scholarly journals New Developments in the Pathophysiology and Management of Primary Immune Thrombocytopenia

2020 ◽  
Author(s):  
Karina Althaus ◽  
Christoph Faul ◽  
Tamam Bakchoul
Keyword(s):  
Platelet Count ◽  
Immune Thrombocytopenia ◽  
Clinical Manifestations ◽  
Bleeding Risk ◽  
Platelet Destruction ◽  
New Developments ◽  
Primary Hemostasis ◽  
Current Therapies ◽  
Low Platelet Count ◽  
Bleeding Manifestation

AbstractImmune thrombocytopenia (ITP) is an autoimmune disease that is characterized by a significant reduction in the number of circulating platelets and frequently associated with bleeding. Although the pathogenesis of ITP is still not completely elucidated, it is largely recognized that the low platelet count observed in ITP patients is due to multiple alterations of the immune system leading to increased platelet destruction as well as impaired thrombopoiesis. The clinical manifestations and patients' response to different treatments are very heterogeneous suggesting that ITP is a group of disorders sharing common characteristics, namely, loss of immune tolerance toward platelet (and megakaryocyte) antigens and dysfunctional primary hemostasis. Management of ITP is challenging and requires intensive communication between patients and caregivers. The decision to initiate treatment should be based on the platelet count level, age of the patient, bleeding manifestation, and other factors that influence the bleeding risk in individual patients. In this review, we present recent data on the mechanisms that lead to platelet destruction in ITP with a particular focus on current findings concerning alterations of thrombopoiesis. In addition, we give an insight into the efficacy and safety of current therapies and management of ITP bleeding emergencies.

scholarly journals Platelet Contraction Force As a Biophysical Biomarker for Bleeding Risk in Patients with Immune Thrombocytopenia

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 517-517
Author(s):  
Oluwamayokun T. Oshinowo ◽  
Renee Copeland ◽  
Carolyn M. Bennett ◽  
Wilbur A Lam ◽  
David R. Myers
Keyword(s):  
Platelet Count ◽  
Single Cell ◽  
Platelet Function ◽  
High Throughput ◽  
Immune Thrombocytopenia ◽  
Conflicts Of Interest ◽  
Bleeding Risk ◽  
Contractile Force ◽  
Diagnostic Potential ◽  
Low Platelet Count

Abstract Background: Immune Thrombocytopenia Purpura (ITP) is defined by a low platelet count in the absence of any known causes and affects over 4,000 US children and 8,000 adults each year (Terrell et al, 2010). Deciding when and how to treat these patients remains difficult as there is no biomarker or diagnostic test that identifies which patients will self-resolve and which are at risk for major bleeding and life-threatening intracranial hemorrhage (~10%). In addition, the medications used to treat ITP all have significant side effects, forcing clinicians to balance risks associated with bleeding and medication. As such, an ongoing debate in the field of clinical hematology centers around which patients require therapy (Flores & Buchanan, 2013)(Cooper 2017)(Gralnek 2008). Here, we show that a new quantitative measurement of platelet function, which is independent of known platelet biomarkers (Myers et al, 2017), has diagnostic potential in identifying bleeding risk in ITP patients. Specifically, using high-throughput platelet contraction cytometry (PCC) measurements of individual platelet forces (Myers et al, 2017), we found that low platelet forces strongly correlate with bleeding symptoms. Unlike existing tests of platelet function that use bulk measurements, our test operates at the single cell level and therefore does not depend on the platelet count, enabling a direct comparison of individual platelet function in health versus disease states. In the broad context of overall function, our findings of impaired force generation agree with previous research demonstrating that impaired platelet function, and not low platelet count, correlates with bleeding in ITP patients (Frelinger et al, 2015). In addition, as the first demonstration of a correlation between single cell force and disease, our novel approach may represent an entirely new class of "physics-based" diagnostics. Platelet Contraction Cytometry (PCC): Within the PCC, a single platelet attaches, spreads, and applies contractile force to a pair of fibrinogen microdots that are attached to a moveable, spring-like, surface. Since the applied platelet contractile force is directly proportional to the microdot displacement, the force is calculated from a single fluorescence image of the platelet. Using microfabrication technology, thousands of microdots are created on a single device to enable high-throughput measurements in tightly controlled mechanical, biochemical, and shear microenvironments (Fig 1). Here, gel-filtered platelets from patients are activated (1U/mL thrombin), plated on the device with a moderately stiff surface (75 kPa), and measured as described previously (Myers et al, 2017). Results: In a cohort of ITP patients (n = 27), we observed that patients with bleeding and/or bruising symptoms exhibited significantly lower average platelet contraction forces than asymptomatic patients regardless of platelet count. Using an average force cutoff value of 26nN, we found that low forces identified bleeding in ITP with 100% sensitivity and 89.4% specificity. From a mechanistic perspective, our preliminary data also suggests that mean platelet volume does not correlate with platelet force or function, although further studies on a single platelet level are needed to confirm this result. While this data indicates that patients with bleeding symptoms have platelets with low forces, it is unclear whether low forces correlate with bleeding or whether the patient always has had low platelet forces that therefore render them susceptible to bleeding. Our preliminary prospective data suggests that low platelet forces correlate with the bleeding symptoms themselves and return to higher values when bleeding symptoms cease. Importantly, as our approach enables "single-cell" examinations of platelet forces, we identified different platelet subpopulations unique to ITP. Healthy individuals have a distribution of contractile forces with a single peak, while ITP patients tend to have two prominent peaks, one with a lower contractile force and one with a higher one. Surprisingly, patients with bleeding symptoms only have a low force peak, suggesting that the lack of highly contractile platelets may be a biophysical biomarker for bleeding (Fig 2). Ongoing studies are focused on using this finding to further improve specificity as well as elucidating the mechanistic underpinnings of low platelet contraction in ITP. Disclosures No relevant conflicts of interest to declare.

Quality of Life Improvements Following Eltrombopag Treatment in Children with Chronic Immune Thrombocytopenia: Case Report

2021 ◽  
Vol 104 (4) ◽  
pp. 672-675
Keyword(s):  
Quality Of Life ◽  
Platelet Count ◽  
Receptor Agonist ◽  
Immune Thrombocytopenia ◽  
Case Series ◽  
Thrombopoietin Receptor ◽  
Thrombopoietin Receptor Agonist ◽  
Low Platelet Count ◽  
Chronic Immune Thrombocytopenia

The present case series described six chronic immune thrombocytopenia patients (cITP), with a median age of 7.7 (7.0 to 13.0) years and low platelet count at 15,500 (7,000 to 20,000)/uL. They were suffering from bleeding symptoms and side effects of treatment. After enrollment, they were treated with thrombopoietin receptor agonist (eltrombopag). Five patients responded positively, showing a median platelet count of 115,000 (39,000 to 433,000)/uL. The median dose of eltrombopag used was 1.3 (0.8 to 2.2) mg/kg/day. The quality of life (QoL) improved for all patients, with their median overall score using a Pediatric QoL questionnaire showing 25.0% improvement. Median scores also showed improvements in each sphere of life functioning as physical (30.8%), emotional (26.4%), social (16.4%), and school (21.4%). The present report demonstrated that a select group of cITP patients, with low platelet count and bleeding symptoms, benefitted from treatment with eltrombopag, as shown by increased platelet counts and improved QoL. Keywords: Chronic ITP, Thrombopoietin receptor agonist, Children

scholarly journals Ethylenediaminetetraacetic Acid‑Dependent Pseudothrombocytopenia in Patient Previously Treated as Dengue Fever

2021 ◽  
Vol 17 (1) ◽  
pp. 65
Author(s):  
Hendra Wana Nur’amin ◽  
Muhammad Darwin Prenggono ◽  
Wivina Riza Devi
Keyword(s):  
Bone Marrow ◽  
Platelet Count ◽  
Dengue Fever ◽  
Complete Blood Count ◽  
Ethylenediaminetetraacetic Acid ◽  
Bone Marrow Aspiration ◽  
Normal Platelet ◽  
Low Platelet Count ◽  
Bleeding Manifestation ◽  
Secondary Hospital

Abstract: One of the most widely used anticoagulants for a complete blood count is ethylenediaminetetraacetic acid (EDTA).  Pseudothrombocytopenia (PTCP) may be caused by EDTA, this condition may lead to inappropriate diagnosis and treatment. We report a 25-year-old female with unspecific headache and joint pain with very low platelet count since 1 month before hospital admission. She was diagnosed with Dengue fever infection and got some platelet transfusion from the previous secondary hospital. She was carried out for a blood test with another anticoagulant (sodium citrate) and bone marrow aspiration. The results showed that she had normal platelet count and bone marrow cellularity. When a patient was identified with thrombocytopenia without any bleeding manifestation, hematology disease, and family history, PTCP should be taken into consideration to prevent unnecessary intervention. Keywords: platelet, pseudothrombocytopenia, ethylenediaminetetraacetic acid, Dengue fever

Severe Thrombocytopenia Delays but Does Not Prevent the Occlusion of an Arterial Prosthesis in Rats

1981 ◽  
Vol 46 (02) ◽  
pp. 558-560 ◽  
Author(s):  
I Reyers ◽  
L Mussoni ◽  
M B Donati ◽  
G de Gaetano
Keyword(s):  
Platelet Count ◽  
Abdominal Aorta ◽  
Immune Thrombocytopenia ◽  
Severe Thrombocytopenia ◽  
Thrombotic Occlusion ◽  
Arterial Prosthesis ◽  
Low Platelet Count ◽  
Experimentally Induced

SummaryThis study shows that experimentally-induced immune thrombocytopenia significantly delayed occlusion of an arterial prosthesis inserted in rat abdominal aorta. Thrombocytopenia was effective when induced several hours or shortly, or even several hours after the insertion of the prosthesis. Maintenance of severe thrombocytopenia by daily administrations of antiplatelet antiserum appeared to further delay thrombotic occlusion.However, though delayed, occlusion eventually occurred in all rats, even in those with very low platelet count. This would imply that any attempt to prevent arterial prosthesis thrombosis solely by interfering with platelets is ultimately bound to fail.

scholarly journals Multiple concomitant mechanisms contribute to low platelet count in patients with immune thrombocytopenia

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Matías Grodzielski ◽  
Nora P. Goette ◽  
Ana C. Glembotsky ◽  
M. Constanza Baroni Pietto ◽  
Santiago P. Méndez-Huergo ◽  
...  
Keyword(s):  
Platelet Count ◽  
Immune Thrombocytopenia ◽  
Low Platelet Count

Epidemiology and Management of Immune Thrombocytopenia in Adult Patients in Algeria: A Non-Interventional, Longitudinal, Nationwide Estimation Study

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 3-4
Author(s):  
Mohamed-Amine Bekadja ◽  
Mohamed Bradai ◽  
Hocine Ait Ali ◽  
Selma Hamdi ◽  
Nadia Boudjerra ◽  
...  
Keyword(s):  
Platelet Count ◽  
Immune Thrombocytopenia ◽  
Epidemiological Data ◽  
Bleeding Risk ◽  
Peripheral Circulation ◽  
Public Hospitals ◽  
Case Report Form ◽  
Low Grade ◽  
Treatment Regimens ◽  
Bleeding Score

Background: Immune thrombocytopenia (ITP), is an acquired immune mediated disease characterized by a platelet count of <50×103/mm3, accelerated destruction of platelets from peripheral circulation, and impaired platelet production. Diagnosis is based on exclusion of other causes of thrombocytopenia. Treatment goal is to ensure sufficient platelet count to prevent bleeding. ITP occurs mainly in women, either at the onset of puberty, or in their 3rd/4th decade, with higher mortality in older patients. To date, no accurate epidemiological data on ITP is available for Algeria. This study assessed the incidence (by age, sex, diagnosis stage, and province), prevalence, characteristics, and treatment regimens received by ITP patients (pts) in Algeria. Methods: This non-interventional, longitudinal, nationwide estimation study investigated the epidemiology and care of ITP pts treated in public hospitals in Algeria from September 2017─August 2018. Data were collected at inclusion visit on a case report form. Data on bleeding score and platelet count were also collected after study termination. Pts ≥16 years (y) of age, either previously (before 1st September 2017) or newly (September 2017─August 2018) diagnosed with ITP, having given written consent, were included. The incidence and prevalence of ITP were estimated with Poisson distribution (95% confidence interval [CI]). Results: Overall 1,746 pts were listed, of whom 587 without consent. Of the 1,164 enrolled pts, 1,159 were included (male: 264 [22.8%]); 5 pts (0.4%) were excluded for major protocol deviations. Among eligible pts, 173 (14.9%) were newly and 986 (85.1%) had been previously diagnosed with ITP. No comorbidities conferring bleeding risk were found in 966 pts (83.3%). At diagnosis, median age was 36y (quartiles: 25y, 50y) and platelet count (103/mm3) was 0-30 in 124 (71.7%), 30-50 in 20 (11.6%), and 50-100 in 28 (16.2%) pts. Khellaf score was ≤8 for 45 (26.0%) and >8 for 8 (4.6%) pts; 120 pts (69.4%) had missing Khellaf score. Bleeding risk (as per WHO bleeding score) was low (grade 0) in 50 (28.9%), grade I in 24 (13.9%), grade II in 34 (19.7%), grade III in 52 (30.1%), and grade IV in 13 (7.5%) pts. 55 (31.8%) pts were asymptomatic, 58 (33.5%) were ecchymotic, and 60 (34.7%) were severely hemorrhagic. Steroids comprised the major treatment for both new (n [%]: 136 [78.6]) and previously (795 [80.7]) diagnosed ITP pts. First line ITP treatments included corticosteroids (937 [80.8]), immunoglobulins (39 [3.4]), antineoplastic agents (15 [1.3]), rituximab (14 [1.2]) and antibacterials (2 [0.2]). Last/ongoing treatments at inclusion comprised corticosteroids (712 [72.2]), rituximab (56 [5.7]), immunoglobulins (30 [3.0]), romiplostim (19 [1.9]), and antibacterials (4 [0.4]). Among previously diagnosed ITP pts, 172 (17.4%) had a splenectomy with a median time from ITP diagnosis of 19 months. Incidence of ITP in pts ≥16y was 0.85 cases (95% CI: 0.75, 0.96) per 100,000 inhabitants. Incidence increased with age from 0.5 (95% CI: 0.43, 0.68) in pts aged 15-35y to 2.4 (95% CI: 1.60, 3.51) in pts ≥75y old. Female pts had a higher incidence of ITP (1.2 [95% CI: 1.02, 1.37]) vs male pts (0.5 [95% CI: 0.43, 0.67]; male:female ratio 0.3). Incidence of ITP varied with diagnosis stage (asymptomatic: 0.4 [95% CI: 0.31, 0.45]; ecchymosis: 0.1 [95% CI: 0.10, 0.19]; severe hemorrhage: 0.1 [95% CI: 0.06, 0.13]), and province (lowest: 0.1 [95% CI: 0.02, 0.92] in a public site in Tebessa; highest: 1.6 [95% CI: 0.93, 2.89] in a public site in Sidi Bel Abbès). Prevalence of ITP was 5.7 (95% CI: 5.39, 5.93) per 100,000 inhabitants. Prevalence increased with age from 3.2 (95% CI: 2.78, 3.67) in pts aged 15-25y to 11.9 (95% CI: 9.68, 13.08) in pts aged 65-75y, then decreased in pts ≥85y old (7.6 [95% CI: 4.79, 12.06]). Female pts had a higher prevalence of ITP (8.8 [95% CI: 8.33, 9.29]) vs male pts (2.6 [95% CI: 2.34, 2.85]). Conclusion: The incidence and prevalence of ITP in Algeria were higher in females and increased with age conforming to global trends, but lower than occidental data thus requiring further investigations. Corticosteroids were the most commonly used agents in different lines of treatment; splenectomy was the second option in cases of corticosteroid failure. Rituximab and romiplostim were the last/ongoing treatment before inclusion for a small number of pts. The study highlighted the need for more data on the use of romiplostim prior to splenectomy for adult ITP pts in Algeria. Disclosures Tiaiba: Amgen Middle East:Current Employment.Saad:Amgen Inc:Current Employment.

scholarly journals Laparoscopic splenectomy for immune thrombocytopenia in patients with a very low platelet count

2018 ◽  
Vol 13 (2) ◽  
pp. 157-163 ◽  
Author(s):  
Anna Zychowicz ◽  
Dorota Radkowiak ◽  
Anna Lasek ◽  
Piotr Małczak ◽  
Jan Witowski ◽  
...  
Keyword(s):  
Platelet Count ◽  
Laparoscopic Splenectomy ◽  
Immune Thrombocytopenia ◽  
Low Platelet Count

scholarly journals Can Immature Platelet Fraction (IPF) be Used to Assess Bleeding Risk in Pediatric Immune Thrombocytopenia (ITP) and to Differentiate ITP from Bone Marrow Failure/Aplastic Anemia? A Retrospective Analysis

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3474-3474 ◽  
Author(s):  
Karen Lee Bride ◽  
Derick Lim ◽  
Michele Paessler ◽  
Michele P Lambert
Keyword(s):  
Bone Marrow ◽  
Platelet Count ◽  
Immune Thrombocytopenia ◽  
Bone Marrow Failure ◽  
Bleeding Risk ◽  
Medical Laboratory ◽  
Bleeding Complications ◽  
Severe Thrombocytopenia ◽  
Immature Platelet Fraction ◽  
Time Of Presentation

Abstract Immune Thrombocytopenia (ITP) usually presents with isolated, severe thrombocytopenia with very low platelet count (generally less than <30 x 109/L) in the absence of other hematologic abnormalities. However, ITP is a diagnosis of exclusion without any definite diagnostic test that can confirm the diagnosis at the time of presentation and clinicians occasionally worry at the time of presentation about other bone marrow processes that may present with thrombocytopenia, which would require considerably different therapy. In light of current guidelines suggesting that observation is likely to be safe in pediatric patients with low platelet counts without significant bleeding, identifying patients at risk for severe hemorrhage is even more important to help guide therapy. In addition, appropriately differentiating ITP from other diagnoses may also prevent inappropriate administration of ineffective therapies. The immature platelet fraction (IPF) is a measure of platelet turnover measuring RNA containing, large platelets by fluorescently labeling the platelets and utilizing flow cytometric gates programmed into the Sysmex XN-3000 hematology analyzer. We examined the medical laboratory records of 134 patients who had an IPF performed over the past 4 months for correlation between IPF and bleeding manifestations. In ITP patients who presented with significant bleeding symptoms (defined as epistaxis which was more than brief, oral bleeding more than palatal petechiae or GI or intracranial hemorrhage), the IPF was significantly lower than in those who presented with no bleeding or cutaneous bleeding only (bruising and petechiae): IPF=4.3%±1.6 SEM in bleeding patients versus 21.8%±1.8 SEM in not bleeding patients; p<0.0001. In two patients with life threatening hemorrhage and ITP (GI bleeding with drop in hemoglobin requiring both PRBC transfusion and treatment to raise the platelet count; ICH resulting in mortality), the IPF was low at the time of initial hemorrhage, but increased after ITP therapy (GI Bleed: plt 1K, IPF 5.3% increased to 20.3% after IVIG; ICH plt 6K, IPF 1.8% increased to 12.8% after IVIG and prednisone). We also examined first platelet count and IPF in 127 patients with ITP and 21 patients with BMF/AA who presented to our institution since October 2013. In this cohort of patients, the IPF in patients with ITP was significantly higher than in the BMF/AA patients and an IPF of >5.3 was associated with a negative predictive value of 80% for BMF/AA (IPF 16.6%±1.2 SEM in ITP vs. 2.9%±1.4 SEM in BMF/AA). In summary, we demonstrate that the IPF is a useful and simple adjunct in diagnosis of ITP which can help differentiate the patients most likely to have ITP from those who may need further diagnostic evaluation and require treatment to prevent bleeding complications. Further studies will focus on the ability of the IPF to prospectively predict the bleeding risk of patients and categorize patients. Disclosures Lambert: GSK: Consultancy; NovoNordisk: Honoraria; Hardin Kundla McKeon & Poletto: Consultancy.

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