Case Report Acute Warfarin Toxicity as Initial Manifestation of...

Case ReportAcute Warfarin Toxicity as Initial Manifestation ofMetastatic Liver Disease

Varalaxmi Bhavani Nannaka1 Nihar Jani2 Masooma Niazi3 and Dmitry Lvovsky1

1Division of Pulmonary and Critical Care Medicine Bronx Lebanon Hospital Center Bronx NY 10457 USA2Department of Internal Medicine Bronx Lebanon Hospital Center Bronx NY 10457 USA3Department of Pathology and Histology Bronx Lebanon Hospital Center Bronx NY 10457 USA

Correspondence should be addressed to Varalaxmi Bhavani Nannaka drnannakagmailcom

Received 13 November 2015 Revised 10 February 2016 Accepted 11 February 2016

Academic Editor Chiara Lazzeri

Copyright copy 2016 Varalaxmi Bhavani Nannaka et al This is an open access article distributed under the Creative CommonsAttribution License which permits unrestricted use distribution and reproduction in any medium provided the original work isproperly cited

Near complete infiltration of the liver secondary to metastasis from the head and neck cancer is a rare occurrenceThe prognosis ofliver failure associated withmalignant infiltration is extremely poor the survival time of patients is extremely lowWe present a caseof acute warfarin toxicity as initial manifestation of metastatic liver disease Our patient is a 64-year-old woman presenting withepigastric pain and discomfort found to have unrecordable International Normalized Ratio She rapidly deteriorated with acuterespiratory failure requiringmechanical ventilation profound shock requiring high dose vasopressor infusion severe coagulopathyworsening liver enzymes with worsening of lactic acidosis and severe metabolic abnormalities and refractory to aggressivesupportive care and died in less than 48 hours Autopsy revealed that gt90 of the liver was replaced by tumor masses

1 Introduction

The coumarin derivative warfarin which was licensed in theUnited States in 1954 as the first human anticoagulant [1]remains themost commonly used oral anticoagulant inNorthAmerica and the United Kingdom [2 3] Warfarin exertsits anticoagulant effect by acting as a vitamin K antagonistand inhibiting the biosynthesis of vitamin K-dependentprocoagulant factors II VII IX and X [2ndash4]

On the basis of a study done in 5077 cases with 99628emergency hospitalizations warfarinwas implicated in 333of such Emergency Department (ED) visits [5]

Acute liver failure (ALF) secondary to malignant infiltra-tion of the liver is rare and is diagnosed often only after deathIn the era of liver transplantation it is important to reacha definitive diagnosis and identify the cause because livertransplantation is not indicated ifmalignant infiltration of theliver is present and alternative therapies may be available

Our case presents a finding of acute warfarin toxicity asinitial manifestation of metastatic liver disease in a patientwith stable dose of warfarin for 15 years with documentedstable International Normalized Ratio (INR) over the sameperiod of time

2 Case Presentation

A 64-year-old woman was brought to ED by a familymember for generalized weakness for 10 days associated withepigastric pain and discomfort Patient also reported havinga fall one week prior to her presentation to ED She noticedto have dark stools and red urine within few days of the fall

Her medical history was significant for atrial fibrillationonwarfarin COPD active smoking and hypertension Addi-tional history of laryngeal cancer was present which wastreated with radiotherapy and chemotherapy four years agoAs a followup after presenting with hoarseness of voice threeyears ago recurrent malignancy was ruled out with vocalcord biopsy No personal or family history of liver diseasewas identified There were no changes to her medicationswhich included warfarin amlodipine metoprolol aspirinand atorvastatin

In ED patient was tachycardic with a pulse of 160minafebrile and normotensive The patient had no evidenceof acute distress or external injury She had right subcon-junctival hemorrhage and mucous membranes were dryHeart examination was significant for tachycardia with nomurmurs rubs or gallops Lungs had good bilateral air

Hindawi Publishing CorporationCase Reports in Critical CareVolume 2016 Article ID 7389087 6 pageshttpdxdoiorg10115520167389087

2 Case Reports in Critical Care

Table 1 Patientrsquos laboratory values during hospitalization until death

Parameter 997888rarr

Hour (hr) 0 hr 6 hr 15 hr 18 hr 22 hr 30PT (seconds) gt169 2753 577 611 72 1303INR Unrecordable 238 51 54 64 114PTT (seconds) 92 668 443 467 541 989Serum albumin (gdL) 28 24 26 21 18Alanine aminotransferase (unitL) 420 1234 1201 1312 2179Aspartate transaminase (unitL) 973 2475 2344 2548 3681Alkaline phosphatase (unitL) 435 393 369 403 379Total bilirubin (mgdL) 1 14 15 13 13Lactic acid level (mmolesL) 133 66 17 18 15LDH (unitL) 8003Troponin (ngmL) 021 032 048 088 158CK (unitL) 872 1059 1220 1179 1283CK-MB (ngmL) 4042 4401 5375 6606 7228CK-MB 46 42 42 56 56Haemoglobin (gdL) 12 72 97 87 78Bicarbonate (mEqL) 10 13 5 6 3

entry with no wheezing crackles or crepitations Abdominalexamination revealed soft butmildly tender epigastriumwithnormal bowel sounds whereas rectal examination showedstool mixed with dark blood She was alert and oriented totimeplaceperson but appeared slightly lethargic no focalneurological deficits on neuro examination were found

Laboratory studies revealed anemia with hemoglobinconcentration of 72mgdL with baseline values around12mgdL less than 3 months ago leukocytosis with whiteblood cell count of 15 kuL normal platelet count of 232 kuLprothrombin time (PT) of 169 seconds partial thrombo-plastin time (PTT) of 92 seconds and unrecordable INRChemistry showed prerenal azotemia with blood urea nitro-gen levels of 54mgdL creatinine of 13mgdL bicarbonateof 10mEqL and normal serum electrolytes Liver functiontests (LFTs) showed hypoalbuminemia with albumin of28 gdL transaminitis with alanine aminotransferase (ALT)of 420UL aspartate transaminase (AST) of 973 unitL andalkaline phosphatase (ALP) of 435 unitL Other significantlaboratory values were elevated lactic acid to 133mmolesLlactate dehydrogenase (LDH) level of 8003 unitL elevatedtroponin of 0206 ngmL creatine kinase (CK) of 872 unitLand creatine kinase MB (CKMB) of 40 ngmL with MB oflt5 Please refer to Table 1 for laboratory values during thehospitalizationHepatitis A B andC serologies were negativeand serum acetaminophen level was lt15 ngdL

Her INR two weeks prior to her presentation was 28 withnormal LFTs four weeks prior to admission She had been onstable dose of warfarin for the past 15 years Please refer toTable 2 for warfarin dosage and INR levels in the past oneyear

Initial chest X-ray (Figure 1) did not show any evidenceof an acute pulmonary edema or pneumonia ComputedTomography (CT) scan of the abdomen (Figure 2) showed

Table 2 Warfarin dosing and INR prior to hospitalization

Time frame INR Warfarin dose (mg)2 weeks ago 28 42 months ago 24 46 months ago 22 41 year ago 29 415 year ago 37 5

Figure 1 Chest X-ray

markedly enlarged abnormal heterogeneous liver suggestiveof an infiltrative process with no obvious free fluid orevidence of significant bleeding CT scan of the head wasnegative for acute intracranial hemorrhage infarction ormasses

Case Reports in Critical Care 3

Figure 2 CT of the abdomen without contrast showed markedlyenlarged abnormal heterogeneous liver

Figure 3 Liver weighed 4950 grams and that is enlarged with intactsmooth capsule with soft tan brown parenchyma which was nearlycompletely replaced by multiple discrete tumor masses

The patient had been given vitamin K and multipletransfusions of Fresh Frozen Plasma (FFP) to reverse coag-ulopathy

After admission to intensive care unit (ICU) there wasa rapidly progressive decline in the patientrsquos clinical statusShe developed acute respiratory failure requiring mechanicalventilation hypotension necessitating vasoactive agents andliver failure with worsening LFTs In addition she progressedto worsening of coagulopathy elevated cardiac markers andlactic acidosis Her multiorgan failure did not improve withaggressive resuscitative measures culminating in cardiacarrest and death

Autopsy revealed that patientrsquos liver weighed 4950 grams(Figures 3 and 4) and it was enlarged with intact smoothcapsule with soft tan brown parenchyma which was nearlycompletely replaced by multiple discrete and near-confluentsheets of white masses some with central punctate hem-orrhage ranging in size from approximately 03 to 3 cm inthe greatest dimension These tumor masses replaced nearly90 of the total liver volume Histopathology (Figures 5 and6) showed poorly differentiated squamous cell carcinomasecondary to metastasis Review of prior pathology fromthe time of LC surgery (Figures 7 and 8) showed mod-erately differentiated squamous cell carcinoma which washistopathologically consistentwith the observedmetastasis inthe liver

Figure 4 Cut section of liver with diffuse showed involvement bynumerous tumor masses and nodules replacing most of the liverparenchyma

Figure 5 Liver diffusely involved by poorly differentiated squamouscell carcinoma (low power magnification)

Figure 6 Autopsy of the liver on high magnification showing areasof poorly differentiated squamous cell carcinoma (high powermagnification)

3 Discussion

Warfarin therapy has a narrow risk-to-benefit profile Itspharmacokinetics is complex The effective half-life of war-farin ranges from 20 to 60 hours with a mean of about40 hours The maximum dose effect occurs up to 48 hrafter administration of a single dose and persists for thenext 5 days The drug is completely absorbed after oraladministration and peak concentrations occur within 4hours The warfarin metabolism occurs mainly in the liver Itinvolves the cytochrome P450 and in particular the CYP2C9isoenzyme Very little is excreted unchanged in the urine andthe bile [6]


Figure 7 Biopsy of the vocal cord showed invasive well differen-tiated squamous cell carcinoma showing cohesive nests and intra-cytoplasmic keratinization

Figure 8 Left vocal cord mass showing deeply invasive moderatelydifferentiated squamous cell carcinoma

Supratherapeutic levels of anticoagulation with warfarinresult from the administration of inappropriately high dosesaltered protein binding decreased vitamin K intake reducedsynthesis or increased clearance of vitamin K-dependentclotting factors and the simultaneous use of other compoundsthat interfere with warfarin metabolism Elderly patients canalso exhibit an exaggerated response to warfarin in partbecause they tend to store less vitamin K than younger people[7] Therefore it is not surprising that the most commoncomplication of warfarin use is adverse bleeding [8]

Before concluding that warfarin toxicity is the responsiblecause for coagulopathy many other conditions need tobe considered Differential diagnosis of prolonged PT andPTT is numerous and can be divided into inherited andacquired Inherited causes include prothrombin fibrinogenfactor V X and combined factor deficiency Acquired causesare mostly due to impaired synthesis loss or increasedconsumption or inhibition of coagulation factors Impairedsynthesis stems from vitamin K deficiency or hepatic diseaseMassive bleeding may be responsible for the loss of coagu-lation factors when the intravascular volume is replaced bycrystalloids colloids and red blood cells without replacingcoagulation factors Disseminated Intravascular Coagulation(DIC) pathophysiology is explained by increased consump-tion of coagulation factors Inhibition of coagulation factorsis seen with presence of inhibitor antibodies to prothrombinfibrinogen factor V X or direct thrombin inhibitor oriatrogenic with use of vitamin K antagonists (warfarin) or

with use of heparin or combined warfarin and heparin useWarfarin is highly bound (approximately 97) to plasma pro-tein mainly albumin The high degree of protein binding isone of several mechanisms whereby other drugs interact withwarfarin Liver failure may be differentiated from vitamin Kdeficiency by measuring factor V which is not vitamin K-dependent [9] The presence of inhibiting antibodies can beconfirmed by mixing studies A diagnosis of DIC may bemade using a simple scoring system based on platelet countPT D-dimer levels and fibrinogen levels [10] In the casedescribed above there was no evidence to suggest intentionaloverdose of warfarin no use of compound that could havepotentially increased the warfarin levels and no prior historyof inherited bleeding disorder In our clinical practice justas reported in Budnitz et al [5] majority of coagulationabnormalities detected upon admission to our hospital arerelated to warfarin

Our patient presented with severe warfarin inducedcoagulopathy Results of autopsy revealed near completeinfiltration of the liver with laryngeal cancer metastasis Theliver is the most common site for metastatic tumor depositswith evidence of hepatic metastasis in 36 of all patientswho die from cancer [11] Diffuse parenchymal metastasisis a rare pattern of liver metastasis Watson reviewed theliterature from the period 1868 to 1954 and reported 18 suchcases [12] Rowbotham and colleagues recognized 18 (044)patients with fulminant hepatic failure (FHF) attributable tocancerous hepatic infiltration among 4020 hospital admis-sions [11] The incidence of distant metastases in squamouscell carcinoma of head and neck approaches 20ndash25 Themost common sites of metastases are lung (70ndash75) liver(17ndash38) and bone (23ndash44) [13] Acute liver failure(ALF) secondary to diffuse metastatic infiltration of the liveris rare and has an extremely poor prognosis

The mechanism of ALF in the setting of neoplasticinfiltration is multifactorial Massive cytokine release hasbeen implicated as a cause of liver failure Cytokine releasecan cause liver failure by damaging bile ducts both directlyand via recruitment of effector cells and by activation ofleucocytes andhepatic sinusoidal cells thus impeding hepaticsinusoidal microcirculation Liver failure may also occurdue to ischemia produced by tumor emboli compromisingthe portal venous circulation or nonocclusive infarctionof liver due to shock from other causes such as sepsis orcardiac dysfunction The direct effect of tumor infiltrationwith replacement of hepatocytes is probably more importantas a mechanism in nonhaematological malignancies IndeedFHF rarely develops in metastatic carcinomatosis in theabsence of hypotension [14] Our patient had normal LFTsfour weeks prior to the development of ALF and thenrapidly progressed She has had infiltration of the liver overa period of time with no evidence of clinical or laboratoryabnormalities which then rapidly progressed to ALF as aresult of further insult from hypotension and cytokine releaselikely secondary to sepsis or cardiac event

Clinical presentation and laboratory findings of neo-plastic infiltration of liver are vague and far from beingpathognomonic Hyperbilirubinemia may be the result ofeither hepatic parenchymal infiltration or extrahepatic biliary


obstruction It is well known that the increase in serumaminotransferases represents liver cell destruction and maybe the only laboratory test indicating liver dysfunction priorto its clinical manifestation But in our patient her LFTs werenormal four weeks prior to admission However elevatedserum LDH levels appear to correlate better with metastasis-related hepatic failure since it is believed that elevated levelsrepresent rapid tumor growth by reflecting either the livercell destruction process or an elevated production of LDHenzyme by neoplastic cells themselves There are reports thatcorrelate LDH serum levels with hepatic metastases frommalignant melanoma small cell lung cancer (SCLC) patients[15ndash18] Extremely high serum LDH levels represent diffusereplacement of the liver parenchyma and are associated witha higher risk of development of FHF and a poor prognosis[19 20] Several authors suggest that an increase in serumLDH levels in cancer patients may prelude ALF [16 21 22]These findings are well supported by the results of LFTs inour patient who had extremely elevated serum LDH levelsDeath is usually a direct consequence of the FHF rather thanthe underlying malignancy Acute warfarin toxicity on thestable dose of warfarinwithout any alternative causewas not apresentation in any of the reported case series Because of therapid progression of FHF appropriate imaging proceduresare usually difficult to perform However CT scan of theabdomen in our patient showedmarkedly enlarged liver withheterogeneity suggesting infiltrative process (Figure 2)

There have been case reports of liver metastasis-inducedFHF from haematologic malignancies [23ndash25] breast cancer[26 27] small cell carcinoma of lung [16 28ndash30] coloncancer urothelial cancer [31] and malignant melanoma [2022 32ndash34] Coagulopathy on stable dose of warfarin wasnot a presenting feature in any of these cases but in ourindexed case the main presentation was severe coagulopathyassociated with ALF secondary to near complete infiltrationof liver with metastatic disease Unfortunately the prognosisof patients with FHF resulting from malignant infiltration isdismal The majority of patients do not survive shortly afterthe onset of liver failure [11 26 35] According to a reviewby Allison et al concerning 21 reported cases of ALF due tometastatic breast carcinoma 18 cases died within 3 days to 7months Regrettably our patient died in less than 24 hours ofadmission to ICU

4 Conclusion

Delayed distant metastasis is rare in head and neck cancerALF secondary to malignant infiltration of the liver due todelayed distant metastasis from laryngeal cancer was neverreported in the literature to our best knowledge Acutewarfarin toxicity on stable dose of warfarin without any alter-native cause is rare Neoplastic infiltration of liver should beconsidered in the differential diagnosis when patients presentwith severe coagulopathy with ALF and laboratory evidenceof cellular destruction Effortsmust bemade to determine theetiology of the disease as it influences prognosis and promptinstitution of specific therapies that might lead to recov-ery Supportive care with close communication concerningend-of-life issues should be considered the standard of care

in patients presenting with ALF secondary to solid tumormalignancies since the prognosis is invariably poor

Conflict of Interests

None of the authors has a financial relationship with acommercial entity that has an interest in the subject of thepaper No financial support was used for this case report

References

[1] C M Kessler ldquoUrgent reversal of warfarin with prothrombincomplex concentrate where are the evidence-based datardquoJournal of Thrombosis and Haemostasis vol 4 no 5 pp 963ndash966 2006

[2] J P Hanley ldquoWarfarin reversalrdquo Journal of Clinical Pathologyvol 57 no 11 pp 1132ndash1139 2004

[3] A C Butler and R C Tait ldquoManagement of oral anticoagulant-induced intracranial haemorrhagerdquo Blood Reviews vol 12 no1 pp 35ndash44 1998

[4] G Pindur and S Morsdorf ldquoThe use of prothrombin complexconcentrates in the treatment of hemorrhages induced by oralanticoagulationrdquo Thrombosis Research vol 95 no 4 pp S57ndashS61 1999

[5] D S Budnitz M C Lovegrove N Shehab and C L RichardsldquoEmergency hospitalizations for adverse drug events in olderAmericansrdquoThe New England Journal of Medicine vol 365 no21 pp 2002ndash2012 2011

[6] J Hirsh J E Dalen D R Anderson et al ldquoOral anticoagulantsmechanism of action clinical effectiveness and optimal thera-peutic rangerdquo Chest vol 119 supplement 1 pp 8Sndash21S 2001

[7] J Hirsh V Fuster J Ansell and J L Halperin ldquoAmerican HeartAssociationAmerican College of Cardiology foundation guideto warfarin therapyrdquo Circulation vol 107 no 12 pp 1692ndash17112003

[8] V Olmos and C M Lopez ldquoBrodifacoum poisoning withtoxicokinetic datardquo Clinical Toxicology vol 45 no 5 pp 487ndash489 2007

[9] B Bailey D K Amre and P Gaudreault ldquoFulminant hepaticfailure secondary to acetaminophen poisoning a systematicreview andmeta-analysis of prognostic criteria determining theneed for liver transplantationrdquo Critical Care Medicine vol 31no 1 pp 299ndash305 2003

[10] K Bakhtiari J C M Meijers E De Jonge and M LevildquoProspective validation of the International Society ofThrombosis and Haemostasis scoring system for disseminatedintravascular coagulationrdquo Critical Care Medicine vol 32 no12 pp 2416ndash2421 2004

[11] D Rowbotham JWendon and RWilliams ldquoAcute liver failuresecondary to hepatic infiltration a single centre experience of 18casesrdquo Gut vol 42 no 4 pp 576ndash580 1998

[12] A J Watson ldquoDiffuse intra-sinusoidal metastatic carcinoma ofthe liverrdquoThe Journal of Pathology and Bacteriology vol 69 no1-2 pp 207ndash217 1955

[13] J G Spector D G Sessions B H Haughey et al ldquoDelayedregional metastases distant metastases and second primarymalignancies in squamous cell carcinomas of the larynx andhypopharynxrdquo Laryngoscope vol 111 no 6 pp 1079ndash1087 2001

[14] P Rajvanshi K V Kowdley W K Hirota J B Meyers and EB Keeffe ldquoFulminant hepatic failure secondary to neoplastic


infiltration of the liverrdquo Journal of Clinical Gastroenterology vol39 no 4 pp 339ndash343 2005

[15] H B Harrison H M Middleton III J H Crosby and M NDasher Jr ldquoFulminant hepatic failure an unusual presentationof metastatic liver diseaserdquo Gastroenterology vol 80 no 4 pp820ndash825 1981

[16] BMMcGuireD L Cherwitz KMRabe and S BHo ldquoSmall-cell carcinoma of the lung manifesting as acute hepatic failurerdquoMayo Clinic Proceedings vol 72 no 2 pp 133ndash139 1997

[17] Y Fujiwara K Takenaka K Kajiyama et al ldquoThe characteristicsof hepatocellular carcinoma with a high level of serum lacticdehydrogenase a case reportrdquoHepato-Gastroenterology vol 44no 15 pp 820ndash823 1997

[18] S J Finck A E Giuliano B D Mann and D L MortonldquoResults of ilioinguinal dissection for stage II melanomardquoAnnals of Surgery vol 196 no 2 pp 180ndash186 1982

[19] F Tas A Aydiner E Topuz H Camlica P Saip and Y EralpldquoFactors influencing the distribution of metastases and survivalin extensive disease small cell lung cancerrdquoActaOncologica vol38 no 8 pp 1011ndash1015 1999

[20] H S Te T D Schiano M Kahaleh et al ldquoFulminant hepaticfailure secondary to malignant melanoma case report andreview of the literaturerdquoThe American Journal of Gastroenterol-ogy vol 94 no 1 pp 262ndash266 1999

[21] R H Schreve O T Terpstra L Ausema J S Lameris AJ van Seijen and J Jeekel ldquoDetection of liver metastasesA prospective study comparing liver enzymes scintigraphyultrasonography and computed tomographyrdquo British Journal ofSurgery vol 71 no 12 pp 947ndash949 1984

[22] P M G Bouloux R J Scott J E Goligher and C KindellldquoFulminant hepatic failure secondary to diffuse liver infiltrationby melanomardquo Journal of the Royal Society of Medicine vol 79no 5 pp 302ndash303 1986

[23] G A Morali E Rozenmann J Ashkenazi G Munter andD Z Braverman ldquoAcute liver failure as the sole manifestationof relapsing non-Hodgkinrsquos lymphomardquo European Journal ofGastroenterology and Hepatology vol 13 no 10 pp 1241ndash12432001

[24] K Esfahani P Gold S Wakil R P Michel and S SolymossldquoAcute liver failure because of chronic lymphocytic leukemiacase report and review of the literaturerdquo Current Oncology vol18 no 1 pp 39ndash42 2011

[25] T M Shehab M S Kaminski and A S F Lok ldquoAcute liverfailure due to hepatic involvement by hematologic malignancyrdquoDigestive Diseases and Sciences vol 42 no 7 pp 1400ndash14051997

[26] H E Nazario R Lepe and J F Trotter ldquoMetastatic breastcancer presenting as acute liver failurerdquo Gastroenterology andHepatology vol 7 no 1 pp 65ndash66 2011

[27] K H Allison C L Fligner and W T Parks ldquoRadiographicallyoccult diffuse intrasinusoidal hepatic metastases from primarybreast carcinomas a clinicopathologic study of 3 autopsy casesrdquoArchives of Pathology and Laboratory Medicine vol 128 no 12pp 1418ndash1423 2004

[28] K Sato Y Takeyama T Tanaka Y Fukui H Gonda and RSuzuki ldquoFulminant hepatic failure and hepatomegaly causedby diffuse liver metastases from small cell lung carcinoma 2autopsy casesrdquo Respiratory Investigation vol 51 no 2 pp 98ndash102 2013

[29] HMiyaaki T Ichikawa N Taura et al ldquoDiffuse livermetastasisof small cell lung cancer causing marked hepatomegaly and ful-minant hepatic failurerdquo Internal Medicine vol 49 no 14 pp1383ndash1386 2010

[30] Y T Hwang J W Shin J H Lee et al ldquoA case of fulminanthepatic failure secondary to hepaticmetastasis of small cell lungcarcinomardquoThe Korean Journal of Hepatology vol 13 no 4 pp565ndash570 2007

[31] M Alcalde M Garcia-Diaz J Pecellin et al ldquoAcute liverfailure due to diffuse intrasinusoidal metastases of urothelialcarcinomardquo Acta Gastro-Enterologica Belgica vol 59 no 2 pp163ndash165 1996

[32] E Bellolio F Schafer R Becker and M A Villaseca ldquoFulmi-nant hepatic failure secondary to diffuse melanoma infiltrationin a patient with a breast cancer historyrdquo Journal of PostgraduateMedicine vol 59 no 2 pp 164ndash166 2013

[33] G G Kaplan S Medlicott B Culleton and K B LauplandldquoAcute hepatic failure andmulti-system organ failure secondaryto replacement of the liver with metastatic melanomardquo BMCCancer vol 5 article 67 2005

[34] T Fusasaki R Narita M Hiura et al ldquoAcute hepatic failuresecondary to extensive hepatic replacement by metastatic ame-lanotic melanoma an autopsy case reportrdquo Clinical Journal ofGastroenterology vol 3 no 6 pp 327ndash331 2010

[35] E Athanasakis E Mouloudi G Prinianakis M Kostaki MTzardi and D Georgopoulos ldquoMetastatic liver disease andfulminant hepatic failure presentation of a case and reviewof the literaturerdquo European Journal of Gastroenterology andHepatology vol 15 no 11 pp 1235ndash1240 2003

Submit your manuscripts athttpwwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014


MEDIATORSINFLAMMATION

of


Behavioural Neurology

EndocrinologyInternational Journal of



Disease Markers


BioMed Research International

OncologyJournal of



Oxidative Medicine and Cellular Longevity


PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of



Computational and Mathematical Methods in Medicine

OphthalmologyJournal of


Diabetes ResearchJournal of



Research and TreatmentAIDS


Gastroenterology Research and Practice


Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom


Table 1 Patientrsquos laboratory values during hospitalization until death

Parameter 997888rarr

Hour (hr) 0 hr 6 hr 15 hr 18 hr 22 hr 30PT (seconds) gt169 2753 577 611 72 1303INR Unrecordable 238 51 54 64 114PTT (seconds) 92 668 443 467 541 989Serum albumin (gdL) 28 24 26 21 18Alanine aminotransferase (unitL) 420 1234 1201 1312 2179Aspartate transaminase (unitL) 973 2475 2344 2548 3681Alkaline phosphatase (unitL) 435 393 369 403 379Total bilirubin (mgdL) 1 14 15 13 13Lactic acid level (mmolesL) 133 66 17 18 15LDH (unitL) 8003Troponin (ngmL) 021 032 048 088 158CK (unitL) 872 1059 1220 1179 1283CK-MB (ngmL) 4042 4401 5375 6606 7228CK-MB 46 42 42 56 56Haemoglobin (gdL) 12 72 97 87 78Bicarbonate (mEqL) 10 13 5 6 3

entry with no wheezing crackles or crepitations Abdominalexamination revealed soft butmildly tender epigastriumwithnormal bowel sounds whereas rectal examination showedstool mixed with dark blood She was alert and oriented totimeplaceperson but appeared slightly lethargic no focalneurological deficits on neuro examination were found

Laboratory studies revealed anemia with hemoglobinconcentration of 72mgdL with baseline values around12mgdL less than 3 months ago leukocytosis with whiteblood cell count of 15 kuL normal platelet count of 232 kuLprothrombin time (PT) of 169 seconds partial thrombo-plastin time (PTT) of 92 seconds and unrecordable INRChemistry showed prerenal azotemia with blood urea nitro-gen levels of 54mgdL creatinine of 13mgdL bicarbonateof 10mEqL and normal serum electrolytes Liver functiontests (LFTs) showed hypoalbuminemia with albumin of28 gdL transaminitis with alanine aminotransferase (ALT)of 420UL aspartate transaminase (AST) of 973 unitL andalkaline phosphatase (ALP) of 435 unitL Other significantlaboratory values were elevated lactic acid to 133mmolesLlactate dehydrogenase (LDH) level of 8003 unitL elevatedtroponin of 0206 ngmL creatine kinase (CK) of 872 unitLand creatine kinase MB (CKMB) of 40 ngmL with MB oflt5 Please refer to Table 1 for laboratory values during thehospitalizationHepatitis A B andC serologies were negativeand serum acetaminophen level was lt15 ngdL

Her INR two weeks prior to her presentation was 28 withnormal LFTs four weeks prior to admission She had been onstable dose of warfarin for the past 15 years Please refer toTable 2 for warfarin dosage and INR levels in the past oneyear

Initial chest X-ray (Figure 1) did not show any evidenceof an acute pulmonary edema or pneumonia ComputedTomography (CT) scan of the abdomen (Figure 2) showed

Table 2 Warfarin dosing and INR prior to hospitalization

Time frame INR Warfarin dose (mg)2 weeks ago 28 42 months ago 24 46 months ago 22 41 year ago 29 415 year ago 37 5

Figure 1 Chest X-ray

markedly enlarged abnormal heterogeneous liver suggestiveof an infiltrative process with no obvious free fluid orevidence of significant bleeding CT scan of the head wasnegative for acute intracranial hemorrhage infarction ormasses










3 Discussion














4 Conclusion





References











































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of

























3 Discussion














4 Conclusion





References











































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of




























4 Conclusion





References











































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of












































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of
















Case Report Acute Warfarin Toxicity as Initial Manifestation of...

Documents

Transcript of Case Report Acute Warfarin Toxicity as Initial Manifestation of...