HIGH-2-LOW risk model to predict venous thromboembolism in allogeneic transplant patients after platelet engraftment

Martens, Kylee L; Costa, Wilson Luiz da; Amos, Christopher I.; Davis, Chris; Kesten, Madeline; Lee, Stephanie J.; Zakai, Neil A.; García, David; Li, Ang

doi:10.1182/bloodadvances.2020003353

Cited by 17 publications

(21 citation statements)

References 25 publications

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“…Although those cases were not included in the present analyses, we have previously shown that HIGH-2-LOW works similarly well when applied to this patient population. 8 Second, an important proportion of VTE events corresponded to CVC-DVT, with a higher prevalence in the MDACC than the FHCRC cohort. The present study did not incorporate into the analyses any specific factors inherent to risk for thrombosis associated to CVC-DVT, such as catheter features (diameter, number of lumens), location of the tip and side of insertion, insertion techniques, and duration before exchange.…”

Section: Table S5 Highlightsmentioning

confidence: 96%

“…The discrimination of this score had a c statistic of 0.69 (0.62-0.76) in the original study. 8 The objective of the present study was to perform a temporal and external validation of the HIGH-2-LOW VTE RAM after platelet engraftment in two independent datasets. Patients who died, received inpatient or outpatient anticoagulation (based on pharmacy data), or did not achieve platelet engraftment by day 30 were excluded.…”

Section: Introductionmentioning

confidence: 99%

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External validation of the HIGH‐2‐LOW model: A predictive score for venous thromboembolism after allogeneic transplant

Martens

Nguyen

et al. 2022

American J Hematol

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In patients undergoing hematopoietic cell transplantation (HCT), venous thromboembolism (VTE) remains a serious complication that lacks validated risk assessment models (RAMs) to guide thromboprophylaxis. To address this dilemma, we performed a temporal and external validation study of the recently derived HIGH‐2‐LOW RAM. We selected adult patients undergoing allogeneic HCT from Fred Hutchinson Cancer Research Center (FHCRC) and MD Anderson Cancer Center (MDACC). Patients who died, received anticoagulation, or did not engraft platelets by day 30 were excluded. Primary outcomes were defined as overall VTE and pulmonary embolism ± lower‐extremity deep venous thromboembolism (PE/LE‐DVT) by day 180. Covariates were weighted according to the original model, except that grade 2–4 GVHD was substituted for grade 3–4. Discrimination and calibration were assessed. A total of 765 patients from FHCRC and 954 patients from MDACC were included. Incident VTE by day 180 was 5.1% at FHCRC and 6.8% at MDACC. The HIGH‐2‐LOW score had a c‐statistic of 0.67 (0.59–0.75) for VTE and 0.75 (0.64–0.81) for PE/LE‐DVT at FHCRC and 0.62 (0.55–0.70) for VTE and 0.70 (0.56–0.83) for PE/LE‐DVT at MDACC. Twenty‐five percent and 23% of patients were classified as high risk (2+ points) in the two cohorts, respectively. High versus low‐risk was associated with odds ratio (OR) of 2.80 (1.46–5.38) for VTE and 4.21 (1.82–9.77) for PE/LE‐DVT at FHCRC and OR of 3.54 (2.12–5.91) for VTE and 6.82 (2.30–20.16) for PE‐LE‐DVT at MDACC. The HIGH‐2‐LOW RAM identified allogeneic HCT recipients at high risk for VTE in both validation cohorts. It can improve evidence‐based decision‐making for thromboprophylaxis post‐transplant.

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Section: Table S5 Highlightsmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

External validation of the HIGH‐2‐LOW model: A predictive score for venous thromboembolism after allogeneic transplant

Martens

Nguyen

et al. 2022

American J Hematol

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“…91 In this study, neither patient sex nor hormone replacement therapy among females were associated with thrombosis risk. Likewise, Martens et al 76 studied risk factors for VTE in days 30 through 100 post-HCT and found no difference in risk based on sex.…”

Section: Hematopoietic Cell Transplantmentioning

confidence: 99%

Sex-Specific Cardiovascular Risks of Cancer and Its Therapies

Wilcox

Rotz

Mullen

et al. 2022

Circulation Research

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In both cardiovascular disease and cancer, there are established sex-based differences in prevalence and outcomes. Males and females may also differ in terms of risk of cardiotoxicity following cancer therapy, including heart failure, cardiomyopathy, atherosclerosis, thromboembolism, arrhythmias, and myocarditis. Here, we describe sex-based differences in the epidemiology and pathophysiology of cardiotoxicity associated with anthracyclines, hematopoietic stem cell transplant (HCT), hormone therapy and immune therapy. Relative to males, the risk of anthracycline-induced cardiotoxicity is higher in prepubertal females, lower in premenopausal females, and similar in postmenopausal females. For autologous hematopoietic cell transplant, several studies suggest an increased risk of late heart failure in female lymphoma patients, but sex-based differences have not been shown for allogeneic hematopoietic cell transplant. Hormone therapies including GnRH (gonadotropin-releasing hormone) modulators, androgen receptor antagonists, selective estrogen receptor modulators, and aromatase inhibitors are associated with cardiotoxicity, including arrhythmia and venous thromboembolism. However, sex-based differences have not yet been elucidated. Evaluation of sex differences in cardiotoxicity related to immune therapy is limited, in part, due to low participation of females in relevant clinical trials. However, some studies suggest that females are at increased risk of immune checkpoint inhibitor myocarditis, although this has not been consistently demonstrated. For each of the aforementioned cancer therapies, we consider sex-based differences according to cardiotoxicity management. We identify knowledge gaps to guide future mechanistic and prospective clinical studies. Furthering our understanding of sex-based differences in cancer therapy cardiotoxicity can advance the development of targeted preventive and therapeutic cardioprotective strategies.

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“…We captured additional time-varying covariates within the first 30 days post-HCT, including the decision to resume anticoagulation (or not) after platelet engraftment (defined as platelets >50 Â 10 9 /L without transfusion support), and components of the recently derived HIGH-2-LOW risk assessment score. 13 This risk assessment model, which incorporates seven clinical predictors, helps stratify allogeneic HCT patients not on therapeutic anticoagulants by day 30 into risk categories for VTE. These predictors, with their assigned integer scores, include: history of CR-DVT (+1), inpatient admission at day 30 (+1), GVHD grade 3-4 at day 30 (+1), history of PE or LE-DVT (+2), lymphoid diagnosis (+1), obesity with body mass index ≥35 kg/m 2 (+1), and white blood cells ≥11 Â 10 9 /L at day 30 (+1).…”

Section: Risk Factors For Vte Recurrence Beyond 30 Daysmentioning

confidence: 99%

“…In our recent study of VTE in the allogeneic HCT setting, we identified patients with history of VTE at higher risk for the development of VTE after HCT. 13 Our study was limited, however, by the exclusion of patients on anticoagulants at the time of HCT. Thus, how to manage patients on anticoagulation for history of VTE during the post-HCT period remains unanswered.…”

Section: Introductionmentioning

confidence: 99%

Impact of anticoagulation on recurrent thrombosis and bleeding after hematopoietic cell transplantation

et al. 2021

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History of venous thromboembolism (VTE) is prevalent among patients undergoing hematopoietic cell transplantation (HCT). Management of anticoagulation is particularly challenging as most patients will have chemotherapy-induced thrombocytopenia while awaiting engraftment post-HCT. We conducted a retrospective study of autologous and allogeneic HCT recipients with prior VTE from 2006-2015 to 1) compare anticoagulant strategies on short-term VTE recurrence and bleeding and 2) assess predictors for VTE recurrence beyond 30 days. Patients with VTE were allocated to two cohorts based on anticoagulant strategy at thrombocytopenia onset and underwent inverse probability weighting to assess primary outcomes of VTE recurrence and bleeding within 30 days post-HCT. Subsequently, multivariable logistic regression model was used to assess the association of 100-day VTE recurrence by the HIGH-2-LOW VTE risk assessment score and whether patients resumed anticoagulation at platelet recovery. Thirteen percent of recipients had VTE prior to HCT; of those meeting inclusion criteria, 227 continued anticoagulation and 113 temporarily discontinued it. Anticoagulant strategy was not significantly associated with decreased risk of VTE recurrence within 30 days (3% vs 4%, p = 0.61); however, risk of overall bleeding was non-significantly higher in those who continued vs discontinued anticoagulation (41% vs 31%, p = 0.08). In a subgroup of 250 allogeneic HCT patients, every one-point increase of HIGH-2-LOW score was significantly associated with VTE recurrence at 100 days (OR 1.57 [95% CI 1.10-2.23]), while anticoagulation resumption upon platelet engraftment was associated with lower

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HIGH-2-LOW risk model to predict venous thromboembolism in allogeneic transplant patients after platelet engraftment

Cited by 17 publications

References 25 publications

External validation of the HIGH‐2‐LOW model: A predictive score for venous thromboembolism after allogeneic transplant

External validation of the HIGH‐2‐LOW model: A predictive score for venous thromboembolism after allogeneic transplant

Sex-Specific Cardiovascular Risks of Cancer and Its Therapies

Impact of anticoagulation on recurrent thrombosis and bleeding after hematopoietic cell transplantation

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