This IBCC chapter has not been fully reviewed or revised. It is being released due to COVID-19. We will refine this further and produce a podcast at a later date.
- DIC refers to dysregulated hemostasis causing widespread clotting. Eventually this causes the consumption of coagulation factors, which may create a tendency to bleed.
- Different flavors of DIC tend to be dominated by either bleeding or clotting, for example:
- Hemorrhage is associated with DIC from pregnancy, leukemia, or trauma.
- Thrombosis is associated with DIC from sepsis or malignancy.
- Thus, DIC isn't a single entity, but rather a collection of heterogeneous conditions.
- Can be asymptomatic
- Petechiae, purpura
- Oozing from intravenous catheters or mucus membranes
- May cause life-threatening bleeding (GI tract, intracranial)
- Primarily venous clots (e.g. PE, DVT)
- Most severe form: purpura fulminans (thrombosis of skin arteries causes gangrene)
- Organ failure due to microvascular thromboses
- Renal failure most common
- Brain involvement may cause delirium, coma, seizure
laboratory studies & diagnosis
- INR, PTT
- Fibrinogen, D-dimer
overview of abnormalities
- D-dimer invariably elevated, often dramatically (e.g. >4,000 ng/ml). A normal D-dimer largely excludes DIC.
- Platelets generally low.
- INR and aPTT are generally prolonged.
- Microangiopathic hemolytic anemia can occur due to thrombotic narrowing of capillaries. This is defined by the presence of schistocytes (fragmented RBCs).
- Fibrinogen isn't always low!
- Contrary to popular belief, normal fibrinogen doesn't exclude DIC. Low fibrinogen supports a diagnosis of DIC, but this isn't always seen.
- Sepsis increases fibrinogen levels, so sepsis-associated DIC may have elevated or normal levels of fibrinogen.
- No single lab test is diagnostic of DIC. Among several DIC scoring systems, the International Society of Thrombosis and Hemostasis score seems to be most widely utilized (table above).
- Diagnosis is based on characteristic pattern of coagulation abnormalities in a compatible clinical context.
- Alternatives to consider include cirrhosis and massive transfusion.
role of thromboelastography (TEG) in DIC?
- Patients with DIC often have reduced levels of both clotting factors and also endogenous anti-coagulant proteins. This may create a situation where patients appears to be hypo-coagulable based on standard labs (e.g. platelet count and INR), but they are actually hyper-coagulable.
- TEG is a whole-blood integrative test which may help clarify the overall balance of coagulation.
causes of DIC
- Tissue damage
- Burns or frostbite
- Surgery, trauma, fat emboli syndrome
- Intravascular hemolysis (e.g. hemolytic transfusion reaction)
- Hematologic malignancy (especially acute promyelocytic leukemia)
- Adenocarcinoma (especially pancreas, prostate, lung, gastric)
- Obstetric catastrophe: placental abruption, amniotic fluid embolism, preeclampsia, fetal demise
- Severe collagen vascular disease, vasculitis
- HITT, acute hemolytic transfusion reaction
- Severe hepatitis
cirrhosis & splenectomy are risk factors
- Both conditions impair ability to clear activated clotting factors from the blood.
- This may partially explain why patients with these conditions are at increased risk from sepsis.
(0) some specific types of DIC require different management:
- Patients with DIC due to acute promyelocytic leukemia (APML) require specific treatment [FILE ON APML].
- Patients with pregnancy-associated DIC and clinical bleeding often need aggressive factor replacement with an emphasis on maintaining adequate fibrinogen levels.
(1) treat the underlying disorder
- For example, DIC is quite common in sepsis. With successful treatment of the sepsis, the DIC will resolve (e.g. resolution of thrombocytopenia is a positive prognostic sign because it reflects improvement in the underlying sepsis syndrome).
(2) generally try to avoid blood products
- Blood products are generally avoided if patient is asymptomatic. Some exceptions may exist however:
- Severe thrombocytopenia (e.g. platelet count <10,000) is treated per usual guidelines (see chapter on thrombocytopenia).
- Very low fibrinogen levels may be a reasonable indication for cryoprecipitate, particularly if there is no clinical evidence of thrombosis. Many sources recommend maintaining the fibrinogen level above 100 g/dL.
- Blood products may be indicated for clinically significant bleeding or a planned high-risk procedure.
- Be careful: patients with sepsis-associated DIC are often hyper-coagulable, which may be exacerbated by platelet transfusion.
- Obtaining a TEG may help determine the patient's true coagulation balance, and thereby avoid giving blood products to a patients who is hyper-coagulable.
- Theoretically, anticoagulation with heparin could impede ongoing thrombosis and thereby treat the DIC. However, this hasn't been proven to be effective.
- Potential exception: heparin may be considered in purpura fulminans (see below).
- DVT prophylaxis should generally be provided in absence of bleeding or profound thrombocytopenia (e.g. platelets <30,000/mm3).
- Therapeutic anticoagulation may be indicated for thrombosis (e.g. DVT, PE).
- Severe form of DIC occasionally seen in severe sepsis. Defined by the presence of widespread subcutaneous bruising (purpura) and often symmetric ischemic necrosis of fingers and toes (picture at the top of this chapter).
- Highly morbid condition which may lead to ischemic loss of limbs or digits.
most common causes
- Bacterial infections
- Streptococcus pneumoniae (especially in post-splenectomy sepsis syndrome)
- Group A streptococcus, Staphylococcus aureus
- Capnocytophagia canimorsus
- Haemophilus influenzae
- Gram-negatives (e.g. Escherichia coli, Pseudomonas, Klebsiella pneumoniae)
- Viral infections (e.g. varicella zoster virus)
- Post-infectious (following resolution of Group A streptococcal or viral infection, due to acquired antibody that inhibits Protein C or Protein S)
- Typically most prominent in extremities, but can extend to the trunk.
- Initially skin appears mottled, with red patches in a lacy distribution.
- Later on, central areas of lesions become black and necrotic. Bullae may develop.
- Clinical diagnosis based on observation of typical changes within a consistent clinical context. Labs should show DIC, usually with thrombocytopenia and hypofibrinogenemia.
- Differential considerations include warfarin-induced skin necrosis, catastrophic anti-phospholipid syndrome, heparin-induced thrombocytopenia, warfarin-induced skin necrosis, and Henoch-Schonlein purpura (Colling 2018).
- Central even appears to be deficient activity of Protein C & Protein S, leading to endothelial damage and unopposed thrombosis. Antithrombin-III is also depleted.
- Antibiotics: Will depend on scenario. Consider the use of meningeal dosing if meningitis is possible (e.g. ceftriaxone 2 grams IV Q12). More on the treatment of meningitis [here].
- Steroid: Adrenal infarction may occur, which may require treatment with stress-dose steroid.
- Heparin and/or Antithrombin-III
- Anticoagulation with heparin is generally used (guidelines do recommend this, because purpura fulminans represents a thrombotic complication of DIC). Unfortunately, therapeutic heparin levels may be difficult to achieve because patients are usually deficient in antithrombin-III (causing heparin resistance). In such situations, large doses of heparin may be needed (Colling 2018). In refractory cases, administration of antithrombin-III may be considered.
- Prolongation of INR and PTT aren't necessarily a contraindication to heparin, as these labs may not correlate with true coagulative tendencies in DIC. Thromboelastography might provide a more accurate sense of coagulation balance.
- Topical nitroglycerine for local vasodilation of hypoperfused extremities.
- Intravenous epoprostanol infusion has been described in case reports to improve distal perfusion and potentially reduce tissue loss (Helviz 2011). This is a short-acting and fairly safe agent, so trialing it may be reasonable especially among patients at risk of digit or extremity loss.
- Extremity compartment syndrome: Extremity compartment syndrome may occur if sufficient tissue damage occurs (e.g. involving the hand, image above). Early fasciotomy may avoid the need for subsequent amputation. This may not be obvious, so when in doubt consult a surgeon.1
- Plasma exchange is an option, using fresh frozen plasma as replacement to re-establish normal levels of pro- and anti-coagulant proteins. However, there is little evidence to support this currently.
- Avoid use of blood products to “fix labs” in a patient with asymptomatic DIC (although this may be warranted for profoundly low platelet count or fibrinogen level).
- There is little evidence on this, but sepsis-associated DIC generally causes patients to be pro-thrombotic. Therefore, holding DVT prophylaxis for patients with mild-moderate thrombocytopenia (e.g. platelet count >30,000) may be inadvisable.