Disseminated intravascular coagulopathy (DIC) is a lifethreatening complication of a multitude of medical illnesses. Some of these illnesses include malignancies, trauma, infections, liver disease, and obstetrical traumas/disease. It is life-threatening in the way that it causes systemic microvascular thrombosis, consumptive coagulopathy, and as a result multi-organ failure and even death. It primarily affects critically ill patients in the intensive care unit (ICU) with rates reported as high as 35% in those patients admitted with sepsis (1).

It is important to emphasize that DIC itself is not a disease but the critical end point of a specific medical complication. As always, prevention is key to avoiding severe morbidity and mortality. As such, the key to preventing DIC is understanding the pathophysiology that could lead to this critical situation and first correcting the underlying etiology. This requires timely and knowledgeable action on the physician’s part to avoid adverse outcomes.

It is commonly known that the maternal morbidity and mortality rate in the United States is on the rise when compared to other developed nations. The top causes of pregnancy-related deaths in the United States are cardiovascular disease, infection, and hemorrhage. DIC is the most common complication from peripartum hemorrhage, which is still the leading cause of worldwide maternal mortality (2,3). The reported incidence of DIC ranges from 0.03% to 0.35% in all pregnancies but more impressively, it has been reported to occur in >50% of cases with obstetrical complications such as placental abruption and amniotic fluid embolism (4).

By recognizing some key clinical features, it is frequently possible to rapidly identify and treat the underlying etiology of the DIC and to largely prevent severe maternal morbidity and mortality. In this chapter, the normal physiologic response to pregnancy of the coagulation system will be presented, along with an easily remembered approach to the clotting cascade that helps in the diagnosis of DIC at the bedside.

The hemostatic system is known to be complex in its intricate balance of fibrin generation and fibrinolysis. Typically, an inciting event will cause an activation of the clotting cascade, but to not have such an exaggerated response, the heavily regulated fibrinolytic system comes into play.

Pregnancy is a unique condition that causes maternal blood volume to increase 50% by the end of pregnancy (5). The mother’s body is at significant risk of hemorrhage around the time of placental implantation and the third stage of labor. To not cause significant harm from this physiologic pregnancy adaptation, the hemostatic system also adapts by balancing these different factors in a way that is procoagulant during the gestational period. Although this does increase the risk for venous thromboembolism, pregnant women overall have uncomplicated pregnancies owing to the fibrinolytic adaptations noted in response to this.

Normal clotting can be viewed in a simplified manner that helps the clinician deal with DIC. When endothelial disruption occurs, platelets and fibrin rapidly adhere to the area of endothelial damage. The fibrin helps stabilize the platelets and provides a meshwork for the clot to form. A feedback mechanism provided by plasmin, protein C, and protein S regulates the size of the clot in a process of fibrinolysis that creates fibrin split products (FSPs) that are cleared via the kidney.

In this chapter, we have taken a pragmatic approach to the coagulation cascade with an abbreviated and simplified algorithm shown in Figure 6.3.1. The intent is to ensure ongoing
memory of the crucial components related to clinical management, rather than to present a detailed and intricate cascade that may not be front of mind during a clinical crisis. Using graphic representation and mnemonics, the reader can picture the important components of the clotting cascade with a simple memory aid. The intention here is not to show the cascade in its finest detail but rather to highlight the most important practical aspects that are used by the clinician at the bedside. The reader should view the algorithm as such, and if a more detailed exposition of the clotting cascade is needed, there are many excellent articles and chapters that address this in detail.

The extrinsic (also called tissue factor [TF]) pathway (e), whose function is measured using the prothrombin time (PT or international normalized ratio [INR]), is depicted on the left of the figure (labeled PeT, whereby the “e” in PT stands for “extrinsic”) and the intrinsic pathway (i), whose function is assessed using the partial thromboplastin time (PTT) (labeled PiTT, where “i” stands for “intrinsic”) is shown on the right side of the figure (Figure 6.3.1).

Under the extrinsic pathway (“PeT”) the mnemonic “CaT-7” is used to represent calcium, TF, and factor VII. The memory aid here is that a CaT is a PeT. TF originates from an outside (extrinsic) source and activates the clotting cascade with examples being abruption or endotoxin from an infection.

If the PT is prolonged, it is usually an indication that the extrinsic pathway (CaT-7) is taking a prolonged time to make fibrin in vitro. If the PTT is prolonged, the intrinsic system is taking a long time to produce fibrin in vitro.

On the right side of the figure under “PiTT” (intrinsic pathway) is “8, 9, 11, 12, and platelets,” representing factors VIII, IX, XI, and XII as well as platelets.

The extrinsic and intrinsic pathways meet up at a common pathway that consumes calcium and activates factors V and X. A convenient memory aid is “Calcium, Five, and Dime.”

The common pathway drives a number of important steps in the coagulation cascade that each catalyzes the next, and which can be remembered by the successive lines “prothrombin to thrombin,” with thrombin driving “fibrinogen to fibrin,” and finally fibrin catalyzing “plasminogen to plasmin,” which feeds back to break down fibrin via fibrinolysis and to produce FSPs. Increased FSPs indicate active fibrinolysis. Refer to Figure 6.3.1 for the completed “practical” clotting cascade.

In vivo, both the extrinsic (TF) and intrinsic pathways are required to make fibrin. In fact, people who have abnormal function of one arm are unable to make fibrin because the other arm cannot compensate.

Initially, TF binds to activated factor VII (VIIa) and progresses down the common pathway, making a small amount of activated factor X (Xa), thrombin, and fibrin.

The small amount of thrombin and fibrin produced by the extrinsic TF pathway then activates the intrinsic pathway, which becomes self-sustaining and drives the production of fibrin.

Of note, as soon as factor Xa is produced, it interacts with TF pathway inhibitor (TFPI) to turn off the extrinsic TF pathway and leave the intrinsic pathway as the sole driver of the coagulation cascade.

FSPs are commonly recognized as D-dimer.

The intrinsic pathway, apart from initiating coagulation, can also activate another multiprotein cascade known as the Kinin-Kallikrein system, releasing bradykinin (a potent peptide vasodilator). Bradykinin can cause severe hypotension, often out of proportion to observed blood loss, and as such, hypotension of this sort should be regarded as a potential early sign of DIC.