Venous thromboembolism in spinal cord injury—Prophylaxis, diagnosis and treatment

Introduction

The classical Virchow’s postulate links the occurrence of venous thromboembolism (VTE) to the presence of a disruption of the circulatory flux, a damage of the endothelial tissue, or a hypercoagulability state. Immobility and palsy are prominent risk factors for VTE and are frequently seen in clinical rules used for its diagnosis ( ). Individuals with a spinal cord injury (SCI) present frequently not only with impaired mobility due to the associated neurological motor deficit, but endothelial injuries and a hypercoagulability condition may also arise as a consequence of the lesion mechanism, such as trauma or neoplasms, as well as secondary complications like infections or pressure ulcers ( ; ) ( Fig. 1 ). Thus, SCI is associated with an increased risk of venous thromboembolism in its acute phase that may extend to its chronic phase ( ; ; ).

Many advances have been made regarding risk stratification for prophylaxis and diagnostic algorithms for VTE in the general population. The proposed strategies and clinical rules however have not been validated for individuals with SCI, posing a challenge for physicians involved in the care of such patients.

Epidemiology

The reported prevalence of VTE in spinal cord injury is variable. A study by based on screening in asymptomatic patients with serial scintigraphy with labeled fibrinogen identified clots in 100% of the 20 studied patients. Other studies that are based on clinical symptoms or less sensitive screening methods report a prevalence of 10% to 15% for deep venous thrombosis (DVT) and 5% to 10% for pulmonary embolism (PE).

The risk appears to be the highest in the first 12 weeks after the injury ( ; ), with a retrospective cohort study by reporting a 17 times risk increase for DVT and 3.5 times for EP within 3 months after an SCI in comparison to age- and sex-matched individuals from the general population. A study by , however, didn’t find an increased risk in the first 3 days after the lesion. It is postulated that factors like the flaccid paralysis occurring during the spinal shock phase and the need for immobilization secondary to multiple trauma may be of significance in the augmented risk during the acute stage of SCI ( Fig. 2 ). Moreover, the dysregulation of the autonomic nervous system may lead to an imbalance of the hemostatic and fibrinolytic systems, and there is evidence of increased platelet reactivity to collagen and an imbalance in factor VIII to factor VIII-C ration ( ).

Published data on the incidence of VTE during the sub-acute and chronic phases of SCI are conflicting. There appears to be a reduction in this risk, approaching that of the general population, although somewhat higher. A study by reported an incidence of 34.4 VTE events per 100,000 patient-year during the first 90 days which was reduced to 0.3 events per 100,000 patient-year thereafter. Data from a systematic review indicate a PE incidence ranging from 0.5% to 6.0% and a DVT incidence between 2.0% and 8.0% in the sub-acute phase in patients under different prophylaxis strategies ( ). The above-mentioned study by reported a cumulative risk of 1.19 times after the first year of the SCI, and studies evaluating individuals in the chronic stage demonstrated DVT incidences as low as 0.55 per 10,000 patients-day ( ) and as high as 8% ( ) in patients admitted for rehabilitation treatment.

Without adequate treatment, the estimated mortality rates may reach 8% for DVT and 25% for PE. In studies performed with individuals with SCI, VTE may be responsible for up to 3% of all the deaths in those admitted for rehabilitation ( ). In addition, individuals affected by VTE may present further clinical complications such as post-thrombotic syndrome, pulmonary hypertension, and recurrent VTE events ( ).

Screening

The rationale for screening for asymptomatic VTE is based on its high incidence in SCI, therefore being a probable and preventable cause of death during the acute phase. The identification of an asymptomatic thrombus could then lead to immediate treatment, which could hinder further complications. Proposed approaches involve performing serial lower limb duplex ultrasound ( ), D-Dimer testing, or both used in combination ( ; ).

Even though the majority of thrombi have an origin in the lower limb circulation, up to half resolve spontaneously within 72 h, and only around a sixth of them lead to disturbance in the deep vein circulation ( ). Screening studies have been successful in demonstrating high sensitivity and in identifying a high number of asymptomatic VTE. As the majority of these were designed as diagnostic and not therapeutic studies, there is uncertainty about the clinical benefits of this strategy which may well lead to overdiagnosis and consequently overtreatment. Considering the bleeding risk associated with therapeutic anti-coagulation, patients might be exposed to unnecessary use of a dangerous medication.

Prophylaxis