Heparin-induced Thrombocytopenia (HIT)
Conditions
Brief summary
Multicentre (Ottawa and Halifax) prospective cohort study using a diagnostic approach in patients clinically suspected to have HIT that combines pretest probability assessment with quantitative interpretation of anti-PF4 assay.
Detailed description
The proposed is a prospective cohort study exploring a novel diagnostic approach to Heparin Induced Thrombocytopenia (HIT) using a combination of pretest probability assessment and quantitative interpretation of the anti-platelet factor 4 Immunological assay (anti-PF4). Patient with a clinical suspicion of HIT will follow the study diagnostic algorithm (Figure 1). The study algorithm will be considered a safe approach to move forward into a larger RCT if the upper limit of the 95% confidence interval for 'false negative management failures' is ≤ 4% based on a Serotonin Release Assay (SRA) gold standard. The main objective of the pilot study is to inform feasibility and recruitment barriers for a larger randomized control trial.
Interventions
DIAGNOSTIC_TESTDiagnostic algorithm
The treating physician will complete an enrollment assessment including the 4T score pretest probability assessment14. All patients will have laboratory testing for HIT anti-PF4 as well as SRA testing. Results of the anti-PF4 assay (OD value) will be available to the treating physician who will be instructed to follow the study diagnostic algorithm
Sponsors
Ottawa Hospital Research Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patient with clinical suspicion of HIT by treating physician
Exclusion criteria
1. Less than 18 years of age; 2. Prior diagnosis of HIT ever; 3. Patient enrolled within preceding 100 days; 4. Functional/ confirmatory platelet activation results available at the time of enrollment; 5. Requiring cardio-pulmonary bypass or percutaneous cardiac angioplasty or any other cardiac or vascular surgery/procedure requiring intra-operative/procedural heparin administration planned within 30 days; 6. Unable to complete study follow up; 7. Unable to obtain consent (or proxy consent from substitute decision maker where applicable); 8. Life expectancy less than 30 days; 9. Greater than 72 hours from clinical suspicion of HIT and/or request for HIT anti-PF4 ELISA testing.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Recruitment | 2 years | The pilot will be considered feasible if recruitment of at least 7.5 patients per month (total between the two sites) is achieved. |
| False negative management failures | 2 years | The rate of false negative 'management failures' where the study protocol concludes HIT unlikely but SRA (reference standard laboratory test) is positive for HIT (≥50% Serotonin release). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pulmonary embolism | 2 years | Testing performed because of symptoms in a patient with a high probability lung scan (i.e. at least one segmental perfusion mismatch) or CT pulmonary angiography (i.e. intraluminal filling defect in the main, lobar or segmental pulmonary arteries) will be diagnostic for pulmonary embolism. |
| Stroke | 2 years | New infarction or hemorrhagic event confirmed on CT or MRI. |
| Major arterial and venous thromboembolism events | 24 hours of baseline and 24 of study enrolment | Events will be ascertained from the date of study consent. However, venous or arterial thrombotic events detected on investigations ordered within 24 hours of study entry will be captured as baseline events and will be counted separately from thrombotic events which occur after the initial 24 hours of study enrolment. |
| Systemic arterial embolism | 2 years | Acute vascular occlusion confirmed on ultrasound or angiography Adrenal hemorrhagic infarction (indicating adrenal vein thrombosis) - radiologic diagnosis on ultrasound or CT. |
| Death | 30 days of follow up | Due to major arterial or venous thromboembolism within 30days of follow up and major and minor bleeding. |
| Myocardial infarction | 2 years | Detection of rise and/or fall of cardiac biomarkers (preferably troponin) with at least one value above the 99th percentile of the upper reference limit together with evidence of myocardial ischemia with at least one of the following: Symptoms of ischemia for ≥ 20 minutes ECG changes indicative of new ischemia: new ST-T changes ≥0.1 mV or new left bundle branch block Development of pathological Q waves in the ECG; Imaging evidence of new loss of viable myocardium or new regional wall motion abnormality. |
| Proximal deep vein thrombosis | 2 years | Testing performed because of symptoms in a patient with (new) non-compressibility of the common femoral vein, popliteal vein or calf trifurcation vein of the leg on ultrasound; or new non-compressibility or visualization of thrombus in the jugular vein, subclavian vein or axillary vein on ultrasound; or an intraluminal defect seen in one more than one view in proximal leg or arm veins on venography will be diagnostic for deep vein thrombosis. |
Countries
Canada
Contacts
Primary ContactChantal Rockwell, BA
Outcome results
None listed