Evaluating the Presence of Blood Clots in People With Heparin-Induced Thrombocytopenia (HIT) (The HOT Study) (HOT)

HIT Observational Thromboembolism Study (A TMH CTN Study)

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.

Study Overview

• Status: Terminated
• Conditions: Thrombocytopenia

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.

• Study Type: Observational
• Enrollment (Actual): 10

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Tulane University
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland
    • Baltimore, Maryland, United States, 21205
      • Johns Hopkins Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02115
      • Children's Hospital Boston
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Case Western Reserve University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern Medical Center
  • Washington
    • Seattle, Washington, United States, 98104
      • University of Washington
  • Wisconsin
    • La Crosse, Wisconsin, United States, 54601
      • Gunderson Lutheran Clinic
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin, Madison
    • Milwaukee, Wisconsin, United States, 53215
      • St. Luke's Medical Center
    • Milwaukee, Wisconsin, United States, 53226
      • Froedtert Memorial Lutheran Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months and older (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Inpatients at participating clinical centers who have a diagnosis of isolated Heparin-Induced Thrombocytopenia (HIT), determined by a fall in platelet count after heparin treatment and a positive Platelet Factor 4 (PF4)-heparin Enzyme-Linked ImmunoSorbent Assay (ELISA) test

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Measured at Day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Measured at Day 35 (+/- 7days)
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.	Measured within 35 days (+/- 7) after the diagnosis of 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)	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.	Measured within 35 days (+/- 7) after the diagnosis of isolated HIT
The Time to First Bleeding Event With Current Therapies for Isolated HIT	The time to first bleeding event was analyzed using survival analysis.	Measured within 35 days (+/- 7) after the diagnosis of isolated HIT
Time Until Death From All Causes	The time until death from all causes, in days, was determined using survival analysis.	Measured within 35 days (+/- 7) after the diagnosis of isolated HIT
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.	Measured within 35 days (+/- 7) after the diagnosis of isolated HIT
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.	Measured within 35 days (+/- 7) after the diagnosis of isolated HIT
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.	Measured upon hospital discharge
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.	Measured upon hospital discharge
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.	Measured at Day 1
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.	Measured at Day 1 and within 35 days (+/- 7) after the diagnosis of isolated HIT
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.	Measured at Day 1 and within 35 days (+/- 7) after the diagnosis of isolated HIT

Collaborators and Investigators

• Sponsor: HealthCore-NERI
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Eliot C. Williams, MD, PhD, University of Wisconsin, Madison; Principal Investigator: Kenneth D. Friedman, MD, Froedtert Hospital; Principal Investigator: David Kress, MD, St. Luke's Medical Center; Principal Investigator: Ronald Go, MD, Gunderson Clinic; Principal Investigator: Keith McCrae, MD, Case Western Reserve University; Principal Investigator: Jeff Zwicker, MD, Beth Israel Deaconess Medical Center; Principal Investigator: Jodi Segal, MD, MPH, Johns Hopkins University; Study Chair: David Kuter, MD, Massachusetts General Hospital; Principal Investigator: Nigel Key, MB, MRCP, University of North Carolina; Principal Investigator: Ravindra Sarode, MD, University of Texas Southwestern Medical Center

Study record dates

Study Major Dates

• Study Start: January 1, 2008
• Primary Completion (ACTUAL): September 1, 2008
• Study Completion (ACTUAL): September 1, 2008

Study Registration Dates

• First Submitted: January 7, 2008
• First Submitted That Met QC Criteria: January 7, 2008
• First Posted (ESTIMATE): January 16, 2008

Study Record Updates

• Last Update Posted (ESTIMATE): March 13, 2013
• Last Update Submitted That Met QC Criteria: March 11, 2013
• Last Verified: March 1, 2013

More Information

Terms related to this study

• Keywords: Thrombosis; Heparin; Thromboembolism
• Additional Relevant MeSH Terms: Hematologic Diseases; Blood Platelet Disorders; Thrombocytopenia
• Other Study ID Numbers: 556; U01HL072268 (U.S. NIH Grant/Contract); HL072033; HL072291; HL072289; HL072248; HL072191; HL072299; HL072305; HL072274; HL072028; HL072359; HL072072; HL072355; HL072283; HL072346; HL072331; HL072290; U01HL072299 (NIH); U01HL072299-01 (NIH)