Disseminated intravascular coagulation

1. Department of Pathophysiology
(Disseminated intravascular coagulation)
Name: Gustavo Duarte Viana
Group: 17
3rd year 2nd semester
Medical faculty
Supervisor: Associated Professor Antropolskaya, E. V.

2. Contents
Definition
Etiology
Classification
Pathophysiology
Symptoms and signs
Laboratory diagnosis
Differential Diagnosis
Treatment
Complications
Prognosis

3. Definition
 Disseminated intravascular coagulation (DIC) is
characterized by systemic activation of blood
coagulation, which results in generation and
deposition of fibrin, leading to microvascular thrombi
in various organs and contributing to multiple organ
dysfunction syndrome (MODS).[1] Consumption and
subsequent exhaustion of coagulation proteins and
platelets (from ongoing activation of coagulation) may
induce severe bleeding, though microclot formation
may occur in the absence of severe clotting factor
depletion and bleeding.

4.  DIC is not a kind of independent disease, but a middle
process or complication of some diseases .
 It is essentially an imbalance between the coagulation
process and anticoagulation process. It is a syndrome
characterized by massive activation and consumption
of coagulation proteins, fibrinolytic proteins and
platelets.
 Coagulation is usually confined to a localized area by
the combination of blood flow and circulating
inhibitors of coagulation, especially antithrombin Ⅲ .
If the stimulus to coagulation is too great, these
control mechanisms can be overwhelmed, leading to
the syndrome of DIC.

5. Epidemiology
DIC may occur in 30-50% of patients with sepsis, and it
develops in an estimated 1% of all hospitalized
patients.[4] DIC occurs at all ages and in all races, and no
particular sex predisposition has been noted.

6. Etiology
 DIC is not a primary disease, but a disorder secondary to
numerous triggering events such as serious illnesses.
 Several disease states may lead to the development of
DIC, generally via 1 of the following 2 pathways:
1) A systemic inflammatory response, leading to activation
of the cytokine network and subsequent activation of
coagulation (eg, in sepsis or major trauma)
2) Release or exposure of procoagulant material into the
bloodstream (eg, in cancer, crush brain injury, or in obstetric
cases)
 In some situations (eg, major trauma or severe necrotizing
pancreatitis), both pathways may be present.

7. Classification according to
acute or chronic Etiologies

8. Pizza graph for DIC etiology
infectious disease 31%~43%
cancer 24%~34%
obstetric complications 4%~12%
severe tissue injury 1%~5%
ID
systemic disease
Cancer
O
C
STI
SD

9. ACUTE DIC
Type
Infectious
Cause
Bacterial (eg, gram-negative sepsis, gram-positive infections,
rickettsial)
Viral (eg, HIV, cytomegalovirus [CMV], varicella-zoster virus
[VZV], and hepatitis virus)
Fungal (eg, Histoplasma)
Parasitic (eg, malaria)
Malignancy
Hematologic (eg, acute myelocytic leukemia)
Metastatic (eg, mucin-secreting adenocarcinoma)
Obstetric
Placental abruption
Amniotic fluid embolism
Acute fatty liver of pregnancy
Eclampsia
Trauma
Burns
Motor vehicle accidents
Snake envenomation
Transfusion
Hemolytic reactions
Transfusion
Other
Liver disease/acute hepatic failure*
Prosthetic devices
Shunts (Denver or LeVeen)
Ventricular assist devices
*Some do not classify this as DIC; rather, it is liver disease with reduced blood coagulation factor synthesis and reduced clearance
of activate products of coagulation.

10. CHRONIC DIC
Type
Malignancies
Cause
Solid tumors
Leukemia
Obstetric
Retained dead fetus syndrome
Retained products of conception
Hematologic
Vascular
Myeloproliferative syndromes
Rheumatoid arthritis
Raynaud disease
Cardiovascular
Inflammatory
Myocardial infarction
Ulcerative colitis
Crohn disease
Sarcoidosis
Localized DIC
Aortic aneurysms
Giant hemangioma (Kasabach-Merritt
syndrome)
Acute renal allograft rejection

12. Acute Infectious DIC
Bacterial infection (in particular, bloodstream infection
[BSI]) is commonly associated with DIC. There is no
difference in the incidence of DIC between patients with
gram-negative sepsis and those with gram-positive sepsis.
Systemic infections with other microorganisms, such as
viruses and parasites, may lead to DIC as well.
Factors involved in the development of DIC in patients with
infections may be specific cell membrane components of the
microorganism (lipopolysaccharide or endotoxin) or
bacterial exotoxins (eg, staphylococcal alpha toxin). These
components cause a generalized inflammatory response,
characterized by the systemic occurrence of proinflammatory
cytokines.

13. Acute DIC due to trauma
Severe trauma is another clinical condition frequently
associated with DIC. A combination of mechanisms—
including release of tissue material (eg, tissue factor
[thromboplastin], fat or phospholipids) into the
circulation, hemolysis, and endothelial damage—may
contribute to systemic activation of coagulation. In
addition, solid evidence indicates that cytokines also
play a pivotal role in the occurrence of DIC in trauma
patients. In fact, systemic cytokine patterns have been
shown to be virtually identical in trauma patients and
septic patients

14. DIC in cancer
Both solid tumors and hematologic malignancies may be
complicated by DIC. The mechanism by which
coagulation is deranged in this situation is poorly
understood. Solid tumor cells can express different
procoagulant molecules, including TF and a cancer
procoagulant. Cancer procoagulant is found in extracts
of neoplastic cells and in the plasma of patients with
solid tumors. As noted, some tumors are associated with
a form of DIC that is characterized by severe
hyperfibrinolysis on top of an activated coagulation
system.

15. DIC in problems in obstrectics
Acute DIC occurs in obstetric calamities such as
placental abruption (abruptio placentae) and amniotic
fluid emboli. Amniotic fluid has been shown to be able
to activate coagulation in vitro, and the degree of
placental separation correlates with the extent of the
DIC, suggesting that leakage of thromboplastinlike
material from the placental system is responsible for the
occurrence of DIC.

16. DIC in vascular disease
Vascular disorders, such as large aortic aneurysms or
giant hemangiomas (Kasabach-Merritt syndrome), may
result in local activation of coagulation. Activated
coagulation factors can ultimately “overflow” to the
systemic circulation and cause DIC, but systemic
depletion of coagulation factors and platelets as a result
of local consumption is a more common scenario.

17. Pathophysiology
DIC occurs when monocytes and endothelial cells are
activated or injured by toxic substances elaborated in the
course of certain diseases. The response of monocytes
and endothelial cells to injury is to generate tissue factor
on the cell surface, activating the coagulation cascade .
In acute DIC, an explosive generation of thrombin
depletes clotting factors and platelets and activates the
fibrinolytic system. Bleeding into the subcutaneous
tissues, skin, and mucous membranes occurs, along with
occlusion of blood vessels caused by fibrin in the
microcirculation.

18. In chronic DIC, the process is the same, but it is less
explosive. Usually there is time for compensatory
responses to take place, which diminish the likelihood of
bleeding but give rise to a hypercoagulable state.
These changes in the blood can be detected by testing
the coagulation system.
Thromboembolism occurs in this setting, and when oral
anticoagulants are given following heparin therapy,
there is a tendency for it to recur.
Long-term therapy with low-molecular-weight heparin
may be a solution to this problem until the underlying
cause can be brought under control.

19. Stimulation of
Coagulation
Intravascular
thrombosis
Consumption
of
coagulation factors
Secondary
activation
of
thrombolysis
Hypoperfusion
to tissues
and organs
Inability to
form a
stable clot
Release
of
anticoagulants
Ischemic
damage
Bleeding
Bleeding

20. Symptoms and sings
Acute DIC





Clinical findings
Multiple bleeding sites
Ecchymoses of skin, mucous membranes
Visceral hemorrhage
Ischemic tissue

21. Chronic DIC

Clinical findings
 Signs of deep venous or arterial thrombosis or
embolism
 Superficial venous thrombosis, especially
without varicose veins
 Multiple thrombotic sites at the same time
 Serial thrombotic episodes

22. Symptoms and signs
 The symptoms of disseminated intravascular coagulation
(DIC) are often those of the underlying inciting condition
1. Bleeding
•
•
•
•
GI bleed
petechiae and ecchymosis,
intravenous (IV) lines and catheters bleed
surgical sites, drains, and tracheostomies and within serous
cavities.
2. Renal Failure
3. Pulmonary involvement
• dyspnea, hemoptysis, and cough
4. Jaundice

23. SYMPTOMS
Circulatory signs include the following:
1. Signs of spontaneous and life-threatening hemorrhage
2. Signs of subacute bleeding
3. Signs of diffuse or localized thrombosis
4. Bleeding into serous cavities
Central nervous system signs include the following:
1. Nonspecific altered consciousness or stupor
2. Transient focal or neurologic deficits
Cardiovascular signs include the following:
1. Hypotension
2. Tachycardia
3. Circulatory collapse
Respiratory signs include the following:
1. Pleural friction rub
2. Signs of acute respiratory distress syndrome (ARDS)

24. GI signs include the following:
1. Hematemesis
2. Hematochezia
Genitourinary signs include the following:
1. Signs of azotemia and renal failure
2. Acidosis
3. Hematuria
4. Oliguria
5. Metrorrhagia
6. Uterine hemorrhage
Dermatologic signs include the following:
1. Petechiae
2. Jaundice (liver dysfunction or hemolysis)
3. Purpura
4. Hemorrhagic bullae
5. Acral cyanosis
6. Skin necrosis of lower limbs (purpura fulminans)
7. Localized infarction and gangrene
8. Wound bleeding and deep subcutaneous hematomas
9. Thrombosis

25. Features
Affected Patients, %
Bleeding
64%
Renal dysfunction
25%
Hepatic dysfunction
19%
Respiratory dysfunction
16%
Shock
14%
Central nervous system
dysfunction
2%

26. Meningococcemia on the Calves

27. Necrosis of the toes

28. Purpura Fulminans
 Purpura fulminans that is also known as "Purpura
gangrenosa“ is a haemorrhagic condition usually
associated with sepsis or previous infection, it is the
cutaneous manifestation of disseminated intravascular
coagulation. Occurs mainly in babies and small
children, but there are also rare cases reported among
adults. Specially caused by gram-negative bacteria.

29. Purpura fulminans

30. Purpura fulminans of a child's leg

31. Laboratory diagnosis

32. Test
Result
Platelet count
Markedly decreased
Prothrombin time (PT)
Increased
Activated partial thromboplastin
time (APTT)
Increased
Fibrin degradation products
(FDP)
Markedly increased
Fibrinogen
Normal or
decreased
Antithrombin III (AT III)
Markedly decreased

33. Different Diagnosis
 Liver disease: Liver disease may prolong both the PT and PTT, but
fibrinogen levels are usually normal, and the platelet count is
usually normal or only slightly reduced. Severe liver disease may
be difficult to distinguish from DIC.
 Vitamin K deficiency: Vitamin K deficiency will not affect the
fibrinogen level or platelet count, but will decrease the
coagulation factors and will be completely corrected by vitamin K
replacement.
 Sepsis: Sepsis may produce thrombo-cytopenia, and coagulopathy
may be present because of vitamin K deficiency. However, in these
cases, the fibrinogen level should be normal.
 TTP (thrombotic thrombocytopenic purpura): TTP may produce
fever and MAHA (microangiopathic hemolytic anemia). However,
fibrinogen levels and other coagulation studies should be normal.

34. Treatment
Treatment of the underlying disorder
Replacement therapy
Heparin therapy
Other Treatment

35. 


Acute DIC
Without bleeding or evidence of ischemia
No treatment
With bleeding
Blood components as needed
Fresh frozen plasma
Cryoprecipitate
Platelet transfusions
With ischemia
Anticoagulants after bleeding risk is corrected with
blood products

36. Chronic DIC
 Without thromboembolism
 No specific therapy needed but prophylactic
drugs (eg, low-dose heparin, low-molecularweight heparin) may be used for patients at
high risk of thrombosis
 With thromboembolism
 Heparin or low-molecular-weight
heparin, trial of warfarin sodium
(Coumadin). (If warfarin is
unsuccessful, long-term use of lowmolecular-weight heparin may be helpful.)

37. Complications
Severe bleeding
Stroke
Ischemia of extremities or organs

38. Prognosis
 Since DIC is a result of an acute medical
illness, prognoses depends almost entirely upon the
speed of the intensive in handing the bleeding
emergency, as well as the ability to treat the underling
disorder
 The underlying disease that causes the disorder will
usually predict the probable outcome.

39. References
 Lecture of Kursk State Medical university on the




theme Disseminated intravascular coagulation
Robbins, Stanley L.; Cotran, Ramzi S.; Kumar, Vinay;
Collins, Tucker (1999). Robbins' Pathologic Basis of
Disease (6 ed.). Philadelphia: Saunders.
Davidson's Principles and Practice of Medicine (19 ed.).
Churchill Livingstone. 2002
http://emedicine.medscape.com/article/199627overview
http://www.slideshare.net/deepak15/disseminatedintravascular-coagulation

40. Thank you