The college has shown some interest in this condition, but usually, it appears as the answer to a data interpretation question ("What's wrong with these coags?"). Examples include:
Apart from these, DIC comes up frequently in the past papers as an important complication to mention (eg. in the discussion of amniotic fluid embolism, etc etc). Only once have the candidates been asked the fairly relevant question, "how will you manage this situation?" Thankfully, there's plenty of literature, accessible with minimal effort. A basic Google Scholar search for "dissminated intravascular coagulation" will yield a dozen review articles, all titled "Disseminated intravascular coagulation", spanning maybe forty years. The 2016 paper by Boral et al was the main basis for this chapter
This condition has a solid definition, forged from the fires of Mount Doom by the International Society
on Thrombosis and Haemostasis in 2001:
DIC is “...an acquired syndrome characterized by intravascular activation of coagulation with loss of localization arising from different causes that can originate from and cause damage to the microvasculature, which if sufficiently severe, can produce organ dysfunction”
These are the defining features of "overt" DIC. Obviously by the time you have "coagulation with loss of localization" you're already in a pretty bad shape, which is why the same body has proposed a slightly adjusted definition to assist in the making of an earlier diagnosis. They (Iba et al, 2017) framed this adjusted definition in terms of altered parameters, which were all slightly less severe than the original 2001 diagnostic criteria. In this fashion, we have ended up here:
|Total score cut-off:||≥5||≥4|
To simplify this complex system, SIC is a DIC which still hasn't had time to waste all your clotting factors, but which is already associated with the dysfunction of one or more organ systems, because it is associated with sepsis and that's the new definition of sepsis.
Fibrin degradation products seem to be a valuable adjunct for the laboratory diagnosis of DIC.
In essence, a D-dimer is a small protein breakdown product, consising of two crosslinked D-fragments of fibrin. A longer explanation, with pictures and extensive bibliography, is also available. The presence of an elevated D-dimer confirms that somewhere fibrin is being degraded.
If one day the CICM exam candidates are asked, "outline the pathophysiology of DIC in under the minutes", they will have difficulties, unless they've rehearsed this at least once before. Obviously they all know the underlying processes, but to put everything together into a neat structure under pressure and in a short period of time would be challenging for anybody. To prepare them for these end times, here is a pre-digested blurb, describing the pathophysiology of DIC:
The causes of DIC are numerous. Here is a good list of causes, reproduced with zero modification from Papageorgeou et al (2018):
|Clinical Conditions Triggering DIC||Causes of DIC|
|Sepsis or severe infection||Potentially any microorganism but particularly gram-negative bacteria|
|Viral infections (ie, viral hemorrhagic fever)|
|Trauma||Severe tissue injury|
|Heat stroke of shock|
|Organ destruction||Pancreatitis, severe inflammation, tissue necrosis|
|Malignancy||Solid tumors (pancreatic, stomach, colorectal cancer, mucin secreting adenocarcinoma)|
|Hematological malignancies (acute promyelocytic leukemia especially)|
|Obstetrical calamities||Placental abruption|
|Amniotic fluid embolism|
|Vascular abnormalities||Aortic aneurysm|
|Giant hemangiomas (Kasabach-Merritt syndrome)|
|Acute hepatic necrosis|
|Severe toxic or immunological reactions||Graft-versus-host disease|
|Snake bites (such as from those belonging to the genus Echis)|
|Severe transfusion reactions (incompatible blood transfusion reactions)|
In the context of pregnancy and PPH one can narrow down one's list of possibile aetiologies.
Still, there is quite a large number of potential peripartum causes for DIC:
An excellent review article lists these, and others, and delves deep into their pathophysiology and management.
Boral, Benjamin M., Dennis J. Williams, and Leonard I. Boral. "Disseminated intravascular coagulation." American journal of clinical pathology 146.6 (2016): 670-680.
Slofstra, Sjoukje, Arnold Spek, and Hugo ten Cate. "Disseminated intravascular coagulation." The Hematology Journal 4.1 (2013): 295-302.
Levi, Marcel, and Hugo Ten Cate. "Disseminated intravascular coagulation."New England Journal of Medicine 341.8 (1999): 586-592.
Letsky, Elizabeth A. "Disseminated intravascular coagulation." Best Practice & Research Clinical Obstetrics & Gynaecology 15.4 (2001): 623-644.
Carr, J. Meehan, M. McKinney, and J. McDonagh. "Diagnosis of disseminated intravascular coagulation. Role of D-dimer." American journal of clinical pathology 91.3 (1989): 280-287.
Adam, Soheir S., Nigel S. Key, and Charles S. Greenberg. "D-dimer antigen: current concepts and future prospects." Blood 113.13 (2009): 2878-2887.
Iba, Toshiaki, Marcel Levi, and Jerrold H. Levy. "Sepsis-induced coagulopathy and disseminated intravascular coagulation." Seminars in thrombosis and hemostasis. Vol. 46. No. 01. Thieme Medical Publishers, 2020.
Taylor Jr, Fletcher B., et al. "Towards definition, clinical and laboratory criteria, and a scoring system for disseminated intravascular coagulation." Thrombosis and haemostasis 86.11 (2001): 1327-1330.
Iba, Toshiaki, et al. "New criteria for sepsis-induced coagulopathy (SIC) following the revised sepsis definition: a retrospective analysis of a nationwide survey." BMJ open 7.9 (2017): e017046.
Papageorgiou, Chrysoula, et al. "Disseminated intravascular coagulation: an update on pathogenesis, diagnosis, and therapeutic strategies." Clinical and Applied Thrombosis/Hemostasis 24.9_suppl (2018): 8S-28S.
Levi, Marcel, and Marie Scully. "How I treat disseminated intravascular coagulation." Blood, The Journal of the American Society of Hematology 131.8 (2018): 845-854.
Gando, Satoshi, et al. "A randomized, controlled, multicenter trial of the effects of antithrombin on disseminated intravascular coagulation in patients with sepsis." Critical care 17.6 (2013): 1-10.
Aoki, Nobuo, et al. "A comparative double-blind randomized trial of activated protein C and unfractionated heparin in the treatment of disseminated intravascular coagulation." International journal of hematology 75.5 (2002): 540-547.
Saito, H., et al. "Efficacy and safety of recombinant human soluble thrombomodulin (ART‐123) in disseminated intravascular coagulation: results of a phase III, randomized, double‐blind clinical trial." Journal of Thrombosis and Haemostasis 5.1 (2007): 31-41.
Abraham, Edward, et al. "Efficacy and safety of tifacogin (recombinant tissue factor pathway inhibitor) in severe sepsis: a randomized controlled trial." Jama 290.2 (2003): 238-247.
Jaimes, Fabián, et al. "Unfractioned heparin for treatment of sepsis: A randomized clinical trial (The HETRASE Study)." Critical care medicine 37.4 (2009): 1185-1196.