disseminated intravascular coagulation

Disseminated Intravascular CoagulationRobert R. Zaid D.O.

Genesys Regional Medical Center

PGY-I

Barcelona - Gaudi

Disseminated Intravascular Coagulation

-Background

-Pathophysiology

-Etiology

-Clinical Manifestations

-Diagnosis

-Treatment

-Xigris

• Primarily a thrombotic process– Systemic process producing both

thrombosis and hemorrhage– Also called consumption

coagulopathy and defibrination syndrome1

– Its clinical manifestation may be widespread hemorrhage in acute, fulminant cases2.

1. Schafer, A., I., Cecil Textbook of Medicine, Saunders, 2004, chapter 179, HEMORRHAGIC DISORDERS: DISSEMINATED INTRAVASCULAR COAGULATION, LIVER FAILURE, AND VITAMIN K DEFICIENCY2. Uptodote, 2005, www.utdol.com, Clinical feadures, diagnosis and teratment of disseminated intravascular coagulation

http://www.utdol.com/


-Background

-Pathophysiology

-Etiology-Clinical Manifestations-Diagnosis-Treatment-Xigris

• Basic pathophysiology – Entry into the circulation of procoagulant

substances • Trigger systemic activation of the coagulation

system and platelets • Lead to the disseminated deposition of fibrin-

platelet thrombi.

– Procoagulant stimulus is tissue factor (most cases)

• Lipoprotein • Not normally exposed to blood.

– Tissue factor gains access to blood by • Tissue injury, • Malignant cells, • Expression on the surfaces of monocytes and

endothelial cells by inflammatory mediators.

Schafer, A., I., Cecil Textbook of Medicine, Saunders, 2004, chapter 179, HEMORRHAGIC DISORDERS: DISSEMINATED INTRAVASCULAR COAGULATION, LIVER FAILURE, AND VITAMIN K DEFICIENCY

Stein B, Fuster V, Israel DH, et al. Platelet inhibitor agents in cardiovascular disease: an update. J Am Coll Cardiol. 1989;14:813–836.


-Background

-Pathophysiology

-Etiology


-Diagnosis

-Treatment

-Xigris

• Tissue factor triggers – Thrombin

• Protease • Induces fibrin formation and platelet

activation

• Other procoagulants– Cysteine protease– Mucin– Trypsin



-Background

-Pathophysiology

-Etiology


-Diagnosis

-Treatment

-Xigris

• Acute DIC– Coagulation factors are consumed at

a rate in excess of the capacity of the liver to synthesize them,

– Platelets are consumed in excess of the capacity of bone marrow megakaryocytes to release them.



-Background

-Pathophysiology


• Laboratory manifestations– Prolonged prothrombin time (PT) – Prolonged Activated partial thromboplastin time

(aPTT) – Thrombocytopenia. – Increased fibrin formation

• Stimulates compensatory process of secondary fibrinolysis,

• Plasminogen activators generate plasmin to digest fibrin (and fibrinogen) into fibrin(ogen) degradation products (FDPs).

– FDPs are potent circulating anticoagulants that contribute further to the bleeding manifestations of DIC.

• Intravascular fibrin deposition can cause fragmentation of red blood cells and lead to the appearance of schistocytes in blood smears

• Hemolytic anemia is unusual in DIC. • Microvascular thrombosis in DIC can compromise

the blood supply to some organs and lead to multiorgan failure



-Background

-Pathophysiology

-Etiology


-Diagnosis

-Treatment

-Xigris

Citadel Park


-Background

-Pathophysiology

-Etiology


-Diagnosis

-Treatment

-Xigris

• DIC always has an underlying etiology– Must be identified and eliminated to

treat the coagulopathy successfully.– The development of DIC in many of

these disorders is associated with an unfavorable outcome1.

• Occurs in 1% of hospitalized patients2

• Mortality rate approaches 40-80%

1. Schafer, A., I., Cecil Textbook of Medicine, Saunders, 2004, chapter 179, HEMORRHAGIC DISORDERS: DISSEMINATED INTRAVASCULAR COAGULATION, LIVER FAILURE, AND VITAMIN K DEFICIENCY2. Uptodote, 2005, www.utdol.com, Clinical feadures, diagnosis and teratment of disseminated intravascular coagulation

http://www.utdol.com/


-Background

-Pathophysiology

-Etiology


-Diagnosis

-Treatment

-Xigris

• Causes– Infection

• Most common cause of DIC. • The syndrome particularly is associated

with gram-negative or gram-positive sepsis

• Can be triggered by a variety of other– Bacterial

– Fungal

– Viral

– Rickettsial, and protozoal microorganisms.



-Background

-Pathophysiology

-Etiology


-Diagnosis

-Treatment

-Xigris

• Obstetrics– The placenta and uterine contents

are rich sources of• Tissue factor • Other procoagulants that normally are

excluded from the maternal circulation


La Familia


-Background

-Pathophysiology


– Clinical manifestations of DIC may accompany obstetric complications, especially in the third trimester.

• These syndromes range from – Acute, fulminant, and often fatal DIC in

amniotic fluid embolism » Blood is exposed to large amounts

of tissue factor in a short period of time creating large amounts of thrombin

» Multiorgan failure– Chronic or subacute DIC with a retained

dead fetus. » Exposure to small amounts of tissue

factor



-Background

-Pathophysiology

-Etiology


-Diagnosis

-Treatment

-Xigris

– Other obstetric problems associated with DIC include

• Abruptio placentae• Toxemia• Septic abortion.



-Background-Pathophysiology-Etiology-Clinical Manifestations-Diagnosis-Treatment-Xigris

• Clinical manifestations – Determined by

• Nature• Intensity• Duration of the underlying stimulus.

– Chronicity• Low-grade DIC is often asymptomatic

– Diagnosed only by laboratory abnormalities. – Bleeding is most common clinical finding

» Generalized or widespread ecchymoses• Chronic disease

– Thrombotic complications » Trousseau's syndrome in cancer » Gangrene of the digits or extremities» Hemorrhagic necrosis of the skin » Purpura fulminans

– Enhanced by• Coexistence of liver disease


Candy Factory


-Background

-Pathophysiology

-Etiology


-Diagnosis

-Treatment

-Xigris

• Diagnosis of severe, acute (easy)– Prolongation of PT, aPTT and Thrombin

time• Due to consumption and inhibitiion of clotting

factors

– Thrombocytopenia– Fibrin degradatin products

• Increased due to secondary fibrinolysis– Measured by latex agglutination or D-dimer

assays.

– Schistocytes may be seen in the peripheral blood smear

• Neither sensitive nor specific for DIC.



-Background

-Pathophysiology


• Chronic or compensated forms of DIC – Highly variable patterns of abnormalities in

"DIC screen" coagulation tests. – Increased FDPs and prolonged PT are

generally more sensitive measures than are abnormalities of the aPTT and platelet count.

– Overcompensated synthesis of consumed clotting factors and platelets in some chronic forms

• Cause shortening of the PT and aPTT and/or thrombocytosis

• Though, elevated levels of FDPs indicate secondary fibrinolysis in such cases.


Street entertainers


-Background

-Pathophysiology

-Etiology


-Diagnosis

-Treatment

-Xigris

• Treatment– Identify underlying cause and treat– All other therapies are temporizing



-Background

-Pathophysiology

-Etiology


-Diagnosis

-Treatment

-Xigris

• Asymptomatic patients with self-limited DIC – Have only laboratory manifestations

of the coagulopathy– No treatment may be necessary.



-Background

-Pathophysiology

-Etiology


-Diagnosis

-Treatment

-Xigris

• Actively bleeding or who are at high risk of bleeding, – Blood component treatments of choice

• Transfusions of platelets – Improve the thrombocytopenia

• Fresh-frozen plasma (FFP)– Replace all consumed coagulation factors and

correct the prolonged PT and aPTT.

• Large volumes of plasma in severe cases

– The theoretical concern that these blood products may "fuel the fire" and exacerbate the DIC has not been supported by clinical experience



-Background

-Pathophysiology

-Etiology


-Diagnosis

-Treatment

-Xigris

• Special cases– Profound hypofibrinogenemia

• Additional transfusion of cryoprecipitate,• Plasma concentrate enriched in

fibrinogen

– Sepsis• Infusion of antithrombin III concentrate

may be considered as an adjunctive measure



-Background

-Pathophysiology


• Pharmacologic inhibitors of coagulation and fibrinolysis – Heparin – Theoretical benefit

• It blocks thrombin and the secondary fibrinolysis.

• Might exacerbate the bleeding tendency – Usually reserved for – Forms manifested by

» Thrombosis » Acrocyanosis » Cancer» Vascular malformations» Retained dead fetus» Acute promyelocytic leukemia.


-Background

-Pathophysiology

-Etiology


-Diagnosis

-Treatment

-Xigris

• Antifibrinolytic agents, – ε-aminocaproic acid and tranexamic

acid– Generally are contraindicated

• May precipitate thrombosis

– May be effective in decreasing life-threatening bleeding

Festivals


-Background

-Pathophysiology

-Etiology


-Diagnosis

-Treatment

-Xigris

• XIGRIS® (Lilly)Drotrecogin alfa (activated) – Recombinant form of human

Activated Protein C


-Background

-Pathophysiology


• General Pharmacology • Activated Protein C

– Antithrombotic effect – Inhibits Factors Va and VIIIa.

• Indirect profibrinolytic activity through its ability to inhibit plasminogen activator inhibitor-1 (PAI-1)

• Limits generation of activated thrombin-activatable-fibrinolysis-inhibitor.

• In vitro data indicate that Activated Protein C may exert an anti-inflammatory effect by inhibiting human tumor necrosis factor production by monocytes

– Blocks leukocyte adhesion to selectins– Limits the thrombin-induced inflammatory

responses within the microvascular endothelium.


-Background

-Pathophysiology

-Etiology


-Diagnosis

-Treatment

-Xigris

• Clinical study (PROWESS)– 1690 patients with severe sepsis – Entry criteria included a systemic

inflammatory response presumed due to infection and at least one associated acute organ dysfunction

– The study was terminated after a planned interim analysis due to significantly lower mortality in patients on Xigris than in patients on placebo• (210/850, 25% vs. 259/840, 31% p=0.005).


-Background

-Pathophysiology

-Etiology


-Diagnosis

-Treatment

-Xigris

• INDICATIONS AND USAGE – Xigris is indicated for the reduction

of mortality in adult patients with severe sepsis (sepsis associated with acute organ dysfunction) who have a high risk of death (APACHE II)


-Background

-Pathophysiology

-Etiology


-Diagnosis

-Treatment

-Xigris

• Contraindications– Active internal bleeding – Recent (within 3 months) hemorrhagic

stroke – Recent (within 2 months) intracranial or

intraspinal surgery, or severe head trauma – Trauma with an increased risk of life-

threatening bleeding – Presence of an epidural catheter – Intracranial neoplasm or mass lesion or

evidence of cerebral herniation


-Background

-Pathophysiology


• Warnings– Concurrent therapeutic dosing of heparin to treat an active

thrombotic or embolic event – Platelet count <30,000 × 10 6 /L, even if the platelet count is

increased after transfusions – Prothrombin time-INR >3.0 – Recent (within 6 weeks) gastrointestinal bleeding – Recent administration (within 3 days) of thrombolytic therapy – Recent administration (within 7 days) of oral anticoagulants or

glycoprotein IIb/IIIa inhibitors – Recent administration (within 7 days) of aspirin >650 mg per

day or other platelet inhibitors – Recent (within 3 months) ischemic stroke – Intracranial arteriovenous malformation or aneurysm – Known bleeding diathesis – Chronic severe hepatic disease – Any other condition in which bleeding constitutes a significant

hazard or would be particularly difficult to manage because of its location .


-Background

-Pathophysiology

-Etiology


-Diagnosis

-Treatment

-Xigris

• DOSAGE AND ADMINISTRATION – Xigris should be administered

intravenously at an infusion rate of 24 µg/kg/hr for a total duration of infusion of 96 hours.

Any questions?

disseminated intravascular coagulation

Documents

coagulation system

pathophysiology etiology

liver failure

clinical feadures

hemorrhagic disorders

cecil textbook of medicine

platelet activation

tissue injury