Modified IMPROVE VTE Risk Score and Elevated D-Dimer Identify a High Venous Thromboembolism Risk in Acutely Ill Medical Population for Extended Thromboprophylaxis

Abstract

An individualized approach to identify acutely ill medical patients at increased risk of venous thromboembolism (VTE) and a low risk of bleeding to optimize the benefit and risk of extended thromboprophylaxis (ET) is needed. The International Medical Prevention Registry on Venous Thromboembolism (IMPROVE) VTE risk score has undergone extensive external validation in medically ill patients for in-hospital use and a modified model was used in the MARINER trial of ET also incorporating an elevated D-dimer. The MAGELLAN study demonstrated efficacy with rivaroxaban but had excess bleeding. This retrospective analysis investigated whether the modified IMPROVE VTE model with an elevated D-dimer could identify a high VTE risk subgroup of patients for ET from a subpopulation of the MAGELLAN study, which was previously identified as having a lower risk of bleeding. We incorporated the modified IMPROVE VTE score using a cutoff score of 4 or more or 2 and 3 with an elevated D-dimer (>2 times the upper limit of normal) to the MAGELLAN subpopulation. In total, 56% of the patients met the high-risk criteria. In the placebo group, the total VTE event rate at Day 35 was 7.94% in the high-risk group and 2.83% for patients in the lower-risk group. A reduction in VTE was observed with rivaroxaban in the high-risk group (relative risk [RR]: 0.68, 95% confidence interval [CI]: 0.51–0.91, p = 0.008) and in the lower-risk group (RR: 0.69, 95% CI: 0.40 -1.20, p = 0.187). The modified IMPROVE VTE score with an elevated D-dimer identified a nearly threefold higher VTE risk subpopulation of patients where a significant benefit exists for ET using rivaroxaban.

Hematological findings and complications of COVID‐19

“…The use of Risk Assessment Models (RAM) such as IMPROVE‐VTE in internal medicine department may be helpful. The modified IMPROVE‐VTE RAM which includes the D‐Dimers levels together with other clinical predictors of VTE enhances the precision of that score for the identification of high VTE risk patients eligible for an adapted pharmacological thromboprophylaxis 45 . Moreover, it is also important to pay attention to VTE risk in asymptomatic or ambulatory patients with mild COVID‐19 infection.…”

COVID-19 and Thrombotic or Thromboembolic Disease: Implications for Prevention, Antithrombotic Therapy, and Follow-Up

“…After hospital discharge from acute medical illness, extended prophylaxis with LMWH (70) or direct oral anticoagulants (DOACs) (71-74) can reduce the risk of VTE, at the cost of increase in bleeding events, including major bleeding (75,76). While no data specific to COVID-19 exist, it is reasonable to employ individualized risk stratification for thrombotic and hemorrhagic risk, followed by consideration of extended prophylaxis (for up to 45 days) for patients with elevated risk of VTE (e.g., reduced mobility, co-morbidities such as active cancer, and [according to some authors in the writing group], elevated D-dimer >2 times the upper normal limit) who have low risk of bleeding (74,77,78).…”

Emergence of institutional antithrombotic protocols for coronavirus 2019

“…Currently, VTE prophylaxis duration is mainly limited to the period of hospitalization, 21 but most VTE events occur within the first month following hospital discharge 22 . Recent data support the finding that an elevated D‐dimer (>2× upper limit of normal [ULN]) is an important novel biomarker in identifying a high‐VTE‐risk population that would benefit from extended thromboprophylaxis, an observation that is especially important in the hospitalized COVD‐19 population 23 . If all hospitalized patients received universally effective prophylaxis, one quarter of the VTE burden in the community would be prevented 24 .…”

“…Patients hospitalized for COVID‐19 would meet criteria similar to these trials as an infectious disease. There is recent evidence that an IMPROVE score of ≥4 (Table 2) ± elevated D‐dimer (>2× ULN) identifies a >3‐fold higher VTE risk population that significantly benefit from extended out‐of‐hospital thromboprophylaxis up to 39 days or more with rivaroxaban without an increase in major bleeding 12,23,34 . There are also data with betrixaban that reveal net clinical benefit from extended thromboprophlaxis for up to 42 days in hospitalized medically ill patients, including those with severe infection 56 .…”

“…Protocols suggest patients hospitalized with COVID‐19, especially those with an IMPROVE VTE score of ≥4, elevated D‐dimer (>2× ULN), and ≥2 of the following characteristics are met: age > 60, previous VTE, current cancer, or known thrombophilia, should be strongly considered for extended thromboprophylaxis up to 39‐45 days after hospital discharge with either lovenox 40 mg s.c. daily or rivaroxaban 10 mg p.o. daily and low risk of bleeding 23,58 . Insurance coverage investigation should be started early during acute hospital stay to ensure patient affordability.…”