A presentation about DIC (Disseminated Intravascular Coagulopathy). Done by 4th year medical students at the University of Science and Technology, Sana'a, Republic of Yemen, in October 2010.

1. Pathology Seminar
October 2010
Year 4 Medicine
Group 1 UST Sana’a

2. Introduction

 DIC stands for Disseminated intravascular
coagulation.
 It is the disturbance of the blood clotting mechanism.
 Several clots in some vessels  increase
consumption of the blood clotting factors and
platelets deficiency, lack or destruction of those
factors in other body parts Several bleedings in
other areas of the body.

4. Normal Hemostasis

 During vascular injury hemostasis normally occurs
on the affected site. The hemostasis has four phases:
 1. Vasoconstriction then,
 2. Primary phase,
 3. Secondary phase,
 4. Tertiary phase,

5. VASOCONSTRICTION
After vascular injury occurs there are certain
factors of neurohumoral type released causing
transient vasoconstriction to the affected site.

6. PRIMARY HEMOSTASIS
Platelets adhere (via GpIb receptors) to exposed
extracellular matrix by binding to von Willebrand factor
and are activated, undergoing a shape change and granule
release. Released adenosine diphosphate and thromboxane
A2 lead to further platelet aggregation (via binding of
fibrinogen to platelet GpIIb-IIIa receptors), to form the
primary hemostatic plug.

7. SECONDARY HEMOSTASIS
Local activation of the coagulation cascade (involving
tissue factor and platelet phospholipids) results in
fibrin polymerization, "cementing" the platelets into a
definitive secondary hemostatic plug.

8. TERTIARY HEMOSTASIS
Counter-regulatory mechanisms, such as release of t-
PA (Tissue plasminogen activator, a fibrinolytic
product) and thrombomodulin (interfering with the
coagulation cascade), limit the hemostatic process to
the site of injury.

9. 1) Generation of a hyperthrombinemic state
2) Alteration of the physiological anticoagulants
levels
3) Impaired fibrinolysis at the onset of the DIC:
4) Activation and liberation of inflammatory
cytokines in the pathogenesis of DIC

10. Generation of a
1)
hyperthrombinemic state

 The exposing of the tissue factors thromboplastin and
factor III during injury causes a cascade activation of a
factor pathway that has a dominant role in the
hyperthrombinemic state in DIC.
 Cytokines and bacterial endotoxin are all triggers to the
formation of endothelial cell tissue factor.
 In severe trauma also tissue phospholipids initiates the
clotting cascade.

11. cont.: The cascade goes here as follows


12. cont.: The Thrombin in turn activates


13. Alteration of the physiological
2)
anticoagulants levels

 There are 3 most common Anticoagulants in the
body:
 Antithrombin,
 Active Protein C
 Tissue factor pathway inhibitor (TFPI).
 In DIC:
 ↓Antithrombin
 ↓Active Protein C

14. cont.: The cause of the decrease


16. Protein C function

Normally In DIC

17. cont.: Protein C’s Importance


18. Impaired fibrinolysis at the onset of
3)
the DIC:

 Plasminogen activator inhibitor 1 (PAI-1) is a
neurohumoral compound released by the endothelial
cells at the effected site.
 PAI-1 suppresses the normal fibrinolysis activity.
 Some DIC individuals have shown a mutation in the
PAI-1 gene, leading to an increased plasma PAI-1
levels.

20. Activation and liberation of inflammatory
4)
cytokines

 Activation of Clotting sys.  Inflammatory cascade
activation Induced pro-inflammatory cytokines
(thrombin and other serine proteases).
 Pro-inflammatory cytokines + Protease-activated
receptors (of the cell surface of the endothelial cells)
 Inducing an inflammatory and clotting reaction.

22. Signs & symptoms of DIC

 Renal failure.
 Cough
 Confusion.
 Decreased platelets.
 Blood clots.
 Drop in blood pressure.
 Sudden bruising.
 Bleeding, possibly from multiple sites in the body.
 Fever

23. Sites of Thrombosis

Site in decreasing
order of frequency
Brain
Heart
Kidney
Adrenals
Spleen
Lungs
Liver

25. DIC Is most likely to occur after sepsis, obstetric
complications, malignancy, and major trauma
(especially trauma to the brain)

26. Obstetric complications

 Abruption placentae
 Retained dead fetus
 Septic abortion
 Amniotic fluid embolism
 Toxemia

27. Infections

 Sepsis (gram negative and gram positive)
 Meningococcemia
 Rocky Mountain spotted fever
 Histoplasmosis
 Aspergillosis
 Malaria

28. Neoplasms

 Carcinomas of pancreas, prostate, lung, and stomach
 Acute promyelocytic leukemia

29. Massive Tissue Injury

 Trauma
 Burns
 Extensive surgery

30. Miscellaneous

 Acute intravascular hemolysis,
 Snakebite,
 Giant hemangioma
 Shock
 Heat stroke
 Vasculitis
 Aortic aneurysm,
 Liver disease
 Rejection of graft

31. 1. CBC
2. Clotting times:
3. Fibrin related markers important for the
diagnosis of DIC:
4. Coagulation factors:

32. Labinvestigations of DIC
CBC
thrombocytopenia is usually present
Clotting times:

Prothrombin time (PT) – prolonged (may be normal in early or chronic DIC)
Partial thromboplastin time (PTT) – prolonged (may be normal in early or
chronic DIC)
Thrombin time (TT) – may be increased due to consumption of fibrinogen
Fibrin related markers important for the diagnosis of DIC:
D-dimer – increased in acute and chronic DIC (best single test)
A normal d-dimer essentially rules out DIC
Elevated d-dimer levels are seen in a number of conditions in addition to DIC
(eg, pregnancy, acute thrombosis)
Coagulation factors:
Fibrinogen is usually decreased (in an acute phase of DIC, the fibrinogen may not
be decreased, only until DIC is severe)

33. International Society on
Thrombosis and Haemostasis
Scoring System for Diagnosis of
DIC
A score below 5 is
suggestive as a
diagnosis but not
definite; hence the
test must be
repeated.

34. 1. Underlying cause
2. Supportive therapy
3. Heparin therapy

35. Treatment

 The most important fact in the management of DIC, is the
treatment of the underlying cause.
 Supportive therapy may be given to patients with
excessive bleeding:
1) Fluid
2) Blood transfusion
3) Fresh frozen plasma
4) Platelet concentrates
5) Fibrinogen
 Patients with chronic DIC and thrombosis may need
heparin therapy.