Patrick G Northup

University of Virginia, Charlottesville, Virginia, United States

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Publications (83)406.46 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: The complex nature of haemostasis in patients with liver disease can result in bleeding and/or thrombosis. These opposing outcomes, which have multiple contributing factors, can pose diagnostic and therapeutic dilemmas for physicians. With the high rate of haemorrhagic complications in patients with cirrhosis, we examine the various procoagulants available for use in this population. In this Review, we describe the clinical and current rationale for using each of the currently available procoagulants-vitamin K, fresh frozen plasma (FFP), cryoprecipitate, platelets, recombinant factor VIIa (rFVIIa), antifibrinolytics, prothrombin concentrate complexes (PCC), desmopressin and red blood cells. By examining the evidence and use of these agents in liver disease, we provide a framework for targeted, goal-directed therapy with procoagulants.
    Nature Reviews Gastroenterology &#38 Hepatology 07/2014; · 10.43 Impact Factor
  • Hepatology 05/2014; · 12.00 Impact Factor
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    ABSTRACT: BACKGROUND: Hospitalized patients with cirrhosis are at risk to develop venous thromboembolism. Although current guidelines support the routine administration of thromboprophylaxis to hospitalized patients, there is limited data regarding the safety or efficacy of this practice in hospitalized cirrhosis patients. AIMS: We aimed to determine if administration of thromboprophylaxis was associated with increased complication rates for hospitalized cirrhosis patients. METHODS: Data were collected on patients admitted to the University of Virginia between 2007 and 2010. Study personnel systematically collected data on complications, including gastrointestinal bleed, venous thromboembolism and death directly from the medical record. RESULTS: A total of 235 patients (accounting for 355 discrete hospitalizations in which thromboprophylaxis was administered) met inclusion criteria accounting for 1660 person-days of thromboprophylaxis administered to patients. The mean age at admission was 58 (95% CI 57.1-59.2) years and 217 (61%) were male patients. The mean admission model for end-stage liver disease (MELD) score was 16.2 (95% CI 15.5-16.9). The mean hospital length of stay was 6.5 (95% CI 5.9-7.4) days. In patients who received thromboprophylaxis, the mean treatment length was 4.7 days (95% CI 4.2-5.2). There were nine gastrointestinal bleeding events (2.5% of admissions), five venous thromboembolisms (1.4% of admissions), two cases of heparin-induced thrombocytopenia (0.5% of admissions) and 14 deaths overall (3.9% of admissions). CONCLUSIONS: The use of thromboprophylaxis in hospitalized cirrhosis patients is not associated with high rates of gastrointestinal bleeding or death.
    Liver international: official journal of the International Association for the Study of the Liver 05/2013; · 3.87 Impact Factor
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    ABSTRACT: Until recently, it was widely accepted that patients with cirrhosis have a bleeding tendency related to the changes in the hemostatic system that occur as a consequence of the disease. However, it has now been well established that patients with cirrhosis are at risk for both bleeding and thrombotic complications. These thrombotic complications include portal vein thrombosis, deep vein thrombosis and pulmonary embolism, and coronary or cerebrovascular infarctions. Antithrombotic drugs to prevent or treat thrombotic complications in patients with cirrhosis have been used only minimally in the past due to the perceived bleeding risk. As the thrombotic complications and the necessity of antithrombotic treatment in these patients is increasingly recognized, the use of antithrombotic drugs in this population is likely increasing. Moreover, given the rising incidence of fatty liver disease and generally longer survival times of patients with chronic liver diseases, it would be reasonable to presume that some of these thrombotic complications may be increasing in incidence over time. In this review we will outline the indications for antithrombotic treatment in patients with cirrhosis. Furthermore, we will discuss the available antithrombotic drugs and indicate possible applications, advantages, and caveats. Since for many of these drugs, very little experience in patients with cirrhosis exists, these data are essential in the design of future clinical and laboratory studies on mechanisms, efficacy, and safety of the various antithrombotic strategies in these patients.
    Journal of Hepatology 03/2013; · 9.86 Impact Factor
  • Patrick G Northup, Stephen H Caldwell
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    ABSTRACT: The human hemostasis system is complex and poorly understood after decades of intense scientific study. Despite multiple defects in routine coagulation laboratory studies in patients with chronic liver disease, there is growing evidence that these patients are effectively "rebalanced" with regard to procoagulant and anticoagulant activity and that most of these patients remain in a tenuous but balanced state of hemostasis. A major difficulty in the assessment of these patients is that there are no established laboratory tests that accurately reflect the changes in both the procoagulant and anticoagulant systems and therefore routine laboratory testing is misleading to the clinician and may prompt inappropriate or risky therapies with little real benefit to the patient. The international normalized ratio (INR) is an example of this type of misleading test. While the INR is inextricably linked to prognosis and severity of protein synthetic dysfunction in acute and chronic liver disease, it is a very poor marker for bleeding risk and should not be used in isolation for this purpose. Coagulation disorders are critical in the management of frequent clinical scenarios such as esophageal variceal bleeding, invasive and percutaneous procedures, portal vein thrombosis, venous thromboembolism, and acute liver failure. This article summarizes the pathophysiology of hemostasis in liver disease, describes the strengths and weaknesses of various laboratory tests in assessment of these patients, and outlines the optimal management of hemostasis for some common clinical scenarios. Further research is needed for proper understanding of hemostasis in liver disease in order to optimally and safely manage these complex patients.
    Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 03/2013; · 5.64 Impact Factor
  • Gastroenterology 02/2013; · 12.82 Impact Factor
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    ABSTRACT: Several studies have shown a direct role of liver atrophy in the pathogenesis of thrombocytopenia of cirrhosis via reduced production of thrombopoeitin. About 181 patients listed for liver transplantation at a single transplant center were evaluated at the time of listing with laboratory tests and volumetric liver measurements using computed tomography. Expected normal liver volume was calculated using the Heinemann formula. Liver volume ratio (LVR) was calculated as actual liver volume over expected liver volume. Patients were predominantly male (70.7%), with viral hepatitis (60.2%), had a mean age of 51.8 years (SD 8.7), model for end stage liver disease (MELD) of 14 (SD 6.4), LVR of 0.95 (SD 0.3), and platelet count of 105 000/mcL (SD 66 000). Platelet count (P < 0.0001) correlated more strongly with LVR than MELD, MELD components (P = 0.27) or serum albumin (P = 0.003). Platelet count (HR 0.987, 95% CI 0.979-0.994, P = 0.001) was a strong independent predictor of mortality. Patients with platelet count < 100 000/mcL had a shorter survival (935 vs. 1396 days, P = 0.002) and higher death rate (42.2% vs. 23.6%, P = 0.01), but no different transplantation rate (36.7% vs. 33.3%, P = 0.64) compared to those with platelet count ≥ 100 000/mcL. Low platelet count corresponds to higher waiting list mortality and is a sign of advanced liver atrophy.
    Transplant International 01/2013; · 3.16 Impact Factor
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    ABSTRACT: BACKGROUND: Few studies have described the role of multimodality therapy and the complexity of endoscopic management of pancreatic duct disruption. Our study aim was to analyse and confirm factors associated with the resolution of pancreatic duct disruption. METHODS: Over 6 years, retrospective data on patients with pancreatic duct disruption managed endoscopically were retrieved. Success was defined as resolution of the pancreatic duct disruption at 12 months. Logistic regression analysis was performed to determine factors associated with resolution. RESULTS: 113 patients (78 male) with a mean age 51.3 year were included. Resolution of the pancreatic duct leak occurred in 80 cases (70.2%). 72 cases received transpapillary pancreatic duct stents, with 51 demonstrating resolution of pancreatic duct leak (71%) cystenterostomy was performed in 68 patients with 51 resolved (75%). In partial duct disruptions, pancreatic duct stenting combined with endoscopic drainage of fluid collections resulted in an increased rate of resolution (80%) compared to complete disruptions treated in a similar manner (57%). In complete pancreatic ductal disruptions, transpapillary pancreatic duct stenting had no additional benefit (9/17, 52.9%) compared to cystenterostomy or percutaneous drainage alone (24/34, 70.6%; P=0.61). CONCLUSION: Pancreatic duct disruptions require multimodality treatment, addressing not only the integrity of the pancreatic duct but also any fluid collections associated. Partial ductal disruption should be managed by a bridging stent.
    Digestive and Liver Disease 10/2012; · 3.16 Impact Factor
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    Neeral L Shah, Patrick G Northup, Stephen H Caldwell
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    ABSTRACT: Background. The relative incidence of bleeding and thrombotic events and the use of blood products in hospitalized cirrhosis patients have not been widely reported. We aimed to estimate the magnitude of bleeding events and venous thrombosis in consecutive hospitalized cirrhotic patients over a finite time period and to examine the amount and indications for blood product use in cirrhosis patients admitted to a tertiary care center. Results. Among patients admitted with decompensated liver disease, 34 (40%) suffered bleeding events (about one-half non-variceal) and 6 patients (7%) suffered deep venous thrombosis. In the blood product survey, 168 patients were transfused with plasma or platelets during the survey inter- vals. Liver disease patients accounted for 7.7% of the total but disproportionately consumed 32.4% (46 of 142) of the units of plasma mostly administered as prophylaxis. In contrast, cirrhosis patients received only 7 of the 53 units of platelets transfused (13.2%) during the survey intervals. Conclusions. Coagulation issues constitute a common problem in patients with liver disease. Recent advances in laboratory testing have shown that stable cirrhosis patients are relatively hypercoagulable. The result of this prospective survey among decompensated (unstable) cirrhosis patients shows that, while DVT is not uncommon, bleeding (non-variceal in one half) remains the dominant clinical problem. This situation likely sustains the common practice of plasma infusion in these patients although its use is of unproven and questionable benefit. Better clinical tools are needed to refine clinical practice in this setting.
    Annals of hepatology: official journal of the Mexican Association of Hepatology 09/2012; 11(5):686-90. · 1.67 Impact Factor
  • Patrick G Northup, Zachary H Henry
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    ABSTRACT: Non-selective beta-blockers have been a cornerstone of therapy for prevention of esophageal variceal bleeding in cirrhosis patients for more than two decades. When lowering the hepatic vein portal pressure gradient (HVPG) below 12 mm Hg or decreasing the pressure by 20% from baseline, these drugs are of proven benefit in reducing variceal bleeding and improving survival in this patient population. The recent work by Hendández-Gea et al., suggests that initiation of the beta-blocker nadolol in cirrhosis patients with high-risk varices can delay or prevent the first occurrence of clinically evident ascites. This finding comes with some caveats, however. The beneficial effect was only seen in patients who had an improvement by 10% or more from baseline HVPG pressure (only 51% of the treated patients in this study). This class of medications has some risk and tolerance issues, and many patients do not respond, even when the heart rate is optimally decreased. Despite this, the use of beta-blockers may be beneficial in the primary prevention of the formation of ascites and further decompensation of cirrhosis.
    The American Journal of Gastroenterology 03/2012; 107(3):428-30. · 7.55 Impact Factor
  • Patrick G Northup, Carl L Berg
    Liver Transplantation 02/2012; 18(4):381-3. · 3.94 Impact Factor
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    ABSTRACT: Nonalcoholic fatty liver disease (NAFLD) is a spectrum of disorders with a high prevalence in the industrialized world. Despite the high prevalence, the etiology and fundamental pathophysiology for the disease process is poorly understood. There is now a growing fund of knowledge suggesting that the ongoing inflammatory state associated with NAFLD leads to a low-level activation of the coagulation system. Although the data supporting this activation of the coagulation system are significant, the link with end-organ disease, mainly cardiovascular disease, is less firm and mostly epidemiological. In this review, we will explore the evidence for and against a hypercoagulable or thrombophilic state in NAFLD. We will examine possible pathophysiologic explanations and mechanisms, human epidemiologic and population-based data, and the possible therapeutic and preventative implications for treatment of thrombophilia in patients with this disease process.
    Seminars in Liver Disease 02/2012; 32(1):39-48. · 8.27 Impact Factor
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    ABSTRACT: Transcatheter arterial chemoembolization (TACE) improves survival in patients with unresectable hepatocellular carcinoma (HCC). Partial liver radiotherapy with modern techniques has been shown to be safe. The purpose of this study was to evaluate the survival value of external beam radiation therapy (EBRT) with concurrent chemotherapy combined with TACE. A University of Virginia Interventional Radiology patient log was used to identify patients treated with TACE ± another modality from 1999 through 2005. During this time, 44 patients received TACE for unresectable HCC, and 7 of these received adjuvant EBRT. Univariate analysis and multivariable proportional hazards survival modeling were used to identify factors impacting survival. We compared 37 patients receiving TACE alone to 7 receiving TACE and EBRT (5 with concurrent capecitabine). Unadjusted mean transplant-free survival times were TACE only = 376 days (standard error [SE] = 63 days), TACE + EBRT = 879 days (SE = 100 days). EBRT, TNM stage, and MELD score were important predictors for survival on univariate analysis (p < .10). The adjusted hazard ratio for transplant or death in the TACE + EBRT group was 0.15 (0.02-0.95, p = .026). EBRT with concurrent chemotherapy following TACE is feasible and well tolerated with modern treatment techniques. Further research should be directed toward determining the potential overall survival benefit of adjuvant EBRT with chemotherapy following TACE for hepatocellular carcinoma.
    Gastrointestinal cancer research: GCR 01/2012; 5(1):13-7.
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    ABSTRACT: MELD (model for end-stage liver disease) exception awards affect the liver allocation process. Award rates of specific nonhepatocellular carcinoma exceptions, termed symptom-based exceptions (SBE), differ across UNOS regions. We aimed to characterize the regional variability in SBE awards and examine predictive factors for receiving a SBE in the MELD era. The OPTN liver transplant and waiting list dataset was analyzed for waiting list registrants during the MELD allocation on February 27, 2002, until November 22, 2006. Competing risks proportional hazards regression analysis was used to examine predictors for receiving a SBE in 39 169 registrants. The hazard ratios for receiving a SBE differed significantly across regions when adjusted for multiple variables including age, gender, ethnicity, physiologic MELD score, blood group, functional status, etiology of liver disease, insurer and education level. Utilization of SBE is highly significantly variable across UNOS regions, and does not correlate with organ availability as estimated by the regional mean physiologic MELD score at transplantation. Patients with Medicaid as their primary payer have a lower likelihood of receiving a SBE award, while patients with cryptogenic/NASH cirrhosis or cholestatic liver disease have a higher likelihood of receiving a SBE. Reasons for these regional and demographic disparities deserve further investigation.
    American Journal of Transplantation 11/2011; 11(11):2353-61. · 6.19 Impact Factor
  • Transplant International 09/2011; · 3.16 Impact Factor
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    ABSTRACT: This study compared post-transplant outcomes of patients with hepatocellular carcinoma (HCC) who took sorafenib prior to orthotopic liver transplantation (OLT) with those patients who were not treated with sorafenib. Thirty-three patients with HCC who were listed for liver transplantation were studied: 10 patients were treated with sorafenib prior to transplantation in an attempt to prevent progression of HCC while awaiting transplant. The remaining 23 patients were considered controls. The mean duration of sorafenib use was 19.2 (SD 25.2) weeks. Overall death rates were similar between the sorafenib group and control group (20% vs. 8.7%, respectively, P = 0.56). However, the patients in the sorafenib group had a higher incidence of acute cellular rejection following transplantation (67% vs. 22%, OR = 7.2, 95% CI 1.3-39.6, P = 0.04). The sorafenib group also had a higher rate of early biliary complications (67% vs. 17%, OR = 9.5, 1.6-55.0, P = 0.01). The use of sorafenib was found to be an independent predictor of post-transplant biliary complications (OR 12.6, 1.4-116.2, P = 0.03). Sorafenib administration prior to OLT appears to be associated with an increase in biliary complications and possibly in acute rejection following liver transplantation. Caution should be taken in this setting until larger studies are completed.
    Transplant International 07/2011; 24(10):991-8. · 3.16 Impact Factor
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    ABSTRACT: Percutaneous endoscopic gastrostomy (PEG) is an invasive procedure that can result in bleeding. Guidelines recommend discontinuing clopidogrel for 7 to 10 days, but not withholding aspirin, before PEG. Serotonin reuptake inhibitors (SRIs) have been associated with an increased risk of GI bleeding. To determine whether there is an association between periprocedural aspirin, clopidogrel, or SRI use and bleeding in patients who underwent PEG tube placement. Retrospective cohort study. Large quaternary-care academic medical center. A total of 990 patients (525 men) with a median age of 69.8 years who underwent PEG from January 1999 to April 2009. PEG tube placement. GI bleeding. Sixteen patients (1.6%) had evidence of bleeding during the first 48 hours after PEG, and 12 patients (1.2%) had evidence of bleeding between 48 hours and 14 days after PEG. Thirty-six patients (3.6%) received high-dose aspirin (>325 mg), 27 patients (2.7%) received clopidogrel (75 mg), and 99 patients (10%) received an SRI before PEG. Twenty-four patients (2.4%) received high-dose aspirin, 25 patients (2.5%) received clopidogrel, and 130 patients (13.1%) received an SRI after PEG. Multivariate analysis demonstrated no association between periprocedural use of aspirin (at any dose) or clopidogrel and post-PEG bleeding. However, SRIs administered 24 hours or less before PEG were associated with a significantly higher odds of post-PEG bleeding (adjusted odds ratio 4.1; 95% CI, 1.1-13.4; P = .04). Retrospective, single-center study with limited statistical power despite a relatively large cohort of patients. Use of aspirin or clopidogrel before or after PEG was not associated with procedure-related bleeding. SRI use in the 24 hours before PEG was associated with an increased risk of bleeding.
    Gastrointestinal endoscopy 07/2011; 74(1):22-34.e1. · 6.71 Impact Factor
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    ABSTRACT: Ascites leaks (AL) in patients with end-stage liver disease (ESLD) are associated with significant morbidity and mortality regardless if they are medically or surgically managed. In a pilot study, 14 ESLD patients with AL underwent treatment with fibrin glue injection around the leak after failing conservative therapy. The end point of this study was the cessation of AL in the short term and the maintenance of a leak-free abdomen in the long term, allowing for medical optimization of the patients. Median age of the 10 men and 4 women was 50 (range 26-67) years. Underlying ESLDs were chronic hepatitis C (n=5), alcoholic LD (n=2), cryptogenic cirrhosis (n=2), and miscellaneous (n=5). There were six leaking incisions posthernia repair (three umbilical and three inguinal), two leaking/ruptured umbilical hernias, four leaking paracentesis sites, one leaking Jackson-Pratt (JP) drain canal, and one leaking laparoscopic trocar site. Average AL volume per day was 1000 (range 400-2000) mL. All leaks were immediately resolved with a 3-5 mL fibrin glue injection. Five recurred and required a second injection (four within 24 hours). Mental status improved in 7 patients (West Haven Criteria: grade II to I [n=6], grade III to I [n=1]). Median model of end-stage liver disease scores improved from 23 (range 8-33) to 20 (range 14-26). There were no infections, bleeds, or other injection-related complications. Average follow-up for these patients was 441.6 days (range 2-852). Five patients underwent liver transplant (LT) median 15 (range 4-270) days postinjection; 2 of them died. Another 3 patients died (2 from sepsis and 1 from metastatic cancer). Fibrin glue injection for the control of AL is a simple and safe bedside procedure that quickly controls AL, allowing for patient recovery in anticipation of further care.
    Journal of Laparoendoscopic & Advanced Surgical Techniques 05/2011; 21(7):609-14. · 1.07 Impact Factor
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    ABSTRACT: Preoperative staging of pancreatic cancer is crucial for proper therapy. Through this study, we aimed to compare the ability of endoscopic ultrasound (EUS) and magnetic resonance imaging (MRI) to effectively detect and stage pancreatic cancer. One hundred twenty-seven patients undergoing EUS-fine-needle aspiration and MRI for the workup of pancreatic cancer were captured in a prospective database for comparison. The final surgical stage was recorded in patients who went to surgery. Of 127 patients, 48 were surgically explored, and of these, 22 (46%) underwent pancreaticoduodenectomy. Agreement in the patients' staging between EUS and MRI was 94 (74%) of 127. Magnetic resonance imaging was more likely to report metastatic disease or arterial involvement. The overall correlation between EUS and MRI was marginal (κ = 0.42; 95% CI, 0.26-0.58). Of the 48 surgically explored patients, 12 (25%) were understaged by MRI, 13 (27%) were understaged by EUS, and 1 (2%) were overstaged. Endoscopic US and MRI had a sensitivity of 34 (97.2%) of 35 for stage II tumors and 35 (100%) of 35 for lower-stage tumors, respectively. Endoscopic US and MRI had marginal correlation for staging, especially the more advanced tumors. Although EUS has the added advantage of tissue acquisition for confirmation, the tumors understaged by both the modalities were different. Therefore, both tests should be performed for accurate staging.
    Pancreas 05/2011; 40(4):567-70. · 2.95 Impact Factor
  • Gastroenterology 01/2011; 140(5). · 12.82 Impact Factor

Publication Stats

927 Citations
406.46 Total Impact Points

Institutions

  • 2004–2014
    • University of Virginia
      • • Division of Gastroenterology and Hepatology
      • • Digestive Health Research Center
      Charlottesville, Virginia, United States
  • 2013
    • Beth Israel Deaconess Medical Center
      Boston, Massachusetts, United States
  • 2008
    • University of Michigan
      • Department of Internal Medicine
      Ann Arbor, MI, United States