Medication Summary
The goals of pharmacotherapy in cases of disseminated intravascular coagulation (DIC) are to reduce morbidity and to prevent complications. Therapy should be based on etiology and aimed at eliminating the underlying disease. Treatment should be appropriately aggressive for the patient’s age, disease, and severity and location of hemorrhage or thrombosis. Treatment of acute DIC includes anticoagulants, blood components, and antifibrinolytics. Hemostatic and coagulation parameters should be monitored continuously during treatment.
Base therapeutic decisions on clinical and laboratory evaluation of hemostasis. In cases of low-grade DIC, therapy other than supportive care may not be warranted or may include antiplatelet agents or subcutaneous heparin; treatment decisions should be based on clinical and laboratory evaluation of hemostasis.
Anticoagulants, Hematologic
Class Summary
Anticoagulants are used in the treatment of clinically evident intravascular thrombosis when the patient continues to bleed or clot 4-6 hours after initiation of primary and supportive therapy. Thrombosis can present as purpura fulminans or acral ischemia. Take special precaution in obstetric emergencies or massive liver failure. The anti-inflammatory properties of antithrombin may be particularly useful in DIC secondary to sepsis.
Heparin is the only currently available antithrombotic drug that has a role in the treatment of patients with DIC. Although most experience is with standard heparin, low-molecular-weight heparins (LMWHs) are increasingly used. Moreover, although LMWHs usually do not require laboratory monitoring, it may be advisable to check anti-factor Xa levels in critically ill patients with serious renal failure.
Heparin
Heparin augments the activity of antithrombin and prevents conversion of fibrinogen to fibrin. It does not actively lyse but is able to inhibit further thrombogenesis. It prevents reaccumulation of clot after spontaneous fibrinolysis. Usage and dosing of heparin are based on the severity of DIC, the underlying cause, and the extent of thrombosis. Monitoring the results of therapy is mandatory.
Antithrombin (Atryn, Thrombate III)
Antithrombin is used for moderately severe–to–severe DIC or when levels are depressed markedly. It is an alpha2-globulin that inactivates thrombin, plasmin, and other serine proteases of coagulation, including factors IXa, Xa, XIa, XIIa, and VIIa. These effects inhibit coagulation.
Recombinant Human Activated Protein C
Class Summary
Recombinant human APC inhibits factors Va and VIIIa of the coagulation cascade. It may also inhibit plasminogen activator inhibitor-1 (PAI-1). Drotrecogin alfa (Xigris) was withdrawn from the worldwide market on October 25, 2011.
Drotecogin alfa (Xigris)
Withdrawn from the worldwide market on October 25, 2011. Drotrecogin alfa was approved for the reduction of mortality in patients who have severe sepsis associated with acute organ dysfunction and who are at high risk for death. It is a recombinant form of human APC that exerts an antithrombotic effect by inhibiting factors Va and VIIIa.
Drotrecogin alfa exercises indirect profibrinolytic activity by inhibiting PAI-1 and limiting formation of activated thrombin-activatable fibrinolysis inhibitor. It may exert an anti-inflammatory effect by inhibiting human tumor necrosis factor (TNF) production by monocytes, blocking leukocyte adhesion to selectins, and limiting thrombin-induced inflammatory responses within the microvascular endothelium.
Blood Components
Class Summary
Blood components are used to correct abnormal hemostatic parameters. These products should be considered only after initial supportive and anticoagulant therapy. Washed packed red blood cells (PRBCs) and platelet concentrates are considered safe in uncontrolled DIC. Specialized blood components (eg, cryoprecipitate and fresh frozen plasma [FFP]) may interfere with or alleviate DIC.
Packed red blood cells (PRBCs; washed)
PRBCs are preferred to whole blood because they limit volume, immune, and storage complications. Obtain PRBCs after centrifugation of whole blood. Use washed or frozen PRBCs in individuals with hypersensitivity transfusion reactions.
Platelets
Platelets are considered safe for use in acute DIC.
Fresh frozen plasma (FFP)
FFP treatment entails removing blood from the body, spinning it to separate cells from plasma, and replacing cells suspended in fresh frozen plasma, albumin, or saline. FFP contains coagulation factors, as well as protein C and protein S. It can be administered either via 2 large-bore peripheral intravenous lines or via 1 multiple-lumen central line. It is recommended for patients with active bleeding and a fibrinogen level below 100 mg/dL.
Cryoprecipitate or fibrinogen concentrates
Cryoprecipitate and fibrinogen concentrates are not commonly recommended, except when fibrinogen is needed.
Antifibrinolytic Agents
Class Summary
In general, antifibrinolytic agents should be avoided in DIC because they are known to produce thrombotic complications, such as myocardial infarction and renal artery thrombosis when there is systemic clotting. They may have a role in a local intravascular coagulation (LIC) as is seen in genitourinary bleeding after a transurethral resection for Kasabach-Merritt syndrome.
In addition, in patients with trauma and massive bllood loss, antifibrinolytic agents have been shown to be effective in reducing blood loss and improving survival. Similarly, in massive postpartum hemorrhage, antifibrinolytic agents have been shown to be effective. Antifibrinolytics also may be useful in cases of DIC secondary to hyperfibrinolysis associated with acute promyelocytic leukemia and other forms of cancer when alpha-2-antiplasmin is uniquely decreased.
Aminocaproic acid (Amicar)
Aminocaproic acid inhibits fibrinolysis by inhibiting plasminogen activators and, to a lesser degree, exerting antiplasmin activity. The main problem is that the thrombi that form during treatment are not lysed and that the clinical significance of reducing bleeding is uncertain.
Tranexamic acid (Cyklokapron, Lysteda)
Tranexamic acid is used as an alternative to aminocaproic acid. It inhibits fibrinolysis by displacing plasminogen from fibrin.
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Diagnostic algorithm for the diagnosis of overt disseminated intravascular coagulation.
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Coagulation pathway.
Tables
- Table 1. Causes of Acute (Hemorrhagic) Disseminated Intravascular Coagulation
- Table 2. Causes of Chronic Disseminated Intravascular Coagulation
- Table 3. Main Features of Disseminated Intravascular Coagulation in Series of 118 Patients
- Table 4. Japanese Association for Acute Medicine (JAAM) Scoring System for DIC
- Table 5. Japanese Society on Thrombosis and Hemostasis (JSTH) Diagnostic Criteria for DIC
Type |
Cause |
Infectious |
Bacterial (eg, gram-negative sepsis, gram-positive infections, rickettsial) Viral (eg, HIV, cytomegalovirus [CMV], varicella-zoster virus [VZV], and hepatitis virus) Fungal (eg, Histoplasma) Parasitic (eg, malaria) |
Malignancy |
Hematologic (eg, acute myelocytic leukemia) Metastatic (eg, mucin-secreting adenocarcinoma) |
Obstetric |
Amniotic fluid embolism Abruptio placentae Acute peripartum hemorrhage Preeclampsia/eclampsia/hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome Retained stillbirth Septic abortion and intrauterine infection Acute fatty liver of pregnancy [40] |
Trauma |
Burns Motor vehicle accidents Snake envenomation |
Transfusion |
Hemolytic reactions Transfusion |
Other |
Liver disease/acute hepatic failure* Prosthetic devices Shunts (Denver or LeVeen) Ventricular assist devices |
*Some do not classify this as DIC; rather, it is liver disease with reduced blood coagulation factor synthesis and reduced clearance of activate products of coagulation. |
|
Type |
Cause |
Malignancies |
Solid tumors Leukemia |
Obstetric |
Retained dead fetus syndrome Retained products of conception |
Hematologic |
Myeloproliferative syndromes |
Vascular |
Rheumatoid arthritis Raynaud disease |
Cardiovascular |
Myocardial infarction |
Inflammatory |
Ulcerative colitis Crohn disease Sarcoidosis |
Localized DIC |
Aortic aneurysms Giant hemangioma (Kasabach-Merritt syndrome) Acute renal allograft rejection |
Features |
Affected Patients, % |
Bleeding |
64% |
Renal dysfunction |
25% |
Hepatic dysfunction |
19% |
Respiratory dysfunction |
16% |
Shock |
14% |
Central nervous system dysfunction |
2% |
Clinical conditions that should be ruled out |
|
Thrombocytopenia Dilution and abnormal distribution Massive blood loss, massive infusion ITP, TTP-HUS, HIT, HELLP syndrome Disorders of hematopoiesis Liver disease Hypothermia Spurious laboratory results |
|
Diagnostic algorithm for SIRS |
|
Temperature >38°C or < 36°C Heart rate >90 beats/min Respiratory rate >20 breaths/min or PaCO2< 32 mm Hg (< 4.3 kPa) WBC count >12,000 cells/µL, < 4000 cells/ µL, or 10% immature (band) forms |
|
Diagnostic algorithm SIRS criteria |
Score |
>3 |
1 |
0-2 |
0 |
Platelet count (× 109/L) |
|
< 80 or >50 % decrease within 24 hours |
3 |
>80 and < 120 or >30% decrease within 24 hours |
1 |
>120 |
0 |
Prothrombin time (value of patient/normal value) |
|
>1.2 |
1 |
< 1.2 |
0 |
Fibrin/FDPs (mg/L) |
|
>25 |
3 |
>10 and < 25 |
1 |
< 10 |
0 |
Diagnosis 4 points or more |
DIC |
DIC = disseminated intravascular coagulation; FDP = fibrin degradation product; HELLP = hemolysis, elevated liver enzymes, low platelet count; HIT = heparin-induced thrombocytopenia; HUS = hemolytic uremic syndrome; ITP = idiopathic thrombocytopenic purpura; PaCO2 = partial pressure of carbon dioxide in arterial blood; SIRS = systemic inflammatory response syndrome; TTP = thrombotic thrombocytopenic purpura; WBC = white blood cell. |
|
Test Results |
Points |
|
Platelet count (×103/μl)* |
80-120 |
1 |
51-80 |
2 |
|
≤50 |
3 |
|
Fibrin degradation products (FDP; μg/ml)** |
10-19 |
1 |
20-39 |
2 |
|
≥40 |
3 |
|
Fibrinogen (mg/dl) |
101-150 |
1 |
≤100 |
2 |
|
Prothrombin time ratio |
1.25-1.66 |
1 |
≥1.67 |
2 |
|
Antithrombin (%) |
≤70 |
1 |
TAT, SF, or F1+2 |
≥2-fold upper limit of normal |
1 |
Liver failure |
Acute: Prothrombin time activity 40% or International Normalized Ratio ≥1.5) Chronic: Cirrhosis with Child-Pugh B or C (≥7 points) |
-3 |
F1+2= prothrombin fragment 1 + 2; SF=soluble fibrin; TAT=thrombin-antithrombin complex *For a platelet count of >50 × 103/μL, add 1 point if the count decreases ≥30% within 24 h. The maximum score for the platelet count is 3 points. **For institutions that do not measure FDP, a D-dimer increase of ≥2-fold the upper limit of normal scores 1 point. |
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