Disseminated Intravascular Coagulation

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Disseminated Intravascular Coagulation

• Huang Honghui
• Dept. of Hematology, Renji Hospital

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Definition

• DIC clinicopathologic syndrome
• widespread intravascular coagulation is induced
  by procoagulants that are introduced into or
  produced in the blood circulation and overcome
  the natural anticoagulant mechanisms.

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Etiology
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• Stage of
• hypercoagulability

Stage of hypocoagulability
Stage of secondary fibrinolysis
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Pathophysiology

• Stage of hypercoagulability
• Stage of hypocoagulability due to excess of
  consumption of blood coagulation factors
• Stage of secondary fibrinolysis

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Typing of DIC
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Clinical features

• Bleeding
• Thromboembolism
• Circulatory disturbance, shock
• Microangiopathic hemolytic anemia

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Clinical features

• Bleeding
• Mechanism
• consumption of hemostatic components including
  platelets, fibrinogen, and other coagulation
  factors
• secondary fibrinolysis
• anticoagulant effects of fibrinogen/fibrin
  degradation products
• manifestations
• Skin and mucosapetechiae, ecchymosis, oozing
  from veni-punctures, arterial lines, catheters,
  and injured tissues
• internal organmassive bleeding into the
  gastrointestinal, lungs, central nervous system,
  or orbit.

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Clinical features

• Thromboembolism

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Clinical features

• Circulatory disturbance, shock
• ? ?a
• kininogen kallidini
  formation of Fibrinopeptide A
• 
  microvascular thrombi Fibrinopeptide
  B
• thrombin
• dilatation of the
• blood vessles
• 
  returned blood volume?
  vasospasm
• hemorrhage
• SHOCK
• circulating blood volume ? diseases
  underlying DIC

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Clinical features

• Microangiopathic hemolytic anemia
• Mechanism
• Erythrocytes are injured mechanically during
  passage through fibrin networks in the
  microcirculation.
• Manifestation
• production of schistocytes and microspherocytes
• jaundice, hemoglobinuria, anemia.

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Laboratory features

• Basic blood examinations
• Platelet count BPC ?
• Peripheral blood smear schistocytes (in
  approximately 50 of cases)

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Laboratory features

• The coagulation defect
• Partial thromboplastin time (PTT)
• Prothrombin time
• Thrombin time
• Fibrinogen concentration

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Laboratory features

• Tests for fibrinolysis
• Fibrinogen degradation products (FDP)
• D-dimer
• Plasma protamine paracoagulation test (3P)
• Euglobulin lysis time

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Laboratory features

• Other laboratory findings(molecular markers)
• F12
• Thrombin-AT ? complex (TAT)
• Fibrinopeptide A (FPA)
• SFMC (soluble fibrin monomer complex)
• Antithrombin ?
• Products of platelet activationß-TG,PF-4,TXB2,GMP
  -140
• PIC (plasmin-a2 plasmin inhibitor complex)

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• ?a
• prothrombin thrombin AT? TAT
• F12
• fibrinogen fibrin monomer
• FPA,FPB
• Polymerization
• soluble fibrin
• plasmin ??a
• FDP cross-linked fibrin
• SFMC FDP(X)FMFg

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Laboratory features

• Laboratory data change with remarkable rapidity
  in DIC, and in doubtful cases, it is often
  important to repeat the tests at frequent
  intervals, even every 8 to 12 hours and observing
  the dynamics of the process.

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Diagnostic criteria ------ ISTH DIC
score
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• 1.Risk assessment
• does the patient have an underlying disorder
  known to be associated with overt DIC?
• If yes Proceed.
• If no Do not use this algorithm.

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• 2. Order global coagulation tests
• platelet count,
• prothrombin time,
• fibrinogen,
• fibrin-related marker

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• 3. Score global coagulation test results.
• Platelet count
• (gt100 0 lt100 1 lt 50 2)
• Elevated fibrin related marker (e.g. D-dimers
  fibrin degradation products)
• (no increase 0 moderate increase 2 strong
  increase 3)
• Prolonged prothrombin time
• (lt 3 s 0 gt 3 but lt 6 s 1 gt 6 s 2)
• Fibrinogen level
• (gt1.0g/L 0 lt 1.0g/L 1)

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• 4. Calculate score
• If 5 compatible with overt DIC repeat score
  daily
• If lt 5 suggestive (not affirmative) for
  non-overt DIC repeat next 12 days.

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Differential diagnosis

• DIC and severe liver disease
• DIC and TTP

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The distinction between DIC and severe liver
disease
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The distinction between DIC and TTP
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Treatment

• Management of underlying disorders
• intensive antibiotic treatment in patients with
  gram-negative bacteremia
• hysterectomy in patients with abruptio placenta
• resection of an aortic aneurysm
• debridement of crushed tissues
• chemotherapy of acute leukemia
• supportive care fluids, pressors, dialysis, and
  respiratory and ventilator management.

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Heparin
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mechanism

• lysine
• sites
• active arginine
• serine reactive
• center center
• Thrombin antithrombin heparin

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Treatment anticoagulation1.heparin

• Indications
• forms manifested by thrombosis or acrocyanosis
• forms that accompany
• cancer,
• vascular malformations,
• retained dead fetus,
• acute promyelocytic leukemia.

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Treatment anticoagulation1.heparin

• Dosage
• The optimal dosage of heparin is the source of
  some disagreement
• 50u/kg, intravenous infusion, Q6h
• 5000-10000u, subcutaneously,Q12-24h

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Treatment anticoagulation1.heparin

• Laboratory monitoring
• aPTT a prolongation of between 1.5 and 2 times
  normal
• CT
• Reversal of heparin effect
• 1mg protamine sulfate 100u heparin
• infused intravenously
• rate of infusion lt 5mg/min

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Treatment anticoagulation1.heparin

• low-molecular-
• weight heparin
• (LMWH)

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Treatment anticoagulation1.heparin

• LMWH
• Characteristics
• Posses higher anti-?a activity than anti-thrombin
  activity
• Longer half-time and a higher, more reliable
  bioavailability
• A lower incidence of bleeding complications.
• Usage
• 75-150IUA ?a/Kg.d, subcutaneously, 3-5days.

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Treatment anticoagulation2. others

• AT-?
• Decrease the dose of heparin
• Improve the response.
• Dose 1500-3000u Bid-Tid, intravenous
  infusion5-7days

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Treatment Antiplatelet drugs

• Indications
• in hypercoagulability state
• the diagnosis of DIC is still not certain
• in mild cases.
• Usage
• compound danshen infusion
• 20-40ml Bid-Tid3-5days
• Low molecular weight dextran 500-1000ml/d
• 3-5days
• Ticlopidine 250mg Bid p.o. 5-7days
• Dipyridamole 500mg/d 3-5days

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Treatment Haemostatic support

• platelet concentrates
• platelet count lt20109/L or have severe
  life-threatening bleeding
• fresh frozen plasma (FFP)
• 10-15ml/kg body weight when the INR of PT is
  greater than 1.5
• cryoprecipitate
• 1-4 unit/10kg body weight when the fibrinogen
  concentration is 0.8g/l or less.
• Fibrinogen
• 1st dose 2-4g (1-1.5g??50mg/L)
• PPSB
• 200u200ml FFP

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Treatment Fibrinolytic inhibitors

• Indications
• the underlying disorders have already controlled
  or cured
• excessive fibrinolysis is observed
• Late stage of DIC
• Contraindications
• patients with early stage of DIC.

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Treatment Fibrinolytic inhibitors

• Usage
• PAMBA(????) 600-800mg/d
• tranexamic acid(????) 500-700mg/d
• e-aminocaproic acid(????) 4-10g/d
• Attention
• These agents should be preceded by replacement of
  depleted blood components and continuous heparin
  infusion.

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Summary
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