Management of thrombocytopenia in advanced liver disease

Thrombocytopenia (defined as a platelet count <150×10⁹/L) is a well-known complication in patients with liver cirrhosis and has been observed in 76% to 85% of patients. Significant thrombocytopenia (platelet count <50×10⁹/L to 75×10⁹/L) occurs in approximately 13% of patients with cirrhosis. Thrombocytopenia can negatively impact the care of patients with severe liver disease by potentially interfering with diagnostic and therapeutic procedures. Multiple factors can contribute to the development of thrombocytopenia including splenic platelet sequestration, immunological processes, bone marrow suppression by chronic viral infection, and reduced levels or activity of the hematopoietic growth factor thrombopoietin. The present review focuses on the etiologies and management options for severe thrombocytopenia in the setting of advanced liver disease.     

Analysis of 12,517 inhabitants of a Sardinian geographic isolate reveals that predispositions to thrombocytopenia and thrombocytosis are inherited traits

Background

Thrombocytopenia is a common finding in several diseases but almost nothing is known about the prevalence of thrombocytopenia in the general population. We examined the prevalence of thrombocytopenia and determinants of platelet count in a healthy population with a wide age range.

Design and Methods

We performed a cross-sectional study on 12,517 inhabitants of ten villages (80% of residents) in a secluded area of Sardinia (Ogliastra). Participants underwent a complete blood count evaluation and a structured questionnaire, used to collect epidemiological data.

Results

We observed a platelet count lower than 150×10⁹/L in 3.2% (2.8%–3.6%) of females and 4.8% (4.3%–5.4%) of males, with a value of 3.9% (3.6%–4.3%) in the entire population. Thrombocytopenia was mild (platelet count: 100×10⁹/L–150×10⁹/L), asymptomatic and not associated with other cytopenias or overt disorders in most cases. Its standardized prevalence was quite different in different villages, with values ranging from 1.5% to 6.8%, and was negatively correlated with the prevalence of a mild form of thrombocytosis, which ranged from 0.9% to 4.5%. Analysis of platelet counts across classes of age revealed that platelet number decreased progressively with aging. As a consequence, thrombocytopenia was nearly absent in young people and its prevalence increased regularly during lifetime. The opposite occurred for thrombocytosis.

Conclusions

Given the high genetic differentiation among Ogliastra villages with “high” and “low” platelet counts and the substantial heritability of this quantitative trait (54%), we concluded that the propensity to present mild and transient thrombocytosis in youth and to acquire mild thrombocytopenia during aging are new genetic traits.     

Associations of Baseline and Changes in Leukocyte Counts with Incident Cardiovascular Events: The Dongfeng-Tongji Cohort Study

Aim: The aim of the present study was to investigate the associations of baseline and longitudinal changes in leukocyte counts with incident cardiovascular disease (CVD). Methods: We conducted a prospective study to investigate the associations of baseline and 5-year changes in leukocyte counts with incident CVD and its subtypes in middle-aged and elderly Chinese. We estimated the hazard ratios (HRs) and 95% confidence intervals (CIs) for CVD using the Cox proportional-hazards models. Results: In the analyses of baseline total leukocyte count of 26,655 participants, compared with the lowest quartile (＜4.71×10⁹/L), participants in the fourth quartile (＞6.70×10⁹/L) had 11% higher risk for CVD. Consistent with total leukocyte count, neutrophil count also exhibited a significant positive association with the risk of CVD. In the analyses of 5-year changes in total leukocyte count of 11,594 participants, the changes in leukocyte count were categorized into three groups, i.e., the decreased group (＜25%), stable group (25%–75%), and increased group (＞75%). Compared with participants in the stable group (−1.18 to 0.44×10⁹/L), participants in the increased group (＞0.44×10⁹/L) had 14% higher risk for CVD. We also observed significant positive associations of the changes in neutrophil and monocyte counts with the risk of CVD. Furthermore, the total leukocyte count in the second or third tertile at the first follow-up with a 5-year increase was related to higher CVD risk. Conclusion: High baseline total leukocyte count and a 5-year increase in total leukocyte count were related to higher CVD risk.     

Differentiating chronic lymphocytic leukemia from monoclonal B-lymphocytosis according to clinical outcome: on behalf of the GIMEMA chronic lymphoproliferative diseases working group

Background

Optimal lymphocyte parameters and thresholds for the diagnosis of chronic lymphocytic leukemia have been proposed by The National Cancer Institute sponsored Working Group and recently updated by the International Workshop on chronic lymphocytic leukemia. However, it is not clear how these criteria apply to patient management in daily clinical practice and whether the lymphocyte thresholds recommended truly predict clinical outcome in early chronic lymphocytic leukemia.

Design and Methods

For the purpose of this study, an observational database of the GIMEMA (Gruppo Italiano Malattie Ematologiche dell’Adulto) which included 1,158 patients with newly diagnosed Binet stage A chronic lymphocytic leukemia who were observed at different primary hematology centers during the period 1991–2000, was used.

Results

Among 818 consecutive chronic lymphocytic leukemia patients with Rai stage 0 (i.e. no palpable lymphadenopathy or hepatosplenomegaly) who had flow cytometry evaluations at the time of diagnosis and were included in a GIMEMA database, both absolute lymphocyte count and B-cell count were of a similar value in predicting time to first treatment as continuous variables (P<0.0001). Receiver operating characteristic analysis identified an absolute lymphocyte count of 11.5×10⁹/L and an absolute B-cell count of 10.0×10⁹/L as the best thresholds capable of identifying patients who will require treatment from those with stable disease. However, in a Cox’s multivariate analysis only the B-cell count retained its discriminating power (P<0.0001) and the estimated rate of progression to chronic lymphocytic leukemia requiring treatment among subjects with a B-cell count less than 10.0×10⁹/L was approximately 2.3% per year (95% CI 2.1–2.5%) while it was 2-fold higher for patients with a B-cell count of 10.0×10⁹/L or over (i.e. 5.2% per year; 95% CI 4.9–5.5%). Finally, in this community-based patient cohort, the B-cell threshold defined by investigators at the Mayo Clinic (i.e. 11.0×10⁹/L) allowed patients to be divided into two subsets with a higher and lower likelihood of treatment (P<0.0001).

Conclusions

Our results, based on a retrospective patients’ cohort, provide a clear justification to retain the B-cell count as the reference gold standard of chronic lymphocytic leukemia diagnosis and imply that a count of 10×10⁹/L B cells is the best lymphocyte threshold to predict time to first treatment. The use of clinical outcome to distinguish chronic lymphocytic leukemia from other premalignant conditions, such as monoclonal B-cell lymphocytosis, is a pragmatic approach meeting the patients’ need to minimize the psychological discomfort of receiving a diagnosis of leukemia when the risk of adverse clinical consequences is low.     

C-Reactive Protein and White Blood Cell Count as Triage Test Between Urgent and Nonurgent Conditions in 2961 Patients With Acute Abdominal Pain

The purpose of this article is to assess the diagnostic accuracy of C-reactive protein (CRP) and white blood cell (WBC) count to discriminate between urgent and nonurgent conditions in patients with acute abdominal pain at the emergency department, thereby guiding the selection of patients for immediate diagnostic imaging.Data from 3 large published prospective cohort studies of patients with acute abdominal pain were combined in an individual patient data meta-analysis. CRP levels and WBC counts were compared between patients with urgent and nonurgent final diagnoses. Parameters of diagnostic accuracy were calculated for clinically applicable cutoff values of CRP levels and WBC count, and for combinations.A total of 2961 patients were included of which 1352 patients (45.6%) had an urgent final diagnosis. The median WBC count and CRP levels were significantly higher in the urgent group than in the nonurgent group (12.8 ×10⁹/L; interquartile range [IQR] 9.9–16) versus (9.3 ×10⁹/L; IQR 7.2–12.1) and (46 mg/L; IQR 12–100 versus 10 mg/L; IQR 7–26) (P < 0.001).The highest positive predictive value (PPV) (85.5%) and lowest false positives (14.5%) were reached when cutoff values of CRP level >50 mg/L and WBC count >15 ×10⁹/L were combined; however, 85.3% of urgent cases was missed.A high CRP level (>50 mg/L) combined with a high WBC count (>15 ×10⁹/L) leads to the highest PPV. However, this applies only to a small subgroup of patients (8.7%). Overall, CRP levels and WBC count are insufficient markers to be used as a triage test in the selection for diagnostic imaging, even with a longer duration of complaints (>48 hours).     

Clinico-Pathological Spectrum of Primary Plasma Cell Leukemia Diagnosed at a Tertiary Care Centre in South India Over 5?Year Period

Plasma cell leukemia (PCL) represents a rare and aggressive form of plasma cell dyscrasia which can be primary (pPCL) or secondary (sPCL). It is diagnosed based on absolute plasma cell count of more than 2.0 × 10⁹/l or a relative proportion of greater than 20% of the peripheral blood leukocyte count. Although pPCL and sPCL share several clinical features, important differences exist. Patients with pPCL are younger; often have extra osseous organ involvement (liver, spleen and other extramedullary sites), increased frequency of renal failure, fast declining performance status and rapid progression to the terminal stage. Patients with sPCL have advanced bone disease. Presented in this article is India data of a short series of five cases of PCL diagnosed at a tertiary care centre from south India over last 5 years. All cases were de novo and had varied spectrum of presentation and so were not suspected to be plasma cell dyscrasia clinically. Detailed hemato-pathological evaluation clinched the diagnosis in all the cases.     

Vanishing Platelets: Rapid and Extreme Tirofiban-Induced Thrombocytopenia after Percutaneous Coronary Intervention for Acute Myocardial Infarction

Glycoprotein IIb/IIIa inhibitors are established treatment for patients who develop acute coronary syndromes. Thrombocytopenia is known to occur following the administration of various drugs, including heparin and glycoprotein IIb/IIIa inhibitors. In the case of glycoprotein IIb/IIIa inhibitors, the mechanism is thought to be drug-dependent antibodies. In most cases, the thrombocytopenia is mild or moderate in severity. Severe thrombocytopenia (platelet count, <50 × 10⁹/L) is distinctly rare.Herein, we report a case of tirofiban-induced thrombocytopenia in which the overall platelet count dropped precipitously to <1 × 10⁹/L within 12 hours of administration; recovery was relatively prolonged, possibly owing to concomitant renal insufficiency. The severity and the rapidity of onset emphasize the need to routinely check platelet counts early after tirofiban administration, in order to prevent sequelae.Key words: Acute coronary syndromes, glycoprotein IIb/IIIa inhibitors, percutaneous coronary intervention, thrombocytopenia, tirofibanGlycoprotein IIb/IIIa inhibitors (GPIs) are now established treatment for patients who develop acute coronary syndromes before, during, and after percutaneous coronary intervention (PCI). Thrombocytopenia is known to occur after the administration of various drugs, including heparin and GPIs.¹ In the case of GPIs, the mechanism is thought to be drug-dependent antibodies.^1–3 In most cases, the thrombocytopenia is mild or moderate in severity, and a severe (<50 × 10⁹/L) decline in platelet count is distinctly rare—usually under 2% in clinical trials.^4–7We report a case of tirofiban-induced thrombocytopenia in which overall platelet count dropped precipitously to <1 × 10⁹/L within 12 hours, followed by the patient''s relatively prolonged recovery, probably due to concomitant renal insufficiency. The rapidity of onset and the lack of bleeding manifestations emphasize the need to routinely check platelet counts early after tirofiban administration, in order to prevent sequelae.     

HEF-19-induced relaxation of colonic smooth muscles and the underlying mechanisms

AIM:To investigate the relaxant effect of chromane HEF-19 on colonic smooth muscles isolated from rabbits,and the underlying mechanisms.METHODS:The relaxant effect and action mechanisms of HEF-19 were investigated using descending colon smooth muscle of the rabbits.Preparations 1 cm long were mounted in 15-mL tissue baths containing Tyrode’s solution,maintained at 37±0.5℃and aerated with a mixture of 5%CO2in oxygen(Carbogen).The tension and amplitude of the smooth muscle strips were recorded after adding HEF-19(10-6,10-5and 10-4mol/L).After cumulative administration of four antispasmodic agents,including acetylcholine chloride(Ach)(10-4mol/L),histamine(10-4mol/L),high-K+(60 mmol/L)and BaCl2(8.2 mmol/L),HEF-19(3×10-7-3×10-4mol/L)was added to investigate the relaxant effect of HEF-19.CaCl2(10-4-2.5×10-3mol/L)was added cumulatively to the smooth muscle preparations pretreated with and without HEF-19(1×10-6or 3×10-6mol/L)and verapamil(1×10-7mol/L)to study the mechanisms involved.Finally,phasic contraction was induced with ACh(15×10-6mol/L),and CaCl2(4×10-3mol/L)was added to the smooth muscle preparations pretreated with and without HEF-19(3×10-6mol/L or 1×10-5mol/L)and verapamil(1×10-7mol/L)in calcium-free medium to further study the underlying mechanisms.RESULTS:HEF-19(1×10-6,1×10-5and 1×10-4mol/L)suppressed spontaneous contraction of rabbit colonic smooth muscles.HEF-19(3×10-7-3×10-4mol/L)relaxed in a concentration-dependent manner colonic smooth muscle preparations pre-contracted with BaCl2,high-K+solution,Ach or histamine with respective EC50values of 5.15±0.05,5.12±0.08,5.58±0.16and 5.25±0.24,thus showing a spasmolytic activity.HEF-19(1×10-6mol/L and 3×10-6mol/L)shifted the concentration-response curves of CaCl2to the right and depressed the maximum response to CaCl2.The two components contracted by Ach were attenuated with HEF-19(3×10-6mol/L or 10-5mol/L)in calcium-free medium.CONCLUSION:HEF-19 inhibited rabbit colonic smooth muscle contraction,probably through inhibiting opening of     

Causes of Thrombocytosis: A Single-center Retrospective Study of 1,202 Patients

Objective Thrombocytosis can occur as a primary event accompanying hematological diseases or as a secondary event. Since the publication of the World Health Organization classification in 2008, thrombocytosis is now generally defined as a platelet count above 450×10⁹/L. Furthermore, the discovery of driver-gene mutations in myeloproliferative neoplasms (MPNs) has simplified the diagnostic approach for thrombocytosis. To identify the causes of thrombocytosis using this new definition, we conducted a retrospective study. Methods We identified outpatients and inpatients aged 20 years or older with platelet counts ＞450×10⁹/L in a half-year period at a single institute and analyzed the causes of thrombocytosis and associated clinical characteristics. Results Among 1,202 patients with thrombocytosis, 150 (12.5%) had primary and 999 (83.1%) had secondary thrombocytosis. Of these patients with primary thrombocytosis, 129 (86%) had at least 1 molecular marker indicative of MPNs. The major causes of secondary thrombocytosis were tissue injury (32.2%), infection (17.1%), chronic inflammatory disorders (11.7%) and iron deficiency anemia (11.1%). The median platelet count and the incidence of thrombosis were significantly higher in patients with primary thrombocytosis than in those with secondary thrombocytosis. Conclusion Thrombocytosis mainly occurs as a secondary event; however, it is important to determine the cause of and prevent thrombosis, particularly in cases of primary thrombocytosis.     

Fetal alloimmune thrombocytopenia and maternal intravenous immunoglobulin infusion

Background

Different therapeutic approaches have been used in fetal-neonatal alloimmune thrombocytopenia, but many centers administer immunoglobulin G infusions to the pregnant woman. We studied the effect of maternal antenatal immunoglobulin infusions on fetal platelet counts in pregnancies with fetal alloimmune thrombocytopenia.

Design and Methods

We retrospectively analyzed the clinical courses of fetuses with fetal alloimmune thrombocytopenia whose mothers were treated with immunoglobulin G infusions in a single center between 1999 and 2005. In a center-specific protocol, weekly maternal immunoglobulin G infusions were given to 25 pregnant women with previously affected neonates and four women with strong platelet antibodies, but no previous history of fetal alloimmune thrombocytopenia; before each infusion diagnostic fetal blood sampling was performed to determine fetal platelet counts and immunoglobulin G levels.

Results

There were 30 fetuses with fetal alloimmune thrombocytopenia, confirmed by initial fetal blood sampling showing fetal platelet counts between 4×10⁹/L and 130×10⁹/L and antibody-coated fetal platelets using a glycoprotein specific assay. Despite weekly antenatal maternal immunoglobulin G infusions fetal platelet counts did not change significantly. Maternal and fetal immunoglobulin G levels, measured before every infusion, increased significantly with the number of maternal immunoglobulin G infusions.

Conclusions

In this group of fetuses with fetal alloimmune thrombocytopenia no consistent increase of fetal platelets was achieved as a result of regular maternal immunoglobulin G infusions.     

Trends in cord blood banking

Background

Umbilical cord blood (UCB) is a source of hematopoietic precursor cells for transplantation. The creation of UCB banks in 1992 led to the possibility of storing units of UCB for unrelated transplants. The distribution of cell contents in historical inventories is not homogenous and many units are not, therefore, suitable for adults. The aim of this study was to analyse our UCB bank inventory, evaluate the units released for transplantation and calculate the cost of the current process per unit of UCB stored.

Methods

Three study periods were defined. In the first period, from January 1996 to January 2006, the total nucleated cell (TNC) count acceptable for processing was 4–6×10⁸ and a manual processing system was used. In the second period, from October 2006 to July 2010, processing was automated and the acceptable TNC count varied from 8–10×10⁸. In the third period, from January 2009 to June 2010, an automated Sepax-BioArchive procedure was used and the accepted initial TNC count was >10×10⁸. Within each period the units were categorised according to various ranges of cryopreserved TNC counts in the units: A, >16.2×10⁸; B1, from 12.5–16.1×10⁸; B2, from 5.2–12.4×10⁸; and C, <5.1×10⁸.

Results

The third period is best representative of current practices, with homogenous TNC acceptance criteria and automated processing. In this period 15.7% of the units were category A and 25.5% were category B. Overall, the mean TNC count of units released for transplantation was 14×10⁸ (range, 4.6×10⁸ to 36.5×10⁸). The cost of the processed UCB in 2009 was 720.41 euros per unit.

Conclusion

An UCB bank should store units of high-quality, in terms of the TNC count of units issued for transplantation, have a training programme to optimise the selection of donors prior to delivery, use similar volume reduction systems and homogenous recovery indices, express its indicators in the same units, use validated analytical techniques, and bear in mind ethnic minorities.     

Early measurement of CD34+ cells in peripheral blood after cyclophosphamide and granulocyte colony-stimulating factor treatment predicts later CD34+ mobilisation failure and is a possible criterion for guiding “on demand” use of plerixafor

Background

Early identification of predictive factors of failure to mobilise CD34+ cells could enable rational use of plerixafor during first mobilisation, avoiding the need for a second mobilisation course. However, “on demand” administration of plerixafor needs to be driven by established parameters to avoid inappropriate use.

Materials and methods

To address this issue, we studied the value of the peripheral blood CD34+ count, measured early (on days +10, +11, +12 and +13), in predicting the mobilisation outcome in the ensuing days. We retrospectively collected data from three Italian centres on 233 patients affected by multiple myeloma or lymphoma who underwent a first or second attempt at mobilisation with cyclophosphamide 4 g/m² and granulocyte colony-stimulating factor. To assess the diagnostic value of peripheral blood white blood cell and CD34+ cell counts with respect to “mobilisation failure”, we considered failed mobilisation as “disease” and the CD34+ cell count in peripheral blood, on a specific day, as a “diagnostic test”. For various thresholds, we measured sensitivity, false positive rate, specificity and positive predictive value (PPV) as well as the area under the receiver-operating characteristic curves (AUC).

Results

A CD34+ cell count <10×10⁶/L on day 13 had high sensitivity (1.00) and high specificity (1.00) for predicting subsequent mobilisation failure, with an AUC of 1.0. However, good prediction was also obtained using a lower threshold (CD34+ cell count: <6×10⁶/L) at an earlier time (day 12). The PPV of the day 13 threshold was 1.00 while that of the day 12 one was 0.87.

Discussion

We propose that patients with <6×10⁶/L CD34+ cells in peripheral blood on day 12 and <10×10⁶/L on day 13 following mobilisation with cyclophosphamide 4 g/m² and granulocyte colony-stimulating factor are candidates for “on demand” use of plerixafor, making the administration of this expensive agent more efficient and avoiding its inappropriate use.     

Prognostic significance of preoperative platelet count in patients with gallbladder cancer

AIM:To investigate the prognostic value of preoperative platelet count(PLT) in patients with primary gallbladder cancer(GBC).METHODS:The clinical data of 223 GBC patients after surgery was retrospectively reviewed.A receiver operating characteristic(ROC) curve was plotted to verify the optimum cutoff point for PLT.Univariate and multivariate survival analyses were performed to identify the factors associated with the prognosis.RESULTS:The ROC curve showed that the optimum cutoff point for PLT was 178 × 109/L,and the entire cohort was stratified into group A with PLT 178 × 109/L and group B with PLT ≤ 178 × 109/L.Group A had a better survival than group B(P 0.001).There was an obvious difference between the two groups in terms of the differentiation degree,advanced tumor stage,lymph node metastasis(P 0.001) and pathological type(P 0.05).The univariate analysis demonstrated that tumor location,differentiation degree,TNM stage,Nevin stage,lymph node metastasis and PLT were associated with overall survival(P 0.001).In the multivariate analysis,PLT(P = 0.032),lymph node metastasis(P = 0.007),tumor location(P 0.001) and TNM stage(P = 0.005) were independent prognostic factors.CONCLUSION:PLT is closely correlated with GBC prognosis and could be used to identify the population with a poorer prognosis after surgery.     

The role of 9-O-acetylated ganglioside D3 (CD60) and ��4��1 (CD49d) expression in predicting the survival of patients with S��zary syndrome

Background

Sézary syndrome is a rare and very aggressive leukemic variant of cutaneous T-cell lymphoma characterized by extensive skin involvement and a malignant circulating CD4⁺ T-cell clone which homes to the skin, over-expresses CD60, and lacks CD7, CD26 and CD49d. So far prognostic markers in this disease are limited to treatment with systemic steroids, age, serum lactate dehydrogenase, and a white blood cell count of 20×10⁹/L or higher: no other biological marker with prognostic value, especially related to malignant cells, has been described.

Design and Methods

We used flow activated cell sorting analysis to compare the distribution of the T-cell receptor-Vβ repertoire and several surface molecules (CD7, CD26, CD49d and CD60) within the circulating CD4⁺ T-cell population in 62 patients with Sézary syndrome, 180 with mycosis fungoides, 6 with B-cell lymphomas, and 19 with chronic eczema. We calculated the 5-year overall survival of patients with Sézary syndrome after first hospital admission using Kaplan–Meier product–limit estimates and hazard ratios from the Cox proportional hazards model.

Results

We found that both higher number of CD60⁺ and lower number of CD49d⁺ cells within circulating CD4⁺ T cells at disease presentation were significantly associated with a lower probability of survival. An exceedingly high risk of death was observed for patients with a combination of a high proportion of CD4⁺CD60⁺ cells (≥ 0.5×10⁹/L) and low proportion of CD4⁺CD49d⁺ cells (<0.5×10⁹/L) (hazard ratio = 12.303, 95% confidence interval 1.5–95.9; P<0.02). In addition, a skewed usage of T-cell receptor-Vβ subfamilies was observed in the circulating T-cell clone for 61.9% of all patients with Sézary syndrome, T-cell receptor-Vβ 2 and 5.1 subfamilies being the most frequently represented (42.8%), followed by T-cell receptor-Vβ 12 and 13.1.

Conclusions

In this study we showed that up-regulation of CD60 and down-regulation of CD49d on circulating CD4⁺ T cells are two useful markers for predicting a very poor outcome in patients with Sézary syndrome.     

Efficacy and safety of laparoscopic splenectomy in thrombocytopenia secondary to systemic lupus erythematosus

This study aims to investigate the efficacy and safety of laparoscopic splenectomy (LS) in the management of refractory thrombocytopenia associated with systemic lupus erythematosus (SLE). From January 2003 to February 2012, 20 patients underwent splenectomy for thrombocytopenia associated with SLE. Of these, 11 underwent open (SLE-OS group) and 9 underwent laparoscopic splenectomy (SLE-LS group). Another 15 patients with ITP underwent LS (ITP-LS group) were categorized as the control group. Surgical indications, perioperative details, and short- (90 days) and long- (median, 42 months) term hematological outcomes were assessed. Splenectomy was successful in all 20 SLE patients. The mean platelet count increased from 23?×?10⁹/L before splenectomy to 289.2?×?10⁹/L and 144.2?×?10⁹/L after 3 and 6 months, respectively, and was 115.5?×?10⁹/L at the last visit, with a 3-month complete response (CR) rate of 100 %. After a median follow-up of 42 months, 17 patients (85 %) had a CR or partial response (PR) to splenectomy plus medical therapy. SLEDAI score and dosage of steroids decreased significantly after splenectomy. None of these patients experienced any postoperative infection, bleeding, or thrombotic events. SLE-LS group had lower volumes of estimated blood loss and postoperative drainage and shorter postoperative hospital stay than SLE-OS group. There were no statistically significant differences between the SLE-LS and ITP-LS groups in operation time, estimated blood loss, and postoperative hospital stay. Splenectomy is effective and safe in the management of refractory thrombocytopenia secondary to SLE. LS may be safe and effective in thrombocytopenia associated with SLE.     

Murine study of portal hypertension associated endothelin-1 hypo-response

AIM:To investigate endothelin-1 hypo-responsive associated with portal hypertension in order to improve patient treatment outcomes.METHODS:Wild type,e NOS-/-and i NOS-/-mice receivedpartial portal vein ligation surgery to induce portal hypertension or sham surgery.Development of portal hypertension was determined by measuring the splenic pulp pressure,abdominal aortic flow and portal systemic shunting.To measure splenic pulp pressure,a microtip pressure transducer was inserted into the spleen pulp.Abdominal aortic flow was measured by placing an ultrasonic Doppler flow probe around the abdominal aorta between the diaphragm and celiac artery.Portal systemic shunting was calculated by injection of fluorescent microspheres in to the splenic vein and determining the percentage accumulation of spheres in liver and pulmonary beds.Endothelin-1 hypo-response was evaluated by measuring the change in abdominal aortic flow in response to endothelin-1 intravenous administration.In addition,thoracic aorta endothelin-1contraction was measured in 5 mm isolated thoracic aorta rings ex-vivo using an ADI small vessel myograph.RESULTS:In wild type and i NOS-/-mice splenic pulp pressure increased from 7.5±1.1 mm Hg and 7.2±1 mm Hg to 25.4±3.1 mm Hg and 22±4 mm Hg respectively.In e NOS-/-mice splenic pulp pressure was increased after 1 d(P=NS),after which it decreased and by 7 d was not significantly elevated when compared to 7 d sham operated controls(6.9±0.6 mm Hg and 7.3±0.8 mm Hg respectively,P=0.3).Abdominal aortic flow was increased by 80%and 73%in 7 d portal vein ligated wild type and i NOS when compared to shams,whereas there was no significant difference in 7 d portal vein ligated e NOS-/-mice when compared to shams.Endothelin-1 induced a rapid reduction in abdominal aortic blood flow in wild type,e NOS-/-and i NOS-/-sham mice(50%±8%,73%±9%and 47%±9%respectively).Following portal vein ligation endothelin-1 reduction in blood flow was significantly diminished in each mouse group.Abdominal aortic flow was reduced by 19%±9%,32%±10%and 9%±9%in wild type,e NOS-/-and i NOS-/-mice respectively.CONCLUSION:Aberrant endothelin-1 response in murine portal hypertension is NOS isoform independent.Moreover,portal hypertension in the portal vein ligation model is independent of ET-1 function.     

Patients ≥75 years with acute coronary syndrome but without critical epicardial coronary disease: prevalence, characteristics, and outcome

Objective Absence of significant epicardial coronary artery disease (CAD) in patients with acute onset of chest pain and elevation of myocardial necrosis markers is occasionally observed. The aim of this study was to analyse the clinical characteristics and outcome of such patients with advanced age. Methods We retrospectively analysed 4,311 patients with acute onset of chest pain plus necrosis marker elevation. Two hundred and seventy two patients without CAD on angiogram (6.3%) were identified. Out of them, 50 (1.2%) patients ≥ 75 years (Group I) were compared with (1) 222 acute coronary syndrome (ACS) patients without CAD on angiogram < 75 years (Group II), and (2) 610 consecutive patients ≥ 75 years with Non-ST-elevation Myocardial Infarction (NSTEMI) undergoing percutaneous coronary intervention (Group III). Results Group I compared to Group III patients made up for more females (64.0% vs. 49.2%; P < 0.0001), and had more severe anginal symptoms on presentation [Canadian Cardiovascular Society (CCS) class I/II, 26.0% vs. 49.8%; P = 0.02]. Group I patients also had lower troponin levels (0.62 ± 0.8 ng/mL vs. 27 ± 74 ng/mL; P < 0.02), lower leukocyte count (9.4 ± 3.13 × 10⁹ vs. 12 ± 5.1 × 10⁹; P = 0.001) and better preserved left ventricular function (56.7% ± 14.3% vs. 45% ± 11%; P < 0.0001). Event-free survival (cardiac death, myocardial infarction, recurrent angina, and re-hospitalisation) was more frequent in Group I and II patients compared to Group III patients (64.9%, 66.7%, and 41.6%, respectively; P < 0.0001). Conclusions ACS in patients ≥ 75 years without CAD is very infrequent, associated with a (1) similar outcome compared to ACS patients < 75 years without CAD, and (2) significant better outcome compared to NSTEMI patients ≥ 75 years.     

Combined use of peripheral blood blast count and platelet count during and after induction therapy to predict prognosis in children with acute lymphoblastic leukemia

Several studies have reported an association between the rapidity of reduction in peripheral blood blast count or recovery of normal hematopoiesis and treatment outcome during therapy in children with acute lymphoblastic leukemia (ALL). However, little is known about the impact of both of these aspects on prognosis in pediatric ALL. Accordingly, the purpose of this study was to evaluate whether the combined use of blood blast count and platelet count could predict event-free survival (EFS) and overall survival (OS) when minimal residual disease (MRD) detection was not available.A total of 419 patients aged 0 to 14 years diagnosed and treated for ALL between 2011 and 2015 were enrolled.Patients with a blast count ≥0.1 × 10⁹/L on day 8 exhibited significantly lower survival rates than that in those with blast counts <0.1 × 10⁹/L. The EFS and OS in patients with platelet count ≥100 × 10⁹/L on day 33 were significantly higher than those with platelet counts <100 × 10⁹/L. In univariate and multivariate analyses, patients with low blast count on day 8 and high platelet count on day 33 were significantly associated with better EFS and OS. The combination of blast cell count on day 8 and platelet count on day 33 demonstrated a strong association with MRD-based risk stratification.Complete blood count is an inexpensive, easy to perform, and reliable measurement in children with ALL. The combination of blast count and platelet count during and after induction chemotherapy was a significant and independent prognostic factor for treatment outcome in pediatric ALL.     

Low immediate postoperative platelet count is associated with hepatic insufficiency after hepatectomy

AIM: To investigate the relationship between low immediate postoperative platelet count and perioperative outcome after liver resection in patients with hepatocellular carcinoma (HCC).METHODS: In a cohort of 565 consecutive hepatitis B-related HCC patients who underwent major liver resection, the characteristics and clinical outcomes after liver resection were compared between patients with immediate postoperative platelet count < 100 × 10⁹/L and patients with platelet count ≥ 100 × 10⁹/L. Risk factors for postoperative hepatic insufficiency were evaluated by multivariate analysis.RESULTS: Patients with a low immediate postoperative platelet count (< 100 × 10⁹/L) had more grade III-V complications (20.5% vs 12.4%, P = 0.016), and higher rates of postoperative liver failure (6.8% vs 2.6%, P = 0.02), hepatic insufficiency (31.5% vs 21.2%, P < 0.001) and mortality (6.8% vs 0.5%, P < 0.001), compared to patients with a platelet count ≥ 100 × 10⁹/L. The alanine aminotransferase levels on postoperative days 3 and 5, and bilirubin on postoperative days 1, 3 and 5 were higher in patients with immediate postoperative low platelet count. Multivariate analysis revealed that immediate postoperative low platelet count, rather than preoperative low platelet count, was a significant independent risk factor for hepatic insufficiency.CONCLUSION: A low immediate postoperative platelet count is an independent risk factor for hepatic insufficiency. Platelets can mediate liver regeneration in the cirrhotic liver.     

Relationship of admission hematological indexes with myocardial reperfusion abnormalities in acute ST segment elevation myocardial infarction patients treated with primary percutaneous coronary interventions

BACKGROUND:

Elevated values of mean platelet volume (MPV) and elevated white blood cell (WBC) count are predictors of an unfavourable outcome among survivors of ST segment elevation myocardial infarction (STEMI). However, their relationship with reperfusion abnormalities is less clear.

OBJECTIVE:

To evaluate the value of admission MPV and WBC count in predicting impaired reperfusion in patients with acute STEMI who are treated with primary percutaneous coronary intervention (PCI).

METHODS:

Blood samples were obtained on admission from 368 STEMI patients who underwent successful PCI. According to the 60th minute ST segment resolution ratio, patients were divided into impaired reperfusion and reperfusion groups.

RESULTS:

Impaired reperfusion was detected in 40% of study patients. Patients in the impaired reperfusion group had a higher admission MPV (9.8±1.3 fL versus 8.6±1.0 fL; P<0.001) and a higher WBC count (14.4±5.5×10⁹/L versus 12.1±3.8×10⁹/L; P<0.001) compared with the patients in the reperfusion group. In regression analysis, MPV (OR 2.21, 95% CI 1.69 to 2.91; P<0.001) and WBC count (OR 1.08, 95% CI 1.02 to 1.15; P=0.01) were found to be independently associated with impaired reperfusion. The best cut-off value of MPV for predicting impaired reperfusion was determined to be 9.05 fL, with a sensitivity of 74% and a specificity of 73%.

CONCLUSIONS:

The results indicate that leukocytes and platelets have a role in the mediation of reperfusion injury. In patients with STEMI who are undergoing PCI, admission MPV may be valuable in discriminating a higher-risk patient subgroup and thus, may help in deciding the need for adjunctive therapy to improve the outcome.