The ambulance report seems routine: a patient transferring to the hospital from a nursing home for a possible urinary tract infection caused by an indwelling catheter. But on arrival, it’s apparent that this 82-year-old patient does not have a routine UTI. While the urine in the catheter bag does appear cloudy and tests positive for red and white blood cells, the patient is unusually confused and has a decreased level of consciousness. Clinicians observe petechiae all over the body

Lab tests are drawn and sent as an IV line is initiated. The prescribing provider orders antibiotics for apparent sepsis before transfer to the CCU. Within hours, the patient’s condition declines. Lab tests demonstrate low platelet and fibrinogen levels and elevated prothrombin times.

Bright red blood begins to ooze from the patient’s rectum, and the venipuncture and IV sites begin to bleed. The patient becomes unresponsive. The physician diagnoses disseminated intravascular coagulation (DIC) and summons the family to determine whether aggressive treatment should be started.  DIC refers to a complex disorder of the blood characterized by abnormal clotting, leading to consumption of clotting factors that ultimately results in abnormal bleeding. It’s impossible to understand DIC without a basic understanding of the complex structures of the coagulation cascade.

Normally, numerous clotting factors circulate within the blood stream. Under normal conditions, these factors are inactive but can be activated by numerous mechanisms. Once activation initiates, a cascade of events begins that ultimately leads to formation of a blood clot followed by dissolution of that clot. Two primary pathways can activate this cascade: The first is the intrinsic pathway. Normally, the inner lining of the blood vessels, called the endothelium, repels clotting factors circulating in the serum. If a blood vessel is injured, perhaps from a laceration that extends into the blood vessel, the underside of the endothelium will be exposed to the clotting factors within the serum. The underside of the endothelium attracts clotting Factor XII. As Factor XII is attracted to the injured area, it releases chemicals that begin the intrinsic clotting cascade.^{1, 2} A second pathway linked to the activation of the cascade is the extrinsic pathway. It does not require exposure of the endothelium to trauma, rather, the clotting mechanism is activated by substances released into the bloodstream, including free radicals, chemical irritants, or inflammatory mediators, such as tumor necrosis factor and cytokines. These substances will activate Factor VII, which, in turn, starts up the extrinsic pathway.^1,2 Regardless of whether the coagulation cascade is initiated intrinsically or extrinsically, the results are identical. The cascade causes circulating platelets to change into an irregular shape and become “sticky.” This “stickiness” causes them to adhere to uneven surfaces, and the irregular shape allows them to fit together like pieces of a puzzle. They soon will form into a mass known as a “white clot.”

This process potentiates fibrinogen, a substance normally found in the serum, to convert to fibrin. Fibrin forms a mesh that tightens around the mass of platelets, expelling fluid and causing a stable clot to form.¹ This firm, enmeshed conglomeration of blood cells will seal off a bleeding site and stem the flow of blood loss. Underneath the clot, the body begins the process of healing the defect that caused the initial bleeding. Obviously, every clot that forms in the body cannot remain there forever, so simultaneously with clot formation, the body activates a process for breakdown of the blood clot, also known as clot lysis. Once the clot is formed, it actually consumes its own production factors to prevent further clot development.

Other tissues around the clot secrete substances, such as antithrombin III and heparin, which further inactivate clotting factors and prevent growth of the clot. The fibrinolytic system also activates plasmin, another substance in the serum, which is converted to plasminogen. Plasminogen, in turn, begins degradation of the fibrin, causing the mesh to break down. This fibrin degradation releases products into the blood; ultimately, the clot will dissolve, the endothelium under it will be repaired and will become smooth, and the vessel will return to its preinjury state.¹ The process of coagulation is a delicate one, requiring the proper balance of factors and substances to prevent, produce, and lyse clots. A disturbance in this delicate balance may produce DIC, not a disease in and of itself, but an indication of an underlying disorder.²

Down a deadly pathway

Whether initiated by aberrancies in the intrinsic or extrinsic pathway or by sepsis, a snakebite, eclampsia, or cancer, DIC ultimately leads down a similar and deadly pathway. Increased platelet aggregation promotes accelerated and excessive blood clot formation, followed by lysis of these clots. This process will lead to systemic anticoagulation throughout the body, ultimately resulting in bleeding. As clotting pathways are initiated, the blood becomes hypercoagulable, which results in the clumping of platelets throughout the body. Most of these blood clots are small and tend to lodge in the smaller capillaries and blood vessels throughout the body. This causes hypoxia of tissue distal to the clots. Because DIC is marked by excessive, systemic clot formation, the hypoxia becomes widespread, affecting all organ systems and tissues, especially the kidneys, lungs, and liver.⁴

Yet the syndrome does not stop with excessive clotting and resultant hypoxia, but continues to much more deadly consequences. The production of massive clots consumes available clotting factors. Platelets, fibrinogen, and other clotting factors are used faster than the liver and bone marrow can reproduce them, and patients’ serum levels begin to drop. In fact, 98% of patients with DIC will have thrombocytopenia (abnormally low platelet count).⁴ However, another factor comes into play with DIC: the production of fibrinolytic agents. Remember that clots actually produce their own anticoagulant factors, such as antithrombin III and heparin, to prevent the clot from growing excessively large. If a patient has multiple blood clots forming in the microvasculature around the body and each one is releasing its own anticoagulant factors, there will be a systemic anticoagulant effect.⁴ As a result, the patient will begin to lose the ability to form new blood clots. This is compounded by the depletion of clotting factors, as discussed earlier. The process in which plasmin is converted to plasminogen, the substance responsible for lysing clots by causing their breakdown, further complicates the situation. Remember that the blood clot initiates this process and is responsible for breaking itself down. When multiple clots form simultaneously, they will collectively cause the conversion of plasminogen in the blood, resulting in massive clot breakdown.

While this does not present an obstacle for unwanted clots that may have formed, it will be a problem for therapeutic clots that may have been present. For example, if a patient had surgery before developing DIC, the excessive plasminogen in the serum may begin to break down the clots at the surgical site, causing fresh bleeding from a site that had previously been clotted.⁴ Thus, DIC becomes a paradox. It’s a disorder marked by excessive coagulability of the blood at the time a patient may be unable to form new blood clots. Patients may have symptoms of hypoxia and tissue damage secondary to the presence of unnecessary blood clots while they are bleeding from sites as clots are broken down. It is these polar opposites that make DIC difficult to recognize and manage.