scholarly journals A Multicenter Study Evaluating the Safety of Romiplostim at Maximal Dosage for Emergency Bleeding Situations in Immune Thrombocytopenia

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2541-2541 ◽  
Author(s):  
Mathilde Roumier ◽  
Louis Terriou ◽  
Mohamed Hamidou ◽  
Antoine Dossier ◽  
Anne Sophie Morin ◽  
...  
Keyword(s):  
Body Weight ◽  
Platelet Count ◽  
Immune Thrombocytopenia ◽  
High Dose ◽  
Severe Bleeding ◽  
Relative Safety ◽  
Maximal Dosage ◽  
Bleeding Score ◽  
Platelet Transfusions

Abstract Introduction: The serious consequences of severe, life-threatening bleeding in immune thrombocytopenia (ITP) justify the use of several regimens, including platelet transfusions, high-dose parenteral glucocorticoid and intravenous immunoglobulins. The goal of such treatments is to rapidly elevate the platelet count to a level where the risk of severe bleeding is minimized. We lack experience with the use of thrombopoetin receptor agonists (Tpo-RAs) in this situation of emergency. The aim of this study was to evaluate the safety of the use of romiplostim at maximal dosage in patients with severe bleeding manifestations, who have previously failed to respond to corticosteroids (CST) and intravenous immunoglobulin (IVIg). Patients and Methods: We carried out a multicenter retrospective study in France. We included ITP patients with platelet count < 30 x 109/L.and severe bleeding manifestations, who have failed to respond to corticosteroids and IVIg, and have received a rescue therapy with romiplostim at maximal dosage (ie., 10 mg/kg body weight per week). Failure to treatment was defined according to standardized international criteria and severe bleeding manifestations as a score >8 according to the bleeding score previously reported by our group that take into account cutaneous, mucosal and visceral bleeding. Physicians were interviewed and patients' medical charts 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 > 30x109/L with at least a doubling of the baseline value or >100 x109/L. Non-response (NR) was defined as the absence of platelet count increase >30 x109/L with at least a doubling of the baseline count. Results: Fifteen patients (8 men/7 women) were included in the study. The median age was 68 ± 20.9 years [range 17-92]. Two patients presented secondary ITP according to the international definition criteria. Eleven were newly diagnosed ITP, and 4 chronic ITP. Severe bleeding symptoms were the manifestation of ITP in all cases, with a median bleeding score of 16 [9-28], including 4 intracranial hemorrhage, 2 metrorrhagia, 1 macroscopic hematuria, 3 gastrointestinal bleeding and 1 haemoperitoneum. The median platelet count was 1 [0-4]. All patients had received corticosteroids (1mg/bw/day) including 12 pulses of methylprednisolone and IVIg (median dose 2 g/bw). Twelve have also received 8 mg of vinblastine (1 to 3 injections). Nine received platelet transfusions and 4 received blood tranfusions. One patient had received anti-CD20 therapy (rituximab) the same day as TPO-RA therapy, and another hydroxychloroquine before starting TPO-RA therapy. Romiplostim was started 12 days [range 6-32] in median after the first bleeding episode. At that time bleeding symptoms were severe (>8), and the median platelet count was 4 [1-47]. All received 10 mg/kg body weight of romiplostim (including 3 escalating dose). At day 7 after TPO-RA initiation, 9 patients achieved a CR, 1 patient achieved a R and 5 were still non-responder. At days 14, 10 patients achieved a CR and 5 were still non-responder. During the first month of follow-up, the maximal platelets count among the responders was 590 [range: 312-1169], 9 patients experienced a platelet count > 500 x 109/L. One 51 years old patient, bed bound for a muscular hematoma, experienced a deep vein thrombosis with asymptomatic pulmonary embolism, 13 days after IVIg and 5 days after TPO-RA initiation, with a platelet count of 629.109/L. One patient presented superficial thromboembolism of the arm, 14 days after IVIg and 9 days after TPO-RA initiation with a platelet count of 162.109/L. They were both treated with anticoagulation without complication. After a median follow-up of 10 months, no other TPO-RA-related side effects were observed, TPO-RA was discontinuated in 10 patients. Conclusion: Our study demonstrated the relative safety and the interest of the use of romiplostim at the maximal dose in emergency bleeding situation in patients with failure of conventional therapy. However, risk of venous thromboembolism should be carrefully assess in this situation. Disclosures Terriou: amgen: Consultancy; Novartis: Consultancy.

Eltrombopag and High-Dose Dexamethasone As First Line Treatment For ITP

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3544-3544
Author(s):  
David Gomez-Almaguer ◽  
Miguel Angel Herrera-Rojas ◽  
Andres Gomez-de Leon ◽  
Olga Graciela Cantú-Rodríguez ◽  
Cesar H Gutiérrez-Aguirre ◽  
...  
Keyword(s):  
Platelet Count ◽  
Immune Thrombocytopenia ◽  
High Dose ◽  
Line Treatment ◽  
Front Line ◽  
First Line ◽  
High Dose Dexamethasone ◽  
Line Therapy ◽  
First Line Treatment

Abstract Introduction Primary immune thrombocytopenia (ITP) is an acquired autoimmune disorder that involves antibody and cell mediated destruction of platelets as well as suppression of their production. Prednisone is the initial standard therapy in adults1. High-dose dexamethasone as front-line therapy given as pulses of 40 mg per day for 4 consecutive days, was effective in 85% of patients, nevertheless, 50% relapsed within six months2. The prices of ITP drugs for 1 month of treatment in an adult range from prednisone; $16, eltrombopag; $5,934, intravenous immune globulin (IVIG) (80 g); $9,648, to rituximab (2 g); $15,5963. Only prednisone/dexamethasone and eltrombopag are available in oral presentation, for this reason, ambulatory treatment is an alternative for these patients. The trombopoietin receptor agonists are effective for the treatment of patients with chronic ITP, although response is dependent on continued administration. Eltrombopag is a small molecule agonist of the c-mpl (TpoR) receptor, which is the physiological target of thrombopoietin. This drug effectively raises the platelet count in adult patients (aged 18 years and over) as second/third line therapy, that is for patients refractory to corticosteroids and IVIG who have had their spleen removed or when splenectomy is not an option4. Our group, as well as others, has previously sought to improve response rates in these patients, particularly with the use of rituximab5, 6. To our knowledge neither eltrombopag nor romiplostim have been used as front line therapy in ITP, therefore the purpose of this study was to assess the efficacy of eltrombopag and dexamethasone in this setting. Patients and Methods This was a prospective, phase 2 study, using the combination of eltrombopag (50 mg PO once a day for 4 weeks) and high-dose dexamethasone (40 mg PO days 1,2,3,4) in untreated adult patients with immune thrombocytopenia or in patients with less than 7 days of treatment with corticosteroids. Complete response (CR) was defined as an increase in platelet count >100×109/L. Partial response (PR) was defined as an increase in the platelet count greater to 30 ×109/L according to standard criteria. Duration of response was considered from the day of initial administration to the first time of relapse (platelet count <30×109/L). Results Twelve consecutive patients were enrolled from June 2012 to June 2013, 6 women and 6 men. The median age at diagnosis was 50 years (range, 20 - 80 years). The median platelet count at diagnosis was 7 x 109/L (range, 2 - 29 x 109/L). Patients were followed for a median of 2.5 months (range 1.1 - 13). After steroid treatment at day +5, ten patients had responded (83.3%), five had achieved CR (41.7%), and five PR. After completing treatment with eltrombopag at day +34, all patients responded (100%), nine patients achieved CR (75%) and three PR (25%). Two patients relapsed in a median time of 39.5 days (range, 30.1 - 49), both regaining CR after treatment with another high-dose dexamethasone course and low-dose rituximab (4 doses of 100 mg every week). At 3 months follow-up 66.7% remained in CR and 33.3% in PR (n=6). At 6 months follow-up two patients remained in CR and two in PR (n=4). Time to best response achieved was 34 days from diagnosis (range, 19 – 64.1). At the end of follow-up 9 patients (75%) remained in CR and 3 patients in PR (25%). Total treatment cost per patient was $1,640 approximately. Conclusion Currently the initial treatment of ITP patients is based on prednisone or high dose dexamethasone with or without IVIG. This approach is associated with high cost and high relapse rate. The results from our pilot study suggest that high dose dexamethasone and eltrombopag are very effective as first line treatment for acute ITP in adults. This treatment is ambulatory, affordable and well tolerated; however, we still don't know if this approach will have a favorable impact on the relapse rate of this disease. Disclosures: Off Label Use: Eltrombopag as first line treatment for ITP.

Novel Management of Immune Thrombocytopenia in Gaucher Disease Patients

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5006-5006
Author(s):  
Hanna Rosenbaum
Keyword(s):  
Bone Marrow ◽  
Platelet Count ◽  
Avascular Necrosis ◽  
Gaucher Disease ◽  
Immune Thrombocytopenia ◽  
High Dose ◽  
Type I ◽  
Platelet Counts ◽  
Skeletal Complications

Abstract Type I Gaucher disease (GD) the is characterized by hepatosplenomegaly, pancytopenia and skeletal complications due to the accumulation of glucocerebroside in macrophages. Thrombocytopenia is usually related to hypersplenism and infiltration of bone marrow by lipid-laden macrophages namely Gaucher cells. Enzyme replacement therapy (ERT) restores the hemoglobin and platelet count in GD patients. In GD ERT treated patients, manifesting persistent low platelet counts, immune thrombocytopenia (ITP) should be considered.Treatment of GD with concomitant ITP is a challenge. Splenectomy may worsen bone manifestations in GD patients and is controversial. Steroids should be used with caution because of possible induction of osteopenia and joints avascular necrosis. Thrombopoietin receptor analogues (TPO-RA) are therapeutic option in GD patients with ITP. Beneficial use of TPO-RA is reported in 2 cases. Patient 1: 39 YO male with new onset of purpura and low platelet count failed treatment with 1 mg/kg of Prednisone. Bone marrow biopsy (BM) showed Gaucher cells infiltration, numerous atypical megakaryocytes, normal erythropoiesis and myelopoiesis with no fibrosis. Low level of ß-glucocerebrosidase activity with compound heterozygosity for 84GG /R495H mutations, established the diagnosis of Type I GD. Low C4 and detection of IgG platelet antibodies added to the diagnosis of concomitant immune thrombocytopenia. ERT with taliglucerase alfa (ElelysoTM) 60 Units/kg/month was given with Prednisone for six weeks. Occurrence of retinal bleeding and purpura, with decrease of platelet count necessitated addition of high-dose IVIG with no response regarding platelet counts. Splenectomy was not considered due to known bony complication risk in splenectomised GD patients. Rituximab was given to prevent wet purpura recurrence with short response regarding platelet count. Romiplostim was initiated raising platelet count from 29,000/µL to 60,000/µL after 3 wks. and to 90,000/µL after 8 wks. enabling corticosteroids withdrawal. Same dose Romiplostim is maintained for the last 30 months with platelet counts of 90,000 - 110,000/µL with no bleeding events. Repeated BMB showed no increase in collagen fibrosis. Patient 2: 63 YO female patient diagnosed with Gaucher at age 33 with a history of purpura, ecchymosis, and occasional vaginal bleeding episodes. At age 53 the platelet count dropped to < 20,000/µL with presence of Anti Platelets Ab (IgG). BMB revealed megakaryocytic hyperplasia with atypical forms, focal infiltration by Gaucher cells and no fibrosis. Combined therapy by ERT (Imiglucerase® followed by Velaglucerase Alfa®), Prednisone (1mg/kg/d for 2 months) and one course of IVIG yielded no increase in platelet count. The patient refused Rituximab®. Romiplostim was initiated increasing platelet count to100,000/µL maintained throughout a year of follow up. Repeated BMB showed slight increase of fibrosis and marked hyperplasia of atypical megakaryocytes. Discussion: Thrombocytopenia is often present in GD and may be severe in approximately 15% of the patients. Persistent cytopenias may be caused by other underlying pathologies such as autoimmune disorders and are important to be recognized and addressed. Before ERT era GD patients with hypersplenism and severe cytopenia were splenectomised. Risks of splenectomy include serious bacterial infection and vascular complications limiting its use in chronic refractory ITP. Splenectomy is avoided in Gaucher patients, due to risk of exacerbating skeletal complications (bone infarcts, avascular necrosis). Stable bone marrow results regarding fibrosis in our patients are consistent with data from a recent 2-year follow-up of 100 ITP patients receiving Romiplostim treatment with no evidence of BM fibrosis. Conclusion: In patients with type I Gaucher disease and concomitant ITP, adjunctive treatment with Romiplostim was successful in maintaining haemostatic platelet counts with no adverse effects. Traditional treatment regimens of corticosteroids and splenectomy should be used with caution or avoided in GD patients due to possible aggravation of Gaucher skeletal disease and the risk of osteopenia and avascular necrosis resulting in increased morbidity in this cohort of patients. Use of TPO-RA should be considered in GD patients with ITP. Disclosures Off Label Use: Romiplostim in gaucher patients.

scholarly journals Increased FVIII and Anti-Phospholipid Antibodies Do Not Modify the Clinical Course of Chronic Immune Thrombocytopenia

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5013-5013
Author(s):  
Meet Kumar ◽  
Maitryee Bhattyacharyya ◽  
Shyamali Datta
Keyword(s):  
Platelet Count ◽  
Lupus Anticoagulant ◽  
Immune Thrombocytopenia ◽  
Clinical Course ◽  
Conflicts Of Interest ◽  
Age Groups ◽  
Platelet Counts ◽  
Bleeding Score ◽  
Chronic Immune Thrombocytopenia

Abstract INTRODUCTION: Immune thrombocytopenia is a heterogenous disease with majority patients having a mild bleeding phenotype and one-fourth being asymptomatic. Bleeding episodes are usually seen in patients with platelet counts typically <30,000/cumm. There is no study till date to identify patients with platelet count <30,000/cumm and at high risk for bleeding. Although patients who harbor anti phospholipid antibodies have a higher risk of arterial and venous thrombosis, it is not known whether presence of acquired thrombophilia modifies the clinical course of bleeding in low platelet count ITP patients. We evaluated the role of FVIII and lupus anticoagulant in modifying the clinical course of such patients. MATERIALS AND METHODS: Patients of all age groups with persistent and chronic immune thrombocytopenia were eligible for study enrolment. Patients with acute ITP and secondary ITP were excluded. Eligible patients were evaluated with baseline parameters, ITP bleeding score (ITP-BAT, version 1.0 by IWG on ITP) at baseline and then at every visit and FVIII and lupus anticoagulant at baseline and repeat at six months.Patients were called for monthly scheduled visits if platelet counts were >30,000/cummand more frequently at lower platelet counts. Patients with any evidence of underlying infection or raised c-reactive protein and procalcitonin were deferred evaluation.All patients were treated as per institutional protocol to avoid treatment bias. Patients were followed up for one year. We finally calculated the average bleeding scores of all patients at different platelet counts (for eg. average of skin, mucosal and organ bleeding scores of all patients that had platelet counts <10,000/cumm, 10-30,000/cumm etc) and analysed it with FVIII and anti-phospholipid antibody levels. RESULTS: A total of 45 patients were enrolled with M:F=1:3.2. Median age of patients is 28years (3-72 years). Two patients were excluded (both progressed to SLE) and another two were lost to follow-up. Median duration from ITP diagnosis to study enrolment was 62.4months (8-590 months). Median follow-up of all patients was 14.2 months (13.2-16.4 months). Nine patients had persistent and 32 patients had chronic ITP. ITP-BAT could differentiate intensity of bleeding at different platelet counts by means of bleeding scores (Table 1). Correlation of bleeding scores with prothrombotic markers could not establish a disease course modifying relationship between the two (Table 2). CONCLUSION: Presence of high FVIII and anti phosphoilipid antibodies donot modify the bleeding risks in patients with ITP and low platelet counts. Table 1Platelet count (x109/cumm)Total episodesAverage bleeding scoreP value<1014S2.4 M1.4 O0 0.00210-3015S1.4 M0.9 O030-6018S0.3 M0.1 O0>600S0 M0 O0 Table 2 Platelet count <10,000/cumm Platelet count 10-30,000/cumm N Av BS P= N Av BS P= FVIII>150 5 S2.5M1.1O0 0.02 6 S1.1M0.8O0 0.1 FVIII<150 9 S2M0.7O0 11 S1.4M0.6O0 LA1:LA2>2 1 S2.2M1.5O0 0.03 S1.1M0.8O0 0.2 LA1:LA2<1 12 S2.6M1.2O0 S1.2M0.6O0 Table 3 Platelet count 30-60,000/cumm Av BS P= FVIII>150 4 S0.9M0.1O0 0.2 FVIII<150 11 S0.3M0.1O0 LA1:LA2>2 Nil LA1:LA2<1 9 S1.1M0.4O0 Disclosures No relevant conflicts of interest to declare.

scholarly journals Long Term Discontinuation of Eltrombopag after Remission in Primary Immune Thrombocytopenia: 8-Year Follow-up Data from 15 Spanish Centers

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2352-2352
Author(s):  
Tomas Jose Gonzalez-Lopez ◽  
Fernando Fernandez-Fuertes ◽  
Maria Cristina Pascual Izquierdo ◽  
Isabel Caparros ◽  
Silvia Bernat ◽  
...  
Keyword(s):  
Platelet Count ◽  
Median Time ◽  
Research Funding ◽  
Immune Thrombocytopenia ◽  
Previous Treatment ◽  
Complete Response ◽  
Platelet Response ◽  
Platelet Counts

Background: Successful discontinuation of eltrombopag in certain immune thrombocytopenia (ITP) patients after complete response has already been demonstrated. However, the frequency of this phenomenon and type of candidate patients are still matter of discussion. Moreover, possibility of long term discontinuation responses is not clearly established. Methods: Here we retrospectively evaluated our whole cohort of 508 adult patients (aged 18 years or more) with primary ITP treated with eltrombopag included in the Spanish Eltrombopag Registry with a focus on the patients who achieved a durable (at least six months) platelet response after stopping eltrombopag. Successful discontinuation of eltrombopag (SDOE) was defined as those patients who reached remission and maintained platelet counts ≥ 50x109/l for at least 6 months in absence of eltrombopag or any rescue therapies administered. Long term discontinuation of eltrombopag (LTDOE) was defined as those patients who reached remission and maintained platelet counts ≥ 50x109/l for at least 36 months in the absence of eltrombopag or any rescue therapies administered. The study was approved by the Hospital Universitario de Burgos Ethics Committee and fulfilled Helsinki declaration standards. Results: While 37.4% of our patients relapsed of ITP with subsequent platelet count drop sometime during first six months of discontinuation of eltrombopag, a total of 74 patients (14.6%) were able to achieve SDOE. The median age of SDOE patients was 62 [range, 47-79] years. There were 47 women and 27 men. According to the standard definition, patients were allocated to newly diagnosed (n=17), persistent (n=15) and chronic (n=42) ITP groups. The median time from diagnosis to eltrombopag initiation was 31 [range, 4-104] months. The median number of previous therapies was 2 [range, 1-2], including splenectomy (14%), rituximab (18%) and romiplostim (12%). As expected, all patients but 1 achieved a complete response (platelet count ≥100 x 109/L) prior to eltrombopag discontinuation The median duration of eltrombopag treatment was 7 [range, 2-19] months. Reasons for eltrombopag discontinuation were: persistent response despite a reduction in dose over time (n=43), platelet count >400x109/L (n=16), aspartate aminotransferase elevation (n=5), diarrhea (n=4), thrombosis (n=3), patient's request (n=2) and other reasons (n=1). Analysis of these SDOE discontinued patients show that with a median follow-up of 55 [range, 29-79] months, 38 patients (51.3%) maintained treatment-free response 36 months after stopping eltrombopag with no need of additional ITP therapies (median time of eltrombopag discontinuation was 70 [range, 50-77] months).This condition is what we define now as LTDOE. Nevertheless, 36 patients relapsed beyond 6 months but before 36 months of eltrombopag discontinuation (median time of eltrombopag discontinuation was 10 [range,7 -22] months). Characteristics of LTDOE population were a median time since ITP diagnosis of 32 [range, 5-88] months with 15/38 patients having ITP <1 year. 9 patients (24%) were male and their median age was 50 [range, 37-64] years. They had received a median of only two previous treatment lines [range: 1-2 lines]. The median platelet count before starting eltrombopag was 19 x 109/L [range, 8-40]. Meanwhile, platelet count before eltrombopag stop was 218 x 109/L [range, 123-356]. The main characteristics (age, gender, duration of ITP, prior ITP lines, platelet count before starting eltrombopag, duration of eltrombopag treatment, and platelet count before eltrombopag withdrawal) of the 38 patients with LTDOE were compared with those of the SDOE cohort who did not achieve a LTDOE. Unfortunately, no predictive factors of LTDOE could be identified. Conclusion: Durable platelet response following eltrombopag cessation may be observed in only 15% of primary ITP patients treated with this drug. On the contrary, half of patients who achieve a sustained response after eltrombopag withdrawal will get a long term discontinuation. However, we are lacking predictor factors for successful and long-term discontinuation of eltrombopag in primary ITP. Disclosures Gonzalez-Lopez: Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau. Pascual Izquierdo:Novartis: Consultancy; Sanofi: Consultancy. Sánchez-González:Amgen: Consultancy, Speakers Bureau; Gilead: Speakers Bureau; Navartis: Consultancy, Speakers Bureau; Shire: Speakers Bureau; Takeda: Consultancy, Speakers Bureau. Jarque:Takeda: Consultancy, Speakers Bureau; Shire: Consultancy, Speakers Bureau; Shionogi: Consultancy, Speakers Bureau; Servier: Speakers Bureau; Roche: Consultancy, Speakers Bureau; Pfizer: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; MSD: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Grifols: Consultancy; Gilead: Consultancy, Speakers Bureau; CellTrion: Consultancy; Celgene: Consultancy, Speakers Bureau; Bristol-Myers Squibb: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Abbie: Consultancy, Speakers Bureau; Alexion: Consultancy, Speakers Bureau.

scholarly journals Hypovitaminosis D Influences the Clinical Presentation of Immune Thrombocytopenia in Children with Newly Diagnosed Disease

2019 ◽  
Vol 8 (11) ◽  
pp. 1861
Author(s):  
Petrovic ◽  
Benzon ◽  
Batinic ◽  
Culic ◽  
Roganovic ◽  
...  
Keyword(s):  
Immune Thrombocytopenia ◽  
Clinical Presentation ◽  
Coastal Region ◽  
Autoimmune Disorder ◽  
Hypovitaminosis D ◽  
Severe Bleeding ◽  
Newly Diagnosed ◽  
Randomized Controlled Studies ◽  
Bleeding Score ◽  
D Values

Immune thrombocytopenia (ITP) is an acquired autoimmune disorder characterized by isolated thrombocytopenia defined as platelet count in peripheral blood <100 × 109/L. Hypovitaminosis D is very common in children with autoimmune diseases. To analyze whether hypovitaminosis D is associated with the clinical presentation of ITP in children, medical records of 45 pediatric patients with newly diagnosed immune thrombocytopenia in the coastal region of Croatia were evaluated. The severity of bleeding was assessed using two bleeding scores. Children with lower 25-hydroxyvitamin D (25(OH)D) values had higher values of the skin-mucosa-organ-gradation (SMOG) bleeding score and respectively more severe bleeding on diagnosis of ITP. With further analysis of the main domains of that score, we found that patients with a lower 25(OH)D value had more severe bleeding in the skin and organs. When 25(OH)D and ITP Bleeding Scale (IBLS) score were analyzed, a negative correlation was found, but it was not significant. Our findings suggest that hypovitaminosis D influences the severity of the clinical presentation of ITP in children on initial diagnosis of the disease. Therefore, therapy with 25(OH)D could be a new potential option for treatment of ITP. To investigate the connection between 25(OH)D and the incidence and severity of ITP, further studies, especially randomized controlled studies, are needed.

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.

Association Of Platelet Function Markers, Independent Of Platelet Count, With Bleeding Score In Patients With Immune Thrombocytopenia

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3534-3534
Author(s):  
Andrew L. Frelinger ◽  
Anja J Gerrits ◽  
Michelle A. Berny-Lang ◽  
Travis Brown ◽  
Sabrina L. Carmichael ◽  
...  
Keyword(s):  
Platelet Count ◽  
Platelet Activation ◽  
Platelet Function ◽  
Research Funding ◽  
Immune Thrombocytopenia ◽  
Univariate Analysis ◽  
Blood Draw ◽  
Platelet Surface ◽  
Platelet Counts ◽  
Bleeding Score

Abstract Background Immune thrombocytopenia (ITP) patients with similarly low platelet counts differ in their tendency to bleed. Aim To determine if differences in platelet function in ITP patients with similarly low platelet counts partly account for the variation in bleeding tendency. Methods The relationship between bleeding scores and platelet function markers was investigated in a single center cross-sectional study of pediatric patients with ITP. Following informed consent, blood was collected from ITP patients and bleeding was graded using the Buchanan and Adix Score (J Pediatr 2002) at routine clinic visits or while admitted to the hospital. Bleeding scores were obtained by one of three hematologists blinded to platelet function results, and investigators performing platelet function tests were blinded to clinical results. Platelet function was assessed by whole blood flow cytometric measurement of unstimulated, ADP- or TRAP-stimulated platelet surface activated GPIIb-IIIa (as measured by PAC1 binding), P-selectin, and GPIb and by unstimulated, convulxin-, or ADP plus TRAP-stimulated platelet surface phosphatidylserine expression (as determined by annexin V binding). Platelet count, immature platelet fraction (IPF) and mean platelet volume (MPV) were determined by a Sysmex XE-2100, and platelet forward angle light scatter (FSC) was measured by flow cytometry. Results Platelet function and bleeding scores were evaluated in 34 consecutive consenting pediatric ITP patients (16 female, 18 male, age 9.7 ± 5.7 years [mean ± SD]). ITP was newly diagnosed (< 3 months) in 10 patients, persistent (3 -- 12 months) in 7 patients, and chronic (>12 months) in 17 patients. Platelet count at the time of the blood draw was 47 ± 55 x 109/L. The median bleeding score on day of blood draw was 1 (range 0 to 4). By univariate analysis, higher IPF, and lower platelet count were significantly associated with a higher bleeding score (odds ratio [OR] >1, p<0.05) but MPV was not. Multiple measures of platelet function were associated with bleeding scores by univariate analysis: higher levels of platelet FSC (a measure affected by multiple variables including size) surface GPIb on unstimulated, ADP- or TRAP-stimulated platelets, surface P-selectin on unstimulated platelets, and platelet FSC were associated with increased odds for higher bleeding scores (ORs each >1, p<0.05), while higher ADP- and TRAP-stimulated platelet surface activated GPIIb-IIIa and P-selectin were associated with reduced odds of higher bleeding scores (ORs each <1, p<0.05). After adjustment for platelet count, higher levels of platelet surface P-selectin on unstimulated platelets, GPIb on TRAP-stimulated platelets, and FSC remained significantly associated with increased odds for higher bleeding scores (Figure), but IPF did not. Similarly, after adjustment for platelet count, higher TRAP-stimulated percentage of P-selectin and activated GPIIb-IIIa positive platelets remained significantly associated with reduced odds of higher bleeding scores (Figure). These findings were independent of recent ITP-related treatment. Conclusions In this study of pediatric ITP patients, we identified selected platelet function markers which, independent of platelet count, are associated with increased (platelet FSC, platelet surface P-selectin on unstimulated platelets, and GPIb on TRAP-stimulated platelets) or decreased (TRAP-stimulated percent P-selectin and GPIIb-IIIa positive platelets) odds of high bleeding scores. Possible hypotheses to explain these associations are as follows: 1) Increased P-selectin on unstimulated platelets demonstrates in vivo platelet activation, possibly as a consequence of the recent bleeding. 2) Because platelet activation results in a reduction in platelet surface GPIb and increases in platelet surface activated GPIIb-IIIa and P-selectin, the ORs associated with all of these markers could be explained by reduced ability of platelets in patients with higher bleeding scores to respond to agonists. 3) While platelet FSC is partly related to size, the finding that MPV and IPF, adjusted for platelet count, were not associated with bleeding score suggests that factors other than size account for the association of platelet FSC with higher bleeding scores. Further study is required to validate these findings and determine if differences in platelet function are associated with future risk for bleeding. Disclosures: Off Label Use: Eltrombopag was given to WAS/XLT patients for treatment of thrombocytopenia. Neufeld:Shire: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Apopharma: Consultancy. Michelson:Sysmex: Honoraria.

Effect of Pregnancy in Women with a History of Primary Immune Thrombocytopenia Considered As Cured

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2552-2552
Author(s):  
Thibault Comont ◽  
Guillaume Moulis ◽  
Karen Delavigne ◽  
Pierre Cougoul ◽  
Olivier Parant ◽  
...  
Keyword(s):  
Platelet Count ◽  
Complete Remission ◽  
Epidural Analgesia ◽  
Pregnant Women ◽  
Immune Thrombocytopenia ◽  
Specific Treatment ◽  
Severe Bleeding ◽  
Adult Women ◽  
History Of ◽  
The Impact

Abstract Immune thrombocytopenia (ITP) is an autoimmune disease that occurs in young women. Pregnancy is a well-known risk factor for developing newly diagnosed ITP as well as for inducing disease flares in patients with current ITP. However, the impact of pregnancy in women with an old history of ITP, considered as cured, has not been assessed. The aim of this study was to describe the course of ITP in pregnant women with an ITP in complete remission (platelets count >100x109/L and absence of bleeding symptoms) for at least 5 years without any ITP treatment. We retrospectively selected all pregnant women with delivery at Toulouse University Hospital, South of France, between 2010 and 2015 with a hospital discharge code of ITP (international classification of diseases; version 10 code D69.3). This code has a sensitivity of 81.2% and a positive predictive value of 89.8% in this database. All medical charts were reviewed to confirm the diagnosis of ITP. We included adult women (≥18 years) with a diagnosis of primary ITP according to French guidelines (platelet count <150 x 109 /L and exclusion of other causes of thrombocytopenia, especially other causes of thrombocytopenia during pregnancy) in complete remission for at least 5 years. We identified 50 pregnancies in 39 ITP patients during the study period. Eleven pregnancies occurred in 10 patients in long-term complete remission of ITP at the time of pregnancy onset. Baseline characteristics were: median age at ITP diagnosis: 21 years (range: 4-29); median age at pregnancy onset:32 years (range: 26-34; history of ITP during a previous pregnancy: 1; history of bleeding: 4 (36.4%); previous treatment for ITP: 8 (72.7%), corticosteroids-CS (5), CS and intravenously immunoglobulin-IVIg (3), splenectomy (4), dapsone (1); last median platelet count before pregnancy: 170x109/L (range: 118-363). Platelets count decreased below 100x109/L in 3 pregnancies (27.2%) from the first trimester for one patient, from the second trimester for one other and from the third trimester for the last one, with a nadir of 3, 39 and 87 (x109/L) respectively. One of them experienced a severe bleeding (grade 3 according to the International Working Group bleeding classification). All thrombocytopenic patients required treatment during pregnancy: CS+IVIg for 2 (one for bleeding and one to allow epidural analgesia) and IVIg for the other (to allow epidural analgesia). For these 3 women, the median platelet count at delivery was 128 (range: 38-159) and consequently only 2 of them could have epidural analgesia. No bleeding during delivery was observed. Transient thrombocytopenia occurred in 2 newborns. Primary ITP considered as cured may relapse during pregnancy and may induce severe bleeding requiring specific treatment. A tight monitoring should be proposed to all pregnant women with a history of primary ITP, even after several years of complete remission. Disclosures Récher: Celgene, Sunesis, Amgen, Novartis, Chugai: Membership on an entity's Board of Directors or advisory committees, Research Funding.

scholarly journals Poor Platelet Function on Sonoclot Signature Is Associated with High Incidence of Bleeding in Severe Immune Thrombocytopenia

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4991-4991 ◽  
Author(s):  
Kundan Mishra ◽  
Aditya Jandial ◽  
Rajeev Sandal ◽  
Pradakshna Porchezhian ◽  
Samson Charan ◽  
...  
Keyword(s):  
Platelet Count ◽  
Platelet Function ◽  
Immune Thrombocytopenia ◽  
Blood Samples ◽  
Risk Of Bleeding ◽  
Normal Platelet ◽  
Function Analyzer ◽  
Clinically Significant ◽  
Platelet Function Analyzer

Abstract Introduction: Patients of immune thrombocytopenia (ITP) are at an high risk of bleeding, and the risk of bleeding is maximum when platelet counts fall below 30,000/μL (severe ITP). Though it is not known not all patients have a similar risk of bleeding at a given platelet count. In 59th ASH annual meeting, 2017 (poster 2320) Mishra K et al showed that the platelet function measured by 'Sonoclot coagulation and platelet function analyzer' is significantly different in bleeders as compared to non-bleeders severe ITP patients. We aimed to investigate and follow up the non-bleeder severe ITP patients, whose platelet count remains <30,000 with or without treatment, and find out the incidence of bleed. Method: The study was conducted at the department of internal medicine, postgraduate institute of medical education and research, Chandigarh, India. In this prospective observational study, severe ITP (newly diagnosed) and without active bleeding (WHO bleeding grade <2) were included. All these patient were clinically evaluated, and blood samples were collected as per unit protocol for ITP including Sonoclot analysis. For Sonoclot analysis, fresh blood samples were drawn in citrated vacutainer and analyzed by Sonoclot coagulation and platelet function analyzer made by Sienco, Inc, model SCP1 (USA). The sonoclot signature assessment gives activated clotting time (ACT), clot rate (R1) and platelet function (PF). The samples for sonoclot analysis were monthly drawn for six months in patients who continued to have severe ITP. Results: A total of 50 patients with severe ITP were included. Twenty patients were not included in the final analysis as their platelet remained above 30,000/μL during follow up. The remaining 30 patients were divided into two groups based on normal platelet function (PF) (>1.5) and low PF (<1.5) as measured by the Sonoclot analyzer. The normal PF group (n= 17) had only one patient who had clinically significant bleeding (WHO grade > 2), while low PF group had four patients with clinically significant bleeding (Figure 1). Though the statistical significance level could not be achieved, likely due to a small cohort of patients, the results look promising and shows the potential of sonoclot to give valuable input regarding the risk of bleeding in severe ITP. Conclusion: The patients with poor platelet function as measured by 'Sonoclot coagulation and platelet function analyzer' had more bleeding episodes as compared to patients with normal platelet function. Therefore, Sonoclot may work as a point of care investigation to predict the risk of bleeding in severe ITP patients. This will help the clinician in being more conservative in the management of severe ITP patients with low risk of bleeding and avoid unnecessary therapy. We conclude that the use of Sonoclot during follow-up in severe ITP patients has prognostic significance. Disclosures No relevant conflicts of interest to declare.

scholarly journals Treatment of adult chronic autoimmune thrombocytopenic purpura with repeated high-dose intravenous immunoglobulin

Blood ◽  
1993 ◽  
Vol 82 (5) ◽  
pp. 1415-1421 ◽  
Author(s):  
B Godeau ◽  
S Lesage ◽  
M Divine ◽  
V Wirquin ◽  
JP Farcet ◽  
...  
Keyword(s):  
Body Weight ◽  
Platelet Count ◽  
Treatment Protocol ◽  
Complete Response ◽  
Long Term Results ◽  
High Dose ◽  
Thrombocytopenic Purpura ◽  
Autoimmune Thrombocytopenic Purpura ◽  
Platelet Counts

Intravenous (i.v.) infusions of Ig concentrates are an effective but expensive treatment for patients with autoimmune thrombocytopenic purpura (AITP). The optimal treatment protocol and the long-term results are uncertain, and the precise mechanism by which the platelet count increases is poorly understood. Twenty adult patients with chronic AITP were enrolled in a prospective study to compare the respective efficacy of two high-dose IVIgG induction regimens (1 g v 2 g/kg body weight) and the long-term effect of six 1 g/kg body weight i.v. IgG reinfusions. An initial response was observed in all 18 evaluable patients: the platelet count increased to a mean value of 251 x 10(9)/L (range 72 to 836 x 10(9)/L) and the mean pretreatment platelet count was multiplied by 14.6. No difference in efficiency was observed between the two i.v. IgG dosages. The degree of the platelet count increment correlated in both groups with the increase in the clearance of antibody-coated red blood cells, measured by an isotopic method, but not with the serum IgG elevation. Treatment was considered to have failed in 11 patients, 90 days after the last i.v. IgG reinfusion (D90), because the platelet counts were comparable with pretreatment values. In contrast, a complete response was observed at D90 in five patients (mean platelet count: 184 x 10(9)/L; range: 150 to 250 x 10(9)/L) and a partial response at D90 was obtained in the remaining two patients (platelet counts: 70 and 104 x 10(9)/L). Five of the 7 responders at D90 kept a platelet count above 50 x 10(9)/L during the entire follow-up period (mean 33 months; range: 5 to 66) with no further treatment; unfortunately, no clinical or biologic criteria were found to be predictive of the long-term response. This study shows that an i.v. IgG infusion regimen of 1 g/kg body weight could safely replace the classical 2 g/kg body weight dosage, at least in patients who do not have life-threatening thrombocytopenia. Moreover, repeated i.v. IgG reinfusion could be an alternative for AITP patients in whom splenectomy is contraindicated.

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