Disseminated Intravascular Coagulation: Flashcards
(14 cards)
What is DIC?
DIC is a clinicopathologic syndrome in which widespread intravascular coagulation is induced by procoagulants that are introduced or produced in the blood circulation which override the natural anticoagulant mechanisms.
- It is an acquired syndrome characterised by excessive and widespread
activation of coagulation with consequent
consumption of clotting factors and inhibitors
with loss of normal regulatory mechanisms.
Epidemiology
Incidence relates to that of the causative factor eg Obstetric complications, Septicaemia, Transfusion reaction, etc.
No sex, age, race or geographic area is spared.
Causes of DIC
- Infections;
- Gram-negative bacterial sepsis.
- Other bacteria, fungi, viruses, severe malaria.
- Infection generally causes DIC by inducing
severe systemic inflamatory response leading to formation of procoagulant cytokines ( IL 1, & 6 and TNF) and some toxins. - Obstetric complications ;
- Amniotic fluid embolism.
- Retained dead fetus.
- Abruptio placentae.
- Preeclampsia & Eclampsia.
- Septic abortion.
- Malignancies;
- Acute promyelocytic leukemia - AML-M3: This causes
DIC by expressing TF and a procoagulant as well as
release of IL-1 and TNF. - Pancreatic carcinoma - mucinous.
- Adenocarcinomas
- Acute promyelocytic leukemia - AML-M3: This causes
- Trauma, shock;
- Brain injury.- Crush injury.
- Burns.
- Hypothermia/hyperthermia.
- Fat embolism.
- Hypoxia, ischemia – via production of
superoxides and hydroxyl radicals.
- Chronic Liver disease causes DIC via:
Reduced synthesis of natural anticoagulants – protein C & S and AT.
Reduced synthesis of main components of fibrinolytic system – plasminogen, α-2 antiplasmin.
Reduced clearance of activated factors IX, X &XI and t-PA.
Thrombocytopenia due to hypersplenism that is associated with portal hypertension and decreased synthesis of thrombopoietin by the liver. - Others:
- Acute pancreatitis.
- Venomation more esp Vipers (Echis
carinatus) and Eastern diamond rattle
snake which directly activate factor X. - Transfusion reactions.
- Venomation more esp Vipers (Echis
Explain the pathogenesis of DIC
The consequences of DIC are twofold.
Dicuss
First, there is widespread deposition of fibrin within the microcirculation. This can lead to ischemia of the more severely affected or more vulnerable organs (Liver, Kidneys, Lungs & CNS) and to a hemolytic anemia resulting from fragmentation of red cells as they squeeze through the narrowed microvasculature (microangiopathic hemolytic anemia).
Second, a hemorrhagic diathesis. This results from consumption of platelets and clotting factors as well as activation of plasminogen.
Plasmin can not only cleave fibrin, but also digest factors V and VIII, thereby reducing their concentration further.
In addition, fibrinolysis leads to the formation of fibrin(ogen) degradation products, which inhibit platelet aggregation and fibrin polymerization and have antithrombin activity.
All these influences lead to the hemostatic failure seen in DIC
Clinical classification of DIC
Acute (uncompensated) DIC - Rapid and extensive activation of coagulation, fibrinolysis or both, with depletion of procoagulant factors and inhibitors and significant hemorrhage.
Chronic (compensated) DIC - Slow consumption of factors with normal or increased levels; often asymptomatic or associated with thrombosis.
Discuss acute DIC
What are the features and commonly affected organs?
The patient’s general appearance is frequently toxic.
The clinical picture is commonly one of bleeding with signs of shock out of proportion to the amount of blood loss, with poor perfusion, cold extremities, and poor tone in the neonate.
Bleeding may range in severity from past venipuncture sites to severe life-threatening hemorrhage.
Coexisting signs of thrombosis and bleeding may be present.
Cutaneous purpuric or hemorrhagic lesions can develop and spread rapidly, which may progress to frank gangrene formation of the skin - Purpura Fulminans.
The combination of hypovolemia, excessive fibrin formation as well as fibrin degradation can lead to end-organ damage and failure.
Organs commonly affected are kidneys, liver, lungs and CNS.
Discuss Chronic DIC
Chronic onset commonly occurs with chronic inflammation, and certain forms of malignancy (e.g. acute promyelocytic leukemia).
These patients have a low, constant rate of thrombin formation – compensated DIC.
Manifestation is thrombosis from excess thrombin formation, and therefore may present with symptoms and signs of venous thromboembolism.
Lab diagnosis of DIC
Full Blood Count and Blood Film;
- Thrombocytopenia from platelet consumption and
decreased synthesis of thrombopoeitin especially in chronic liver disease.
- Anemia due to bleeding and/or microangiopathic hemolysis.
- White Blood Cell count may be normal or increased depending on the causative factor.
- Peripheral Blood Film may show red blood cells fragmentation attributable to the presence of fibrin and FDP.
Clotting Profile : APTT, PT/INR and TT are all prolonged.
(Normal ranges : PT =11-16sec; APTT=30-40sec).
Fibrinogen Assay : Low (Normal range : 1.5-4g/l).
FDP and D-Dimers : High levels in Serum and Urine. (Normal ranges : FDP <10ug/ml;
D-Dimers <200mg/l)
Other Molecular Markers of DIC includes;
Elevated Thrombin-Antithrombin Complex
Elevated Prothrombin Fragments .
Elevated Fibrinopeptide A (FPA).
Principles of management?
Principles of Management;
- Individualise Therapy.
- Treat or Remove the Triggering
Process.
- Replace Missing Blood Components
as Indicated.
- Stop Intravascular Clotting Process.
- Inhibit Residual Fibrino(geno)lysis.
Discuss Individualisation of Therapy:
This involves careful and adequate assessment of the patients with the aim of arriving at a tentative diagnosis of the cause of the DIC as well as the extend of the tissue damage caused by it.
Then the required therapy needed by individual patient is accessed.
Treatment strategies
Treatment or Removal of the Triggering Process: This is provided as indicated.
In most patients, this alone can provide some arrest of the DIC process.
Replacement of Missing Blood Components:
This involves the replacement of the deranged coagulation factors, natural anticoagulants, fibrinolytic proteins and platelets using either of the following as indicated;
Fresh Frozen Plasma – given at 1-2U 8hourly as indicated.
Cryoprecipitate – indicated when the serum fibrinogen <1g/l at 8-10 pooled units.
Content – Factor VIII at 70 IU/ml, Fibrinogen at 140mg/unit. Other factors are vWF, Fibronectin & XIII.
Platelet Concentrate – indicated when the platelet count is <50,000/cmm. This is given targeting platelet count of between 50,000 and 100,000/cmm. This is collected via PRP, Buffy-coat method or by aphesis using cell separator.
Antithrombin concentrate – in some cases of fatty liver of pregnancy.
These replacements are given while monitoring Platelets Count, PT, APTT and the Volume Status of the patient
8 hourly and can be repeated as indicated.
Fresh Whole Blood - indicated when there is profound bleeding or in centres where the above are not available.
Inhibition of Residual Fibrino(geno)lysis: By Aminocaproic acid or its analog Tranexamic acid. These inhibit fibrinolysis by competitive inhibtion of plasminogen activator.
Indicated in;
Heat stroke, Amniotic fluid embolism, Metastatic ca prostate and some forms of liver disease where there is FAILURE OF REPLACEMENT THERAPY OR WHEN EXCESSIVE FIBRINO(GENO)LYSIS IS OBSERVED.
Complications
SHOCK
RENAL Complications – due to microthrombi and/or prolonged renal hypoperfusion.
- Renal Cortical Ischemia,
- Acute Tubular Necrosis, and
- Acute Renal Failure.
CNS Complications - due to Micro/Macrothrombi, Emboli, and Hemorrhage in the cerebral vasculature. These can lead to coma, delirium, Transient Ischemic Attacks, and signs of meningeal irritation.
PULMONARY Complications;
- Transient Hypoxemia.
- Pulmonary Hemorrhage.
- Adult Respiratory Distress Syndrome (ARDS).
OTHER COMPLICATIONS;
- Purpura Fulminans.
- Gangrene and
- DEATH
Prognosis
The determinants of the prognosis of DIC includes;
The underlying triggerring factor.
The presentation of the DIC itself – thrombotic DIC carries worst prognosis than hemorrhagic type.
The aggresiveness of the therapy renderred.
DIC generally increases mortality of its cause.
