Basic Science applied to medicine

1. It is not death that a man should fear, but he should fear never beginning to live
-Marcus Aurelius
INTRODUCTION
● AKA consumption coagulopathy and defibrination syndrome
● Systemic process
● Causing thrombosis and hemorrhage
● Can present as
○ Acute, life-threatening emergency
○ Chronic, subclinical process
PATHOGENESIS
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by Dr. Eashan Srivastava

2. It is not death that a man should fear, but he should fear never beginning to live
-Marcus Aurelius
● Intravascular coagulation and fibrinolysis
○ Normal hemostasis ensures formation of a blood clot at the site of vessel injury
○ Multiple feedbacks built into this system to prevent activation of coagulation in the
absence of vessel injury
○ Restrict the clot to the site of injury
○ In DIC, the processes of coagulation and fibrinolysis become abnormally
activated
● Typical sequence of events
○ Procoagulant exposure
■ Bacterial products - lipopolysaccharides
■ Meningococcal microparticles containing Tissue Factor
■ Cancer procoagulant produced by mucinous tumors
■ Placental products
■ Transfusion reaction
● TF release by monocytes
● Generation of cytokines
○ Coagulation
■ Activation of the coagulation cascade
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by Dr. Eashan Srivastava

3. It is not death that a man should fear, but he should fear never beginning to live
-Marcus Aurelius
■ Production of thrombi
■ Consumption of endogenous coagulation factors
○ Excessive Fibrinolysis
○ End organ damage
■ Reduced perfusion
■ Thrombosis
■ Endothelial damage
● Role of extracellular cell-free DNA and DNA-binding proteins
○ DAMPs
■ Damage-associated pattern molecules
■ aka "alarmins"
■ Increasing evidence = play a critical role
■ Released from dying cells or secreted from immune cells in response to
infection or tissue injury
■ Formation of neutrophil extracellular traps (NETs)
■ NETs are web-like structures composed of
● Chromatin
● Cellular proteins
● Myeloperoxidase
● Neutrophil elastase
● Histones
■ Appears to be a component of innate immunity
■ Becomes dysregulated in severe inflammatory conditions
■ NETosis are
● Cytotoxic
● Highly procoagulant
● Endothelial damage
● Compensatory changes
○ Depend on
■ Severity
■ Duration
○ Consumption of coagulation factors and platelets ​can be compensated
○ Acute DIC
■ Decompensated DIC
■ Generation of thrombin = +++
■ Short period of time
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by Dr. Eashan Srivastava

4. It is not death that a man should fear, but he should fear never beginning to live
-Marcus Aurelius
■ Rapid consumption of coagulation factors
■ Leads to the severe bleeding diathesis
○ Chronic DIC
■ Compensated DIC
■ Intermittent exposure to smaller amounts of tissue factor
■ Production is able to compensate
■ Thrombosis generally predominates
● DIC versus other TMAs
○ DIC
■ Microvascular thrombi contain fibrin + platelets
○ TMAs
■ Microthrombi = Platelets without significant fibrin
Parameter
Acute (decompensated)
DIC
Chronic (compensated)
DIC
Platelet count Reduced Variable
Prothrombin time (PT) Prolonged Normal
Activated partial thromboplastin
time (aPTT)
Prolonged Normal
Thrombin time Prolonged Normal to slightly
prolonged
Plasma fibrinogen Reduced Normal to elevated
Plasma factor V Reduced Normal
Plasma factor VIII Reduced Normal
Fibrin degradation products Elevated Elevated
D-dimer Elevated Elevated
CAUSES OF DIC
Major causes of disseminated intravascular coagulation
Events that initiate DIC
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by Dr. Eashan Srivastava

5. It is not death that a man should fear, but he should fear never beginning to live
-Marcus Aurelius
Septicemia - Gram negative and Gram positive
Crush injury or complicated surgery
Severe head injury
Cancer procoagulant (Trousseau's syndrome)
Acute leukemia, especially promyelocytic
Complications of pregnancy
Amniotic fluid embolism
Abruptio placentae
HELLP syndrome
Eclampsia and severe preeclampsia
Septic abortion
Amphetamine overdose
Giant hemangioma (Kasabach-Merritt syndrome)
Abdominal aortic aneurysm
Peritoneovenous shunt
Acute hemolytic transfusion reaction (ABO incompatibility)
Paroxysmal nocturnal hemoglobinuria
Snake and viper venoms
Liver disease
Fulminant hepatic failure
Reperfusion after liver transplantation
Heat stroke
Burns
Purpura fulminans
Events that complicate and propagate DIC
Shock
Complement pathway activation
CLINICAL MANIFESTATIONS
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by Dr. Eashan Srivastava

6. It is not death that a man should fear, but he should fear never beginning to live
-Marcus Aurelius
● Acute DIC
○ H/O trauma, sepsis, malignancy (especially acute promyelocytic leukemia), or
ABO-incompatible blood transfusion
○ Bleeding
○ Thrombocytopenia
○ Prolonged PT and aPTT
○ Low plasma fibrinogen
○ Elevated plasma D-dimer
○ Microangiopathic changes on peripheral blood smear
● Chronic DIC
○ H/O malignancy
○ Thromboembolism
○ Mild or no thrombocytopenia
○ Normal or mildly prolonged PT and aPTT
○ Elevated plasma D-dimer
○ Microangiopathic changes
● Bleeding
○ Petechiae
○ Ecchymoses
○ Oozing from wound sites
○ Bleeding can be life-threatening
● Thrombosis
○ DVT/PE
● Organ dysfunction
○ Renal
○ Hepatic
○ Pulmonary
○ Neurologic abnormalities
○ Adrenal failure
DIAGNOSTIC EVALUATION
● DIC is a clinical ​and​​ laboratory diagnosis
DIFFERENTIAL DIAGNOSIS
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by Dr. Eashan Srivastava

7. It is not death that a man should fear, but he should fear never beginning to live
-Marcus Aurelius
● Severe liver disease
○ Can cause DIC
○ DIC associated with liver failure
○ Heparin-induced thrombocytopenia
○ Thrombotic microangiopathy (TMA)
TREATMENT
● Treat the underlying cause
● Supportive measures
○ Hemodynamic and/or ventilatory support
○ Hydration
○ Transfusion for severe bleeding
● Prevention/treatment of bleeding
○ Prophylactic administration of platelets and coagulation factors
■ Lack of evidence
○ Treatment is justified in
■ Bleeding +
● Platelet count <50,000
● Significantly prolonged PT/aPTT
● Fibrinogen level <50 mg/dL
■ High risk for bleeding
■ Require invasive procedures
■ Platelet count <10,000
■ Fresh Frozen Plasma or cryoprecipitate
■ Plasma fibrinogen level is <100 mg/dL= administer cryoprecipitate to
increase it to >100 mg/dL
■ Plasma fibrinogen >100 mg/dL and the PT or aPTT remains significantly
elevated = FFP
○ Antifibrinolytic agents such as tranexamic acid
■ Generally ​contraindicated
■ Blockade of the fibrinolytic system may increase the risk of thrombotic
complications
■ May be appropriate in patients who have severe bleeding
● Prevention/treatment of thrombosis
○ Prophylactic anticoagulation
■ Not recommended
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by Dr. Eashan Srivastava

8. It is not death that a man should fear, but he should fear never beginning to live
-Marcus Aurelius
○ DVT/PE
■ Rx as per guidelines
PROGNOSIS
Dependent on the treatability of the underlying condition
Mortality rate ranges from 40 to 80%
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by Dr. Eashan Srivastava