Heparin-Induced Thrombocytopenia - Retrospective Analysis of Data on Incidence and Outcomes Study (HIT-RADIO)

Heparin-Induced Thrombocytopenia - Retrospective Analysis of Data on Incidence and Outcomes Study (HIT-RADIO Study)

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.

Study Overview

• Status: Completed
• Conditions: Heparin Induced Thrombocytopenia

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 668

Contacts and Locations

Study Locations

• United States
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Tulane University
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Johns Hopkins
    • Baltimore, Maryland, United States, 21201
      • University of Maryland Greenebaum Cancer Center
  • 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
  • New York
    • New York, New York, United States, 10065
      • Cornell University
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina, Chapel Hill
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
    • Cleveland, Ohio, United States, 44106
      • Case Western Reserve University School of Medicine
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh
  • Washington
    • Seattle, Washington, United States, 98104
      • Fred Hutchinson Cancer Research Center
  • Wisconsin
    • LaCrosse, Wisconsin, United States, 54601
      • Gunderson Clinic
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Comprehensive Cancer Center
    • Milwaukee, Wisconsin, United States, 53215
      • St. Luke's Medical Center
    • Milwaukee, Wisconsin, United States, 53201
      • Froedtert

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: ADULT; OLDER_ADULT; CHILD
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Subjects with a positive heparin PF-4 antibody test drawn between 1/21/2008 and 9/25/2008

Description

Inclusion Criteria:

• All subjects with a positive heparin PF-4 antibody test occurring between 1/21/2008 and 9/25/2008
• Medical record available for the admission during which the positive heparin PF-4 antibody test was obtained

Exclusion Criteria:

• None

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	From the time that the positive heparin PF-4 antibody test was drawn until hospital discharge or day 45, whichever occurred first.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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".	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".	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.	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.	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.	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.	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.	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.	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.	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.	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	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		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		From the time that the nadir platelet count was drawn until hospital discharge, death, or day 45, whichever occurred first

Collaborators and Investigators

• Sponsor: HealthCore-NERI
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Ronald Go, MD, Gunderson Clinic; Principal Investigator: Eliot Williams, MD PHD, University of Wisconsin, Madison; Principal Investigator: Kenneth Friedman, MD, Versiti; Principal Investigator: Ellis Neufeld, MD PHD, Boston Children's Hospital; Principal Investigator: James Bussel, MD, Cornell University; Principal Investigator: Thomas Ortel, MD PHD, Duke University; Principal Investigator: Jodi Segal, MD MPH, Johns Hopkins University; Principal Investigator: Barbara Konkle, MD, Bloodworks; Principal Investigator: Ann Zimrin, MD, University of Maryland Greenebaum Cancer Center; Principal Investigator: Bruce Sachais, MD PHD, University of Pennsylvania; Principal Investigator: Joseph Kiss, MD, University of Pittsburgh Institute for Transfusion Medicine

Study record dates

Study Major Dates

• Study Start: June 1, 2010
• Primary Completion (ACTUAL): December 1, 2010
• Study Completion (ACTUAL): December 1, 2010

Study Registration Dates

• First Submitted: August 6, 2010
• First Submitted That Met QC Criteria: August 6, 2010
• First Posted (ESTIMATE): August 10, 2010

Study Record Updates

• Last Update Posted (ESTIMATE): May 22, 2015
• Last Update Submitted That Met QC Criteria: May 6, 2015
• Last Verified: March 1, 2013

More Information

Terms related to this study

• Keywords: Heparin; Thrombocytopenia
• Additional Relevant MeSH Terms: Hematologic Diseases; Blood Platelet Disorders; Thrombocytopenia
• Other Study ID Numbers: 678; U01HL072268 (U.S. NIH Grant/Contract)