This document summarizes key findings from a study on coagulation abnormalities in patients with acute or chronic liver disease. It finds that while routine coagulation tests often indicate a bleeding tendency, the situation is complex as both pro-coagulant and anti-coagulant factors are affected. Patients can be in a balanced state but are at risk of tipping into a hypo- or hyper-coagulable condition. Tests such as thromboelastography and thrombin generation testing provide a more comprehensive assessment than standard coagulation tests. The balance of factors in liver disease patients may shift with conditions like sepsis or renal failure, increasing bleeding or thrombosis risk.
Seminar present the Upper Gastrointestinal Bleeding problems
Edited by : Dr. Inzar Yassen & Dr. Ammar L. Aldwaf
in Hawler Medical Uni. collage of medicine in 14/01/2014
Iraq - Kurdistan - Erbil
Thrombocytopenia is generally defined as platelet count <150 × 109/L. It can occur due to several reasons, like decreased platelet production (e.g., inherited bone marrow failure syndromes, acquired aplastic anemia, leukemia), ineffective platelet production (myelodysplastic syndrome, megaloblastic anemia), increased destruction (ITP, HLH), increased consumption (DIC, TTP, HUS), sequestration (hypersplenism), or may be due to combination of multiple mechanisms described above.
During evaluating a case of thrombocytopenia, the first step is getting a detailed history and doing a proper clinical examination. Then the next step would be checking the other parameters of complete blood count (CBC), especially hemoglobin (Hb) and the total WBC count, complemented by a peripheral smear (PS) examination, which will clear many doubts and will help us pinpointing our diagnostic approach.
Many a times pseudo-thrombocytopenia is encountered in a PS due to platelet clumping by EDTA and can be rectified by collecting blood samples in a citrate or heparin vials or by doing a direct finger prick smear. Any accompanying cytopenia will expand the differential diagnosis and an isolated thrombocytopenia will further narrow it down. Presence of any additional abnormalities of red cells (megaloblasts) or white cells (presence of hyper-segmented neutrophils, atypical lymphoid/myeloid cells) could be present in megaloblastic anemia/MDS, leukemia respectively, while in the presence of fragmented red cells microangiopathic hemolytic anemia should always be ruled out by doing PT and aPTT (DIC, TTP, HUS). In case of isolated thrombocytopenia, the platelet morphology is also important. In many patients in India, especially in eastern region many people have large platelets with their normal platelet count around 100 × 109/L with normal platelet function (Harris platelet syndrome). However, presence of any abnormal platelet morphology along with a low platelet count may indicate a platelet function disorder (large platelets in Bernard Soulier syndrome/ Glanzmann thrombasthenia or small platelets in Wiskott-Aldrich syndrome), especially if encountered in early part of life during evaluation for bleeding symptoms. In case of isolated thrombocytopenia, presence of additional congenital anomalies may point out towards an inherited marrow failure syndrome, e.g. amegakayocytic thrombocytopenia. Exposure to certain drugs may result in isolated low platelet count, e.g., ceftriaxone, piperacillin, heparin. Presence of toxic changes in neutrophils may indicate sepsis related thrombocytopenia. By excluding all these, immune thrombocytopenia (ITP) to be thought as no specific tests or markers are available for this entity and its diagnosis is largely clinical. A further work up complemented by bone marrow examination and in few cases a platelet function test will definitely help in reaching the final diagnosis.
So, summarizing, in the evaluation of a case of thrombocytopenia, all the
Thrombocytopenia is most frequently encountered Hematological problem in hospitalized patients. The most common causes and differential diagnosis of In-patient and Outpatient presentations of Thrombocytopenia is discussed here. Useful for Internal Medicine Boards . Archer Internal Medicine Board review lectures will be released soon.
Thrombotic Microangiopathy (TMA) in Adults and Acute Kidney Injury - Dr. GawadNephroTube - Dr.Gawad
- English version of this lecture is available at:
https://youtu.be/zrFm0hAZk2A
- Arabic version of this lecture is available at:
https://youtu.be/M_BV8WJVbx0
- Visit our website for more lectures: www.NephroTube.com
- Subscribe to our YouTube channel: www.youtube.com/NephroTube
- Join our facebook group: www.facebook.com/groups/NephroTube
- Like our facebook page: www.facebook.com/NephroTube
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Seminar present the Upper Gastrointestinal Bleeding problems
Edited by : Dr. Inzar Yassen & Dr. Ammar L. Aldwaf
in Hawler Medical Uni. collage of medicine in 14/01/2014
Iraq - Kurdistan - Erbil
Thrombocytopenia is generally defined as platelet count <150 × 109/L. It can occur due to several reasons, like decreased platelet production (e.g., inherited bone marrow failure syndromes, acquired aplastic anemia, leukemia), ineffective platelet production (myelodysplastic syndrome, megaloblastic anemia), increased destruction (ITP, HLH), increased consumption (DIC, TTP, HUS), sequestration (hypersplenism), or may be due to combination of multiple mechanisms described above.
During evaluating a case of thrombocytopenia, the first step is getting a detailed history and doing a proper clinical examination. Then the next step would be checking the other parameters of complete blood count (CBC), especially hemoglobin (Hb) and the total WBC count, complemented by a peripheral smear (PS) examination, which will clear many doubts and will help us pinpointing our diagnostic approach.
Many a times pseudo-thrombocytopenia is encountered in a PS due to platelet clumping by EDTA and can be rectified by collecting blood samples in a citrate or heparin vials or by doing a direct finger prick smear. Any accompanying cytopenia will expand the differential diagnosis and an isolated thrombocytopenia will further narrow it down. Presence of any additional abnormalities of red cells (megaloblasts) or white cells (presence of hyper-segmented neutrophils, atypical lymphoid/myeloid cells) could be present in megaloblastic anemia/MDS, leukemia respectively, while in the presence of fragmented red cells microangiopathic hemolytic anemia should always be ruled out by doing PT and aPTT (DIC, TTP, HUS). In case of isolated thrombocytopenia, the platelet morphology is also important. In many patients in India, especially in eastern region many people have large platelets with their normal platelet count around 100 × 109/L with normal platelet function (Harris platelet syndrome). However, presence of any abnormal platelet morphology along with a low platelet count may indicate a platelet function disorder (large platelets in Bernard Soulier syndrome/ Glanzmann thrombasthenia or small platelets in Wiskott-Aldrich syndrome), especially if encountered in early part of life during evaluation for bleeding symptoms. In case of isolated thrombocytopenia, presence of additional congenital anomalies may point out towards an inherited marrow failure syndrome, e.g. amegakayocytic thrombocytopenia. Exposure to certain drugs may result in isolated low platelet count, e.g., ceftriaxone, piperacillin, heparin. Presence of toxic changes in neutrophils may indicate sepsis related thrombocytopenia. By excluding all these, immune thrombocytopenia (ITP) to be thought as no specific tests or markers are available for this entity and its diagnosis is largely clinical. A further work up complemented by bone marrow examination and in few cases a platelet function test will definitely help in reaching the final diagnosis.
So, summarizing, in the evaluation of a case of thrombocytopenia, all the
Thrombocytopenia is most frequently encountered Hematological problem in hospitalized patients. The most common causes and differential diagnosis of In-patient and Outpatient presentations of Thrombocytopenia is discussed here. Useful for Internal Medicine Boards . Archer Internal Medicine Board review lectures will be released soon.
Thrombotic Microangiopathy (TMA) in Adults and Acute Kidney Injury - Dr. GawadNephroTube - Dr.Gawad
- English version of this lecture is available at:
https://youtu.be/zrFm0hAZk2A
- Arabic version of this lecture is available at:
https://youtu.be/M_BV8WJVbx0
- Visit our website for more lectures: www.NephroTube.com
- Subscribe to our YouTube channel: www.youtube.com/NephroTube
- Join our facebook group: www.facebook.com/groups/NephroTube
- Like our facebook page: www.facebook.com/NephroTube
- Follow us on twitter: www.twitter.com/NephroTube
Liver transplant (LT) is becoming the need of the hour and often the last ray of hope for many of our cirrhotic patients. The dearth of deceased donors, acceptance of living-related donors, better operative skills, and post transplant outcomes have played an important role is making LT accessable to more and more needy people. However, for best outcome it is important to stick to the established criteria laid down for listing a patient for LT for both best outcomes and better distribution of donor livers.
Bleeding and coagulation in cirrhosis.pptxShivPathak11
this presentation contains different parameter to be kept in mind before dealing a patient of cirrhosis regarding any bleed or coagulation abnormality.
Investigation of bleeding disorder || bleeding disorderparveen singh
this is a topic on investigation of bleeding disorder.
This may result from:
1 Vascular disorders
a] Thrombocytopenia
2Platelet Disorder
b] Defective platelet function
3Defective coagulation
4Defective Fibrinolysis
it is due to
-Inherited bleeding disorders
-Acquired bleeding disorders
investigation include:
first line test {basic test daily done in coagulation lab}
second line test {some important test done whenever all first line investigation test are normal }
Main Credit Goes To__-----___--- nitin dudeja {senior}
Liver Fibrosis: Difficulties in Diagnostic and Treatment: A Review-Crimson Pu...CrimsonGastroenterology
Early discovery of liver fibrosis and cirrhosis is becoming more relevant because of enhanced incidence of hepatocellular carcinoma. There a many underlying factors in developing liver fibrosis (i.e. viral hepatitis, steatohepatitis). Diagnosis of liver fibrosis is difficult; chronic liver failure and less distinct fibrosis stages can be underestimated, when laboratory routine parameters and native ultrasound of the liver are unsuspicious. Liver biopsy is a common element of diagnostic workup in hepatic cirrhosis, alongside clinical examination and abdominal ultrasound, and is the accepted diagnostic gold standard. But there is no unitary system of histological classification used to evaluate the degree of fibrosis, and individual systems are often validated only for individual disease entities. On the other hand liver biopsy is of less tolerance for patients. In the last years serological markers for detecting liver fibrosis were developed with different validity. Various imaging modalities have been proposed as methods for assessing liver fibrosis
by liver stiffness measurement. They are sufficient to approve the suspicious of liver fibrosis and/or to uncover unknown chronic liver failure. Studies showed the clinical usefulness of acoustic radiation force impulse shear wave elasticity imaging (ARFI-SWEI) is efficient as a preventive screening method to uncover fibrosis. The ARFI-SWEI system is integrated in an ultrasound device has a good accuracy and high reproducibility. Therapy of liver fibrosis depends on underlying disease and degree of liver failure. When liver failure can be cured liver fibrosis can regress. Direct antifibrotic drugs are
actually not available but in progress.
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
The Gram stain is a fundamental technique in microbiology used to classify bacteria based on their cell wall structure. It provides a quick and simple method to distinguish between Gram-positive and Gram-negative bacteria, which have different susceptibilities to antibiotics
Basavarajeeyam is a Sreshta Sangraha grantha (Compiled book ), written by Neelkanta kotturu Basavaraja Virachita. It contains 25 Prakaranas, First 24 Chapters related to Rogas& 25th to Rasadravyas.
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
Adv. biopharm. APPLICATION OF PHARMACOKINETICS : TARGETED DRUG DELIVERY SYSTEMSAkankshaAshtankar
MIP 201T & MPH 202T
ADVANCED BIOPHARMACEUTICS & PHARMACOKINETICS : UNIT 5
APPLICATION OF PHARMACOKINETICS : TARGETED DRUG DELIVERY SYSTEMS By - AKANKSHA ASHTANKAR
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
2. Coagula4on
and
Liver
• Disturbed
• Elevated
INR
• Low
/
normal
/
elevated
fibrinogen
• Low
platelets
• Elevated
D
Dimer
• APTT
• Percep4on
of
being
at
risk
of
bleeding
– Spontaneous
– Procedure
related
3. • Altera4ons
in
liver
disease
affect
the
whole
spectrum
of
coagula4on
factors
as
compared
to
a
single
deficiency
• Deficiencies
in
procogulant
factors
and
an4coagulant
factors
• At
baseline
likely
in
“balance”
• Haemosta4c
phenotype
is
likely
to
change
with
physiological
varia4on
– Sepsis
– Renal
failure
– Endothelial
ac4va4on
–
inflamma4on
• Rou4ne
coagula4on
tests
do
not
test
or
reflect
these
interac4on
4. disease and progressive liver disease [15]. Patients with NAFLD
may initially present with hemostatic alterations linked to gen- hype
the o
bleed
hemo
existe
iceal
Howe
ally t
[50].
serva
Th
volum
vatio
of pa
plant
[27–2
produ
is thu
Table 1. Alterations in the hemostatic system in patients with liver disease
that contribute to bleeding (left) or counteract bleeding (right).
Changes that impair
hemostasis
Changes that promote hemostasis
Thrombocytopenia Elevated levels of von Willebrand factor
(VWF)
Platelet function defects Decreased levels of ADAMTS-13
Enhanced production of nitric
oxide and prostacyclin
Elevated levels of factor VIII
Low levels of factors II, V, VII,
IX, X, and XI
Decreased levels of protein C, protein S,
antithrombin, a2-macroglobulin, and heparin
cofactor II
Vitamin K deficiency
Dysfibrinogenemia Low levels of plasminogen
Low levels of a2-antiplasmin,
factor XIII, and TAFI
Elevated t-PA levels
Hemostasis and thrombosis in patients with liver disease: The
ups and downs
Ton Lisman1,2,*, Stephen H. Caldwell3
, Andrew K. Burroughs4
, Patrick G. Northup3
, Marco Senzolo5
,
R. Todd Stravitz6
, Armando Tripodi7
, James F. Trotter8
, Dominique-Charles Valla9
, Robert J. Porte1
,
Coagulation in Liver Disease Study Group
1
Section Hepatobiliairy Surgery and Liver Transplantation, The Netherlands; 2
Surgical Research Laboratory, Department of Surgery,
University Medical Center Groningen, University of Groningen, Groningen, The Netherlands; 3
Division of GI/Hepatology,
Department of Internal Medicine, University of Virginia, Charlottesville, VA, USA; 4
The Sheila Sherlock Hepatobiliary-Pancreatic
and Liver Unit, Royal Free Hospital, London, United Kingdom; 5
Gastroenterology, Department of Surgical and Gastroenterological Sciences,
University Hospital of Padua, Italy; 6
Section of Hepatology, Hume-Lee Transplant Center, Virginia Commonwealth University,
Richmond, VA, USA; 7
Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, University Medical School and IRCCS Ospedale Maggiore
Policlinico, Mangiagalli and Regina Elena Foundation, Milan, Italy; 8
Baylor University Medical Center, Dallas, TX, USA; 9
Centre de Référence des
Maladies Vasculaires du Foie, AP-HP, Hôpital Beaujon, Service d’Hépatologie, Clichy, France
Abstract
Patients with chronic or acute liver failure frequently show profound
abnormalities in their hemostatic system. Whereas routine laboratory
tests of hemostasis suggest these hemostatic alterations result in a
bleeding diathesis, accumulating evidence from both clinical and labora-
tory studies suggest that the situation is more complex. The average
patient with liver failure may be in hemostatic balance despite pro-
longed routine coagulation tests, since both pro- and antihemostatic fac-
tors are affected, the latter of which are not well reflected in routine
coagulation testing. However, this balance may easily tip towards a
hypo- or hypercoagulable situation. Indeed, patients with liver disease
may encounter both hemostasis-related bleeding episodes as well as
thrombotic events. During the 3rd International Symposium on Coagu-
lopathy and Liver disease, held in Groningen, The Netherlands (18–19
September 2009), a multidisciplinary panel of experts critically reviewed
the current data concerning pathophysiology and clinical consequences
of hemostatic disorders in patients with liver disease. Highlights of this
symposium are summarized in this review.
Ó 2010. Published by Elsevier B.V. All rights reserved.
Introduction
In patients with liver disease, substantial changes in the hemo-
static system are frequently found [1]. These changes include
thrombocytopenia and platelet function defects, decreased circu-
lating levels of coagulation factors and inhibitors, and decreased
levels of proteins involved in fibrinolysis. Consequently, routine
diagnostic tests of hemostasis, such as the platelet count, the pro-
thrombin time (PT), and the activated partial thromboplastin
time (APTT) are frequently abnormal. In patients with isolated
hemostatic defects, such abnormalities in these laboratory tests
often indicate a true bleeding tendency. However, interpretation
of these tests is much less straightforward in the patient with a
complex hemostatic disorder as can be found in patients with
liver disease. In recent years, traditional concepts on the clinical
consequences of the hemostatic disorder in patients with liver
disease have dramatically changed. In particular, it is now estab-
Chronic liver disease – rebalanced hemostasis?
Thrombocytopenia, platelet function defects, and decreased lev-
els of pro- and anticoagulant proteins are frequently observed
in patients with cirrhosis [5]. Although routine hemostatic tests
Journal of Hepatology 2010 vol. 53 j 362–371
D, non-alcoholic fatty liver disease; PAI-1, pl-
SH, non-alcoholic steatohepatitis; INR, inter-
ndoscopic variceal ligation; ALF, acute liver
Ia; ICP, intracranial pressure; PVT, portal vein
hrombosis; AASLD, American society for the
6. Thrombosis
and
Hypercoagulability
• INR
designed
to
measure
warfarin
not
bleeding
risk
• Detects
varia4ons
in
factors
I,II,V,
VII
and
X
• Insensi4ve
to
an4coagulant
factors
–
Protein
C,
S,
ATIII
• Insensi4ve
to
haemosta4c
modulators
on
endothelium
(eg)
thrombomodulin
• Only
assess
5%
of
thrombin
• Assessment
should
consider
ETP,
thromboelastography
and
more
novel
tests
such
as
thrombin
genera4on
tes4ng
(TGT)
7. TEG
R = reaction time
K=kinetics
Alpha = slope between
R and K
MA=mean amplitude
CL= clot lysis
ROTEM
CT=clotting time
CFT = clot formation
time
Alpha = slope of tangent
at 2 mm
MCF= maximal clot
firmness
LY=Lysis
PSC,
PBC
pro-‐coagulant
8. Wilma
Potze
Thrombosis
Research
(2015)
Fibrinogen
levels
strongly
correlated
with
the
clot
density
Endogenous
thombin
genera4on
+
TM
increased
in
CP
–
C
Correla4on
between
APTT
and
clot
density
Con4nuous
monitoring
of
clot
growth
in
non-‐s4rred
plasma
ini4ated
by
a
thin
layer
of
immobilized
4ssue
factor
(TF)
9. Ra4o
of
endogenous
thrombin
poten4al
(ETP-‐Ra4o)
measured
in
the
presence
vs.
absence
of
thrombomodulin.
Armando
Tripodi,
Journal
of
Hepatology
2013
vol.
59
j
265–270
10. Table 1. Demographic, clinical and laboratory characteristics on hospital admission for ALI/ALF and subgroups according to outcome. (Mean ± SD or median [range])
Feature Normal Range Entire Group
(n = 51)
Spontaneous Survivors
(n = 29)
Death or OLT
(n = 22)
Demographics:
Age (years) 43.1 ± 14.7 40.3 ± 15.0 46.7 ± 13.8
Female Gender (%) 61 59 64
Caucasian Race (%) 65 66 64
BMI (Kg/m2
) 28.2 ± 6.6 26.7 ± 5.1 30.3 ± 8.0
Clinical Characteristics:
Etiology of ALI/ALF (N [%]):
Acetaminophen
Autoimmune hepatitis
Hepatitis B
Idiosyncratic drug
Indeterminate
Hepatic ischemia
Mushroom poisoning
Heat stroke
22 [43]
7 [14]
7 [14]
6 [12]
4 [8]
2 [4]
1 [2]
1 [2]
1 [2]
17 [59] 5 [23]**
Hepatic encephalopathy (ALF) (%) 73 55 96**
Number of SIRS 1.6 ± 1.2 1.2 ± 1.0 2.1 ± 1.3**
Pulse (beats/min) 95 ± 21 93 ± 21 97 ± 22
Mean arterial pressure (mmHg) 86 ± 14 87 ± 13 85 ± 16
Respiratory rate (breaths/min) 20 ± 6 18 ± 4 22 ± 8*
Temperature (°C) 36.7 ± 0.7 37.0 ± 0.7 36.3 ± 0.6***
Laboratory Data:
White blood cell count (x 109
/L) 3.9-11.7 11.8 ± 7.2 11.1 ± 6.7 12.5 ± 7.8
Creatinine (mg/dl) 0.5-1.0 1.0 [0.4-8.1] 0.9 [0.4-7.5] 1.5 [0.5-8.1]
Total bilirubin (mg/dl) 0.0-1.3 6.5 [0.3-44.2] 4.7 [0.9-29.4] 21.0 [0.3-44.2]**
Albumin (g/dl) 3.7-5.2 2.9 ± 0.5 3.0 ± 0.5 2.7 ± 0.4*
Venous ammonia (µmol/L) 0-35 80 ± 38 71 ± 36 91 ± 38
Lactate (mmol/L) 0.5-2.2 3.4 [0.4-21.4] 2.5 [0.4-6.6] 5.6 [0.7-21.4]**
Phosphate (mg/dl) 2.5-4.6 3.6 ± 2.4 2.8 ± 1.3 4.8 ± 3.1**
Malignant infiltration
JOURNAL OF HEPATOLOGY
hepatitis and hepatitis B in 7 patients (14%) each, idiosyncratic
drug reactions in 6 (12%), indeterminate etiology in 4 patients
(8%), ischemia in 2 patients (4%), and malignant infiltration of
the liver, heat stroke, and mushroom (Amanita) poisoning in 1
(2%) case each. Hepatic encephalopathy of some degree (ALF)
was present in 37 (73%) of patients. At the time of TEG measure-
ment, the mean number of SIRS components was 1.6; 8 patients
had a mean arterial pressure (MAP) of 670 mm Hg. Fourteen
patients (28%) died and 8 (16%) underwent orthotopic liver trans-
plantation (OLT), yielding a transplant-free survival (TFS) of 29
patients (57%). Clinical features and laboratories predictive of
poor outcome (death or OLT) included non-APAP etiology, the
presence of hepatic encephalopathy, lower body temperature,
albumin, and fibrinogen, and higher number of SIRS, respiratory
rate, bilirubin, lactate, phosphate, aPTT, INR, and MELD score
(Table 1).
Mean/median TEG parameter values were within normal
limits for the entire study population (Table 1; mean R-time
Creatinine (mg/dl) 0.5-1.0 1.0 [0.4-8.1] 0.9 [0.4-7.5] 1.5 [0.5-8.1]
Total bilirubin (mg/dl) 0.0-1.3 6.5 [0.3-44.2] 4.7 [0.9-29.4] 21.0 [0.3-44.2]**
Albumin (g/dl) 3.7-5.2 2.9 ± 0.5 3.0 ± 0.5 2.7 ± 0.4*
Venous ammonia (µmol/L) 0-35 80 ± 38 71 ± 36 91 ± 38
Lactate (mmol/L) 0.5-2.2 3.4 [0.4-21.4] 2.5 [0.4-6.6] 5.6 [0.7-21.4]**
Phosphate (mg/dl) 2.5-4.6 3.6 ± 2.4 2.8 ± 1.3 4.8 ± 3.1**
Fibrinogen (mg/dl) 200-450 195 ± 84 223 ± 55 154 ± 102**
PTT (sec) 25-36 49 ± 17 41 ± 10 59 ± 19****
INR 3.4 ± 1.7 3.0 ± 1.3 4.0 ± 1.9*
MELD score 31.3 ± 8.6 27.7 ± 7.1 36.2 ± 8.3***
TEG Parameters:
R-time (min) 2.5-7.5 4.7 ± 1.9 4.1 ± 1.5 5.5 ± 2.2**
K-time (min) 0.8-2.8 1.7 [0.8-20.0] 1.9 [0.8-20.0] 1.7 [0.9-10.5]
α-Angle (degrees) 55.2-78.4 63.7 ± 12.2 63.6 ± 12.7 63.7 ± 11.8
Maximum Amplitude (mm) 50.6-69.4 55.0 ± 10.9 55.0 ± 11.2 55.1 ± 10.6
Lysis 30 (%) 0.0-7.5 0.0 [0.0-2.1] 0.0 [0.0-1.8] 0.0 [0.0-2.1]
⁄
p <0.05, ⁄⁄
p 60.01, ⁄⁄⁄
p <0.001, ⁄⁄⁄⁄
p 60.0001 indicates significant difference between spontaneous survivors and those who died or underwent OLT.
TEG parameters in patients with ALI/ALF reflect specific
phases of blood clot formation and are associated with specific
aspects of the clinical syndrome. The R-time mirrors activation
of the coagulation cascades and procoagulant factor levels. Con-
sistent with the well-recognized importance of the INR and factor
V in predicting outcome in patients with ALF [21,22], the R-time
directly correlated with the SIRS, specific laboratories which pre-
dict poor outcome (lactate and phosphate), complications of the
ALI/ALF syndrome other than hepatic encephalopathy, and poor
outcome. R-time was significantly higher in patients with infec-
tion, those requiring CVVH, and in those with bleeding complica-
tions. The TEG was, in fact, more sensitive than the INR for
predicting bleeding, since the INR was not significantly different
in those who bled and those who did not (p = 0.14). This observa-
Factor VIII -0.27 -0.31* 0.38** 0.33*
Protein C Activity -0.19 0.02 -0.14 -0.04
Protein S Activity -0.14 0.11 -0.20 -0.14
Antithrombin Activity -0.14 -0.02 -0.06 0.17
SIRS Components:
Pulse 0.18 -0.43** 0.29* 0.44**
Respirations 0.46*** -0.34* 0.15 0.31*
Temperature -0.20 0.03 0.02 -0.06
WBC 0.29* -0.13 0.19 0.30*
Chemistries:
Lactate 0.58**** 0.16 -0.23 0.01
Ammonia (venous) 0.13 -0.37** 0.38** 0.38**
Phosphate 0.47*** -0.04 0.00 0.25
Creatinine 0.11 -0.05 0.13 0.23
Total Bilirubin -0.14 -0.16 0.22 0.10
⁄
p <0.05, ⁄⁄
p <0.01, ⁄⁄⁄
p <0.001, ⁄⁄⁄⁄
p 60.0001 indicates significant correlation.
0 1 2 3 4
30
40
50
60
70
80
Maximum
amplitude(mm)
SIRS (N)
Fig. 2. Maximum amplitude of clot formation according to the number of
SIRS concurrently determined in patients with acute liver injury/failure on
admission to study. Data represent mean values with lower/higher 95%; width of
R time higher in infection
and those requiring RRT
and appeared to predict
bleeding risk whilst INR
did not
Minimal effects of acute liver injury/acute liver failure on
hemostasis as assessed by thromboelastography
R. Todd Stravitz1,⇑
, Ton Lisman3
, Velimir A. Luketic1
, Richard K. Sterling1
, Puneet Puri1
,
Michael Fuchs1
, Ashraf Ibrahim2
, William M. Lee4
, Arun J. Sanyal1
1
Section of Hepatology and Hume-Lee Transplant Center, Virginia Commonwealth University, Richmond, VA, USA; 2
Department of
Anesthesiology, Virginia Commonwealth University, Richmond, VA, USA; 3
Department of Surgery, University Medical Center Groningen,
University of Groningen, Groningen, The Netherlands; 4
Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center,
Dallas, TX, USA
Background & Aims: Patients with acute liver injury/failure (ALI/
ALF) are assumed to have a bleeding diathesis on the basis of ele-
vated INR; however, clinically significant bleeding is rare. We
hypothesized that patients with ALI/ALF have normal hemostasis
despite elevated INR.
Methods: Fifty-one patients with ALI/ALF were studied prospec-
tively using thromboelastography (TEG), which measures the
dynamics and physical properties of clot formation in whole
blood. ALI was defined as an INR P1.5 in a patient with no pre-
vious liver disease, and ALF as ALI with hepatic encephalopathy.
Results: Thirty-seven of 51 patients (73%) had ALF and 22
patients (43%) underwent liver transplantation or died. Despite
a mean INR of 3.4 ± 1.7 (range 1.5–9.6), mean TEG parameters
were normal, and 5 individual TEG parameters were normal in
32 (63%). Low maximum amplitude, the measure of ultimate clot
strength, was confined to patients with platelet counts
<126 Â 109
/L. Maximum amplitude was higher in patients with
ALF than ALI and correlated directly with venous ammonia con-
centrations and with increasing severity of liver injury assessed
by elements of the systemic inflammatory response syndrome.
All patients had markedly decreased procoagulant factor V and
VII levels, which were proportional to decreases in anticoagulant
proteins and inversely proportional to elevated factor VIII levels.
Conclusions: Despite elevated INR, most patients with ALI/ALF
maintain normal hemostasis by TEG, the mechanisms of which
include an increase in clot strength with increasing severity of
liver injury, increased factor VIII levels, and a commensurate
decline in pro- and anticoagulant proteins.
Ó 2011 European Association for the Study of the Liver. Published
by Elsevier B.V. All rights reserved.
Introduction
Acute liver injury and acute liver failure (ALI/ALF) are syndromes
defined by ‘‘coagulopathy’’ on the basis of increased prothrombin
time (PT)/INR; ALF represents a more severe liver injury resulting
in hepatic encephalopathy [1]. Thrombocytopenia frequently
accompanies ALI/ALF, although its pathogenesis remains poorly
defined [2]. Consequently, patients with ALI/ALF have been
assumed to have a bleeding diathesis [3], even though most ser-
ies report a low incidence of spontaneous, clinically significant
bleeding [4]. Although invasive procedures such as intracranial
pressure (ICP) monitor placement are also rarely associated with
bleeding complications (<5% [5]), coagulation factor and platelet
transfusion remain a routine practice despite potential adverse
effects [6].
In patients with cirrhosis, who also have thrombocytopenia
and elevated INR, a concept of ‘‘re-balanced hemostasis’’ has been
proposed to explain the fact that patients rarely bleed outside of
the consequences of portal hypertension [7]. As shown by Tripodi
[8], thrombin generation is normal in patients with cirrhosis pro-
vided that thrombomodulin is added to the reaction mixture to
activate the anticoagulant protein C system. These and other
Keywords: Acute liver failure; Coagulopathy; Hepatic encephalopathy; Hemos-
tasis; Thromboelastography.
Received 26 January 2011; received in revised form 29 March 2011; accepted 6 April
2011; available online 19 May 2011
⇑ Corresponding author. Address: Section of Hepatology, P.O. Box 980341,
Virginia Commonwealth University, Richmond, VA 23298-0341, USA. Tel.: +1
804 828 4060; fax: +1 804 828 4945.
effects of procoagulant and antic
platelets, and red blood cells. Com
Journal of Hepatology 2012 vol. 56 j 129–136
disease score; ADAMTS13, a disintegrin and metalloprotease with thrombospon-
din type-1 motifs 13; vWF, von Willebrand factor.
13. ETP
endogenous
thrombin
poten4al
ra4o
sugges4ng
hypercoagulability.
Habib
et
al
Liver
Int
2013
T.
Lisman
et
al
Journal
of
Thrombosis
and
Haemostasis,
2013
10:
1312–1319
14. T.
Lisman
et
al
Journal
of
Thrombosis
and
Haemostasis,
10:
1312–1319
16. Heparinase
effect
HEPATOLOGY
1999;29:1085-‐1090
Resolu4on
of
infec4on
resulted
in
Improved
r
and
alpha
angle
Montalto
et
al
J
Hepatology
2002
37(4):463
17. Philipp
A.
Reuken
Liver
Int.
2015;
35:
37–45
Prothrombo4c
state
correlated
with
OF
19. Retrospective chart study in patients undergoing RRT without initial anticoagulation
Anticoagulation added to a sub group and filter life increased from 5.6 to 19 hours
Citrate well tolerated in liver failure
Coagulation data
Circuit life
20. Kidney
Interna4onal
(2013)
84,
158–163;
AKI
stage
3
associated
with
low
platelets
,
factor
V,
Protein
C
and
AT
III
Tissue
factor
levels
increased,
along
with
Von
Willibrand
factor
Increased
micropar4cles
No
increased
bleeding
Increased
circuit
clolng
21. Statistical decrease in platelets and fibrinogen and other TEG functions
but no evidence of clot lysis / fibrinolysis however
Doria et al
Clinical Transplantation
2004;18:365
Significant worsening of
PT, all TEG variables,
factor VIII, von WB,
DDimers
24. Nicolas
M.
Intagliata
Liver
Int.
2014:
34:
26–32
9
gastrointes4nal
bleeding
events
(2.5%
of
admissions)
5
venous
thromboembolisms
(1.4%
of
admissions)
2
cases
of
HIT
(0.5%
of
admissions)
and
14
deaths
overall
(3.9%
of
admissions)
DVT
prophylaxis
25%
CLD
admissions
Monitoring
Low
ATIII
levels
in
cirrhosis
results
in
falsely
elevated
APTT
levels
and
falsely
Decreased
an4Xa
levels
-‐
Lau
Clin
Med
2015
Potze
Drug
Monit
2015
37;2,
BJH
2013;163:666
25.
26. Treat
Ac4ve
Bleeding
:
Prevent
thrombosis
Ensure
appropriate
monitoring
• Overt
ooze
/
bleed
– low
fibrinogen
and
platelets
<
30
and
elevated
INR
/APTR
/
fibrinolysis
– Avoid
procedures
if
possible
– Isolated
eleva4on
of
INR
:
ignore
– Platelets
>
30-‐
50
:
no
Rx
• Ac4ve
bleeding
/varices
Rx
as
per
standard
bleed
• Rx
bleeding
– Fresh
frozen
plasma
(10-‐15
ml/kg)
or
concentrate
– Cryoprecipitate
–
if
bleeding
and
fibrinogen
<
0.8
mg/dl
– Concentrates
:
balance
of
pro
and
an4coagulant
factors
– Platelets
– Tranexamic
acid
–
watch
for
overt
thrombosis
and
early
Rx
(CRASH)
An4coagula4on
DVT
prophylaxis
Avoid
/
Rx
PVT
Full
an4coagula4on
monitoring
complex
be
aware
of
APTR
/
an4Xa
issues
HIT
high
screen
rate
If
concern
Rx
with
Agatroban