Prevention of Thromboembolism in Spinal Cord Injury

Patients with an SCI have a higher likelihood of thromboembolic disease as it relates to the risk factors of the Virchow triad (ie, venous stasis, hypercoagulability, intimal injury). Stasis from paralyzed muscles and hypercoagulability remain the two major factors contributing to the development of thrombosis in this patient population. ^[2]  In a meta-analysis by Wei et al, several SCI-specific DVT risk factors were identified, including the following ^[7] :           

• Age over 45 years
• Male sex
• Complete paralysis
• Personal or family history of DVT
• History of smoking
• Lack of compression therapy
• Presence of a lower limb or pelvic fracture
• Paraplegia - Limited evidence suggests that paraplegia is a greater risk factor than tetraplegia in DVT occurrence
• Diabetes

Oral contraceptive use/pregnancy are also risk factors.

Published data regarding risk factors for DVT have several limitations, including comorbidities lacking association with other risk factors and pooled analyses with small numbers. Regardless, data has consistently demonstrated that individuals with an SCI are at a significantly greater risk for development of DVTs. ^[4]

In patients with an SCI, diagnostic signs and symptoms of DVT may differ from those found in non-injured patients and may be more difficult to identify.

Typically, the hallmark of DVT is rapid onset of unilateral leg swelling, although swelling of the lower extremities may in some cases be bilateral. Edema may be the only presenting symptom; leg pain is nonspecific, includes a vast differential diagnosis, and is generally not a useful diagnostic symptom in patients with insensate lower extremities following an SCI.

Although the diagnostic properties of the clinical examination are poor and it is virtually impossible to distinguish DVT from other processes, the following findings should raise clinical suspicion:

• Leg swelling that is principally unilateral but may be bilateral
• Tenderness on compression of the calf muscles or over the course of the deep veins in the thigh or calf
• Increased temperature over the thigh or calf
• Pain during forced dorsiflexion of the foot (Homan sign), although this is a nonspecific and insensitive test
• Low-grade fever that cannot be explained after investigation of other possible sources
• Superficial thrombophlebitis felt as a palpable cord and/or superficial venous distention at the knee, groin, or anterior abdominal wall

The clinical signs and symptoms of a PE may be the primary manifestation in patients with confirmed DVT. Symptoms may include pleuritic chest pain, dyspnea, hemoptysis, and feelings of impending doom. Further physical signs of a PE may include the following:

• Tachycardia
• Tachypnea
• Hypoxia
• Change in mental status
• Pleural friction rub, pleural effusion
• Fever
• Cyanosis
• Rales

As noted above, the accurate diagnosis of a DVT by clinical signs and symptoms alone is unreliable. Signs of unexplained fever, unilateral leg swelling (although swelling can be bilateral), or erythema should alert the clinician to the possibility of a DVT. The sudden onset of chest pain, tachycardia, tachypnea, hypoxia, hypotension, or cardiac arrhythmia should suggest a PE.

Conditions that should be also considered in a patient with an SCI and a suspected thromboembolism include fractures, muscle or soft-tissue injury, dependent edema, ruptured Baker cyst, and hematoma. Other conditions in the differential diagnosis include the following:

• Achilles tendon injuries and tendonitis
• Bursitis
• Cellulitis
• Heterotopic ossification
• Lymphedema
• Superficial thrombophlebitis

Diagnostic testing to confirm a DVT can include laboratory testing as well as the use of imaging modalities such as Doppler ultrasonography, ventilation and perfusion (V/Q) scans, spiral computed tomography (CT) scans, and pulmonary angiography. It should be noted that routine screening for a DVT in an individual with an SCI when clinical signs and symptoms are lacking is not recommended. ^[2]

Laboratory testing

D-dimer assays are a useful adjunct to noninvasive testing for suggested DVT. D-dimer assays rule out DVT if the results are negative, but the assays are less helpful if the results are positive. ^[8]

Radiologic studies

The following imaging studies may be used in the diagnosis of thromboembolic disease:

• Radiocontrast venography
• Doppler ultrasonography
• Iodine-125 (¹²⁵I) fibrinogen scintigraphy
• V/Q scanning
• Spiral CT scanning
• Pulmonary angiography

Radiocontrast venography

Radiocontrast venography is the criterion standard for the diagnosis of DVT. This is a costly, invasive procedure that may have adverse effects, including pain, and there is potential for contrast-mediated thrombosis and a dye allergy.

Doppler ultrasonography

Doppler ultrasonography has become the preferred initial test in the diagnosis of DVT, being sensitive and noninvasive. ^[8] Doppler ultrasonography allows direct imaging of major veins and assessment of flow velocity in these vessels. Its diagnostic accuracy compares favorably with that of venography, but it is dependent on operator expertise.

¹²⁵I fibrinogen scintigraphy

¹²⁵I fibrinogen scanning has the greatest sensitivity for calf vein DVT. However, this imaging modality is rarely used in the clinical setting. Disadvantages include cost, a 24-hour delay from injection to reading, failure to detect established thrombi, and the danger of viral transmission.

V/Q scanning

V/Q lung scanning is indicated as part of the diagnostic evaluation of PEs. A definitive diagnosis occurs if the results are normal or if they indicate a high probability of a PE, especially if clinical suspicion is confirmed by results. Low- or intermediate-probability scan results require further evaluation (with, for example, lower extremity Doppler ultrasonography or pulmonary angiography).

Spiral CT scanning

Spiral CT scanning of the lung is the initial modality of choice in many scenarios. ^[8] Comparative studies have found that in patients with nondiagnostic V/Q scans and negative Doppler ultrasonography of the leg, pulmonary angiography can be replaced by spiral CT scanning. ^[9]

CT pulmonary angiography

When acute pulmonary emboli are present, filling defects within the pulmonary vasculature can be seen on CT pulmonary angiography (CTPA). An axial plane view of the artery will reveal a thin rim of contrast, called the Polo mint sign, surrounding the central filling defect. ^[10]

The high risk of thromboembolic complications makes routine prophylaxis in patients with SCI essential. ^[11] The prevention of DVT and its sequelae is an important aspect of treatment for patients who have sustained such an injury.

Mechanical prophylaxis modalities (eg, compression hose, external pneumatic devices, electrical stimulation, venous foot pumps, range of motion [ROM] exercises) have been shown to be effective for reducing the incidence of DVT in acute SCI. However, if mechanical prophylaxis devices are the sole method of DVT prophylaxis, they must be used continuously and removed only briefly for patient bathing; ^[2]  this is a more viable option during acute hospitalizations but is less feasible during acute rehabilitation hospitalizations.

Compression hose

Compression hose (elastic stockings) distribute pressure uniformly over the extremity, improve lower extremity venous return, and help to control edema. However, they require that the integrity of underlying skin be examined daily and are ineffective alone. ^[2]

No known study has evaluated whether the incidence of DVT varies between patients wearing thigh-length elastic stockings and those wearing the calf-length type.

External pneumatic devices

External pneumatic devices have a mode of compression that is graded as sequential, multicompartment uniform, or single-chamber uniform pressure. These devices improve lower extremity venous return but are ineffective alone. ^[2]

External pneumatic devices may be knee or thigh length and are contraindicated in patients with severe arterial insufficiency.

Electrical stimulation

Electrical stimulation mechanically stimulates dorsiflexion and plantar flexion of the lower extremity. This modality reduces lower extremity stasis but is ineffective alone.

Electrical stimulation must be used 24 hours per day, hindering the patient's ability to participate in therapies. Stimulation is painful in sensate patients. This modality has not been fully established by the medical literature.

Other

Venous foot pumps have not been studied in larger trials or in patients with SCI, so their efficacy in the prevention of DVT in this population has not been established.

Active and passive ROM exercises reduce lower extremity stasis. Some indirect evidence exists that ROM could be beneficial in the prevention of DVT; however, it is ineffective alone.

As previously noted, routine prophylaxis for thromboembolism in patients who have suffered an SCI is essential due to the high risk of thromboembolic complications. ^[11]  The prevention of a PE is the primary reason why the diagnosis and treatment of venous thrombosis are urgent.

All patients with an SCI should be on some type of anticoagulation therapy (unless otherwise contraindicated due to bleeding risk), such as the following:

• Low-dose heparin (LDH) or adjusted-dose heparin
• Low–molecular weight heparin (LMWH)
• Warfarin
• Direct oral anticoagulants (DOACs)

Historically, LDH was been used for DVT prophylaxis, but many studies demonstrate that LMWH is superior for the prevention of thromboembolism, with evidence suggesting that anticoagulant thromboprophylaxis with LMWH results in a significant decrease in PEs, fewer DVTs, and fewer major bleeding events, compared with LDH use. ^[2]  Clinical practice guidelines now recommend LMWH for anticoagulant prophylaxis. ^[2]

Commercially available LMWH preparations do not appear to differ with regard to their effectiveness in preventing DVT subsequent to SCI. Clinical practice guidelines have recommended against the use of LDH for prevention of DVTs unless LMWH is unavailable or contraindicated. ^[2]

The use of oral vitamin K antagonists (eg, warfarin) is not recommended in the acute phase following SCI but is appropriate for use in the post-acute rehabilitation phase if clinically indicated. ^[2]

DOAC medications are relatively novel and have been suggested for use as thromboprophylaxis during the rehabilitation phase following an SCI. However, they are not currently appropriate in the early phase after SCI, due to a lack of clinical evidence and a relatively long half-life. ^[2]

Guidelines do endorse combined mechanical and anticoagulant thromboprophylaxis use as early as possible following injury, as indicated, especially in the acute-care phase. ^[2]

Duration of prophylaxis

The current guideline-based recommendation is that DVT prophylaxis be continued for a minimum of 8 weeks following injury in patients with limited mobility. ^[2] LMWH, oral vitamin K antagonists (international normalized ratio [INR] goal 2.0-3.0), and DOAC thromboprophylaxis are all recommended for patients in the post-acute rehabilitation phase. LMWH has been noted to have the highest level of evidence for use. ^[2]

If the patient is discharged from the hospital before the recommended duration of prophylaxis is over, then DVT prophylaxis can be continued on an outpatient basis, provided that adequate home care and close medical follow-up can be arranged.

Patients with an SCI who have recurrences of thromboembolic disease may require prolonged therapy.

Placement of a vena cava filter is indicated in patients who have not achieved success with anticoagulant prophylaxis or who have a contraindication to anticoagulation. ^[12] This procedure is not a substitute for thromboprophylaxis, due to the morbidity related to DVT (eg, post-phlebitic syndrome) and the propagation of vena caval embolisms. Possible complications include vena caval thrombosis, filter migration, and vena caval perforation.

Thromboembolectomy is indicated when anticoagulant therapy is ineffective, unsafe, or contraindicated. A thromboembolectomy can be performed to restore venous patency.

As it relates to the timing of surgical decompression in acute traumatic central cord syndrome (ATCCS), a literature review by Sattari et al demonstrated a reduction in the incidence of DVTs in those patients who underwent surgical decompression less than 24 hours after injury compared with those who underwent surgical decompression 24 hours or more post trauma. The odds ratio for DVT in patients with ATCCS who underwent the earlier decompression was 0.41. ^[13]

PE is the most serious and potentially fatal complication of DVT. Acute PE may even occur despite adequate thromboprophylaxis.

Recurrence of a DVT is a complication in patients with SCI. Post-phlebitic syndrome is a late complication of DVT and is associated with venous insufficiency.

Hemorrhagic complications from anticoagulants are also possible; thus, the appropriate method and selection of thromboembolism prevention is patient specific and should carefully be considered.

The prompt and accurate diagnosis of a DVT is vital to the initiation of proper treatment; such treatment can prevent more serious complications, such as clot progression and/or PE. Therefore, patients, family members, and caregivers should be educated in the recognition and prevention of DVT.

For patients with an acute SCI, the risk of death due to PE is 210 times greater than that for a similar, healthy population. According to clinical practice guidelines, this risk decreases to 19.1 times the normal risk during years 2-5; it further decreases (to 8.9 times the normal risk) in patients who survive longer than 5 years. ^{[14, 2]}