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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; sumit.sohal@amitahealth.org

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 [1]. 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. [2]. 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 [3]. 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-
2. Case Presentation ity at the left lung base, a nodular opacity in the right midlung
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
hypertension, hyperlipidemia, orthostatic hypotension, atrial was done and showed chronic diffuse emphysema, minimal
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 × 0:6 cm which had
ized Ratio (INR) was reported as 6.3, without any signs or slightly increased in conspicuity (previously 0:4 × 0:5 cm).
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
low-dose warfarin. She was also started on empiric antibi- 8th 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
Her platelets on the 3rd 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
and her warfarin was held. A peripheral blood film showed 22 k/cu mm). On the next day, interventional radiology-
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
0.4 mg/dl (ref range: 0.0-1.0 mg/dl). Hematology was con- appeared confused with slurring of speech and had rightward
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].
On the 10th 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 [12], Japanese Ministry Health,
consistent with adenocarcinoma (Figure 3), and simulta- Labour and Welfare (JMHLW) [13], and Japanese Associa-
neously, it was reported that her left lower extremity turned tion of Acute Medicine (JAAM) [14]. 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 [15]. 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 [2].
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. Discussion 3.2. DIC and Cancer. Professor Trousseau in 1865 first

described an association between recurrent migratory
DIC can be defined as a widespread hypercoagulable state thrombophlebitis and cancer, and since then, several studies
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
in multiple organ dysfunction syndrome (MODS) [4]. At of cancer are not limited to venous thromboembolism and
the same time, the use and subsequent depletion of platelets may appear as DIC [16, 17].
and coagulation proteins resulting from the ongoing coagula- Cancer-related DIC may present in one of these 3 forms:
tion may induce severe bleeding [5]. In addition to coagula- firstly, the “procoagulant” form, where excess thrombin gen-
tion activation, fibrinolytic activation occurs and the degree erated causes thrombosis in microvascular and macrovascu-
of activation of this system leads to the classification of the lar fields and thus clinically manifest as DIC with thrombotic
two major types of symptoms in DIC, i.e., bleeding symp- features; secondly, the “hyperfibrinolytic” form, where acti-
toms and organ symptoms (dysfunction) [6]. When dealing vation of the fibrinolytic system dominates the picture and
with patients with cancer-related DIC, it is useful to consider thus clinically presents as bleeding; and last but not the least,
the different pathogenic mechanisms that can lead to the the “subclinical” form, where the amounts of thrombin and
abovementioned different clinical manifestations [7]. plasmin generated do not cause obvious clinical manifesta-
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
tee for DIC of the Scientific and Standardization Committee tumors come under the umbrella of subclinical DIC, pancre-
(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 [7]. Though the
ture from the British Committee for Standards in Haema- association between solid cancers and DIC is well-known and
tology (BCSH), the Japanese Society of Thrombosis and has been described in almost all histologic types [18], the
4 Case Reports in Oncological Medicine

mortality rate from DIC is higher in patients with lung of various organ systems. This happened when her diagnosis
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.
[19]. Many studies have shown that patients with adeno-
carcinoma are at a very high risk of DIC [7] especially 4. Conclusion
in lung adenocarcinoma [20] due to the procoagulant
mucin in the cancer cells [21]; however, one recent study Early diagnosis and identification of underlying condition is
has refuted this claim [19]. the key to reduce mortality in these patients with DIC. It
Our patient with evidence of pulmonary embolism, can often be challenging to establish the underlying cause,
stroke, and acute limb ischemia presented with thrombotic especially if the patient is on anticoagulants or has other risk
features of DIC. There was no biopsy performed; however, factors for bleeding/thrombosis. Malignancy should always
the malignant cells found on the pleural fluid analysis be considered in laboratory findings of subclinical DIC, espe-
were consistent with metastatic adenocarcinoma of lung cially without overt cause and with risk factors for lung
primary. cancer.

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
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