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The Association Between Platelet Reactivity and Bleeding Risk in Adult ITP

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ClinicalTrials.gov Identifier: NCT03377439
Recruitment Status : Recruiting
First Posted : December 19, 2017
Last Update Posted : December 19, 2017
Sponsor:
Collaborators:
Traditional Chinese Medicine Hospital Affiliated to Shandong University
Jinan Central Hospital
Qianfoshan Hospital
Shandong Provincial Hospital
Shandong University Second Hospital
Information provided by (Responsible Party):
Ming Hou, Shandong University

Brief Summary:
It seems reasonable to assume that patients who present significant bleeding symptoms may have different quality of platelets than those without bleeding. This question was addressed in a study that examined platelet function in adult ITP patients, which try to determine whether this correlated with bleeding risk. Previous reports have suggested that measuring platelet function may help define patients at highest risk of bleeding. In addition, Middelburg and colleagues corrected platelet function for quartile of platelet count, using <32×10^9/L as the lowest cohort and >132×10^9/L as the top quartile. They demonstrated that increased platelet reactivity (as measured by flow cytometry) was associated with decreased risk of bleeding but particularly for those patients with the lowest platelet counts. Further studies in a larger cohort are needed to confirm this correlation. Our study aimed at standardizing a prediction model to evaluate the bleeding risk of adult ITP patients with the use of platelet function tests.

Condition or disease Intervention/treatment
Immune Thrombocytopenia Other: Platelet function tests

Detailed Description:

The investigators are undertaking a prospective multicenter double-blind study of 400 adult patients with immune thrombocytopenia from 6 medical centers in China. We adopted three different assays that examined platelet function and reactivity. 1) Flow cytometry: Citrate anticoagulated whole blood was diluted in PBS to result in 20×10^9/L platelets, and 20 μl was aliquoted into polystyrene test tubes. Ten microliters of anti-CD42b-PE was added and incubated at room temperature for 10 min. Agonists (TRAP-6 12.5 μMol/L, Collagen 20 μg/mL, ADP 2 μM, Epinephrin 20 μM, Arachidonic acid 0.275 mM, Ristocetin 1.5 mg/mL) or PBS were added (10 μl each) and incubated again for 10 min. Then mAb PAC-1-FITC or anti-CD62p-FITC (10 μl each) or the corresponding isotype-matched controls were added. After 15-min incubation in the dark, the reaction was stopped with 500 μl PBS. Samples were analyzed on a flow cytometer (FACScan, Becton-Dickinson) by measuring 10,000 events in the CD42b-positive fraction. 2) Filopodia quantification: Briefly, platelets in Tyrode's buffer were allowed to adhere to VWF (9×10^6 cells/coverslip) in the presence of botrocetin (1 μg/mL) and Integrilin (40 μg/mL) at 37°C. After 15 min, non-adherent platelets were removed by washing and adherent platelets were fixed with 4% PFA, stained with TRITC-phalloidin (2 μg/mL) and viewed by epifluorescence microscopy for filopodia count. 3) Platelet aggregation: Measured on an automated platelet aggregation analyzer.

Understanding bleeding risk and underlying determinants of bleeding is important in order to help recognize patients that will require pharmacologic therapy even at higher platelet counts. Previous studies have suggested that low platelet counts, increased patient age, use of concurrent medications, and male sex are associated with increased bleeding risk. The present investigation will answer whether platelet function predicts the severity of bleeding in adult ITP patients. Clinical information of recruited participants includes gender, age, platelet count and physical/laboratory examination. Blinding was set between investigators who evaluated bleeding risks and those who performed experiments.


Study Type : Observational
Estimated Enrollment : 400 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: The Association Between Platelet Reactivity and Bleeding Risk in Adult ITP Patients: a Prospective Multicenter Double-blind Study
Actual Study Start Date : December 1, 2017
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : December 2018


Group/Cohort Intervention/treatment
Group A
Participants with platelet counts <32×10^9/L.
Other: Platelet function tests
Platelet reactivity was measured by flow cytometry, filopodia detection and the platelet aggregation analyzer.

Group B
Participants with platelet counts between 32×10^9/L and 132×10^9/L.
Other: Platelet function tests
Platelet reactivity was measured by flow cytometry, filopodia detection and the platelet aggregation analyzer.

Group C
Participants with platelet counts >132×10^9/L.
Other: Platelet function tests
Platelet reactivity was measured by flow cytometry, filopodia detection and the platelet aggregation analyzer.




Primary Outcome Measures :
  1. The severity of bleeding manifestations at onset was assessed using a previously described clinical scoring system with minor modifications. The total bleeding score was calculated by adding the scores for each item. [ Time Frame: No more than three months after platelet function assessment. ]
    The bleeding score system: 1) Age: Age over 65 years (2'); Age over 75 years (5'). 2) Cutaneous bleeding: Localized petechial purpura (1'); Localized ecchymotic purpura (2'); Two locations of petechial purpura (2'); Generalized petechial purpura (3'); Generalized ecchymotic purpura (4'). 3) Mucosal bleeding: Unilateral epistaxis (2'); Bilateral epistaxis (3'); Hemorrhagic oral bullae and/or gingival bleeding (5'). 4) Gastrointestinal bleeding: Gastrointestinal hemorrhage without anemia (4'); Gastrointestinal hemorrhage with acute anemia and/or shock (15'). 5) Urinary bleeding: Macroscopic hematuria without anemia (4'); Macroscopic hematuria with acute anemia (10'). 6) Genitourinary tract bleeding: Major meno/metrorrhagia without anemia (4'); Major meno/metrorrhagia with acute anemia (10'). 7) Central nervous system bleeding: Central nervous system bleeding and/or life-threatening hemorrhage (15').



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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Untreated adult ITP patients of both genders between the ages of 18 and 80 years.
Criteria

Inclusion Criteria:

  1. Untreated adult ITP patients of both genders between the ages of 18 and 80 years.
  2. Participants of either acute or chronic phase; with or without thrombocytopenia; with or without bleeding manifestation.

Exclusion Criteria:

  1. Received high-dose steroids or IVIG within 3 weeks prior to the test.
  2. Received second-line ITP-specific treatments (eg, cyclophosphamide, 6-mercaptopurine, vincristine, vinblastine, etc) within 3 months prior to the test.
  3. Current HIV infection, hepatitis B virus or hepatitis C virus infections.
  4. Severe medical condition (liver and kidney function impairment).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03377439


Contacts
Contact: Ming Hou Hou, MD, PhD 86-531-82169879 qlhouming@sina.com.cn

Locations
China, Shandong
Qilu Hospital, Shandong University Recruiting
Jinan, Shandong, China, 250012
Principal Investigator: Ming Hou, MD, PhD         
Sponsors and Collaborators
Shandong University
Traditional Chinese Medicine Hospital Affiliated to Shandong University
Jinan Central Hospital
Qianfoshan Hospital
Shandong Provincial Hospital
Shandong University Second Hospital
Investigators
Study Director: Jun Peng, MD, PhD Qilu Hospital, Shandong University

Publications:

Responsible Party: Ming Hou, Professor and Director, Shandong University
ClinicalTrials.gov Identifier: NCT03377439     History of Changes
Other Study ID Numbers: Plt function and bleeding risk
First Posted: December 19, 2017    Key Record Dates
Last Update Posted: December 19, 2017
Last Verified: December 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Ming Hou, Shandong University:
Platelet function
Bleeding risk
Immune Thrombocytopenia

Additional relevant MeSH terms:
Hemorrhage
Thrombocytopenia
Purpura, Thrombocytopenic, Idiopathic
Pathologic Processes
Blood Platelet Disorders
Hematologic Diseases
Purpura, Thrombocytopenic
Purpura
Blood Coagulation Disorders
Thrombotic Microangiopathies
Hemorrhagic Disorders
Autoimmune Diseases
Immune System Diseases
Skin Manifestations
Signs and Symptoms