scholarly journals Analysis of Interleukin-4 in Thrombocytopenia Autoimmune Patients

Biomedika ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 131-135
Author(s):  
Sitti Nurfaizah ◽  
Mansyur Arief ◽  
Uleng Bahrun
Keyword(s):  
Platelet Count ◽  
Medical Records ◽  
Immune Thrombocytopenia ◽  
Interleukin 4 ◽  
Subject Group ◽  
Elisa Method ◽  
Platelet Production ◽  
Cytokine Levels ◽  
Primary Immune Thrombocytopenia ◽  
Loss Of Tolerance

Thrombocytopenia is a disease characterized by a decreased platelet count. Some of the causes are decreased platelet production, increased platelet use, such as due to infection, and autoimmune causes, namely the loss of tolerance of the immune system to self-antigens on the surface of the platelets and megakaryocytes marked with a platelet count <100,000 / μL and based on the pathomechanism classified as primary Immune Thrombocytopenia (ITP) and secondary, as well as several other causes. IL-4, one of the cytokines produced by Th2 which stimulates B cells to increase antibody production. The aim of this study was to compare IL-4 levels in primary ITP patients and non-primary ITP tombocytopenia. This study involved 30 primary ITP subjects and 30 non-ITP primary tombocytopenia subjects obtained based on data medical records, examination of IL-4 cytokine levels by the ELISA method. The results of this study that the IL-4 levels of the primary non ITP tombocytopenia subject group were higher than the primary ITP subject group, which means that there were differences in IL-4 levels in the primary ITP subject group and the non-ITP primary tombocytopenia subject group.

scholarly journals Analysis of Interleukin-17 Levels in Patients with Thrombocytopenia

Biomedika ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 68-73
Author(s):  
Lidwina Septie Christyawardani ◽  
Mansyur Arief ◽  
Uleng Bahrun
Keyword(s):  
Blood Circulation ◽  
Immune Thrombocytopenia ◽  
Research Unit ◽  
Comparative Test ◽  
P Value ◽  
Interleukin 17 ◽  
Platelet Production ◽  
Immune Mediated ◽  
Significant Difference ◽  
Primary Immune Thrombocytopenia

Thrombocytopenia or platelet deficiency is a condition, in which platelet level in the blood circulation is below normal, which is less than 150,000 cells/µl. Thrombocytopenia is classified into some conditions, including decreased platelet production, increased need for platelets, and other thrombocytopenia. The need for increased platelets can be subdivided into primary immune thrombocytopenia, secondary immune thrombocytopenia, non-primary ITP, and thrombocytopenia that are not immune-mediated. Several cytokines play a role in the process of thrombocytopenia, one of which is Interleukin-17 (IL-17) that will be further discussed in this study. A previous study reported that IL-17 production increased in ITP and cITP patients. The objective of this study was to analyze the IL-17 levels and figure out the differences in IL-17 levels in the serums of patients with primary ITP and secondary ITP. The samples were taken from Wahidin Sudirohusodo Hospital and the specimens were examined in the Research Unit Laboratory of the Faculty of Medicine, Universitas Hasanuddin/Hospital of Universitas Hasanuddin. The comparative test resulted in p-value = 0.005, where p <α = 0.05; and therefore, there was a significant difference between IL 17 levels in ITP and non-primary ITP.

How I Manage cyclic thrombocytopenia

Blood ◽  
2020 ◽  
Author(s):  
Paul A Kyrle ◽  
Sabine Eichinger
Keyword(s):  
Platelet Count ◽  
Immune Thrombocytopenia ◽  
Hematological Malignancies ◽  
Severe Bleeding ◽  
Typical Pattern ◽  
Periodic Fluctuation ◽  
Thrombopoietin Receptor ◽  
Primary Immune Thrombocytopenia ◽  
Platelet Count Monitoring ◽  
Mucocutaneous Bleeding

Cyclic thrombocytopenia (CTP) is a rare disease, which is characterized by periodic fluctuation of the platelet count. The pathogenesis of CTP is unknown and most likely heterogeneous. Patients with CTP are almost always misdiagnosed as having primary immune thrombocytopenia (ITP). The interval between ITP and CTP diagnosis can be many years. CTP patients often receive ITP-specific therapies including corticosteroids, thrombopoietin receptor agonists, rituximab and splenectomy which are followed by a transient increase in platelet count that is wrongly attributed to treatment effect with inevitable "relapse". CTP can be diagnosed by frequent platelet count monitoring which reveals a typical pattern of periodic platelet cycling. An early diagnosis of CTP will prevent these patients from being exposed to possibly harmful therapies. The bleeding phenotype is usually mild and consists of mucocutaneous bleeding at the time when the platelet count is at its nadir. Severe bleeding from other sites can occur but is rare. Some patients respond to cyclosporine A or to danazol, but most patients do not respond to any therapy. CTP can be associated with hematological malignancies or disorders of the thyroid gland. Nevertheless, spontaneous remissions can occur, even after many years.

Autologous 111 Indium-Oxinate-Labelled Platelet Sequestration Study in Patients with Immune Thrombocytopenia Treated By Thrombopoietic Receptor-Agonists

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2555-2555
Author(s):  
Matthieu Mahevas ◽  
Sandrine Van Eeckhoudt ◽  
Guillaume Moulis ◽  
Christine Dosquet ◽  
Marc Michel ◽  
...  
Keyword(s):  
Platelet Count ◽  
Life Span ◽  
Kinetic Study ◽  
Immune Thrombocytopenia ◽  
Complete Response ◽  
Splenic Sequestration ◽  
Platelet Production ◽  
Receptor Agonists ◽  
Day Range ◽  
The Impact

Abstract Introduction In immune thrombocytopenia (ITP), isotopic assessment of the site of platelet destruction using autologous111Indium-oxinate-labelled platelet sequestration study could be an helpful parameter to determine whether or not to perform splenectomy. Two independent studies have suggested that a purely splenic sequestration could be a significant predictive factor of long-term complete response after splenectomy. An increasing number of patients receives thrombopoietic receptor-agonists (TPO-RAs) but such treatments are not curative and therefore do not necessarily prevent from considering splenectomy in the course of ITP. TPO-RAs increase platelet production by inducing proliferation and differentiation of the megakaryocyte lineage. We have only very few data evaluating the impact of TPO-RAs, on mean platelet life span (MPLS), platelet production and platelet site of destruction. The aim of this study was to assess these parameters and clinical outcome of patients treated with TPO-RAs who underwent kinetic study of autologous111Indium-oxinate-labelled platelet. Patients and Methods We carried out a retrospective study in the Ile de France region, between 2008 and 2016. Patients were retrospectively selected from a prospective clinical database at the Cellular Biology Department of Saint Louis Hospital. We selected adult patients with definite ITP according to the international criteria. The isotopic method used to study platelet lifespan was previously described. Analyses were based on the radioactivity accumulation slopes in the hepatic or splenic area. We excluded patients who had received less than 3Mbeq of 111In. Data from patients' medical charts were collected using the standardized form of the Referral Center for Adult ITP. Complete response (CR) and Response (R) were defined according to standardized international criteria: platelet count > 30x 109/L with at least a doubling of the baseline value or >100 x 109/L. Results of platelet kinetic study from patients treated with TPO-RAs were compared with those from patients receiving no treatments. Results Two hundred and fifty three adults ITP patients were included. At the time of platelet kinetic study, 24 patients (10 men/14 women) with a median age of 63 years [range: 22-83] were treated with TPO-RAs (romiplostim n= 10, eltrombopag n = 14) and 229 (81 men/148 women) had no treatment. Among the TPO-RAs treated patients, some also received low dose steroids (n=6), dapsone (n=1) or intravenous immunoglobulins (n=2) at least two weeks before the kinetic study. Three were newly diagnosed, 9 had persistent ITP and 12 chronic ITP. The median platelet count was 62 x109/L [range: 22-175], and 7 patients had a platelet count > 100 x109/L. The median Mean Platelet Life Span (MPLS) was reduced in both groups (1.44 day [range: 0.4-7.5] (normal: 7-10) in patients treated with TPO-RAs), but was significantly higher in untreated patients (2.3 day [0.4-11], p = 0.004). The median turnover platelets ratio was increased in both groups (48% per day [range: 11-173] in patients treated with TPO-RAs), but was significantly lower in untreated patients (30% per day [range: 0.8-247]). Ratio of platelet production was significantly increased in patients treated with TPO-RAs (median: 2, [range: 0.1-5.0]) compared with untreated patients (median: 0.84, [range: 0.1-85.0]). Repartition of the site of platelet sequestration was similar in the two groups, 12 (50%) patients treated with TPO-RAs had a splenic uptake, versus 112 (49.1%) in untreated patients, and 2 (20%) patients treated with TPO-RAs had an hepatic uptake versus 9 (3.9%) in untreated patients. A splenectomy was performed in 9 out of the 12 patients with a purely splenic sequestration. After a median follow-up of 26 months [range 0-53], 8 (88%) had achieved CR and 1 had relapsed 5 months after splenectomy. Conclusion Our study shows that despite an increase production and turnover of platelets due to the stimulation of the megakaryopoiesis by TPO-RAs, the MPLS was clearly reduced and the repartition of platelet sequestration was not modified in patients receiving these drugs. Moreover, it would seem that a purely splenic sequestration is also predictive of CR after splenectomy in this group of patients. More importantly platelet kinetic study can be used in patients treated with TPO-RAs to position the splenectomy in the therapeutic management. Disclosures No relevant conflicts of interest to declare.

scholarly journals Maternal and fetal outcomes of primary immune thrombocytopenia during pregnancy: A retrospective study

2017 ◽  
Vol 11 (1) ◽  
pp. 12-16 ◽  
Author(s):  
KS Gilmore ◽  
C McLintock
Keyword(s):  
Platelet Count ◽  
Immune Thrombocytopenia ◽  
Post Partum ◽  
Bleeding Complications ◽  
Platelet Response ◽  
Thrombocytopenic Purpura ◽  
Primary Immune Thrombocytopenia ◽  
Secondary Outcomes ◽  
Post Partum Haemorrhage ◽  
Auckland Hospital

Objective We reviewed outcomes of 52 pregnancies in 45 women with immune thrombocytopenic purpura who delivered at Auckland Hospital with an antenatal platelet count of <100 × 109/L. Outcome measures Primary outcomes were maternal platelet count at delivery and treatment response. Secondary outcomes included post-partum haemorrhage (PPH). Results Most women had thrombocytopenia at delivery. Treatment with prednisone was given in 14 (27%) pregnancies with responses considered safe for delivery in 11 pregnancies (79%). Women in eight pregnancies also received intravenous immunoglobulin; in five pregnancies (63%) a platelet response acceptable for delivery was achieved. Seventeen pregnancies (33%) were complicated by a PPH ≥500 mL. Ten pregnancies (19%) were complicated by a PPH ≥1000 mL. PPH was reported in all women with a platelet count <50 × 109/L at delivery. Conclusions There were no antenatal bleeding complications but PPH was common among women with platelet counts <50 × 109/L at the time of birth.

scholarly journals Interleukin (IL)-1 family cytokine in primary immune thrombocytopenia: a comparison with systemic lupus erythematosus-associated thrombocytopenia

2020 ◽  
Author(s):  
Yanxia Zhan ◽  
Boting Wu ◽  
Chanjuan liu ◽  
Luya Cheng ◽  
Lili Ji ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Platelet Count ◽  
Lupus Erythematosus ◽  
Immune Thrombocytopenia ◽  
Serum Levels ◽  
Healthy Controls ◽  
Systemic Lupus ◽  
Primary Immune Thrombocytopenia ◽  
Polymerase Chain

Abstract Background : Primary immune thrombocytopenia (ITP) is an autoimmune-mediated disorder characterized by decreased platelet count. Systemic lupus erythematosus (SLE) is also an autoimmune disease which thrombocytopenia is a common hematologic manifestation. Interleukin (IL)-1 family cytokines are major proinflammatory and immunoregulatory mediators. This study aimed to investigate the role of IL-1 cytokines in patients with ITP and SLE and the potential pathophysiologic mechanism to differentiate SLE-associated thrombocytopenia (SLE-TP) from ITP. Methods : Multiplex cytokine assay and real-time polymerase chain reaction (RT-PCR) were used to measure the IL-1 cytokines in 17 newly diagnosed ITP patients, 17 SLE-TP patients, 19 SLE patients without thrombocytopenia (SLE-NTP) and 10 healthy controls. Results : The serum levels of IL-1β, IL-18, IL-36α, IL-36β, IL-36γ and IL-33 were decreased significantly in ITP patients as compared with SLE-TP, SLE-NTP patients and healthy controls ( p <0.05). There was no significantly difference in the serum level of IL-37 between ITP and SLE-TP patients, however, there is a positive correlation between platelet count with IL-37 level in ITP patients. Our data suggested that serum IL-1β, IL-18, IL-36α, IL-36β, IL-36γ, IL-33 and IL-37 were involved in the pathogenesis of ITP. Conclusions : Serum IL-1β, IL-18, IL-36α, IL-36β, IL-36γ and IL-33 could be considered biomarkers to differentiate SLE-TP from ITP patients.

Increased Microparticle-Linked Procoagulant Activity In Patients with Primary Immune Thrombocytopenia.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3707-3707
Author(s):  
Elena G. Arias Salgado ◽  
Ihosvany Fernández Bello ◽  
Mayte Álvarez Román ◽  
Isabel Rivas ◽  
Mónica Martín Salces ◽  
...  
Keyword(s):  
Platelet Count ◽  
Immune Thrombocytopenia ◽  
Thrombin Generation ◽  
Conflicts Of Interest ◽  
Lag Time ◽  
Peak Height ◽  
Procoagulant Activity ◽  
Control Group ◽  
Increased Risk ◽  
Primary Immune Thrombocytopenia

Abstract Abstract 3707 Primary immune thrombocytopenia (ITP) is an acquired immune-mediated disorder characterized by isolated thrombocytopenia (platelet count less than 100,000/μL) and the absence of any obvious initiating and/or underlying cause for the thrombocytopenia. In spite of the low platelet number, some thrombocytopenic patients seldom bleed, indicating the existence of other factors that regulate haemostasis in these patients. Elevated levels of plasma microparticles (MPs) had been observed in IPT patients. MPs are vesicles with a size less than 0.5 micrometers, derived from cell membranes after their activation or apoptosis. Most MPs are highly procoagulant, expressing annexin V binding sites and tissue factor. However, relatively little is known of their specific functions in ITP. In the present study we aim to elucidate if a relationship exists between microparticle-linked procoagulant activity and haemostasis in ITP patients. Twenty-two ITP patients, 3 male and 19 female, aged between 25 to 92 years, were included. Sixteen age- and sex-matched healthy individuals were used as control group. Platelet-related primary haemostasis was evaluated with an automated platelet function analyzer (PFA-100®, Siemens Healthcare Diagnostics). Samples of citrated blood were aspirated under a shear rate of 4,000–5,000/s through a 150-micrometer aperture cut into a collagen-ADP (COL-ADP) or collagen-epinephrine (COL-EPI) coated membrane. The platelet haemostatic capacity is indicated by the time required for the platelet plug to occlude the aperture (closure time), which is expressed in seconds. MP procoagulant activity was determined with ZYMUPHEN MP-Activity kit (Aniara, Mason, Ohio) and by calibrated automated thrombography (CAT) in plasma samples obtained after 2 centrifugations at room temperature (first: 15 min at 1,500 g, second: 2 min at 13,000 g). These methods measure endogenous thrombin generation. CAT evaluates four parameters of thrombin generation: the endogenous thrombin potential (ETP), lag time, time to peak (TTP) and peak height. PFA-100® determinations with COL-EPI and COL-ADP cartridges in blood samples from ITP patients with less than 50,000/μL showed longer closure times than control group (p<0.05), whereas samples from ITP patients with a platelet count between 50,000/μL and 100,000/μL showed closure times of the same order of magnitude as control ones (platelet count ranging from 162,000 to 368,000)μL).Plasma from these patients had higher MP-mediated procoagulant activity evaluated with ZYMUPHEN kit (control 6.1+3.9 nM, ITP group 10,1±8.2 nM, p<0.05) as well as with CAT (ETP (nM*min): control: 1692.6±341.9, ITP: 2191,8±398.9, p<0.01; lag time (min): control: 19.9±8.2, ITP: 14.3±4.3, p<0.05; TTP (min): control: 22.0±8.3, ITP:16.3±4.4, p<0.05; peak height (nM): control: 389.7±70.6, ITP: 498,8±97.5, p<0.01). Our results indicate that increased MP procoagulant activity in ITP patients may be protective against bleeding events that should be observed in those thrombocytopenic conditions. Three of the ITP patients included in this study had been splenectomyced and we consider of interest to point out that two of them in spite of recovering a normal platelet count still maintain a high MP procoagulant activity. This observation agrees with a recent work that postulates that MPs might contribute to an increased risk of thrombosis, progression of atherosclerosis and cardiovascular disease following splenectomy (Fontana et al, Thromb Research, 2008;122:59). Disclosures: No relevant conflicts of interest to declare.

Dexamethasone plus rituximab yields higher sustained response rates than dexamethasone monotherapy in adults with primary immune thrombocytopenia

Blood ◽  
2010 ◽  
Vol 115 (14) ◽  
pp. 2755-2762 ◽  
Author(s):  
Francesco Zaja ◽  
Michele Baccarani ◽  
Patrizio Mazza ◽  
Monica Bocchia ◽  
Luigi Gugliotta ◽  
...  
Keyword(s):  
Platelet Count ◽  
Adverse Events ◽  
Salvage Therapy ◽  
Immune Thrombocytopenia ◽  
Sustained Response ◽  
Effective Treatment Option ◽  
Serious Adverse Events ◽  
Primary Immune Thrombocytopenia ◽  
Grade 3 ◽  
To Receive

Abstract Previous observational studies suggest that rituximab may be useful in the treatment of primary immune thrombocytopenia (ITP). This randomized trial investigated rituximab efficacy in previously untreated adult ITP patients with a platelet count of 20 × 109/L or less. One hundred three patients were randomly assigned to receive 40 mg/d dexamethasone for 4 days with or without 375 mg/m2 rituximab weekly for 4 weeks. Patients who were refractory to dexamethasone alone received salvage therapy with dexamethasone plus rituximab. Sustained response (ie, platelet count ≥ 50 × 109/L at month 6 after treatment initiation), evaluable in 101 patients, was greater in patients treated with dexamethasone plus rituximab (n = 49) than in those treated with dexamethasone alone (n = 52; 63% vs 36%, P = .004, 95% confidence interval [95% CI], 0.079-0.455). Patients in the experimental arm showed increased incidences of grade 3 to 4 adverse events (10% vs 2%, P = .082, 95% CI, −0.010 to 0.175), but incidences of serious adverse events were similar in both arms (6% vs 2%, P = .284, 95% CI, −0.035 to 0.119). Dexamethasone plus rituximab was an effective salvage therapy in 56% of patients refractory to dexamethasone. The combination of dexamethasone and rituximab improved platelet counts compared with dexamethasone alone. Thus, combination therapy may represent an effective treatment option before splenectomy. This study is registered at http://clinicaltrials.gov as NCT00770562.

scholarly journals Assessment of Romiplostim Immunogenicity in Pediatric Patients in Clinical Trials and in a Global Postmarketing Registry

2021 ◽  
Author(s):  
Charles Bowers ◽  
Daniel T. Mytych ◽  
Tatiana Cristina Lawrence ◽  
Kejia Wang ◽  
Troy E. Barger ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Platelet Count ◽  
Neutralizing Antibodies ◽  
Receptor Agonist ◽  
Immune Thrombocytopenia ◽  
First Generation ◽  
Pediatric Patients ◽  
Cross Reactivity ◽  
Platelet Response ◽  
Primary Immune Thrombocytopenia

Development of first-generation thrombopoietins (TPOs) was halted due to antibodies that neutralized endogenous TPO, causing protracted thrombocytopenia in some patients. The second-generation TPO receptor agonist romiplostim, having no homology to TPO, was developed to circumvent potential immunogenicity. We examined development of binding and neutralizing antibodies to romiplostim and TPO among pediatric patients with primary immune thrombocytopenia (ITP) in 5 trials and a global postmarketing registry. In the trials, 25/280 (8.9%) patients developed anti-romiplostim binding antibodies. The first positive result was detected 67 weeks (median) after starting romiplostim; median romiplostim dose was 8 µg/kg and median platelet count 87 x 109/L. Most patients who developed anti-romiplostim binding antibodies (18/25 [72%]) had ≥ 90% platelet assessments showing response. Anti-romiplostim neutralizing antibodies developed in 8/280 (2.9%) patients; this was unrelated to romiplostim dose, and most patients who developed anti-romiplostim neutralizing antibodies (7/8 [88%]) had platelet response. Nine of 279 (3.2%) patients developed anti-TPO binding antibodies, and 1 (0.4%) developed transient anti-TPO neutralizing antibodies. In 8 patients who developed anti-romiplostim neutralizing antibodies, no TPO cross-reactivity was observed. In the postmarketing registry, 3/19 (15.8%) patients had anti-romiplostim binding antibodies; 1 (5.3%) had anti-romiplostim neutralizing antibodies. These results show that immunogenicity to romiplostim occurs infrequently in children with ITP and is generally not associated with loss of platelet response or other negative clinical sequelae.

Combination of Recombinant Factor VIIa and Fibrinogen Corrects Clot Formation in Primary Immune Thrombocytopenia At Very Low Platelet Counts

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4667-4667
Author(s):  
Ole Halfdan Larsen ◽  
Jesper Stentoft ◽  
Deepti Radia ◽  
J∅rgen Ingerslev ◽  
Benny S∅rensen
Keyword(s):  
Platelet Count ◽  
Board Of Directors ◽  
Research Funding ◽  
Immune Thrombocytopenia ◽  
Recombinant Factor Viia ◽  
Factor Viia ◽  
Advisory Committees ◽  
Platelet Counts ◽  
Primary Immune Thrombocytopenia

Abstract Abstract 4667 Introduction: Primary immune thrombocytopenia (ITP) is an autoimmune disorder characterized by a low platelet count and an increased risk of bleeding. Hemostatic treatment modalities, bypassing the need for platelet transfusion, would be desirable for control of serious acute bleeds in patients with ITP. This study aimed at (i) performing a thorough characterization of the coagulopathy of ITP, (ii) investigate new ways to obtain acute correction of the coagulopathy performing in vitro experiments with recombinant factor VIIa (rFVIIa, NovoSeven®), fibrinogen (RiaSTAP®), and the combination of rFVIIa and fibrinogen, and finally (iii) investigate the correlation of the hemostatic response to the baseline platelet counts of the ITP patients. We challenged the hypothesis that rFVIIa combined with fibrinogen concentrate can correct whole blood (WB) clot formation in patients suffering from ITP even at very low platelet counts. Methods: Blood from 12 ITP patients and 15 healthy controls was drawn into 3.2% citrate containing corn trypsin inhibitor 18.3μg mL−1 to inhibit artificial contact activation. The WB (mean platelet count 22 × 109L−1 (range 0–42)) was spiked in vitro with buffer (control), fresh donor platelets (+40×109 L−1), rFVIIa (1 or 4μg mL−1), or fibrinogen (1 or 3mg mL−1) as well as the combination of rFVIIa and fibrinogen. Dynamic WB coagulation profiles were recorded by ROTEM® Thromboelastometry using activation with tissue factor (0.03pM) and re-calcification. Parameters of clot initiation (clotting time, CT), clot propagation (maximum velocity, MaxVel) as well as clot termination (maximum clot firmness, MCF) were evaluated. Thrombin generation in “platelet-rich” ITP plasma was evaluated using calibrated automated thrombography. Overall differences between groups were evaluated by paired and unpaired t-tests as appropriate. Simple linear regression analyses were performed using the differences observed after addition of the various interventions (intervention – baseline) as the dependent variable (y) and the platelet count as the independent variable (x). The slope was used to evaluate dependency of the hemostatic response on the platelet count, whereas the intercept was used to evaluate the hemostatic response at very low platelet counts. A p-value less than 0.05 was considered statistically significant. Results: Compared with healthy controls the WB coagulation profiles of the ITP patients were characterized by a prolonged CT (mean: 1490 vs. 941s, p<0.001) as well as a markedly reduced MaxVel (3.4 vs. 9.7mm×100s−1, p<0.001) and MCF (38.2 vs. 49.4mm, p=0.01). Fibrinogen showed no positive hemostatic effect. Recombinant FVIIa reduced the CT (744s, p<0.001) and increased the MaxVel (6.28mm×100s−1, p<0.001) whereas no change was observed in the MCF. Thrombin generation in “platelet-rich” plasma supported the findings in WB. The improvement in CT following addition of rFVIIa was independent of the platelet count (p-values > 0.45) and the intercept showed a significant improvement at very low platelet counts (1μg mL−1: −643s, p<0.001; 4μg mL−1: −811s, p<0.001). In contrast, the increase in MaxVel after addition of rFVIIa was highly dependent on the platelet count (1μg mL−1: R2 = 0.81, p < 0.001; 4μg mL−1: R2 = 0.86, p < 0.001) and the intercept was not significant (1μg mL−1: 0.05mm×100s−1 p=0.87; 4μg mL−1: 0.54 mm×100s−1 p=0.15). The combination of fibrinogen and rFVIIa revealed a synergistic effect also showing an increased MCF (50.7mm) in addition to a reduced CT (794s) and improved MaxVel (7.9 mm×100s−1) displaying larger effects than following fresh donor platelet substitution (CT 1164s; MaxVel 6.96mm×100s−1; MCF 49.6mm). Furthermore, rFVIIa together with fibrinogen also showed a significant response at very low platelet counts in all parameters (Intercept: CT −788s, MaxVel 3.3mm×100s−1, MCF 13.9mm, p-values<0.004) Conclusions: Data suggest that rFVIIa combined with fibrinogen can correct the coagulopathy of ITP even at very low platelet counts, and may be an alternative to platelet transfusion. Clinical trials are needed to further investigate if this new treatment modality holds the potential to serve as an effective acute treatment option in ITP. Disclosures: Off Label Use: Recombinant activated factor VII (NovoSeven) and fibrinogen concentrate (RiaSTAP). In vitro data suggesting a haemostatic effect in primary immune thrombocytopenia will be presented. S∅rensen:Novo Nordisk: Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau; Baxter: Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau; CSL Behring: Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau; Bayer: Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau; SOBI: Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau; Pentapharm: Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau; Grifols: Research Funding; LFB: Research Funding; Octapharma: Research Funding.

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