Disseminated Intravascular Disseminated Intravascular CoagulationCoagulation

WangXinWangXin

Department of Emergency MedicineDepartment of Emergency Medicine

Tianjin Medical University General Tianjin Medical University General HospitalHospital

General ConsiderationsGeneral Considerations

DIC is not a kind of independent DIC is not a kind of independent disease, but a middle process or disease, but a middle process or complication of some diseases .complication of some diseases .

It is essentially an imbalance It is essentially an imbalance between the coagulation process and between the coagulation process and anticoagulation process. It is a syndrome anticoagulation process. It is a syndrome characterized by massive activation and characterized by massive activation and consumption of coagulation proteins, consumption of coagulation proteins, fibrinolytic proteins and platelets. fibrinolytic proteins and platelets.

Coagulation is usually confined Coagulation is usually confined to a localized area by the to a localized area by the combination of blood flow and combination of blood flow and circulating inhibitors of circulating inhibitors of coagulation, especially coagulation, especially antithrombin Ⅲ . If the stimulus to antithrombin Ⅲ . If the stimulus to coagulation is too great, these coagulation is too great, these control mechanisms can be control mechanisms can be overwhelmed, leading to the overwhelmed, leading to the syndrome of DIC.syndrome of DIC.

ClassificationClassificationAcute DIC :It happened Acute DIC :It happened

rapidly, the coagulopathy is rapidly, the coagulopathy is dominant and major symptoms dominant and major symptoms are bleeding and shock, mainly are bleeding and shock, mainly seen in severe infection, amniotic seen in severe infection, amniotic fluid embolism. fluid embolism.

Chronic DIC: it happened Chronic DIC: it happened slowly and last several weeks, slowly and last several weeks, thrombosis and clotting may thrombosis and clotting may predominate mainly seen in predominate mainly seen in cancer.cancer.

EtiologyEtiology

DIC is not a primary DIC is not a primary disease, but a disorder disease, but a disorder secondary to numerous secondary to numerous triggering events such as triggering events such as serious illnesses.serious illnesses.

infectious disease 31%~43%infectious disease 31%~43%

cancer 24%~34%cancer 24%~34%

obstetric complications obstetric complications 4%~12%4%~12%

severe tissue injury 1%~5%severe tissue injury 1%~5%

systemic diseasesystemic disease

ID

Cancer

OC

STI

SD

●●infectious disease 31%~43%infectious disease 31%~43%(bacterial, viral, rickettsial, parasitic (bacterial, viral, rickettsial, parasitic

diseases and so on) Bacterial infection, diseases and so on) Bacterial infection, in particular septicemia, is commonly in particular septicemia, is commonly associated with DIC. However, systemic associated with DIC. However, systemic infections with other microorganisms, infections with other microorganisms, such as viruses and parasites, also may such as viruses and parasites, also may lead to DIC. lead to DIC.

●●cancer 24%~34%cancer 24%~34%(Acute promyelocytic (Acute promyelocytic

leukemia, acute myelomonocytic leukemia, acute myelomonocytic or monocytic leukemia, or monocytic leukemia, disseminated prostatic carcinomadisseminated prostatic carcinomaLung, breast, gastrointestinal Lung, breast, gastrointestinal malignancy)malignancy)

●●obstetric obstetric complications 4%~12%complications 4%~12%

(amniotic fluid (amniotic fluid embolus, septic abortion, embolus, septic abortion, retained fetus and so on)retained fetus and so on)

●●severe tissue injury 1%~5%severe tissue injury 1%~5%(burn, heart shock, fracture and (burn, heart shock, fracture and

so on) Head trauma in particular is so on) Head trauma in particular is strongly associated with DIC; both strongly associated with DIC; both local and systemic activation of local and systemic activation of coagulation may be detected after coagulation may be detected after such an event. The increased risk of such an event. The increased risk of DIC after head trauma is DIC after head trauma is understandable in view of the understandable in view of the relatively large amount of tissue relatively large amount of tissue factor in the cerebral compartment. factor in the cerebral compartment.

●●systemic diseasesystemic disease

(malignant (malignant hypertension , Acute hypertension , Acute respiratory distress respiratory distress syndrome<ARDS>, syndrome<ARDS>, hemolytic transfusion hemolytic transfusion reaction)reaction)

PathophysiologyPathophysiologyDIC occurs when monocytes DIC occurs when monocytes

and endothelial cells are activated and endothelial cells are activated or injured by toxic substances or injured by toxic substances elaborated in the course of certain elaborated in the course of certain diseases. The response of diseases. The response of monocytes and endothelial cells to monocytes and endothelial cells to injury is to generate tissue factor injury is to generate tissue factor on the cell surface, activating the on the cell surface, activating the coagulation cascade . coagulation cascade .

In acute DIC, an explosive In acute DIC, an explosive generation of thrombin depletes generation of thrombin depletes clotting factors and platelets and clotting factors and platelets and activates the fibrinolytic system. activates the fibrinolytic system. Bleeding into the subcutaneous Bleeding into the subcutaneous tissues, skin, and mucous tissues, skin, and mucous membranes occurs, along with membranes occurs, along with occlusion of blood vessels caused occlusion of blood vessels caused by fibrin in the microcirculation. by fibrin in the microcirculation.

In chronic DIC, the In chronic DIC, the process is the same, but process is the same, but it is less explosive. it is less explosive. Usually there is time for Usually there is time for compensatory responses compensatory responses to take place, which to take place, which diminish the likelihood of diminish the likelihood of bleeding but give rise to bleeding but give rise to a hypercoagulable state. a hypercoagulable state.

These changes in the These changes in the blood can be detected by blood can be detected by testing the coagulation testing the coagulation system.system.

Thromboembolism Thromboembolism occurs in this setting, and occurs in this setting, and when oral anticoagulants when oral anticoagulants are given following heparin are given following heparin therapy, there is a therapy, there is a tendency for it to recur. tendency for it to recur.

Long-term therapy with Long-term therapy with low-molecular-weight heparin low-molecular-weight heparin may be a solution to this may be a solution to this problem until the underlying problem until the underlying cause can be brought under cause can be brought under control. control.

Stimulation of Coagulation

Intravascular thrombosis

Consumption of

coagulation factors

Secondary activation of

thrombolysis

Hypoperfusion to tissues

and organs

Inability to form a

stable clot

Release of

anticoagulants

Ischemic damage

Bleeding Bleeding

DiagnosisDiagnosis

●Symptoms and Signs●Symptoms and Signs

●Laboratory Findings●Laboratory Findings

●Different Diagnosis●Different Diagnosis

Symptoms and SignsSymptoms and Signs

BleedingBleedingThrombosisThrombosisHypotension or shockHypotension or shockOrgan dysfunctionOrgan dysfunction

●● Bleeding :84%~95% Bleeding :84%~95%

It may occur at It may occur at any site, but any site, but spontaneous bleeding spontaneous bleeding and oozing at and oozing at venipuncture sites or venipuncture sites or wounds are important wounds are important clues to the diagnosis. clues to the diagnosis.

Meningococcemia on the Calves

Meningococcemia on the Leg

Meningococcemia Associated Purpura

Thrombosis: It is most Thrombosis: It is most commonly manifested by commonly manifested by digital ischemia and digital ischemia and gangrene, renal cortical gangrene, renal cortical necrosis and hemorrhagic necrosis and hemorrhagic adrenal infarction may adrenal infarction may occur.occur.

Necrosis of the toes

Acute DICAcute DIC

Clinical findings Clinical findings Multiple bleeding sites Multiple bleeding sites Ecchymoses of skin, mucous Ecchymoses of skin, mucous

membranes membranes Visceral hemorrhage Visceral hemorrhage Ischemic tissue Ischemic tissue

Chronic DICChronic DIC

Clinical findings Clinical findings Signs of deep venous or Signs of deep venous or

arterial thrombosis or embolism arterial thrombosis or embolism Superficial venous Superficial venous

thrombosis, especially without thrombosis, especially without varicose veins varicose veins

Multiple thrombotic sites at Multiple thrombotic sites at the same time the same time

Serial thrombotic episodesSerial thrombotic episodes

Purpura fulminans

Purpura fulminans of a child's leg

Necrosis - of a child's toes

Laboratory FindingsLaboratory Findings

TestTest ResultResult

Platelet count Platelet count Markedly Markedly decreased decreased

Prothrombin time (PT) Prothrombin time (PT) Increased Increased

Activated partial Activated partial thromboplastin time thromboplastin time (APTT) (APTT)

Increased Increased

Fibrin degradation Fibrin degradation products (FDP)products (FDP)

Markedly Markedly increased increased

Fibrinogen Fibrinogen Normal or Normal or decreased decreased

Antithrombin III (AT III)Antithrombin III (AT III) Markedly Markedly decreased decreased

Protein C Protein C Markedly Markedly decreased decreased

Different DiagnosisDifferent Diagnosis

Liver disease

Vitamin K deficiency

Sepsis

TTP (Thrombotic thrombocytopenic purpura )

Liver diseaseLiver disease

Liver disease may prolong Liver disease may prolong both the PT and PTT, but both the PT and PTT, but fibrinogen levels are usually fibrinogen levels are usually normal, and the platelet count is normal, and the platelet count is usually normal or only slightly usually normal or only slightly reduced.reduced.

Severe liver disease may be Severe liver disease may be difficult to distinguish from DIC.difficult to distinguish from DIC.

Vitamin K deficiencyVitamin K deficiency

Vitamin K deficiency will Vitamin K deficiency will not affect the fibrinogen level not affect the fibrinogen level or platelet count and will be or platelet count and will be completely corrected by completely corrected by vitamin K replacement.vitamin K replacement.

SepsisSepsis

Sepsis may produce Sepsis may produce thrombo-cytopenia, and thrombo-cytopenia, and coagulopathy may be coagulopathy may be present because of vitamin present because of vitamin K deficiency. However, in K deficiency. However, in these cases, the fibrinogen these cases, the fibrinogen level should be normal.level should be normal.

TTP TTP (Thrombotic thrombocytopenic purpura )(Thrombotic thrombocytopenic purpura )

TTP may produce fever TTP may produce fever and MAHA (and MAHA (microangiopathic microangiopathic

hemolytic anemiahemolytic anemia). However, ). However, fibrinogen levels and other fibrinogen levels and other coagulation studies should coagulation studies should be normal.be normal.

TreatmentTreatment

Treatment of the underlying Treatment of the underlying disorder disorder

Replacement therapyReplacement therapyHeparin therapyHeparin therapyOther TreatmentOther Treatment

Treatment of the underlying disorderTreatment of the underlying disorder

The primary focus The primary focus should be the diagnosis should be the diagnosis and treatment of the and treatment of the underlying disorder underlying disorder that has given rise to that has given rise to DIC.DIC.

Treatment of the Treatment of the underlying disease is the underlying disease is the mainstay of management of mainstay of management of either acute or chronic DIC. either acute or chronic DIC. Avoid delay treat vigorously Avoid delay treat vigorously (eg, shock, sepsis, (eg, shock, sepsis, obstetrical problems).obstetrical problems).

Replacement therapyReplacement therapy

Coagulation factor Coagulation factor deficiency require deficiency require replacement with FFP (fresh replacement with FFP (fresh frozen plasma).frozen plasma).

Platelet transfusion Platelet transfusion should be used to maintain a should be used to maintain a platelet count greater than platelet count greater than 30000/μl, and 50000/μl.30000/μl, and 50000/μl.

Fibrinogen is replaced Fibrinogen is replaced with cryoprecipitate. One with cryoprecipitate. One unit of cryoprecipitate unit of cryoprecipitate usually raises the usually raises the fibrinogen level by fibrinogen level by 6~8mg/dl,so that 15 units 6~8mg/dl,so that 15 units of cryoprecipitate will of cryoprecipitate will raise the level from 50 to raise the level from 50 to 150mg/dl.150mg/dl.

Heparin therapyHeparin therapy In some cases heparin In some cases heparin

therapy is contraindicated, therapy is contraindicated, but when DIC is producing but when DIC is producing serious clinical consequences serious clinical consequences and the underlying cause is and the underlying cause is not rapidly reversible, not rapidly reversible, heparin may be necessary.heparin may be necessary.

Dose:500~750u/h is Dose:500~750u/h is necessary.necessary.

Attention:Attention:Heparin therapy Heparin therapy

must be used in must be used in combination with combination with replacement therapy, replacement therapy, it can lead to severe it can lead to severe

bleedingbleeding..

It cannot be effective if It cannot be effective if ATATⅢⅢ levels are markedly levels are markedly depleted. ATⅢ levels should depleted. ATⅢ levels should be measured, and FFP used be measured, and FFP used to raise levels to greater to raise levels to greater than 50%.FDP will decline than 50%.FDP will decline over 1~2d.Improvement in over 1~2d.Improvement in the platelet count may lag as the platelet count may lag as much as 1 week behind much as 1 week behind control of the coagulopathy.control of the coagulopathy.

Other TreatmentOther Treatment

Aminocaproic acid, 1g/h iv Aminocaproic acid, 1g/h iv

Tranexamic acid, 10mg/kg, Tranexamic acid, 10mg/kg, iv,q8h,iv,q8h,

Those two drugs should be Those two drugs should be added to decrease the rate of added to decrease the rate of fibrinolysis, raise the fibrinogen fibrinolysis, raise the fibrinogen level, and control bleeding.level, and control bleeding.

Attention Attention ::Aminocaproic Aminocaproic acid can never be used without acid can never be used without heparin in DIC because of the heparin in DIC because of the risk of thrombosis.risk of thrombosis.

Acute DICAcute DIC    Without bleeding or evidence of Without bleeding or evidence of

ischemiaischemiaNo treatmentNo treatment

With bleedingWith bleedingBlood components as neededBlood components as neededFresh frozen plasmaFresh frozen plasmaCryoprecipitateCryoprecipitatePlatelet transfusionsPlatelet transfusions

   With ischemiaWith ischemiaAnticoagulants after bleeding risk Anticoagulants after bleeding risk is corrected with blood productsis corrected with blood products

Chronic DICChronic DIC

Without Without thromboembolismthromboembolism

No specific therapy No specific therapy needed but prophylactic needed but prophylactic drugs (eg, low-dose drugs (eg, low-dose heparin, low-molecular-heparin, low-molecular-weight heparin) may be weight heparin) may be used for patients at high used for patients at high risk of thrombosisrisk of thrombosis

With thromboembolismWith thromboembolism

Heparin or low-molecular-Heparin or low-molecular-weight heparin, trial of weight heparin, trial of warfarin sodium (Coumadin). warfarin sodium (Coumadin). (If warfarin is unsuccessful, (If warfarin is unsuccessful, long-term use of low-molecular-long-term use of low-molecular-weight heparin may be helpful.)weight heparin may be helpful.)

ComplicationsComplications

Severe bleedingSevere bleedingStrokeStrokeIschemia of extremities or Ischemia of extremities or

organs organs

PrognosisPrognosis

Since DIC is a result of an acute Since DIC is a result of an acute medical illness, prognoses depends medical illness, prognoses depends almost entirely upon the speed of the almost entirely upon the speed of the intensivist in handing the bleeding intensivist in handing the bleeding emergency, as well as the ability to emergency, as well as the ability to treat the underling disordertreat the underling disorder

The underlying disease that The underlying disease that causes the disorder will usually causes the disorder will usually predict the probable outcome. predict the probable outcome.

SummarySummaryAn awareness of the clinical

settings in which DIC can occur and the diagnostic features that warn of its presence should enable the physician to diagnose and treat DIC appropriately.

New treatments that are more effective and less hazardous are clearly needed, and a number of such agents are now undergoing clinical trial.