Thrombocytopenia
Conditions
Keywords
Heparin, Thromboembolism, Thrombosis
Brief summary
Heparin-induced thrombocytopenia (HIT), a condition characterized by low platelet levels and possible blood clots, occurs in a small number of people after treatment with the drug heparin. Some people with HIT may show symptoms of a blood clot at the time of HIT diagnosis, but in another form of HIT, known as isolated HIT, people do not show blood clot symptoms even though they might have a blood clot. This study will use ultrasound tests to evaluate the presence of blood clots at the time of an HIT diagnosis and in the following month.
Detailed description
Heparin is a blood thinning medication that is often prescribed to treat or prevent blood clots. HIT is a life-threatening immune disorder that occurs in 1 to 3% of people who receive heparin. In this disorder, heparin does the opposite of what it is supposed to do: it promotes new blood clot formation, rather than preventing it. In people with HIT, the immune system triggers a response against heparin, leading to the destruction of platelets and a low platelet count, which is known as thrombocytopenia. Symptoms usually occur between 5 to 14 days after starting heparin therapy. Isolated HIT is a form of the condition that occurs when people have a low platelet count, but there is no sign of a blood clot, or thrombosis. Several small research studies have shown that at the time of isolated HIT diagnosis, between 15 to 50% of people actually have asymptomatic thrombosis, which means that they are not showing any signs of a blood clot, but in fact have one. In the month following HIT diagnosis, up to 50% of people experience symptomatic thrombosis, which means that they are showing signs of a blood clot. It is not currently known how to best treat isolated HIT and how to test for unrecognized blood clots. This study will use ultrasound imaging to evaluate the number of people who have asymptomatic thrombosis at the time of isolated HIT diagnosis and to determine the rate of symptomatic and asymptomatic thrombosis in the following month. The results of this study will assist researchers in assessing current approaches to treating isolated HIT and in designing new clinical trials. By exploring the use of non-invasive evaluation techniques in people with HIT, thrombosis research in HIT will move forward, similar to thrombosis research in other medical conditions. This 29-day study will enroll hospital patients who have a diagnosis of HIT but show no signs of a blood clot at the time of HIT diagnosis. On Day 1, participants will undergo blood collection and an ultrasound. While participants are in the hospital, study researchers will review participants' medical records on a daily basis to collect data on current medications, medication compliance, symptoms, bleeding, thrombosis complications, and laboratory test results. Once participants leave the hospital, this data will be collected at least once a week through phone calls with the participant and/or the treating physician. On Day 29, participants will undergo a repeat ultrasound and blood collection.
Interventions
None listed
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
Carelon Research
Study design
Observational model
CASE_ONLY
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
6 Months to No maximum
Healthy volunteers
No
Inclusion criteria
* In the 72 hours prior to study entry, participant has been diagnosed with isolated HIT, as defined by an unexplained platelet count drop of over 50% that occurs after exposure to UFH (UnFractionated Heparin)/LMWH (Low Molecular Weight Heparin) at any time in the 4 to 14 days before the positive heparin-PF4 antibody test was sent(even if the person is no longer on UFH/LMWH) * Currently hospitalized * Available for study follow-up for at least 28 days after study entry * No contraindications to ultrasound examination of upper and lower extremities * For participants less than 7 years old, no contraindications to ultrasound examination of abdomen * Participants are eligible whether or not they are receiving any therapy for isolated HIT
Exclusion criteria
* Documented new venous or arterial thrombosis while on heparin * Pregnant * Ongoing active bleeding (as determined by the site investigator) * Currently using a extracorporeal membrane oxygenator, chronic veno-venous hemofiltration, left ventricular support device, intra-aortic balloon pump, or any other mechanical heart pump * Coronary artery bypass surgery occured within 96 hours prior to the time when the positive HIT test was drawn
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Percentage of Participants With Asymptomatic Thrombosis at the Time Isolated Heparin-Induced Thrombocytopenia (HIT) is Diagnosed, Determined by Four-limb Ultrasound | Measured at Day 1 | The percentage of participants with asymptomatic thrombosis at the time isolated HIT is diagnosed as determined by four-limb ultrasound. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Number of Participants With Symptomatic Venous or Arterial Thromboembolism in the Month Following the Diagnosis of Isolated HIT | Measured within 35 days (+/- 7) after the diagnosis of isolated HIT | There were two versions of the data collection form used in this study, and only the revised version collected information on whether the event was symptomatic. |
| The Number of Participants With Incidental Arterial and Venous Thromboembolism (i.e., a Clot Diagnosed by Radiographic Tests Done for Reasons Other Than to Diagnose or Rule Out a Thromboembolic Event) | Measured within 35 days (+/- 7) after the diagnosis of isolated HIT | There were two versions of the data collection form used in this study, and only the revised form contained information on whether the event was incidental. |
| The Time to First Bleeding Event With Current Therapies for Isolated HIT | Measured within 35 days (+/- 7) after the diagnosis of isolated HIT | The time to first bleeding event was analyzed using survival analysis. |
| Time Until Death From All Causes | Measured within 35 days (+/- 7) after the diagnosis of isolated HIT | The time until death from all causes, in days, was determined using survival analysis. |
| Time to Platelet Count Recovery | Measured within 35 days (+/- 7) after the diagnosis of isolated HIT | The time to platelet recovery was defined as the time from the nadir platelet count observed in the five days after the positive HIT test was sent to observing a platelet count of 100K or greater. Survival analysis was used. |
| The Percentage of Participants With Asymptomatic Thrombosis 4 Weeks After the Diagnosis of Isolated HIT, Determined by Four-limb Ultrasound | Measured at Day 35 (+/- 7days) | The percentage of participants with asymptomatic thrombosis 4 weeks after the diagnosis of isolated HIT, determined by four-limb ultrasound, and 95% exact binomial confidence interval. |
| Length of Hospital Stay | Measured upon hospital discharge | The length of time between the date of HIT diagnosis and first hospital discharge was calculated. Subjects were censored at death. Survival analysis was used. |
| Length of Hospital Stay (With Deaths Not Censored) | Measured upon hospital discharge | The length of time between the date of HIT diagnosis and first hospital discharge was calculated. Subjects were not censored at death. Survival analysis was used. |
| Relationship Between the Platelet Factor 4 (PF4)-Heparin Enzyme-Linked ImmunoSorbent Assay (ELISA) Test, the Serotonin-release Assay, and D-dimer Test Results | Measured at Day 1 | Analysis not performed since central laboratory tests were not done. |
| Relationship Between PF4-heparin ELISA Test, Serotonin-release Assay, and D-dimer Test Results and Thromboembolism | Measured at Day 1 and within 35 days (+/- 7) after the diagnosis of isolated HIT | Analysis not performed since central laboratory tests were not done. |
| Relationship Between the Presence of the Factor V Leiden Mutation or the Prothrombin 20210 Mutation and the Risk of Thrombosis | Measured at Day 1 and within 35 days (+/- 7) after the diagnosis of isolated HIT | Analysis not performed since central laboratory tests were not done. |
| Number of Days That Medications Were Given to Participants at Participating Institutions | Measured within 35 days (+/- 7) after the diagnosis of isolated HIT | Per the protocol, descriptive statistics on the types and durations of therapeutic approaches used will be presented. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Isolated HIT Hospitalized patients with isolated Heparin-Induced Thrombocytopenia (HIT), diagnosed by a fall in platelet count and a positive Platelet Factor 4 (PF4)-heparin Enzyme-Linked ImmunoSorbent Assay (ELISA) test | 10 |
| Total | 10 |
Baseline characteristics
| Characteristic | Isolated HIT |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants |
| Age Continuous | 54.5 years STANDARD_DEVIATION 13.9 |
| Region of Enrollment United States | 10 participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 10 |
| serious Total, serious adverse events | 2 / 10 |
Outcome results
Primary
The Percentage of Participants With Asymptomatic Thrombosis at the Time Isolated Heparin-Induced Thrombocytopenia (HIT) is Diagnosed, Determined by Four-limb Ultrasound
The percentage of participants with asymptomatic thrombosis at the time isolated HIT is diagnosed as determined by four-limb ultrasound.
Time frame: Measured at Day 1
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Isolated HIT | The Percentage of Participants With Asymptomatic Thrombosis at the Time Isolated Heparin-Induced Thrombocytopenia (HIT) is Diagnosed, Determined by Four-limb Ultrasound | 20 Percentage of participants |
Secondary
Length of Hospital Stay
The length of time between the date of HIT diagnosis and first hospital discharge was calculated. Subjects were censored at death. Survival analysis was used.
Time frame: Measured upon hospital discharge
Population: Two subjects were known to be readmitted to the hospital after initially being discharged.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Isolated HIT | Length of Hospital Stay | 10.4 Days | Standard Error 1.3 |
Secondary
Length of Hospital Stay (With Deaths Not Censored)
The length of time between the date of HIT diagnosis and first hospital discharge was calculated. Subjects were not censored at death. Survival analysis was used.
Time frame: Measured upon hospital discharge
Population: Two subjects were known to be readmitted to the hospital after initially being discharged.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Isolated HIT | Length of Hospital Stay (With Deaths Not Censored) | 10.1 Days | Standard Error 1.4 |
Secondary
Number of Days That Medications Were Given to Participants at Participating Institutions
Per the protocol, descriptive statistics on the types and durations of therapeutic approaches used will be presented.
Time frame: Measured within 35 days (+/- 7) after the diagnosis of isolated HIT
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Isolated HIT | Number of Days That Medications Were Given to Participants at Participating Institutions | Alteplase (Activase) - 1 subject | 11 Days medication was given |
| Isolated HIT | Number of Days That Medications Were Given to Participants at Participating Institutions | Argatroban - 4 subjects | 3.5 Days medication was given |
| Isolated HIT | Number of Days That Medications Were Given to Participants at Participating Institutions | Aspirin - 4 subjects | 36.5 Days medication was given |
| Isolated HIT | Number of Days That Medications Were Given to Participants at Participating Institutions | Clopidogrel (Plavix) - 2 subjects | 20.5 Days medication was given |
| Isolated HIT | Number of Days That Medications Were Given to Participants at Participating Institutions | Fondaparinux (Arixtra) - 3 subjects | 10 Days medication was given |
| Isolated HIT | Number of Days That Medications Were Given to Participants at Participating Institutions | Ibuprofen (Motrin, Advil) - 1 subject | 5 Days medication was given |
| Isolated HIT | Number of Days That Medications Were Given to Participants at Participating Institutions | Unfractionated Heparin - 3 subjects | 14 Days medication was given |
| Isolated HIT | Number of Days That Medications Were Given to Participants at Participating Institutions | Warfarin (Coumadin) - 5 subjects | 20 Days medication was given |
Secondary
Relationship Between PF4-heparin ELISA Test, Serotonin-release Assay, and D-dimer Test Results and Thromboembolism
Analysis not performed since central laboratory tests were not done.
Time frame: Measured at Day 1 and within 35 days (+/- 7) after the diagnosis of isolated HIT
Population: Analysis not performed since central laboratory tests were not done.
Secondary
Relationship Between the Platelet Factor 4 (PF4)-Heparin Enzyme-Linked ImmunoSorbent Assay (ELISA) Test, the Serotonin-release Assay, and D-dimer Test Results
Analysis not performed since central laboratory tests were not done.
Time frame: Measured at Day 1
Population: Analysis not performed since central laboratory tests were not done.
Secondary
Relationship Between the Presence of the Factor V Leiden Mutation or the Prothrombin 20210 Mutation and the Risk of Thrombosis
Analysis not performed since central laboratory tests were not done.
Time frame: Measured at Day 1 and within 35 days (+/- 7) after the diagnosis of isolated HIT
Population: Analysis not performed since central laboratory tests were not done.
Secondary
The Number of Participants With Incidental Arterial and Venous Thromboembolism (i.e., a Clot Diagnosed by Radiographic Tests Done for Reasons Other Than to Diagnose or Rule Out a Thromboembolic Event)
There were two versions of the data collection form used in this study, and only the revised form contained information on whether the event was incidental.
Time frame: Measured within 35 days (+/- 7) after the diagnosis of isolated HIT
Population: Two subjects did not have information on whether the event was incidental. These subjects were censored in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Isolated HIT | The Number of Participants With Incidental Arterial and Venous Thromboembolism (i.e., a Clot Diagnosed by Radiographic Tests Done for Reasons Other Than to Diagnose or Rule Out a Thromboembolic Event) | 0 Participants |
Secondary
The Number of Participants With Symptomatic Venous or Arterial Thromboembolism in the Month Following the Diagnosis of Isolated HIT
There were two versions of the data collection form used in this study, and only the revised version collected information on whether the event was symptomatic.
Time frame: Measured within 35 days (+/- 7) after the diagnosis of isolated HIT
Population: Two subjects did not have information on whether the event was symptomatic or asymptomatic. These two subjects were censored in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Isolated HIT | The Number of Participants With Symptomatic Venous or Arterial Thromboembolism in the Month Following the Diagnosis of Isolated HIT | 0 Participants |
Secondary
The Percentage of Participants With Asymptomatic Thrombosis 4 Weeks After the Diagnosis of Isolated HIT, Determined by Four-limb Ultrasound
The percentage of participants with asymptomatic thrombosis 4 weeks after the diagnosis of isolated HIT, determined by four-limb ultrasound, and 95% exact binomial confidence interval.
Time frame: Measured at Day 35 (+/- 7days)
Population: Four subjects had missing data for this endpoint (no ultrasound performed on end-of-study date) and are not included in this analysis.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Isolated HIT | The Percentage of Participants With Asymptomatic Thrombosis 4 Weeks After the Diagnosis of Isolated HIT, Determined by Four-limb Ultrasound | 19 Percentage of participants |
Secondary
The Time to First Bleeding Event With Current Therapies for Isolated HIT
The time to first bleeding event was analyzed using survival analysis.
Time frame: Measured within 35 days (+/- 7) after the diagnosis of isolated HIT
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Isolated HIT | The Time to First Bleeding Event With Current Therapies for Isolated HIT | 10.1 Days | Standard Error 2.2 |
Secondary
Time to Platelet Count Recovery
The time to platelet recovery was defined as the time from the nadir platelet count observed in the five days after the positive HIT test was sent to observing a platelet count of 100K or greater. Survival analysis was used.
Time frame: Measured within 35 days (+/- 7) after the diagnosis of isolated HIT
Population: One subject's nadir platelet count was \> 100K, so that subject is not included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Isolated HIT | Time to Platelet Count Recovery | 2.9 Days | Standard Error 1 |
Secondary
Time Until Death From All Causes
The time until death from all causes, in days, was determined using survival analysis.
Time frame: Measured within 35 days (+/- 7) after the diagnosis of isolated HIT
Population: One subject was censored at the time that the study was terminated.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Isolated HIT | Time Until Death From All Causes | 12.2 Days | Standard Error 1.1 |
Post Hoc
Time to First Asymptomatic or Symptomatic Venous or Arterial Thromboembolism in the Month Following the Diagnosis of Isolated HIT
Since two versions of the data collection form were used in this study, and only the revised version contained information on whether the event was asymptomatic or symptomatic, a post-hoc analysis was performed which included all thromboses, whether symptomatic, asymptomatic, or of unknown type. Survival analysis was used.
Time frame: Measured within 35 days (+/- 7) after the diagnosis of isolated HIT
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Isolated HIT | Time to First Asymptomatic or Symptomatic Venous or Arterial Thromboembolism in the Month Following the Diagnosis of Isolated HIT | 24.9 Days | Standard Error 2.8 |