scholarly journals Incidence of Silent Thrombosis in Myeloproliferative Neoplasm Patients below 60 Years : Single Center Egyptian Study

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5476-5476
Author(s):  
Mervat Mattar ◽  
Sahar Nassef ◽  
Noha M El Husseiny ◽  
Mohamed Abdel Kader Morad ◽  
Marwa Salah ◽  
...  
Keyword(s):  
Venous Thrombosis ◽  
Conflicts Of Interest ◽  
Color Doppler ◽  
Myeloproliferative Neoplasm ◽  
Myeloproliferative Disorders ◽  
Color Doppler Ultrasound ◽  
Lower Limbs ◽  
P Value ◽  
Allele Burden ◽  
Venae Cavae

Abstract Background : Identification of JAK-2 mutation even in absence of myeloproliferative disorders was found to be related to venous thromboembolism occurrence. The aim of this work is to screen myeloproliferative neoplasm ( MPN) patients for venous thrombosis and study its correlation with both JAK 2 allele burden and with symptoms the patients presented with. Methods: We enrolled 73 cases with JAK2 positive MPN in the period between August 2015 till Feb 2017. All patients were screened for thrombosis in venous system in neck, upper and lower limbs, superior and inferior Venae Cavae and portal and mesenteric venous systems system using color Doppler Ultrasound. Results: 53 patients (72.6%) were below 60 years. Forty even (64.4%) were females and 26(35%) were males. Twenty two (30%) of cases were Essential Thrombocytosis (ET), 35(248%) were Polycythemia Vera (PV) and 16 (22%) were Myelofibrosis (MF). Twenty seven venous thrombotic attacks were reported in twenty two patients (30.1%). Seventeen patients (23%) had mesenteric and portal vein thrombosis,six patients had iliofemoral (8%) and 4 (5%) had combined lower limb and portal thrombosis. Eight patients (10.8%) had active thrombosis at screening. Only three (4%) patient were symptomatising with pain during screening. Sixteen patients with thrombosis were below 60 (30% of those below 60 years) and 6 were above sixty years (also 30% of those above sixty years). Correlation analysis between JAK2 allele burden and thrombosis was not statistically significant (r=0.3 ,p value=0.5). However, JAK 2 allele burden was statistically higher in those above sixty years in both thrombosed and non-thrombosed cases in comparison to those below sixty years (p= 0.03, 0.017 respectively). The incidence of pruritis (p =0.02) and of abdominal pain (p=0.039) was significantly different between thrombosed and non-thrombosed cases. Comparison of 8 cases with active thrombosis to old thrombosis revealed no statistical difference in the MPN10 score (p>0.05). Conclusion: We recommend routine screen for venous thrombosis in any case of MPNs once diagnosed and screening for MPNs in any case with venous thrombosis . Further research in MPN group age below 60 years of age is highly recommended. Disclosures No relevant conflicts of interest to declare.

scholarly journals Prenatal Sonographic Image of Sirenomelia with Anencephaly and Craniorachischisis Totalis

2018 ◽  
Vol 2018 ◽  
pp. 1-5
Author(s):  
Takako Sugiura ◽  
Yuka Sato ◽  
Naoyuki Nakanami ◽  
Kiyomi Tsukimori
Keyword(s):  
Ultrasound Examination ◽  
Color Doppler ◽  
Three Dimensional ◽  
Final Diagnosis ◽  
Color Doppler Ultrasound ◽  
Lower Limbs ◽  
Ultrasound Images ◽  
Two Dimensional ◽  
Prenatal Counselling ◽  
Medical Termination

Sirenomelia is a rare congenital malformation characterized by varying degrees of fusion of the lower extremities. It is commonly associated with severe urogenital and gastrointestinal malformations; however, the association of sirenomelia with anencephaly and rachischisis totalis is extremely rare. To our knowledge, the prenatal sonographic images of this association have not been previously published. Here, we present prenatal sonographic images of this association, detected during the 17th week of gestation through combined two-dimensional, four-dimensional, and color Doppler ultrasound. Two-dimensional ultrasound images showed anencephaly, spina bifida, and possible fusion of the lower limbs. Three-dimensional HDlive rendering images confirmed the final diagnosis of sirenomelia with anencephaly and rachischisis totalis. The patient opted to undergo medical termination of pregnancy and delivered a fetus with fused lower limbs, anencephaly, and rachischisis totalis confirming the in utero imaging findings. Awareness of these rare associations will help avoid misdiagnoses and facilitate prenatal counselling. This case highlights the importance of a thorough ultrasound examination.

Metabolic and Inflamatory Proteins Differently Expressed in Platelets From Deep Venous Thrombosis Patients

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5256-5256
Author(s):  
Mariane Cristina Flores Nascimento ◽  
Karina Kleinfelder-Fontanesi ◽  
Fernanda Loureiro de Andrade Orsi ◽  
Steven H Seeholzer ◽  
Harry Ischiropoulos ◽  
...  
Keyword(s):  
Venous Thrombosis ◽  
Deep Venous Thrombosis ◽  
Conflicts Of Interest ◽  
Lower Limbs ◽  
Apolipoprotein A1 ◽  
Blood Samples ◽  
Orbitrap Mass Spectrometer ◽  
Inflammatory Processes ◽  
History Of

Abstract Abstract 5256 BACKGROUND: Deep venous thrombosis (DVT) is multi-causal disease associated to a high morbi-mortality due to complications as pulmonary embolism and post-flebitic syndrome. The incidence is about 20 to 30%, and 25% of the patients will present recurrence in 5 years. The identification of new risk factors is important in clinical practice to prevent new thrombotic events. The role of the platelets on DVT is still not well defined. AIM: The objective of this study was to analyze the hole proteins profile of platelets obtained from DVT patients and compare to the same matherial derived from healthy controls. PATIENTS: peripheral blood samples were collected from 3 spontaneous DVT patients and from 1 sibling and 1 neighbor for each patient in order to minimize the genetic and environmental interferences. These patients presented spontaneous and recurrent episodes of lower limbs proximal DVT and all of them mentioned a familiar history of coagulation disorders. METHODS: the platelets were washed, lysed, and the proteins were alkylated, reduced, precipitated with acetone and hydrolyzed by trypsin. 100mg of peptides were then separated by hydrophobicity using HPLC, and 8 fractions were obtained and directed to the LTQ-Orbitrap mass spectrometer. The proteins search was performed by Sorcerer-SEQUEST. RESULTS: We identified 5 proteins that were present on patients and absent in all the controls: Apolipoprotein A1 Binding-Protein, Coatomer (z1 sub-unit), Estradiol 11–17-b Dehydrogenase, Leucotriene A-4 Hydrolase and Sorbitol Dehydrogenase. Western-Blotting was performed with specific antibodies and validated the results. CONCLUSIONS: with this study it was possible to identify proteins up to date non-related to the physiopathology of DVT, that could be involved with metabolic and inflammatory processes. Disclosures: No relevant conflicts of interest to declare.

Causes of recurrent lower limb varicose veins after surgical interventions in 141 limbs – Five-year retrospective analysis of two centers

Vascular ◽  
2013 ◽  
Vol 22 (4) ◽  
pp. 267-273 ◽  
Author(s):  
Wang Rui Hua ◽  
Meng Qing Yi ◽  
Wu Xue Jun ◽  
Jin Xing ◽  
Liu Zhao Xuan ◽  
...  
Keyword(s):  
Lower Limb ◽  
Varicose Veins ◽  
Color Doppler ◽  
Color Doppler Ultrasound ◽  
Lower Limbs ◽  
Venous Reflux ◽  
Surgical Interventions ◽  
Venous Valves ◽  
Second Surgery ◽  
Clinical Changes

Aim The purpose of this study was to explore the causes of recurrent lower limb varicose veins after surgical interventions. Methods A retrospective five-year survey was conducted on patients who underwent second surgery due to recurrent lower limb varicose veins after surgical interventions. A total of 141 limbs (112 cases), including 72 cases of left lower limbs, 47 of right lower limbs and 22 of both limbs, were involved in the study. All patients underwent lower limb venography (141 limbs were anterograde and 28 cases were retrograde), and then examined with color-Doppler ultrasound. Results The major causes that urged patients to undergo second surgery are clinical changes graded above CEAP IV (93.6%), limb edema without changes on skin (5%), and single varicosity (1.4%). Up to 127 (83%) limbs exhibited perforating venous reflux, 67 (47.5%) limbs had varied degrees of deep venous insufficiency and 68 (48.2%) limbs had through or above-the-knee great saphenous vein trunk residual. Conclusions Preoperative venography before operation is indispensible in confirming the diagnosis and operation strategies. Patients with severe primary deep venous reflux and symptoms up to C3 may need simultaneous repair of the deep venous valves.

scholarly journals The Effect of Continuous Positive Airway Pressure on Total Cerebral Blood Flow in 23 Healthy Awake Volunteers

2011 ◽  
Author(s):  
Theresia I. Yiallourou ◽  
Céline Odier ◽  
Bryn A. Martin ◽  
José Haba-Rubio ◽  
Raphael Heinzer ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Continuous Positive Airway Pressure ◽  
Airway Pressure ◽  
Positive Airway Pressure ◽  
Color Doppler ◽  
Cerebral Arteries ◽  
Color Doppler Ultrasound ◽  
P Value ◽  
Pharyngeal Airway

Continuous Positive Airway Pressure (CPAP) is used as the gold standard treatment for sleep disordered breathing, acting as a pneumatic splint to prevent collapse of the pharyngeal airway. However, the influence that CPAP has on Cerebral Blood Flow (CBF) dynamics is not well understood. This preliminary study investigates the influence of CPAP on total CBF in 23 healthy awake subjects by measuring flow velocity and lumen diameter of the left and right proximal Internal Carotid Arteries (ICA), Vertebral Arteries (VA), and Middle Cerebral Arteries (MCA) using Duplex Color Doppler Ultrasound (US) with and without CPAP at a level of 15 cm H2O. Transcutaneous Carbon Dioxide (PtcCO2) level, heart rate, Blood Pressure (BP), and oxygen saturation (SaO2) were monitored before and after each test. The preliminary measurements indicate that CPAP results in a decrease of CBF by 17% (p-value < 0.05). The theoretically predicted decrease in CBF from PtcCO2 variation was 6%. The study should be further explored in patients with sleep apnea and various types of cerebrovascular and craniospinal disorders.

Rivaroxaban versus Warfarin in the Management of Deep Venous Thrombosis

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Mahmoud Shawky El-metieni ◽  
Tamer Mohamed Fekry ◽  
Mohammed Ahmed Hassan Rady ◽  
Ahmed Magdy Farrag ◽  
Ahmed Mohamed Ismail
Keyword(s):  
Venous Thrombosis ◽  
Deep Venous Thrombosis ◽  
Randomized Study ◽  
Duplex Ultrasound ◽  
Lower Limbs ◽  
P Value ◽  
Vein Thrombosis ◽  
Warfarin Group ◽  
Blood Clots ◽  
Study Population

Abstract Background Deep venous thrombosis (DVT) refers to the formation of one or more blood clots in one of the body’s large veins, most commonly in the lower limbs. The clot can cause partial or complete blocking of circulation in the vein, which in some patients leads to pain, swelling, tenderness, discolouration of the skin that is warm to touch. Aim of the Work Compare the effect of direct Oral Anticoagulant (Rivaroxaban) versus Antivitamin K (warfarin) in treatment of lower limb Deep Venous Thrombosis. Patients and Methods Type of study: prospective single blinded randomized study, study setting: was conducted at Kobri Elkobba hospitals, study period: 6 months, study population: Eligible all patients above 18 years had femoropopliteal vein thrombosis, confirmed with duplex ultrasound scanning and D-dimer test and qualified under the inclusion and exclusion criteria of the study. Results Our study shows that Rivaroxaban alone is as effective as standard therapy, with similar safety, for the treatment of acute DVT and in preventing recurrence and has low risk of bleeding. There was statistically significant increase in INR monitoring during 6 months in warfarin group than Rivaroxaban group with p-value &lt; 0.001. This because warfarin has many drug and food interaction. There's no response in treatment out come after 3 months duplex as the study was on patient of femoro popliteal DVT, however there were clinical improvement in both groups. Complete recanalization with normal augmentation by muscle compression occurred in all Rivaroxaban patients compared to 5% were partially compressible with incomplete recanalization in warfarin group after 6 months of treatment. Conclusion We concluded in patients with unprovoked VTE, rivaroxaban has the potential to reduce both the risk of major bleeding and recurrent VTE compared to warfarin. And there’s no need for adjusting the dose and INR monitoring, and Rivaroxaban has no food nor drug interactions.

Sub-Clinical Activation of Thrombosis May Predict Survival in Cancer Patients

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5075-5075
Author(s):  
Anupam Batra ◽  
Syed A. Mehdi ◽  
Frank Brodzik ◽  
Donald Pasquale
Keyword(s):  
Venous Thrombosis ◽  
Cancer Patients ◽  
Cell Activation ◽  
Conflicts Of Interest ◽  
Threshold Value ◽  
Coagulation System ◽  
P Value ◽  
Increased Risk ◽  
Cancer Outcome ◽  
Sensitivity Specificity

Abstract Background: Approximately 10% of newly diagnosed cancer patients will develop thromboembolic disease (TED) in the first year following diagnosis. We hypothesize that a subgroup of cancer patients at diagnosis will have subclinical changes in their coagulation system that will indicate increased risk for subsequent TED and/or predict increased adverse cancer outcome. Methods: We performed a prospective, non-interventional study of recently diagnosed cancer patients who were scheduled to start chemotherapy. We obtained a single plasma sample at the time of diagnosis and prior to therapy, and measured prothrombin 1.2 fragment (F1.2), a measure of thrombin activation, and plasma microparticle levels (MP), a measure of platelet, endothelial, and other cell activation. We reviewed subsequent clinical outcomes including survival and incidence of venous thrombosis. We accrued 22 patients with mean age 63 years (range 39 to 89; 20 males, 2 females), 12 with lung, 6 with colorectal, and 4 with head and neck cancer. Mean follow-up was 24 months (range 3 to 57). Plasma F1.2 and MP were assayed using commercially available ELISA kits. Results: T1.2 concentrations were significantly higher in the deceased subgroup (table 1; p<0.002), and in patients with venous thrombosis (table 2; p<0.05). MPs were not informative. Sensitivity and specificity for prediction of survival and venous thrombosis (table 3) were determined by comparing patients in highest quartile of levels with lower quartiles combined and by using threshold value of mean +2.5 SD’s determined by measuring levels in 8 healthy controls. Table 1. Survival: F1.2 and MP (Mann-Whitney) Deceased Patients (N=7) Alive Patients (N=15) Mean +/- SD Median Mean +/- SD Median p-value F1.2 (pM) 436+/-214 355 121+/-117 105 <0.002 MP (nM) 10+/-10 3 8.8+/-2.8 2.8 Not Significant Table 2. Venous Thrombosis: F1.2 and MP (Mann-Whitney) Thrombosis (N=4) No Thrombosis (N=18) Mean +/- SD Median Mean +/- SD Median p-value F1.2 (pM) 368+/-267 313 189+/-191 163 <0.05 MP (nM) 5.9+/-5.3 3.9 9.8+/-15.6 2.7 Not Significant Table 3. Sensitivity/Specificity Analysis >mean + 2.5 SD’s Highest Quartile MP T1.2 MP T1.2 Death SENSITIVITY 43% 43% 43% 71% Death SPECIFICITY 87% 100% 87% 93% Thrombosis SENSITIVITY 25% 25% 25% 50% Thrombosis SPECIFICITY 78% 89% 78% 78% Conclusion: T1.2 levels measured at time of diagnosis of cancer correlated with increased mortality and development of venous thrombosis. MP levels were not informative, possibly due to the limited size of the study population. Additional studies are needed to elucidate whether these biomarkers may be useful in identifying a higher risk population for death and/or venous thrombosis, and to help guide enhanced therapy for such higher risk patients. Disclosures No relevant conflicts of interest to declare.

Interclonal and Intraclonal Heterogeneity in Patients with Early Myelodysplastic Syndrome (MDS)

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1670-1670
Author(s):  
Maya Thangavelu ◽  
Wanlong Ma ◽  
Steven Brodie ◽  
Christopher Mixon ◽  
Wayne Chen ◽  
...  
Keyword(s):  
Allele Frequency ◽  
Mutant Allele ◽  
Conflicts Of Interest ◽  
Myeloproliferative Neoplasm ◽  
Refractory Anemia ◽  
Early Event ◽  
Trisomy 8 ◽  
Cytogenetic Abnormalities ◽  
Allele Burden ◽  
Mutant Allele Frequency

Abstract Introduction: Recent data suggest that MDS evolves by accumulating mutations. Early mutations may involve genes that require additional mutations prior to clinical manifestation as MDS. We explored if mutant allele burden and the relative mutation of one gene to another gene could provide information on the interclonal and intraclonal progression of MDS using next generation sequencing (NGS) in patients with early MDS. Methods: NGS data was generated from 96 patients diagnosed with MDS with marrow blast count <5% using a targeted sequencing covering mutations in the following genes: TET2, SF3B1, ASXL1, DNMT3A, SRSF2, RUNX1, NRAS, ZRSR2, EZH2, ETV6, TP53, CBL, NPM1, JAK2, U2AF1, IDH1, KRAS, IDH2, FLT3, PTPN11, SETBP1, and BCOR. The average depth of sequencing was 10,000X. Differences in mutant allele frequency between two genes in the same sample were considered significant if they were >10%. A difference of 10% to 20% was considered mild, 20%-30% moderate, and >30% severe. A heat map reflecting these differences in mutant allele frequency was generated. Results: In this group of early MDS patients, 63 patients (66%) had more than one gene mutated and 38 (40%) had a significant (>10%) difference in allele frequency. The median number of genes mutated was 2 (range 1 to 5). Difference in mutant allele frequency was severe in 15 patients (16%), intermediate in 15 patients (16%), and mild in 13 patients (14%). TET2 was the most commonly mutated gene (43 patients, 45%) and was rarely the sole mutation with most cases exhibiting a mutation in a second gene (39 patients, 91%). The mutant allele burden was highest in TET2 in 26 of these 39 patients (67%), reflecting early event in the tumorigenic process. Of the 13 cases with TET2 mutation and allele burden less than the companion gene, 6 had a mutation in SF3B1, 3 had significant cytogenetic abnormalities (monosomy 5, del(7q), and trisomy 8), 2 had a mutation in SRSF2, 1 had a mutation in ZRSR2 and 1 had a mutation in ASXL1, which suggests that these abnormalities might be the initiating event. A second TET mutation (biallelic mutation) was detected in 16 of the 39 patients. SF3B1 was the most common gene having a solitary mutation (10% of all patients), although mutation in SF3B1 was detected in 27 patients (26% of all patients). All solitary SF3B1 mutations were associated with normal karyotypes, except for one patient with del(11q). JAK2 was mutated with SF3B1 in two cases diagnosed as RARS-T (refractory anemia with ring sideroblasts and thrombocytosis). In one case, the JAK2 and SF3B1 mutation allele frequencies were similar, but in the other, the JAK2 mutant allele frequency was 23% higher, suggesting that a myeloproliferative neoplasm was the initiating process. ASXL1 was mutated in 14 cases, 13 of which had additional mutations. DNMT3A gene was mutated in 18 cases, 5 of which were solitary; two of these five showed cytogenetic abnormalities. TP53 was mutated in 13 cases, but except for one case, all had either mutation in another gene or a cytogenetic abnormality. Conclusion: These data suggest that in patients with clinically confirmed early MDS, TET2 mutations are most likely the initiating oncogenic event, but mutations in other genes or cytogenetic abnormalities most likely lead to clinically confirmed MDS. In contrast, patients with SF3B1 mutation can have clinical disease without additional mutations. Our data suggest that SRSF2, ZRSR2, and ASXL1 may initiate mutagenesis in patients with MDS. Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals Ruxolitinib for the Treatment of Polycythemia Vera: Response on Alternative Dose Versus Standard Dose

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 28-28
Author(s):  
Emma Cacciola ◽  
Veronica Vecchio ◽  
Elio Gentilini Cacciola ◽  
Rossella Rosaria Cacciola
Keyword(s):  
Polycythemia Vera ◽  
Conflicts Of Interest ◽  
Standard Dose ◽  
Myeloproliferative Neoplasm ◽  
Symptom Burden ◽  
Janus Kinase ◽  
Inadequate Response ◽  
Allele Burden ◽  
Night Sweats ◽  
Jak2v617f Allele Burden

The polycythemia vera (PV) is a chronic myeloproliferative neoplasm characterized by increased hematocrit (HCT), elevated white-cell and platelet counts and splenomegaly. The most commonly used first line cytoreductive agent is hydroxyurea (HU). However, some patients have an inadequate response or have inacceptable side effects from HU. Ruxolitinib, a Janus kinase (JAK) 1 and 2 inhibitor, was shown to have a clinical benefit in patients with PV. A phase 3 study (RESPONSE) have shown that PV patients on Ruxolitinib at dose of 10 mg twice daily at week 32 had a complete hematologic remission. In this study were enrolled 40 patients with PV (30 men, 10 women; mean age 54 years, range 51-57) according to WHO criteria, assigned to Ruxolitinib at dose of 5 mg twice daily for clinical evidence of liver dysfunction. All patients were evaluated for JAK2V617F allele burden, HCT, white cells and platelets, splenomegaly and symptom burden, including pruritus, fatigue and night sweats. The mean duration of disease was 9 years. All patients received low-dose aspirin and underwent phlebotomy. Before Ruxolitinib, all patients had JAK2V617F allele burden &gt; 50%, HCT control on phlebotomy, high white cells (12x109/L) and elevated platelets (600x109/L) and spleen volume of 450 cm3 or more as measured by magnetic resonance imaging (MRI) or computed tomography (CT). After Ruxolitinib we observed a shortened response time at week 6 marked by JAK2V617F allele burden &lt; 50%, HCT &lt; 45% in the absence of phlebotomy, normal white cells and platelets (6x109/L and 320x109/L, respectively) and reduced spleen size as assessed by palpation and absence of symptoms. These data suggest that the Ruxolitinib treatment at the alternative dose of 5 mg twice daily can be effective in achieving a rapid and complete hematologic remission that is still present in these patients receiving this dose of Ruxolitinib at the time of this analysis. Disclosures No relevant conflicts of interest to declare.

Procoagulant Platelet-Derived Microparticles Are Lower in Calreticulin-Than in-JAK2-Mutated Essential Thrombocythemia

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 110-110 ◽  
Author(s):  
Agnes Charpentier ◽  
Nathalie Cambier ◽  
Anne Bauters ◽  
Nathalie Trillot ◽  
Matthieu Wemeau ◽  
...  
Keyword(s):  
Essential Thrombocythemia ◽  
Lower Risk ◽  
Conflicts Of Interest ◽  
Myeloproliferative Neoplasm ◽  
Jak2 V617f ◽  
Procoagulant Activity ◽  
P Value ◽  
Thrombotic Risk ◽  
Testing Procedures ◽  
Increased Risk

Abstract Rationale: Essential Thrombocythemia (ET) is a Philadelphia-negative myeloproliferative neoplasm characterized by an increased risk of thrombosis. Previous reports suggest a role for microparticles (MP) in the pathogenesis of thrombosis in ET. MPs are small plasma membrane vesicles bearing potent procoagulant proteins and phospholipids. They are released into the circulation by various blood and endothelial cells after cellular activation and/or apoptosis. The recently described somatic calreticulin (CALR) exon 9 mutations in almost 20% of ET defines a lower-risk thrombosis ET subtype. We extensively studied phenotype and procoagulant activity of plasma MPs in order to assess MP contribution to the thrombotic risk in CALR versus JAK2 (V617F) mutated ET patients. Patients and methods: We analyzed MP count, phenotype and procoagulant activity in 45 JAK2 V617F+ and 15 CALR+ consecutive and newly diagnosed ET patients in accordance to WHO criteria recruited between november 2010 and april 2013. After given informed consent, blood samples were obtained in all patients before initiating any cytoreductive therapy. Pre-analytical and testing procedures complied with the recommendations of the ISTH Standardization Sub-Committee and each test was performed in duplicate . Using flow cytometry (FC500 flow-cytometer, Beckman-Coulter™), MPs were characterized and measured in platelet-free plasma samples. MPs were characterized by their size and co-expression of bound Annexin V and the following cell-specific monoclonal antibodies: CD41 (Platelet-MP, PMP), CD235a (Red cell-MP, RMP), CD14 (Monocytes-MP, MoMP), CD11b (Granulocytes-MP, GMP), CD144 (Endothelial-MP, EMP), CD62P and CD41 (P-Selectin+ PMP), CD142 and CD41 (Tissue Factor (TF)+ PMP, TF+PMP). MP-associated procoagulant activity was also measured using a-thrombin generation assay (Zymuphen™ MP-activity). Statistical analysis was performed with SPSS software. Results are expressed as median [interquartile range]. Results: Patients characteristics: The platelet count (109/L) was higher in CALR+ than in JAK2+ patients (866 [666 – 918], 659 [571 – 807] respectively, p= 0.049), and all other clinical and hematological characteristics were also distributed in agreement with previous reports. Furthermore, CALR+ patients were preferentially distributed in the lower risk categories of the IPSET-thrombosis and IPSET-survival scores than in JAK2+ patients (p<0.00001 and p= 0.04 respectively). The main results are summarized in table 1. MP count and MP/Platelets ratio were significantly lower in CALR+ than in JAK2+ patients. PMP count, PMP percentage of all MPs and PMP/Platelets ratio were lower in CALR+ than in JAK2+ patients. Furthermore, CALR+ patients had lower PMP surface P-Selectin. MP-associated procoagulant activity/Platelets ratio was significantly lower in CALR+ than in JAK2+ patients. There were no significant differences in TF-carrying PMP or in other cell-derived MP (RMP, MoMP, GMP, EMP). Conclusion: Our results demonstrate a decreased in circulating procoagulant PMP in CALR+ ET-patients compared to JAK2+ patients and lower platelet activation in CALR+ ET patients as measured by P-Selectin expression on PMP. Thus, as CALR+ patients have lower thrombotic-risk according to the literature and the IPSET-survival and IPSET-thrombosis scores observed in our study, the lower level of procoagulant PMP could account, at least in part, for a lower thrombotic risk of CALR+ ET patients. Table 1 main results CALR + JAK2 V617F + p value MP (/µL) 3289 [1662-4240] 4961 [2697-6687] 0.04 MP/Platelets 3.6 [2.8-5.3] 6.9 [4.7-9.6] 0.01 PMP (/µL) 3100 [2068–3887] 5702 [3423-10257] 0.004 PMP/Platelets 3.38 [2.97–6.33] 7.55 [5.12–12.66] 0.002 % PMP 90 [84–92] 93 [90–96] 0.03 MP-activity(nM)/platelet 0.015 [0.008–0.028] 0.029 [0.019–0.041] 0.05 P-Selectin+ PMP (/µL) 195 [152-219] 747 [383-965] 0.001 RMP (/µL) 4 [1.7–8.2] 4 [2.5–9.7] ns MoMP (/µL) 43 [27–52] 74.5 [22–135] ns GMP (/µL) 31.5 [24–48] 30 [11–55] ns EMP (/µL) 99.4 [32–110] 95.6 [51–140] ns TF+ PMP (/µL) 22.3 [9.8–115] 27.1 [20.8–94.4] ns Disclosures No relevant conflicts of interest to declare.

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