Rivaroxaban use in vein thrombosis and VTE risk in spinal cord injury patients

Rivaroxaban could be a therapy option, especially if it is administered early, explained Prof. Dr. Jan Beyer-Westendorf in a session at the GTH in Vienna. The physician presented a small series of cases from the prospective non-interventional multicentre Dresden NOAC registry.

Splanchnic vein thrombosis (SVT) is a challenging VTE incidence to treat

Rivaroxaban could be a therapy option, especially if it is administered early, explained Prof. Dr. Jan Beyer-Westendorf in a session at the GTH in Vienna. The physician presented a small series of cases from the prospective non-interventional multicentre Dresden NOAC registry.

Most patients with SVT are treated with low molecular weight heparin and some with VKA. A study looked into whether rivaroxaban had advantages in SVT therapy due to its oral administration and its specific pharmacological profile.

26 patients received rivaroxaban for SVT therapy, 65% were men, with the median age being 55 years. 53.8% of the subjects had portal vein thrombosis (n=14), 15.4% spleen vein thrombosis (n=4) and 30.8% multisegmental SVTs (n=8). 38.5% of SVTs were unprovoked, 61.5% were provoked (intraabdominal infection in 34.6%, advanced cirrhosis in 23.1% and cancer in 15.4%).

The median time between diagnosis and administration of rivaroxaban was 28 days, the dosage was highly variable and ranged from 10 mg 1x daily to 15 mg 2x daily). The mean follow-up was 23 months, the mean intake of rivaroxaban was 14 months.

No thromboembolic event occurred under rivaroxaban. However, there were 21 bleeding complications in 11 patients: 9 mild bleeding, 7 clinically relevant bleeding and 5 major bleedings (including 3 gastrointestinal, 1 hemorrhoid and one traumatic intracranial bleeding).

At the end of the follow-up, 13 patients continued to take rivaroxaban. 6 patients completed the rivaroxaban treatment and 2 patients had switched to prophylactic doses of apixaban for long-term secondary prevention.

5 patients stopped oral anticoagulation and 5 patients died during the follow-up (2 due to traumatic intracranial bleeding and 3 due to terminal malignancies).

Of 11 patients who started with rivaroxaban within 30 days of SVT diagnosis, 9 showed complete coagulation dissolution, one patient showed improvement and one maintained stable coagulation load. This represents a 91% improvement. Of 8 patients who started later with rivaroxaban (> 30 days), one showed complete resolution, one improvement and 6 presented stable clots. This represents a 25% improvement.

According to Beyer-Westendorf, rivaroxaban therapy is sufficiently effective in acute and long-term treatment. However, some SVT patients had initially received low molecular weight heparin before rivaroxaban was switched. If rivaroxaban was administered early, high rates of clot dissolution were observed. Major bleedings were common, but were mainly non-fatal gastrointestinal bleeding and usually occurred 3 months after therapy. This suggests that a reduction of the rivaroxaban dose should be considered for long-term SVT treatment, emphasizes Beyer-Westendorf. However, the results would first have to be proven at adequate RCT settings.

Possibly, higher F XII levels are not associated with an increased risk of recurrent VTEs, while lower FXI levels may reduce the risk of developing another VTE. This is the result of a prospective cohort study presented by Dr. Lisbeth Eischer from the Medical University of Vienna.

The aim of the study was to establish the relationship between coagulation factors of the contact system and the risk of recurrent VTE in high-risk patients.

Included were 850 patients, an average age 53 years, 34% women, with the first unprovoked, symptomatic DVT of the leg and/or pulmonary embolism who received VKA ≥ 3 months. Patients with provoked VTE (surgery, trauma, pregnancy, hormone administration), previous VTEs, cancer, severe thrombophilia and antithrombotic long-term therapy were excluded.

In the median, the patients had been anticoagulated for 7 months. The study began with the end of the VKA therapy, the patients presented themselves after 6, after 12 months and thereafter annually in the study center. Factor XI and Factor XII were determined using one-stage assays 3 weeks after discontinuation of VKA anticoagulation. Study endpoints were symptomatic DVT and symptomatic PE, the median follow-up was 8 years.

The researchers compared factor XII levels in patients without recurrent VTE (n=550) and in patients with recurrent VTE (n=265) and found that the levels did not differ significantly:112 ± 31 vs. 114 ± 30 U/dl (p=0.3).

There was no risk reduction in patients with lower factor FXII levels. The risk of recurrence of VTE was the same in all 3 groups (range < 98 -> 125 U/dl).

In contrast to factor XII, patients with recurrent VTE had significantly higher factor XI levels than those without recurrent VTE. It was found that the patients with the lowest FXI levels had the lowest risk of recurrent VTE (HR: 0.7).

FXII levels are not associated with the risk of recurrence of VTE, said Eischer. On the other hand, low factor XI levels appear to be associated with a 30% risk reduction for a recurrence of VTE.

Oskar Steinbrecher, from the Medical University of Vienna, pointed out that patients with spinal cord injuries (SCI) have a VTE risk during rehabilitation that is not always taken into account, and that the data available on the risk of thrombosis is not extensive, while thrombosis prophylactic strategies are heterogeneous and not standardized.

The aim of the study was to evaluate the long-term risk for VTEs and thrombotic risk factors and bleeding events in SCI patients during rehabilitation. Included were 185 patients (average age 48 years) with acute SCI of the rehabilitation clinic Tobelbad between January 2007 and February 2017.

VTEs were diagnosed by measuring the D-dimer at admission (if the dimer was high followed by bilateral CUS/venography and/or CT) and clinical probability (then followed by imaging).

Risk factors for VTE include age (one risk increase per 10 years, HR 1.04), BMI (risk increases per 5kg/m²), D-dimer (if they are twice as high, HR is 2.33) and the type of plegia (tetra vs. para HR 0.87). In 21 patients, 23 bleedings occurred, including 15 minor bleedings at the site of heparin injection, 6 clinically relevant bleedings and 2 major bleedings.

8 of 185 SCI patients (4.3%) were diagnosed with VTE, on average after 5.1 months. However, 5 out of 8 VTEs were diagnosed when they were admitted to rehab, so they were likely to occur in the primary care facility. Overall, the probability of developing VTE during rehab is low and is 2%, provided that adequate thromboprophylaxis is performed. The high incidence of VTE diagnosis on admission to rehabilitation should lead to awareness of the VTE risk of these patients.

Lecture: Venous Thromboembolism February 22, 2018, GTH Vienna