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 RECENT ADVANCES IN HEMATOLOGY RESEARCH

DISSEMINATED INTRAVASCULAR
COAGULATION (DIC)
CLINICAL MANIFESTATIONS,
DIAGNOSIS AND
TREATMENT OPTIONS

No part of this digital document may be reproduced, stored in a retrieval system or transmitted in any form or
by any means. The publisher has taken reasonable care in the preparation of this digital document, but makes no
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rendering legal, medical or any other professional services.
 RECENT ADVANCES
IN HEMATOLOGY RESEARCH

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under the Series tab.

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under the e-book tab.
 RECENT ADVANCES IN HEMATOLOGY RESEARCH

DISSEMINATED INTRAVASCULAR
COAGULATION (DIC)
CLINICAL MANIFESTATIONS,
DIAGNOSIS AND
TREATMENT OPTIONS

BALWINDER SINGH, M.D.

EDITOR

New York
Copyright © 2014 by Nova Science Publishers, Inc.

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 Contents

Preface vii
Chapter I Disseminated Intravascular Coagulation:
Clinical Manifestations 1
Akhilesh Kumar Tiwari, MD, Michell Gulabani, MD,
Prashant Dass, MD and Rishi Raj Sanjay, MD
Chapter II Risk Factors for Disseminated Intravascular
Coagulation 15
Akhilesh Kumar Tiwari, MD, Rajiv Ratan Singh, MD,
Rishi Raj Sanjay, MD, Naveen Ganjoo, MD
and Balwinder Singh, MD
Chapter III Thrombomodulin and Disseminated
Intravascular Coagulation 41
Shu-Min Lin MD and Han-Pin Kuo MD, PhD
Chapter IV Diagnostic Scoring System for Disseminated
Intravascular Coagulation 57
R. K. Singh, MD
Chapter V Outcome of Critically Ill Patients with Disseminated
Intravascular Coagulation in a Tertiary Care Center 77
Balwinder Singh MD, Rabe’ Elias Alhurani MBBS
and Pablo Moreno Franco MD
Chapter VI Sepsis and Disseminated Intravascular Coagulation 93
Luis Aurelio Diaz Caballero, MD
vi Contents

Chapter VII Coagulopathy of Liver Disease versus Disseminated

Intravascular Coagulation: Who is Who? 119
Pablo Moreno Franco MD, Jose Yataco MD
Balwinder Singh MD and Juan Canabal MD
Chapter VIII Disseminated Intravascular Coagulation in
Urological Malignancy 143
Aydin Pooli MD and Dharam Kaushik MD
Chapter IX Chronic Disseminated Intravascular Coagulation
(DIC) in Solid Tumors: When, Whom and
How to Treat? 155
Felice Vito Vitale, MD, Giovanna Antonelli, MD,
Rosalba Rossello, MD and Francesco Ferraù, MD
Chapter X Treatment Options for Disseminated
Intravascular Coagulation 167
Vaibhav Wadhwa MD and Kriti Kalra MD
Index 181
 Preface

Disseminated Intravascular Coagulation is a devastating syndrome

characterized by the systemic activation of widespread activation of the
coagulation cascade and thrombosis, which may result in severe bleeding and
may lead to organ failure. Recent studies have shown that the incidence of
DIC is decreasing, especially in men. Despite the improvements in health care
delivery, the morbidity and mortality due to DIC remains very high. Early
diagnosis and accurate prognosis are important in improving the outcomes of
patients with DIC.
However, there is a lack of a gold standard diagnostic test to diagnose DIC
and there is a scarcity of treatment or management strategies. Therefore, an
understanding of the pathophysiology, ability to diagnose the DIC syndrome
and to treat early, is the key. This book provides an important timely update on
the clinical manifestations, important risk factors, and treatment strategies for
DIC, and provides in-depth information on pathophysiological aspects and
various diagnostic scores used to diagnose DIC. Furthermore, we focused on
certain important factors related to DIC such as Sepsis, chronic DIC in cancer
patients, coagulopathy of liver disorders vs DIC, and DIC in urological
malignancies.
In addition, this book provides evidence from an important study
determining the predictors influencing the hospital mortality rates of the
critically ill patients with DIC. This book offers a wide scope of information
for physicians in all fields, whether they are intensivists, primary care
physicians or oncologists, this will be an important source for identifying the
DIC syndrome early, and the appropriate steps to improve patient outcomes
will be taken sooner.
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viii Balwinder Singh

I would like to thank all the contributing authors from different fields,
who have made a sincere effort to provide in-depth knowledge of DIC in
various different settings. I hope that this book would be able to impart
important knowledge and understanding on this serious syndrome and help the
physicians to diagnose and manage DIC appropriately.
In: Disseminated Intravascular Coagulation (DIC) ISBN: 978-1-62948-323-8
Editor: Balwinder Singh © 2014 Nova Science Publishers, Inc.

Chapter I

Disseminated Intravascular
Coagulation: Clinical
Manifestations

Akhilesh Kumar Tiwari, MD1*, Michell Gulabani, MD2,

Prashant Dass, MD3 and Rishi Raj Sanjay, MD2
1
Department of Anaesthesia and Critical Care,
National University Hospital, Singapore.
2
Department of Anaesthesia and Critical Care,
Batra Hospital and Medical Research Centre, New Delhi, India
3
Department of Pharmacology, M R Medical College,
Gulbarga, Karnataka, India

Abstract
Disseminated intravascular coagulation is a disorder found to be
associated with a number of underlying predisposing factors. It has come
to be known by various names such as consumption coagulopathy,
defibrination among various others. DIC; however, is the most widely
used and accepted. The grave prognosis of DIC warrants an early

* Corresponding Author address: Dr. Akhilesh KumarTiwari, National University Hospial, 5

Lower Kent Ridge Road, Singapore. Email:[email protected].
2 Akhilesh Kumar Tiwari, Michell Gulabani, Prashant Dass et al.

diagnosis and prompt management. To achieve this, clinicians should

have in-depth knowledge of underlying predisposing factors, clinical
features and laboratory diagnostic protocols. The present chapter will
focus mainly on the clinical features which are very variable, ranging
from severe hemorrhagic manifestation in acute cases of DIC to sub-
clinical thrombotic episode in patients suffering from chronic DIC.

Keywords: Disseminated Intravascular coagulation, consumptioncoagulo-

pathy, Waterhouse-Friderichsen syndrome, Trousseau syndrome

Introduction
Disseminated Intravascular Coagulation (DIC) is an acquired syndrome,
associated with various underlying disorders such as sepsis, malignancy,
haematological disorders, trauma and obstetric conditions [1-3]. In an acute
setting it is a potentially fatal and rapidly progressive disorder, mandating a
prompt diagnosis and rapid treatment; whereas, at the same time in a sub-acute
or chronic setting it has a very indolent course and often may be overlooked
due to normal or near normal hematological and coagulation profile. This
condition is associated with widespread activation of coagulation system
leading to multiple organ dysfunction syndrome (MODS) which is either
ischaemic or inflammatory in origin [4]. This condition is associated with
combination of both thrombosis and hemorrhage, and due to its potentially
fatal nature it has also been referred as ―Malignant syndrome.‖ [5]
DIC is never a primary disorder and is almost always associated with an
underlying condition the details of which have been discussed in a different
chapter. DIC tends to occur in about 1% of all the hospital admission [6]. The
main symptoms of bleeding and thrombosis and the consequences thereof
depends on the underlying cause and the rapidity with which it progresses.
There are two main clinical forms which have been described: acute and
chronic; although, a lot of overlap exists between these two entities. We will
initially be concentrating upon two clinical forms of DIC: acute and chronic .
One should always remember that it is the underlying process which
dominates the clinical presentation in most of the acute DIC cases.In cases of
chronic DIC the initial presentation may not be of the underlying
disorder.Thrombosis involving both arteries and veins have often been
observed in these patients.
 Disseminated Intravascular Coagulation: Clinical Manifestations 3

The clinical manifestation is variable, with symptoms arising either due to

hypercoagulable state or hemorrhagic tendency. The clinical course of the
patient suffering from DIC can be further subdivided into [7]:

1) Stage of hypercoagulability.
2) Stage of exhaustion (Consumption coagulopathy)
3) Hyperfibrinolysis.

Acute DIC
Acute DIC has fulminant course, developing in conditions which are
associated with massive release of tissue factor leading to explosive generation
of thrombin. The fulminant nature of acute DIC is because the consumption
coagulopathy is way ahead of the capacity of the liver to synthesize
coagulation factors, and bone marrow to produce platelets. This leads to
massive bleeding tendency, which is potentially lethal and evolves over period
of hours to days. The common conditions associated with acute DIC are
sepsis, trauma, shock, peri-operative states, certain obstetric conditions and
should always be regarded and treated as medical emergency

Chronic DIC
Chronic DIC usually runs an indolent and subtle course and takes months
to progress. The laboratory parameters used to diagnose acute DIC may be
normal or near normal in these clinical scenarios. Chronic DIC arises due to
presence of chronic low grade persistent stimulation of intravascular
coagulation as observed in cases such as retained dead fetus, subdural
hematoma [8, 9], post-biopsy renal hematoma [10], carcinomatosis, aortic
aneurysm, giant haemangiomas [11]. Rarely chronic DIC has also shown to
manifest itself as a renal mass mimicking Wilm‘s tumour [12]. In these
conditions the counter regulatory mechanism of the body is effective to
prevent the rapid progression of disease as a result of which the laboratory
values are not diagnostic as in cases of acute DIC. Malignancy is often
associated with chronic DIC, but certain malignancies like acute
promyelocytic leukemia (APL) may lead to acute DIC.
4 Akhilesh Kumar Tiwari, Michell Gulabani, Prashant Dass et al.

Table 1. Enumerates important differentiating point between both acute

and chronic DIC

Acute DIC Chronic DIC

Etiology Septicemia (Gram positive, Malignancies, connective
negative, viral, fungal, tissue disorders, chronic
protozoal, e.t.c.), acute infections, haemangioma,
obstetric complications, acute retained dead fetus
tissue injury
Clinical course Hours to days Months
Clinical External and internal bleeding, Superficial and Deep vein
features easy bruisabiity, Ischemia thrombosis, Trousseau
infarction and inflammation syndrome among few notable
leading to MODS ones
Laboratory Prothrombin time (PT), They may be normal to near
parameters activated partial normal
thromboplastin time, D-Dimer,
Thrombin time, fibrinogen
level, fibrinogen degradation
products along with the
presence of fragmented red
cells in the peripheral smear is
sufficient enough to make a
diagnosis.

Table 2 enumerates the common symptoms which a patient suffering from

DIC may have [13].

Table 2. Common clinical manifestation of DIC

Symptom Incidence (%)

Bleeding 64
Renal Dysfunction 25
Hepatic dysfunction 19
Pulmonary Manifestation 16
Shock 14
Thrombosis 7
Neurological impairment 2

We will now be discussing the common symptoms observed in patients

suffering from DIC.
 Disseminated Intravascular Coagulation: Clinical Manifestations 5

Bleeding

Bleeding manifestation in DICis variable, and may range from small

petechiae to massive internal or external bleeding. External bleeding can be in
the form of persistent oozing from cannulation, surgical or tissue injury sites.
Internal bleeding can be within the serous cavities of the body or in the form
of intra-cranial hemorrhage. Patients having bleeding manifestations due to
DIC usually have grave prognosis, and the body, often cannot compensate for
this stage of consumptive coagulopathy. This clinical course has often been
referred to as ―Overt syndrome/DIC.‖ [7] Patient may start to have hematuria,
and in cases of bleeding into gastrointestinal tract the patients may have black
tarry stools, blood in nasogastric tube, hematemesis, abdominal pain and
distension along with absent or hyper-active bowel sounds. Black tarry stool
occurring in these patients have also been implicated to extensive necrosis of
the colon known as ―terminal hemorrhagic necrotizing enteropathy.‖ [14]
Focal neurological deficits should raise the suspicion towards possible
intracranial hemorrhage in susceptible individuals. Patients with chronic DIC
usually exhibit minor skin and mucosal bleeding.
Profuse bleeding from three different sites which may be unrelated is not
uncommon especially in acute form of DIC.

Renal Dysfunction

Kidneys are one of the commonest organ system affected. Renal faiure
and the consequent complications have been reported in the literature in
established cases of DIC. Renal failure; however, presenting as a sign of DIC
is extremely rare [15]. The possible mechanism of renal injury in patients
suffering from DIC is microthombus formation in afferent arterioles and
lumina of glomerular capillary. Complete blockage of these afferent arterioles
often leads to ―Bloodless Glomeruli.‖ Other possible mechanism of renal
dysfunction in these patients is secondary to circulatory collapse, which leads
to renal hypo-perfusion, acute tubular necrosis (ATN) and acute renal failure
(ARF) [16].
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