Relative Frequencies of Etiologies of Disseminated Intravascular Coagulation (DIC)
The Most Common Etiologies of Disseminated Intravascular Coagulation (DIC) are Infection, Malignancy, and Trauma/Surgery (Thromb Haemost, 1978) [MEDLINE] (Thromb Haemost, 1980) [MEDLINE]
Each Account for Approximately 10-20% of the Total Cases (Depending on the Study)
Hereditary Homozygous Protein C Deficiency Commonly Presents in Early Infancy with Purpura Fulminans, But Older Patients are Also Occasionally Seen
In Contrast, Heterozygous Protein C Deficiency with Venous Thromboembolism Typically Does Not Have Disseminated Intravascular Coagulation (DIC) as a Component of its Pathogenesis
Severe Acquired Protein C Deficiency (Such as May Cases Associated with Severe Meningococcal Infection) May Also Present with Purpura Fulminans
The Diagnosis of Disseminated Intravascular Coagulation (DIC) Post-Cardiopulmonary Bypass is Clinically Difficult (Since the Identification of Microthrombi is Difficult and Hemolysis and Consumption of Coagulation Factors May Be Commonly Observed Following Cardiopulmonary Bypass)
However, Some Consider This to Be a Coagulopathy/Thrombotic Microangiopathy Which is Distinct from Disseminated Intravascular Coagulation (DIC) (Semin Thromb Hemost, 2010) [MEDLINE]
Findings Such as Thrombocytopenia, Hypofibrinogenemia, and Elevated D-Dimer are Considered to Be Relatively Sensitive for the Diagnosis of Disseminated Intravascular Coagulation (DIC), But Not Specific
However, Data from Clinical Trials Addressing Sensitivity and Specificity are Lacking
Many of the Laboratory Abnormalities Used to Diagnose Disseminated Intravascular Coagulation (DIC) are Present in Normal Pregnancy
Testing is Often Repeated Serially to Determine if Coagulation and Fibrinolysis are Worsening or Improving
The Frequency of Repeat Testing Depends on the Severity of Clinical Findings
Clinical Differentiation of Hemolytic Syndromes
International Society of Thrombosis and Hemostasis Disseminated Intravascular Coagulation (DIC) Scoring System (Thromb Res, 2015) [MEDLINE] (Ann Lab Med, 2016) [MEDLINE]
General Comments
The International Society of Thrombosis and Hemostasis (ISTH) Disseminated Intravascular Coagulation (DIC) Scoring System Utilizes Laboratory Features, Including the International Normalized Ratio (INR), Platelet Count, Fibrinogen Level, and D-Dimer
Scoring System Has Been Validated, But is Not Widely Used
International Society of Thrombosis and Hemostasis Disseminated Intravascular Coagulation (DIC) Scoring System Adapted for Use in Pregnancy (PLoS One, 2014) [MEDLINE]
Parameters
Platelets <50k or 100-185k or Fibrinogen 400-450 mg/dL: 1 points
Platelets 50k-100k: 2 points
PT Difference 0.5-1.0: 5 points
Fibrinogen 300-400 mg/dL): 6 points
PT Difference 1-1.5: 12 points
PT Difference >1.5 or Fibrinogen ≤300 mg/dL: 25 points
Score
Cutoff Point of ≥26 Had a Sensitivity of 88%, a Specificity of 96%, Positive Likelihood Ratio of 22, and a Negative Likelihood Ratio of 0.125 for the Diagnosis of Disseminated Intravascular Coagulation (DIC)
Differentiation of Disseminated Intravascular Coagulation (DIC) from Severe Liver Disease (see Cirrhosis)
Liver Disease Severe Enough to Impair the Hepatic Synthesis of Coagulation Factors Can Result in a Severe Coagulopathy
Severe Liver Disease is Associated with Decreases in Both Procoagulant and Anticoagulant Factors as Well as Thrombocytopenia (and Therefore, May Result in Bleeding or Thrombosis)
Similar to Disseminated Intravascular Coagulation (DIC)
The Decrease in Coagulation Factors and Thrombocytopenia in Severe Liver Disease are Due to a Combination of Hypersplenism and Thrombopoietin Deficiency
Liver is the Primary Site of Thrombopoietin Synthesis
Patients with Severe Liver Disease Typically Present with a Known Source of Liver Injury (Such as Acute Hepatitis or Alcoholic Cirrhosis) and Abnormal Liver Function Tests (Although the Transaminases May Appear to Normalize if Liver Synthetic Function is Severely Impaired)
Dissimilar to Disseminated Intravascular Coagulation (DIC)
Some Clinicians Utilize the Measurement of Factor VIII Levels to Aid in the Differentiation of Disseminated Intravascular Coagulation (DIC) from Severe Liver Disease, Since Factor VIII is Not Produced by Hepatocytes and Therefore, is Frequently Decreased in Disseminated Intravascular Coagulation (DIC) and Increased in Severe Liver Disease
Differentiation of Disseminated Intravascular Coagulation (DIC) from Thrombotic Microangiopathy (TMA) (see xxxx)
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Differentiation of Disseminated Intravascular Coagulation (DIC) from Hemophagocytic Lymphohistiocytosis (HLH) (see Hemophagocytic Lymphohistiocytosis)
Hemophagocytic Lymphohistiocytosis is an Aggressive, Life-Threatening Syndrome of Excessive Immune Activation Which, Untreated, Can Result in Tissue Damage and a High Mortality Rate
Acute Illness with Cytopenias, Prolonged Clotting Times, Hypofibrinogenemia, and Increased D-Dimer May Be Present
Similar to Disseminated Intravascular Coagulation (DIC)
Patients May Also Have Fever, Hepatic Dysfunction, Neurologic Deficits, and Severe Hyperferritinemia
Patients with Hemophagocytic Lymphohistiocytosis (HLH) Have Evidence of Immune Activation, with Pathogenic Variants in One of Several Immune Regulatory Genes and Often Including Low/Absent Natural Killer (NK) Cell Activity, Increased Soluble Interleukin 2 (IL-2) Receptor α (sCD25) and/or CXCL19
Dissimilar to Disseminated Intravascular Coagulation (DIC)
Patients with Hemophagocytic Lymphohistiocytosis (HLH) Typically Require Treatment Directed at the Underlying Etiology (if Present), as Well as Treatment Directed at Stopping the Immune Activation
Dissimilar to Disseminated Intravascular Coagulation (DIC)
The Most Impaired Coagulation Tests are the Prothrombin Iime/International Normalized Ratio (INR), Partial Thromboplastin Time, Thrombin Time, and the Platelet Count
The Degree of Abnormality of These Coagulation Tests is Correlated to the Degree of Organ Involvement
However, Since Patients with Sepsis/Malignancy/Other Inflammatory Disorders May Have Significantly Increased Fibrinogen Synthesis (as Fibrinogen is an Acute Phase Reactant), a Normal Plasma Fibrinogen Level May Represent a Substantial Consumption (and a Significant Abnormality) for that Patient Despite the Value Being in the Normal Range
Since Factor VIII is Not Synthesized by the Liver, it is Often High in the Setting of Liver Disease, But is Decreased in the Setting of Disseminated Intravascular Coagulation (DIC)
Changes Consistent with Microangiopathic Hemolytic Anemia (MAHA) (see Hemolytic Anemia): schistocytes, helmet cells, etc
Microangiopathic Changes May Be Less Pronounced than Those Observed in Other Thrombotic Microangiopathies (such as Thrombotic Thrombocytopenic Purpura, TTP)
Severe Anemia Due to Microangiopathic Hemolytic Anemia is Uncommon (Although Most of the Underlying Etiologies of Disseminated Intravascular Coagulation Can Cause Anemia by Other Mechanisms, Such as Bone Marrow Suppression, Anemia of Chronic Disease/Inflammation, etc)
Clinical
General Comments
In Trauma-Associated Cases, Pulmonary Dysfunction is Common, While Hepatic/Renal Dysfunction are Rare (Thromb Haemost, 1978) [MEDLINE]
In Contrast, in Infection-Associated Cases, Hepatic/Renal Dysfunction are Common, While Pulmonary Dysfunction is Rare (Thromb Haemost, 1978) [MEDLINE]
This Variability Indicates that the Clinical Manifestations are Affected Not Only by the Process of Intravascular Coagulation, But Also by the Underlying Clinical Disorder
Hemorrhage
General Comments
Hemorrhage is More Common in Acute Disseminated Intravascular Coagulation (DIC) Than in Chronic Disseminated Intravascular Coagulation (DIC)
Hemorrhage Occurs in 64% of Acute Disseminated Intravascular Coagulation (DIC) Cases (Thromb Haemost, 1978) [MEDLINE]
Acute Kidney Injury Occurs in 25% of Acute Disseminated Intravascular Coagulation (DIC) Cases (Thromb Haemost, 1978) [MEDLINE]
Prognosis
The mortality (overall 54.7%) increased independently with age, with the number of clinical manifestations and with the degree of abnormality of the above-mentioned four most impaired coagulation tests (Thromb Haemost, 1978) [MEDLINE]
In addition, older patients were more likely to have an increased number of clinical manifestations and more impaired coagulation tests
Mortality was similar in the various etiologies except for trauma patients in whom it was lower (30%)
Thrombin Time is More Sensitive than INR/PTT to the Effects of Increased D-Dimers and Fibrin Degradation Products in Chronic Disseminated Intravascular Coagulation (DIC)
Changes Consistent with Microangiopathic Hemolytic Anemia (MAHA) (see Hemolytic Anemia): schistocytes, helmet cells, etc
Microangiopathic Changes May Be Less Pronounced than Those Observed in Other Thrombotic Microangiopathies (such as Thrombotic Thrombocytopenic Purpura, TTP)
Severe Anemia Due to Microangiopathic Hemolytic Anemia is Uncommon (Although Most of the Underlying Etiologies of Disseminated Intravascular Coagulation Can Cause Anemia by Other Mechanisms, Such as Bone Marrow Suppression, Anemia of Chronic Disease/Inflammation, etc)
Clinical
Chronic Disseminated Intravascular Coagulation (DIC) May Be Asymptomatic
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Hemorrhage
General Comments
Hemorrhage is More Common in Acute Disseminated Intravascular Coagulation (DIC) Than in Chronic Disseminated Intravascular Coagulation (DIC)
Thrombosis
General Comments
Thrombosis is More Common in Chronic Disseminated Intravascular Coagulation (DIC) Than in Acute Disseminated Intravascular Coagulation (DIC)
Typically in the Setting of a Solid Tumor
Clinical Types
Arterial Thrombosis (Especially without a Clear Precipitating Factor) with Organ Ischemia
Hemodynamic Support (Pressors, Intravenous Fluids): as required
Mechanical Ventilation: as required
Treatment of Thrombotic Complications
Anticoagulation: as required to treat thrombotic complications
Treatment of Bleeding Complications
Antifibrinolytic Agents (Tranexamic Acid, Epsilon-Aminocaproic Acid, Aprotinin): contraindicated (since blockade of the fibrinolytic system may increase the risk of thrombosis)
However, these agents may be used in patients who have severe bleeding associated with a hyperfibrinolytic state
Antithombin: trials have shown this to be ineffective in DIC
One unit of cryoprecipitate (10-20 ml) contains the cold insoluble protein from one unit of FFP (contains vWF, factor VIII, factor XIII, fibrinogen, and fibrinonectin)
Some blood suppliers now provide one bag of pre-pooled cryoprecipitate which contains 5 (or more) units in 120-160 mL: use two bags of pre-pooled cryoprecipitate (ie: from 10 units of FFP)
Fresh Frozen Plasma (FFP) (see Fresh Frozen Plasma): as required to treat coagulopathy in the setting of significant hemorrhage or need for invasive procedures
Packed Red Blood Cells (see Packed Red Blood Cells): as required to treat hemorrhage-related anemia
Transfuse for Platelet Count <50k: in the setting of significant hemorrhage or need for invasive procedures
Transfuse for Platelet Count <10k: in all patients (due to the risk of spontaneous hemorrhage)
Prothrombin Complex Concentrates: likely contraindicated (due to risk of more thrombotic complications in the setting of an already hypercoagulable state)
Fresh Frozen Plasma (FFP) (see Fresh Frozen Plasma): the administration of FFP as a source of protein C is problematic because of the short plasma half-life of protein C
Due to short plasma protein C half-life, FFP 2-3 units may be administered approximately every 6 hrs
Protein C Concentrate (see Protein C Concentrate): proven to decrease mortality rate in purpura fulminans
Expected Course of Resolution
Factors Impacting the Rate of DIC Resolution: DIC does not usually resolve immediately once the inciting factor is corrected
Resolution requires the synthesis of coagulant factors (which are synthesized at different rates)
Resolution requires hepatic clearance of anticoagulant factors and fibrin degradation products
Resolution requires bone marrow production of new platelets (which may take several days)
Resolution of DIC-Related Laboratory abnormalities: usually improve within a few days after the inciting stimulus is removed
Impact of Renal Failure on the Rate of DIC Resolution: does not impact the rate DIC resolution (unless there is a component of hepatorenal syndrome or if the kidneys are a major site of thrombosis)
References
General
xxx
Diagnosis
Clinical and laboratory aspects of disseminated intravascular coagulation (DIC): a study of 118 cases. Thromb Haemost. 1978;39(1):122 [MEDLINE]
Management of disseminated intravascular coagulation: a survey of the International Society on Thrombosis and Haemostasis. Thromb Res. 2015;136(2):239 [MEDLINE]
Current Pathological and Laboratory Considerations in the Diagnosis of Disseminated Intravascular Coagulation. Ann Lab Med. 2016;36(6):505 [MEDLINE]
Clinical
Clinical and laboratory aspects of disseminated intravascular coagulation (DIC): a study of 118 cases. Thromb Haemost. 1978;39(1):122 [MEDLINE]
