Endogenous Heparinoids Detected by anti-Xa Activity are Present in Blood during Acute Variceal Bleeding in Cirrhosis. A Prospective Study

2014 ◽  
Vol 23 (2) ◽  
pp. 187-194 ◽  
Author(s):  
Christos Triantos ◽  
Emmanuel Louvros ◽  
Maria Kalafateli ◽  
Anne Riddell ◽  
Ulrich Thalheimer ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Variceal Bleeding ◽  
Blood Cells ◽  
Venous Pressure ◽  
White Blood Cells ◽  
International Normalized Ratio ◽  
Ulcer Bleeding ◽  
Factor X ◽  
Packed Red Blood Cells ◽  
Bacterial Peritonitis

Background & Aims: Endogenous heparinoids have been detected by thromboelastography and quantified by clotting based anti-Xa activity assays in patients with cirrhosis, but their presence in variceal bleeding has not been established yet.Methods: Clotting based anti-Xa activity was measured in A) 30 cirrhotics with variceal bleeding, B) 15 noncirrhotics with peptic ulcer bleeding, C) 10 cirrhotics without infection or bleeding, and D) 10 cirrhotics with hepatocellular carcinoma (HCC).Results: Anti-Xa activity was not detected in ulcer bleeders or in cirrhotics without infection or bleedingbut was present in seven (23%) variceal bleeders (median levels: 0.03 u/mL (0.01-0.07)) and was quantifiable for 3 days in six of seven patients. Four of seven variceal bleeders with anti-Xa activity present had HCC (p=0.023). Age, creatinine, platelet count and total infections the second day from admission were significantly correlated with the presence of measureable anti-Xa levels (p=0.014, 0.032, 0.004 and 0.019, respectively). In the HCC group, anti-Xa activity was present in three patients (30%) [median levels: 0.05 u/mL (0.01-0.06)].Conclusions: In this study, variceal bleeders and 30% of the patients with HCC had endogenous heparinoids that were detected by a clotting based anti-Xa activity assay, whereas there was no anti Xa activity present in patients with cirrhosis without infection, or bleeding or HCC, nor in those with ulcer bleeding. Thus, the anti-Xa activity is likely to be a response to bacterial infection and/or presence of HCC in cirrhosis.List of abbreviations: AFP, alpha-fetoprotein; aPTT, activated partial thromboplastin time; CP, Child-Pugh; FXa, activated factor X; GAGS, glycosaminoglycans; Hb, hemoglobin; HCC, hepatocellular carcinoma; HVPG, hepatic venous pressure gradient; INR, International normalized ratio; LMWHs, low molecular weight heparins; MELD, Model for End-stage Liver Disease; PPP, platelet-poor plasma; PRBC, packed red blood cells; PT, prothrombin time; SBP, sponataneous bacterial peritonitis; TEG, thromboelastography; WBC, white blood cells.

scholarly journals Detection of circulating donor white blood cells in patients receiving multiple transfusions

Blood ◽  
1992 ◽  
Vol 80 (2) ◽  
pp. 551-555 ◽  
Author(s):  
PT Adams ◽  
RD Davenport ◽  
DA Reardon ◽  
MS Roth
Keyword(s):  
Blood Cells ◽  
White Blood Cells ◽  
Future Application ◽  
Pcr Analysis ◽  
Packed Red Blood Cells ◽  
Female Patients ◽  
Routine Administration ◽  
Exact Etiology ◽  
Multiple Blood ◽  
Dyz1 Locus

Abstract Significant morbidities are associated with the routine administration of blood products. Although the exact etiology of these complications may be unknown, many are thought to arise from the incidental cotransfusion of “donor” lymphocytes. We have developed an assay to detect small numbers of male white blood cells (WBCs) circulating in female patients who have received multiple blood transfusions using the polymerase chain reaction (PCR). Twenty female patients undergoing major surgical procedures were studied and received an average of 9.3 U of packed red blood cells (4.8 U from male donors) and 11.7 U of platelets (6.1 U from male donors). DNA was extracted from whole blood or peripheral blood buffy coats posttransfusion and PCR performed using oligonucleotides designed to amplify a segment within the repetitive Y- chromosome DYZ1 locus. Posttransfusion, 15 of 20 women showed evidence of circulating male WBCs for an average of 2.0 days (range, 1 to 6). We conclude that (1) DYZ1 PCR analysis is a useful approach for the detection of small numbers of circulating transfused male WBCs in female patients; and (2) circulating donor WBCs persist for a mean of 2.0 days in the majority of women receiving multiple transfusions. Future application of this technique may detect persisting or proliferating WBCs and lead to an improved understanding of common transfusion-related morbidities.

Mirasol™ Pathogen Reduction of Packed Red Blood Cells (PRBCs) and Apheresis Platelet (Aplt) Concentrates Decreases Neutrophil Priming Activity Generated during Storage.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2893-2893
Author(s):  
Daniel R. Ambruso ◽  
Gail Thurman ◽  
Susanne Marschner ◽  
Ray Goodrich
Keyword(s):  
Blood Cells ◽  
Blood Donation ◽  
Uv Light ◽  
White Blood Cells ◽  
Biologically Active ◽  
Control Group ◽  
Superoxide Anion Production ◽  
Packed Red Blood Cells ◽  
Pathogen Reduction ◽  
Priming Activity

Abstract Introduction: During storage of cell containing components including PRBCs and Aplts, biologically active compounds such as lysophosphatidylcholine and other lipids are generated. Identified by their ability to enhance the fMLP stimulated respiratory burst in neutrophils, these biologic response modifiers (BRMs) have been implicated in the pathogenesis of transfusion related acute lung injury (TRALI). The Mirasol pathogen reduction system is a process that uses riboflavin and UV light to modify nucleic acids, reduce infectious pathogen load and inactivate white blood cells in blood components. An additional effect of the Mirasol in PRBCs and Aplts is a decrease in priming activity accumulated during storage. Methods: PRBCs were produced by standard technique from whole blood donation. PRBCs were treated with Mirasol (8) and stored; untreated, washed and stored in AS-3 additive solution (2); or produced untreated and stored in AS-3 (6). For platelets collected on Trima, one set of products was treated with Mirasol procedure on day 0. Another set was exposed to 25Gy of gamma irradiation. The control group was untreated and stored under standard conditions. Samples were removed on day 0 and 43 (PRBCs) and day 0, 5, 7 (Aplts); cells removed from residual supernatant/plasma by centrifugation and frozen at -70°C. Samples (10% by volume) were assayed to measure the ability to enhance the fMLP stimulated superoxide anion production (O2−) by peripheral blood neutrophils. O2− was measured as SOD inhibitable cytochrome c reduction and expressed as a ratio of the response to plasma followed by fMLP compared to fMLP alone. Priming by platelet activating factor (PAF) was a positive control. Priming is defined as >1.5 fold increase in O2− over the results for fMLP alone. Results: Samples from Mirasol treated PRBCs show no enhancement of fMLP stimulated O2− production either at day 0 or after 43 days of storage (Top figure). Washed controls exhibit a similar pattern. Unwashed controls demonstrate a small amount of priming on day 0 which further increased on day 43. For Aplts (Bottom figure), day 0 samples exhibited minimal priming. For Mirasol treated products, no changes were seen on days 5 and 7. In contrast, both gamma irradiated and untreated Aplts showed an increase comparable to that seen with PAF. Conclusion: Treatment of PRBCs and Aplts with Mirasol reduced the generation of priming activity normally developed during storage, possibly representing a decrease in production of BRMs including priming lipids. Mirasol treatment of cell containing components may reduce one class of etiologic agents associated with TRALI and may be a potential approach to reduce risk for this adverse event of transfusion. Figure Figure

scholarly journals Assessment of the feasibility of TACE combined with intratumoral injection of cisplatin in hepatocellular carcinoma

Open Medicine ◽  
2015 ◽  
Vol 10 (1) ◽  
Author(s):  
Song Zhaomin ◽  
Liu Zifeng ◽  
Yin Chenghui ◽  
Yang Jiali ◽  
Peng Xun ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Blood Cells ◽  
White Blood Cells ◽  
Tumor Stage ◽  
Intratumoral Injection ◽  
Intrahepatic Metastasis ◽  
Test Cases ◽  
Point Injection ◽  
Tace Group ◽  
Student’S T

Abstract The feasibility of transcatheter arterial chemoembolization (TACE) combined with intratumoral injection of cisplatin as treatment for hepatocellular carcinoma. 30 cases receiving TACE were denoted the TACE group, another 30 cases receiving TACE combined with an intratumoral multi-point injection of cisplatin were denoted the TACE/cisplatin group. Cases with partial remission/complete remission (PR/CR) were analyzed using 2 tests; alpha fetoprotein (AFP), aspartate amino transferase (AST), total bilirubin (TBIL), erythrocyte, and platelet levels were detected and the differences between two groups were analyzed using the Student’s t-test; cases with complications, including intrahepatic metastasis (IM), upper gastrointestinal bleeding (UGB), and liver failure were also counted. The correlation of clinical parameters with PR/CR was analyzed using multifactorial correlation analysis. Cases with PR/CR in the TACE/cisplatin group were significantly more than in TACE group, accompanied by significant declination in FAP. There were no significant differences of AST, ALT, TBIL, blood urea nitrogen (BUN), white blood cells (WBC), red blood cells (RBC), and platelets (PLT) between two groups; 3 cases with IM, one case with UGB and one case with LF were found in the TACE group, but only 1 case with IM was found in the TACE/cisplatin group. In addition, tumor stage was correlated with PR/CR. We concluded that TACE combined with intratumoral injection of cisplatin was more effective than TACE, and with fewer complications and side effects.

scholarly journals Rifaximin has the potential to prevent complications of cirrhosis

2018 ◽  
Vol 11 ◽  
pp. 175628481880030 ◽  
Author(s):  
Steven L. Flamm ◽  
Kevin D. Mullen ◽  
Zeev Heimanson ◽  
Arun J. Sanyal
Keyword(s):  
Acute Kidney Injury ◽  
Variceal Bleeding ◽  
Hepatorenal Syndrome ◽  
Kidney Injury ◽  
International Normalized Ratio ◽  
Meld Score ◽  
Bacterial Peritonitis ◽  
Complications Of Cirrhosis ◽  
End Stage ◽  
Post Hoc

Background: Cirrhosis-related complications are associated with poor prognosis. With our analyses, we examined the potential benefit of rifaximin in reducing the risk of developing cirrhosis-related complications. Methods: Adults with cirrhosis and hepatic encephalopathy (HE) in remission were randomly assigned to receive rifaximin 550 mg twice daily or placebo for 6 months with concomitant lactulose permitted. Post hoc analyses examined time to cirrhosis-related complications (HE, spontaneous bacterial peritonitis (SBP), variceal bleeding, acute kidney injury/hepatorenal syndrome). Subgroup analyses evaluated efficacy for select baseline disease characteristics. Results: Of patients receiving rifaximin ( n = 140) and placebo ( n = 159), 53.6% and 49.1%, respectively, had baseline Model for End-Stage Liver Disease (MELD) score ⩾ 12 and international normalized ratio (INR) ⩾ 1.2. Baseline ascites was observed in 36.4% (rifaximin) and 34.6% (placebo) of patients. In patients with MELD score ⩾ 12 and INR ⩾ 1.2, rifaximin reduced the relative risk (RR) of any first complication experienced during trial by 59% [hazard ratio (HR) = 0.41, 95% confidence interval (CI): 0.25–0.67; p < 0.001] versus placebo. For patients with baseline ascites, rifaximin reduced the RR of any first complication experienced during trial by 42% versus placebo (HR = 0.58, 95% CI: 0.34–1.0; p = 0.045). For some subgroups, there was a decrease in RR of complications of SBP, variceal bleeding, and acute kidney injury/hepatorenal syndrome with rifaximin versus placebo, although there were few events reported in the study. Conclusion: Rifaximin may reduce the incidence of cirrhosis-related complications and the recurrence of overt HE. [ ClinicalTrials.gov identifier: NCT00298038.]

scholarly journals Should vasoconstrictors be considered in a cirrhotic patient with acute non-variceal upper gastrointestinal bleeding?

2017 ◽  
Vol 5 (4) ◽  
pp. 240-244 ◽  
Author(s):  
Xingshun Qi ◽  
Hongyu Li ◽  
Xiaodong Shao ◽  
Zhendong Liang ◽  
Xia Zhang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cirrhosis ◽  
Gastrointestinal Bleeding ◽  
Variceal Bleeding ◽  
Upper Gastrointestinal Bleeding ◽  
International Normalized Ratio ◽  
Endoscopic Examination ◽  
Vein Thrombosis ◽  
Acute Upper Gastrointestinal Bleeding ◽  
Upper Gastrointestinal

Abstract Varices manifest as a major etiology of upper gastrointestinal bleeding in patients with chronic liver diseases, such as liver cirrhosis and hepatocellular carcinoma. By contrast, non-variceal upper gastrointestinal bleeding is rare. Pharmacological treatment differs between patients with variceal and non-variceal bleeding. Vasoconstrictors are recommended for the treatment of variceal bleeding, rather than non-variceal bleeding. In contrast, pump proton inhibitors are recommended for the treatment of non-variceal bleeding, rather than variceal bleeding. Herein, we present a case with liver cirrhosis and acute upper gastrointestinal bleeding who had a high risk of rebleeding (i.e., Child–Pugh class C, hepatocellular carcinoma, portal vein thrombosis, low albumin, and high international normalized ratio and D-dimer). As the source of bleeding was obscure, only terlipressin without pump proton inhibitors was initially administered. Acute bleeding episode was effectively controlled. After that, an elective endoscopic examination confirmed that the source of bleeding was attributed to peptic ulcer, rather than varices. Based on this preliminary case report, we further discussed the potential role of vasoconstrictors in a patient with cirrhosis with acute non-variceal upper gastrointestinal bleeding.

scholarly journals Detection of circulating donor white blood cells in patients receiving multiple transfusions

Blood ◽  
1992 ◽  
Vol 80 (2) ◽  
pp. 551-555 ◽  
Author(s):  
PT Adams ◽  
RD Davenport ◽  
DA Reardon ◽  
MS Roth
Keyword(s):  
Blood Cells ◽  
White Blood Cells ◽  
Future Application ◽  
Pcr Analysis ◽  
Packed Red Blood Cells ◽  
Female Patients ◽  
Routine Administration ◽  
Exact Etiology ◽  
Multiple Blood ◽  
Dyz1 Locus

Significant morbidities are associated with the routine administration of blood products. Although the exact etiology of these complications may be unknown, many are thought to arise from the incidental cotransfusion of “donor” lymphocytes. We have developed an assay to detect small numbers of male white blood cells (WBCs) circulating in female patients who have received multiple blood transfusions using the polymerase chain reaction (PCR). Twenty female patients undergoing major surgical procedures were studied and received an average of 9.3 U of packed red blood cells (4.8 U from male donors) and 11.7 U of platelets (6.1 U from male donors). DNA was extracted from whole blood or peripheral blood buffy coats posttransfusion and PCR performed using oligonucleotides designed to amplify a segment within the repetitive Y- chromosome DYZ1 locus. Posttransfusion, 15 of 20 women showed evidence of circulating male WBCs for an average of 2.0 days (range, 1 to 6). We conclude that (1) DYZ1 PCR analysis is a useful approach for the detection of small numbers of circulating transfused male WBCs in female patients; and (2) circulating donor WBCs persist for a mean of 2.0 days in the majority of women receiving multiple transfusions. Future application of this technique may detect persisting or proliferating WBCs and lead to an improved understanding of common transfusion-related morbidities.

Venous Ulceration: The Role of the White Blood Cell

1989 ◽  
Vol 4 (3) ◽  
pp. 153-159 ◽  
Author(s):  
H.J. Scott ◽  
G.M. McMullin ◽  
P.D. Coleridge Smith ◽  
J.H. Scurr
Keyword(s):  
Blood Cell ◽  
White Blood Cell ◽  
Chronic Venous Insufficiency ◽  
Blood Cells ◽  
Venous Insufficiency ◽  
Venous Pressure ◽  
White Blood Cells ◽  
Venous Ulceration ◽  
Cell Trapping

White blood cells (WBC) become trapped in the legs of patients with chronic venous insufficiency (CVI), in response to raised venous pressure. We have sampled blood from the foot and arm veins in normal patients and those with CVI. When the venous pressure in the arm was raised to 80 mmHg we demonstrated white cell trapping in both the hand and forearm, but we were unable to demonstrate WBC trapping in the foot, as opposed to the leg, in response to changes in posture. Capillary microscopy of the supra-malleolar skin of the ankle confirmed that a reduction of the number of funtional capillaries occured in response to an increase in venous pressure.

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