Venous Thromboembolism in Hematologic Malignancy and Hematopoietic Cell Transplant Patients: a Retrospective Study

March 15, 2024 updated by: Mount Sinai Hospital, Canada

Venous Thromboembolism in Hematologic Malignancy and Hematopoietic Cell Transplant Patients: a Retrospective Study of Thrombosis / Bleeding Incidence and Prophylaxis Trends

Venous thromboembolism (VTE) is the second leading cause of death in patients with cancer, after disease progression. VTE is increasingly recognized as a complication in patients with hematologic malignancies and various studies have reported high rates of VTE. Critically ill patients are at high risk of VTE and should all receive thromboprophylaxis. Given the increasing number of patients with HM (hematologic malignancies) / HCT (Hematopoietic cell transplantation) who develop critical illness, and their often prolonged course, it is imperative to understand the incidence and risk factors for VTE, and to evaluate the efficacy and risks associated with both chemical and mechanical thromboprophylaxis Therefore, the investigators plan to evaluate retrospectively the VTE / PE (pulmonary embolism) incidence in HM /HCT patients at the University of Toronto, and the complications associated with it (including death). In addition, the investigators want to evaluate the use, type (mechanical or pharmacological) and timing of thromboprophylaxis. And lastly, the investigators will determine the incidence of bleeding and of complications associated with chemical and mechanical thromboprophylaxis. The investigators will describe the change in VTE incidence over the last 10 years.

The investigators know that patients with COVID-19 infection are at higher risk of thrombosis than non-COVID patients. As such, HM/HCT COVID-19 pts will comprise a subgroup, which will be compared with patients who are not not positive for COVID-19. If these numbers are low, COVID-19 status will be included as a predictive variable in our modelling.

The results of this research program will help define indications and safety of VTE prophylaxis; and will inform the development of clinical practice guidelines.

Study Overview

Status

Active, not recruiting

Conditions

Detailed Description

2.0 BACKGROUND AND SIGNIFICANCE Venous thrombosis is a disease of aging, with a low rate of about 1 per 10,000 annually before the fourth decade of life, rising rapidly after age 45 years, and approaching 5-6 per 1000 annually by age 801. The most common risk factors are hospitalization, cancer and surgery. Up to 20% of patients admitted to a medical service will have thrombosis and up to 40% of those admitted to a surgical service. About 10% of all deaths in hospitals are related to pulmonary embolism, and many times it was not suspected before death.

Venous thromboembolism (VTE) is the second leading cause of death in patients with cancer, after disease progression2. The incidence of venous thrombosis during the first 6 months after cancer diagnosis is 12.4 per 1000, with varying incidences depending of the type of cancer, i.e., cancers of the bone (56/1000), ovary (45/1000), uterus (38/1000), Hodgkin's lymphoma (36/1000), breast (35/1000) and brain (32/1000) had the highest incidence. Cancers of the ovary, pancreas, lung, stomach, and hematological malignancies tend to present a high incidence of venous thromboembolism in the year before the cancer diagnosis.

VTE is increasingly recognized as a complication in patients with hematologic malignancies and various studies have reported high rates of VTE. Another high risk population for bleeding and DVT is the HSCT (hematopoietic stem cell transplant), with a 3.7% 1-year incidence of VTE, and 8-20% incidence of catheter-related thrombosis (CRT)3. In addition to a risk of thrombosis, HSCT recipients also have an increased risk of bleeding because of prolonged and severe thrombocytopenia. The initiation of therapeutic anticoagulation during days 1-180 after HSCT was the strongest predictor of bleeding (odds ratio (OR) 3.1[95% confidence interval (CI) 1.8-5.5)].

The timing of hemostatic complications is also an important consideration as bleeding events are more likely to occur early in the post-transplant course when patients are profoundly thrombocytopenic, whereas thrombotic events occur more frequently after hematopoietic recovery Critically ill patients are at high risk of VTE and should all receive thromboprophylaxis. Patients with HM or HCT who are thrombocytopenic (platelets <30) are ineligible for pharmacologic prophylaxis because of the high risk of bleeding. In these patients, it has been suggested to apply mechanical antithrombotic measures 4, but not all centers have sequential compression devices (SCD). In the general population of patients admitted to the hospital, it has been suggested that SCDs do not reduce the risk of VTE 5. In critically ill patients, evidence of benefit of SCD use is lacking. Further, their use is associated with costs, discomfort, skin breakdown, and mobility restrictions. In healthcare settings lacking SCDs, patients receive no thromboprophylaxis until the platelet count recovers.

Early after chemotherapy or HCT, two recent studies in non-ICU patients suggest that rates of non catheter-related VTE are low, raising the question of whether any prophylaxis is required. In a prospective study of 1,072 consecutive adult cancer patients, only 30 VTE events were observed during follow-up, 5 (2.3%) in HM patients and 25 (2.9%) in solid tumor patients (relative risk [RR]: 0.79, 95% CI: 0.30-2.03; p=.79) (2). Four of the five episodes in HM patients were related to a catheter. Major bleeding was infrequent in both groups (1.8 vs. 3.9%; RR: 0.48, 95% CI: 0.17-1.33; p=.21), and thromboprophylaxis was not associated with an increased incidence of major bleeding.

While thromboprophylaxis may not be necessary in non-ICU patients, data in critically ill patients regarding the incidence of VTE, effectiveness of thromboprophylaxis, and bleeding risk, is lacking. Moreover, the risk of VTE may be higher later in the course, when the platelet count recovers, or in patients with graft vs host disease or sinusoidal obstructive syndrome.

Given the increasing number of patients with HM/HCT who develop critical illness, and their often prolonged course, it is imperative to understand the incidence and risk factors for VTE, and to evaluate the efficacy and risks associated with both chemical and mechanical thromboprophylaxis.

3.0 HYPOTHESES AND SPECIFIC AIMS 3.1 Specific Aim 1 Determine the use, type (mechanical or pharmacological) and timing of thromboprophylaxis.

3.2 Specific Aim 2 Determine incidence of catheter and non catheter-related VTE (upper / lower extremity DVT and PE) and explore variables that are independently associated with it.

3.3 Specific Aim 3 Determine incidence of bleeding, complications associated with SCDs, and complications associated with VTE, including death. Bleeding severity will be classified according to current accepted standards6.

3.4 Hypothesis In critically ill patients with hematologic malignancy (HM) who are thrombocytopenic, venous thromboembolism (VTE) is infrequent within the first 30 days following induction chemotherapy or hematopoietic cell transplant (HCT), rendering it possible to avoid the use of thromboprophylaxis (mechanical or pharmacological) and the associated risks (i.e. serious bleeding).

The investigators propose a program of research on VTE in HM/HCT patients. This program consists of several projects which will inform the design of a future international multi-center RCT. It will consist of three consecutive phases:

  1. To conduct a systematic review to evaluate the incidence and timing of VTE, and the threshold for initiation of chemical thromboprophylaxis.
  2. To evaluate retrospectively VTE incidence in HM / HCT patients at the University of Toronto.
  3. To design a 2-center pilot feasibility RCT of sequential compression devices (SCD) versus no thromboprophylaxis in thrombocytopenic HM/HCT patients admitted to ICU.

Regarding the second objective, the investigators will perform a retrospective analysis of VTE incidence in HM/HCT patients at University of Toronto.

Study Type

Observational

Enrollment (Actual)

813

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M4Y 1G3
        • Federico Carini

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

All patients 18 years and older admitted to an adult intensive care unit during the current admission episode and that also had an active HM / HCT diagnosis.

Description

Inclusion Criteria:

  • All patients 18 years and older admitted to an adult intensive care unit during the current admission episode and that also had an active HM / HCT diagnosis.

Exclusion Criteria:

  • Patients not admitted to the ICU, even though they had a diagnosis of HM / HCT.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Retrospective

Cohorts and Interventions

Group / Cohort
Patients with an active hematological malignancy admitted to ICU

All patients 18 years and older admitted to an adult intensive care unit during the current admission episode and that also had an active HM / HCT diagnosis.

We plan to the analyze patients outcomes according to:

  1. Thrombocytopenia We will analyze bleeding and thrombosis risk taking into account platelets levels.
  2. Patients receiving thromboprophylaxis (VTE vs Bleeding)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
VTE
Time Frame: Through study completion, an average of 1 month
The primary outcome will be the number of patients who suffered a catheter and non catheter related VTE (upper/lower extremity DVT and PE) during their ICU admission. For DVT diagnosis venous ultrasonography is the first-line imaging test. Alternative imaging modalities will include computed tomographic imaging, magnetic resonance (MR) imaging, and contrast computed tomography (CT)(12). For the diagnosis of PE, confirmatory imaging (i.e., CT pulmonary angiography, ventilation-perfusion scan) will be required for definitive diagnosis
Through study completion, an average of 1 month

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Thromboprophylaxis use
Time Frame: Through study completion, an average of 1 month
Frequency of use, type (mechanical or pharmacological) and timing of thromboprophylaxis
Through study completion, an average of 1 month
Bleeding
Time Frame: Through study completion, an average of 1 month
No bleeding, Minor bleeding or major bleeding, collected from chart review.
Through study completion, an average of 1 month
Outcome
Time Frame: Through study completion, an average of 1 month
Discharge to home, transfer to another hospital, transfer to rehabilitation facility, death
Through study completion, an average of 1 month

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Mount Sinai Hospital, Canada

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 1, 2021

Primary Completion (Estimated)

August 2, 2024

Study Completion (Estimated)

December 1, 2024

Study Registration Dates

First Submitted

January 5, 2022

First Submitted That Met QC Criteria

May 24, 2022

First Posted (Actual)

May 31, 2022

Study Record Updates

Last Update Posted (Actual)

March 19, 2024

Last Update Submitted That Met QC Criteria

March 15, 2024

Last Verified

August 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CariniDVT2021

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

No individual patient information will be included in the analysis. All data will be anonymized.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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