Disseminated Intravascular Coagulation: Robert R. Zaid D.O. Genesys Regional Medical Center Pgy-I

Disseminated Intravascular Coagulation
Robert R. Zaid D.O.

Genesys Regional Medical Center
PGY-I
Barcelona - Gaudi
-Background
-Pathophysiology
• Primarily a thrombotic process
-Etiology – Systemic process producing both
-Clinical Manifestations thrombosis and hemorrhage
-Diagnosis
-Treatment – Also called consumption
-Xigris 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 DEFICIENCY
2. Uptodote, 2005, www.utdol.com, Clinical feadures, diagnosis and teratment of disseminated intravascular coagulation
-Background • Basic pathophysiology

-Pathophysiology
– Entry into the circulation of procoagulant
-Etiology
-Clinical Manifestations
substances
-Diagnosis • Trigger systemic activation of the coagulation
-Treatment system and platelets
-Xigris • 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,
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
• Tissue factor triggers
-Etiology – Thrombin
-Clinical Manifestations • Protease
-Diagnosis
• Induces fibrin formation and platelet
-Treatment
activation
-Xigris
• Other procoagulants
– Cysteine protease
– Mucin
– Trypsin
-Background
-Pathophysiology
• Acute DIC
-Etiology – Coagulation factors are consumed at
-Clinical Manifestations a rate in excess of the capacity of
-Diagnosis
the liver to synthesize them,
-Treatment
-Xigris – Platelets are consumed in excess of
the capacity of bone marrow
megakaryocytes to release them.
-Background
• Laboratory manifestations
-Pathophysiology – Prolonged prothrombin time (PT)
-Etiology – Prolonged Activated partial thromboplastin time
-Clinical Manifestations (aPTT)
-Diagnosis – Thrombocytopenia.
-Treatment
-Xigris – 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
• DIC always has an underlying
-Etiology etiology
– Must be identified and eliminated to
-Diagnosis
-Treatment
treat the coagulopathy successfully.
-Xigris – 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,
2. Uptodote, 2005, www.utdol.com, Clinical feadures, diagnosis and teratment of disseminated intravascular coagulation
-Background
-Pathophysiology
• Causes
-Etiology – Infection
-Clinical Manifestations • Most common cause of DIC.
-Diagnosis
• The syndrome particularly is associated
-Treatment
with gram-negative or gram-positive
-Xigris
sepsis
• Can be triggered by a variety of other
– Bacterial
– Fungal
– Viral
– Rickettsial, and protozoal
microorganisms.
-Background
-Pathophysiology
• Obstetrics
-Etiology – The placenta and uterine contents
-Clinical Manifestations are rich sources of
-Diagnosis
• Tissue factor
-Treatment
-Xigris • Other procoagulants that normally are
excluded from the maternal circulation
La Familia
-Background – Clinical manifestations of DIC may

-Pathophysiology
-Etiology
accompany obstetric complications,
-Clinical Manifestations especially in the third trimester.
-Diagnosis • These syndromes range from
-Treatment – Acute, fulminant, and often fatal DIC in
-Xigris 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 – Other obstetric problems associated

-Pathophysiology
-Etiology
with DIC include
-Clinical Manifestations • Abruptio placentae
-Diagnosis • Toxemia
-Treatment • Septic abortion.
-Xigris
-Background • Clinical manifestations

-Pathophysiology – Determined by
-Etiology • Nature
-Clinical Manifestations • Intensity
-Diagnosis • Duration of the underlying stimulus.
-Treatment – Chronicity
-Xigris • 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 • Diagnosis of severe, acute (easy)

-Pathophysiology
-Etiology – Prolongation of PT, aPTT and Thrombin time
-Clinical Manifestations • Due to consumption and inhibitiion of clotting
-Diagnosis factors
-Treatment
-Xigris
– 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 • Chronic or compensated forms of DIC

-Pathophysiology
-Etiology – Highly variable patterns of abnormalities in
-Clinical Manifestations "DIC screen" coagulation tests.
-Diagnosis
– Increased FDPs and prolonged PT are
-Treatment
-Xigris
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
• Treatment
-Etiology – Identify underlying cause and treat
– All other therapies are temporizing
-Diagnosis
-Treatment
-Xigris
-Background
-Pathophysiology
• Asymptomatic patients with self-
-Etiology limited DIC
– Have only laboratory manifestations
-Diagnosis
-Treatment
of the coagulopathy
-Xigris – No treatment may be necessary.
-Background • Actively bleeding or who are at high risk

-Pathophysiology
-Etiology of bleeding,
-Clinical Manifestations – Blood component treatments of choice
-Diagnosis
-Treatment
• Transfusions of platelets
-Xigris – 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
• Special cases
-Etiology – Profound hypofibrinogenemia
-Clinical Manifestations • Additional transfusion of cryoprecipitate,
-Diagnosis
• Plasma concentrate enriched in
-Treatment
fibrinogen
-Xigris
– Sepsis
• Infusion of antithrombin III concentrate
may be considered as an adjunctive
measure
-Background • Pharmacologic inhibitors of

-Pathophysiology
-Etiology coagulation and fibrinolysis
-Clinical Manifestations – Heparin
-Diagnosis
-Treatment – Theoretical benefit
-Xigris • 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
• Antifibrinolytic agents,
-Etiology – ε-aminocaproic acid and tranexamic
-Clinical Manifestations acid
-Diagnosis
-Treatment – Generally are contraindicated
-Xigris • May precipitate thrombosis
– May be effective in decreasing life-
threatening bleeding
Festivals
-Background
-Pathophysiology
• XIGRIS® (Lilly)
-Etiology Drotrecogin alfa (activated)
– Recombinant form of human
-Diagnosis
-Treatment
Activated Protein C
-Xigris
-Background
-Pathophysiology
• General Pharmacology
-Etiology • Activated Protein C
-Diagnosis
– Antithrombotic effect
-Treatment – Inhibits Factors Va and VIIIa.
-Xigris • 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 • Clinical study (PROWESS)

-Pathophysiology
-Etiology – 1690 patients with severe sepsis
-Clinical Manifestations – Entry criteria included a systemic
-Diagnosis
inflammatory response presumed due to
-Treatment
-Xigris
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
• INDICATIONS AND USAGE
-Etiology – Xigris is indicated for the reduction
-Clinical Manifestations of mortality in adult patients with
-Diagnosis
severe sepsis (sepsis associated
-Treatment
-Xigris with acute organ dysfunction) who
have a high risk of death (APACHE
II)
-Background • Contraindications
-Pathophysiology
-Etiology – Active internal bleeding
-Clinical Manifestations – Recent (within 3 months) hemorrhagic
-Diagnosis
stroke
-Treatment
-Xigris – 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 • Warnings
-Pathophysiology – Concurrent therapeutic dosing of heparin to treat an active
-Etiology thrombotic or embolic event
-Clinical Manifestations – Platelet count <30,000 × 10 6 /L, even if the platelet count is
-Diagnosis increased after transfusions
-Treatment – Prothrombin time-INR >3.0
-Xigris – 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
• DOSAGE AND
-Etiology ADMINISTRATION
– Xigris should be administered
-Diagnosis
-Treatment
intravenously at an infusion rate of
-Xigris 24 µg/kg/hr for a total duration of
infusion of 96 hours.
Any questions?

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Disseminated Intravascular Coagulation

Robert R. Zaid D.O.

-Background • Basic pathophysiology

-Background – Clinical manifestations of DIC may

-Background – Other obstetric problems associated

-Background • Clinical manifestations

-Background • Diagnosis of severe, acute (easy)

-Background • Chronic or compensated forms of DIC

-Background • Actively bleeding or who are at high risk

-Background • Pharmacologic inhibitors of

-Background • Clinical study (PROWESS)

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