Disseminated Intravascular Coagulation

DR NORA AZURA DINTANANAESTHESIOLOGY DEPT

HOSPITAL KUALA LUMPUR

DIC

– Clinicopathological syndrome in response to some pathologic condition in the human body

– Systemic activation of coagulation cascade– process producing both thrombosis and hemorrhage– Also called consumption coagulopathy and

defibrination syndrome– Its clinical manifestation may be widespread

hemorrhage in acute, fulminant cases

Process in DICUnderlying disorder associated with DIC

Systemic activation of coagulation

Widespread fibrin depositionConsumption of PLT& coagulation factors

Microvascular thrombosis

Tissue injury/ Organ failure

Thrombocytopenia & coagulation factor deficiency

BLEEDING

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.

.

• Tissue factor triggers – Thrombin• Protease • Induces fibrin formation and platelet activation

• Other procoagulants– Cysteine protease– Mucin– Trypsin

Overt or 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

Nonovert DIC-Mild & clinically insignificant

Etiology

• 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 patients• Mortality rate approaches 40-80%

• Obstetrics– The placenta and uterine contents are rich sources of

• Tissue factor • Other procoagulants that normally are excluded from the maternal circulation

– 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

– Other obstetric problems associated with DIC include • Abruptio placentae• Toxemia• Septic abortion.

Diagnosis

• Diagnosis of severe, acute – Prolongation of PT, aPTT and Thrombin time

• Due to consumption and inhibition of clotting factors– Thrombocytopenia– Fibrin degradation 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.

Diagnosis• 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.

Scoring system for overt DIC

• International Society on Thrombosis and Hemostasis (ISTH) Scoring System

• Risk assessment: Does the pt have an underlying disorder known to be associated with overt DIC?

• If yes: proceed• If no: do not use this algorithm• Order global coagulation tests (PT, PLT count, fibrinogen,

fibrin related marker• Calculate score

– 5 and above compatible with overt DIC, repeat score daily– <5 suggestive for non overt DIC, repeat next 1-2 days

ISTH Diagnostic Scoring System for DIC

Laboratory Test Result Score

Platelet count (cells/L) >100,00050,000 – 100,000<50,000

012

Increase in fibrinogen & fibrin related markers eg D –dimer, FDP

No increaseModerate increaseStrong increase

023

Prolonged PT <3 s3-5.9 s>6 s

012

Fibrinogen level >1g/dL<1g/dL

01

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

Treatment

• Treatment– Identify underlying cause and treat– All other therapies are temporizing

• Asymptomatic patients with self-limited DIC – Have only laboratory manifestations of the

coagulopathy– treatment may be not necessary.

1. Plasma(FFP) and platelets

• Should not base on lab results alone• Actively bleeding or who are at high risk of bleeding eg post

op patients or patients undergoing invasive procedure • Severe hypofibrinogenaemia (<1g/L) that persists despite FFP

replacement may be treated with fibrinogen concentrate or cryoprecipitate

• If FFP transfusion not possible eg fluid overload, consider using factor concentrates such as prothrombin complex concentrate

Replacement therapy Suggested dosage Clinical indicators for use

Fresh frozen plasma (FFP) 15-20ml/kg Symptomatic bleeding with fibrinogen <100mg/dL

platelet concentrates 1-2 U/10 kg PLT <20,000 orPLT <50,000 with bleeding

cryoprecipitate 1 U/10 kg Symptomatic bleeding with fibrinogen <80-100mg/dL

Fibrinogen concentrates 2-3 g Symptomatic bleeding with fibrinogen <100mg/dL

2. Anticoagulant

• To be considered in DIC where thrombosis predominates, eg arterial or venous thromboembolism, severe purpura fulminans a/w acral ischaemia or vascular skin infarction

• Unfractionated heparin (UFH), short life & reversibility- 10g/kg/H

• In critically ill, non bleeding patients with DIC, prophylaxis for venous thromboembolism with Heparin or LMWH is recommended

3. Anticoagulant factor concentrates- activated protein C

• Consider treating patients with severe sepsis & DIC with recombinant human activated protein C, continuous infusion, 24/kg/H for 4 days

• Contraindicated if– High risk of bleeding– PLT <30,000– If patients going for invasive procedures,

discontinued shortly before intervention

4. Antifibrinolytic

– Generally are contraindicated • May precipitate thrombosis

– If DIC characterized by a primary hyperfibrinolytic state and who present with severe bleeding could be treated with lysine analogues such as tranexamic acid eg 1g every 8 H