Similar Platelet Counts Research Articles

PS1588 FIBRINOLYSIS IN PATIENTS WITH CHEMOTHERAPY INDUCED THROMBOCYTOPENIA AND THE EFFECT OF PLATELET TRANSFUSION

Background:Bleeding events in chemotherapy induced thrombocytopenic (CIT) patients with similar platelet counts might be influenced by changes in clot lysis potential.Aims:In this observational study we investigated thromboelastographic lysis parameters, alterations in clot strength and susceptibility to clot lysis in CIT patients and identified factors associated with fibrinolytic profiles. Furthermore, the effects of platelet transfusions were evaluated.Methods:Independent determinants of tPA‐ROTEM lysis parameters were identified with multivariable linear regression. Clot formation, strength and lysis parameters were compared with results of healthy individuals. Characteristics of CIT patients with and without hyperfibrinolytic profiles were compared. tPA‐ROTEM results before, 1 hour and 24 hours after platelet transfusion were compared.Results:A total of 72 consecutive CIT patients were included. tPA‐ROTEM lysis parameters correlated with changes in fibrinolytic proteins. Compared to healthy individuals, clot formation time was longer, maximum clot firmness was weaker and lysis times were shorter. CIT patients had low PAI‐1 and TAFI levels and forty percent exhibited hyperfibrinolytic profiles. Platelet transfusions resulted in less hyperfibrinolytic profiles in many, but not all CIT patients. Patients without hyperfibrinolytic profiles had higher fibrinogen, FVIII and a2‐AP levels.Summary/Conclusion:tPA‐ROTEM can be used as a fast and reliable assay to detect hyperfibrinolytic profiles in CIT patients. CIT patients have weaker clots which are more susceptible to clot lysis compared to healthy individuals. Besides platelets, other factors are likely to influence clot susceptibility to fibrinolysis in CIT patients. The impact of a hyperfibrinolytic tPA‐ROTEM profile on bleeding remains to be investigated.

PB2256 DISSOLVED PSEUDO‐THROMBOCYTOPENIA BY USING EVIDENCE‐BASED RESEARCH

Background:Platelet clumping is a common laboratory phenomenon that causes pseudo‐thrombocytopenia (PTC), spurious thrombocytopenia due to persistence of antibody or agglutinins. Microscopic examination of the peripheral blood smear is of key importance to confirm the diagnosis and to avoid any inappropriate or dangerous clinical and therapeutic decision. How to dissolve platelet clumping and make sure correct platelet count is an important procedure. Ethylenediaminetetraacetic acid (EDTA) is a well‐known anticoagulant for the hematological tests (CBC). EDTA‐dependent pseudo‐thrombocytopenia is the most common causes of platelet clumping in medical laboratory.Aims:To dissolved platelet clumping ex vivo and correct platelet count in medical laboratory avoid further inappropriate treatment and waste of medical resource.Methods:We drew blood of the patient in three tubes containing three different types of anticoagulants; EDTA, Sodium Citrate and Heparin. The three blood samples were run in fully automated Hematology analyzer (SYSMEX XN‐3000).Three tubes also process in water bath at 37 °C 10 minute and vortex until run automated Hematology analyzer again.Results:54 years old female patient was referred to our lab for investigations as a case of implicated thrombocytopenia. The CBC revealed normal parameters apart from a low platelet count; 35 x10^9/L. A blood smear was ordered and it revealed server platelet clumping. Using different types anticoagulants, EDTA, Citrate, heparin result similar platelet count and still reveal platelet clumping on blood smear. We further pre‐treated warm water bath(37 °C) plus vortex before analysis. Platelet count was counted 138 x10^9/L by automatic hematologic analyzer in pre‐warm blood specimen. The smear also checked by microscopy without phenomenon of platelet clumping.Summary/Conclusion:Platelet cold agglutinin is confirmed by pre‐warm blood specimen which is a rare cause in pseudo‐thrombocytopenia. We used methods of evidence‐based medicine (EBM) to find out patient with cold agglutinins that affect platelet counting.

THROMBOCYTOSIS: A RETROSPECTIVE STUDY OF 573 DOGS (2016-2017)

Abstract Thrombocytosis refers to the increase in number of platelets per microliter (µL) of blood. Platelet counts greater than 1,000,000/µL may be associated with clinical signs of bleeding or thrombosis. Previous studies on underlying causes of thrombocytosis have aroused the interest of researchers about its clinical importance in dogs. The objective of this study was to analyze the blood cell counts in dogs in order to define the main diseases or clinical conditions that were associated with thrombocytosis, from 2016 to 2017. This was done to determine the incidence of thrombocytosis, and categorize the increase in platelet count with respect to severity. Of the 12,676 blood samples analyzed, 4.5% presented thrombocytosis (n = 573). Similar mean platelet counts were observed in all diagnosis or different categories of clinical conditions (neoplasms; gastrointestinal, endocrine, and ophthalmological diseases; trauma and surgery; dermatological, cardiac, neurological, infectious, respiratory, genitourinary, idiopathic, and multiple diseases; and pregnancy) with no significant difference (P ≥ 0.05). The disorders most commonly associated with thrombocytosis were gastrointestinal diseases, followed by neoplasms. Furthermore, increased platelet counts were observed in dogs treated with glucocorticoids and vincristine drugs. As for the degree of severity, extreme thrombocytosis occurred more frequently in the presence of gastrointestinal diseases.

Real-Life Management of Immune Thrombocytopenia in the Elderly: A Multicentre Study on 526 Patients

Real-Life Management of Immune Thrombocytopenia in the Elderly: A Multicentre Study on 526 Patients

Maximising platelet availability by delaying cold storage.

Cold-stored platelets may be an alternative to conventional room temperature (RT) storage. However, cold-stored platelets are cleared more rapidly from circulation, reducing their suitability for prophylactic transfusion. To minimise wastage, it may be beneficial to store platelets conventionally until near expiry (4 days) for prophylactic use, transferring them to refrigerated storage to facilitate an extended shelf life, reserving the platelets for the treatment of acute bleeding. Two ABO-matched buffy-coat-derived platelets (30% plasma/70% SSP+) were pooled and split to produce matched pairs (n = 8 pairs). One unit was stored at 2-6°C without agitation (day 1 postcollection; cold); the second unit was stored at 20-24°C with constant agitation until day 4 then stored at 2-6°C thereafter (delayed-cold). All units were tested for in vitro quality periodically over 21 days. During storage, cold and delayed-cold platelets maintained a similar platelet count. While pH and HSR were significantly higher in delayed-cold platelets, other metabolic markers, including lactate production and glucose consumption, did not differ significantly. Furthermore, surface expression of phosphatidylserine and CD62P, release of soluble CD62P and microparticles were not significantly different, suggesting similar activation profiles. Aggregation responses of delayed-cold platelets followed the same trend as cold platelets once transferred to cold storage, gradually declining over the storage period. The metabolic and activation profile of delayed-cold platelets was similar to cold-stored platelets. These data suggest that transferring platelets to refrigerated storage when near expiry may be a viable option for maximising platelet inventories.

Platelet-predominate gene expression and reticulated platelets in nonvalvular atrial fibrillation: Effect of pulmonary veins isolation.

Reticulated platelet (RP) content is increased in nonvalvular atrial fibrillation (NVAF). The purpose of this study was to determine if platelet content, morphology, and RP proportion are modulated by platelet genes. Expression of six platelet-predominate genes impacting platelet formation and release, platelet count, and RP content was assessed in NVAF patients before and 3-4 months after pulmonary veins isolation (PVI) and compared to normal sinus rhythm (NSR) controls. RNA from isolated platelets was reverse-transcribed assayed against selected genes utilizing real-time qPCR, and expressed as mean cycle threshold (ΔCt) using beta-2-microglobulin as endogenous control. RP content was assessed by flow cytometry. A fourfold lower expression of CFL1 gene coding for nonmuscle cofilin (7.8 ± 0.9vs. 5.7 ± 1.6, P<0.001) and twofold lower expression of four other genes were associated with similar platelet counts but fourfold higher (28.7+7.0vs. 6.7+5.4, P<0.001) RP content (%) in 97 NVAF cases compared to 51 NSR controls. Three to 4 months after PVI, RP decreased by 28%, while CFL1 gene expression increased over twofold but TUBA4A gene expression decreased almost twofold; NFE2 and MYL6 gene expression remained unchanged. NVAF is associated with notable downregulation of genes directing platelet production and size but increased RP content. PVI impacts the expression of many of these genes, implying a direct relationship between atrial fibrillation and platelet biogenesis.

Fibrinogen levels compensation of thrombocytopenia-induced bleeding following cardiac surgery.

After cardiopulmonary bypass (CPB) thrombocytopenia is a relatively common pattern which may trigger postoperative bleeding. The purpose of this study is to verify if the endogenous fibrinogen levels are independent determinants of chest drain blood loss and need for allogeneic blood products transfusions in a clinical model of post-CPB thrombocytopenia. Retrospective analysis on 445 consecutive patients having a platelet count <100×1000cells/μL after CPB. Based on the fibrinogen levels the patients were divided into three groups with similar platelet count and low (LF, median 170mg/dL), intermediate (IF, median 215mg/dL), and high (HF, median 280mg/dL), fibrinogen levels. Chest drain blood loss (mL/12h), transfusion rate of red blood cells (RBC), fresh frozen plasma (FFP) and platelet concentrates were assessed and compared between groups. There was a significant (P=0.001) difference in chest drain blood loss with higher values in the LF group (487mL/12h, IQR 300-600mL/12h) than in the IF group (350mL/12h, IQR 200-500mL/12h) and the HF group (300mL/12h, IQR 200-475mL/12h). Transfusion rates of FFP significantly (P=0.014) differed between groups (LF: 18.4%, IF: 7.9%, HF: 9.2%) and platelet concentrate transfusions significantly (P=0.020) differed between groups (LF: 23.5%, IF: 16.5%, HF: 10.7%). In multivariable models, these differences were confirmed. Thromboelastography parameters showed an effective compensation of clot firmness in group HF vs. IF and LF. Levels of fibrinogen >240mg/dL compensate the decrease in clot firmness observed in thrombocytopenic patients following CPB, and reduce bleeding and transfusion needs.

Evaluation of platelet function in thrombocytopenia

Whole blood aggregometry is a functional assay for determination of platelet function. Until now, whole blood aggregometry has not been considered feasible at low platelet counts. Hence, the objectives of the present study were to explore platelet function in thrombocytopenia using a novel index of impedance aggregometry adjusted for platelet count and evaluate the association to platelet function assessed by flow cytometry. Hirudin anticoagulated blood was collected from 20 healthy volunteers, 20 patients with primary immune thrombocytopenia (ITP), and 17 hematological cancer patients. Platelet function was analyzed by impedance aggregometry and by flow cytometry. Collagen, adenosine diphosphate, thrombin receptor agonist peptide-6, and ristocetin were used as agonists for both analyses. Thrombocytopenia in healthy whole blood was induced in vitro employing a recently published method. Platelet aggregation of thrombocytopenic patients was evaluated relative to the aggregation of healthy volunteers at the same platelet count. In flow cytometry, platelet function was described as expression of the platelet surface glycoproteins: bound fibrinogen, CD63, and P-selectin. Similar platelet counts were obtained in the patient groups (p = 0.69) (range: 13–129 × 109/l). Aggregation adjusted for platelet count was significantly increased in ITP patients compared to healthy platelets across all agonists. The platelet aggregation was high in the 95% prediction interval, with 18 ITP patients above the prediction interval in at least two agonists. In contrast, the platelet aggregation was low in the prediction interval in cancer patients, and three cancer patients with platelet aggregation below the prediction interval in at least one agonist. ITP patients displayed increased expression of bound fibrinogen and CD63 following activation, compared with particularly cancer patients, but also compared with healthy platelets. This study demonstrated the feasibility of a novel approach to perform platelet function analyses in thrombocytopenia using impedance aggregometry adjusted for platelet count.

Inherited and Acquired Thrombophilia As a Modifier of Clinical Course of Chronic Idiopathic Thrombocytopenia - a Prospective Study

Background: Patients with idiopathic thrombocytopenia exhibit striking heterogeneity in bleeding manifestations even at similar platelet counts. Proposed mechanisms are generation of platelet microparticles, complement activation, NO depletion, and impact of various treatment modalities. In the present study, we studied the prevalence of thrombophilic markers in persistent and chronic ITP patients and that whether the presence of such markers modifies the clinical course of these patients.Methods: Patients diagnosed as persistent or chronic ITP (of any age group) were eligible. All patients were evaluated at baseline and at regular follow-up visits using newly available Bleeding Assessment Tool (ITP-BAT, version 1.0) proposed by International Working Group on ITP. For analyses, severity of bleeding was defined as no bleeding (bleeding score zero at all domains I.e. skin, mucosa and organ), mild bleeding (skin and mucosal bleeding score 0-2, organ bleeding score 0-1) and severe bleeding (skin and mucosa bleeding score >2, and organ bleeding score >1). Baseline thrombophilia profile was obtained for all patients, that included clot-based assays for protein C (PC), protein S (PS), ProCGlobal, FVIII levels (F8), and lupus anticoagulant assay (LA). We then compared the patients expressing atleast one thrombophilia marker (TM+) and those without (TM-), for the number of times patients in each group presented with a bleeding episode. We derived the parameter bleeding episodes per visit to estimate severity of bleeding in each group [mild bleeding episode/visit (MBE/visit) and severe bleeding/visit (SBE/visit)].Statistical analysis was done using odds ratio calculation and correlation regression analysis.Results: Of the total 88 patients enrolled, 21 were males (23.4%), and remaining 67 (76.5%) were females. Out the total, 57 patients (64.7%) tested positive for at least one thrombophilic marker, and remaining 31 patients (35.2%) were negative for all markers. Raised factor VIII was found in 36 patients (40.9%), low protein S in 29 patients (32.9%), low protein C in 14 patients (15.9%), abnormal Pro® C global in 22 patients (25%), and lupus anticoagulant positive in 9 patients (10.2%). Thirty three (37.5%) patients expressed thrombophilic markers in various combinations. Evaluation for impact of thrombophilia marker on bleeding is as shown in Table 1.Summary: Sixty-five percent of patients had thrombophilia marker positive in various combinations. Those with thrombophilia had lower bleeding tendency compared to those with none. Patients with low protein C and S, abnormal ProcGlobal and lupus positivity had significantly lower bleeding tendencies, while FVIII abundance did not impact the bleeding scores.Conclusion: We conclude that a part of the heterogeneity in the clinical presentation of persistent and chronic ITP can be explained by the presence or absence of thrombophilia, and that work-up of patients with ITP should include thrombophilia evaluation, the results of which may have a role in therapeutic decision making. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Procoagulant Profile of Platelets from Immune Thrombocytopenia Patients

Introduction: Immune thrombocytopenia (ITP) is an autoimmune disorder in which both increased platelet destruction and insufficient platelet production are involved. Patients can have a range of bleeding manifestations from none to severe at a similar platelet count. In some cases, patients have fewer bleeding symptoms than expected considering the low platelet count that they might have.Objective: The aim of this study was to determine the procoagulant profile of platelets from ITP patients in order to determine whether any of their features may explain this observation.Methods: Twenty-five patients with chronic ITP [(68±100)x109 platelets/L, mean age: 59.6 ± 16.1 years old, 56% female)] and thirty-five healthy controls [(256±36)x109 platelets/L, mean age: 41.6 ± 13.5 years old, 51% female) were included. Platelet counts were determined with a Coulter Ac. T Diff cell counter (Beckman Coulter, Madrid, Spain). Citrated blood was centrifuged at 152 g 10 min at 23°C for obtaining platelet rich plasma (PRP).To obtain washed platelets, the top two-thirds volumes of PRP were collected and centrifuged (650 g for 10 min at 23°C) after the addition of acid-citrate-dextrose (ACD, 1:10) and the pellet was resuspended in an equal volume of HEPES buffer.Platelet activation was determined by flow cytometry through binding of FITC-PAC1 (a mAb that recognizes activated conformation of fibrinogen receptor) to quiescent and 100 micromol/L thrombin receptor-activating peptide 6 (TRAP, Bachem, Switzerland) or 20 micromol/L ADP.Apoptosis was determined by flow cytometry analysis through FITC-annexin V binding to phosphatidylserine (PS) exposed on platelet membrane under basal conditions.To characterize platelet ability to bind coagulation factors, washed platelets (1x108/mL) were activated with 100 micromol/L TRAP and then incubated with FVa and/or FXa (5nM each, 10 min, ambient temperature). After fixation with 2% paraformaldehyde to cross-link the platelet-bound factors Va and Xa, platelets were washed two times with Hepes Buffer. Non-specific binding sites were blocked with 8% bovine serum albumin (30 min, room temperature). Following centrifugation, platelets were first incubated with anti-CD41-PE, anti-FVa and/or anti-FXa and then with a secondary FITC-goat anti-mouse IgG and stored at 4°C until flow cytometry analyses.Results: Platelets from ITP patients showed a basal expression of activated fibrinogen receptor similar to controls and a reduced ability for being activated by agonists (% of positive platelets for TRAP-induced PAC1 binding: 60±20 % in controls and 35±23 % in ITP, p<0.01; ADP-induced PAC1 binding: 63±14 % in controls and 50±23 % in ITP, p<0.05). Diminished responses to activation were not due to a reduction in surface expression of fibrinogen receptor in platelets from ITP patients.Platelets from ITP patients expressed more PS than controls under basal conditions [mean fluorescence (MF) for FITC-annexin V binding was: 336±128 in controls, 588±25 in ITP, p<0.05].Since the PS is the anchor site of the prothrombinase complex, we studied the binding of FVa and FXa at baseline and after activating platelets with TRAP. The binding of these factors in both conditions was higher in the group of patients with ITP (MF for basal FVa binding: 41.4±14.4 in controls, 58.1±24 in ITP, p <0.02; MF for TRAP-induced FVa binding: 44.1±11.4 in controls, 81.4±38 in ITP, p<0.001; MF for basal FXa binding: 45.7±18.4 in controls, 58.1±24 in ITP, p <0.005; MF for TRAP-induced FXa binding: 46.1±16.4 in controls, 72.0±24 in ITP, p<0.05). The lower the platelet count the higher increase in PS exposure (Spearman r =-0,518, p <0.001) and the union of FVa (Spearman r = -0.8571, p <0.001) and FXa (Spearman r = -0.7455, p<0.05).Conclusions: Platelets from ITP patients, despite having less capacity of activation by agonist stimulation, have an increased procoagulant surface with greater ability to bind prothrombinase complex (FXaVa) than those from healthy controls. This feature might be a procoagulant compensatory mechanism that could reduce the risk of bleeding in patients with ITP.This work was supported by a grants from the FIS-FEDER, PI12/01831 and PI15/01457 DisclosuresNo relevant conflicts of interest to declare.

Undertreatment of Patients (Pts) with Myelodysplastic Syndromes (MDS): Analysis of a Large Electronic Medical Records (EMR) Database Cohort of US Pts with MDS

Introduction: Little is known about current care patterns for pts with MDS across the US with respect to the use of available therapeutic agents. Using a cohort of 5,162 MDS pts we previously identified from the GE Centricity EMR database (GE Healthcare IT, Princeton, NJ) (Ma X, et al. Blood. 2015;126:abstract 3319), we examined associations between pt characteristics and treatment patterns, including sequence of therapies for pts with MDS.Methods: Pts with data in the EMR from Jan 2006 to end of Feb 2014 were included in this analysis. Pts were grouped by treatment received (erythropoiesis-stimulating agents [ESA], lenalidomide [LEN], hypomethylating agents [HMA; azacitidine or decitabine], and iron chelation therapy [ICT]), either alone, in combination, or as part of a sequence with other therapies. Transfusions were not included in this analysis, as transfusion data were often unrecorded due to transfusions occurring in facilities outside the EMR system. Pt characteristics were evaluated for each treatment group.Results: Of 5,162 pts evaluated, 1,843 (35.7%) received only 1 therapy, 2,079 (40.3%) received ≥ 1 therapy, with only 236 (4.6%) receiving ≥ 2 therapies. Pts who received ≥ 1 treatment of interest are shown in the Figure. Baseline characteristics for treatment groups are shown in the Table. A total of 85 pts were recorded as having deletion 5q by International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) coding; of these, 66 were recorded as receiving ≥ 1 treatment. Pts were in the EMR system for a median of 29 days (date of first entry to date of last entry), with 36%, 26%, and 15% of pts present in the system for > 6 months, 1 year, and 2 years, respectively.The most common initial therapy was ESA (n = 1,508; 72.5% of treated pts). Pts treated with ESA first had a median age of 78.0 years; 1,330 (88%) received ESA exclusively. ESA-only pts were the oldest among the treatment groups (median age 79.0 years), had the highest proportion with comorbidities at baseline (69%), and most commonly had isolated anemia. Only a small proportion of pts treated with ESA first subsequently received LEN (n = 79; 5.2%) or HMA (n = 68; 4.5%) as second therapy; median ages of these patients were 76.0 and 73.5 years, respectively.682 pts (32.7% of treated pts) received a therapy approved specifically for MDS, i.e. HMA and/or LEN, during their treatment.Pts who received LEN as first treatment (n = 258; 12.4% of treated pts) had a median age of 74.0 years. These pts had a lower median hemoglobin (Hb), lower median absolute neutrophil count (ANC), and similar median platelet count vs pts receiving ESA as first treatment. Most pts who received LEN as their first therapy received it exclusively (244; 94.6% of treated pts); a small number (n = 14) were subsequently treated with HMAs. Pts who received LEN second (n = 99) or third (n = 13) in a sequence of therapies were similar in age (median 76.0 and 74.0 years, respectively) and had similar Hb levels, higher ANCs, and higher platelet counts at baseline than pts who received LEN as first therapy. Most pts (n = 79; 80%) who received LEN as second therapy previously received ESA.Of 252 pts (12.1% of treated pts) who received HMA as first therapy, 228 (90.4%) received HMA only; median age of patients who received HMAs as first therapy was 75.0 years, and median Hb level, median ANC, and median platelet count were lower than in pts who received ESA as first therapy. Another 100 pts and 28 pts received HMA as second and third therapies, respectively; median age was 73.0 years in each group. Pts receiving HMA third had higher median Hb level, ANC, and platelet count than pts who received HMA as first therapy. Only 61 pts (2.9% of treated pts) received ICT as first therapy.Conclusions: Pts diagnosed with MDS in the USA are likely to be undertreated. Consistent with findings from physician surveys (e.g. Sekeres M., et al. J Natl Cancer Inst. 2008;100:1542-51), ESAs are the most commonly used therapies despite the lack of a labeled indication for MDS. ESAs are usually the first therapy chosen by physicians and often the only therapy pts with MDS receive. Use of LEN and HMA, which have been approved for the treatment of MDS for ~10 years, appears low in this EMR. [Display omitted] [Display omitted] DisclosuresSteensma:Genoptix: Consultancy; Celgene: Consultancy; Millenium/Takeda: Consultancy; Ariad: Equity Ownership; Amgen: Consultancy; Janssen: Consultancy. Scott:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees. Ma:Celgene Corporation: Consultancy. Fliss:Celgene Corporation: Employment, Equity Ownership. Kiselev:Celgene Corporation: Employment, Equity Ownership. Swern:Celgene: Employment, Equity Ownership. Sugrue:Celgene Corporation: Employment, Equity Ownership.

Rapid Evaluation of Platelet Function With T2 Magnetic Resonance.

Objectives: The clinical diagnosis of qualitative platelet disorders (QPDs) based on light transmission aggregometry (LTA) requires significant blood volume, time, and expertise, all of which can be barriers to utilization in some populations and settings. Our objective was to develop a more rapid assay of platelet function by measuring platelet-mediated clot contraction in small volumes (35 µL) of whole blood using T2 magnetic resonance (T2MR).Methods: We established normal ranges for platelet-mediated clot contraction using T2MR, used these ranges to study patients with known platelet dysfunction, and then evaluated agreement between T2MR and LTA with arachidonic acid, adenosine diphosphate, epinephrine, and thrombin receptor activator peptide.Results: Blood from 21 healthy donors was studied. T2MR showed 100% agreement with LTA with each of the four agonists and their cognate inhibitors tested. T2MR successfully detected abnormalities in each of seven patients with known QPDs, with the exception of one patient with a novel mutation leading to Hermansky-Pudlak syndrome. T2MR appeared to detect platelet function at similar or lower platelet counts than LTA.Conclusions: T2MR may provide a clinically useful approach to diagnose QPDs using small volumes of whole blood, while also providing new insight into platelet biology not evident using plasma-based platelet aggregation tests.

Severe Thrombocytopenia in Adults with Severe Acute Respiratory Distress Syndrome: Impact of Extracorporeal Membrane Oxygenation Use.

Extracorporeal membrane oxygenation (ECMO) use is perceived to cause thrombocytopenia (T), but the role of non-ECMO factors in the development of T remains unclear. We sought to evaluate the incidence and factors associated with severe T (platelet count ≤ 50,000/μl) in adults with severe acute respiratory distress syndrome (ARDS) managed with or without ECMO. The ECMO (n = 32) versus the non-ECMO (n = 53) groups had a similar baseline platelet count (214,000 vs. 179,000/μl), Acute Physiology and Chronic Health Evaluation (APACHE) II score (p = 0.13), unfractionated heparin (UFH) exposure (p = 0.62), and severe T incidence (25 vs. 19%, p = 0.5). Although the APACHE II score (p = 0.01), presence of liver failure (p = 0.08), and platelet transfusion (p = 0.0009) were different between the severe T (18/85 [21%]) and non-severe T groups (67/85 [79%]), the incidence of septic shock (p = 0.64), heparin infusion use (p = 0.41), exposure to non-heparin T-causing medications (p = 0.77) and ECMO use (p = 0.5) were not. An adjusted multivariate linear regression model revealed that only the APACHE II score was independently associated with the development of severe T (p = 0.01) but use of ECMO was not (p = 0.32) ECMO use may not affect the incidence of severe T among adults with severe ARDS. Larger studies that are prospective in nature are required to confirm this finding.

Dynamics of platelet count in critically ill medical patients as a prognostic marker and its associated risk factors – Experience at a tertiary care center of North-West India

Abstract Aim To find proportion of medical ICU patients developing thrombocytopenia and its associated risk factors, and to study dynamics of platelet counts and outcomes. Methods A descriptive observational study done on 205 patients admitted in MICU for >48 h and had platelet count >150 × 10 9 /L at admission in ICU. Patients having hematological disorders or drugs that could affect platelet count and died/discharged Result Patients developing thrombocytopenia ( n = 101) had significantly younger age ( p p p p Platelet counts were almost similar in both groups at admission in ICU, but fall in platelet count among thrombocytopenic patients on days 3–5 during ICU stay was significantly greater ( p Thrombocytopenic patients who expired had similar platelet count at admission as patients who survived ( p > 0.05), but had a significant drop between days 3 and 5 ( p Mortality showed a significant association with severity of thrombocytopenia. Conclusion Thrombocytopenia is common in medical ICU patients (49.26%). Severity of thrombocytopenia and dynamics of platelet count between 3 and 5 days of ICU stay are associated with mortality.

Prevalence of "Flat-Line" Thromboelastography During Extracorporeal Membrane Oxygenation for Respiratory Failure in Adults.

We evaluated the prevalence of a thromboelastography reaction time (R time) >90 min ("flat-line") reversible with heparinase during extracorporeal membrane oxygenation (ECMO). We evaluated the association between "flat-line" thromboelastography, other coagulation tests, and risk of bleeding during ECMO. Thirty-two consecutive patients on ECMO were included. Anticoagulation was provided by continuous infusion of unfractionated heparin to maintain an activated partial thromboplastin time (aPTT) ratio between 1.5 and 2.0. Activated clotting times (ACTs) thromboelastography without and with heparinase were measured. Occurrence of bleeding was recorded. Median heparin infusion rate was 16 (12-20) IU/kg/h, aPTT ratio was 1.67 (1.48-1.96), and ACT was 173 (161-184) sec. One hundred forty-five (46%) of 316 paired thromboelastography samples were "flat lines" all reversed with heparinase. Patients with "flat-line" thromboelastography received more heparin (p = 0.001) but had similar platelet count (p = 0.164) and fibrinogen level (p = 0.952) than those without. Activated partial thromboplastin time, ACT, and R time without heparinase weakly correlated between each other (Spearman correlation ≤0.36) with poor agreement (Cohen's κ ≤0.10). Major bleeding occurred in seven (22%) patients. Bleeding during ECMO was not predicted by any of the used test. In conclusion, adjusting heparin infusion to maintain aPTT ratio between 1.5 and 2.0 frequently resulted in "flat-line" thromboelastography.

Association of conventional haemostasis and coagulation tests with the risk of acute upper gastrointestinal bleeding in liver cirrhosis: a retrospective study.

Objective: A retrospective study was performed to compare the difference in platelet count (PLT), prothrombin time (PT), international normalized ratio (INR), and activated partial thromboplastin time (APTT), between cirrhotic patients with and without acute upper gastrointestinal bleeding (AUGIB) or acute oesophageal variceal bleeding (AEVB).Methods: Between January 2012 and June 2014, a total of 1734 cirrhotic patients were enrolled and were classified into ‘AUGIB’ (n = 497) and ‘no AUGIB’ (n = 1237) groups according to their disease history. They were further divided into ‘AEVB’ (n = 297) and ‘no AEVB’ (n = 1259) groups according to the endoscopic findings. Additionally, 178 patients with AUGIB were not assigned to either the ‘AEVB’ or ‘no AEVB’ groups due to the absence of any endoscopic findings.Results: Compared with the ‘no AUGIB’ group, the ‘AUGIB’ group had similar PLT (99.99 ± 89.90 vs.101.47 ± 83.03; P = 0.734) and APTT (42.96 ± 15.20 vs.43.77 ± 11.01; P = 0.219), but significantly higher PT (17.30 ± 5.62 vs.16.03 ± 4.68; P < 0.001) and INR (1.45 ± 0.69 vs.1.31 ± 0.59; P < 0.001). A lower PT was independently associated with the absence of AUGIB (OR = 0.968; 95% CI: 0.942–0.994). Compared with the ‘no AEVB’ group, the ‘AEVB’ group had significantly lower PLT (86.87 ± 62.14 vs.101.74 ± 83.62; P = 0.004) and APTT (40.98 ± 7.9 vs.43.72 ± 10.97; P < 0.001), but similar PT (16.53 ± 3.71 vs.16.04 ± 4.68; P = 0.088) and INR (1.35 ± 0.41 vs.1.31 ± 0.59; P = 0.225). A higher PLT was independently associated with the absence of AEVB (OR = 1.004; 95% CI: 1.002–1.006; P = 0.001).Conclusions: PLT was associated with the occurrence of portal hypertension-related bleeding in liver cirrhosis.

Clinical Characteristics, Treatment and Outcomes for Patients with Myelodysplastic Syndromes and Chromosome 5q Abnormalities in the Republic of Ireland

IntroductionMyelodysplastic Syndromes are diverse group of bone marrow failure syndromes and current treatment options are guided by International Prognostic scoring systems (IPSS and IPSS-R) based on clinical phenotype and cytogenetics. Deletion of long-arm of chromosome 5 is the commonest cytogenetic abnormality and confers distinct biological and clinical implications. A specific subgroup of MDS patients with isolated Del(5q) was described as a separate entity in WHO 2008 classification owing to its unique clinical features, a low risk of leukemic transformation and a relatively good prognosis. Lenalidomide is proven to induce high erythroid response rates (frequently abolishing transfusion requirements) with a median response time of over 2 years in MDS patients with Del(5q). However, with time their anaemia worsens and most patients will become transfusion dependent with subsequent iron overload. Other treatment strategies were explored for those who failed Lenalidomide.MethodThis retrospective multi-centre analysis involved collecting data for MDS patients with 5q abnormalities (isolated Del(5q), Del(5q) with one additional cytogenetic abnormality, or Del(5q) within a complex karyotype) diagnosed between 2006 and 2014 in the Republic of Ireland. Six haematology units participated and the data of 47 patients were available for analysis.ResultsThe median age of diagnosis was 72(29-91) with male-female ratio of 1:1.6. A range of WHO subgroups were identified and classic 5q Syndrome was documented in only 6.4% of patients. Cytogenetic results showed 47% isolated Del(5q), 17% Del(5q) plus one other abnormality and 36% Del(5q) in a complex karyotype. Patients with isolated Del(5q) or Del(5q) plus one other abnormality had similar haemoglobin, higher neutrophil and platelet count and lower marrow blasts than those with having a complex karyotype as previously described. IPSS-R scores were available in 37 patients as very low(7), low(8), intermediate(6), high(5) and very high(11). IPSS risks were available for 40 patients as low risk(12), intermediate-1(11), Intermediate-2(8) and high risk(9).Treatment options included red cell transfusion(85%), Recombinant Erythropoietin(45%), Lenalidomide(17%), Azacitidine(36%), Intensive chemotherapy(7%), transplantation(5%) and others(21%). All 8 patients in Lenalidomide group had either isolated Del(5q) or Del(5q) plus one other abnormality and received a median of 3 cycles (range 1-50). Responses were as follows: stable disease (3,38%), complete response (3,38%), and no response (2,25%). Three patients (38%) became transfusion independent with Lenalidomide.In 16 patients treated with Azacitidine, 50% had Del(5q) in a complex karyotype and 19% had failed Lenalidomide previously. A median of 10 cycles(range 1-18) were given. Four(25%) patients achieved a complete response, 1(6%) partial response, 1(6%) haematological improvement and 8(50%) stable disease. Response patterns were similar between the two groups with a trend towards improved survival in patients with isolated Del(5q) or Del(5q) plus one other abnormality compared to those with a complex karyotype treated with Azacitidine(23 vs. 15 months, p=0.0862).Transformation to AML was observed in 44% of patients without any difference between different cytogenetic groups. Median time to AML was 14 months. Median overall survival was 15 months(range <1-152) and 5-year survival was 9.6%. A significant difference in survival was observed between patients with isolated Del(5q) or Del(5q) plus one other abnormality compared to those with Del(5q) in a complex karyotype (26 vs. 10 months, p=0.009).ConclusionsIrish patients with Del(5q) have similar pattern of disease with previously published data. Only a small proportion of patients were treated with Lenalidomide. Irish patients showed a good response to Azacitidine, even when Lenlalidomide failed and this is an important consideration for selected patients. A high rate of AML transformation was observed in Irish MDS patients with Del5q abnormalities. [Display omitted] [Display omitted] DisclosuresO'Dwyer:Celgene: Honoraria, Research Funding.

Coated platelets and severe haemophilia A bleeding phenotype: Is there a connection?

Coated platelets are a subpopulation of platelets that possess highly prothrombotic properties. Previous observational data suggest that bleeding phenotype in severe haemophilia A is associated with coated platelet levels. Haemophilia A patients with higher coated platelet levels may have a mild bleeding phenotype; those with lower levels may have a more severe bleeding phenotype. The aim of the study was to test the hypothesis that coated platelet levels are correlated with clinical bleeding phenotype. This cross-sectional, observational study enrolled 20 severe haemophilia A patients, including 15 with severe and five with a mild bleeding phenotype, and a control group of 12 healthy volunteers. The haemophilia bleeding phenotype was determined by the patient's medical history and haemophilia treatment centre records. Blood was obtained from each patient by venipuncture and platelets were analysed by flow cytometry. Patients categorized as having a severe bleeding phenotype experienced a median eight bleeds per year compared to one bleed annually in the mild bleeding phenotype group. Both groups had similar total platelet counts and fibrinogen levels. There was no difference in coated platelet percentage between severe and mild bleeding phenotype (17 and 16% respectively), however, both groups had significantly lower % coated platelets compared to controls (44%, P < 0.0001). Coated platelet levels were not associated with bleeding phenotype in this study; however, these data may suggest coated platelet levels are lower in haemophilia patients relative to healthy volunteers.

Immature platelet fraction measurement is influenced by platelet size and is a useful parameter for discrimination of macrothrombocytopenia

BackgroundReticulated platelets (RPs) as measured using flow cytometry are useful parameters of thrombopoiesis; however, difficulties remain with standardization between laboratories. On the other hand, immature platelet fraction (IPF) measurement, as determined using an automated hematology analyzer, is simple, reproducible, and displays a good correlation with RP, although specific factors may affect its value. We previously noticed that a small proportion of patients exhibit extremely high IPF values that do not correlate with flow cytometrically measured RP.ObjectivesWe investigated the mechanism of the aberrant increase in IPF values of different types of macrothrombocytopenia.Patients/methodsIPF, RP, and other platelet indexes were analyzed using samples from 15 congenital macrothrombocytopenic patients from 12 families, 150 immune thrombocytopenic patients, and 27 normal individuals. We further monitored the change in IPF values and morphology during platelet agglutination.ResultsIPF values were about five times higher in MYH9 disorders (IPF 48.6 ± 1.9%) and about twice as high in other macrothrombocytopenias (IPF 18.4 ± 2.1%) than in immune thrombocytopenic patients with similar platelet counts (IPF 9.2 ± 0.3%). We then examined changes in IPF values during ethylenediaminetetraacetic acid- and macroglobulinemia-induced platelet agglutination. The IPF value significantly increased in a time-dependent manner along with the formation of platelet clumps and was strongly influenced by a few tiny platelet aggregates.ConclusionsThese results suggested that IPF values are influenced by platelet size. Furthermore, IPF could be a useful and convenient parameter for screening of macrothrombocytopenia, which presents with a disproportionately high IPF value.

Diabetes and the blood – white cells and platelets

Diabetes and the blood – white cells and platelets