An observational study in Heparin Induced Thrombocytopenia, sponsored by Carelon Research. Completed at 21 sites in United States. Per ClinicalTrials.gov, last updated 2015-05-22.
Sponsored by Carelon Research · Observational
HIT-RADIO is a study of patients who had a positive heparin PF-4 antibody test between 1/21/2008 and 9/25/2008 at selected hospitals. The study will collect and analyse information that is already in the patients' medical records. Information about laboratory values (such as platelet counts), treatments (such as medications), and outcomes (such as blood clots, amputation, and death) will be included.
HIT-RADIO is a retrospective chart-review study of patients who had a positive heparin PF-4 antibody test between 1/21/2008 and 9/25/2008 at selected hospitals associated with the Transfusion Medicine/Hemostasis Clinical Trials Network .
Heparin-induced thrombocytopenia (HIT) is a major complication of the administration of heparin and can result in life-threatening thrombosis with or without thrombocytopenia (HIT-T) or can produce thrombocytopenia without clinically symptomatic thrombosis ("isolated" HIT). Isolated heparin-induced thrombocytopenia is defined as a fall in platelet count associated with a positive heparin PF-4 antibody test, in the absence of clinically overt thrombosis. While the treatment of HIT-T (HIT with thrombosis) with anticoagulation is well established, the risks and treatment of isolated HIT are unclear.
It is anticipated that this data analysis will provide a current overview of the implications of a positive heparin PF-4 antibody test in clinical practice. It should determine the percentage of positive heparin PF-4 antibody tests that are associated with thrombocytopenia and thrombosis (HIT-T) or "isolated" HIT at diagnosis and the subsequent major clinical outcomes of death, limb amputation/gangrene, and new thrombosis. No "snapshot" of such HIT patients has been conducted in the past decade and the results will be important in assessing the impact of HIT in current medical care as well as documenting current treatment strategies.
703 studies on the registry are indexed under Thrombocytopenia; 150 are open to participants now.
This study's enrollment of 668 is above the median of 120 across 186 observational studies indexed under Thrombocytopenia.
Browse Thrombocytopenia studies →Carelon Research is the lead sponsor of 59 studies on the registry; 4 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Subjects with a positive heparin PF-4 antibody test drawn between 1/21/2008 and 9/25/2008
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Time to Occurrence of a Composite Triple Endpoint Consisting of Death, Limb Amputation/Gangrene, and New Thrombosis
The mean time to an event is estimated by the area under the survival function. If the largest time is an event time, then the survival function goes to zero at that time, and the mean survival estimate is finite. Otherwise, the mean time cannot be estimated and may lead to a bias.
Time frame: From the time that the positive heparin PF-4 antibody test was drawn until hospital discharge or day 45, whichever occurred first.
Time to Occurrence of a Composite Triple Endpoint Consisting of Death, Limb Amputation/Gangrene, and New Thrombosis
The median survival time is reported by each group for the time to occurrence of a composite triple endpoint consisting of death, limb amputation/gangrene, and new thrombosis.
Time frame: From the time that the positive heparin PF-4 antibody test was drawn until hospital discharge or day 45, whichever occurred first.
Time to Death
The mean time to an event is estimated by the area under the survival function. If the largest time is an event time, then the survival function goes to zero at that time, and the mean survival estimate is finite. Otherwise, the mean time cannot be estimated and may lead to a bias.
Time frame: From the time the positive heparin PF-4 antibody test was drawn until hospital discharge, death, or day 45, whichever occurred first
Time to Death
The median survival time is reported by each group for the time to death.
Time frame: From the time the positive heparin PF-4 antibody test was drawn until hospital discharge, death, or day 45, whichever occurred first
Time to Occurrence of Limb Amputation or Limb Gangrene
Due to the small number of events, the median or mean survival time could not be defined. Therefore, the number of subjects with limb amputation or limb gangrene was reported in "Outcome Measure Data Table".
Time frame: From the time the positive heparin PF-4 antibody test was drawn until hospital discharge, death, or day 45, whichever occurred first
Time to Occurrence of Radiographically Confirmed Thromboembolism
The mean time to an event is estimated by the area under the survival function. If the largest time is an event time, then the survival function goes to zero at that time, and the mean survival estimate is finite. Otherwise, the mean time cannot be estimated and may lead to a bias. However, the median survival times could not be defined for all three groups, so the mean time was reported in "Outcome Measure Data Table".
Time frame: From the time the positive heparin PF-4 antibody test was drawn until hospital discharge, death, or day 45, whichever occurred first
Time to Occurrence of Major Bleeding
The mean time to an event is estimated by the area under the survival function. If the largest time is an event time, then the survival function goes to zero at that time, and the mean survival estimate is finite. Otherwise, the mean time cannot be estimated and may lead to a bias.
Time frame: From the time that the positive heparin PF-4 antibody test was drawn until hospital discharge, death, or day 45, whichever occurred first
Time to Occurrence of Major Bleeding
The median survival time is reported by each group for the time to occurrence of major bleeding.
Time frame: From the time that the positive heparin PF-4 antibody test was drawn until hospital discharge, death, or day 45, whichever occurred first
Proportion of Subjects With HIT With Thrombosis (HIT-T) and Isolated HIT
Proportion of subjects who, at the time the positive heparin PF-4 antibody test was drawn, were in each of the following categories: * Group 1: Those with thrombosis and or without thrombocytopenia (HIT-T): 16% of 442 subjects. * Group 2: Those with thrombocytopenia but not thrombosis (Isolated HIT): 64% of 442 subjects. * Group 3: Those with neither thrombocytopenia nor thrombosis (Neither HIT-T nor Isolated HIT): 20% of 442 subjects.
Time frame: From the date 5 days before the positive heparin PF-4 antibody test was drawn to the date it was drawn
Type of Heparin Exposure - Unfractionated Heparin (UFH)
Two types of heparins are commonly used as anticoagulants - unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH). UFH has been used for the prevention and treatment of thrombosis for several decades.
Time frame: Hospital admission to date the positive heparin PF-4 antibody test was drawn, or 28 days prior to the date it was drawn, whichever is later, through the date it was drawn
Type of Heparin Exposure - Low Molecular Weight Heparin (LMWH)
Two types of heparins are commonly used as anticoagulants - unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH). LMWHs are derived from UFH by depolymerization. Each LMWH product has a specific molecular weight distribution that determines its anticoagulant activity and duration of action.
Time frame: Hospital admission to date the positive heparin PF-4 antibody test was drawn, or 28 days prior to the date it was drawn, whichever is later, through the date it was drawn
Relationship of the Heparin PF-4 (Platelet Factor 4) Antibody Titer to the Clinical Diagnosis
Heparin PF-4 (platelet factor 4) optical density (OD) test results were the dichotomous outcome (\<1.0 vs. \>=1.0). Clinical diagnosis was three groups (HIT-T, Isolated HIT and No HIT). The Heparin PF-4 optical density test looks for antibodies to complexes of heparin combined with platelet factor 4. Higher optical density indicates higher antibody concentration. We could say that generally OD values above 0.4 are considered a positive result, and that the higher the OD, the greater the concentration of antibodies in the patient's blood.
Time frame: From the time the positive heparin PF-4 antibody test was drawn until hospital discharge, death, or day 45, whichever occurred first
Relationship of the Heparin PF-4 Antibody Titer to the Degree of Thrombocytopenia
Heparin PF-4 optical density (OD) test results were the dichotomous outcome (\<1.0 vs. \>=1.0). Nadir Platelet Count (x10\^9 / L) was used for the degree of thrombocytopenia. The Heparin PF-4 optical density test looks for antibodies to complexes of heparin combined with platelet factor 4. Higher optical density indicates higher antibody concentration. We could say that generally OD values above 0.4 are considered a positive result, and that the higher the OD, the greater the concentration of antibodies in the patient's blood.
Time frame: From the time the positive heparin PF-4 antibody test was drawn until hospital discharge, death, or day 45, whichever occurred first
Relationship of the Heparin PF-4 Antibody Titer to the Primary Endpoint
Heparin PF-4 OD test results were the dichotomous outcome (\<1.0 vs. \>=1.0). Primary endpoint was the composite endpoint of death, limb amputation/gangrene, or new thrombosis.
Time frame: From the time the positive heparin PF-4 antibody test was drawn until hospital discharge, death, or day 45, whichever occurred first
Use of Treatment (Non-heparin Anticoagulant) Used in Hospital
Types of treatment (direct thrombin inhibitor, fondaparinux, warfarin, no treatment) provided to subjects in hospital
Time frame: From the time that the positive heparin PF-4 antibody test was drawn until hospital discharge, death, or day 45, whichever occurred first
Use of Treatment (Non-heparin Anticoagulant) Used at the Time of Discharge
Time frame: From the time that the positive heparin PF-4 antibody test was drawn until hospital discharge, death, or day 45, whichever occurred first
Time to Platelet Recovery, Among Subjects With a Low Platelet Count When the Positive PF4 Antibody Test Was Drawn
Time frame: From the time that the nadir platelet count was drawn until hospital discharge, death, or day 45, whichever occurred first
Of 668 consecutive patients with a positive heparin-PF4 ELISA test, 226 were excluded, primarily due to lack of recent heparin exposure. Of 442 eligible patients, 71 had HIT-T, 284 had Isolated HIT and 87 had no HIT.
| Milestone | HIT-T | Isolated HIT | No HIT |
|---|---|---|---|
| Started | 71 | 284 | 87 |
| Completed | 71 | 284 | 87 |
| Not completed | 0 | 0 | 0 |
The mean time to an event is estimated by the area under the survival function. If the largest time is an event time, then the survival function goes to zero at that time, and the mean survival estimate is finite. Otherwise, the mean time cannot be estimated and may lead to a bias.
| days | HIT-T | Isolated HIT | No HIT |
|---|---|---|---|
| Time to Death | 23.6 ± 1.43 | 35.4 ± 1.11 | 34.5 ± 2.64 |
The median survival time is reported by each group for the time to death.
| days | HIT-T | Isolated HIT | No HIT |
|---|---|---|---|
| Time to Death | 31.0 (23.0 to NA) | NA (NA to NA) | NA (29.0 to NA) |
Due to the small number of events, the median or mean survival time could not be defined. Therefore, the number of subjects with limb amputation or limb gangrene was reported in "Outcome Measure Data Table".
| participants | HIT-T | Isolated HIT | No HIT |
|---|---|---|---|
| Time to Occurrence of Limb Amputation or Limb Gangrene | 5 | 6 | 1 |
The mean time to an event is estimated by the area under the survival function. If the largest time is an event time, then the survival function goes to zero at that time, and the mean survival estimate is finite. Otherwise, the mean time cannot be estimated and may lead to a bias. However, the median survival times could not be defined for all three groups, so the mean time was reported in "Outcome Measure Data Table".
| days | HIT-T | Isolated HIT | No HIT |
|---|---|---|---|
| Time to Occurrence of Radiographically Confirmed Thromboembolism | 11.1 ± 0.48 | 26.1 ± 0.74 | 5.74 ± 0.11 |
The mean time to an event is estimated by the area under the survival function. If the largest time is an event time, then the survival function goes to zero at that time, and the mean survival estimate is finite. Otherwise, the mean time cannot be estimated and may lead to a bias.
| days | HIT-T | Isolated HIT | No HIT |
|---|---|---|---|
| Time to Occurrence of Major Bleeding | 15.6 ± 1.54 | 26.5 ± 1.36 | 17.2 ± 0.97 |
The median survival time is reported by each group for the time to occurrence of major bleeding.
| days | HIT-T | Isolated HIT | No HIT |
|---|---|---|---|
| Time to Occurrence of Major Bleeding | 17.0 (8.0 to 28.0) | 36.0 (31.0 to NA) | NA (16.0 to NA) |
Proportion of subjects who, at the time the positive heparin PF-4 antibody test was drawn, were in each of the following categories: * Group 1: Those with thrombosis and or without thrombocytopenia (HIT-T): 16% of 442 subjects. * Group 2: Those with thrombocytopenia but not thrombosis (Isolated HIT): 64% of 442 subjects. * Group 3: Those with neither thrombocytopenia nor thrombosis (Neither HIT-T nor Isolated HIT): 20% of 442 subjects.
| participants | HIT-T | Isolated HIT | No HIT |
|---|---|---|---|
| Proportion of Subjects With HIT With Thrombosis (HIT-T) and Isolated HIT | 71 | 284 | 87 |
Two types of heparins are commonly used as anticoagulants - unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH). UFH has been used for the prevention and treatment of thrombosis for several decades.
| participants | HIT-T | Isolated HIT | No HIT |
|---|---|---|---|
| Number of subjects with heparin exposure:UFH | 67 | 263 | 79 |
| Number of subjects without heparin exposure:UFH | 4 | 21 | 8 |
Two types of heparins are commonly used as anticoagulants - unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH). LMWHs are derived from UFH by depolymerization. Each LMWH product has a specific molecular weight distribution that determines its anticoagulant activity and duration of action.
| participants | HIT-T | Isolated HIT | No HIT |
|---|---|---|---|
| Number of subjects with heparin exposure:LMWH | 15 | 48 | 11 |
| Number of subjects without heparin exposure:LMWH | 56 | 236 | 76 |
Heparin PF-4 (platelet factor 4) optical density (OD) test results were the dichotomous outcome (\<1.0 vs. \>=1.0). Clinical diagnosis was three groups (HIT-T, Isolated HIT and No HIT). The Heparin PF-4 optical density test looks for antibodies to complexes of heparin combined with platelet factor 4. Higher optical density indicates higher antibody concentration. We could say that generally OD values above 0.4 are considered a positive result, and that the higher the OD, the greater the concentration of antibodies in the patient's blood.
| participants | HIT-T | Isolated HIT | No HIT |
|---|---|---|---|
| Optical density Results less than 1.0 | 34 | 163 | 61 |
| Optical density Results greater or equal to 1.0 | 37 | 120 | 26 |
Heparin PF-4 optical density (OD) test results were the dichotomous outcome (\<1.0 vs. \>=1.0). Nadir Platelet Count (x10\^9 / L) was used for the degree of thrombocytopenia. The Heparin PF-4 optical density test looks for antibodies to complexes of heparin combined with platelet factor 4. Higher optical density indicates higher antibody concentration. We could say that generally OD values above 0.4 are considered a positive result, and that the higher the OD, the greater the concentration of antibodies in the patient's blood.
| X10^9 / L | OD Result < 1.0 | OD Result >= 1.0 |
|---|---|---|
| Relationship of the Heparin PF-4 Antibody Titer to the Degree of Thrombocytopenia | 87.7 ± 92.4 | 83.1 ± 76.4 |
Heparin PF-4 OD test results were the dichotomous outcome (\<1.0 vs. \>=1.0). Primary endpoint was the composite endpoint of death, limb amputation/gangrene, or new thrombosis.
| participants | OD Result < 1.0 | OD Result >= 1.0 |
|---|---|---|
| Composite endpoint | 85 | 66 |
| No composite endpoint | 173 | 117 |
Types of treatment (direct thrombin inhibitor, fondaparinux, warfarin, no treatment) provided to subjects in hospital
| participants | HIT-T | Isolated HIT | No HIT |
|---|---|---|---|
| Number of subjects with treatment in hospital | 58 | 167 | 43 |
| Number of subjects without treatment in hospital | 13 | 117 | 44 |
The mean time to an event is estimated by the area under the survival function. If the largest time is an event time, then the survival function goes to zero at that time, and the mean survival estimate is finite. Otherwise, the mean time cannot be estimated and may lead to a bias.
| days | HIT-T | Isolated HIT | No HIT |
|---|---|---|---|
| Time to Occurrence of a Composite Triple Endpoint Consisting of Death, Limb Amputation/Gangrene, and New Thrombosis | 17.5 ± 1.66 | 27.8 ± 1.30 | 31.4 ± 2.67 |
The median survival time is reported by each group for the time to occurrence of a composite triple endpoint consisting of death, limb amputation/gangrene, and new thrombosis.
| days | HIT-T | Isolated HIT | No HIT |
|---|---|---|---|
| Time to Occurrence of a Composite Triple Endpoint Consisting of Death, Limb Amputation/Gangrene, and New Thrombosis | 13.0 (9.0 to NA) | 33.0 (25.0 to NA) | NA (29.0 to NA) |
| participants | HIT-T | Isolated HIT | No HIT |
|---|---|---|---|
| Number of subjects with treatment at discharge | 57 | 159 | 39 |
| Number of subjects with no treatment at discharge | 14 | 125 | 48 |
| days | HIT-T | Isolated HIT | No HIT |
|---|---|---|---|
| Time to Platelet Recovery, Among Subjects With a Low Platelet Count When the Positive PF4 Antibody Test Was Drawn | 5.16 ± 0.92 | 5.16 ± 0.38 | 2.96 ± 0.33 |
Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| HIT-T | — | — | — |
| Isolated HIT | — | — | — |
| No HIT | — | — | — |
Of 668 consecutive patients with a positive heparin-PF4 ELISA test, 225 were excluded, primarily due to lack of recent heparin exposure. Of 442 eligible patients, 71 had HIT-T, 284 had Isolated HIT and 87 had no HIT.
| Age, Continuous(years) | HIT-T | Isolated HIT | No HIT | Total |
|---|---|---|---|---|
| Mean | 62 ± 16 | 59 ± 18 | 60 ± 19 | 60 ± 18 |
| Sex: Female, Male(Participants) | HIT-T | Isolated HIT | No HIT | Total |
|---|---|---|---|---|
| Female | 39 | 144 | 40 | 223 |
| Male | 32 | 140 | 47 | 219 |
| Baseline Platelet Count(x 10^9/L) | HIT-T | Isolated HIT | No HIT | Total |
|---|---|---|---|---|
| Mean | 282 ± 268 | 270 ± 149 | 215 ± 172 | 261 ± 158 |
| Heparin exposure this admission before Day 0: use (or non-use) of unfractionated heparin (UFH)(participants) | HIT-T | Isolated HIT | No HIT | Total |
|---|---|---|---|---|
| Use of unfractionated heparin | 67 | 263 | 79 | 409 |
| Non-use of unfractionated heparin | 4 | 21 | 8 | 33 |
| Heparin exposure this admission before Day 0: use (or non-use) of low molecular weight heparin(participants) | HIT-T | Isolated HIT | No HIT | Total |
|---|---|---|---|---|
| Use of low molecular weight heparin | 15 | 48 | 11 | 74 |
| Non-use of low molecular weight heparin | 56 | 236 | 76 | 368 |
| Heparin-PF4 (platelet factor 4) OD (optical density) test results(participants) | HIT-T | Isolated HIT | No HIT | Total |
|---|---|---|---|---|
| Less than 1.0 | 34 | 163 | 61 | 258 |
| Greater than or equal to 1.0 | 37 | 120 | 26 | 183 |
| Missing | 0 | 1 | 0 | 1 |
| Admitting service(participants) | HIT-T | Isolated HIT | No HIT | Total |
|---|---|---|---|---|
| CV/thoracic surgery | 18 | 78 | 18 | 114 |
| Orthopedic surgery | 2 | 9 | 4 | 15 |
| Other surgery | 15 | 33 | 8 | 56 |
| Medicine | 36 | 161 | 56 | 253 |
| Missing | 0 | 3 | 1 | 4 |
The record gives a start of Jun 2010, a primary completion of Dec 2010 and a completion of Dec 2010. It does not say whether these dates are actual or estimated.
Results were first posted in May 2015, 4 years 5 months after primary completion.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Mar 2013. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Carelon Research