Disseminated intravascular coagulation: Viva

This is the acute, fulminant, thrombosis-dominated disseminated intravascular coagulation of meningococcal sepsis. The structured oral runs from the ISTH score through the cause-driven resuscitation, the components for the bleeding, the heparin for the purpura fulminans, and the anticoagulant evidence. [1][2]

Opening: make the diagnosis

Examiner. The platelet count is 38 times ten to the nine per litre, the fibrinogen is 0.8 grams per litre, and the D-dimer is strongly raised. What is the diagnosis, and how do you confirm it? [1]

Candidate. This is disseminated intravascular coagulation, an acquired, trigger-driven syndrome of the systemic intravascular coagulation, and the trigger here is the septic shock with the purpura fulminans. I confirm it with the ISTH overt-DIC score, which totals the platelet count, the fibrinogen, the D-dimer, and the prothrombin time. This boy scores two for the platelets under fifty, one for the fibrinogen under one gram per litre, three for the strongly raised D-dimer, and at least one for the prolonged prothrombin time, for a total well above five, the threshold for the overt disease. The fragmented red cells on the film are the microangiopathic haemolysis. [1][2]

Examiner (probe). What would make you look for a different trigger? [3]

Candidate. The triggers in children are the sepsis, the malignancy, the trauma, and the obstetric and neonatal catastrophes. If the child had the bruising and the pallor with the blast cells on the film, I would suspect the acute leukaemia, especially the acute promyelocytic leukaemia. If the child had the major trauma or the burns, I would recognise the tissue-factor release. The chronic, low-grade picture with the isolated thrombocytopenia would raise the Kasabach-Merritt haemangioma. The trigger drives both the cause treatment and the prognosis. [3]

Branch 1: the cause-driven resuscitation

Examiner. This boy is in septic shock. What is your first action? [2]

Candidate. The definitive treatment of disseminated intravascular coagulation is the treatment of the trigger, so my first action is the broad-spectrum antibiotics within the first hour, the fluid resuscitation, and the vasopressors, alongside the source control and the paediatric intensive-care referral. The DIC does not resolve until the trigger is removed, and every other measure buys time for the cause treatment to work. The British Committee for Standards in Haematology guideline of Levi and colleagues sets out this cause-driven principle, and it is the central management point. [2]

Examiner (probe). The team wants to transfuse platelets and plasma to bring the score down. Do you agree? [2]

Candidate. I do not transfuse for the score, because the prophylactic transfusion does not change the outcome and it carries its own volume and transfusion risks. I transfuse for the bleeding or the high bleeding risk. The boy receives the platelet transfusion for the count under fifty times ten to the nine per litre, the fresh-frozen plasma at ten to fifteen millilitres per kilogram for the prolonged clotting times, and the cryoprecipitate or the fibrinogen concentrate to hold the fibrinogen over one gram per litre. The score is followed, but the transfusion is driven by the bleeding. [2]

Branch 2: the thrombosis-dominated picture

Examiner. The purpura fulminans and the cool dusky digits are worsening. What do you add? [3]

Candidate. The thrombosis-dominated picture shifts the plan toward the anticoagulation. I add the therapeutic unfractionated heparin, because it is titratable and reversible, and I titrate it to the partial thromboplastin time. I continue the components for the bleeding and the cause treatment, and I involve the plastic surgery early for the skin and the limb salvage, because the survivor may face the amputations and the skin grafting. The heparin does not replace the cause treatment or the components, and it is reserved for the thrombosis-dominated course, because the routine heparin for the bleeding-dominated DIC is not supported. [2][3]

Examiner (probe). A normal fibrinogen was reported earlier. Is that reassuring? [2]

Candidate. It is not reassuring, because the fibrinogen is an acute-phase reactant and it rises in the septic child. A fibrinogen that is normal or only mildly low in the severe sepsis may already be inappropriately low, because the consumption has pulled it down from a raised baseline. I repeat the fibrinogen across the two or three samples, I read the trend, and I treat the falling trend, because the single value understates the consumption. [2]

Branch 3: a different trigger

Examiner. Suppose the trigger were the acute promyelocytic leukaemia. What changes? [3]

Candidate. One critical thing changes: the all-trans retinoic acid is started immediately, the moment the diagnosis is suspected, and not delayed for the confirmatory marrow. The acute promyelocytic leukaemia releases the procoagulant granules from the leukaemic blasts, and the DIC is present at the diagnosis in the majority of children, with the early fatal haemorrhage the chief cause of the early death. The components and the heparin continue as for the sepsis picture, but the all-trans retinoic acid is the measure that prevents the catastrophic early bleed. [3]

Branch 4: the anticoagulant evidence

Examiner. What is the place of the antithrombin concentrate and the recombinant activated protein C? [2]

Candidate. Neither is routine. The antithrombin concentrate, given to replace the consumed antithrombin, has not shown the survival benefit, and it is not recommended routinely. The recombinant activated protein C, the drotrecogin alfa, was withdrawn in 2011 after the PROWESS-SHOCK trial showed no benefit, and it is no longer available. The recombinant soluble thrombomodulin, the ART-123, is the newer agent, and the meta-analysis suggested a benefit in the sepsis-associated coagulopathy with the overt DIC, though the paediatric data remain limited. The cause treatment remains the definitive treatment. [2][4]

Closing: the sepsis-induced coagulopathy score and the prognosis

Examiner. Tell me about the sepsis-induced coagulopathy score and the outlook for this boy. [4]

Candidate. The sepsis-induced coagulopathy score of Iba and colleagues sits upstream of the ISTH score, and it combines the platelet count, the international normalised ratio, and the organ-dysfunction score, with a threshold of four points or more in the child with sepsis. The sepsis-induced coagulopathy state precedes the ISTH overt-DIC state and predicts the high mortality. The outlook for this boy is dominated by the trigger, and the mortality in the severe, intensive-care cases sits around a quarter to a half. With the early antibiotics, the cause treatment, the components for the bleeding, and the heparin for the purpura fulminans, the boy has the best chance, and the daily ISTH score that falls signals the recovery. [4]