Slow vs Standard Platelet Transfusion for Low Platelet Count

Overseen By Willy A Flegel, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Institutes of Health Clinical Center (CC)

Must not be taking: IVIg, Eculizumab, Immunosuppressives

Disqualifiers: Pregnancy, ITP, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 4

Duration: 3 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether slower platelet transfusions could benefit individuals with very low platelet counts who do not respond to the usual transfusion speed. The aim is to reduce bleeding risk for those experiencing platelet transfusion refractoriness (PTR). Participants will receive both quick and slow transfusions to determine which is more effective. This trial suits adults needing platelet transfusions and diagnosed with PTR. As a Phase 2 trial, the research measures the treatment's effectiveness in an initial, smaller group of participants.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you are on immunosuppressive therapy like IVIg or eculizumab, you must not have received it in the last 3 months to be eligible.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that platelet transfusions, whether long or short, are generally well-tolerated by people with low platelet counts. This procedure is crucial for preventing or stopping bleeding in those with low platelet levels or platelet disorders.

Studies have found that longer transfusions can be safe even for patients with very low platelet counts, reducing the risk of bleeding. In many cases, a platelet transfusion can be lifesaving.

Short platelet transfusions are also safe and effective, particularly in preventing bleeding in stable patients with conditions like cancer or blood disorders. Research supports using platelet transfusions for patients with very low platelet counts to lower the risk of unexpected bleeding.

Overall, both long and short platelet transfusions have strong safety records and are vital options for patients needing assistance with low platelet counts. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this trial because it explores the optimal timing for platelet transfusions in patients with low platelet counts, a condition known as thrombocytopenia. Unlike the standard practice where transfusion speed is often based on clinical judgment, this trial compares the effects of slower (LONG) versus faster (SHORT) transfusion rates on patient outcomes. By alternating between these two rates, the trial aims to determine which method is more effective or safer, potentially leading to improved protocols for managing thrombocytopenia. This could help tailor treatment to individual patient needs, minimizing complications and enhancing recovery.

What evidence suggests that this trial's platelet transfusion treatments could be effective for low platelet count?

Research has shown that platelet transfusions are crucial for preventing or stopping bleeding in people with low platelet counts. In this trial, participants will receive either a long or short platelet transfusion. Studies have found that both long and short transfusions effectively lower the risk of bleeding. One study found that platelet transfusions successfully prevent bleeding episodes about 68.7% of the time. Additionally, whether platelets are given quickly or slowly, they reduce the risk of bleeding compared to not receiving them at all. Both methods aim to increase platelet levels and reduce bleeding risks for those who do not respond well to platelet transfusions. ^{1 6 7 8 9}

Who Is on the Research Team?

Willy A Flegel, M.D.

Principal Investigator

National Institutes of Health Clinical Center (CC)

Are You a Good Fit for This Trial?

Adults aged 18-100 with very low platelet counts who need a transfusion and have platelet transfusion refractoriness (PTR), meaning standard transfusions don't increase their platelet count enough. They must understand the study and agree to participate. Excluded are those responsive to certain immune therapies, under 18, unable to consent, with autoimmune thrombocytopenia or pregnant women.

Inclusion Criteria

Thrombocytopenia is generally defined as: <10K/uL without bleeding, <20K/uL for 'complicated prophylaxis' in patients determined to be at increased risk of bleeding or other complications, <50K/uL with evidence of active bleeding such as intracranial hemorrhage, GI bleeding, pulmonary hemorrhage, uncontrolled epistaxis, or hematuria

I understand this study is experimental and I can give my consent.

My doctor can adjust my platelet transfusion needs based on my health status.

Exclusion Criteria

Pregnant female

My low platelet count improved with special immune treatments in the last 3 months.

I am unable to understand or sign the consent form.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 day

1 visit (in-person)

Treatment

Participants undergo up to three 12-hour treatment blocks with alternating LONG and SHORT platelet transfusions

3 days

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 days

Daily hemostatic assessments

What Are the Treatments Tested in This Trial?

Interventions

• Platelet Transfusion - LONG Platelet Transfusion
• Platelet Transfusion - SHORT Platelet Transfusion

Trial Overview

The trial is testing if giving platelets more slowly than usual can help people whose bodies don't respond well to normal transfusions. Participants will receive two types of transfusions: one over an hour (SHORT) and another over four hours (LONG). They'll be randomly assigned an order for these treatments.

How Is the Trial Designed?

Group I: Group A: LONG then SHORT transfusion Active Control 2 Interventions

Subjects with thrombocytopenia (due to congenital causes, bone marrow failure, hematologic malignancies, and treatment-related) randomized to receive LONG platelet transfusion (Transfused over 4-HOURS via infusion pump or gravity) with follow up until 6 hours and then SHORT platelet transfusion (Transfused over 60-minutes via infusion pump or gravity) with follow up until 6 hours for a combined total of 12 hours. Subjects may receive up to two further subsequent blocks (one per day) to be administered to a subject in alternating order of SHORT and LONG platelet transfusions, for a maximum number of three blocks per subject.

Group II: Group B: SHORT then LONG transfusion Active Control 2 Interventions

Subjects with thrombocytopenia (due to congenital causes, bone marrow failure, hematologic malignancies, and treatment-related) randomized to receive SHORT platelet transfusion (Transfused over 60-minutes via infusion pump or gravity) with follow up until 6 hours and then LONG platelet transfusion (Transfused over 4-HOURS via infusion pump or gravity) with follow up until 6 hours for a combined total of 12 hours. Subjects may receive up to two further subsequent blocks (one per day) to be administered to a subject in alternating order of LONG and SHORT platelet transfusions, for a maximum number of three blocks per subject.

Platelet Transfusion - LONG Platelet Transfusion is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Platelet Transfusion for:

• Severe thrombocytopenia
• Bleeding disorders
• Hematologic malignancies

Approved in United States as Platelet Transfusion for:

• Severe thrombocytopenia
• Bleeding disorders
• Hematologic malignancies
• Surgical bleeding

Approved in Canada as Platelet Transfusion for:

• Severe thrombocytopenia
• Bleeding disorders
• Hematologic malignancies

Approved in Japan as Platelet Transfusion for:

• Severe thrombocytopenia
• Bleeding disorders
• Hematologic malignancies

Who Is Running the Clinical Trial?

National Institutes of Health Clinical Center (CC)

Lead Sponsor

Trials

391

Recruited

30,880,000+

Published Research Related to This Trial

In a study of 56 platelet concentrates (PC), 26 induced adverse reactions (AR) in patients, highlighting the risks associated with platelet transfusions, particularly in those with severe thrombocytopenia.

The study found significant increases in platelet activation markers and damage-associated molecular patterns (HMGB1) in PCs that caused AR, suggesting that these markers could be used to predict and understand the mechanisms behind transfusion-related complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

DAMPS and complement activation in platelet concentrates that induce adverse reactions in patients. de Wit, YES., Hamzeh-Cognasse, H., Cognasse, F., et al.[2022]

Platelet transfusions are crucial for treating thrombocytopenia, especially when platelet counts drop below 20,000/microliters for asymptomatic patients or 50,000/microliters for those experiencing bleeding or requiring surgery.

The effectiveness of these transfusions should be monitored through the corrected count increment (CCI) at 1 and 24 hours post-transfusion, as various factors like fever or infections can affect platelet recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Thrombocyte transfusion: clinical aspects, follow-up and complications]. Söhngen, D., Schneider, W.[2020]

A working group from the Superior Health Council in Belgium developed standardized guidelines for platelet transfusions to improve consistency across hospitals.

The guidelines were created through expert discussions and aimed to optimize the indications for transfusions, the type of platelet concentrate used, and the overall transfusion therapy process.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Guidelines for the transfusion of platelets. Bosly, A., Muylle, L., Noens, L., et al.[2016]

Platelet transfusions are crucial for patients with low platelet counts due to conditions like chemotherapy or stem cell transplants, but their short shelf life (5 days) makes optimal use essential, as highlighted by recent guidelines and randomized controlled trials.

Recent studies suggest that determining the right platelet dose and transfusion thresholds can improve outcomes, and innovations in processing may enhance transfusion efficiency, potentially reducing the need for prophylactic transfusions in non-bleeding patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Platelet transfusion goals in oncology patients. Fasano, RM., Josephson, CD.[2016]

Recent studies involving over 1,000 patients have demonstrated that a lower threshold of 10,000 platelets/microliter for prophylactic transfusions is safe for stable patients, particularly those with acute leukemia, potentially reducing unnecessary transfusions.

Adopting a restrictive platelet transfusion strategy not only decreases the risk of complications like infections and allergic reactions but also lowers healthcare costs by 20%-30% and minimizes hospital visits for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New strategies for prophylactic platelet transfusion in patients with hematologic diseases. Wandt, H., Ehninger, G., Gallmeier, WM.[2019]

The therapeutic platelet transfusion strategy reduced the mean number of transfusions by 33.5% compared to the standard prophylactic approach in patients with hypoproliferative thrombocytopenia, indicating a more efficient use of transfusions.

While the therapeutic strategy showed no increased risk of major hemorrhage in autologous transplantation patients, it did increase the risk of non-fatal grade 4 bleeding in those with acute myeloid leukemia, suggesting that careful monitoring is essential.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic platelet transfusion versus routine prophylactic transfusion in patients with haematological malignancies: an open-label, multicentre, randomised study. Wandt, H., Schaefer-Eckart, K., Wendelin, K., et al.[2022]

Platelet concentrates prepared by the apheresis method (APC) generally contain lower levels of bioactive substances like histamine, PAI-1, and VEGF compared to those prepared by the buffy-coat method (BCPC), which may reduce the risk of side effects during transfusion.

Despite the initial lower levels of bioactive substances in APC units, significant accumulation of these substances occurs during storage, indicating that all platelet concentrates can potentially release bioactive compounds over time, which may impact patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extracellular accumulation of bioactive substances during preparation and storage of various platelet concentrates. Edvardsen, L., Taaning, E., Dreier, B., et al.[2013]

In a study of 326 critically ill cancer patients receiving 1470 platelet transfusions, over half of the transfusions resulted in poor platelet increments, indicating that these patients often do not respond well to transfusions.

Factors such as lower body mass index, spleen enlargement, and concurrent severe illness were linked to poor responses, suggesting that addressing these issues could improve transfusion outcomes and reduce bleeding risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Post-transfusion platelet responses in critically ill cancer patients with hypoproliferative thrombocytopenia. Baron, E., Charpentier, J., François, A., et al.[2020]

This study evaluated platelet function in 24 chemotherapy-treated patients before and after transfusion, revealing that platelet transfusion increased the number of adhering platelets, indicating improved function post-transfusion.

However, the study found that platelets stored for more than 70 hours had significantly lower P-selectin expression, suggesting that longer storage may negatively impact platelet function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Function of platelets in apheresis platelet concentrates and in patient blood after transfusion as assessed by Impact-R. Horvath, M., Eichelberger, B., Koren, D., et al.[2010]

Platelet concentrates, while accounting for 10% of blood components, are linked to over 25% of adverse events, highlighting the need for improved safety measures during collection and storage.

Research indicates that whole blood buffy coat pooled platelets are safer than apheresis platelets, showing lower risks of infections and inflammatory reactions, suggesting a need to reconsider current transfusion practices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improving platelet transfusion safety: biomedical and technical considerations. Garraud, O., Cognasse, F., Tissot, JD., et al.[2018]

In a study of 154 preterm neonates, it was found that lower gestational age and birth weight were significantly associated with higher mortality rates, rather than the frequency or threshold of platelet transfusions.

The research suggests that platelet transfusions do not impact survival rates in preterm neonates, indicating that mortality is more closely linked to the infants' developmental factors rather than transfusion practices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association Between Platelet Transfusion and Mortality Rate Among Preterm Neonates in the Eastern Province, Saudi Arabia. Alhamad, FA., Hussien, A., Alqahtani, F.[2022]

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