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

2 Participants Needed

Trial Summary

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.

What data supports the idea that Slow vs Standard Platelet Transfusion for Low Platelet Count is an effective treatment?

The available research shows that platelet transfusion is a common treatment for low platelet count, especially in patients with conditions like cancer or those undergoing chemotherapy. It helps increase platelet counts to prevent or treat bleeding. For example, one study highlights that platelet transfusions are crucial for patients with severe low platelet counts to prevent life-threatening bleeding. However, the research also notes that frequent and high-threshold transfusions might increase risks, such as higher mortality rates in preterm neonates. Overall, while platelet transfusions are effective in increasing platelet counts and preventing bleeding, they must be carefully managed to avoid potential complications. ^{1 2 3 4 5}

What safety data exists for platelet transfusion treatments?

Platelet transfusions are associated with a high incidence of adverse reactions, including pro-inflammatory responses due to bioactive components in platelets. Studies have shown that therapeutic platelet transfusion strategies can be safe and may reduce risks such as infectious disease transmission and febrile reactions compared to traditional prophylactic strategies. Whole blood buffy coat pooled platelet components are considered extremely safe compared to apheresis components. Further research is needed to optimize safety and determine the best transfusion strategies for different patient conditions. ^{2 6 7 8 9}

Is the treatment 'Platelet Transfusion - LONG Platelet Transfusion, Platelet Transfusion - SHORT Platelet Transfusion' promising for low platelet count?

Yes, platelet transfusion is a promising treatment for low platelet count. It is a common therapy used to prevent or treat bleeding in patients with low platelet levels. Studies show that it is effective in increasing platelet counts and is considered a standard care practice for patients with severe low platelet levels. ^{1 2 5 10 11}

What is the purpose of this trial?

Background: Platelets are cell fragments in the blood that help it clot. Some people get very low platelet counts during a disease or treatment. Low platelet counts can cause severe bleeding. Some people are not helped by platelet transfusions at the standard transfusion rate. This is called platelet transfusion refractoriness (PTR). Researchers want to learn more about transfusing platelets so they can make transfusions more effective. Objectives: To study the effects of transfusing platelets more slowly than the standard rate. To obtain data to improve the effectiveness of platelet transfusions in people with PTR and decrease the risk of bleeding in some people. Eligibility: Adults ages 18-100 who have very low platelet counts requiring platelet transfusion, and have evidence of PTR Design: Participants will be screened with a review their recent NIH medical records. They will have blood drawn. Participants will have up to three 12-hour treatment blocks. They can have only one block per day. During each block, they will have 2 platelet transfusions in those 12 hours. One transfusion will take place over 1 hour (SHORT infusion). The other will take place over 4 hours (LONG infusion). Participants will be randomly put in 1 of 2 treatment groups. This will dictate whether they get the SHORT or LONG infusion first. Participants will have blood drawn: * When they enroll * Right before each transfusion * 2, 4, and 6 hours after each transfusion Each blood draw will consist of a complete blood count. Smaller tubes that require only small amounts of blood will be used to minimize the amount of blood drawn.

Research Team

Willy A Flegel, M.D.

Principal Investigator

National Institutes of Health Clinical Center (CC)

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

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]

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 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]

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Platelet transfusion goals in oncology patients. [2016]

2. England pubmed.ncbi.nlm.nih.gov

Therapeutic platelet transfusion versus routine prophylactic transfusion in patients with haematological malignancies: an open-label, multicentre, randomised study. [2022]

3. Germany pubmed.ncbi.nlm.nih.gov

[Thrombocyte transfusion: clinical aspects, follow-up and complications]. [2020]

4. United States pubmed.ncbi.nlm.nih.gov

Post-transfusion platelet responses in critically ill cancer patients with hypoproliferative thrombocytopenia. [2020]

5. Bosnia and Herzegovina pubmed.ncbi.nlm.nih.gov

Association Between Platelet Transfusion and Mortality Rate Among Preterm Neonates in the Eastern Province, Saudi Arabia. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

DAMPS and complement activation in platelet concentrates that induce adverse reactions in patients. [2022]

7. Italy pubmed.ncbi.nlm.nih.gov

Improving platelet transfusion safety: biomedical and technical considerations. [2018]

8. England pubmed.ncbi.nlm.nih.gov

New strategies for prophylactic platelet transfusion in patients with hematologic diseases. [2019]

9. United States pubmed.ncbi.nlm.nih.gov

Extracellular accumulation of bioactive substances during preparation and storage of various platelet concentrates. [2013]

10. United States pubmed.ncbi.nlm.nih.gov

Function of platelets in apheresis platelet concentrates and in patient blood after transfusion as assessed by Impact-R. [2010]

11. England pubmed.ncbi.nlm.nih.gov

Guidelines for the transfusion of platelets. [2016]