Presence Of Thrombocytopenia Research Articles

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Introduction: Heparin-induced thrombocytopenia (HIT) is a serious adverse effect of heparin treatment characterized by formation of antibodies to heparin–platelet factor 4 (H–PF4) complexes. Clinically, patients with HIT demonstrate a fall in platelet count of more than fifty percent, occurring 5–10 days after the start of heparin treatment; some also develop HIT related thrombosis (HITT). Cardiopulmonary bypass (CPB) is associated with platelet activation, thrombocytopenia and the release into the plasma of large amounts of PF4, as well as exposure to high doses of unfractionated heparin (UFH). Up to 50% of patients develop antibodies to H–PF4 complexes following CPB. However, less than 3% of those patients develop actual HITT, characterized by a second episode of thrombocytopenia 5-10 days after CPB ("P1 pattern" reported by Pouplard et al.). ECMO is a modified CPB circuit that critically ill patients may be exposed to for days and weeks. The incidence of HIT in patients undergoing ECMO is unknown. Furthermore, clinical scores used to diagnose HIT may not be useful in ECMO patients given the high prevalence and persistence of thrombocytopenia caused by artificial circuit and underlying disease. We sought to determine the incidence of HIT/HITT and platelet patterns potentially suggestive of HIT in a cohort of ECMO patients at our institution Methods: After IRB approval, a prospectively collected data set encompassing all ECMO patients from 2009 to 2012 at our institution was reviewed. To compare platelet trends, we only included patients who survived longer than 48 hours after ECMO initiation. Patients were tested for HIT based on presence of thrombocytopenia and clinical suspicion. Institutional criteria defines patients as "HIT positive" if they meet any of the following serological criteria: HIT ELISA Ab(+)/SRA(+); HIT ELISA Ab(-)/SRA(+); HIT ELISA(+) with optical density (OD)>1. "HIT positive" patients with evidence of thrombosis were considered as having HITT. Patients who didn't meet these criteria, or were not tested due to lack of clinical suspicion, were considered "HIT negative". Daily platelet counts were recorded for 10 days inclusive of day of ECMO initiation. Statistical analysis was done using the Wilcoxon rank sum test and Fisher exact test as appropriate for the data sets. Results: 85 patients underwent ECMO from 2009 to 2012. 68 (80%) patients survived longer than 48 hours after ECMO initiation. Of those, 50 patients(73.5%) were tested for HIT ELISA, SRA or both. 4 patients were deemed "HIT positive" and 3 of those patients had documented thrombo-embolic events (HITT) based on predefined criteria (HIT and HITT incidence in the study group of 5.9% and 4.4% respectively). HIT positive patients were significantly younger (53.1 vs. 37.5 years, p=0.048) and had a trend toward higher average HIT ELISA OD (1.246 vs. 0.258, p=0.056). Only significantly different average platelet count between "HIT negative" and "HIT positive group" was at day 10 (163 vs. 53.7, p=0.024).This difference remained significant when we excluded patients from "HIT negative" group who were not tested for HIT ELISA, SRA or both (127.9 vs. 53.7, p=0.033). No other platelet parameter, such as average highest platelet count, platelet nadir, days to nadir and percentage platelet drop, differed significantly between the groups. However, plots of average daily platelet counts suggests a potentially revealing pattern in "HIT positive" group, where a gradual drop to platelet nadir (post ECMO day 5-6) is followed by a period of persistently depressed platelet counts (days 6-10). Conclusions: Incidence of both HIT and HITT is relatively high in patients who survive ECMO for longer than 48 hours at our institution. Traditional clinical scores for diagnosis of HIT such as "4 Ts", or presence of "P 1" platelet pattern (typical of HIT in cardiac surgery patients) are not useful in ECMO patients. Pattern of depressed platelet counts after nadir may be suggestive of HIT in these patients.

Hematologic Abnormalities Improve The Clinical Suspicion Of Malaria In Non-Endemic Countries

Malaria is one of the most frequent hemoparasitic infections in developing countries, responsible for a high health burden; with increasing world travel, growing numbers of patients present with malaria in non-endemic areas. While the clinical presentation of malaria is well characterized in the literature, it is non-specific, and suspicion is often raised simply by a fever and a report of a recent stay in an endemic area. Due to the connection of Europe with its former colonies, with bilateral migratory patterns, this anamnestic suspicion is frequent. To determine whether the addition of classic malaria hematology findings (thrombocytopenia, anemia and increased serum lactate dehydrogenase – LDH - levels) can improve clinical suspicion in patients presenting in non-endemic countries, We reviewed all malaria testing resulting from emergency room (ER) visits between 01-01-2000 and 06-30-2013. Repeated tests related to the same ER visit were analysed together; patients with more than one unrelated ER visit with suspected malaria were treated as separate subjects. Results 1357 subjects (69.0% male) fulfilled our criteria (median of 96 per year); the percentage of yearly Positive results varied between 2.6 and 17.0%, with no discernible temporal pattern, for an overall average of 9.5% of Positives. The monthly distribution of testing was balanced, with each month accounting for 6.4 to 10.2% of yearly tests; however, the percentage of Positives had a bimodal distribution, with two significant peaks in April (14.3% positivity) and December (16.5%); males were twice as likely to be Positive (11.0 vs 6.2%, p=0.005). There was a significant decrease in the mean haemoglobin of malaria-Positive patients (12.8±2.6 vs 13.5±2.2 g/dL, p<0.001), leading to a higher incidence of anemia (39.8 vs 18.6%, p<0.001). The positivity for malaria in anemic patients was 18.6% (vs the overall 9.5%). Mean platelet counts decreased in Positives (102.2±82.8 vs 227.1±91.8 G/L, p<0.001), leading to an increase in thrombocytopenia from 16.1 to 80.6%, p<0.001. Malaria-positivity in thrombocytopenic patients was 34.9%, rising to 36.6% when anemia was also present. Mean leukocyte counts decreased in Positives (5.5±2.4 vs 8.3±4.2 G/L, p<0.001), affecting all lineages, with overt leukopenia present in 20.9 vs 6.8%, p<0.001. Positivity for malaria in leukopenic patients was 20.9%. Leukocytosis was more frequent in suspicious patients without malaria (38.0 vs 17.8%, p<0.001), as was an elevated erythrocyte sedimentation rate (30.8±38.1 vs 16.5±16.8 mm, p=0.005). Serum LDH increased in Positives from 263±287 to 414±201 U/L, p=0.003, with values over the upper limit of normal being more likely in Positives (78.7 vs 35.8%, p<0.001); however, among Positives, high LDH was as likely to be found in patients with anemia as without (87.5 vs 74.2%, p=NS). Malaria-positivity was 19.5% in the presence of high LDH, rising to 35.9% with concomitant anemia or 53.1% with thrombocytopenia. The simultaneous presence of thrombocytopenia, anemia and high LDH (irrespective of leukopenia) resulted in 62% of Positive results, although only 10% of malaria patients fulfilled these criteria. Only 1.8% of patients who were normal on all three counts had malaria, and only 3% of malaria patients were negative for all three. We found that malaria was suspected more often in males, who were in fact more likely to have a positive result. Although suspicion was spread out across the year, there were two seasonal peaks of positive diagnoses, around Easter and Christmas, temporally coinciding with the migratory movements of expatriates and their families. Compared to patients with a clinical suspicion of malaria but without infection, patients who tested positive were more likely to be anemic, thrombocytopenic or leukopenic and to present with elevated LDH levels (irrespective of anemia). Patients with normal haemoglobin, platelets and LDH had a very low likelihood of malaria. The incorporation of these laboratory findings into the clinical scenario improved on clinical suspicion nearly 6-fold (with the percentage of positivity rising from just under 10% to over 60%), although at a high cost of false-negatives. In patients presenting at the ER in non-endemic countries with a fever and recent travel, the presence of combinations of anemia, thrombocytopenia and high LDH greatly increased the likelihood of malaria, although their absence should not impede testing. Disclosures: No relevant conflicts of interest to declare.

English

INTRODUCTION: Plasmodium Vivax malaria is endemic in the northern and eastern part of India. Although Plasmodium falciparum has been commonly implicated as the cause of complicated malaria but now the trend is changing and vivax is increasingly presenting with severe complications. AIMS AND OBJECTIVES: To study the occurrence and severity of thrombocytopenia in patients of vivax malaria. MATERIAL AND METHODS: A total of 100 patients were included in the study and identified positive for malaria parasites on peripheral smear examination with conventional microscopy. Platelet count was done on a fully automated, quantitative, hematology Counter at the time of presentation of patient. INCLUSION CRITERIA: freshly diagnosed cases of vivax malaria. EXCLUSION CRITERIA: Patients with associated falciparum, dengue, leptospirosis or any other known cause of thrombocytopenia. RESULTS: Platelet count was found to be normal in 32 patients. The mean platelet count in vivax malaria was 1,15,390/μl (SD 64,580) with a range of 8000-5,73,000/μl, Mild thrombocytopenia (50000 to 150000) was found in 36 patients. Moderate thrombocytopenia(20000 to 50000) was found in 20 patients. Severe thrombocytopenia (<20000) was found in 12 patients. Platelet transfusion was given in 9 patients and bleeding manifestations were noted in 4 patients. Thrombocytopenia was found to be more common among males (80.59%) and more common in younger age groups. CONCLUSION: Presence of thrombocytopenia is not a distinguishing feature between Vivax and Falciparum types. Thrombocytopenia less than 20,000/μl can occur in P. vivax malaria. The mechanism of occurrence of complications in vivax malaria is still poorly understood but this study can have therapeutic implications regarding more aggressive treatment of plasmodium vivax which was once considered purely benign and uncomplicated.

Antiplatelet antibodies detected by the MAIPA assay in newly diagnosed immune thrombocytopenia are associated with chronic outcome and higher risk of bleeding

Immune thrombocytopenia (ITP) results in part from the presence of platelet antibodies, which can be demonstrated by the Monoclonal Antibody-Specific Immobilization of Platelet Antigens (MAIPA) assay. The aim of our study was to correlate the presence of antiplatelet autoantibodies and the natural history of ITP. We performed a retrospective, single-center study of 108 adults with newly diagnosed ITP who had indirect MAIPA assay performed at disease onset. Chronic ITP was defined by the presence of thrombocytopenia after 1year. Bleeding diathesis was evaluated with a bleeding score. At baseline, patients with a positive indirect MAIPA have a greater bleeding score than patients with negative MAIPA assay [median (interquartile) = 8 (6-12) vs 2 (0-6), p = 0.002]. Patients with a positive indirect MAIPA also had a higher rate of chronic ITP (92.9 vs 68.7%, p = 0.06). In multivariate analysis, a positive indirect MAIPA result and a platelet count at onset ≥10 × 10(9)/L remained independently associated with chronic ITP [adjusted OR (aOR) = 8.01; 95% confidence interval (CI), 0.98-66.6; p = 0.05 and aOR = 3.09; 95% CI, 1.18-8.10; p = 0.02, respectively]. Furthermore, when we analyzed together the results of direct (n = 41) and indirect MAIPA, the same results were observed. Thus, indirect MAIPA positivity at disease onset is associated with more severe hemorrhage and predicts a chronic course in adult ITP patients. MAIPA assay could be useful in the management of ITP patients when it is performed at diagnosis.

Thrombocytopenia, a new marker of bad prognosis in patients with infective endocarditis

Aim: Thrombocytopenia in patients with sepsis has been described as a marker of bad prognosis. Our purpose was to analyze if the presence of thrombocytopenia has a prognostic impact in patients with left-sided infective endocarditis (IE). Methods: We analyzed 698 consecutive episodes of IE prospectively recruited in three referral hospitals between 1996 and 2011. They were classified in two groups: Group I (n=213) episodes of IE who had thrombocytopenia in blood analysis at admission; and Group II (n=485) those who did not have it. Thrombocytopenia was defined as a platelet count below 150000/μl. Results: The age and gender distribution were similar in both groups. Regarding to comorbidities, diabetes (25.4% vs. 18.3%, p=0.03), chronic anemia (24.5% vs. 17.6%, p= 0.03) and immunosuppression (11.8% vs. 4.5%, p<0.001) were more frequent in Group I. We found a greater percentage of prosthetic valves in Group II, while patients without any previous cardiopathy were more prevalent in Group I (29.6% vs. 21.6%, p=0.02). S. aureus (28.6% vs. 10.9%, p<0.001) and Gram negative bacilli (8% vs. 3.1%, p=0.004) were more frequently isolated in Group I, were S. viridans (8% vs. 15.1%, p=0.01) and culture negative IE (10.3 vs. 16.3, p=0.04) were more common in Group II. Clinical presentation with neurological (p<0.001), renal (p=0.05), cutaneous (p<0.001) manifestations and septic shock (12.2% vs. 3.5%, p<0.001) at admission were more frequent in Group I. These patients showed also more frequency of hemorrhagic skin lesions (11% vs. 4%, p=0.002), splenomegaly (14.2% vs 7.4%, p=0.005) and coma (5.6% vs. 0.8%, p<0.001). Presence of pseudoaneurysms were more frequently found in Group II (12.2% vs. 18.9%, p=0.03). There were no differences in other echocardiographic findings (valvular insufficiency, presence and size of vegetations). During hospitalization, persistent signs of infection (44.5% vs. 31.8%, p=0.001) and septic shock were more frequent in Group I (27% vs. 13.5%, p<0.001). The need of surgery was similar in both groups (53.5% vs. 56.1%, p=0.535), but much higher mortality was observed in patients with thrombocytopenia (40.4% vs. 25.3%, p<0.001). Conclusions: Thrombocytopenia at admission of patients with IE identifies a highest risk group. Causative microorganisms are more virulent in this group. These patients develop septic shock more frequently and showed higher mortality.

G177 A Single-Centre Experience of Central Venous Lines in Paediatric Haematology/Oncology Patients Over Five Years

Background and AimsSafe central venous access is required for the management of paediatric patients with solid and haematological malignancies. The objective of this study was to retrospectively review central venous...

FRI0273 Plasma levels of pf-4var/cxcl4l1, a nonallelic variant of platelet factor-4 (PF-4/CXCL4), are elevated in patients with antiphospholipid syndrome (APS).

BackgroundPlatelet derived chemokines, such as PF-4 and a recently isolated protein product of its nonallelic variant gene PF-4var, are implicated in several aspects of vascular thrombosis and inflammation. The above...

Chronic hepatitis C-associated thrombocytopenia: aetiology and management

Thrombocytopenia is perhaps the most common haematological abnormality in patients with chronic hepatitis C virus (HCV) infection. In these patients, the presence of thrombocytopenia may be a limiting factor when considering antiviral therapy and may be associated with decreased sustained virological response rates. Thrombocytopenia may interfere with diagnostic procedures such as liver biopsy, because of risk of bleeding. Pathogenetic mechanisms include hypersplenism secondary to portal hypertension, bone marrow suppression resulting from either HCV itself or interferon treatment, and aberrations of the immune system resulting in the formation of anti-platelet antibodies and/or immune-complexes that bind to platelets and facilitate their premature clearance. The ability to increase platelet levels could significantly reduce the need for platelet transfusions and facilitate the use of interferon-based antiviral therapy and other medically indicated treatments in patients with liver disease. Therapeutic options include pharmacological and non-pharmacological therapies. This review summarizes the available data on these therapeutic options.

Hematological aspects in malaria

<b>Background:</b> Malaria is a major health problem at the global level. In Indian subcontinent, it is a major cause of mortality in immunosuppressed patients and in extreme ages of life. This study is based on early detection of malaria by hematological parameters to reduce the mortality in such cases. <b>Materials and Methods:</b> All patients with fever of less than 7 days in duration were included in the study. Hematological parameters were determined by using automated cell counter. Peripheral blood smear examination for malaria parasite was taken as gold standard for the diagnosis of malaria. <b>Result:</b> A total of 110 patients were included in the study. Ninety nine patients had a positive peripheral smear for malarial parasite. Thrombocytopenia (52.52%) alone (platelet count less than 1, 50,000/mm ³ ) was a predictor for malaria and in combination with anemia (Hb < 10 gm/dl) it was next best parameter. Leucocyte count was not predictive. <b>Conclusion:</b> The conclusion of this study is that the presence of thrombocytopenia in a patient with acute febrile illness increases the probability of malarial infection.

A Novel Test for the Rapid Rule Out of Heparin-Induced Thrombocytopenia Diagnosis in Intensive Care unit patients

AbstractAbstract 1119 IntroductionDiagnosis of heparin-induced thrombocytopenia (HIT) in intensive care unit (ICU) patients represents a major challenge mainly because both the use of unfractionated heparin and the presence of thrombocytopenia are quite common. Despite the existence of several laboratory tests, accurate and prompt HIT diagnostics remains difficult. The ideal combination of an immunological and a functional test is restrictedto specialized laboratories, due to the complexity of the latter. We are in need of an easy-to-perform, widely accessible, rapid and reliably assay. Aim of the studyTo prospectively evaluate the performance of the latelar-flow immunoassay STic HIT Expert® (Diagnostica Stago, France) for the detection in ICU patients suspected for HIT. Patients-methodsSeventy two patients (40 males/32 females) hospitalized in ICU from January to June 2012 were included. Thirty one patients presented with sepsis, 27 underwent extracorporeal circulation (ECC), 21 were hemodialysed and 3 patients were receiving chemotherapy. Sixty one patients were treated with unfractionated heparin and 11 patients received low molecular weight heparin (LMWH). A 4T’s score was performed for all patients. All samples were tested in polyspecific ELISA (Zymutest Hyphen Biomed, Neuville-Sur-Oise, France), STic HIT Expert® (Diagnostica Stago, France) and serotonin release assay. In case of a positive polyspecific ELISA, IgG, IgM et IgA isotypes were also performed. Sensitivity, specificity, positive and negative predictive values (PPV an NPV) of STic HIT Expert® were determined against SRA. ResultsAll three tests (polyspecific ELISA, STic HIT Expert®, SRA) were negative in forty patients and had a low HIT suspicion (4T’s score: 0–4). In 10 out of 72 patients polyspecific all immunological tests and SRA were positive and HIT suspicion was intermediate or high (4T’s score: 4–7). In 9 patients, ELISA tests and STic HIT Expert® were positive but SRA was negative. These patients had a low HIT suspicion (4T’s score: 1–4) and underwent ECC (6 out of 9), were hemodialyzed (3 out of 9) or complicated by sepsis (2 out of 9). On the other hand 13 out of 72 patients had ELISA tests positive but STic HIT Expert® and SRA negative. The prevalence of sepsis was high in these patients (8 out of 13), 3 patients underwent ECC and one patient was hemodialysed. STic HIT Expert®, polyspecific and IgG specific ELISA had an excellent sensitivity and negative predictive value at 100%. Moreover STic HIT Expert® was associated with a smaller number of false positive results than the ELISAs. (Table)TableResults of Stic expert, polyspecific and IgG specific ELISA against SRASRA positiveSRA negativeSensitivity %Specificity %PPV %NPV %STic HIT® expertPositive1091008553100Negative053Polyspecific ELISAPositive10221003531100Negative040IgG specific ELISAPositive10181007136100Negative044 ConclusionSTic HIT Expert® has an excellent performance with a high negative predictive value (100%) and a satisfactory specificity (85%). Less false positive results are detected with STic HIT Expert® than with polyspecific and IgG specific ELISAs. Moreover the test offers a shorter turnaround than ELISA tests and is an easy-to-use single sample test. These characteristics could help avoid HIT over diagnosis in ICU patients. Disclosures:No relevant conflicts of interest to declare.

An in-Vitro Model Using Thromboelastography to Evaluate the Effects of Anticoagulants On Clot Formation in Plasma Enriched with Autologous Platelets

Abstract 1091 Background:In the presence of thrombocytopenia, antithrombotic therapy in patients with thrombosis is a challenge for the managing physicians. Current guidelines are based on anecdotal data and expert opinion. Hereby, we used an in-vitro model with thrombelastography (TEG) to study the interactions of anticoagulants with plasma clotting proteins and varying concentrations of platelets. The objective of this study is to better elucidate the range of platelet concentrations in plasma which will permit clot formation in the presence of anticoagulant. Methods:Fresh human platelet-rich plasma and platelet-poor plasma were obtained from the same donors to produce plasma samples with predefined platelet counts. For each experiment, these samples were incubated with a reaction mixture containing 30 μg/mL corn trypsin inhibitor and one of the following anticoagulants at therapeutic concentrations: heparin (0.3 IU/mL), dalteparin (1.0 IU/mL), fondaparinux (1.25 mg/L), rivaroxaban (150 ng/mL) or dabigatran (180 ng/mL). Clotting was initiated with 10 mM CaCl2 and tissue factor (TF) (Thromborel® S). The amount of tissue factor for each anticoagulant was pre-optimized so that the plasma did not clot in the absence of platelets but the clotting time would return to baseline when platelet count increased to 150 x109/L, corresponding to the expected clinical profile. All parameters for TEG (R,a, MA, TMA) were monitored for 180 min. The area under the curve for each TEG tracing in the first 15 min (AUC15) after clot initiation was estimated as it represents a global measurement of clot strength during its formation. Williams’ t-test was used to compare multiple data points with its corresponding baseline control. A p < 0.05 was considered statistically significant. Results:The TF concentration in Thromborel S® was 3140 pM as determined by ELISA. We found that the optimal TF concentrations required for each anticoagulant were 1.2 pM, 0.7 pM, 0.07 pM for heparin, dalteparin, and fondaparinux respectively. No extrinsic tissue factor was required for rivaroxaban and dabigatran. In the presence of an anticoagulant, clot formation was significantly delayed when platelet counts were below 50 x109/L (fig.1). In contrast, when platelet counts were between 50–150 x109/L, there were no significant differences in all TEG parameters. The AUC15 linearly decreased when platelet counts fell below 150 x109/L. In the presence of heparinoids, the overall AUCs are reduced by an average of 6-fold comparing to the controls without anticoagulants (fig.2). In the presence of rivaroxaban or dabigatran the reduction in the overall AUCs was minimal compared to the heparinoids. The slopes of AUC15 against platelet count in the heparinoids were similar, with an average slope of 15. In contrast, the direct factor specific anticoagulants had distinctly different slopes that averaged at 56. Conclusion:Our findings suggest that, in the presence of therapeutic concentration of an anticoagulant, coagulation is delayed when platelet count is below 50 x109/L and clot formation is globally attenuated with lower platelet counts. Due to the fact that the clotting time is significantly prolonged when platelet counts fall below the threshold of 50 x109/L, we recommend withholding or reducing anticoagulants when patients with thrombocytopenia have platelet counts lower than this level. This data is consistent with the current clinical practice in adult population. Furthermore, since rivaroxaban and dabigatran required no extrinsic TF to initiate clot formation in our model, these new anticoagulants may have a wider safety margins for the treatment of thrombosis in thrombocytopenic patients. Yet, without the availability of specific antidote for these new anticoagulants, their use in patients with high bleeding risk warrants further evaluation. [Display omitted] [Display omitted] Disclosures:No relevant conflicts of interest to declare.

786 Low Platelet Count is Associated with Ductus Arteriosus Patency in Preterm Newborns

Background and AimsTo determine whether there is an association between platelet counts and patent ductus arteriosus (PDA) incidence and/or closure in preterm newborns.MethodsPremature infants with hemodynamically significant PDA (n=154) and...

Thrombocytopenia as an Indicator of Malaria in Adult Population

Objectives. To evaluate the predictive value of thrombocytopenia in malaria. Patients and Methods. It was a prospective observational study on all febrile patients with thrombocytopenia presenting to the Medical Unit of Hayat Abad Medical Complex during November 2008 to November 2010. Results. Of the total of 228 patients with fever and thrombocytopenia, 121 patients (53%) proved to be suffering from malaria. Of them 82 patients (68%) had falciparum malaria while 39 patients (32%) had vivax infection. Of these 121 patients, platelet counts ranged between 25,000 and 150,000/dL with a mean value of 101,000/dL (SD ± 47, 500) and a median of 75,000/dL. Of the 107 patients who were not suffering from malaria, the counts ranged between 10,000 and 150,000/dL with a mean value of 58,000/dL (SD ± 54, 000) and median of 50,000/dL. Conclusions. The presence of thrombocytopenia may be a predictor of malaria in adult population.

Low platelet count is associated with ductus arteriosus patency in preterm newborns

Background/aimTo determine whether there is an association between platelet counts and patent ductus arteriosus (PDA) incidence and/or closure in preterm newborns. Study design and subjectsPremature infants with hemodynamically significant PDA (n=154) and a control group without PDA (n=207) who were hospitalized in the NICU were retrospectively evaluated. Platelet counts and other platelet indices including mean platelet volume (MPV) and platelet distribution width (PDW) of the infants in both groups during the first 3days of life were recorded. Ibuprofen was started in infants with hemodynamically significant PDA and echocardiography was repeated 48h thereafter to assess the closure of ductus. ResultsMedian gestational age and birth weight of the infants with PDA were 28 (range 26–29) weeks and 1060 (range 892–1250) g respectively. Platelet counts were significantly lower in the patient group than in the control group (p<0.001). Multivariate analysis including gestational age, presence of RDS, presence of thrombocytopenia and PDW showed that hemodynamically significant PDA was independently associated with platelet count <150,000 (OR=2.13, 95% CI 1.26–3.61; p=0.005), high PDW (>17) (OR=2.68, 95% CI 1.41–5.09; p=0.003) and the presence of RDS (OR=2.25, 95% CI 1.41–3.59; p=0.001). Baseline platelet counts of the infants in whom ductus closed or persisted after ibuprofen treatment were similar. ConclusionsPDA was associated with low platelet count and high PDW but not with other platelet indices in preterm infants. We could not show an association between platelet counts and persistence or closure after medical treatment.

Identification of two HCC phenotypes based on thrombocytopenia.

e14720 Background: Clinical phenotypes of small and larger HCCs are not well characterized. Aims. To characterize small HCC phenotypes. Methods: A cohort of 430 small HCCs that were diagnosed through screening, were dichotomized by size of &lt; 3cm or &gt; 3cm maximum tumor diameter and compared for radiologic and blood test parameters and analyzed by Chi-square test for categorical variables and Mann-Whitney test for continuous variables. Results: Significant differences between the tumor size groups included AFP values and platelet counts, with thrombocytopenia and elevated bilirubin levels being associated with smaller tumors. In comparing PVT+ and PVT- patients, AFP levels and platelet counts were also significantly different between the 2 groups. Conclusions: Larger tumors were associated with normal platelets and bilirubin levels, compared to smaller tumors that were more typically found in the presence of thrombocytopenia, suggesting that smaller and larger HCCs might have different developmental pathways.

Tromboembolismo pulmonar no sospechado en el Servicio de Urgencias

Background and objectivesPulmonary embolism (PE) is a disease that sometimes has a significant delay in diagnosis. This situation may lead to an increase in morbidity and mortality in patients who have it. The aim of our study has been to define the clinical profile of patients with unsuspected PE in the emergency department and the factors that influence the delayed diagnosis. Patients and methodsA total of 148 patients admitted with diagnosis of PE confirmed by CT (n=133) or by high-probability ventilation-perfusion scintigraphy scan (n=15) were retrospectively analyzed. They were divided into two groups: those with unsuspected disease in the emergency department (USPE) and those who it was suspected (SPE). Baseline characteristics of the patients, risk factors, signs and symptoms in the emergency department, complementary test, days of hospitalization and mortality were studied. ResultsThe USPE was found in 63/148 patients (42.6%) in the emergency department. Dyspnea and chest pain were the most frequent clinical manifestations of this disease, this being more commonly identified in the SPE group than in the USPE group, with significant differences (OR=0.4 [0.2-0.9] for dyspnea and OR=0.3 [0.2-0.7] for chest pain). However, However, the presence of thrombocytopenia (OR=3.4 [1.1-10.2], P<.05), normal electrocardiogram (EC) (OR=3.4 [1.1-10.2], P<.05), and localization of PE in right lung (OR=4.7 [2-11.3], P<.001) were risk factors for not suspect it. Days of hospitalization, days of symptoms and mortality were not statistically different between groups. ConclusionsAccording to the results, the proportion of unsuspected PE in the emergency department was high (close to 40%). The presence of dyspnea and chest pain was associated to suspicion of SPE. On the contrary, the presence of thrombocytopenia, normal EC and right localization of PE were associated to the non-suspicion of SPE in the emergency department.

Recommendations of the Infectious Diseases Work Group (GTEI) of the Spanish Society of Intensive and Critical Care Medicine and Coronary Units (SEMICYUC) and the Infections in Critically Ill Patients Study Group (GEIPC) of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) for the diagnosis and treatment of influenza A/H1N1 in seriously ill adults admitted to the Intensive Care

The diagnosis of influenza A/H1N1 is mainly clinical, particularly during peak or seasonal flu outbreaks. A diagnostic test should be performed in all patients with fever and flu symptoms that require hospitalization. The respiratory sample (nasal or pharyngeal exudate or deeper sample in intubated patients) should be obtained as soon as possible, with the immediate start of empirical antiviral treatment.Molecular methods based on nucleic acid amplification techniques (RT-PCR) are the gold standard for the diagnosis of influenza A/H1N1. Immunochromatographic methods have low sensitivity; a negative result therefore does not rule out active infection. Classical culture is slow and has low sensitivity. Direct immunofluorescence offers a sensitivity of 90%, but requires a sample of high quality. Indirect methods for detecting antibodies are only of epidemiological interest.Patients with A/H1N1 flu may have relative leukopenia and elevated serum levels of LDH, CPK and CRP, but none of these variables are independently associated to the prognosis. However, plasma LDH>1500IU/L, and the presence of thrombocytopenia <150×109/L, could define a patient population at risk of suffering serious complications.Antiviral administration (oseltamivir) should start early (<48h from the onset of symptoms), with a dose of 75mg every 12h, and with a duration of at least 7 days or until clinical improvement is observed. Early antiviral administration is associated to improved survival in critically ill patients. New antiviral drugs, especially those formulated for intravenous administration, may be the best choice in future epidemics.Patients with a high suspicion of influenza A/H1N1 infection must continue with antiviral treatment, regardless of the negative results of initial tests, unless an alternative diagnosis can be established or clinical criteria suggest a low probability of influenza.In patients with influenza A/H1N1 pneumonia, empirical antibiotic therapy should be provided due to the possibility of bacterial coinfection. A beta-lactam plus a macrolide should be administered as soon as possible. The microbiological findings and clinical or laboratory test variables may decide withdrawal or non-withdrawal of antibiotic treatment. Pneumococcal vaccination is recommended as a preventive measure in the population at risk of suffering severe complications.Although the use of moderate- or low-dose corticosteroids has been proposed for the treatment of influenza A/H1N1 pneumonia, the existing scientific evidence is not sufficient to recommend the use of corticosteroids in these patients.The treatment of acute respiratory distress syndrome in patients with influenza A/H1N1 must be based on the use of a protective ventilatory strategy (tidal volume <10ml/kg and plateau pressure <35mmHg) and positive end-expiratory pressure set to high patient lung mechanics, combined with the use of prone ventilation, muscle relaxation and recruitment maneuvers. Noninvasive mechanical ventilation cannot be considered a technique of choice in patients with acute respiratory distress syndrome, though it may be useful in experienced centers and in cases of respiratory failure associated with chronic obstructive pulmonary disease exacerbation or heart failure.Extracorporeal membrane oxygenation is a rescue technique in refractory acute respiratory distress syndrome due to influenza A/H1N1 infection. The scientific evidence is weak, however, and extracorporeal membrane oxygenation is not the technique of choice. Extracorporeal membrane oxygenation will be advisable if all other options have failed to improve oxygenation. The centralization of extracorporeal membrane oxygenation in referral hospitals is recommended. Clinical findings show 50–60% survival rates in patients treated with this technique.Cardiovascular complications of influenza A/H1N1 are common. Such problems may appear due to the deterioration of pre-existing cardiomyopathy, myocarditis, ischemic heart disease and right ventricular dysfunction. Early diagnosis and adequate monitoring allow the start of effective treatment, and in severe cases help decide the use of circulatory support systems.Influenza vaccination is recommended for all patients at risk. This indication in turn could be extended to all subjects over 6 months of age, unless contraindicated. Children should receive two doses (one per month). Immunocompromised patients and the population at risk should receive one dose and another dose annually. The frequency of adverse effects of the vaccine against A/H1N1 flu is similar to that of seasonal flu. Chemoprophylaxis must always be considered a supplement to vaccination, and is indicated in people at high risk of complications, as well as in healthcare personnel who have been exposed.

Syndrome d’Evans : attention aux diagnostics par excès

IntroductionEvans syndrome (ES) is characterized by the coexistence of an autoimmune hemolytic anemia (AIHA) and immune thrombocytopenic purpura (ITP). Despite being frequently evocated in the simultaneous presence of anemia and thrombocytopenia, this rare disease only accounts for 0.8 to 3.7% of patients with ITP or AIHA. Case reportsWe report three suspected cases of ES, diagnosed in the presence of thrombocytopenia and hemolytic anemia association, with a positive direct Coombs test in two patients. Standard ES treatment failure and occurrence of aditional features subsequently led to correct diagnosis to thrombotic thrombocytopenic purpura, myelodysplastic syndrome with AIHA, and ITP with hemorrhagic anemia, respectively. ConclusionBicytopenias, even in an immunological context, are not sufficient to ascertain ES diagnosis. Our cases illustrate the diagnostic difficulties that may arise in daily practice, and induce over-diagnosis of this rare disease.

Recomendaciones del Grupo de Trabajo Enfermedades Infecciosas (GTEI) de la Sociedad Española de Medicina Intensiva, Crítica y Unidades Coronarias (SEMICYUC) y el Grupo de Estudio de Infecciones en el Paciente Crítico (GEIPC) de la Sociedad Española de Enfermedades Infecciosas y Microbiología clínica (SEIMC) para el diagnóstico y tratamiento de la gripe A/H1N1 en pacientes adultos graves hospitalizados en las Unidades

The diagnosis of influenza A/H1N1 is mainly clinical, particularly during peak or seasonal flu outbreaks. A diagnostic test should be performed in all patients with fever and flu symptoms that require hospitalization. The respiratory sample (nasal or pharyngeal exudate or deeper sample in intubated patients) should be obtained as soon as possible, with the immediate start of empirical antiviral treatment.Molecular methods based on nucleic acid amplification techniques (RT-PCR) are the gold standard for the diagnosis of influenza A/H1N1. Immunochromatographic methods have low sensitivity; a negative result therefore does not rule out active infection. Classical culture is slow and has low sensitivity. Direct immunofluorescence offers a sensitivity of 90%, but requires a sample of high quality. Indirect methods for detecting antibodies are only of epidemiological interest.Patients with A/H1N1 flu may have relative leukopenia and elevated serum levels of LDH, CPK and CRP, but none of these variables are independently associated to the prognosis. However, plasma LDH> 1500 IU/L, and the presence of thrombocytopenia <150x109/L, could define a patient population at risk of suffering serious complications.Antiviral administration (oseltamivir) should start early (<48h from the onset of symptoms), with a dose of 75mg every 12h, and with a duration of at least 7 days or until clinical improvement is observed. Early antiviral administration is associated to improved survival in critically ill patients. New antiviral drugs, especially those formulated for intravenous administration, may be the best choice in future epidemics.Patients with a high suspicion of influenza A/H1N1 infection must continue with antiviral treatment, regardless of the negative results of initial tests, unless an alternative diagnosis can be established or clinical criteria suggest a low probability of influenza.In patients with influenza A/H1N1 pneumonia, empirical antibiotic therapy should be provided due to the possibility of bacterial coinfection. A beta-lactam plus a macrolide should be administered as soon as possible. The microbiological findings and clinical or laboratory test variables may decide withdrawal or not of antibiotic treatment. Pneumococcal vaccination is recommended as a preventive measure in the population at risk of suffering severe complications.Although the use of moderate- or low-dose corticosteroids has been proposed for the treatment of influenza A/H1N1 pneumonia, the existing scientific evidence is not sufficient to recommend the use of corticosteroids in these patients.The treatment of acute respiratory distress syndrome in patients with influenza A/H1N1 must be based on the use of a protective ventilatory strategy (tidal volume <10ml / kg and plateau pressure <35mmHg) and positive end-expiratory pressure set to high patient lung mechanics, combined with the use of prone ventilation, muscle relaxation and recruitment maneuvers. Noninvasive mechanical ventilation cannot be considered a technique of choice in patients with acute respiratory distress syndrome, though it may be useful in experienced centers and in cases of respiratory failure associated with chronic obstructive pulmonary disease exacerbation or heart failure.Extracorporeal membrane oxygenation is a rescue technique in refractory acute respiratory distress syndrome due to influenza A/H1N1 infection. The scientific evidence is weak, however, and extracorporeal membrane oxygenation is not the technique of choice. Extracorporeal membrane oxygenation will be advisable if all other options have failed to improve oxygenation. The centralization of extracorporeal membrane oxygenation in referral hospitals is recommended. Clinical findings show 50-60% survival rates in patients treated with this technique.Cardiovascular complications of influenza A/H1N1 are common. Such problems may appear due to the deterioration of pre-existing cardiomyopathy, myocarditis, ischemic heart disease and right ventricular dysfunction. Early diagnosis and adequate monitoring allow the start of effective treatment, and in severe cases help decide the use of circulatory support systems.Influenza vaccination is recommended for all patients at risk. This indication in turn could be extended to all subjects over 6 months of age, unless contraindicated. Children should receive two doses (one per month). Immunocompromised patients and the population at risk should receive one dose and another dose annually. The frequency of adverse effects of the vaccine against A/H1N1 flu is similar to that of seasonal flu. Chemoprophylaxis must always be considered a supplement to vaccination, and is indicated in people at high risk of complications, as well in healthcare personnel who have been exposed.

Cancer and Cardiovascular Disease. A New Entity

Cancer and cardiovascular disease (CVD) are the two most common cause of mortality [1]. With an increase in the aging population worldwide, it is not uncommon for these two conditions to coexist. Amongst older patients diagnosed with cancer, heart and vascular disease is the most frequent concomitant condition [2]. About 20% of patients older than 70 years of age with newly diagnosed cancer have coexisting CVD [2]. Patients with a recent diagnosis of cancer also have an increased risk of death from cardiovascular causes [3]. Among patients undergoing coronary revascularization, greater than 50% of the deaths are due to non cardiac causes, of which 20% are related to neoplasia [4]. CVD sometimes precedes the diagnosis of cancer and can also occur as a complication of cancer therapy. Cancer and its treatment can also accelerate or worsen pre-existing cardiac disease. Both chemotherapy and radiation causes long term cardiovascular side effects. Chemotherapy agents can cause a wide range of cardiotoxicity, ranging from vascular events to heart failure and cardiomyopathy [5]. Some of the common agents predisposing to chemotherapy induced cardiomyopathy include anthracyclines and trastuzumab [6]. Certain other newer agents such as tyrosine kinase inhibitors and some newer investigational agents have also been recognized to cause cardiac side effects [6]. Radiation causes long term side effects which can affect the pericardium, valves, conduction system and myocardium [7]. Management of underlying cardiac disease may pose complex problem in patients with cancer. Due to concern about bleeding, presence of thrombocytopenia, poses particular problem in the management of patients with coronary stents or prosthetic valve. Due to exclusion of cancer patients from large cardiovascular clinical trials, there is limited data available on the treatment of cardiac disease in cancer population. Physicians involved in the care of patients with cancer should have a low threshold for screening and treating patients with cardiac side effects of cancer and its treatment. The key is early detection of these side effects, as treatment in these cases may halt the disease process or in some cases even reverse it. In patients with chemotherapy induced cardiomyopathy, treatment with standard cardiac medications like beta blockers and angiotensin converting enzyme inhibitors, will improve left ventricular ejection fraction, in particular if cardiomyopathy is detected early and therapy started promptly [8].