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Blood Reviews Jun 2024Immune thrombocytopenia (ITP) is an autoimmune bleeding disease caused by immune-mediated platelet destruction and decreased platelet production. ITP is characterized by... (Review)
Review
Immune thrombocytopenia (ITP) is an autoimmune bleeding disease caused by immune-mediated platelet destruction and decreased platelet production. ITP is characterized by an isolated thrombocytopenia (<100 × 10/L) and increased risk of bleeding. The disease has a complex pathophysiology wherein immune tolerance breakdown leads to platelet and megakaryocyte destruction. Therapeutics such as corticosteroids, intravenous immunoglobulins (IVIg), rituximab, and thrombopoietin receptor agonists (TPO-RAs) aim to increase platelet counts to prevent hemorrhage and increase quality of life. TPO-RAs act via stimulation of TPO receptors on megakaryocytes to directly stimulate platelet production. Romiplostim is a TPO-RA that has become a mainstay in the treatment of ITP. Treatment significantly increases megakaryocyte maturation and growth leading to improved platelet production and it has recently been shown to have additional immunomodulatory effects in treated patients. This review will highlight the complex pathophysiology of ITP and discuss the usage of Romiplostim in ITP and its ability to potentially immunomodulate autoimmunity.
PubMed: 38942688
DOI: 10.1016/j.blre.2024.101222 -
Blood Jun 2024Immune thrombotic thrombocytopenic purpura (iTTP) is a rare, life-threatening autoimmune disorder caused by ADAMTS13 deficiency. Caplacizumab, an anti-VWF nanobody, is...
Immune thrombotic thrombocytopenic purpura (iTTP) is a rare, life-threatening autoimmune disorder caused by ADAMTS13 deficiency. Caplacizumab, an anti-VWF nanobody, is approved for iTTP treatment, reducing the need for therapeutic plasma exchange (TPE) and improving platelet count recovery and survival. We conducted a retrospective study on 42 acute iTTP cases in Austria and Germany, treated with a modified regimen aimed at avoiding TPE if platelet count increased after the first caplacizumab dose. Baseline characteristics and patient outcomes were compared with a control group of 59 patients with iTTP, receiving frontline treatment with TPE, caplacizumab, and immunosuppression. The main outcome was the time to platelet count normalization. Secondary outcomes included clinical response, exacerbation, refractory iTTP, iTTP-related deaths, and the time to platelet count doubling. The median time to platelet count normalization was similar between the two cohorts (3 and 4 days; P = 0.31). There were no significant differences in clinical response, exacerbations, refractoriness, iTTP-related deaths, or time to platelet count doubling reflecting the short-term treatment response. Four patients did not respond to the first caplacizumab dose and TPE was subsequently initiated. Cytomegalovirus infection, HIV/hepatitis B co-infection, an ovarian teratoma with associated anti-platelet antibodies, and multiple platelet transfusion before the correct diagnosis may have impeded immediate treatment response in these patients. In conclusion, caplacizumab and immunosuppression alone, without TPE, rapidly controlled thrombotic microangiopathy and achieved a sustained clinical response in iTTP. Our study provides a basis for TPE-free iTTP management in experienced centers via shared decision-making between patients and treating physicians.
PubMed: 38838300
DOI: 10.1182/blood.2023023780 -
Transfusion Jan 2024Recently the US Food and Drug Administration has granted variances to select blood centers to supply cold-stored platelet components (CSP). In hemorrhage resuscitation...
BACKGROUND
Recently the US Food and Drug Administration has granted variances to select blood centers to supply cold-stored platelet components (CSP). In hemorrhage resuscitation warming of blood components with approved fluid warming devices is common.
STUDY DESIGN AND METHODS
Pathogen-reduced apheresis platelet units were collected and stored in one of two ways: (1) CSP-I, (2) CSP-D. CSP-I were collected and immediately stored at 1-6°C until used. CSP-D were collected and stored at 20-24°C for 5 days and transferred to storage at 1-6°C until use. Aggregometry using arachidonic acid (AA), adenosine diphosphate (ADP) and collagen as agonists was performed on the unit samples before and after the units were infused through a Ranger blood-warming device.
RESULTS
CSP-I, 23 units, had very high aggregation responses to all agonists (all ≥47.6 ± 20.7). There was a statistically significant reduction in ADP-induced aggregometry results from 55.1 ± 23.2 before compared to 33.5 ± 14.6 following infusion of the PLT through the blood warmer (p < .001). There were no differences in AA and collagen aggregometry results before and after the infusion of the platelets through the blood warmer. CSP-D had 5 of the 15 units with visible clotting in the bag. The 10 CSP-Ds studied had lower aggregation than all agonists before and after infusion through the blood-warming device (all ≤49.9 ± 35.9).
CONCLUSION
We detected a statistically significant reduction in ADP-induced aggregometry in CSP-I run through a Ranger blood-warming device with no change with AA or collagen agonist aggregometry.
Topics: Humans; Platelet Transfusion; Platelet Aggregation; Blood Platelets; Collagen; Adenosine Diphosphate; Blood Preservation; Cold Temperature
PubMed: 38115202
DOI: 10.1111/trf.17624 -
Transfusion Sep 2023While prior studies of platelet transfusion in critical care have focused on transfusions given, proper analysis of clinical transfusion practice also requires...
BACKGROUND
While prior studies of platelet transfusion in critical care have focused on transfusions given, proper analysis of clinical transfusion practice also requires consideration of the decision not to transfuse.
STUDY DESIGN AND METHODS
We introduce a new method to assess transfusion practice based on decision time intervals (DTIs). Each patient's intensive care (ICU) stay was segmented into a series of DTIs defined by a time interval following results of a complete blood count (CBC). We studied the presence of 17 clinical factors during each DTI whether transfusion was given or not. We used a generalized linear mixed model to assess the most influential clinical triggers for platelet transfusion.
RESULTS
Among 6125 ICU patients treated between October 2016 and October 2021, we analyzed 39,745 DTIs among patients (n = 2921) who had at least one DTI with thrombocytopenia (≤150,000/μL). We found no association between platelet count and two markers of bleeding: drop in hemoglobin and chest tube drainage. We found that the majority of DTIs were associated with no platelet transfusion regardless of the platelet count; that no specific platelet value triggered transfusion; but rather that multiple clinical factors in conjunction with the platelet count influenced the decision to transfuse.
DISCUSSION
DTI analysis represents a new method to assess transfusion practice that considers both transfusions given and not given, and that analyzes clinical circumstances present when decisions regarding transfusion are made. The method is easily adapted to blood components other than platelet transfusions and is easily extended to other ICU and other hospital settings.
Topics: Humans; Platelet Transfusion; Blood Transfusion; Critical Care; Blood Platelets; Platelet Count
PubMed: 37606376
DOI: 10.1111/trf.17508 -
Arteriosclerosis, Thrombosis, and... Oct 2023Platelets for transfusion are stored for 5 to 7 days. Previous studies have shown that HETE levels in the storage bag negatively correlate with platelet performance in...
BACKGROUND
Platelets for transfusion are stored for 5 to 7 days. Previous studies have shown that HETE levels in the storage bag negatively correlate with platelet performance in vivo, suggesting that the dysregulation of bioactive lipid mediators may contribute to the storage lesion. In the current study, we sought to understand how genetic deletion and pharmacological inhibition of 12-LOX (12-lipoxygenase) affects platelets during storage and after transfusion.
METHODS
Platelets from 12-LOX (wild-type [WT]) and 12-LOX mice were stored for 24 and 48 hours and profiled using liquid chromatography-tandem mass spectrometry-multiple reaction monitoring or transfused into thrombocytopenic hIL4R (human interleukin 4 receptor)-transgenic mice. Platelet function was assessed by flow cytometry and in vivo thrombosis and hemostasis models. To test the role of the COX-1 (cyclooxygenase-1) pathway, donor mice were treated with acetylsalicylic acid. Human platelets were treated with the 12-LOX inhibitor, VLX-1005, or vehicle, stored, and transfused to NOD/SCID (nonobese diabetic/severe combined immunodeficiency) mice.
RESULTS
Polyunsaturated fatty acids increased significantly in stored platelets from 12-LOX mice, whereas oxylipin concentrations were significantly higher in WT platelets. After transfusion to thrombocytopenic mice, we observed significantly more baseline αIIbβ3 integrin activation in 12-LOX platelets than in WT platelets. Stored platelets from 12-LOX mice occluded vessels significantly faster than stored WT platelets. In hemostasis models, significantly more stored 12-LOX than WT platelets accumulated at the site of venous injury leading to reduced blood loss. Inhibition of COX-1 abrogated both increased integrin activation and thromboxane generation in stored 12-LOX platelets, highlighting the critical role of this pathway for improved post-transfusion function. Consistent with our mouse studies, human platelets stored with VLX-1005, showed increased integrin activation compared with vehicle-treated platelets after transfusion.
CONCLUSIONS
Deleting 12-LOX improves the post-transfusion function of stored murine platelets by increasing thromboxane generation through COX-1-dependent arachidonic acid metabolism. Future studies should determine the feasibility and safety of 12-LOX-inhibited platelets transfused to humans.
Topics: Humans; Mice; Animals; Arachidonate 12-Lipoxygenase; Mice, Inbred NOD; Mice, SCID; Blood Platelets; Mice, Transgenic; Platelet Glycoprotein GPIIb-IIIa Complex; Thromboxanes
PubMed: 37650322
DOI: 10.1161/ATVBAHA.123.319021 -
International Journal of Laboratory... Apr 2024Platelet transfusion is a standard treatment to prevent bleeding in patients with hematological malignancies. Although transfusions can improve platelet count, their...
INTRODUCTION
Platelet transfusion is a standard treatment to prevent bleeding in patients with hematological malignancies. Although transfusions can improve platelet count, their impact on platelet function remains controversial.
METHODS
We conducted flow cytometry to assess platelet function before and after transfusion and performed subgroup analyses to examine differences based on blood type, corrected count increment (CCI), and platelet microparticles.
RESULTS
Overall, 50 patients who received prophylactic platelet transfusion were enrolled. CD42b expression increased, whereas CD41 expression decreased after transfusion. Apheresis platelets exhibited the lowest expression of PAC-1 and P-selectin when exposed to agonist stimulations. PAC-1 expression increased under high adenosine diphosphate (ADP) stimulation, while P-selectin expression increased under both high ADP and thrombin receptor-activating peptide stimulation. In the subgroup analysis, patients with a CCI >4500 and those with the same blood types exhibited a more significant increase in PAC-1 and P-selectin expression under agonist stimulation. When comparing apheresis platelets collected on different days, only the percentage of platelet-derived microparticles showed a significant increase.
CONCLUSION
Prophylactic transfusion improved platelet function. Platelet function significantly improved in patients with a CCI >4500, those with the same blood types as that of apheresis platelets, or those with platelet-derived microparticle levels <4.7%. No significant improvement in platelet function was noted after the transfusion of different blood types with acceptable compatibility or the transfusion of incompatible blood types. Our results suggest that transfusing platelets with the same blood type remains the optimal choice.
PubMed: 38682289
DOI: 10.1111/ijlh.14283 -
British Journal of Haematology May 2024Immune thrombocytopenia (ITP) is characterized by early platelet destruction and impaired platelet production. Helicobacter pylori (H. pylori) infection seems to... (Comparative Study)
Comparative Study
Immune thrombocytopenia (ITP) is characterized by early platelet destruction and impaired platelet production. Helicobacter pylori (H. pylori) infection seems to contribute to the pathogenesis in certain ITP patients in Japan. We compared the effectiveness of platelet transfusion in severe ITP in the presence or absence of H. pylori. The median corrected count increment (CCI) at 24 h after platelet transfusion (CCI-24) of the H. pylori-positive ITP patients was higher than that of the H. pylori-negative ITP patients (6463 vs. 754, p < 0.001), and the CCI-1 was also in the same direction but not significant (23 351 vs. 11 578). Multiple regression analyses showed that H. pylori infection was independently associated with CCI-24. Our study suggests that platelet transfusion may be more effective in H. pylori-positive ITP patients.
Topics: Humans; Helicobacter pylori; Helicobacter Infections; Male; Purpura, Thrombocytopenic, Idiopathic; Female; Middle Aged; Platelet Transfusion; Aged; Adult; Platelet Count; Treatment Outcome; Aged, 80 and over
PubMed: 38522847
DOI: 10.1111/bjh.19413 -
British Journal of Haematology May 2024ABO-non-identical (ABO-ni) platelets may be another risk factor for immune platelet transfusion refractoriness (i-PTR). We examined the effect of such platelets on i-PTR...
ABO-non-identical (ABO-ni) platelets may be another risk factor for immune platelet transfusion refractoriness (i-PTR). We examined the effect of such platelets on i-PTR and subsequent platelet support through retrospective analysis of 17 322 New Zealand patients receiving ≥1 platelets. Immune PTR was defined as PTR with anti-HLA-I/HPA positivity. Univariate and multivariate analyses determined the independent risk factors for i-PTR. One hundred and eighty-eight patients (1.1%) had i-PTR and received more ABO-ni platelets than non-refractory patients (53.2% vs. 29.5%; p < 0.001). More non-O than group O patients had received ABO-ni platelets before i-PTR diagnosis (67.6% vs. 32.5%; p < 0.001). Female sex (p < 0.001), age ≤ 60 years (p = 0.004), haematology patients (p < 0.001) and ≥2 ABO-ni platelets (p < 0.001) were the independent risk factors for i-PTR. More i-PTR patients with anti-HLA-I were non-O compared to group O (90.1% vs. 75.3%; p = 0.007). More with anti-HLA-I + anti-HPA were group O than non-O (24.7% vs. 9.0%; p = 0.003). ABO-ni platelet-exposed i-PTR patients required matched platelets for longer than those receiving only ABO-i platelets (96.5 vs. 59.0 days; p = 0.02). ABO-ni platelets may be a risk factor for i-PTR with dose effect. ABO-i platelets should be considered whenever possible for at-risk patients.
Topics: Humans; ABO Blood-Group System; Female; Male; Platelet Transfusion; Middle Aged; Retrospective Studies; Adult; Aged; Risk Factors; Adolescent; Blood Platelets; Blood Group Incompatibility; Child; Young Adult; Child, Preschool
PubMed: 38419302
DOI: 10.1111/bjh.19359 -
Platelet transfusion in patients with liver cirrhosis cross-talk with neutrophil: Prospective study.Hematology, Transfusion and Cell Therapy 2023Immune dysfunction and thrombocytopenia are common features in liver cirrhosis. Platelet transfusion is the most widely used therapeutic approach for thrombocytopenia...
INTRODUCTION
Immune dysfunction and thrombocytopenia are common features in liver cirrhosis. Platelet transfusion is the most widely used therapeutic approach for thrombocytopenia when indicated. The transfused platelets are prone to lesions during their storage that empower their interaction with the recipient leucocyte. These interactions modulate the host immune response. The impact of platelet transfusion on the immune system in cirrhotic patients is little understood. Therefore, this study aims to investigate the impact of platelet transfusion on neutrophil function in cirrhotic patients.
METHODS
This prospective cohort study was implemented on 30 cirrhotic patients receiving platelet transfusion and 30 healthy individuals as a control group. EDTA blood samples were collected from cirrhotic patients before and after an elective platelet transfusion. Flowcytometric analysis of neutrophil functions (CD11b expression and PCN formation) was performed.
RESULTS
There was a significant increase in expression of CD11b on neutrophils and Frequency of platelet-complexed neutrophils (PCN) in patients with cirrhosis compared with controls. Platelet transfusion increased level of CD11b and the frequency of PCN even more. There was a significant positive correlation between change in PCN Frequency pefore and after transfusion and the change in expression of CD11b among cirrhotic patients.
CONCLUSIONS
Elective platelet transfusion appears to increase level of PCN in cirrhotic patients, moreover, exacerbate the expression of activation marker CD11b on both neutrophils and PCN. More research and studies are needed to corroborate our preliminary findings.
PubMed: 36813682
DOI: 10.1016/j.htct.2022.08.009 -
Haematologica Oct 2023Heparin-induced thrombocytopenia (HIT) is a severe immune-mediated prothrombotic disorder caused by antibodies (Ab) reactive to complexes of platelet factor 4 and...
Heparin-induced thrombocytopenia (HIT) is a severe immune-mediated prothrombotic disorder caused by antibodies (Ab) reactive to complexes of platelet factor 4 and heparin. Platelets (PLT) and their interaction with different immune cells contribute to prothrombotic conditions in HIT. However, the exact mechanisms and the role of different PLT subpopulations in this prothrombotic environment remain poorly understood. In this study, we observed that HIT patient Ab induce a new PLT population that is characterized by increased P-selectin expression and phosphatidylserine (PS) externalization. Formation of this procoagulant PLT subpopulation was dependent on engagement of PLT Fc-γ-RIIA by HIT Ab and resulted in a significant increase of thrombin generation on the PLT surface. Using an ex vivo thrombosis model and multi-parameter assessment of thrombus formation, we observed that HIT Ab-induced procoagulant PLT propagated formation of large PLT aggregates, leukocyte recruitment and most importantly, fibrin network generation. These prothrombotic conditions were prevented via the upregulation of PLT intracellular cAMP with Iloprost, a clinically approved prostacyclin analogue. Additionally, the functional relevance of P-selectin and PS was dissected. While inhibition of P-selectin did not affect thrombus formation, the specific blockade of PS prevented HIT Ab-mediated thrombin generation and most importantly procoagulant PLT-mediated thrombus formation ex vivo. Taken together, our findings indicate that procoagulant PLT are critical mediators of prothrombotic conditions in HIT. Specific PS targeting could be a promising therapeutic approach to prevent thromboembolic events in HIT patients.
Topics: Humans; Phosphatidylserines; P-Selectin; Thrombin; Thrombocytopenia; Heparin; Thrombosis; Antibodies; Platelet Factor 4
PubMed: 37102605
DOI: 10.3324/haematol.2022.282275