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Hindawi Case Reports in Oncological Medicine Volume 2020, Article ID 9147105, 5 pages https://doi.org/10.1155/2020/9147105 Case Report Disseminated Intravascular Coagulation and Malignancy: A Case Report and Literature Review Sumit Sohal , Akhilesh Thakur, Aleena Zia , Mina Sous, and Daniela Trelles Department of Internal Medicine, AMITA Health Saint Francis Hospital, 355 Ridge Avenue, Evanston, IL 60202, USA Correspondence should be addressed to Sumit Sohal; email@example.com Received 6 July 2019; Accepted 18 December 2019; Published 2 January 2020 Academic Editor: Jose I. Mayordomo Copyright © 2020 Sumit Sohal et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Disseminated Intravascular Coagulation (DIC) is a disorder of coagulation which is commonly seen as a complication of infections, traumas, obstetric diseases, and cancers especially hematological and rarely solid cancers. DIC may rarely be the presenting feature of an undiagnosed malignancy. It may present in the form of diﬀerent phenotypes which makes its diagnosis diﬃcult and leads to high mortality. The treatment comprises supportive, symptomatic treatment and removal of the underlying source. Here, we present a patient with history of being on warfarin for atrial ﬁbrillation and other comorbidities who presented with elevated INR of 6.3 and increasing dyspnea on exertion. Over the course of her stay, her platelet counts started dropping with a concurrent decrease in ﬁbrinogen levels. She eventually developed pulmonary embolism, followed by stroke and limb ischemia, which was indicative of the thrombotic phenotype of DIC. Her pleural ﬂuid analysis showed huge burden of malignant cells in glandular pattern suggestive of adenocarcinoma and was started on heparin drip. However, the patient had cardiac arrest and expired on the same day of diagnosis. 1. Introduction symptoms of bleeding. On review of systems, the patient endorsed increased dyspnea on exertion over the last few Disseminated Intravascular Coagulation (DIC) is a condition weeks. She did not endorse a change in dose or diet and no characterized by systemic activation of coagulation, poten- new medications except for methylprednisolone (Medrol) tially leading to thrombotic obstruction of small and midsize dose pack about a week prior to admission. vessels, thereby contributing to organ dysfunction . It may Physical exam on presentation was signiﬁcant for a result as a complication of infection, solid cancers, hemato- temperature of 97.4 F, blood pressure of 130/70, heart rate logical malignancies, obstetric diseases, trauma, aneurysms, of 83 beats per minute (bpm), and an oxygen saturation of liver diseases, etc. . DIC reportedly develops in 10% to 96% on room air. She had decreased breath sounds at lung 15% of patients with cancer where it may exhibit a chronic bases and superﬁcial scratches on bilateral upper extremities phenotype or present as an acute phenomenon . We with no overt signs of bleeding. Laboratory ﬁndings were present a case of a patient who was admitted with unrelated signiﬁcant for white blood count of 13.5 k/mm cu (ref range: complaints and developed DIC during her hospital course, 4.0-11.0 k/mm cu), hemoglobin 10.8 g/dl (ref range: 12- with her workup revealing an underlying malignancy. 15.3 g/dl), and platelet count 285 k/cu mm (ref range: 150- 450 k/cu mm). Chest X-ray showed minimal increased opac- ity at the left lung base, a nodular opacity in the right midlung 2. Case Presentation unchanged from the prior study, and slight blunting of the An 81-year-old female with a past medical history of costophrenic angles bilaterally. CT chest without contrast was done and showed chronic diﬀuse emphysema, minimal hypertension, hyperlipidemia, orthostatic hypotension, atrial ﬁbrillation, and bioprosthetic mitral valve replacement on bilateral pleural eﬀusion, and a reidentiﬁed spiculated left warfarin presented at clinic after the International Normal- upper lobe mass that measured 0:7×0:6cm which had ized Ratio (INR) was reported as 6.3, without any signs or slightly increased in conspicuity (previously 0:4×0:5cm). 2 Case Reports in Oncological Medicine (a) (b) Figure 1: (a, b) A CT angiogram of the chest shows ﬁlling defects in the subsegmental arteries (arrows). (a) (b) Figure 2: (a, b) CT angiogram of the head shows abrupt occlusion of the branch of the middle cerebral artery (arrows). Warfarin was held and IV Vitamin K 5 mg was given. INR vegetation on valves. Her blood cultures and urine cultures dropped to 1.4 the next day, and the patient was started on remained negative. Her platelets continued to drop. On the th low-dose warfarin. She was also started on empiric antibi- day of admission, her respiratory status continued to otics (vancomycin and piperacillin/tazobactam) as she worsen, and hence, CT angiogram of the chest was done showed worsening respiratory status. which revealed multiple subsegmental pulmonary emboli rd Her platelets on the 3 day of admission dropped by (SSPE) (Figures 1(a) and 1(b)) and signiﬁcant pleural eﬀu- >50% to 127. She had no exposure to heparin or its products, sion (no anticoagulation given as SSPE and platelet level 22 k/cu mm). On the next day, interventional radiology- and her warfarin was held. A peripheral blood ﬁlm showed no schistocytes. Her hemoglobin dropped to 7 g/dl. Her (IR-) guided thoracentesis was done (after platelet transfu- ﬁbrinogen was 147 mg/dl (ref range: 163-463 mg/dl), INR sion) and drained 920 cc of sanguineous ﬂuid. This was com- 1.3, haptoglobin 86 mg/dl (ref range: 44-215 mg/dl), LDH plicated by pneumothorax, followed by chest tube placement. 593 IU/l (ref range: 140-271 IU/l), and total bilirubin Later on the same day, her mental status declined, as she appeared confused with slurring of speech and had rightward 0.4 mg/dl (ref range: 0.0-1.0 mg/dl). Hematology was con- sulted, and various other tests to exclude multiple diagnoses gaze preference. CT head was done followed by CT angio- were initiated. Transthoracic echocardiography was done gram of the head and neck which demonstrated right and showed an ejection fraction of 59% and ruled out any MCA, M1 occlusion (Figures 2(a) and 2(b)), but she was Case Reports in Oncological Medicine 3 (a) (b) Figure 3: (a, b) Microscopic picture of pleural ﬂuid analysis (200x/400x). Numerous tumor cells arranged in well-diﬀerentiated glandular pattern consistent with metastatic adenocarcinoma. not a candidate for tissue plasminogen (tPA) due to low Hemostasis (JSTH), and the Italian Society for Thrombosis platelet count and thrombectomy was not pursued due to and Hemostasis (SISET). Though DIC does not have any her multiple comorbidities. She was then conservatively gold standard test, ISTH favors the use of scoring systems managed in the ICU. to diagnose DIC [8–11]. th On the 10 day, her lung ﬂuid cytology revealed multiple Three diﬀerent diagnostic scoring systems have been malignant cells arranged in a well-deﬁned glandular pattern devised by the ISTH/SSC , Japanese Ministry Health, consistent with adenocarcinoma (Figure 3), and simulta- Labour and Welfare (JMHLW) , and Japanese Associa- neously, it was reported that her left lower extremity turned tion of Acute Medicine (JAAM) . A prospective study blue concerning for acute limb ischemia. Her laboratory in Japan reported no signiﬁcant diﬀerences in the odds ratio values of ﬁbrinogen and INR also worsened (87 mg/dl and for predicting DIC outcomes among these three diagnostic 1.7, respectively), and she was started on heparin drip for criteria . The bleeding type of DIC can be easily diag- the diagnosis of DIC with multiple thrombotic events nosed using the ISTH overt-DIC and JMHLW criteria, while secondary to occult malignancy. Unfortunately, the patient the organ failure type of DIC is diagnosed according to the had a cardiac arrest and expired that day. The tumor cells JAAM diagnostic criteria . came back positive for TTF-1 and negative for Napsin, Our patient was positive for DIC as per these criteria as GATA-3, Calretinin, and CK 5/6, consistent with metastatic her platelet count (26 k/cu mm), ﬁbrinogen level (87 mg/dl), adenocarcinoma of lung primary. and INR (1.7) were conclusive for DIC. 3.2. DIC and Cancer. Professor Trousseau in 1865 ﬁrst 3. Discussion described an association between recurrent migratory thrombophlebitis and cancer, and since then, several studies DIC can be deﬁned as a widespread hypercoagulable state that can lead to both microvascular and macrovascular have proven a tight relationship between thrombosis and clotting and compromised blood ﬂow, ultimately resulting malignant disease. However, the thrombotic complications of cancer are not limited to venous thromboembolism and in multiple organ dysfunction syndrome (MODS) . At the same time, the use and subsequent depletion of platelets may appear as DIC [16, 17]. Cancer-related DIC may present in one of these 3 forms: and coagulation proteins resulting from the ongoing coagula- ﬁrstly, the “procoagulant” form, where excess thrombin gen- tion may induce severe bleeding . In addition to coagula- erated causes thrombosis in microvascular and macrovascu- tion activation, ﬁbrinolytic activation occurs and the degree lar ﬁelds and thus clinically manifest as DIC with thrombotic of activation of this system leads to the classiﬁcation of the two major types of symptoms in DIC, i.e., bleeding symp- features; secondly, the “hyperﬁbrinolytic” form, where acti- vation of the ﬁbrinolytic system dominates the picture and toms and organ symptoms (dysfunction) . When dealing thus clinically presents as bleeding; and last but not the least, with patients with cancer-related DIC, it is useful to consider the diﬀerent pathogenic mechanisms that can lead to the the “subclinical” form, where the amounts of thrombin and plasmin generated do not cause obvious clinical manifesta- abovementioned diﬀerent clinical manifestations . tions but can be reﬂected in laboratory markers of coagula- 3.1. Diagnosis of DIC. The active members of the subcommit- tion or ﬁbrinolysis activation. While most of the solid tumors come under the umbrella of subclinical DIC, pancre- tee for DIC of the Scientiﬁc and Standardization Committee (SSC) of the International Society on Thrombosis and atic and lung adenocarcinomas are procoagulant whereas Haemostasis (ISTH) attempted to harmonize the three acute promyelocytic leukemia and metastatic prostate cancer guidelines for DIC that have been published in the litera- are likely to be in the hyperﬁbrinolytic form . Though the ture from the British Committee for Standards in Haema- association between solid cancers and DIC is well-known and has been described in almost all histologic types , the tology (BCSH), the Japanese Society of Thrombosis and 4 Case Reports in Oncological Medicine of various organ systems. This happened when her diagnosis mortality rate from DIC is higher in patients with lung cancer than in non-lung cancer patients and prevalence was unclear, and eventually when the diagnosis was made, of DIC varies among the pathologic types of lung cancer she was well beyond recovery. . Many studies have shown that patients with adeno- carcinoma are at a very high risk of DIC  especially 4. Conclusion in lung adenocarcinoma  due to the procoagulant Early diagnosis and identiﬁcation of underlying condition is mucin in the cancer cells ; however, one recent study the key to reduce mortality in these patients with DIC. It has refuted this claim . can often be challenging to establish the underlying cause, Our patient with evidence of pulmonary embolism, especially if the patient is on anticoagulants or has other risk stroke, and acute limb ischemia presented with thrombotic features of DIC. There was no biopsy performed; however, factors for bleeding/thrombosis. Malignancy should always be considered in laboratory ﬁndings of subclinical DIC, espe- the malignant cells found on the pleural ﬂuid analysis cially without overt cause and with risk factors for lung were consistent with metastatic adenocarcinoma of lung cancer. primary. 3.3. Treatment of Cancer-Related DIC. The cornerstone of Conflicts of Interest DIC treatment is providing treatment for the underlying disorders, such as the administration of antibiotics or The authors declare that they have no conﬂicts of interest. surgical drainage in patients with infectious diseases and anticancer drugs or surgery in patients with malig- References nant diseases . However, patients with DIC resulting from sepsis, hematologic malignancy, or obstetric disease  M. Levi and M. Scully, “How I treat disseminated intravascular can be successfully treated for DIC, whereas DIC associ- coagulation,” Blood, vol. 131, no. 8, pp. 845–854, 2018. ated with solid cancers may not respond to standard  H. Wada, T. 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