Disseminated Intravascular Coagulation

DR NORA AZURA DINTAN ANAESTHESIOLOGY 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 DIC
Underlying disorder associated with DIC Systemic activation of coagulation

Widespread fibrin deposition

Consumption of PLT & coagulation factors Thrombocytopenia & coagulation factor deficiency

Microvascular thrombosis

Tissue injury/ Organ failure

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 Platelet count (cells/L) Result >100,000 50,000 100,000 <50,000 No increase Moderate increase Strong increase <3 s 3-5.9 s >6 s >1g/dL <1g/dL Score 0 1 2 0 2 3 0 1 2 0 1

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

Fibrinogen level

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 Fresh frozen plasma (FFP) platelet concentrates cryoprecipitate

Suggested dosage 15-20ml/kg 1-2 U/10 kg 1 U/10 kg

Clinical indicators for use Symptomatic bleeding with fibrinogen <100mg/dL PLT <20,000 or PLT <50,000 with bleeding 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 concentratesactivated 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