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DIC. Dr MB Dhlamini Department of Molecular Medicine and Haematology WITS University. Objectives for the DIC lecture. Definition of DIC Describe the pathogenesis of DIC Discuss mechanisms of acute DIC Definition of subacute/chronic DIC - PowerPoint PPT Presentation
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DIC
Dr MB Dhlamini
Department of Molecular Medicine and Haematology
WITS University
Objectives for the DIC lecture
Definition of DIC Describe the pathogenesis of DIC Discuss mechanisms of acute DIC Definition of subacute/chronic DIC Discuss sequelae of activation of coagulation
cascade. Describe examples of underlying disease and DIC. Discuss principles of laboratory diagnosis of DIC Describe management principles of DIC
Disseminated Intravascular Coagulopathy Definition: -Clinicopathological syndrome in which wide spread intravascular coagulation
is induced by procoagulants that are introduced /produced in the blood & overcome the natural anticoagulant mechanism.
DIC characterised by:
Systemic intravascular coagulation – widespread fibrin deposition in circulation
Results : microvascular dysfunction & organ failure
Massive ongoing activation may result in depletion of platelets & coagulation factors– bleeding.
Secondary fibrinolysis
Clinical Picture - DIC
O R G A N F A IL U R E
M ic ro va su la r th rom b o tic o b s tru c tion
W id esp rea d de p os it ion
B L E E D IN G
D e c re a sed P la te le ts & C o a gu la tio n fac to r d e ficie n cy
C o nsu m p tion o f P la te le ts
S ys te m ic a c tiva tio n o f coa g u la tion
Underlying disorder
Pathogenesis of DIC
Acute DIC : Triggering mechanisms (TMS)
1. Entry of thromboplastins with high phospholipid concentration into circ.
e.g. a) following extensive tissue
trauma during surgery.
b) Acute Vascular haemolytic episode
(ffg incompatible blood transfusion)
Acute DIC TMS cont’d
2. Direct activation of Factor X or Prothrombin(Factor II) by specific proteolytic enzymes in snake venom.
3. Severe Vascular Endothelial Injury e.g. gram negative septicaemia viral/protozoal diseases extensive burns – exacerbated by prolonged hypotension, hypoxia, acidosis
Acute DIC TMS cont’d
4. Direct platelet activation in
septicaemia and viraemic states or
activation of platelets following:
a) vessel wall endothelial damage
b) thrombin generation by the
coagulation cascade
Subacute/Chronic DIC
Slow activation of haemostatic system Spontanteous bruising rather than major
bleeds Chronic compensated DIC can continue
for many years – usu. Assoc. with vascular malformations
Sequelae of Activation of the Coagulation Cascade Thrombin generation– fibrinogen converted to
fibrin Trace amts of thrombin inactivated by
formation of thrombin-antithrombin complexes ( protective mechanisms)
If excess thrombin– cleavage of fibrinopeptide A & B from Aά & Bβ forming monomers
Fibrin monomers polymerize to form fibrin clot
Sequelae cont’d
Fibrin strands/platelet aggregates cause blockage of arterial circ.
Loose fibrin platelet plugs form a fine mesh sieve– red cells passing through distorted & fragmented ---- intravascular
haemolysis
Sequelae cont’d
Secondary activation of the fibrinolytic pathway. ffg fibrin deposition – tPA released from vascular endothelium converting plasminogen to plasmin within fibrin clot
Free plasmin – cleavage of fibrinogen and lysis of cross linked fibrin
Breakdown of fibrinogen– formation of fragments D/E ( via X-Y)
Sequelae cont’d
Specific lysis of fibrin—formation of specific FXIII cross linked complexes incl. D-Dimers
Fibrinogen/fibrin breakdown—FDPs or D-Dimers)
Free plasmin may also cleave other peptides e.g.FV, FVIII & 1st component of complement.
Sequelae cont’d
Liver cell synthesis fails to compensate for their consumption thus decreased Factors V, VIII, XIII, fibrinogen
BM megakaryocyte production unable to maintain normal plt count
Sequelae cont’d
Combination of :
- coagulation factor deficiency
- thrombocytopenia
- impaired platelet function
- inhibitory action of raised FDPs
= generalised/continued widespread
bleeding
Underlying Dx
Bacterial infections
- most common cause
gram negative lipopolysaccharide
gram positive exotoxin
cytokines
Meningococcemia- Purpura on the calves
Meningococcemia-2
Underlying Dx cont’d
Other infections
1) Viral e.g. viral haemorrhagic fever
probably via endothelial damage
2) Protozoa e.g. Malaria
Underling Dx cont’d
Trauma
- frequently associated with
1) release of phospholipid
2) endothelial damage
3) Cytokines also play a role
Underlying Dx cont’d
Malignancy - low grade or subacute DIC - Trigger Tissue Factor: usu. assd with
metastatic disease e.g. Ca Pancreas, Ca lung, Ca stomach - APL : hyperfibrinolysis, TF on
leukaemic cells
Underlying Dx cont’d
Obstetrics
- implicated in the following
1) Septic abortion
2) Abruptio Placenta
3) Ecalmpsia
4) Placent Praevia
5) Amniotic fluid embolism
Underlying Dx obstetrics cont’d
Mechanisms - entrance of cellular elements of the
decidua/placenta with thromboplastin-like activity into maternal circ.
- meconium and fetal squamous cells from amniotic fluid into maternal circulation– activation of coagulation
- IUD – slow progressive DIC– bleeding late manifestation
Underlying Dx cont’d
Vascular disorders
1) large aortic aneurysms
2) Kasabach-Merrit syndrome
---- result in local activation of coagulation
---- overflow into systemic circ.
Diagnosis of DIC
-Investigate underlying dx-Evidence of consumption eg.
Thrombocytopenia,prolonged INR/PTT,decreased factors
-Evidence of activation of fibrinolytic pathway : elevated D-Dimer levels and presence of FDP’s
-Decrease in coagulation inhibitors: Antithrombin,Protein C&S
Management of DIC
NB: Rx of the underlying disease Supportive management eg. Platelets,
FFP’s, cryoprecipitate Coagulation inhibitors : Heparin,
Antithrombin and Activated Protein C
Stroke
Case Studies
38yr male,RVD positive, neutropenic Confused, not on warfarin or heparin INR 1.08, PTT 34.90s, D-Dimers
1.66mg/l, fibrinogen 3.81g/l ,antithrombin 110% and platelets 182x10^9/l
Case 2
66yr old female post- NSTEMI, treated with antibiotics for infection
INR 2.73, correct. 1.01,PTT 32.6s, D-Dimers 0.87mg/l, fibrinogen 4.1g/l ,Factor VII 17%, Antithrombin 84% and Plt 204x10^9/l.
Case3
52yr female with perforation of the bowel and sepsis
INR1.82, correct. 1.33, PTT 65.5s,correct 34.1s, D-Dimers 4.71mg/l, fibrinogen 1.96g/l, antithrombin 57% and platelets 35x10^9/l.
Thrombin ratio 0.78 (within normal range)