1. Disseminated intravascular coagulation (DIC) is a condition where excessive blood clotting leads to formation of clots throughout the small blood vessels, consuming clotting factors and platelets and causing bleeding complications. 2. DIC can be caused by infections, cancer, trauma, pregnancy complications, and other medical conditions. It involves an imbalance between coagulation and anticoagulation pathways that leads to thrombosis and hemorrhage. 3. Treatment of DIC focuses on treating the underlying cause, replacing clotting factors, administering anticoagulants in some cases, and restoring natural anticoagulant pathways.

1. Disseminated Intravascular
Coagulation
DR.M.KRISHNA VASUDEV

2. DEFINITION

3. Disseminated intravascular coagulation
(DIC) is a clinicopathologic syndrome
characterized by widespread
intravascular fibrin formation in
response to excessive blood protease
activity that overcomes the natural
anticoagulant mechanisms.

4. CAUSES

5. 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.

6. 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

8. PATHOPHYSIOLOGY

10. 1. Increased thrombin generation: Mediated predominantly by tissue
factor/factor VIIa pathway
2. Impaired function of physiological anticoagulant pathway
a) Reduction of antithrombin levels -- The result of a combination of increased
consumption, enzyme degradation, impaired liver synthesis and vascular
leakage
b) Depression of protein C system -- The result of a combination of increased
consumption, impaired liver synthesis, vascular leakage and down- regulation
of thrombomodulin
c) Insufficient tissue factor pathway inhibitor (TFPI)
3. Impaired fibrinolysis: Mediated by release of plasminogen activators from
endothelial cells immediately followed by an increase in the plasma levels of
plasminogen activator inhibitor type 1 (PAI-1)
4. Activation of inflammatory pathway: Mediated by activated coagulation
proteins and by depression of the protein C system

11. SIGNS AND SYMPTOMS

12. HISTORY
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

13. 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)

14. 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

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

16. DIFFERENTIAL DIAGNOSIS

17. 1.
2.
3.
4.
5.
6.
7.
Atypical hemolytic-uremic syndrome
Hemolytic-Uremic Syndrome
Heparin-induced thrombocytopenia and thrombosis syndrome
Idiopathic Thrombocytopenic Purpura
Liver disease
Primary hemostatic disorders (eg, dysfibrinogenemias; inhibitors
to factors II, V, X)
Thrombotic Thrombocytopenic Purpura

18. DIAGNOSIS

19. •Platelet -- moderate-to-severe thrombocytopenia is present in DIC.
•Activated partial thromboplastin time [aPTT] and prothrombin time
[PT]) are typically prolonged.
•Protein C and antithrombin are 2 natural anticoagulants that are
frequently decreased in DIC.
•Elevated levels D-dimer and FDPs
•Thrombomodulin is elevated in DIC, a marker for early identification
and monitoring of DIC.
•Chronic DIC diagnosis when the schistocytes are seen in concert with
normal coagulation values and increased D-dimer levels.

21. Clinical conditions that should be ruled out
Thrombocytopenia
Dilution and abnormal distribution
Massive blood loss, massive infusion
ITP, TTP-HUS, HIT, HELLP syndrome
Disorders of hematopoiesis
Liver disease
Hypothermia
Spurious laboratory results
Diagnostic algorithm for SIRS
Temperature >38°C or < 36°C
Heart rate >90 beats/min
Respiratory rate >20 breaths/min or PaCO2 < 32 mm Hg (< 4.3 kPa)
WBC count >12,000 cells/µL, < 4000 cells/ µL, or 10% immature (band) forms
Diagnostic algorithm
SIRS criteria
Score
>3
1
0-2
0
Platelet count (× 109/L)
< 80 or >50 % decrease within 24 hours
3
>80 and < 120 or >30% decrease within 24 hours
1
>120
0
Prothrombin time (value of patient/normal value)
>1.2
1
< 1.2
0
Fibrin/FDPs (mg/L)
>25
3
>10 and < 25
1
< 10
0
Diagnosis
4 points or more
DIC

22. TREATMENT

23. 1) Replacement therapy
- Fresh-frozen plasma
2) Anticoagulants
- Unfractionated and low-molecular-weight
heparin
- Danaparoid sodium
- Recombinant hirudin
- Recombinant tissue factor pathway inhibitor
- Recombinant nematode anticoagulant protein
c2
3) Restoration of anticoagulant pathways
- Antithrombin
- Recombinant human activated protein C
4) Other agents
- Recombinant activated factor VII
- Antifibrinolytic agents
- Antiselectin antibodies
- Recombinant interleukin-10
- Monoclonal antibodies against TNF and CD14

24. Management of Underlying Disease
•The management of acute and chronic forms of disseminated intravascular
coagulation (DIC) should primarily be directed at treatment of the underlying
disorder.
Administration of Blood Components and Coagulation Factors
•Platelet transfusion may be considered in patients with DIC and severe
thrombocytopenia, in particular, in patients with bleeding or in patients at risk
for bleeding
•The PT (>1.5 times the normal) Replacement with FFP is indicated
•Low levels of fibrinogen (<100 mg/dL) or brisk hyperfibrinolysis will require
infusion of cryoprecipitate. The replacement of 10 U of cryoprecipitate for every
2–3 U of FFP is sufficient to correct the hemostasis.
•In case of a (relative) vitamin K deficiency in the face of consumption,
administration of vitamin K may be required.

25. Anticoagulation
•Experimental studies have suggested that heparin can at least partly inhibit
the activation of coagulation in cases of sepsis and other causes of
DIC. However, a beneficial effect of heparin on clinically important outcome
events in patients with DIC has not yet been demonstrated in controlled
clinical trials.
•Therapeutic doses of heparin are indicated in cases of obvious
thromboembolic disease or where fibrin deposition predominates
(eg, purpura fulminans or acral ischemia).
• A dose of 4-5 U/kg constant infusion without a 80-U/kg bolus is a safe
means to deliver heparin to the DIC without increasing the bleeding risk.
Restoration of Anticoagulant Pathways
•Antithrombin concentrate, recombinant human APC, tissue factor (TF)
pathway inhibitor (TFPI) and recombinant thrombomodulin (rTM)

26. Antifibrinolytic treatment
In the coagulopathy associated with acute promyelocytic leukemia
(AML-M3) and in some cases of DIC secondary to malignancies (e.g.
prostate carcinoma) lysine analogues such as tranexamic acid can be
utilized
Investigational Treatments
Tissue factor (TF)-VIIa complex include inactivated factor VII and
recombinant nematode anticoagulant peptide (NAPc2)