Thrombocytopenic Group Research Articles

Preoperative moderate thrombocytopenia is not associated with increased blood loss for low-risk cesarean section: a retrospective cohort study

BackgroundThe occurrence of thrombocytopenia is as high as 7–12% in pregnancy, yet minimum platelet count safe for cesarean section remains unknown.MethodsIn this retrospective noninferior cohort study, we consecutively included patients undergoing cesarean section for a period of 6 years in a tertiary hospital and excluded patients at very high risk for excessive hemorrhage. The included patients with preoperative platelet count of 50–100 × 109/L were defined as the thrombocytopenic group. The control group were eligible patients with preoperative platelet count>150 × 109/L, matched to the thrombocytopenic group by age and operation timing in a 1:2 ratio. Mixed effect model was used to analyze the effect of thrombocytopenia based on a noninferiority assumption. The predefined noninferiority delta of bleeding was 50 mL.ResultsThere was no significant difference of the calculated blood loss between the thrombocytopenic and the control group (mean difference = 8.94, 95% CI − 28.34 mL to 46.09 mL). No statistical difference was observed in the requirement for blood transfusion, visually estimated blood loss, or the incidence of adverse events between groups. Although there were more patients admitted to intensive care unit (odds ratio = 12, 95% CI 2.69–53.62, p = 0.001) in the thrombocytopenic group, most of them required critical care for reasons other than hemorrhage. The thrombocytopenic group had longer length of hospital stay (mean difference = 0.40 days, 95% CI 0.09–0.71, p = 0.011), but the difference was considered as clinically insignificant.ConclusionsPreoperative moderate thrombocytopenia is not associated with increased blood loss, blood transfusion, or occurrence of adverse events in patients undergoing cesarean section in absence of additional bleeding risk.

Correlation between platelet count and outcome of chronic HCV patients treated with direct-acting antivirals

Background: Egypt has the highest prevalence of chronic hepatitis C virus (HCV) infection. Thedirect acting anti-virus (DAAs) are available, with a reported 95% sustained virological responseafter treatment for 12 weeks (12w-SVR).Objectives: The current study aimed to assess the correlation between platelet count and theDAAs therapy outcome in chronic HCV (CHC) patients.Patients and methods: three hundred CHC patients, Child–Pugh grade A, both naive andtreatment experienced patients were enrolled in this study, from outpatient Clinic, Department ofGastroenterology, Hepatology and Tropical medicine, Qena university hospital, Qena, Egypt,treated with DAAs for 12 weeks, either dual or triple therapy, according to criteria recommendedby the national committee for chronic viral hepatitis (NCCVH). Patients categorized into threegroups: (1) Group I (non-thrombocytopenic group): included 100 CHC patients with platelet count≥ 150 (109/L); (2) Group II (mild thrombocytopenic group): included 100 CHC patients withplatelet count 100-149 (109/L); (3) Group III (moderate thrombocytopenia): included 100 CHCpatients with platelet count 50–99 (109/L).Results: The Overall CHC patient's mean age were (48.2 ± 11), 226 (75.33%) were males and 74(24.67%) were females. 97.6% (293/300)of CHC patients attainedSVR; 97 % in (Group I), and 98% in both (Group II), and (Group III), after 12 weeks DAAs therapy with no significant differencebetween groups.Conclusion: both DAAs treatment modalities were efficient in the eradication of HCV; however,thrombocytopenia in CHC patients does not affect the DAAs therapy outcome.

Platelets Accumulation In The Liver : A novel Mechanism Of Thrombocytopenia In Chronic Hepatic C Patients

Background and aim: Thrombocytopenia is a common complication of chronicliver diseases and is due to various causes.The effect of thrombocytopenia on liver damage and the exact mechanisms that lead to thrombocytopenia in chronic liver disease and cirrhosis are still unclear. As Platelets Derived Growth Factor s (PDGF-s) is released from platelets (PLTs) upon activation. We tried to identify PLTs and PDGFR- s in the liver to shed some light on the pathophysiology of thrombocytopenia and liver fibrosis in chronic hepatic C patients. Patients and Methods: Analytical cross-sectional study was conducted on fiftypatients with proven chronic hepatitis C. All patients were referred to Tropical Medicine and Gastroenterology Department, Sohag University Hospital. Patients were categorized into two groups. Group 1 includes patients with PLT count less than 150000/µL (thrombocytopenia). Group 2 includes patients with normal PLT count (150000-450000/µL). All patients were subjected to full history taking, complete clinical examination, complete blood count, liver function tests. Liver biopsy was obtained for histological staging and grading. Immunohistochemical study of PLTs and PDGFR- s were done using monoclonal antibodies against PLT's surface marker CD41 and PDGFR- s. Results: The included patients were 80 % males and 20 % females. Their mean agewas 44.42± 11.17 years. The mean average weighted score (AWS) of Imunohisto-chemical expression of CD41was significantly higher in thrombocytopenic group compared to normal PLTs group (5.8±2.86 vs 3.43±3.03; P<0.001). There was a significant negative correlation between CD41 expression and peripheral PLT count (r=-0.4; P=0.007). PDGFR- s expression was significantly stronger in thrombocytopenic patients than patients with normal PLT count (6.9±3.6 vs 5.27±3.92; P=0.001). It showed also a significant negative correlation with peripheral PLT count (r=-0.34, P=0.045). Both CD41 and PDGFR- s expression were significantly elevated in patients with advanced stage of fibrosis than in those with earlier stages (7.26±5.23 vs 5.88±3.24; P=0.04 &9.2±2.7 vs 6.7±3.6; P Conclusion: The accumulation of PLTs in the liver in patients with chronic hepatitisC may be involved in thrombocytopenia and liver fibrosis.

524: Fetal thrombocytopenia in alloimmunized patients

The objective of this study was to characterize the patterns of platelet counts in a modern cohort of fetuses undergoing percutaneous umbilical cord blood sampling (PUBS) for alloimmunization. This is a retrospective cohort study of all patients undergoing PUBS at our institution from 2000-2017. Demographic and clinical data were abstracted from the medical record. Patients were categorized into anti-D alone, anti-D and other antibodies, or other antibodies only. The primary outcome was fetal thrombocytopenia, defined as platelet count <150 x 109/L and classified as moderate (50 - 150 x 109/L) or severe (<50 x 109/L). The associations between antibody group and fetal thrombocytopenia, as well as between thrombocytopenia and fetal hemoglobin level, were determined using mixed models to account for repeated measures (i.e. PUBS procedures) in each patient. Of the 50 patients in the study, 15 patients had anti-D alone, 15 had anti-D and other antibodies, and 20 had other antibodies only. A total of 158 PUBS procedures were performed with 143 in-utero transfusions. Opening platelet counts (range 8-485 x 109/L) were available for 120 PUBS. Of these, 71 (59.2%) had no thrombocytopenia, 36 (30.0%) had moderate thrombocytopenia, and 13 (10.8%) had severe thrombocytopenia. Thrombocytopenia was found in 44.4% of PUBS in patients with anti-D antibodies only, in 27.8% % of PUBS in patients with anti-D and other antibodies, and in 47.9% of PUBS in patients with only other kinds of antibodies (p=0.17). There was no significant association between antibody class and degree of fetal thrombocytopenia (p=0.30). The mean hemoglobin in the thrombocytopenic group was 6.8 g/dL (standard deviation 2.8 g/dL); while in the non-thrombocytopenic group it was 8.1 g/dL (standard deviation 3.1 g/dL), p=0.02. This association was not modified by antibody type (p for interaction 0.19). Thrombocytopenia is common in fetuses undergoing PUBS for alloimmunization, regardless of antibody type. The presence of thrombocytopenia is associated with more severe fetal anemia. More work is needed to understand the biological mechanism and consequences of this finding.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Thrombocytopenia as a Preoperative Risk Assessment Tool in Patients With Rheumatic Heart Disease Undergoing Valve Replacement Surgery.

BackgroundPostoperative thrombocytopenia has been reported to be correlated with adverse events, but the prognostic value of baseline thrombocytopenia is unclear. This study was undertaken to evaluate the relationship between preoperative thrombocytopenia and adverse outcomes in patients with rheumatic heart disease who underwent valve replacement surgery.Methods and ResultsA total of 1789 patients with rheumatic heart disease undergoing valve replacement surgery were consecutively enrolled and postoperatively followed up for 1 year. Patients were stratified on the basis of presence (n=495) or absence (n=1294) of thrombocytopenia (platelet count, <150×109/L), according to hospital admission platelet counts. During the hospitalization period, 69 patients (3.9%) died. The in‐hospital all‐cause mortality rate was significantly higher in the thrombocytopenic group (6.9% versus 2.7%; P<0.001). Multivariate analyses revealed that thrombocytopenia was independently associated with in‐hospital all‐cause mortality (odds ratio, 2.21; 95% confidence interval, 1.29–3.80; P=0.004). Platelet counts could predict in‐hospital all‐cause mortality for patients both with and without previous atrial fibrillation (areas under the curve, 0.708 [P<0.001] and 0.610 [P=0.025], respectively). One‐year survival was significantly lower in patients with thrombocytopenia compared with controls (91.3% versus 96.1%; log‐rank=14.65; P<0.001). In addition, thrombocytopenia was an independent predictor for postoperative 1‐year all‐cause mortality in multivariate Cox regression analysis.ConclusionsPlatelet counts, as simple and inexpensive indexes, were reliable to be used as a preoperative risk assessment tool for patients with rheumatic heart disease undergoing valve replacement surgery.

Thrombocytopenia is associated with a dysregulated host response in critically ill sepsis patients

AbstractPreclinical studies have suggested that platelets influence the host response during sepsis. We sought to assess the association of admission thrombocytopenia with the presentation, outcome, and host response in patients with sepsis. Nine hundred thirty-one consecutive sepsis patients were stratified according to platelet counts (very low <50 × 109/L, intermediate-low 50 × 109 to 99 × 109/L, low 100 × 109 to 149 × 109/L, or normal 150 × 109 to 399 × 109/L) on admission to the intensive care unit. Sepsis patients with platelet counts <50 × 109/L and 50 × 109 to 99 × 109/L presented with higher Acute Physiology and Chronic Health Evaluation scores and more shock. Both levels of thrombocytopenia were independently associated with increased 30-day mortality (hazard ratios with 95% confidence intervals 2.00 [1.32-3.05] and 1.72 [1.22-2.44], respectively). To account for baseline differences besides platelet counts, propensity matching was performed, after which the association between thrombocytopenia and the host response was tested, as evaluated by measuring 17 plasma biomarkers indicative of activation and/or dysregulation of pathways implicated in sepsis pathogenesis and by whole genome blood leukocyte expression profiling. In the propensity matched cohort, platelet counts < 50 × 109/L were associated with increased cytokine levels and enhanced endothelial cell activation. All thrombocytopenic groups showed evidence of impaired vascular integrity, whereas coagulation activation was similar between groups. Blood microarray analysis revealed a distinct gene expression pattern in sepsis patients with <50 × 109/L platelets, showing reduced signaling in leukocyte adhesion and diapedesis and increased complement signaling. These data show that admission thrombocytopenia is associated with enhanced mortality and a more disturbed host response during sepsis independent of disease severity, thereby providing clinical validity to animal studies on the role of platelets in severe infection.

Comparative evaluation of platelet augmentation activity of Carica papaya leaf juice and hydrocortisone in thrombocytopenic rats

Aim The study aims at determining the possible effects of Carica papaya leaf juice and hydrocortisone in increasing the platelet count in thrombocytopenia similar to dengue fever. Methodology The study was carried out on 24 Long Evans Norwegian strain healthy rats to investigate the comparative platelet increasing effect of Carica papaya leaf juice and hydrocortisone in experimentally induced thrombocytopenic rats. Thrombocytopenia was induced by 3 doses of cyclophosphamide (100mg/kg body weight) given subcutaneously. The rats were divided into 4 groups comprising of six animals in each group. These groups included a normal control and a cyclophosphamide induced thrombocytopenic control and the remaining two cyclophosphamide induced thrombocytopenic groups were administered Carica papaya leaf juice and hydrocortisone respectively. The duration of study was 15 days. The clotting time was determined on the 15th day although blood samples were obtained from the rat tails at various time intervals to determine the platelet count. Collected data was tabulated and Statistical analysis was performed by using appropriate significant test. A probability value P &lt; 0.05 was considered to be statistically significant. Result Average platelet counts of the test and control groups were (6.89)×105/?L and (6.75)×105/?L respectively before the experiment. In the experiment there was no significant difference in the platelet counts during the first 3 days in either group. However, platelet counts within the test group started to fall after Day 3 and remarkable thrombocytopenia developed after 7days and the average value was (2.68)×105/?L. From day 11 Carica papaya leaf juice and Hydrocortisone was given in two test groups following cyclophosphamide and platelet counts observed to reach a peak level at Day 14 (7.83)×105/?L in case of following Carica papaya leaf juice, and (4.05)×105/?L in case of following Hydrocortisone. The clotting time was determined on day 15 and it was found to be considerably lower (95.5 ± 2.762 sec) in case of Carica papaya leaf juice than (129±3.124 sec) in Hydrocortisone. Conclusion Carica papaya leaf juice has more platelet increasing effect than hydrocortisone and this study also reflects that Carica papaya leaf juice may be a potential candidate for further research leading to the development of a herbal therapeutic agent for thrombocytopenia manifested in diseases such as dengue. DOI: http://dx.doi.org/10.3329/bjpp.v30i2.22681 Bangladesh J Physiol Pharmacol 2014; 30(2): 32-40

Assessment of thrombocytopenia in critically ill patients

BackgroundThrombocytopenia is commonly observed among critically ill patients.AimThe aim of this study was to evaluate the incidence, risk factors, and the outcome of thrombocytopenia in patients admitted to the respiratory intensive care unit (RICU).Materials and methodsData were collected from 50 adult patients admitted to the RICU in a 6-month period. The baseline platelet count was measured and was repeated every other day during the RICU stay period. Thrombocytopenia was defined as platelet count of less than 150´109/l.ResultsThe incidence of thrombocytopenia was 20% (10 patients). The overall mortality was 16%, of which 50% of the patients were having thrombocytopenia. The thrombocytopenic group had a higher mortality (40 vs. 10%, P < 0.05), a lower admission platelet count (215.3 ± 85.6 vs. 252.8 ± 73.2, P < 0.05), a lower nadir platelet count (111.1 ± 22.6 vs. 213.9 ± 53.2, P < 0.001), an increased transfusion requirement (30 vs. 2.5%, P < 0.05), and increased septic shock (40 vs. 2.5%, P < 0.05) compared with the nonthrombocytopenic group. Comorbidities, indications for RICU admission, the length of RICU stay, mechanical ventilation, days on mechanical ventilation, admission severity scores, bleeding, ICU-related complications, and medications administrated during the RICU stay did not differ significantly. A prolonged RICU stay of more than 15 days carried a 4.7 times higher incidence of development of thrombocytopenia. Thrombocytopenia differed significantly between survivors and nonsurvivors (P < 0.05), with a significant effect on mortality (P = 0.034).ConclusionThrombocytopenia is common among critically ill patients and affects the mortality significantly. Prolonged ICU stay and septic shock are among the risk factors for thrombocytopenia. Egypt J Broncho 8:143–148

Severe thrombocytopenia in hantavirus-induced nephropathia epidemica.

Nephropathia epidemica is a milder form of hemorrhagic fever with renal syndrome, caused by Puumala virus. The clinical picture is characterized by a rapid loss of renal function (acute kidney injury) and thrombocytopenia. The purpose of the current analysis was to compare the clinical course of patients presenting with or without severe thrombocytopenia. In 47 out of 456 patients with acute nephropathia epidemica, the nadir count of thrombocytes was available for the acute course of the disease. The clinical course of these patients was further analyzed. No major bleeding (e.g., intracranial bleeding or gastrointestinal bleeding) occurred in either group. Creatinine peak levels were higher and proteinuria was more frequently present in the severely thrombocytopenic group. In conclusion, severe thrombocytopenia is common in nephropathia epidemica and is associated with a more severe course of the disease; however, bleeding complications are rare.

Effect of thrombocytopenia on mode of analgesia/anesthesia and maternal and neonatal outcomes

Objectives: The purpose was to correlate the use of regional analgesia/anasthesia among women with different degrees of thrombocytopenia relative to women with normal platelet counts, and note maternal and neonatal outcome, and mode of delivery.Methods: A case-control paradigm was developed based on women who delivered during 2007–2011 with platelet counts ≤80 000/mm3. For each woman in this “severe” thrombocytopenic group, an age- and parity-matched control was found who delivered a singleton within the same year but whose platelets were either 81 000–150 000/mm3 (“moderate” thrombocytopenia) or ≥151 000/mm3 (normal platelet counts).Results: 168 women were identified for each group; mean maternal age (28.4 years), mean gravidity (4.3), mean parity (3.7), mean gestational age (39.2 weeks) and mean birth weight (3283 g) were comparable. However, only in the severe thrombocytopenic women were there very early preterm deliveries, lowest birth weight, lowest Apgar scores, the greatest number with serious post-partum hemorrhage (>500 ml); use of regional analgesia/anesthesia was lowest, and percent cesarean sections highest.Conclusions: This study highlights potential for adverse maternal outcome of post-partum hemorrhage and adverse neonatal outcomes of prematurity, low birth weight, and low Apgar scores (but not neonatal death), and limited regional analgesia/anesthesia in women who present at delivery with severe (≤80 000/mm3) thrombocytopenia.

Thrombocytopenia in patients with hepatitis B virus-related chronic hepatitis: Evaluation of the immature platelet fraction

The immature platelet fraction (IPF) measures the number of reticulated platelets in peripheral blood, and can be used to help determine if thrombocytopenia is secondary to low-platelet production or increased platelet turnover. The aim of this study was to determine whether abnormalities in the IPF were associated with thrombocytopenia in patients with hepatitis B virus-related chronic hepatitis (CHB). One hundred fifty-six patients with chronic hepatitis B, including 80 thrombocytopenia, 76 without thrombocytopenia, and 48 healthy controls were enrolled in the study. The IPF percentages (IPF%) were measured using a XE-2100 multiparameter automatic hematology analyzer. We demonstrated that in the thrombocytopenic group, the IPF% was significantly increased compared with that in healthy controls and the non-thrombocytopenic group (both p < 0.001). Multivariate analysis demonstrated that IPF%, splenomegaly, and the model for end-stage liver disease score were independent predictors for thrombocytopenia (both p < 0.001). High IPF% during the course of thrombocytopenia suggests that platelet destruction/sequestration due to hypersplenism is a major factor contributing to thrombocytopenia in patients with CHB.

Study of anticardiolipin antibody in hepatitis C virus-positive patients

Several antibodies, including anticardiolipin antibodies (ACA), have been detected among chronically infected hepatitis C virus (HCV) patients. The present work aimed at ascertaining the clinical significance of ACA levels among HCV infection associated with two commonly encountered diseases, thrombocytopenia and arteriovenous-shunt malfunction. Six groups were studied, 11 HCV-positive thrombocytopenic patients (group I), 14 HCV-positive non-thrombocytopenic patients (group II) and 15 healthy controls (group III), 11 anti-HCV-positive hemodialysis patients with non-functioning shunt (group IV), 14 anti-HCV-positive hemodialysis patients with patent shunt (group V) (Bain Medical Equipment Co., China) and 15 healthy controls (group VI). Anticardiolipin antibody (ACA) assay was performed on all patients and controls whereas tumor necrosis factor α (TNF-α) assay was carried out on thrombocytopenic patients and controls. Thrombocytopenic groups presented an inverse correlation between IgG ACA levels and both thrombocytopenia and TNF-α levels. During the follow-up period, no other clinical manifestations related to ACA were developed. Hemodialysis groups showed a significant elevation in IgG ACA levels in groups IV and V compared to the controls, with statistically higher levels in group IV than group V. Three group IV patients were hypercholesterolemic. We can conclude that induction of proinflammatory cytokines such as TNF-α by persistent HCV infection may promote the generation of ACA. Complications of HCV, including thrombocytopenia and thrombosis in arteriovenous shunt, are more strongly correlated with IgG ACA than with IgM ACA.

Significance of immature platelet fraction and CD41-positive cells at birth in early onset neonatal thrombocytopenia

Early thrombocytopenia is a common hematological abnormality in sick neonates. Here, we examined the relationship between early thrombocytopenia in neonates and parameters associated with thrombopoiesis to identify predictive factors at birth. Two hundred and forty-four neonates admitted to the neonatal intensive care unit were divided into thrombocytopenic (n = 55, 23%) and non-thrombocytopenic (n = 189, 77%) groups based on platelet counts, which were monitored within 72 h of birth. Immature platelet fraction (IPF) and platelet count at birth were determined simultaneously soon after phlebotomy with an automated hematology analyzer. Megakaryocytes and their precursors positive for CD41 in peripheral blood were examined at birth by flow cytometry. The thrombocytopenic group showed significantly higher IPF percentage and lower percentage of CD41+ mononuclear cells (MNCs) than did the non-thrombocytopenic group (P < 0.01). Moreover, the percentage of CD41+ MNCs significantly differentiated neonates with platelet counts >150 x 10(3)/microL at birth and nadir platelet count <150 x 10(3)/microL over the clinical course from neonates without thrombocytopenia. These observations suggest that the percentage of CD41+ MNCs at birth and IPF percentage are useful predictors of early thrombocytopenia in the majority of sick neonates.

Terminal Complement Inhibitor Eculizumab Improves Complement-Mediated Platelet Consumption and Thrombocytopenia in Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH).

Abstract 4030Poster Board III-966PNH is a hematopoietic stem cell disorder in which unregulated activation of the complement system leads to significant morbidities with shortened lifespan. Life threatening thromboembolism (TE) is the most feared complication of PNH, accounting for 45% of patient deaths. Approximately 40% of PNH patients experience a clinically evident TE and 60% of patients without clinically diagnosed TE demonstrate TE by high-sensitivity MRI, indicating the ongoing thrombotic risk in PNH patients. Thrombocytopenia is found in 25-50% of PNH patients at presentation. PNH platelets are extremely sensitive to terminal complement activation, and circulating platelets are activated in thrombocytopenic PNH patients without clinically diagnosed TE. Eculizumab, a monoclonal antibody targeted to complement C5, blocks the production of both C5a and C5b-9, and has been demonstrated to reduce TE events by up to 92% in PNH patients. Eculizumab has also been shown to beneficially impact several prothrombotic processes in PNH patients including hemolysis, nitric oxide consumption, thrombin generation, tissue factor pathways, and inflammation. We hypothesized that terminal complement activation of PNH platelets contributes to ongoing platelet activation, which is reflected by platelet consumption, contributing to chronic thrombocytopenia defined as platelets <100×109/L. This hypothesis was tested by examining whether chronic inhibition of terminal complement activation with eculizumab increases platelet counts in thrombocytopenic PNH patients. The study population was comprised of the 49 thrombocytopenic PNH patients identified from the total 195 patients in the SHEPHERD, TRIUMPH, and Phase 2 eculizumab trials. Platelet counts were measured at baseline, 26 and 52 weeks of eculizumab treatment. At baseline the median platelet count in the thrombocytopenic group was 68×109/L (range 23 to 97). Patients with thrombocytopenia were more likely to have a history of TE than patients with normal platelet counts (45% vs 27%; P<0.022). Treatment with eculizumab markedly inhibited terminal complement activity in all thrombocytopenic patients, as measured by a significant reduction in LDH at 26 and 52 weeks (median values at baseline, 26 weeks, and 52 weeks: 1746 IU/L, 290 IU/L, 286 IU/L, respectively, UNL 220 U/L); P<0.00001 for each time point vs. baseline). Chronic terminal complement inhibition with eculizumab significantly increased platelet counts to a non-thrombocytopenic level in 33% (95% CI: 20-48%) and 36% (95% CI: 22-51%) of thrombocytopenic patients at 26 and 52 weeks, respectively, of treatment. By inhibiting C5 activity, the median platelet counts significantly increased in thrombocytopenic patients from 68×109/L at baseline to 80 and 85×109/L (P<0.001) at 26 and 52 weeks, respectively. Eculizumab treatment significantly increased platelet counts in both thrombocytopenic patients with a history of TE and no history of TE (P<0.05 vs baseline in both groups). Treatment with eculizumab significantly increased platelet counts at 52 weeks in this thrombocytopenic patient population irrespective of a history of bone marrow failure (P<0.05 vs baseline for each group). As expected, there was no apparent impact of terminal complement inhibition on marrow blood cell production as measured by no change in absolute neutrophil count at 26 and 52 weeks. This suggests that the mechanism of platelet increase may be due to inhibition of terminal complement-mediated consumption of platelets in thrombocytopenic patients with PNH. The present study indicates that thrombosis in PNH patients is more frequent in patients with thrombocytopenia. Terminal complement deposition on PNH platelets results in platelet activation which in turn would be expected to result in platelet consumption, suggestive of a chronic prothrombotic state, in PNH patients. Earlier studies have shown that chronic terminal complement inhibition with eculizumab reduces thrombotic risk in patients with PNH. The current study shows that chronic terminal complement inhibition with eculizumab treatment improves pre-existing thrombocytopenia in a significant proportion of patients with PNH. These clinical findings warrant further investigation and suggest that terminal complement C5 activity contributes to platelet activation and consumption with subsequent thrombocytopenia and an increased thrombotic risk in patients with PNH. Disclosures:Socie:Alexion: Consultancy, Membership on an entity's Board of Directors or advisory committees. Muus:Alexion Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees. Schrezenmeier:Alexion: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Höchsmann:Alexion: Honoraria. Hill:Alexion: Honoraria. Bessler:Alexion: Membership on an entity's Board of Directors or advisory committees. Risitano:Alexion Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Estimating platelet production in patients with HIV‐related thrombocytopenia using the immature platelet fraction

Thrombocytopenia is common in patients with HIV infection. However, given the number of potential etiologies of low-platelet counts in this patient population, it is often difficult to determine the underlying cause. The immature platelet fraction (IPF) measures the number of reticulated platelets in peripheral blood and can be used to help determine if thrombocytopenia is secondary to low-platelet production or increased platelet turnover. We studied the performance characteristics of the IPF% in 50 inpatients with HIV-related thrombocytopenia and compared the results with 34 inpatients with HIV and normal platelet counts. The mean IPF% in the HIV thrombocytopenic group was 10.2% as compared with 6.8% in the HIV normal platelet count group (P = 0.001) and 3.1% in historical non-HIV controls (P < 0.001). In multivariate analyses, the presence of ITP, active infection, log CD4 count, platelet count, and diabetes mellitus were significantly associated with a higher IPF%. These findings suggest that increased platelet turnover plays an important role in the pathogenesis of HIV thrombocytopenia. Platelet turnover is also increased in patients with HIV in general, even when overt thrombocytopenia is absent.

Prevalence of heparin-induced antibody in African-American hemodialysis patients – comparison to non-dialysis patients

Heparin-induced antibody formation and thrombocytopenia are well-established complications of heparin use and may be associated with thromboembolic events. Our study aimed to establish the prevalence of heparin-induced antibodies (HIA), otherwise known as platelet factor 4 (PF4) antibodies, and their relationship to thrombocytopenia and thrombotic events in a group of predominantly African-American hemodialysis patients over 12 months. For comparison, the prevalence of HIA in thrombocytopenic patients with serum creatinine of less than 2.0 mg/dl tested for the antibody in the same period was evaluated. 36 hemodialysis patients on thrice-weekly, in-center treatments receiving heparin on dialysis were selected to have blood drawn predialysis for PF4 heparin antibodies (HIA). Complete blood counts (CBC) were also checked that day and monthly for the next 3 months. Outpatient records were reviewed for thromboembolic events, including thrombosis of dialysis access lines, grafts and fistulas. The HIA results for the dialysis patients were compared with HIA performed at the same lab for non-dialysis thrombocytopenic patients during the same period. 17 out of 36 (47%) hemodialysis patients had detectable HIA. There were no differences in gender, ethnicity, disease states, or duration of hemodialysis. None of the patients had thrombocytopenia, and the incidence of thromboembolic events was statistically not different from patients without HIA. The non-CKD thrombocytopenic group had a lower incidence, 16/88 (18%) of positive HIA. Heparin-induced antibodies are relatively common in patients receiving hemodialysis. However, their presence does not appear to be associated with clinical consequences. Therefore, testing for HIA should be done only if a clinical indication is present.

Immature platelet fraction as novel laboratory parameter predicting the course of neonatal thrombocytopenia

Immature platelet fraction as novel laboratory parameter predicting the course of neonatal thrombocytopenia

Soluble Platelet Glycoprotein V in Distinct Disease States of Pathological Thrombopoiesis

Quantitative platelet disorders (i.e., thrombocytosis or thrombocytopenia) may also be associated with qualitative platelet alterations. Clonal thrombocythemia (CT), reactive thrombocytosis (RT), immune thrombocytopenic purpura (ITP), and thrombocytopenia of aplastic pancytopenia (AA) or infiltrative bone marrow disorders represent the major classes of pathological thrombopoiesis. Glycoprotein V may serve as an in vivo marker of platelet activation in thrombotic and hemorrhagic states. The aim of this study was to assess circulating plasma soluble platelet glycoprotein V (sGPV) concentrations in distinct disease states of pathological thrombopoiesis. The whole study group comprised 20 patients with thrombocytopenia, 32 patients with thrombocytosis and 14 healthy adults as the control group. sGPV was significantly increased in the group of thrombocytosis patients in comparison to the thrombocytopenic group and the healthy control groups. When sGPV levels were corrected according to platelet number (sGPV/tr), this ratio was very high in patients with thrombocytopenia compared to patients with thrombocytosis and the control group. Our results suggest that there is an ongoing platelet activation associated with thrombocytosis regardless of its origin is either CT or RT. Therefore, glycoprotein V system may serve to activate residual platelets in thrombocytopenia regardless of its origin is either ITP or AA.

Mechanism of Thrombocytopenia in Hepatitis C as Determined by the Immature Platelet Fraction.

Thrombocytopenia is a frequent complication in patients with hepatitis C. Possible mechanisms include hypersplenism, immune-mediated platelet destruction, and drug-induced impairment of platelet production. The immature platelet fraction (IPF), determined on an automated blood cell analyzer (Sysmex XE-2100), has been shown to be useful in differentiating consumptive and aplastic causes of thrombocytopenia. We studied 31 patients known to have hepatitis C, 21 with thrombocytopenia (platelet count <100,000/uL) and 10 with normal platelet counts (>140,000/uL). None of the patients was taking interferon. Blood samples were drawn for CBC with platelet count, IPF (%), and thrombopoietin (TPO) assay (Quantikine TPO ELISA). The presence or absence of splenomegaly and liver function test results were noted. In the thrombocytopenic group IPF was elevated above the upper limit of the reference range (>7.1%) in 12/21 (57%) patients, suggestive of peripheral platelet consumption. TPO levels (known to correlate inversely with platelet/megakaryocyte mass) were within the normal range (<146pg/mL) in 11/12 (92%) of these patients, implying adequate megakaryocyte mass, which is further evidence of peripheral platelet consumption in this group. Splenomegaly was present in 8 of these 12 patients, suggesting that hypersplenism may be the mechanism for thrombocytopenia in this sub-group. IPF was within normal limits in 9/21 (43%) of the thrombocytopenic patients, implying either decreased platelet production or ineffective thrombopoiesis as the major cause of thrombocytopenia in this group. TPO levels were within the normal range in 8/9 (89%) of these patients, again implying adequate megakaryocyte mass, and suggesting that ineffective or impaired thrombopoiesis, rather than decreased platelet production, may be the major mechanism for thrombocytopenia in this group. Splenomegaly was present in 7 of these 9 patients, thus hypersplenism cannot be ruled out as at least a contributory factor in this sub-group (in spite of normal IPF values). One patient in this group had an elevated TPO level, suggestive of megakaryocyte hypoplasia. In the group of patients with normal platelet counts IPF was within normal limits in 8/10 patients, and minimally elevated in the other 2 patients. TPO levels were within normal limits in this entire group, and no patients in this group had splenomegaly. In conclusion, our findings suggest that peripheral platelet consumption is a major cause of thrombocytopenia in patients with hepatitis C (at least 57% of patients in this study), predominantly secondary to hypersplenism. Other possible causes of peripheral platelet consumption (in those without splenomegaly) include immune-mediated platelet destruction secondary to antibodies, immune complexes or drugs. In the remaining patients (43% in this study) ineffective thrombopoiesis may be the major mechanism of thrombocytopenia, possibly related to the effect of virus, cytokines, drugs or antibodies on thrombopoiesis, in the presence of adequate megakaryocytes in the marrow. Decreased platelet production (megakaryocyte hypoplasia) appears to be an unusual mechanism of thrombocytopenia in these patients.

The Immature Platelet Fraction in HIV Patients with Thrombocytopenia.

Thrombocytopenia is a common clinical feature of HIV infection. Given the number of possible etiologies of thrombocytopenia in a patient with known HIV, a peripheral blood test effective in determining the likely pathophysiologic basis of the thrombocytopenia would be a valuable clinical tool. Immature platelets are released early from the bone marrow in response to increased platelet turnover. These platelets contain residual megakaryocyte mRNA and have been termed reticulated platelets. A new assay, the Immature Platelet Fraction (IPF), measures the reticulated platelet count in peripheral blood. Patients with increased destruction of platelets from such conditions as ITP consistently have a higher IPF percent, while patients with decreased platelet production have a low or normal IPF percent. The goal of our study was to determine the performance characteristics of the IPF assay in HIV patients with thrombocytopenia and to see if the IPF percent could be used to help elucidate the etiology of low platelet counts in this group of patients. All adult patients admitted to the Johns Hopkins Hospital with a diagnosis of HIV and a platelet count less than 150,000 were eligible for enrollment. 62 patients were identified from February 2007 to June 2007. 34 control samples were obtained from inpatients with HIV who were not thrombocytopenic. In addition, 81 samples were available from non-HIV historical controls with normal platelet counts. The mean platelet count in the HIV thrombocytopenic group was 92,000 while the mean platelet count in the HIV control group was 254,000 (p value <.001). The mean platelet count in the non-HIV historical control group was 274 (p=.34 when compared to the HIV control group). The mean IPF percent in the HIV thrombocytopenic group was 10.2% as compared to 6.8% in the HIV control group (p=.001). The mean IPF in historical non-HIV controls was 3.1% (p<.001 for both the HIV thrombocytopenic and the HIV control group). Univariate analyses were conducted to identify potential individual predictors of a high IPF percent. Backward selection was then performed using multivariate linear models with a threshold Wald test p-value of 0.05. ITP, diabetes mellitus and cirrhosis were significantly associated with a higher IPF percent with a co-efficient (95% confidence interval) of 6.98 (3.05–10.91), 4.73 (1.39–8.06), and 14.18 (9.7–18.66), respectively. CD4 count, HIV viral load, hepatitis C and reticulocyte count were not correlated with IPF percent. Our results suggest that patients with HIV have increased platelet turnover as compared to patients without HIV. Thrombocytopenic patients with HIV have increased platelet turnover relative to both non-thrombocytopenic HIV patients and to historical non-HIV controls. History of ITP, diabetes mellitus, and cirrhosis are predictive of an elevated IPF percent. Reticulocyte count is not correlated to IPF percent, suggesting that a low reticulocyte count is not a reliable marker for decreased bone marrow production in HIV thrombocytopenia. It is unlikely that the IPF assay alone can be used to determine the pathophysiologic basis of thrombocytopenia in any single patient with HIV. Further work needs to be done to clarify the utility of the IPF assay in this group of patients.