1. Intravascular Coagulation
Disseminated
Intravascular Coagulation
Sidney F. Rhoades, M.D.

2. No off label usage of medications or products of any kind
NO disclosures
No off label usage of medications or products of any kind

3. Objectives To attempt to not confuse you in regards to DIC
Define DIC and understand classification
Understand the epidemiology, etiology and risk factors of DIC
Describe signs and symptoms of DIC
Understand the laboratory findings in DIC

4. Defining DIC Acquired Condition
Also known as consumption coagulopathy and defibrination syndrome
Acquired Condition
Systemically producing thrombosis and hemorrhage
Initiated by several disorders or “illnesses”
Consist of exposure of blood to procoagulants
- tissue factor
- cancer procoagulant

5. Defining DIC Formation of Fibrin within the circulation Fibrinolysis
Depletion of clotting factors
End Organ Damage

6. Defining DIC
A systemic disorder of clotting and bleeding after exposure to blood procoagulants thereby causing fibrin formation and degradation (FDP).
Abnormal acceleration of the coagulation cascade, resulting in thrombosis
Depletion of the clotting factors causing hemorrhage

8. DIC is a disorder of diffuse activation of the clotting cascade that results in depletion of clotting factors in the blood.

9. Epidemiology of DIC Incidence:
DIC is complication of underlying illness occurring in 1% of hospitalized patients

10. Classification: Acute or Chronic
Acute DIC
-develops rapidly over a period of hours
-presents with sudden bleeding from multiple sites
-treated as a medical emergency
Chronic DIC
-develops over a period of months
-maybe subclinical
-eventually evolves into an acute DIC pattern
(Otto, 2001)

11. Classification: Acute or Chronic
-blood is exposed to a large amount of tissue factor
over a brief period of time
-massive generation of thrombin
-acutely triggers the coagulation cascade
-overwhelming the inhibitory mechanisms

12. Classification: Acute or Chronic
Tissue factor :
-integral membrane glycoprotein not normally
expressed on the vascular cell surface
-caused by vessel wall damage
-circulates in the blood as a derivative of monocytes and macrophages
-platelets also generate tissue factor
in order to generate thrombin

14. Classification: Acute or Chronic
Secondary Fibrinolysis:
-process of degrading fibrin creating FSP
normally cleared from circulation
-interrupts normal fibrin polymerization
-binds to platelet surface glycoprotein Iib/IIIa
-caused by tissue plasminogen activator
plasminogen  plasmin
-cleaves other proteins other than fibrin like fibrinogen
-eats up other clotting factors

16. Classification: Acute or Chronic
-also known as compensated DIC
-blood is continuously or intermittently exposed to small amounts of tissue factor
-liver and bone marrow are able to replenish the
depleted coagulation proteins and platelets

17. Etiology and Pathology of DIC
Extrinsic (endothelial)
-Shock or trauma
-Infection –gram positive
and gram negative
*bacterial and nonbacterial infection
-Obstetric complications
*eclampsia, placenta abruption, fetal death
-Malignancies
*Acute promyleocytic leukemia, AML, cancers of lung, colon, breast, &
prostate
Intrinsic (blood vessel)
-Infectious vasculitis *certain viral infections
*rocky mountain spotted fever
-Vascular disorders
-Intravascular hemolysis
*hemolytic transfusion reactions
-Miscellaneous
snakebite, pancreatitis, liver disease

18. Extrinsic (endothelial) continued…
Shock
-reduced blood flow and tissue damage
encourages thrombin formation
Trauma
-extensive surgery
-release of tissue enzymes and phospholipids
-head injury
one study of 159 patients found
coagulopathy in 41% of pt’s with CT
evidence of brain injury and 25% of those without

19. Gunshot wound to the carotid artery

20. Extrinsic (endothelial) continued…
Trauma (cont.)
-syndrome developed one to four hours after injry
-studies show direct evidence of procoagulant release
and thrombin formation in cerebrovenous
blood within six hours of isolated head trauma
-studies showed increased D-dimer and soluble fibrin
concentrations indicating coagulation and fibrinolysis
Infection
–both gram positive and gram negative
*bacterial and nonbacterial infection
*Overt DIC reportedly occurs in 30-50% of Pt’s with
gram negative sepsis
*Activation of the endothelial pathway via endotoxin
*Endotoxin also activates factor XII of the intrinsic pathway

21. Question:
Are we missing out in regards to coding and increased severity/mortality?

22. Extrinsic (endothelial) continued…
Malignancies
-3rd most frequent cause of DIC
-accounts for 7 % of clinically evident cases
-can cause acute DIC in Acute Promyelocytic Leukemia
-pulmonary or cerebrovascular hemmorrhage in up to 40% patients
-treat with rapid induction tumor cell differentiation with all-trans retinoic acid
*down-regulates the receptor annexin II,
a RC for plasminogen on the promyelocyte

23. DIC with microangiopathic hemocytic anemia in a 34 y/o female, Hb 8
DIC with microangiopathic hemocytic anemia in a 34 y/o female, Hb 8.6 g/dL, MCV fL, MCHC 32.8 g/dL, platelets 11,000/uL, WBC 59,000/uL. Patient had a history of disseminated non-small cell carcinoma of the lung. She presented to the ER in extremis and expired within a few hours of admission. (

24. Extrinsic (endothelial) continued…
Obstetric complications
-seen in more than 50% of amniotic fluid embolism and abrupteoplacentae
- the greater the abruption the higher the severity
- thromboplastins integrated into mother’s blood system
- peripartum hemorrhage may be spontaneous
- 20% in women with HELLP
- septic abortions
- dead fetus syndrome

26. Clinical Manifestations
Bleeding (64%)
Renal dysfunction (25%)
Hepatic dysfunction (19%)
Respiratory dysfunction (16%)
Shock (14%)
Thromboembolism (7%)

27. Clinical Manifestations
Bleeding
-petechiae
-ecchymoses
-blood oozing from wound sites
-intravenous lines
-mucosal surfaces
Acute Renal Failure
-microthrombosis of afferent arterioles
-cortical ischemia
-necrosis
-hypotension  ATN

28. Clinical Manifestations
Hepatic Dysfunction
-jaundice (from liver disease and hemolysis)
-hepatocellular injury (from sepsis/shock)
Pulmonary Disease
-hemorrhage with hemoptysis
-ARDS
-pulmonary microthrombosis

29. Clinical Manifestations
Central Nervous System
-coma
-delirium
-transient focal neurologic symptoms
-microthrombi, hemorrhage, and hypoperfusion are causes

30. CASE
STUDY

31. Case Study Cc: chest pain, N/V
HPI: 67 y.o. female significant PMHx of rheumatoid arthritis
on Enbrel, pericarditis presently on prednisone taper and known previous pleural effusion with a negative previous workup for tuberculosis. Pt. presented complaining of N/V and 7/10 sharp chest pain at her anterior chest wall radiating across the upper part of the chest, worsening with inspiration. She had productive green sputum and white count 42,000. Pt’s temp was

32. Case Study
PMhx : GERD, depression, hypercholesterolemia, pericarditis, pleural
Effusion, rheumatiod arthritis
PSHhx: noncontributory
Meds: Enbrel, Votaren, Ultram, Nexium, Zocor, Pristiq, tylenol#4,
hydrocodone-apap, Melatonin, Erythromycin, prednisone,
Gel eye drops
Allergies:NKDA
ROS: ten point review otherwise negative
Social history: Patient lives with her family, no hx of tobacco or Etoh

33. Case Study Physical exam Vitals T 100.3 RR 20 P 128 BP 103/60 95% RA
WD WN Elderly female appearing ill no acute distress
and oriented to person, place and time
HEENT: AT, NC Anicteric…no conjuctival pallor mmm
Neck Supple with no JVD and negative HJR
Chest: Moderately good air entry bilaterally with few
bibasilar crackles
CVS: tachycardic, Regular S1:S2

34. Case Study Labs at 21:45 on 7/17/10 Na 137 CL101 BUN 23 glucose 158
K CO2 23 Cr0.57
Bilirubin total PT 13.7 INR 1.0
SGOT PTT 17.3
SGPT trp 0.04
Alk Phos BNP 79
WBC’s Hgb 14.7 plt 385
EKG sinus tachycardia, 114 no ST-T changes
CXR: enlarged cardiac silhouette no infiltrates
or pulmonary congestion

35. Case Study Pt. became more hypotensive , clammy and diaphoretic
She was transferred to the ICU and given fluid boluses as well as pressors
Due to Pt’s immunocompromised state Pt. was placed on Imipenem and Vancomycin.
Pt was ultimately intubated after ABG’s returned and were noted to be significantly worse.

36. Case Study Labs at 02:40 on 7/18/10 Na 137 CL106 BUN 24 glucose 168
K CO2 22 Cr 0.73
Bilirubin total 1.3
SGOT
SGPT trp 0.16
Alk Phos
WBC’s Hgb 11.8 plt 416

37. Case Study Labs at 07:10 on 7/18/10 Na 133 CL109 BUN 22 glucose 224
K CO2 15 Cr0.67
Bilirubin total 0.9
SGOT
SGPT
Alk Phos
WBC’s Hgb 12.6 plt 438
U/A Nitrite negative, leukocyte est negative
Bilirubin negative, Urobilinogen 0.2E. U/dl

38. Case Study Labs at 13:40 on 7/18/10 Na 134 CL105 BUN 22 glucose 279
K CO2 12 Cr1.13
Bilirubin total PT 39.7 INR 3.8
SGOT PTT 80.2
SGPT LDH 1261
Alk Phos amylase 126
Fibrinogen 157 ( mcg/dl)
Fibrin Spit products (Less than 10)
D.DIMER ( mcg/dl)

40. Case Study Risk Factors for Death 1. Increased age
2. Severity of organ dysfunction
3. Severity of hemostatic abnormalities

41. Treatment of DIC
Patients bleed from thrombocytopenia and coagulation factor deficiency
-transfuse platelets and coagulation factors in Pt’s bleeding or with high risk of bleeding
-after surgery or those requiring invasive procedures
-Patients with marked thrombocytopenia <20,000
-moderate thrombocytopenia <50,000/microL and bleeding
-serious bleeding should have 1-2 units per 10kg per day

42. Treatment of DIC Actively bleeding patients
-with elevated prothrombin time/INR or Fibrinogen concentration < 50mg/dl
-transfuse FFP
-cyroprecipitate for fibrinogen replacement
-preferable to keep fibrinogen level >100mg/dl

43. Treatment of DIC Heparin no controlled trials indicating benefit
little evident that it improves organ dysfunction
use is limited to specific Patients with chronic DIC and
mostly thrombotic manifestations
-migratory thrombophlebitis
used in retained dead fetus and hypofibrinogenemia
prior to induction of labor
excessive bleeding assoc with giant hemangioma
aortic aneurysm prior to resection

44. Treatment of DIC

45. Treatment of DIC Xigris activated protein C
anticoagulant and anti-inflammatory activities
direct anti-inflammatory effect on endothelial cells
studies show modulation of gene expression
inhibits TNF expression of cell adhesion molecules
ICAM-1, VCAM-1, E-selectin by down
regulation of Transcrition facor NF-kB
enhances anti-apoptotic genes

46. Comparison of DIC to TTP/HUS
has normal coagulation components
little or no prolongation of the PT or PTT
will share microangiopathic blood smear
TTP will have thrombocytopenia and schistocytes
clinical settings are usually different than DIC
associated sepsis, trauma, malignancy, OB

47. The End