted that this has been examined in depth in the literature.

Table 1 Incidence of DVT Post SCI

Author/Year Treatment (n size) % of DVTs Test
Serial color duplex
Germing et al.(2010) 139 45.3%
sonography
Sugimoto et al. 2009 45 21% Doppler Ultrasonography
Colachis & Clinchot Contrast venography
Prophylaxis Treatment (n=209) 14%
(1993) Ultrasound
Low-dose Heparin
Gunduz et al. (1993) 53% Venography
(n= 31)
Prophylactic anticoagulant therapy
Yelink et al. (1991) 23% Venography
(n=147)
125
I fibrinogen scan
Impedance
Merli et al. (1988) Untreated group 47%
Plethysmography
Venography
125
I fibrinogen scan
Myllynen et al. (1985) Anticoagulant therapy (n=37) 100% of SCI pts
Venography
External pneumatic calf
78% untreated pts Platelet aggregation
Green et al. (1982) compression (ENCP) or ENCP +
33% treated pts studies
aspirin + dipyrid (n=28)
125
Rossi et al. (1980) N/A (n=18) 72% I fibrinogen scan

More recent and widespread reports, according to Aito et al. (2000), place the incidence of
DVTs at between 10-30% (Yelnick et al. 1991; Kulkarni et al. 1992; Colachis & Clinchot 1993;
Powell et al. 1999; Winemiller 1999). No significant difference was noted in the incidence of
DVT based on AIS scores (p=0.58, Sugimoto et al. 2009).

The high risk of DVT in acute SCI patients is due to the simultaneous presence of the 3 factors
of Virchows triad: hypercoagulability, stasis and intimal (inner vessel layer) injury (Aito et al.
2000). Venous thromboembolism usually begins with a calf DVT (Nicolaides et al. 1971;
Philbrick et al. 1988; Cogo et al. 1998). 20% of DVTs extend into the proximal veins (Kakkar et
al. 1969; Lagestedt et al. 1985; Brandstater et al. 1992) and, over 80% of symptomatic DVTs
involve the popliteal or more proximal veins (Kearon et al. 1998). Non-extending distal (i.e. calf)

15-1
DVTs rarely cause PEs and as such are rarely worrisome (Kakkar et al. 1969) although they
may account for over 80% of the incidence of DVT (Germing et al. 2010). Proximal (i.e. knee or
above) DVTs often lead to PEs and are a cause for concern (Kakkar et al. 1969).

Pulmonary emboli (PE) are not uncommon post SCI and most are asymptomatic or
unrecognized. Symptomatic PEs are large If large PEs are fatal, they are fatal within the first
few minutes.

Conclusions
Deep venous thrombosis is common in SCI patients not receiving prophylactic
treatment.

Deep venous thrombosis is common in spinal cord injured patients not receiving
prophylaxis.

3.0 Diagnosis of Venous Thromboembolism Post SCI

3.1 Deep Venous Thrombosis
3.1.1 Clinical Presentation of DVT
The signs and symptoms of DVT are varied and depend on the severity. Generally DVTs can
cause pain, swelling, tenderness, skin discolouration and increased warmth of the affected area.
The signs and symptoms of PE are nonspecific and can include: sudden chest pain, shortness
of breath, difficulty breathing, or rapid breathing, coughing up blood, and loss of consciousness
(fainting), which often leads to difficulties with diagnosis. Several methods and techniques are
currently used for diagnosis.

Although the various methods of DVT detection will be discussed, it is important for health care
professionals, patients, family members and caregivers to be educated in the early signs and
symptoms. Expert consensus, as noted by the PVA Consortium of Spinal Cord Medicine (2005)
guideline for the prevention of thromboembolism, suggests that all extremities should be
inspected twice daily for an increase in the calf or thigh venous pattern or circumference, low-
grade fever of unknown origin or pain/tenderness/heaviness of an affected extremity. Since
patients can sometimes be asymptomatic, it is also suggested that health care providers,
including family and caregivers, be familiarized with risk factors such as lower limb fractures,
dehydration, obesity, age, malignancy, congestive heart failure, estrogen therapy, pregnancy,
and a history of thrombosis.

Another measure, considered by expert consensus to be important and preventative, is the

routine practice of active and passive range-of-motion exercises. Mobilization and movement of
the extremities (with careful consideration of spinal stability in the acute phase) should be
essential to the prevention of DVT in SCI.

3.1.2 Venous Ultrasound

Venous ultrasound is often used to diagnose a DVT. Furlan and Fehlings (2007) note that it has
become the primary noninvasive diagnostic test for DVT. According to Furlan and Fehlings
(2007), Kadyan et al. (2004) reported that duplex ultrasound is a cost-effective tool for
surveillance in individuals with acute SCI who are admitted to rehabilitation centers (30). The

15-2
same authors note that ultrasound is well recognized as an important tool in the initial workup of
clinically suspected DVT. However, concern exists for ultrasound as a screening tool of
asymptomatic DVTs because of relatively low sensitivities in other populations (Furlan &
Fehlings 2007).

3.1.3 Venography
Venography is an invasive study whereby contrast dye is injected into the leg veins and is
considered a definitive test for DVT. Diagnosis of DVT is made if an intraluminal-filling defect is
noted. Furlan and Fehlings (2007) note that, Although contrast venography is considered as
the gold standard for investigation of symptomatic or asymptomatic DVT, venography has been
considered an unsuitable tool for routine assessment of asymptomatic DVT due to its invasive
nature, potential complications, technical issues and costs (Kelly et al. 2001, Tapson et al. 1999,
Zierler 2004).

3.1.4 D-Dimer Assay

D-dimer assay tests are rapid, noninvasive and inexpensive (Gill & Nahum 2000). Fibrin is the
main component of thrombus formation and fibrin degradation products include d-dimers (Gill &
Nahum 2000). A positive d-dimer test is highly sensitive but lacks specificity since d-dimers are
found in other disease states, including cancer, congestive heart failure and inflammatory
conditions (Raimondi et al. 1993). D-dimer assays have a high negative predictive value, which
means when it is negative it is unlikely that the patient has a DVT. However, it has poor positive
predictive value so that when it is positive the cause could be a condition other than DVT (i.e.
false positive). To illustrate, Akman et al. (2004) reported that the sensitivity and negative
predictive values of the D-dimer test were high, at 95.2% and 96.2% respectively, in a group of
68 rehabilitating patients admitted with a diagnosis of stroke, spinal cord injury, hip arthroplasty
or traumatic brain injury. The specificity and positive predictive value were low, at 55.3% and
48.7%. Therefore, the d-dimer test appears to be a useful test for ruling out venous
thromboembolism although a positive test is not diagnostic and must be confirmed with other
testing.

3.1.5 Diagnosis of DVT

A positive diagnosis of a DVT can only be made if the venogram is positive or there is a positive
venous ultrasound at two or more sites of the proximal veins. A negative diagnosis for DVT can
be made if there is a negative venogram, a negative d-dimer test or a normal venous
ultrasound. A normal venous ultrasound requires one of the following findings to be considered
negative: 1) low clinical suspicion for DVT, 2) normal d-dimer test, or 3) normal serial testing
with the test interval being no greater than 1 week. Furlan and Fehlings (2007) in their review
noted that, there is insufficient evidence to support (or refute) a recommendation for routine
screening for DVT in adults with acute traumatic SCI under thromboprophylaxis. The same
authors note that, The screening test of choice for asymptomatic DVT needs to be determined.
A systematic review on noninvasive diagnosis of DVT from the McMaster Diagnosis of Deep
Venous Thrombosis Working Group indicated that: 1)venography is the only reliable test for the
diagnosis of asymptomatic DVT; 2) the role of surveillance testing with ultrasound in
asymptomatic patients at high risk of DVT is uncertain; and 3) surveillance testing with
impedance plethysmography is not recommended (Kearon et al. 1998).

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3.2 Pulmonary Embolism
3.2.1 Clinical Presentation of Pulmonary Embolus
The clinical diagnosis of pulmonary emboli is unreliable, being both insensitive and nonspecific.
Many cases are clinically silent with only 30% having the clinical features of a DVT and only
70% demonstrating a DVT on venography. Patients with a massive pulmonary embolus who
suffer compromise of more than 60% of the pulmonary circulation are considered critically ill.
Right heart failure may progress to cardiovascular collapse with hypertension, coma and death.
A submassive pulmonary embolus presents with tachycardia, tachypnea and signs of
pulmonary infarction with consolidation, rales, hemoptysis, pleuritic chest pain, pleural friction
rub, pleural effusion and fever. In most cases there are usually only a few clinical findings and
the presentation may be nonspecific with the major clinical complaints of malaise and fever.

3.2.2 Ventilation/Perfusion (V/Q) Scanning

Nuclear ventilation/perfusion scans are often used to diagnose a PE. A normal perfusion scan
usually excludes a PE but can be found in a minority of patients with a PE. Perfusion defects
are non-specific; about a third of those with defects actually have a PE. The probability that a
perfusion defect is a PE increases with the size, shape and number of defects as well as the
presence of a normal ventilation scan. Mismatched perfusion defects (normal ventilation scan),
which are segmental in size or larger are high probability defects and are associated with an
approximately 80% prevalence of PE. Three or more mismatched defects are associated with a
prevalence of approximately 90%. If a patient has a positive V/Q scan and high clinical
suspicion of a PE then they should be treated.

Table 2 Probability of Pulmonary Embolism Based on Ventilation-perfusion Scan Results

and Clinical Suspicion in Prospective Investigation of Pulmonary Embolism Diagnosis
Study (PIOPED) Study
Clinical suspicion of pulmonary embolism*
Ventilation-perfusion scan results
Low Intermediate High
High probability 56% 88% 96%
Intermediate probability 16% 28% 66%
Low probability 4% 16% 40%
Normal/near-normal probability 2% 6% 0%
* Percentage of patients with pulmonary embolism
Adapted from the PIOPED Investigators (Gill & Nahum 2000, PIOPED Investigators 1990).

PIOPED (prospective investigation of pulmonary embolism diagnosis) demonstrated that a low-

probability or normal ventilation-perfusion scan with a low clinical suspicion of pulmonary
embolism essentially excludes the diagnosis of pulmonary embolism (negative predictive values
of 96% and 98% respectively) (Gill & Nahum 2000; PIOPED Investigators 1990). When clinical
suspicion is high and the scan indicates a high probability of pulmonary embolism, the positive
predictive value is 96% (Gill & Nahum 2000; PIOPED Investigators 1990).

3.2.3 Pulmonary Angiography

Pulmonary angiography is the definitive diagnosis for pulmonary embolism (Gill & Nahum 2000).
It involves percutaneous catheterization and injection of contrast dye into a pulmonary artery
branch (Gill & Nahum 2000). It is used when the V/Q scan is nondiagnostic but the clinical
suspicion remains high. It is an expensive test and is associated with a significant risk of
complications. Relative contraindications include significant bleeding risk, allergy to contrast
medium, and renal insufficiency (Gill & Nahum 2000). It is associated with a mortality rate of up
to 0.5% (Newman 1989; Stein et al. 1992). Pulmonary angiography is most commonly used

15-4
when ventilation-perfusion scanning is nondiagnostic but clinical suspicion remains high
(Tapson et al. 1999). A negative pulmonary angiogram excludes clinically relevant pulmonary
embolism (Tapson et al. 1999; Gill & Nahum 2000).

3.2.4 Spiral CT Scan

A spiral CT scan is a quick, less expensive CT scan which can scan the entire thorax in one
breath-hold. It has a sensitivity ranging from 64-93% with a specificity of 89-100% - it is most
accurate when the embolism is large and less accurate when the clot is small. It actually
visualizes the clot and has the added benefit of diagnosing other disease states in the
differential diagnosis. The majority of ventilation perfusion scans have nondiagnostic results,
requiring further testing (PIOPED Investigators 1990), and spiral CT is a useful additional test in
this regard.

3.2.5 Right Bundle Branch Block

The electrocardiogram (ECG) abnormality of RBBB has been used to screen for PE. Only one
study examined its use in diagnosing PE post SCI (Frisbie & Sharma, 2009); however, its use in
able-bodied individuals indicates there is a high specificity for the diagnosis of PE (Nielsen et al
1989; Punukollu et al. 2005). It is an intriguing diagnostic finding thattends to be associated
with pulmonary hypertension secondary to PE and may provide additional information which
could assist with the diagnosis of a PE.

4.0 Prophylaxis of Venous Thromboembolism Post SCI

Anticoagulants can prevent thrombi from forming in the deep veins of the leg. Thrombosis in
the deep veins (DVTs) can break off and travel to the lungs, resulting in a pulmonary embolism
(PE) the most clinically important consequence of DVT. However, anticoagulants can lead to
serious complications such as intracerebral hemorrhaging.

The consortium for spinal cord medicine published clinical practice guidelines for the prevention
of thromboembolism in SCI (1999). They recommended 5,000 units of unfractionated heparin
for motor-incomplete patients for 8 weeks and either heparin adjusted to high normal activated
partial thromboplastin time or low molecular weight heparin for motor-complete patients for 8-12
weeks. Chiou-Tan et al. (2003) note that this recommendation is based on studies that showed
that the risk of thromboembolism in SCI increases rapidly after injury and is maximal between
days 7 and 10 (Green et al. 1982; Merli et al. 1988; Geerts et al. 1994).

4.1 Pharmacological Agents for DVT Prophylaxis

4.1.1 Unfractionated Heparin as Prophylaxis for Venous Thromboembolism Post SCI
Heparin acts as an anticoagulant by forming a complex with antithrombin, catalysing the
inhibition of several activated blood coagulation factors: XIIa, XIa, IXa, Xa and thrombin.
Heparins onset of action is immediate. It is most often used in acute conditions, and must be
given parenterally. Although low molecular weight heparin has become more popular in the
treatment of DVT, the effects of intravenous heparin can be reversed rapidly. Bleeding is the
most common adverse effect of heparin. Osteoporosis is associated with the prolonged use of
high doses of heparin, although its occurrence is infrequent. Thrombocytopenia is an
uncommon but serious side-effect of the treatment (Pineo & Hull 2004).

15-5
Table 3 Efficacy of Unfractionated Heparin vs. Placebo as Prophylaxis
Author Year
Country
Score Methods Outcomes
Research Design
Sample Size
Population: SCI; Mean age: 32yrs; 1. Three cases (1.8%) in the study group
Agarwal & Mathur.
M/F:74%/26% and four control cases (3%) developed
2009
Treatment: Patients were randomly DVT (p>0.05).
India
allocated into the treatment group receiving 2. Factors that are significantly correlated
PEDro=4
5000 IU of unfractionated low-dose heparin with incidence of DVT are fever
RCTs
or the control group. (p<0.05) and increase in calf girth
N= 385
Outcome Measures: Incidence of DVT (p<0.001) .
Population: SCI. 1. Electric stimulation plus heparin
Merli et al. 1988 Treatment: Administration of low-dose significantly lowered (p<0.05) the
USA heparin combined electric stimulation. incidence of DVT.
PEDro=4 Outcome Measures: Incidence of DVT. 2. No differences were noted between
RCT the heparin and placebo group.
Initial N=53; Final N=48 3. Pooled data (heparin and placebo
group) and comparing it to the
heparin plus electric stimulation
group, level of significance was much
greater (p<0.008).
Population: Mean age = 27 yrs 1. Venous thrombosis was
(treatment), 28 yrs (control); Level of unexpectedly uncommon in both the
Frisbie & Sasahara 1981 injury: cervical-lumbar; paraplegic = 8, control (1/17) and the heparinised
USA tetraplegic = 24. (1/15) group.
Downs & Black score=10 Treatment: Patients in the heparin
Prospective Controlled group were treated with 5000 units
Trial aqueous sodium heparin
N=32 subcutaneously every 12h until the 60th
day post injury occurred.
Outcome Measures: Incidence of DVT.

Table 4 Fixed vs. Adjusted Dose Heparin in Prophylaxis of Thromboembolism in SCI

Author Year;
Country
Score Methods Outcomes
Research Design
Sample Size
Population: Age = 13-81 yrs; Gender: 1. Patients on the adjusted-dose
males = 63, females = 12; Severity of regimen received a mean of
injury: complete = 75. 132002200U of heparin per dose
Treatment: Patients were randomized and had a APTT 1 and 1/2 times
to one of 2 regimens of heparin higher than those on a fixed-dose
treatment: fixed dose or adjusted dose regimen.
Green et al. 1988
heparin. 2. Thromboembolism was detected in
USA
Outcome Measures: Incidence of DVT 9/29 patients randomized to the
PEDro=7
and bleeding. fixed-dose regimen and 2/29 on the
RCT
adjusted-dose regimen.
Initial N=75; Final N=58
3. While no patient who received the
adjusted-dose and whose APTT
reached the target level had a
thrombosis, bleeding occurred in 7
patients. No patient on the fixed-dose
regimen bled.
Note: APTT=Activated Partial Thomboplastin Time

15-6
Discussion
Unfractionated heparin (UFH) has been the standard treatment for venous thromboembolism
post SCI for years. Evidence for its effectiveness, however, is unclear. Agarwal & Mathur
(2009) randomly divided patients into a treatment and control group. The treatment group
received 5000IU of unfractionated low-dose heparin (ULDH) subcutaneously 2 times a day from
admission to 3 months post injury; while the control group received no treatment. The study
found no significant difference between the control group and treatment group in incidence of
DVT (3% vs. 1.8%). Merli et al. (1988) evaluated 53 acute SCI patients who were randomly
assigned to placebo saline (n=17), 5000 IU heparin (n=16) and heparin plus electrical
stimulation of the tibialis anterior and gastrocnemius muscles (n=15) over 28 days. There was
no difference between the placebo saline and heparin groups in the incidence of DVT while
there was a significant improvement in the heparin and electrical stimulation group. The study
was prematurely discontinued because of the benefit of the heparin plus electrical stimulation
group and lack of efficacy in the control group. Frisbie and Sasahara (1981) in a controlled, non-
randomized trial of 32 SCI patients saw half the patients receive no treatment and the other
group receive 5,000 units s/c q12h until day 60 post SCI onset. Venous thrombosis was
unexpectedly uncommon in both the control (1/17) and the heparinized group (1/15). Green et
al. (1988) studied 75 SCI patients who were randomized to receive either fixed dose or adjusted
dose heparin. The fixed dose heparin was 5,000 units s/c q12h while the second group started
off at 5,000 units s/c q12h which was adjusted according to the aPTT (activated Partial
Thromboplastin Time) to a maximum of 15,000 units s/c q12h. Patients on the adjusted-dose
regimen received a mean of 13,200 units s/c q12h. Thromboembolism was detected in 9/29 on
fixed dose regimen with no bleeding complications while 2/29 on the adjusted-dose regimen
developed thromboembolism and 7 had bleeding complications.

Typically prophylactic treatment involves 5,000 units s/c of heparin. One RCT and one
controlled study examining the efficacy of this dose and a placebo found no difference in the
incidence of venous thrombosis in both the treatment and the placebo groups. Interestingly,
Merli et al. (1988) found that heparin plus electrical muscle stimulation significantly reduced the
incidence of venous thrombosis when compared to heparin alone. Green et al. (1988)
compared 5,000 units s/c of heparin q12h with an adjusted dose of heparin according to the
APTT (mean dose of 13,000 units s/c q12h) and the adjusted dose significantly reduced the
incidence of venous thrombosis. Hence, although it appears that 5,000 units s/c of heparin
q12h was not an effective dose in reducing the incidence of thromboembolism, higher doses
were more effective but had a higher risk of bleeding complications. Further research is needed
before a definitive statement can be made.

Conclusions
There is level 2 evidence (based on two low quality RCT and one non-randomized
controlled trial) that 5,000 units s/c of unfractionated heparin is no more effective than
placebo in the prophylaxis of venous thrombosis post SCI.

There is level 1b evidence (based on one RCT) that adjusted (higher) dose s/c heparin is
more effective in prophylaxis of venous thromboembolism than 5,000 s/c heparin q12h
but has a higher incidence of bleeding complications.

15-7
 5,000 units subcutaneously every 12 hours of unfractionated heparin does not prevent
venous thrombosis post SCI while higher dose, adjusted anticoagulation is more effective,
although risk of bleeding complications is higher.

4.1.2 Low Molecular Weight Heparin (LMWH) as Prophylaxis Post SCI

Low-molecular-weight heparin (LMWH) is derived from standard heparin through either
chemical or enzymatic depolymerization. Whereas standard heparin has a molecular weight of
5,000 to 30,000 Daltons, LMWH ranges from 1,000 to 10,000 Daltons. LMWH binds less
strongly to protein, has enhanced bioavailability, interacts less with platelets and yields a very
predictable dose response. The clinical advantages of LMWH include predictability, dose-
dependent plasma levels, a long half-life and less bleeding for a given antithrombotic effect.
Thrombocytopenia is not associated with short-term use of low-molecular-weight heparin.
LMWH is administered once or twice daily, both during the high-risk period when prophylaxis for
DVT is recommended and also while waiting for oral anticoagulation to take effect in the
treatment of DVT. The activated partial thromboplastin time (aPTT) does not need to be
monitored, and the dosedoes not need to be adjusted (Rydberg et al. 1999).

Danaparoid sodium (Orgaran) is an alternative anticoagulant for patients who develop heparin-
induced thrombocytopenia from heparin therapy. Danaparoid is a low molecular weight
heparinoid. Its active components consist of heparan sulfate, dermatan sulfate and chondroitin
sulfate. The major difference between danaparoid and other low molecular weight heparins
(LMWH) is that danaparoid is devoid of heparin or heparin fragments. However, it exerts effects
similarly to other LMWHs. Danaparoid acts by inactivating thrombin.

Table 5 Generic and Trade-names of Low Molecular Weight Heparin

Generic Name Trade-name
Dalteparin Fragmin
Danaparoid Orgaran
Enoxaparin Lovenox
Ardeparin Normiflo
Parnaparin, Reviparin Clivarine
Tinzaparin Logiparin, Innohep
Certoporain Alphaparin, Sandoparin

4.1.3 LMWH vs. UFH as Prophylaxis for Venous Thromboembolism Post SCI
The most commonly studied LMWH for the prophylaxis of venous thromboembolism post SCI is
enoxaparin. Enoxaparin was the first LMWH in the United States. Enoxaparin has a plasma
half-life of 4.4 hours compared with 0.35 hours for UFH and its subcutaneous bioavailability is
50%, compared to 20% for UFH (Tomaio et al. 1998). In a meta-analysis, Paciaroni et al.
(2008) compared the effectiveness of low dose unfractionated heparin to that of LMWH in
reducing DVT incidence in individuals post SCI. The study found no significant reduction in DVT
between the UFH group and the control group and the UFH group and the LMWH group.
However, LMWH was reported to significantly reduce the rate of PE (p=0.04).

15-8
Table 6 LMWH vs. Unfractionated Heparin as Prophylaxis
Author Year
Country
Score Methods
Research Design
Sample Size
Population: Gender: males = 389,
females = 87; Severity of injury: AIS A-
Spinal Cord Injury D; Chronicity = acute; Cause of injury
Thromboprophylaxis = trauma.
Investigators Treatment: Enrolled patients were
2003a assigned to receive
USA thromboprophylaxis with either the
PEDro=9 combination of low-dose UFH (5000 U
RCT subcutaneously every 8 h) plus
Initial N=476; intermittent pneumatic compression
Final N=107 (IPC) (to be used at least 22h/day) or
enoxaparin (30 mg subcutaneously
every 12 h).
Outcome Measures: DVT, PE, major
bleeding.
Green et al. 1990 Population: Mean age = 28 yrs;
USA Gender: males = 34, females = 7;
PEDro=8 Severity of injury: complete = 41.
RCT Treatment: Patients were assigned to
Initial N=41; Final N=32 receive either UFH LMWH
(5000uts/8hrs or 3500 anti-Xa
uts/daily).
Outcome Measures: Documentation
of thromboembolism.
Population: UFH group (n=60): Mean
age = 34 yrs; Gender: males = 47,
females = 13; Level of injury:
paraplegic = 18, tetraplegic = 32; EP
group (n=59): Mean age = 30.5 yrs;
Spinal Cord Injury Gender: males = 53, females = 634;
Thromboprophylaxis Level of injury: paraplegic = 15,
Investigators 2003b tetraplegic = 34.
USA Intervention: Continuation of above
Downs & Black score=21 2003 study. Patients previously
Case Cohort receiving low-dose UFH (5000 U
Initial N=172; Final N=119 subcutaneously every 8 h) continued
on this regimen. Those previously on
the enoxaparin had an increase in
doasage to 40mg.
Outcome Measures: DVT, PE, major
bleeding.
Population: Age: 10-60 yrs; SCI;
Severity of injury:
complete/incomplete; Chronicity =
acute; Cause of injury = trauma.
Intervention: 101 received a
Thumbikat et al. 2002
combination of heparin followed by
UK
warfarin and mechanical treatments for
Downs & Black score=19
thromboprophylaxis. 72 received
Case Control
enoxaparin as a thromboprophylactic
N=173
agent, started on the day of admission.
Outcome Measure: Documentation of
DVT, PE, Complication and duration of
anticoagulation, results of Doppler
studies, V/Q scans and unexplained
15-9
Outcomes
1. Among 107 assessable patients, the
incidence of venous
thromboembolism was 63.3% with
UFH-IPC versus 65.5% with
enoxaparin (p=0.81).
2. The incidence of pulmonary
embolism was 18.4% with UFH-IPC
versus 5.2% with enoxaparin
(p=0.03).
3. Among all randomized patients, the
incidence of major bleeding was
5.3% with UFH-IPC versus 2.6% with
enoxaparin (p=0.14).
1. The cumulative event rate was
34.7% (95% CI, 13.7%-55.2%).
None of the patients treated with
LMWH had thrombosis or bleeding
(95% CI, 0%-14%).
2. The difference between the 2 groups
was significant (p=0.006, log-rank
test)
1. New VTE was demonstrated in 13 of
60 UFH versus 5 of 59 enoxaparin
patients (21.7% vs. 8.5%; p = 0.052).
2. Enoxaparin appeared more effective
than heparin in the prevention of
thromboembolic complications during
rehabilitation after spinal cord injury.
3. Both interventions were safe in this
population.
No statistical results reported.
1. 4 patients in UFH and 13 patients in
LMWH developed venous
thromboembolic episodes.
2. 3 of 13 on enoxaparin 40mg OD and
10 of 59 on 20 mg OD.
3. In the UFH group, one of the
thrombotic events occurred post-
mobilization.
4. 6 of the 13 thrombotic events in
LMWH occurred after the patients
had been mobilized and
anticoagulation stopped.
5. 2 periods of peak incidence of
 Author Year
Country
Score Methods
Research Design
Sample Size
decrease in Hgb and platelet levels.
Population: Mean age = 25yrs;
Severity of injury: Frankel scores A or
B; Chronicity = acute; Cause of injury
= trauma.
Treatment: SCI patients with DVT or
Winemiller et al. 1999 PE were put on antithrombotic
USA prophylaxis for 42 days after injury.
Downs & Black score=13 Outcome Measures: Demographic
Case Series characteristics; venous
N=285 thromboembolism risk factors;
methods of surveillance and
prophylaxis, and thromboembolic
events within the first 6 weeks
following injury.
Population: Age = 14-83 yrs; Gender:
males = 39, females = 9; Chronicity =
acute.
Green et al. 1994 Treatment: LMWH at a dose of
USA 3500anti-Xa U given subcutaneously
Downs & Black score=13 once daily- all subjects received this
Pre-post medication at this dose for 8 wks, then
N=48 if tvenous colour flow ultrasonography
was negative meds were discontinued.
Outcome Measures: Incidence of
DVT, PE, and bleeding.
Note: AIS=ASIA Impairment Scale; LMWH=Low Molecular Weight Heparin; UFH=Unfractionated Heparin
Discussion
Outcomes
venous thromboembolism were
noticed in both groups - the first at
20-30 days following injury and the
second at 90-100 days post-injury.
1. Multivariate analysis suggested that
sequential pneumatic compression
devices (SCD) or gradient elastic
stockings (GES) were associated
with a reduced risk of venous
thromboembolism.
2. Multivariate analysis also suggested
adecreased risk of thromboembolism
in patients with SCI treated with
heparin within the first 14 days or
anytime within 42 days.
3. Although the estimated risk reduction
for heparin was about twice that for
SCD/GES, it was not statistically
significant.
The differences in bleeding between the
two forms of heparin are significant
(p=0.04) favoring LMWH. There is a trend
toward fewer thrombotic events with
LMWH (p=0.15).

Low Molecular Weight Heparin (LMWH) is the newest treatment for prophylaxis of venous
thromboembolism and has already been described in the introduction. Because UFH has been
the standard treatment for years and LMWH appears to offer advantages over UFH it is not
surprising that there are a number of trials comparing the 2 treatments.

There have been three trials which have compared UFH and LMWH. The SCI
Thromboprophylaxis Investigators (2003b) conducted a controlled non-randomized trial of low
dose UFH (5,000 units s/c q8h) and enoxaparin (40 mg once daily) during a 6-week
rehabilitation phase. A new venous thromboembolism was detected in 21.7% of UFH and 8.5%
of enoxaprin patients (p = 0.052). Enoxaprin appeared to be more effective in this population
than UFH.

One trial compared UFH plus intermittent pneumatic compression to LMWH. SCI
Thromboprophylaxis Investigators (2003a) conducted a RCT of 476 SCI patients who were
assigned to receive thromboprophylaxis with either a combination of low-dose UFH (5000 units
s/c q8h) plus intermittent pneumatic compression (IPC) to be used at least 22 hours each day or
enoxaparin 30 mg s/c q12h. Among 107 assessable patients, the incidence of venous
thromboembolism was 63.3% with UFH/IPC versus 65.5% with enoxaparin (p=0.81). The
incidence of PE was 18.4% in the UFH/IPC group versus 5.2% with enoxaparin (p=0.03).

15-10
Among all the randomized patients, the incidence of major bleeding was 5.3% in the UFH/IPC
versus 2.6% with enoxaparin (p=0.14). This is the only study where the incidence of venous
thromoboemolism was not significantly less with LMWH when compared to UFH. HThis is
undoubtedly a result of the added benefit of pneumatic compression given with UFH only in this
study. Nonetheless, the incidence of PEs was still significantly greater in the UFH/IPC group.

Thumbikat et al. (2002) in a retrospective study compared a group of SCI patients (n=101) who
received a combination of heparin followed by warfarin to another group (n=72) who received
enoxaparin. Four patients in the UFH group and 13 patients in the LMWH group developed
venous thromboembolic episodes. Of the 72 patients on enoxaparin, 2/13 on 40 mg daily (OD)
and 10/59 on 20 mg daily developed DVT/PE. One patient in group 1 and 6 patients in group 2
developed DVT post-mobilization with discontinuation of anticoagulation.

Green et al. (1990) in an RCT randomized 41 SCI subjects to either standard heparin or LMWH.
Five patients in the standard heparin group had thrombotic events including 2 patients with fatal
pulmonary embolism. Two other patients had bleeding severe enough to necessitate
withdrawal of the heparin. The cumulative event rate was 34% while the LMWH group had no
thrombotic events or bleeding. The difference between the 2 groups was significant (p=0.006).
Green et al. (1994) studied 60 acute SCI patients with complete motor paraplegia who all
received low molecular weight heparin in a dose of 3500 units s/c daily. Forty-eight were able to
complete the study. Treatment began within 72 hours of injury and continued for 8 weeks. Forty
patients completed the 8 weeks of prophylaxis uneventfully while 8 suffered a thrombotic event.
Of the thrombotic events, 2 were pulmonary emboli, 4 were proximal DVTs while 2 were distal
calf DVTs. The differences in bleeding between standard heparin, when combining data from a
previous study (68 LMWH (20 from previous study) and 79 UFH), were significant (p=0.04)
favoring LMWH with a trend toward fewer thrombotic events with the LMWH (P=0.15).

There is strong evidence based on the results from these RCTs that LMWH,is more effective
than standard UFH. This strong evidence in favour of LMWH outweighs the conflicting
conclusions of a large, nonrandomized study by Thumbikat et al. (2002).

Table 7 Studies Evaluating Low Molecular Weight Heparin vs. Unfractionated Heparin
N
Author/Year Treatments Results
& Type of Study
SCI Thromboprophylaxis 119
UFH vs. Enoxaparin Enoxaparin more effective
Investigators 2001 nonrandomized
UFH plus intermittent Enoxaparin more effective for
SCI Thromboprophylaxis 107
pneumatic compression only PE with fewer
Investigators 2003a RCT
vs enoxaparin complications
172 UFH followed by warfarin UFH and warfarin more
Thumbakit et al. 2002
nonrandomized vs enoxaparin effective
41 LMWH more effective with
Green et al. 1990 UFH vs LMWH
RCT fewer complcations
Trend to LMWH more effective.
147
Green et al. 1994 UFH vs LMWH Significantly fewer bleeding
nonrandomized
complications
- Indicates a reduction in the incidence of DVT compared to placebo/alternative treatment
+ Indicates no difference in the incidence of DVT compared to placebo/alternative treatment

Conclusions

There is level 1a evidence (based on 2 RCTs) that low molecular weight heparin, in
particular enoxaparin, is more effective in reducing venous thromboembolic events,

15-11
when compared to the standard subcutaneous heparin prophylaxis. Moreover, the
incidence of bleeding complications was less in the LMWH group.
Low molecular weight heparin reduces the risk of venous thromboembolism post SCI more
effectively than standard or unfractionated heparin prophylaxis with fewer bleeding
complications.
4.1.5 LMWH as a Prophylaxis of Venous Thrombosis
Three studies were found which examined LMWH alone, compared different dosages of LMWH
or compared different LMWHs.
Table 8 LMW Heparin Alone in Prophylaxis of Venous Thromboembolism Post SCI
Author Year
Country
Score Methods
Research Design
Total Sample Size
Population: Mean age = 36 yrs; Severity
of injury: complete/incomplete; Mean time
since injury = <6 wks.
Treatment: Enrolled patients were
Chiou-Tan et al. 2003 randomized into two treatment groups.
USA One group received 30 mg of enoxaparin
PEDro=6 subcutaneously every 12 hr and the other
RCT received 5000 IU of dalteparin
N=95 subcutaneously once daily.
Outcome Measures: Daily Logbook, Short
Form Health Status Survey, follow-up
questionnaire.
Population: Enoxaparin (n=63): Mean
age=40.6yrs; Gender: males=45; Level of
injury: cervical=26, thoracic=7, lumbar=0;
Severity of injury: AIS A=17, B=4, C=3,
D=4, E=4, uknown=1; Dalteparin (n=72):
Mean age=45.4yrs; Gender: males=58;
Slavik et al. 2007
Level of injury: C=27, thoracic=9,
Canada
Downs & Black score=19
lumbar=4; Severity of injury: AIS A=22,
B=4, C=3, D=0, E=5, unknown=6
Case Control
N=135
Treatments: Effectiveness of enoxaparin
administration protocol was retrospectively
compared to dalteparin administration
protocol in patients with orthopedic trauma
or acute spinal cord injury.
Outcome Measures: Incidence of
DVT/PE, Adverse effects, cost savings
Population: LDUH group(n=47): Mean
age=46yrs; Gender: males=40, females=7;
Worley et al. 2008 Level of injury: tetraplegia=35,
Canada paraplegia=12; Severity of injury: AIS
Downs & Black score=19 A=19, B=5, C=7, D=16; Dalteparin
Case Control (LMWH) group (n=43): Mean age=38yrs;
N=90 Gender: males=39; females=4; Level of
injury: tetraplegia=24, paraplegia=18;
Severity of injury: AIS A=17, B=3, C=12,
15-12
Outcomes
No statistically significant results reported
1. 6% of the patients developed DVT
while receiving enoxaparin and 4%
2
while receiving dalteparin (X =.44,
p=.51).
2. 4% developed bleeding while receiving
dalteparin and 2% while receiving
2
enoxaparin (X =.13, p=.72).
3. There were no DVTs or hemorrhages
reported after discharge to home.
2
4. There was 99% compliance (X =.88,
p=.5) with taking medication while in
hosp.
1. Both groups received prophylactic
doses of treatment in greater than 3
days post injury.
2. No significant difference between the
two groups was seen in:
In-hospital proximal DVT or PE
(p=0.103).
mean number of in-hospital
diagnostic tests.
major bleeding.
3. Use of Dalteparin resulted in a LMWH
acquisition cost savings of $12,485.19
(CAD).
1. No significant difference was seen
between the two groups in:
the incidence of VTE.
the location of DVT (proximal vs.
distal).
Bleeding complications.
2. Patients with paraplegia compared to
tetraplegia were more likely to have
VTE regardless of type of prophylactic
 Author Year
Country
Score Methods Outcomes
Research Design
Total Sample Size
D=10, E=1 treatment.
Treatment: Effectiveness of LDUH
treatment on acute SCI patients was
compared to those receiving LMWH.
Outcome Measure: Incidence of VTE,
adverse effects
Population: Chronicity = acute. 1. Equivalent prophylaxis efficacy was
Treatment: Administration of seen in both enoxaparin groups.
subcutaneous Enoxaparin (40mg once 2. Symptomatic venous
daily or 30mg twice daily). thromboembolism did not differ, with
Outcome Measures: Safety and efficacy DVT occurring in 1 of 49 (2.0%)
of enoxaparin, cost analysis. patients receiving twice-daily
enoxaparin, and 1 of 80 (1.25%)
patients receiving once-daily
Hebbeler et al. 2004; 2
enoxaparin (X = 0.125, NS).
USA
3. PE was seen in 1 of 49 (2.0%) patients
Downs & Black score=15
treated with twice-daily enoxaparin
Case Control
and in none of the patients in the
N=129 2
once-daily group (X = 1.64, NS).
4. Bleeding complications also did not
differ between the 2 treatment groups;
these were observed in 2 of 49 (4.1%)
patients receiving twice-daily
enoxaparin and in 5 of 80 (6.3%)
patients receiving once-daily
2
enoxaparin (X = 0.228, NS).
Population: Age 15-84 years; Severity of No statistical results reported
Harris et al. 1996;
injury: complete/incomplete; Time since 1. No patient developed clinical evidence
USA
injury = 6-104 dys. of thromboembolism, and none of the
Downs & Black score=7
Treatment: All patients received 30 mg of 60 venous ultrasound examinations
Case Series
enoxaparin subcutaneously every 12 h showed a DVT.
Initial N=105;
beginning at the time of admission.
Final N=101
Outcome Measures: Not specified.
Note: AIS=ASIA Impairment Scale

Authors; Country Method: Conclusions

Date included in the Level of evidence
review Questions
Number of articles
AMSTAR
Christie et al. 2011 Method: Comprehensive literature 1. DVT prophylaxis should
Canada search of English RCT, Cohort be instituted within 72
Date included in the review studies, case series, and review hours post injury.
not stated articles of relating to prophylaxis 2. LMWH should be held
N= 5 LMWH for DVT in traumatic SCI in on the morning of
AMSTAR: 5 adult age group (18 + years). surgery and resumed
Databases: PubMed within 24 hours
Questions/measures/hypothesis: following surgery.
1. Examine the ideal time for
initiation of DVT prophylaxis
with LMWH: after SCI or after

15-13
 surgery

Discussion

From the previous discussion it is clear that LMWH is superior to UFH both in venous
thromboembolism prophylaxis and in reducing the risk of bleeding complications. In line with
this, Harris et al. (1996) studied 105 subjects of whom 66 had SCI in an observational
retrospective study. All patients received 30 mg of enoxaparin s/c q12h beginning at the time of
admission. If a patient was scheduled for surgery, the drug was withheld for the morning of the
operation, resumed 24 hours later, and continued until the patients discharge. No patient
developed clinical evidence of venous thromboembolism and none of the 60 venous ultrasound
examinations showed a DVT.

The optimal dose of enoxaparin has not been established to date. Hebbeler et al. (2004)
reported on a nonrandomized trial of 129 acute SCI patients who received either enoxaparin 40
mg daily vs. 30 mg twice daily prophylactically. Symptomatic thromboembolism did not differ
between the two groups with DVT occurring in only one patient in each group. There was no
difference in bleeding complications between the 2 groups.

There are many new LMWHs available and it is inevitable that there will be studies comparing
their efficacy. One RCT (Chiou-Tan et al. 2001) and two case control studies (Slavik et al.
2007; Worley et al. 2008) compared acute SCI patients who received enoxaparin (30-40 mg s/c
q12h) to those who received dalteparin (2000- 5000IU) s/c daily. There were no significant
group differences between the two groups in terms of incidence and location of DVTs or
bleeding complications. Worley et al. (2008) found having paraplegia was the only condition
which increased risk of VTE regardless of the type of prophylactic treatment. Enoxaparin was
more expensive than dalteparin ($12,485.19 CAD is this the price for enoxaparin/dalteparin or
the difference in price over what time period?) (Slavik et al. 2007).

In terms of timing of treatment, one systematic review evaluated the ideal time for initiating DVT
treatment with LMWH. Five articles met their inclusion criteria but only a single study examined
the effects of timing on the efficacy of treatment. The review concluded that LMWH prophylaxis
for DVT should be administered within 72 hours post injury. However, this conclusion should be
interpreted with caution, as it was based on one single study.

Conclusion
There was level 4 (limited) evidence that 40 mg Enoxaparin is no more effective than 30
mg of Enoxaparin in reducing the incidence of deep venous thrombosis or bleeding
complications when used prophylactically.

There is level 1b evidence (based on one RCT) 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 appears to be no difference between Enoxaparin and Dalteparin in reducing

the risk of venous thrombosis post-SCI.

15-14
5.0 Prevention of DVT through Mechanical Methods
Although pharmacological measures have been generally the preferred treatment for venous
thromboembolism prophylaxis post SCI, mechanical means of limiting venous stasis can also
serve to reduce the incidence of DVT post SCI. Mechanical treatments are designed to limit
stasis in the paralyzed lower extremities. However, it should be noted that use of these devices
should be accompanied by the twice daily inspection for skin discolourations or breakdown, or
broken blood vessels. As well, pneumatic compression devices are not suitable for patients
with severe arterial insufficiency.

Table 9 Evaluating Physical Methods for the Prevention of DVT

Author Year
Country
Score Methods Outcomes
Research Design
Sample Size
Population: Mean age = 27.9 yrs; 1. Popliteal vein: no differences
Gender: males = 20; Level of injury: between devices.
tetraplegic = 20; Time since injury = 2 2. Femoral vein: VFM & MVV during
mos-17 yrs; All negative for VT or IPC vs. SCD (p<0.05).
chemophylaxia. 3. Rest vs. compression: VFM, AVV &
Intervention: Randomized into one of MVV, all during compression
two groups: 1) Slow sequential (p<0.001).
Nash et al. 2000
compression (SCD) 15 sec
USA
compression, 45 sec relaxation at
PEDro=8
35mmHg (ankle), 30mmHg (calf) or
RCT
20mmHh (thigh); 2) Intermittent pulsatile
N=20
compression (IPC) 2 sec compression,
18 sec relaxation at 160 mmHg.
Outcome Measures: Venous flow/min
(VFM); Average venous velocity (AVV);
Maximum venous velocity (MVV); for
bilateral popliteal & femoral veins @ rest
(baseline) & during compression.
Population: Age = 17 to 75 yrs; Gender: 1. 4/5 control patients developed
males = 11, females = 3; Severity of positive fibrinogen leg scans.
Becker et al. 1987 injury: complete/incomplete; Chronicity = 2. All had also become positive by
USA acute. impedance plethysmography. Four of
PEDro=6 Treatment: Rotating treatment tables. the treatment patients developed
RCT Outcome Measures: Impedance blood fibrinogen but not impedance
N=15 plethysmography. plethysmography. This difference
was significant with p=0.017.
Population: Acute SCI; Mean age: 53; AIS: 1. 16 of 37 patients (43%) developed DVT
Chung et al. A=10, B=7, C=12, D=8; 19 patients with a days (mean, 17.2 days) after injury.
2011 traumatic injury and 18 patients with non- 2. 81.2% of DVT occurred in the distal leg
Korea traumatic injury vein.
D&B=16 Treatment: Mechanical prophylaxis was 3. Age, sex, type of impairment and cause
Pre-Post provided to individuals admitted to SCI of SCI were not found to be a factor in
N= 476 rehabilitation. relation to incidence of DVT.
Outcome Measures: Incidence of DVT
Population: Mean age = 25yrs; Severity 1. Multivariate analysis suggested that
of injury: Frankel scores A or B; Chronicity sequential pneumatic compression
Winemiller et al. 1999
= acute; Cause of injury = trauma. devices (SCD) or gradient elastic
USA
Treatment: Prophylaxis on SCI patients stockings (GES) were associated
Downs & Black
with deep vein thrombosis or pulmonary with a reduced risk of venous
score=13
embolism were put on antithrombotic thromboembolism.
Case Series
prophylaxis for 42 days after injury. 2. Multivariate analysis also suggested
N=285
Outcome Measures: Demographic an decreased risk of
characteristics; venous thromboembolism thromboembolism in patients with

15-15
 Author Year
Country
Score Methods Outcomes
Research Design
Sample Size
risk factors; methods of surveillance and SCI treated with heparin within the
prophylaxis, and thromboembolic events first 14 days or anytime within 42
within the first 6 weeks following injury. days.
3. Although the estimated risk reduction
for heparin was about twice that for
SCD/GES, it was not statistically
significant.

Discussion
Winemiller et al. (1999) did chart audits to conduct a case-control study of 285 SCI patients.
Multivariate analysis suggested that sequential pneumatic compression devices (SCD) or
gradient elastic stockings (GES) were associated with a reduced risk of venous
thromboembolism. Multivariate analysis also suggested a decreased risk of venous
thromboembolism in SCI patients treated with heparin in the first 14 days or anytime within 42
days. Although the risk reduction was approximately twice that of SCD/GES it was not
statistically significant. A pre-post study by Chung et al. (2011) found a high incidence (43%) of
DVT post SCI in individuals receiving prophylactic mechanical compression on their lower limbs.
The treatment involved the use of gradient elastic stockings, external sequential pneumatic
compression and early ambulation. In order to better examine the effectiveness of mechanical
compression, individuals were not offered pharmacological prophylaxis. This may account for
the high rate of DVT incidence.

Becker et al. (1987) studied whether rotating treatment tables would prevent the development
and progression of DVT in acute SCI patients. The authors noted that rotating treatment tables
had been used up to that time in acute SCI patients to maintain spinal cord alignment while
facilitating nursing care, allowing even distribution of ventilation and preventing pressure sores.
It was hypothesized that because these appliances rotated continuously, they might serve to
inhibit thrombosis formation by reducing venous stasis. This randomized trial involved 15
patients with acute SCIs. Four of the 5 control (nonrotated) patients developed distal and
proximal thrombi, assessed by I125 fibrinogen scanning and impedance plethysmography while
only one of the 10 treated (rotated) SCI patients developed both distal and proximal venous
thrombi (p=0.007).

Conclusion
There was level 4 (limited) evidence that sequential pneumatic compression devices
(SCD) or gradient elastic stockings (GES) were associated with a reduced risk of venous
thromboembolism post SCI.

There is level 1b evidence (based on one small RCT) that rotating treatment tables
reduce the incidence of venous thrombi in acute SCI patients.

15-16
 Mechanical compression may reduce the incidence of venous thromboembolism post
SCI.
The use of rotating treatment tables reduces the incidence of
venous thrombo-embolism post SCI.

Table 10 Combined Pharmacological and Physical Measures for the Prophylaxis of

Venous Thromboembolism Post SCI
Author Year
Country
Score Methods
Research Design
ample Size
Population: Gender: males = 389,
females = 87; Severity of injury: AIS: A-D;
Chronicity = acute; Cause of SCI =
trauma.
Spinal Cord Injury
Treatment: Enrolled patients were
Thromboprophylaxis
assigned to receive thromboprophylaxis
Investigators 2003a
with either the combination of low-dose
USA
unfractionated heparin (UFH) (5000 U
PEDro=9
subcutaneously every 8 h) plus
Level 1 RCT
intermittent pneumatic compression (IPC)
Initial N=476;
(to be used at least 22h/day) or
Final N=107
enoxaparin (30 mg subcutaneously every
12 h).
Outcome Measures: DVT, PE, major
bleeding.
Population: Gender: males = 24, females
= 4; Severity of injury: complete = 28.
Treatment: Subjects were randomized to
one of two regimens: EPCC alone (n=15),
and EPCC combined with aspirin (ASA),
300 mg bid, and dipyridamole (Dip) 75 mg
bid (n=13).
Green et al. 1982
Outcome Measures: Incidence of DVT;
USA
PAR; Factor VIII coagulant activity.
PEDro=7
RCT
Initial N=28; Final N=27
Population: UFH group (n=60): Mean
Spinal Cord Injury age = 34 yrs; Gender: males = 47,
Thromboprophylaxis females = 13; Level of injury: paraplegic =
Investigators 2003b 18, tetraplegic = 32; EP group (n=59):
USA Mean age = 30.5 yrs; Gender: males =
Downs & Black 53, females = 6; Level of injury:
score=21 paraplegic = 15, tetraplegic = 34.
Case Series Intervention: Continuation of above 2003
Initial N=172; Final study. Patients previously receiving low-
N=119 dose UFH (5000 U subcutaneously every
Outcomes
1. Among 107 assessable patients, the
incidence of venous
thromboembolism was 63.3% with
UFH-IPC versus 65.5% with
enoxaparin (p=0.81).
2. The incidence of pulmonary
embolism was 18.4% with UFH-IPC
versus 5.2% with enoxaparin
(p=0.03).
3. Among all randomized patients, the
incidence of major bleeding was
5.3% with UFH-IPC versus 2.6% with
enoxaparin (p=0.14).
1. Of the 27 patients that completed the
study, DVT was detected in 9/27
patients, an incidence significantly
less than the 78 % they previously
recorded in 37 patients not receiving
prophylaxis (p<0.001).
2. Thrombi developed in 6/15 patients
treated solely with EPCC, and in 3/12
receiving ASA/Dip as well as EPCC
(p<0.1).
3. No differences were observed in the
PAR of patients treated with EPCC
alone or EPCC combined with ASA
and Dip.
4. Factor VIII levels of patients treated
with EPCC alone as compared to
those also receiving ASA and Dip
revealed that the latter in general had
lower levels.
1. Diagnosis of VTE: UFH group =
13/60, EP group = 5/59 (21.7% vs.
8.5%).
2. Diagnosis of DVT: UFH group =
11/60, EP group = 4/59 (18.3%% vs.
6.8%).
3. Diagnosis of PE: UFH group = 2/60,
EP group = 1/59 (3.3% vs. 1.7%).
4. In UFH group, one patient had a fatal
PE. Both groups had one patient

15-17
 Author Year
Country
Score Methods Outcomes
Research Design
ample Size
8 h) continued on this regimen. Those drop out due to major bleeding.
previously on the enoxaparin had an
increase in doasage to 40mg.
Outcome Measures: DVT, PE, major
bleeding.
Population: Level of injury: cervical=150, 1.
2.9% of patients developed clinical
thoracic and lumbar=126; Severity of evidence of DVT or PE.
Deep et al. 2001 injury: complete=51, incomplete=29. 2. Patients were either complete or
UK Methods: SCI patients receiving full incomplete in severity.
Downs & Black length anti-thromboembolic stockings 3. None of the patients with cervical
score=17 from admission to discharge and 40mg of injury developed DVT.
Case series exnoxaparin/day were retrospectively 4. Only 1 neurologically intact patient
N=276 reviewed. developed PE; this patient did not
Outcome Measures: Incidence of receive enoxaparin for the first 6 days
DVT/PE of injury.
Population: Gender: males = 25, females 1. Of the 19 patients, 17 had negative
= 11; Severity of injury: fibrinogen scanning upon completion
complete/incomplete, Frankel A&B; of the study.
Chronicity = acute. 2. The 2 remaining patients developed
Merli et al. 1992
Treatment: Patients received prophylaxis a positive fibrinogen scan on days 6
USA
with external pneumatic compression plus and 8 of the study.
Downs & Black score=
gradient elastic stockings and low dose 3. In comparison, the control group
12
heparin for 2 weeks. developed positive 125 I fibrinogen
Case Series
Outcome Measures: Incidence of DVT; scans in 6/17 patents and all were
Initial N=38; Final N=36
Marder score. confirmed by venography.
4. The incidence of thrombosis was
significantly different than that of the
treated group (p=0.04).
Population: Mean age = 42 years; No statistical results reported.
Severity of injury: AIS A-D; Time since 1. DVT incidence in early admitted pts
injury: within 72 hrs of being injured was 2%. The incidence of DVT in
(n=99) or post 8 days (n=176); Chronicity later admitted pts was 26%.
Aito et al. 2000
= acute. 2. Of those 60% were detected on
Italy
Treatment: PGES, Subcutaneous admission, while the remaining 40%
Downs & Black
LMWH (nadroparin) .4 ml once a day. developed in a period not exceeding
score=12
ESPC. 6 wks of hospitalization. 65% of
Case Series
Outcome Measure: Diagnosis of DVT. detected DVT did not show any
N=275
evident clinical sign.
3. ASIA A were more likely to develop
DVT (36%) while in ASIA D on
admission only 7% did so.
Note: AIS=ASIA Impairment Scale; EPCC=external pneumatic calf compression; ESPC=External sequential
pneumatic compression; PAR; platelet aggregation ratios; PGES=Permanently dressed gradient elastic stockings;

Discussion
Merli et al. (1992) studied 37 SCI patients who received 2 weeks of prophylaxis with external
pneumatic compression plus gradient elastic stockings and low dose heparin 5,000 s/c q12h.
Of 19 patients treated, 17 had negative fibrinogen scanning upon completion of the study while
the 2 remaining patients developed a positive fibrinogen scan on days 6 and 8 of the study. In
comparison, the control group developed positive I125 fibrinogen scans in 6/17 patients and all
were confirmed by venography. The incidence of thrombosis was significantly different than
that of the treated group (p=0.04).

15-18
Deep et al. (2001) reported the use of prophylactic DVT treatment involving anti-
thromboembolic stockings and 40mg of exnoxaparin during their entire rehabilitation stay
resulted in only 2.9% incidence rate of DVT or PE in individuals post SCI.

Spinal Cord Injury Thromboprophylaxis Investigators conducted two studies (2003a; 2003b)
which examined the effect of low-dose unfractionated heparin (UFH) (5000 U subcutaneously
every 8 h) plus intermittent pneumatic compression (IPC) (to be used at least 22h/day) or
enoxaparin (30 mg subcutaneously every 12 h). The first study (2003a) found no significant
difference between the two groups in the rate of DVT. The second study found that over a
longer term, individuals in the UFH and IPC group had a greater chance of VTE and DVT than
those in the enoxaparin group.

Aito et al. (2000) studied 275 SCI patients, 99 of whom were treated within 72 hours of injury
while 176 were treated after 8 days post SCI. The treatment involved permanently dressed
gradient elastic stockings, s/c LMWH 0.4 ml once a day, and external sequential pneumatic
compression (ESPC) of the lower limbs 3 hrs per day given in 2 applications. There was early
mobilization of the lower limbs. The complete prophylactic treatment lasted at least 30 days
post SCI; LMWH and ESPC were continued for 2 more months depending on the patients
progress. For the earlier treated group, DVT incidence was 2% while the incidence in the later
treated group was 26%. Of those 60% were detected at the time of later admission, while the
remaining 40% developed in a period not exceeding 6 weeks of hospitalization. Sixty-five
percent of detected DVT did not show any obvious clinical sign. ASIA A patients were more
likely to develop a DVT (36%) while only 7% of ASIA D patients did so on admission.

Green et al. (1982) randomized 28 SCI patients with complete injuries, were randomized to
either external pneumatic calf compression (EPCC) alone, and EPCC combined with aspirin
(ASA) 300 mg bid and dipyridamole 75 mg bid. Twenty-seven subjects completed the study
DVT was detected in 9/27 patients, an incidence significantly less than the 78% previously
recorded in the 37 patients not receiving prophylaxis (p<0.001). Thrombi developed in 6/15
patients treated solely with EPCC and in 3/12 receiving ASA/Dipyridamole as well as EPCC
(p<0.1). The authors concluded that early application of pharmacological plus mechanical
treatments markedly reduced the risk of DVT complications.

Although there was a lack of moderate or strong evidence that combined measures provide
more effective DVT prophylaxis, study quality was limited. However, improved effectiveness has
face validity, given that treatment of different aspects of Virchows triadwould have an additive
effect and therefore more effective than individual treatments.

Conclusions

There is level 4 (limited) evidence that a comprehensive prophylactic treatment of

external pneumatic compression, gradient pressure stockings and low dose heparin
reduces venous thrombosis post SCI.

There is level 4 (limited) evidence that a comprehensive prophylactic regimen of

pharmacological and physical measures is more effective in preventing venous
thrombosis post SCI when instituted earlier rather than later.

There was a trend (supported by one RCT) that pneumatic compression plus antiplatelet
agents (ASA and Dipyridamole) was more effective than pneumatic compression alone.

15-19
Although an RCT, the numbers were small and the trend was not statisticallysignificant
(p<0.1).

A combined regiment of pneumatic compression, pressure stockings and low-dose

heparin given prophylactically may reduce the incidence of venous thrombosis and
this effect is better in early post SCI.

6.0 Vena Cava Filtration

Vena cava filtration involves inserting a mechanical filter into the inferior vena cava to prevent
devastating pulmonary emboli from occurring.

Table 11 Prophylactic Greenfield Filter Placement in Selected High-Risk Trauma Patients

Author Year
Country
Score Methods Outcomes
Research Design
Sample Size
Population: Mean age = 37 yrs; Gender: 1. There were no statistical differences
males = 151 females = 48; Chronicity = between the two groups.
acute; Cause of injury = trauma. 2. None of the patients in the PGF
Khansarinia et al. 1995 Treatment: Prophylactic Greenfield filter group had a PE.
USA (PGF) placement. 3. In the control group, 13 patients had
Downs & Black Outcome Measures: Injury Severity a PE, nine of which were fatal.
score=20 Score, Glasgow Coma Scale, 4. These differences were statistically
Case Control fluoroscopy, B-mode ultrasonography, significant for both PE (p < 0.009)
Initial N=324; ventilation/perfusion scanning, pulmonary and PE-related death (p < 0.03).
Final N=259 arteriography. 5. The overall mortality rate was
reduced in the PGF group (18 of 108,
16%) versus the control group (47 of
216, 22%); not statistically significant.
Population: Cervical (n=11): Mean 1. The most common complication
age=38.8yrs; Level of injury: cervical; (45.5%) in cervical patients with IVC
Control (non-cervical, n=16): Mean filter insertions was migration.
Kinney et al. 1996
age=48.6yrs; Gender: males=62%; 2. The mean migration distance was
USA
females=38% significantly higher in the cervical
Downs & Black
Treatment: Charts of SCI patients with patients than the noncervical patients
scores=18
acute cervical injury and those without (13.3mm vs. 2.3mm, p<0.05).
Case Control
cervical injury who underwent
N=26
prophylactic Greenfield IVC filter
placement were reviewed.
Outcome Measures: Complications

Table 12 Prophylactic Vena Cava Insertion in Patients with Traumatic SCI

Author Year
Country
Score Methods Outcomes
Research Design
Sample Size
Gorman et al. 2009 Population: IVC filter (N=54): Mean 1. IVC filters were more likely to be
USA age=37.1yrs; Gender: males=52%, placed on individuals with major
Downs & Black females=48%; Level of injury: trauma than those without IVC filters.
score=21 tetraplegic=38.8%; No IVC filter (N=58): 2. Patients without IVC filter were
Case Control Mean age=48.1yrs; Gender: males=40%, significantly less likely to experience

15-20
 Author Year
Country
Score Methods
Research Design
Sample Size
N=114 females=60%; Level of injury:
tetraplegic=51.7%
Treatment: Charts were reviewed of SCI
patients admitted to rehabilitation.
Patients were retrospectively divided into
two groups: patients that received a
prophylactic IVC filter and patients that
did not. Risk of DVT was assessed.
Outcome Measures: Presence of DVT
Population: Age = 15-91 yrs; Mean
hospital length of stay 23.5 dys;
Chronicity = acute; Cause of injury =
trauma.
Treatment: DVT prophylaxis with
sequential compression devices and
unfractionated heparin 5,000 units
subcutaneously every 12 hours (then to
Maxwell et al. 2002
30 mg subcutaneously every 12 hours.
USA
Outcome Measures: Injury Severity
Downs & Black
Score, incidence of DVT and PE.
score=19
Case Series
N=111
Population: Age = 18-49 yrs; Severity of
injury: Injury Severity Score = 25-41;
Chronicity = acute; Cause of injury =
Wilson et al. 1994
trauma.
USA
Treatment: Prophylactic Vena Cava Filter
Downs & Black
Insertion.
score=18
Outcome Measures: Injury Severity
Case Control
Score, Impedance Plethysmography,
N=22
Lower extremity Duplex Ultrasound.
Rogers et al. 1995 Population: Mean age = 38.9 yrs;
USA Gender: males = 73%, females = 27%;
Downs & Black Severity of injury: Injury Severity Score
15-21
Outcomes
DVT than those with an IVC filter
(5.2% vs. 20.4%, p=0.021).
3. No significant difference in DVT rates
between the two groups were
attributed to severity of injury (based
on AIS score).
4. A higher rate of DVT was reported in
patients with a motor vehicle crash
than those with other causes of
injury; however, this rate did not
reach significance.
5. Further analysis indicated, that
individuals with an Injury Severity
Score (ISS) of greater than 30 were
significantly more likely to have DVT
than those with a score less than 30,
p=0.007.
6. Individuals with a greater than or
equal to ISS 30 score were also
significantly more likely to have
prophylactic IVC filters, p=0.0001.
1. 111/8269 SCI pts with an incidence
of DVT and PE of 9.0% and 1.8%,
respectively.
2. 41.4% were paraplegics and 58.6%
were tetraplegics, and 17.1% of
patients had severe closed-head
injury.
3. Hospital stay: 2320 days for SCI
patients.
4. The incidence of DVT and PE in
those patients with SCDs alone was
7.1% and 2.3%; for SCDs plus
subcutaneous heparin, the incidence
was 11.1% and 2.8%; and for SCDs
plus low-molecular-weight heparin,
the incidence was 7.4% and 0%,
respectively
5. The incidence of DVT in SCI patients
with long bone fractures was 37.5%,
which was significantly greater than
the total SCI population (p < 0.02).
1. No complications were associated
with vena cava filter insertion.
2. No patients developed venous
thrombosis during acute
hospitalization (median 22 d), and no
patients have developed PE after
filter insertion.
3. A follow-up deep abdominal Duplex
scan of the vena cava was
performed, with a 30-day patency of
100% and 1-year follow-up is felt to
represent the trapping of thrombus.
1. Time from admission to prophylactic
insertion of a vena cava filter was
4.33.9 days.
 Author Year
Country
Score Methods Outcomes
Research Design
Sample Size
score=13 31.5; Cause of injury = trauma. 2. 3 cases of deep vein thrombosis
Case Control Treatment: The insertion of prophylactic occurred after discharge from
Initial N=71; Final N=63 vena cava filters. hospital.
Outcome Measures: Incidence of 3. Overall there were 19 patients (30%)
pulmonary embolism. with prophylactic vena cava filters
who had deep vein thrombosis
develop.
4. When the incidence of pulmonary
embolism was compared in the high-
risk trauma population before and
after instituting a policy of inserting a
prophylactic vena cava filter, there
was a significant (p<0.00072)
reduction in the incidence of
pulmonary embolism in the group
receiving filters.
Roberts et al. Population: Acute SCI; 37 men and 8 1. 17 of 45 (37%) patients removed the
2011 women; mean age: 39.7 years old (range: 17- filter successfully within 6-8 weeks of
U.S 67 years); Mean ISS score: 34.2 insertion
D&B=11 Treatment: Patients received the insertion of 2. No complications related to IVCF
Case series retrievable inferior vena cava filters (IVCF) insertion were observed.
N= 45 Outcome Measures: Incidence of DVT;
adverse events
Population: Chronicity = acute. No statistical findings reported
Treatment: The Kim-Ray Greenfield filter 1. All patients with an indication for the
is inserted into the IVC below the renal Kim-Ray Greenfield filter were
veins to interrupt the IVC. The patient technically capable of having the
remains on full anti-coagulation device inserted.
Jarrell et al. 1983
throughout the performance of the 2. There has been one death due to PE
USA
procedure. A repeat IVC gram is in a patient with a filter to date.
Downs & Black
performed if there is any doubt about the 3. There have been no other instances
score=11
position of the filter or patency of the IVC. of suspected or proved PE after
Case Series
Outcome Measures: Documentation of insertion of a filter since the institution
N=21
DVT or PE. of requiring a preoperative IVC gram
and postoperative studies to prove
proper location.
4. Follow-up on the 23 remaining
patients revealed 2 instances of
thrombosis of the IVC.

Discussion
Four case control studies examined the effect of prophylactic IVC filter insertions on the
incidence of DVT after SCI. Gorman et al. (2009) conducted a retrospective chart review of
individuals admitted to SCI rehabilitation receiving IVC filters compared to those that did not.
The study found individuals with IVC filters had a significantly lower incidence rate of DVT than
those not on IVC, p=0.021. The study found DVT was more likely to occur in patients who have
experienced a motor vehicle crash than those that have not; furthermore IVC filters were more
likely to be inserted in these patients. A 30 or greater Injury Severity Score was highly correlated
with the development of DVT.

Khansarinia et al. (1995), in a case control study, compared 108 patients who sustained multiple
trauma with known high risk of PE (including SCI patients) and received a prophylactic
Greenfiled filter (PGF) to 216 historically matched control patients. None of the patients in the

15-22
PGF group had a pulmonary embolism while 13 patients in the control group had a PE
(p<0.009), 9 of which were fatal (p<0.03). The overall mortality rate was reduced in the PGF
group (18 of 108, 16%) versus the control group (47 of 216, 22%) but this result was not
deemed to be statistically significant.

A case control study compared the installation of Greenfield IVC filter placement in SCI
individuals with acute cervical injury to those without cervical injury (Kinney et al. 1996). The
study found filters in cervical patients frequently migrated (45.5%) and the mean migration
distance was significantly higher than those individuals with noncervical injury (p<0.05).
Duperier et al. (2001) in a case series involving high risk trauma patients, reported negligible
complications and movement of Greenfield filter placement. Hence, it is an effective and safe
prophylactic option for DVT.

Rogers et al. (1995) in a case control study, pre-post and comparison with historical controls
studied 63 patients receiving a prophylactic vena cava filter 15 of these patients had head
injuries, 25 had SCIs and 23 had pelvic fractures. Of 3151 admissions to a trauma service, 71
were considered to be in a high-risk category for PE of whom 63 received a prophylactic vena
cava filter. The mean time to insertion of the vena cava filter was 4.3 days post-admission.
Overall, there were 19 patients (30%) with prophylactic vena cava filters who developed a DVT.
When the incidence of pulmonary embolism in a high-risk patient population was compared
before and after the prophylactic vena cava filter policy was instituted, there was a significant
reduction (p<0.00072) in the incidence of PE in the group receiving the filters.

In a case series, Roberts et al. (2011) found that the use of a retrievable inferior vena cava filter
(IVCF) was effective in reducing incidence of DVT, without any related complications. Jarrell et
al. (1983) studied 21 acute SCI patients in whom a Kim-Ray Greenfield filter was inserted in the
inferior vena cava. One patient with a filter died of a PE. On follow-up no other PEs were noted
while there were two instances of thrombosis of the inferior vena cava
.
Wilson et al. (1994) in a retrospective chart audit studied 22 acute traumatic SCI patients who
were treated with a vena cava filter insertion. No complications were associated with vena cava
filter insertion. No patients developed venous thrombosis during acute hospitalization (median
22 days) and no patients developed PE after filter insertion.

Maxwell et al. (2002) in a retrospective chart audit studied 111 SCI patients to determine if they
were different than other trauma patients in terms of the incidence of DVT and PE. They
concluded that inferior vena cava filters were not necessarily needed for SCI patients as the
incidence of DVTs and PEs were not that much different than other trauma patients. Maxwell et
al. have noted, there are high risk patients with SCI that probably deserve prophylactic IVC
filter placement. They include patients that have failed DVT prophylaxis or have
contraindications to anticoagulation. SCI patients with long bone fractures also appear to be at
extreme risk for DVT and may also benefit from IVC filter placement (p. 902).

Conclusion
There is level 3 evidence that inferior vena cava filters significantly reduce the risk of
pulmonary emboli in high-risk SCI patients.

15-23
 Inferior vena cava filters significantly reduce the risk of pulmonary emboli in high-risk SCI
patients.

7.0 Treatment of Acute Venous Thromboembolism in SCI

Virtually all research to date on thromboembolism in SCI has focused on prevention rather than
treatment. . The standard treatment is anticoagulation, generally with intravenous
unfractionated heparin immediately followed by a gradual transition to Coumadin which is
generally maintained for 3-6 months. We were able to find one small study which compared
UFH to LMWH.

Table 13 Unfractionated Heparin vs. LMW Heparin

Author Year
Country
Score Methods Outcomes
Research Design
Sample Size
Population: Age = 33-60 yrs; 1. The average cost of initial
Severity of injury: AIS A-D. anticoagulation of Group 1 (IV
Treatment: 3 were give IV Heparin Heparin) patients was $413.33
followed by warfarin, while 3 were (range $331.20-$502.80), which
treated with SQ Enoxaparin followed includes the cost of heparin, IV pump
by warfarin. and tubing, and laboratory monitoring
Outcome Measures: Cost analysis. of the PTT.
2. The average cost in Group 2
(enoxaparin) patients was $362.27
Tomaio et al. 1998
(range $197.60-$617.50), which
USA
includes only the cost of medication.
Downs & Black score=11
3. Enoxaparin is slightly less expensive
Case Series
(mean cost of enoxaparin = $362.27,
N=6
IV heparin = $413.33) when
peripheral cost are taken into
account.
4. Subcutaneous enoxaparin is a safe,
cost-effective, and less labor-
intensive treatment, and can be of
substantial benefit in the treatment of
DVT in SCI patients in the
rehabilitation setting.

Discussion
Again, there are remarkably few studies examining treatment of venous thrombolembolism post
SCI with most of the research focus to date on prophylaxis. Tomaio et al. (1988) studied 6 SCI
patients with acute DVT, half of whom were treated withy IV Heparin followed by Warfarin and
half who were treated withy s/c enoxaparin followed by Warfarin. Though the study was
extremely small the author did a careful cost analysis. S/C enoxaparin was regarded as a safe,
cost-effective and less labour intensive treatment and could be of substantial benefit in the
treatment of DVT in SCI patients. Obviously more research needs to be done.

Conclusions

15-24
There is level 4 (limited) evidence that Enoxaparin subcutaneously appears to be a safe,
cost-effective and less labour-intensive treatment than intravenous heparin for acute
DVTs post SCI.

Enoxaparin subcutaneously can be considered as an alternative to intravenous Heparin

for acute DVTs post-SCI although more research needs to be done.

8.0 Summary
Venous thromboembolism following SCI is a source of significant morbidity and mortality.
Virtually all of the research is focused on prophylaxis of venous thromboembolism in this very
high-risk population. Guidelines based on best evidence for DVT prophylaxis in SCI include use
of sequential compression devices for 2 weeks and anticoagulant for 8-12 weeks after injury
(Maxwell et al. 2002). There is evidence in the literature that 5,000 units S/C of unfractionated
heparin delivered every 12 hours in this population may not be sufficient to provide adequate
protection. The good news is that low molecular weight heparin with enoxaparin ( primary drug
studied), appears to be more effective and should be considered the new standard of treatment,
given the added benefit of lower risk of bleeding complications. Physical measures in particular
gradient pressure stockings and intermittent pneumatic compression are designed to reduce the
impact of stasis due to prolonged and immobilized lower extremities and have been shown to
have a limited impact. There is an intuitive benefit to combining treatment (i.e. pharmacological
with mechanical treatment) although the evidence suggests pharmacological measures are the
more important of the two in prophylaxis.

Deep venous thrombosis is common in SCI patients not receiving prophylaxis.

There is level 2 evidence (based on one low quality RCT and one non-randomized
controlled trial) that 5,000 units s/c of unfractionated heparin is no more effective than
placebo in the prophylaxis of venous thrombosis post SCI.

There is level 1b evidence (based on one RCT) that adjusted (higher) dose s/c heparin is
more effective in prophylaxis of venous thromboembolism than 5,000 s/c heparin q12h
and has a higher incidence of bleeding complications.

There is level 1a evidence (based on 2 RCTs) that low molecular weight heparin, in
particular enoxaparin, is more effective in reducing venous thromboembolic events,
when compared to the standard s/c heparin prophylaxis. Moreover, the incidence of
bleeding complications was less in the LMWH group.

There was level 4 (limited) evidence that 40 mg Enoxaparin is no more effective than 30
mg of Enoxaparin in reducing the incidence of deep venous thrombosis or bleeding
complications when used prophylactically.

There is level 1b evidence (based on one RCT) 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 was level 4 (limited) evidence that sequential pneumatic compression devices
(SCD) or gradient elastic stockings (GES) were associated with a reduced risk of venous
thromboembolism post SCI.

15-25
There is level 1b evidence (based on one small RCT) that rotating treatment tables
reduce the incidence of venous thrombi in acute SCI patients.

There is level 4 (limited) evidence that a comprehensive prophylactic treatment of

external pneumatic compression, gradient pressure stockings and low dose heparin
reduces venous thrombosis post SCI.

There is level 4 (limited) evidence that a comprehensive prophylactic regimen of

pharmacological and physical measures is more effective in preventing venous
thrombosis post SCI when instituted early rather than later.

There was a trend (supported by one RCT) that pneumatic compression plus antiplatelet
agents (ASA and Dipyridamole) was more effective than pneumatic compression alone.
Although an RCT, the numbers were small thus the trend was non-significant (p<0.1).

There is level 3 evidence that inferior vena cava filters significantly reduce the risk of
pulmonary emboli in high-risk SCI patients.

There is limited evidence that Enoxaparin subcutaneously appears to be a safe, cost-

effective and less labour-intensive treatment than intravenous heparin for acute DVTs
post SCI.

15-26
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