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Title: Disseminated Intravascular Coagulation


1
Disseminated Intravascular Coagulation
  • Robert R. Zaid D.O.
  • Genesys Regional Medical Center
  • PGY-I

2
Barcelona - Gaudi
3
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
4
(No Transcript)
5
Disseminated Intravascular Coagulation
  • -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
6
Stein B, Fuster V, Israel DH, et al. Platelet
inhibitor agents in cardiovascular disease an
update. J Am Coll Cardiol. 198914813836.
7
Disseminated Intravascular Coagulation
  • -Background
  • -Pathophysiology
  • -Etiology
  • -Clinical Manifestations
  • -Diagnosis
  • -Treatment
  • -Xigris
  • Tissue factor triggers
  • Thrombin
  • Protease
  • Induces fibrin formation and platelet activation
  • Other procoagulants
  • Cysteine protease
  • Mucin
  • Trypsin

Schafer, A., I., Cecil Textbook of Medicine,
Saunders, 2004, chapter 179, HEMORRHAGIC
DISORDERS DISSEMINATED INTRAVASCULAR
COAGULATION, LIVER FAILURE, AND VITAMIN K
DEFICIENCY
8
Disseminated Intravascular Coagulation
  • -Background
  • -Pathophysiology
  • -Etiology
  • -Clinical Manifestations
  • -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.

Schafer, A., I., Cecil Textbook of Medicine,
Saunders, 2004, chapter 179, HEMORRHAGIC
DISORDERS DISSEMINATED INTRAVASCULAR
COAGULATION, LIVER FAILURE, AND VITAMIN K
DEFICIENCY
9
Disseminated Intravascular Coagulation
  • 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
  • -Clinical Manifestations
  • -Diagnosis
  • -Treatment
  • -Xigris

Schafer, A., I., Cecil Textbook of Medicine,
Saunders, 2004, chapter 179, HEMORRHAGIC
DISORDERS DISSEMINATED INTRAVASCULAR
COAGULATION, LIVER FAILURE, AND VITAMIN K
DEFICIENCY
10
Disseminated Intravascular Coagulation
  • -Background
  • -Pathophysiology
  • -Etiology
  • -Clinical Manifestations
  • -Diagnosis
  • -Treatment
  • -Xigris

11
Citadel Park
12
Disseminated Intravascular Coagulation
  • -Background
  • -Pathophysiology
  • -Etiology
  • -Clinical Manifestations
  • -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
13
Disseminated Intravascular Coagulation
  • -Background
  • -Pathophysiology
  • -Etiology
  • -Clinical Manifestations
  • -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.

Schafer, A., I., Cecil Textbook of Medicine,
Saunders, 2004, chapter 179, HEMORRHAGIC
DISORDERS DISSEMINATED INTRAVASCULAR
COAGULATION, LIVER FAILURE, AND VITAMIN K
DEFICIENCY
14
Disseminated Intravascular Coagulation
  • -Background
  • -Pathophysiology
  • -Etiology
  • -Clinical Manifestations
  • -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

Schafer, A., I., Cecil Textbook of Medicine,
Saunders, 2004, chapter 179, HEMORRHAGIC
DISORDERS DISSEMINATED INTRAVASCULAR
COAGULATION, LIVER FAILURE, AND VITAMIN K
DEFICIENCY
15
La Familia
16
Disseminated Intravascular Coagulation
  • -Background
  • -Pathophysiology
  • -Etiology
  • -Clinical Manifestations
  • -Diagnosis
  • -Treatment
  • -Xigris
  • 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

Schafer, A., I., Cecil Textbook of Medicine,
Saunders, 2004, chapter 179, HEMORRHAGIC
DISORDERS DISSEMINATED INTRAVASCULAR
COAGULATION, LIVER FAILURE, AND VITAMIN K
DEFICIENCY
17
Disseminated Intravascular Coagulation
  • -Background
  • -Pathophysiology
  • -Etiology
  • -Clinical Manifestations
  • -Diagnosis
  • -Treatment
  • -Xigris
  • Other obstetric problems associated with DIC
    include
  • Abruptio placentae
  • Toxemia
  • Septic abortion.

Schafer, A., I., Cecil Textbook of Medicine,
Saunders, 2004, chapter 179, HEMORRHAGIC
DISORDERS DISSEMINATED INTRAVASCULAR
COAGULATION, LIVER FAILURE, AND VITAMIN K
DEFICIENCY
18
Disseminated Intravascular Coagulation
  • -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

Schafer, A., I., Cecil Textbook of Medicine,
Saunders, 2004, chapter 179, HEMORRHAGIC
DISORDERS DISSEMINATED INTRAVASCULAR
COAGULATION, LIVER FAILURE, AND VITAMIN K
DEFICIENCY
19
Candy Factory
20
Disseminated Intravascular Coagulation
  • -Background
  • -Pathophysiology
  • -Etiology
  • -Clinical Manifestations
  • -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.

Schafer, A., I., Cecil Textbook of Medicine,
Saunders, 2004, chapter 179, HEMORRHAGIC
DISORDERS DISSEMINATED INTRAVASCULAR
COAGULATION, LIVER FAILURE, AND VITAMIN K
DEFICIENCY
21
Disseminated Intravascular Coagulation
  • -Background
  • -Pathophysiology
  • -Etiology
  • -Clinical Manifestations
  • -Diagnosis
  • -Treatment
  • -Xigris
  • 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.

Schafer, A., I., Cecil Textbook of Medicine,
Saunders, 2004, chapter 179, HEMORRHAGIC
DISORDERS DISSEMINATED INTRAVASCULAR
COAGULATION, LIVER FAILURE, AND VITAMIN K
DEFICIENCY
22
Street entertainers
23
Disseminated Intravascular Coagulation
  • -Background
  • -Pathophysiology
  • -Etiology
  • -Clinical Manifestations
  • -Diagnosis
  • -Treatment
  • -Xigris
  • Treatment
  • Identify underlying cause and treat
  • All other therapies are temporizing

Schafer, A., I., Cecil Textbook of Medicine,
Saunders, 2004, chapter 179, HEMORRHAGIC
DISORDERS DISSEMINATED INTRAVASCULAR
COAGULATION, LIVER FAILURE, AND VITAMIN K
DEFICIENCY
24
Disseminated Intravascular Coagulation
  • -Background
  • -Pathophysiology
  • -Etiology
  • -Clinical Manifestations
  • -Diagnosis
  • -Treatment
  • -Xigris
  • Asymptomatic patients with self-limited DIC
  • Have only laboratory manifestations of the
    coagulopathy
  • No treatment may be necessary.

Schafer, A., I., Cecil Textbook of Medicine,
Saunders, 2004, chapter 179, HEMORRHAGIC
DISORDERS DISSEMINATED INTRAVASCULAR
COAGULATION, LIVER FAILURE, AND VITAMIN K
DEFICIENCY
25
Disseminated Intravascular Coagulation
  • -Background
  • -Pathophysiology
  • -Etiology
  • -Clinical Manifestations
  • -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

Schafer, A., I., Cecil Textbook of Medicine,
Saunders, 2004, chapter 179, HEMORRHAGIC
DISORDERS DISSEMINATED INTRAVASCULAR
COAGULATION, LIVER FAILURE, AND VITAMIN K
DEFICIENCY
26
Disseminated Intravascular Coagulation
  • -Background
  • -Pathophysiology
  • -Etiology
  • -Clinical Manifestations
  • -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

Schafer, A., I., Cecil Textbook of Medicine,
Saunders, 2004, chapter 179, HEMORRHAGIC
DISORDERS DISSEMINATED INTRAVASCULAR
COAGULATION, LIVER FAILURE, AND VITAMIN K
DEFICIENCY
27
Disseminated Intravascular Coagulation
  • -Background
  • -Pathophysiology
  • -Etiology
  • -Clinical Manifestations
  • -Diagnosis
  • -Treatment
  • -Xigris
  • 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.

28
Disseminated Intravascular Coagulation
  • -Background
  • -Pathophysiology
  • -Etiology
  • -Clinical Manifestations
  • -Diagnosis
  • -Treatment
  • -Xigris
  • Antifibrinolytic agents,
  • e-aminocaproic acid and tranexamic acid
  • Generally are contraindicated
  • May precipitate thrombosis
  • May be effective in decreasing life-threatening
    bleeding

29
Festivals
30
Disseminated Intravascular Coagulation
  • -Background
  • -Pathophysiology
  • -Etiology
  • -Clinical Manifestations
  • -Diagnosis
  • -Treatment
  • -Xigris
  • XIGRIS (Lilly)Drotrecogin alfa (activated)
  • Recombinant form of human Activated Protein C

31
Disseminated Intravascular Coagulation
  • -Background
  • -Pathophysiology
  • -Etiology
  • -Clinical Manifestations
  • -Diagnosis
  • -Treatment
  • -Xigris
  • 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-activatabl
    e-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.

32
Disseminated Intravascular Coagulation
  • -Background
  • -Pathophysiology
  • -Etiology
  • -Clinical Manifestations
  • -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 p0.005).

33
Disseminated Intravascular Coagulation
  • -Background
  • -Pathophysiology
  • -Etiology
  • -Clinical Manifestations
  • -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)

34
Disseminated Intravascular Coagulation
  • -Background
  • -Pathophysiology
  • -Etiology
  • -Clinical Manifestations
  • -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

35
Disseminated Intravascular Coagulation
  • -Background
  • -Pathophysiology
  • -Etiology
  • -Clinical Manifestations
  • -Diagnosis
  • -Treatment
  • -Xigris
  • Warnings
  • Concurrent therapeutic dosing of heparin to treat
    an active thrombotic or embolic event
  • Platelet count lt30,000 10 6 /L, even if the
    platelet count is increased after transfusions
  • Prothrombin time-INR gt3.0
  • 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
    gt650 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 .

36
Disseminated Intravascular Coagulation
  • -Background
  • -Pathophysiology
  • -Etiology
  • -Clinical Manifestations
  • -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.

37
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