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

Disseminated Intravascular Coagulation

Sidney F. Rhoades, M.D.

NO disclosures

No off label usage of medications or products of any kind

•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

Objectives

Defining DIC

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

Defining DIC

Formation of Fibrin within the circulation

Fibrinolysis

Depletion of clotting factors

End Organ Damage

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

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

the blood.

http://health-pictures.com/disseminated-intravascular-coagulation.htm

Epidemiology of DIC

Incidence:

DIC is complication of underlying illness occurring in 1% of hospitalized patients

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)


Acute

-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

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


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



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

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

-Miscellaneoussnakebite, pancreatitis, liver disease

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 foundcoagulopathy in 41% of pt’s with CTevidence of brain injury and 25% of those

without

Extrinsic (endothelial) continued…

Gunshot wound to the carotid artery

http://www.trauma.org/index.php/main/image/588/C1

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


Question:

Are we missing out in regards to coding and increased

severity/mortality?

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


DIC with microangiopathic hemocytic anemia in a 34 y/o female, Hb 8.6 g/dL, MCV 104.5 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. (http://commons.wikimedia.org/wiki/File:DIC_With_Microangiopathic_Hemolytic_Anemia_(301920983).jpg)

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


Clinical Manifestations

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

Bleeding-petechiae-ecchymoses-blood oozing from wound

sites-intravenous lines-mucosal surfaces

Acute Renal Failure-microthrombosis of

afferent arterioles-cortical ischemia-necrosis -hypotension ATN


Hepatic Dysfunction-jaundice (from liver disease and

hemolysis)-hepatocellular injury (from sepsis/shock)

Pulmonary Disease-hemorrhage with hemoptysis-ARDS-pulmonary microthrombosis


Central Nervous System-coma-delirium-transient focal neurologic

symptoms-microthrombi, hemorrhage, and hypoperfusion are causes


CASE

STUDY

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 100.3

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

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 distressand 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 fewbibasilar crackles

CVS: tachycardic, Regular S1:S2

Case Study

Labs at 21:45 on 7/17/10

Na 137 CL101 BUN 23 glucose 158K 4.2 CO2 23 Cr0.57

Bilirubin total 0.7 PT 13.7 INR 1.0SGOT 60 PTT 17.3SGPT 37 trp 0.04Alk Phos 73 BNP 79

WBC’s 42.1 Hgb 14.7 plt 385EKG sinus tachycardia, 114 no ST-T changesCXR: enlarged cardiac silhouette no infiltrates

or pulmonary congestion

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.

Labs at 02:40 on 7/18/10

Na 137 CL106 BUN 24 glucose 168K 3.5 CO2 22 Cr 0.73

Bilirubin total 1.3 SGOT 38 SGPT 29 trp 0.16Alk Phos 46

WBC’s 46.5 Hgb 11.8 plt 416

Case Study

Labs at 07:10 on 7/18/10


Bilirubin total 0.9 SGOT 30 SGPT 26 Alk Phos 45

WBC’s 44.4 Hgb 12.6 plt 438

U/A Nitrite negative, leukocyte est negativeBilirubin negative, Urobilinogen 0.2E. U/dl

Case Study

Case Study

Labs at 13:40 on 7/18/10


Bilirubin total 2.0 PT 39.7 INR 3.8SGOT 527 PTT 80.2SGPT 724 LDH 1261Alk Phos 39 amylase 126

Fibrinogen 157 (221-480 mcg/dl)

Fibrin Spit products 10-40 (Less than 10)

D.DIMER 14.48 (0.00-0.48 mcg/dl)

Case Study

Risk Factors for Death1. Increased age2. Severity of organ dysfunction 3. Severity of hemostatic abnormalities

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

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

Treatment of DIC

Heparinno controlled trials indicating benefitlittle evident that it improves organ dysfunctionuse 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 hemangiomaaortic aneurysm prior to resection

Treatment of DIC

http://www.xigris.com/Pages/index.aspx

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

Comparison of DIC to TTP/HUS

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

The End

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

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