Acute Aortoiliac and Femoral ArteryThrombosis Complicating Diabetic KetoacidosisStan Zipser, MD, JD, Carl M. Kirsch, MD, Conway Lien, MD, Tej M. Singh, MD, and Young S. Kang, MD

Acute abdominal aortic occlusion is a devastating event with high associated rates of morbidity and mortality evenwith surgical intervention. This report describes a case of acute aortoiliac and femoral artery occlusion likely resultingfrom a hypercoagulable state caused by diabetic ketoacidosis (DKA). Vascular thrombosis is a little-known butpotentially devastating complication of DKA that should be considered in every patient treated for DKA and shouldbe added to the differential diagnoses when attempting to determine the etiology of a thrombosed vessel.

J Vasc Interv Radiol 2005; 16:1737–1739

Abbreviation: DKA � diabetic ketoacidosis

ACUTE abdominal aortic occlusion isa devastating event with high associ-ated rates of morbidity and mortalityeven with surgical intervention (1,2). Itis most often caused by a cardiac em-bolus or in situ thrombosis from anatherosclerotic abdominal aorta. Otherreported etiologies include suddenthrombosis of a small abdominal aor-tic aneurysm, thrombosis from a hy-percoagulable state, and trauma (1,2).We present a case of acute aortoiliacand femoral artery occlusion that webelieve was caused by a hypercoagu-lable state resulting from diabetic ke-toacidosis (DKA).

CASE REPORT

Our institution does not require in-stitutional review board approval for

retrospective reports. A 52-year-oldman was brought to the emergencyroom by paramedics because of in-creasing lethargy and altered mentalstatus. The patient’s blood pressurewas 96/48 mm Hg, heart rate was 66bpm, respiration rate was 18 breathsper minute, and temperature was37.2°C. Additional history included 3weeks of polydipsia and polyuria. Thepatient had a history of asthma and aremote history of smoking. There wasno history of diabetes, hypertension,heart disease, peripheral vascular oc-clusive disease, or hypercoagulablestate. Initial laboratory tests revealed aserum glucose level of 1,584 mg/dL(normal, 70–200 mg/dL), serum ace-tone ratio of 1:16, and serum osmolal-ity of 393 mOsm/kg (normal, 281–297mOsm/kg). Other laboratory resultsincluded a creatinine level of 4.1 mg/dL(normal, 0.7–1.4 mg/dL) and arterialblood gas with a pH of 7.19. Completeblood count showed a white blood cellcount of 14,300/�L. Electrocardiogra-phy revealed sinus tachycardia.

The patient was confused and inco-herent. A new diagnosis of diabeteswas made and the patient was admit-ted to the intensive care unit for treat-ment of DKA. On the morning afterthe admission, the patient reported ab-dominal pain. He was found to havecool lower extremities and only a rightfemoral pulse was detected. The Vas-

cular surgery service was consultedemergently who suspected acute aor-toiliac thrombosis, and full-dose un-fractionated peripheral intravenousheparin drip was started. Because ofthe patient’s increased creatinine level,noncontrast computed tomography(CT) and gadolinium-enhanced mag-netic resonance arteriography (MRA)of the abdominal aorta and iliac andlower-extremity arteries were per-formed. CT was remarkable for distalaorta with a normal diameter and lackof atherosclerotic calcification. MRAdemonstrated near-complete occlusivethrombus within the distal abdominalaorta extending into the common iliacarteries bilaterally. The left commoniliac artery was completely occludedand the right was nearly completelyoccluded (Fig). Flow beyond the com-mon iliac arteries was likely from col-lateral flow through internal iliac ar-teries; however, the MR acquisitionplane did not include this entire re-gion. Thrombus was also present inthe left common femoral artery and,except for a short proximal segment,the left superficial femoral artery wascompletely occluded just beyond itsorigin. No patent vessels were presentbelow the level of the knees bilaterally.

A hypercoagulability laboratorypanel was obtained, which revealedan activated protein C concentrationof 20% (normal, 73%–174%), activated

From the Department of Diagnostic Imaging (S.Z.,C.L., Y.S.K.); Division of Respiratory and CriticalCare Medicine, Department of Medicine (C.M.K.);and Division of Vascular Surgery, Department ofSurgery (T.M.S.), Santa Clara Valley Medical Center;751 Bascom Avenue, San Jose, California 95128. Re-ceived April 24, 2005; revision requested May 12;revision received May 29; accepted June 2. Addresscorrespondence to S.Z.; E-mail: stanzipser@hotmail.com

None of the authors have identified a conflict ofinterest.

© SIR, 2005

DOI: 10.1097/01.RVI.0000175321.56202.8D

Brief Reports

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protein S concentration of 19% (nor-mal, 63%–155%), antithrombin III func-tion of 24% (normal, 80%–131%), andfibrinogen level of 151 mg/dL (normal,200–400 mg/dL). Cardiolipin screen,lupus anticoagulant, factor V Leiden,and prothrombin 20210A were nega-tive. No echocardiogram was obtained.The patient underwent an emergentaortic and bilateral iliofemoral arteryembolectomy and bilateral below-kneeamputations. On postoperative day 1,the patient developed worsening hypo-tension despite three vasopressiveagents. Creatinine kinase measured150,000 U/L and renal function wors-ened rapidly with corresponding hyper-kalemia and increasing metabolic acido-sis consistent with rhabdomyolysis andreperfusion injury. Hemodialysis wasinitiated. On postoperative day 4, afterall resuscitative measures were ex-hausted, the patient died. No autopsywas performed.

DISCUSSION

DKA has been found to promote aprothrombotic state and to activate thevascular endothelium. Free protein S

and protein C activity levels have beenshown to decrease, and von Wille-brand factor has been shown to in-crease, during DKA and its treatment,raising the risk of vascular thrombosis(3). The metabolic insult of DKA mayalso initiate or perturb the steady stateof vascular endothelial cells, changingthe hemostatic profile and resulting ina prothrombotic state (3). In addition,even in the absence of DKA, diabetesmellitus has been asserted to present ahypercoagulable state. Coagulationmarkers and multiple clotting factors,including factors VII, VIII, XI and XII,and von Willebrand factor, are in-creased in diabetes (4). Protein C hasalso been shown to be decreased, andthere is increased platelet aggregationin diabetes. Various investigators havefound normal, increased, and de-creased levels of antithrombin III inuncomplicated diabetes (4).

For review, von Willebrand factoris synthesized and secreted by endo-thelial cells, facilitates platelet adhe-sion, and serves as a carrier protein forfactor VIII. Proteins C and S and anti-thrombin III are inhibitors that limitthrombin generation and fibrin forma-

tion. Defects in any of these proteinspredispose patients to thrombus for-mation. Heparin enhances the inhibi-tory effects of antithrombin III. Acti-vated protein C may also stimulatefibrinolysis and accelerate clot lysis(3–5).

Many clinical instances of hyperco-agulability and vascular thrombus for-mation in the setting of DKA havebeen reported in the literature. In astudy of 610 patients with DKA orhyperosmolar coma during a 16-yearperiod, six of 38 deaths were attrib-uted to mesenteric or iliac arterythromboses (6). No discussion aboutetiology was presented in this study.Two studies (7,8) have shown an in-creased incidence of deep venousthrombosis (DVT) in pediatric patientswith femoral vein catheters in DKAcompared with age-matched controlpatients with circulatory shock whoalso had femoral vein catheters but notin DKA. In these studies, the authorsconjectured that the increase in throm-botic events may be a result of hyper-glycemia and DKA causing an in-crease in platelet aggregability, redblood cell rigidity, resistance to blood

Figure. Images from a 52-year-old man with DKA. (a) Gadolinium-enhanced coronal collapsed MR angiographic image (repetitiontime/echo time, 5.9 msec/1.152 msec; flip angle, 45°) demonstrates distal aortic, bilateral common and external iliac, and left femoralartery occlusion. (b) Gadolinium-enhanced coronal source MR angiographic image (repetition time/echo time, 5.9 msec/1.152 msec; flipangle, 45°) demonstrates a narrow patent region through the right common iliac artery.

1738 • Aortoiliac and Femoral Artery Thrombosis in Diabetic Ketoacidosis December 2005 JVIR

flow, and possibly dehydration (7,8).Interestingly, in two of three patients,all 18 months of age or younger, pro-tein S levels were decreased, but pro-tein C, antithrombin III, homocysteine,and factor VIII concentrations werenormal. Pediatric patients with DKAare also known to be at risk for cere-bral ischemic events (3). Additionally,in a case report (9) in which DKA wasimplicated as the cause of pulmonarythromboembolism in an adult, the au-thors proposed that patients withDKA be routinely evaluated for lower-extremity DVT because of their in-creased risk of thromboembolic com-plications.

Our patient’s hypercoagulabilityprofile comports with the studies as-serting that DKA and diabetes pro-mote a prothrombotic state. The pa-tient’s protein S, protein C, andantithrombin III levels were decreasedwhereas the remainder of the hyper-coagulability laboratory panel results,assessing for an inherited hypercoag-ulable state, was negative. The patienthad no clinical history of a clottingdisorder or peripheral arterial occlu-sive disease significantly decreasingthe likelihood this event was a resultof in situ thrombosis from one of thesecauses. Although no echocardiogramwas obtained, there was no history ofcardiac disease including arrhythmia.The patient was in sinus rhythm dur-ing the period before the thrombosis

was diagnosed, which makes cardiacembolus an unlikely cause for thisevent.

As exemplified by this case, imag-ing findings of a thrombosed vessel asa result of DKA are nonspecific. Estab-lishing DKA as the etiology of thethrombosis involves excluding othercauses of thrombosis such as otherprothrombotic states and a cardiacsource. As in other cases of vascularthrombosis, in addition to correctingthe DKA, treatment will vary with thelocation and severity of the thrombo-sis. Anticoagulation, catheter-directedpharmacologic or mechanical throm-bolysis, or surgical thrombectomymay be undertaken as indicated.

CONCLUSION

In conclusion, we present a case ofacute aortoiliac and lower-extremityarterial thrombosis in a patient withDKA. We believe that DKA caused aprothrombotic, hypercoagulable statethat led to the acute thrombotic event.Acute vascular thrombosis from DKAin the adult population is a little-known but potentially devastatingcomplication of DKA that should beconsidered in every patient treated forDKA. In addition, the interventionalradiologist should add this entity tothe differential diagnosis when en-countering an acutely thrombosedvessel.

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Acute occlusion of the abdominal aorta.Am J Surg 1998; 176:193–197.

2. Dossa CD, Shepard AD, Reddy DJ, et al.Acute aortic occlusion: a 40-year experi-ence. Arch Surg 1994; 129:603–608.

3. Carl GF, Hoffman WH, Passmore GG, etal. Diabetic ketoacidosis promotes aprothrombotic state. Endocr Res 2003;29:73–82.

4. Carr ME. Diabetes mellitus: a hyperco-agulable state. J Diabetes Compl 2001;15:44–54.

5. Handin RI. Disorders of coagulationand thrombosis. In: Fauci AS,Braun-wald E, Isselbacher KJ, eds. Harrison’sPrinciples of Internal Medicine, 15th ed.New York: McGraw-Hill, 2001; 756.

6. Hamblin PS, Topliss DJ. Chosich N, etal. Deaths associated with diabetic ke-toacidosis and hyperosmolar coma,1973–1988. Med J Aust 1989; 151:439–444.

7. Gutierrez JA, Bagatell R, Samson MP, etal. Femoral central venous catheter-as-sociated deep venous thrombosis inchildren with diabetic ketoacidosis. CritCare Med 2003; 31:80–83.

8. Worly JM, Fortenberry JD, Hansen I, etal. Deep venous thrombosis in chil-dren with diabetic ketoacidosis andfemoral central venous catheters. Pedi-atrics 2004; 113:e57–e60.

9. Quigley RL, Curran RD, Stagl RD, Alex-ander JC Jr. Management of massivepulmonary thromboembolism compli-cating diabetic ketoacidosis. Ann ThoracSurg 1994; 57:1322–1324.

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