DIC is one condition that always trouble patients and doctor, though its a nightmare for any clinician , its also a potent question in both UG and PG exams. I hope this will help you in answering those questions well.

1. DISSEMINATED INTRAVASCULAR
COAGULATION
DR AKSHAYA TOMAR , MD
IMMUNOHEMATOLOGY AND BLOOD TRANSFUSION
AFMC, PUNE

2. INTRODUCTION
• Clinicopathologic syndrome characterized by:
EXCESSIVE BLOOD PROTEASE
ACTIVITY
DECREASED NATURAL
ANTICOAGULATION
INCREASED INTRAVASCULAR
FIBRIN FORMATION

3. DEFINITION
• According to International Society on Thrombosis
and Haemostasis ,
- DIC is an acquired syndrome characterized by the
intravascular activation of coagulation with loss of
localization arising from different causes
- It can originate from and cause damage to the
microvasculature, which if sufficiently severe, can
produce organ dysfunction

4. HISTORICAL ASPECTS
• First description in 1950,by
Walter H Seegers
• Lecture named “ Factors
in the Control of Bleeding”
where he postulated that
thromboplastin may be
associated with the
hemorrhage that are seen
with amniotic fluid embolism.

5. HISTORICAL ASPECTS
• Later Ratnoff , Pritcher
and Colopy in an article
entitled “Hemorrhagic
States During Pregnancy”
described about the
hemorrhagic syndromes
of pregnancy now called DIC
• After a mid-1960s DIC became a clinically
accepted and recognized syndrome

7. NORMAL HEMOSTASIS

8. ROLE OF ENDOTHELIUM

9. CELL BASED MODEL OF COAGULATION

10. THROMBIN

11. FIBRINOLYTIC SYSTEM

13. PATHOPHYSIOLOGY
MASSIVE
TISSUE
DESTRUCTION
SEPSIS
ENDOTHELIAL
INJURY
RELEASE OF TISSUE FACTOR
Widespread
microvascular
thrombosis
Platelet aggregation
Activation of plasmin
FIBRINOLYSIS
Proteolysis of
clotting factors
BLEEDING
Consumption of platelets
and clotting factors
FDP
-PLATELET AGGREGATION
-THROMBOSIS
-FIBRIN POLYMERISATION
VASCULAR
OCCLUSION

15. CAUSES OF DIC
SEPSIS
TRAUMA
MISC
CANCER
OBSTETRIC
DRUGS
ENVENOMATION

16. CAUSES

17. ACUTE VS CHRONIC DIC
ACUTE DIC CHRONIC DIC
• Due to consumption and
inhibition of clotting factors
• Thrombocytopenia
• Faster rate of consumption
• Sudden exposure of massive
amount of thromboplastin
ex: Abruptio placenta,
extensive tissue
trauma,meningococcimea
• Due to overcompensation of
clotting factors
• Thrombocytosis or normal
platelets
• Slower rate of consumption
• Blood is continuously exposed to
small amount of thromboplastin
ex: prostate and pancreatic
adenocarcinoma, aortic
aneurysms

20. CLINICAL MANIFESTATION
• Related to the magnitude of imbalance of
hemostasis, to the underlying disease or to both
• Most common is bleeding ranging from oozing from
venipuncture sites,petechiae and ecchymoses
• Severe hemorrhage from GIT , lung or CNS
• In chronic DIC, bleeding symptoms are discrete &
restricted to skin & mucosal surfaces
• Microvascular occlusion and resultant organ failure

21. CLINICAL MANIFESTATIONS
• Bleeding from at least 3 unrelated sites is
particularly suggestive of DIC.
• Patients with pulmonary involvement can present
with dyspnea, hemoptysis, and cough.
• Comorbid liver disease as well as rapid hemolytic
bilirubin production may lead to jaundice.
• Neurologic changes (eg, coma, obtunded mental
status, and paresthesias) are also possible.

22. SIGNS

23. SIGNS

24. DERMATOLOGICAL SIGNS
Hemorrhagic bulla
Echymosis
Petechiae
Acral cyanosis and superficial skin necrosis

29. INTRODUCTION
• Clinicopathologic syndrome characterized by:
EXCESSIVE BLOOD PROTEASE
ACTIVITY
DECREASED NATURAL
ANTICOAGULATION
INCREASED INTRAVASCULAR
FIBRIN FORMATION

30. PATHOPHYSIOLOGY
MASSIVE
TISSUE
DESTRUCTION
SEPSIS
ENDOTHELIAL
INJURY
RELEASE OF TISSUE FACTOR
Widespread
microvascular
thrombosis
Platelet aggregation
Activation of plasmin
FIBRINOLYSIS
Proteolysis of
clotting factors
BLEEDING
Consumption of platelets
and clotting factors
FDP
-PLATELET AGGREGATION
-THROMBOSIS
-FIBRIN POLYMERISATION
VASCULAR
OCCLUSION

31. DIAGNOSIS
• No single test is diagnostic of DIC
• It is the overall clinical picture supported by
some investigations, which should guide the
management.
• Of these tests , thrombocytopenia and
hypofibrinogenemia (or a 50% drop in either
value) are the most sensitive in making a
laboratory diagnosis of DIC.

32. SCORING SYSTEM
• The International Society on Thrombosis and
Haemostasis (ISTH) developed a simple
scoring system for the diagnosis of overt DIC
that makes use of laboratory tests available in
almost all hospital laboratories

33. ISTH CRITERIA FOR DIC

34. IMPORTANCE OF SCORING SYSTEM
• A score of 5 or higher indicates overt DIC,
whereas a score of less than 5 does not rule out
DIC but may indicate DIC that is not overt.
• The sensitivity of the DIC score for a
diagnosis of DIC is 91-93%, and the
specificity is 97-98%.

35. COMMON LAB FINDINGS
• Prolongation of PT/aPTT
• Thrombocytopenia (often <1lac/µl3)
or a rapid decline in platelet number
• Peripheral blood smear – Schistocytes (fragmented
RBC)
• Increased FDP levels (most sensitive test), DIC is
unlikely in presence of normal FDP
• Elevated D-Dimer

36. SPECIALIZED LAB TESTS
• Excess thrombin generation
- Increased thrombin-antithrombin complexes
- Increased fibrinopeptides
- Increased prothrombin fragments 1 and 2
• Decreased protein C / protein S and antithrombin
• Increased fibrinolysis
- Increase in plasmin
- Decreased plasminogen levels
- Decrease in α2 antiplasmin
- High levels of plasminogen activators inhibitors

37. SPECIALIZED LAB TESTS
• Newer markers (signifying thrombosis-inflammation cross-link)
- Increased soluble thrombomodulin
- Decreased ADAMTS-13 (a disintegrin and metalloproteinase
with a thrombospondin type 1 motif, member 13)

38. D-Dimer
• D-dimers are little chunks of broken up fibrin, like FDPs, but with
an important difference: they contain an extra linkage.
• When fibrin seals up a clot,
factor XIII creates cross-links
between the fibrin molecules
• When the fibrin in a clot breaks, some
of the resulting fragments will contain these
cross-links. These fragments contain
one “E” fibrin subunit and two “D” subunits
and are called D-dimers.

39. D-Dimer
• D-dimers are more specific for actual clots than
FDPs are – because you only get D-dimers from
the breakdown of real clots (not from the
breakdown of fibrinogen).
• Serial monitoring of D-dimer assays are of value
in evaluation of response to therapy.

41. GENERAL CONSIDERATION
• Morbidity & Mortality is mainly related to underlying disease rather
than the complications of DIC.
• Control or elimination of underlying cause should be the primary
concern.
• Attempts to teat DIC without accompanying treatment of causative
disease are likely to fail.

42. Management of hemorrhagic symptoms
• Marked thrombocytopenia (<10,000/µl3) and PT> 1.5 X Normal
require replacement therapy.
• Low levels of fibrinogen (<100mg/dl) -> Cryoprecipitate 1U/10kg
• Replacement of 10U of Cryoprecipitate for every 2-3 U of FFP is
sufficient to correct hemostasis.
• Platelet concentrate 1-2U/10kg -> severe thrombocytopenia.
• Clotting factors conc. are not recommended for control of bleeding
in DIC ;limited efficacy

43. Replacement of coagulation and
fibrinolysis inhibitors
• Heparin (5-10U/kg/hr) may be effective in low grade DIC associated
with – Solid tumor/Acute Promyelocytic Leukemia/Recognized
thrombosis/some cases of purpura fulminans(dead fetus syndrome)
• In acute DIC, heparin can aggravate bleeding
• EACA/Tranaexemic acid may reduce bleeding in DIC and confirmed
hyperfibrinolysis, however they can increase the risk of thrombosis
& concomitant use of heparin is indicated.
• Activated protein C concentrate to treat Purpura Fulminans (In
Protein C deficiency and meningococcemia) proven efficacious.

44. • In the acute coagulopathy of trauma, in which
hyperfibrinolysis predominates, antifibrinolytic agents
are beneficial for those with persistent bleeding after
adequate replacement
of fresh frozen plasma.
• Another clinical situation is massive postpartum
hemorrhage, for which fibrinolysis is a prime
pathophysiological factor in the coagulopathy and
tranexamic acid has been demonstrated to be beneficial.

46. Activated Protein C
• In a phase III clinical trial of recombinant APC (rAPC) in patients
with severe sepsis in a dose of 24 μg/Kg/h over 96 h, significant
reduction in 28 day mortality was seen.
• Most significant complication was bleeding
• It is recommended in patients with severe sepsis
Clinical efficacy of APC in severe sepsis was demonstrated in a
Large randomized controlled trial (the protein C worldwide evaluation
In severe sepsis [PROWESS] trial), in which its use was
Associated with a reduced mortality (24.7%) compared with that of
The placebo (30.8%) with highest benefit for those who had DIC.

47. Antithrombin III (AT III)
• In a large double blind placebo controlled multicentre phase III trial
(Kybersept trial) AT was used in a dose of 30,000 IU over 4 days.
There was no difference in mortality between the treatment and the
placebo group.
• More bleeding complications.

48. Tissue factor pathway inhibitor(TFPI)
• It was tested in a phase III trial in patients with severe sepsis.
• Tifacogin (TFPI) was given in a dose of .025mg/kg/hr for 96 hrs.
• There was no effect on mortality and the risk of bleeding was
increased.

49. Protease inhibitors
• Gabexate mesylate is a synthetic inhibitor of serine proteases,
including thrombin and plasmin.
• It seems to be a potentially useful agent
• In a limited number of patients, the drug (2mg/kg/hr x 7 days)
could not inhibit coagulation or fibrinolysis

50. C1- Inhibitor (C1- Inh)
• Activation of factor XIa leads to a thrombin burst , therefore
inhibition of factor XIa by C1 inhibitor might be beneficial.
• In a pilot study with limited number of patients C1- Inh was
administered to patients with severe sepsis or septic shock
• Organ dysfunction improved significantly but no effect on mortality
was observed due to small number of patients.

51. Synthetic Inhibitors
• Heparin treatment may be ineffective because it requires
antithrombin for anticoagulant activity
• Direct thrombin inhibitors may be more effective as they do not
require antithrombin.
• Recombinant hirudin reduces thrombin activity in DIC, but clinical
benefit has not yet been evaluated.
• Desirudin and related compounds, might be more effective than
heparin, and experimental studies have had promising results.

52. REFERENCES
• Rossi’s Principles of Transfusion Medicine 5th edition.
• Harrison’s principles of Internal medicine 19th edition Vol 1
• Transfusion Therapy: Clinical Principles and Practice 3rd Edition-
Paul D Mintz
• Colman Basic Principles of Hemostasis and Thrombosis 5th edition
• Robin’s Basic Pathology 9th edition.
• DIC current concepts by R kumar and V Gupta; Indian journal of
pediatrics 2008.