Review Question - QID 215125

This patient with a history of lung adenocarcinoma presents with progressive fatigue, petechia, mucosal bleeding, laboratory evidence of anemia, thrombocytopenia, prolonged PT/PTT, elevated D-dimer, and fragmented “schistocyte” red blood cells (RBCs) on peripheral blood smear, most likely has diffuse intravascular coagulation (DIC). Malignancy is one of many triggers for DIC.

DIC is caused by over-activation of platelets and clotting factors with subsequent overconsumption and promotion of widespread hemolytic anemia and bleeding, a process also known as a “consumptive coagulopathy.” Common inciting etiologies for DIC include sepsis, obstetrical complications, acute pancreatitis, trauma, nephrotic syndrome, transfusion, and malignancy; all mechanisms promote extensive up-regulation of tissue factor and thrombin which lead to coagulation. As DIC is a derangement of both primary hemostasis (platelet activation) and secondary hemostasis (clotting cascade), the classic laboratory presentation includes prolonged PT/PTT with elevated D-dimer (from clot fibrin degradation) and thrombocytopenia. DIC is often a critical illness, as patients can quickly destabilize secondary to severe hemolytic anemia, bleeding, and hypotension. Treatment strategies involve administration of fresh frozen plasma, platelets, RBC transfusions, and targeted therapy for the underlying disorder.

Squizzato et al. review supportive treatments for DIC. The authors find that platelet transfusions should be given to maintain platelet count above 50,000/mm^3 in patients who are bleeding. By contrast, the authors recommend a platelet transfusion threshold of 20,000-30,000/mm^3 for DIC without bleeding.

Figure/Illustration A shows a peripheral blood smear with evidence of fragmented RBCs (blue arrows), also known as “schistocytes” or “helmet cells.” In DIC, fibrin and platelets form intravascular microthrombi which mechanically shear RBCs and create the phenomenon known as “microangiopathic hemolytic anemia."

Incorrect Answers:
Answer 1: Autoimmune hemolytic anemia (AHA) is caused by autoantibodies to RBC surface antigen. It is diagnosed by a positive “Coombs test” which reveals clumping of RBCs in the presence of anti-IgG antibodies. While malignancy is a known trigger for AHA, this patient has a negative Coombs test.

Answer 3: Hemolytic uremic syndrome (HUS) is a microangiopathic hemolytic anemia most commonly caused by infection from “Shiga-like toxin” producing O157:H7 E. coli. In contrast to DIC, HUS primarily affects platelets (not clotting factors) and generates platelet microthrombi that shear RBCs; thus PT and PTT are not classically prolonged in HUS.

Answer 4: Immune thrombocytopenia (ITP) is an autoimmune platelet consumptive process driven by anti-GpIIb/IIIa auto-antibodies and can be caused by malignancy, viral illnesses, drug reactions, and autoimmune disorders. In contrast to DIC, ITP classically presents with bleeding, petechia, and isolated thrombocytopenia without evidence of hemolytic anemia.

Answer 5: Myelodysplastic syndrome is a disorder of myeloid progenitor stem cells (often from damage by chemotherapy or radiation) and leads to ineffective hematopoiesis with the potential to transform into acute myeloid leukemia. It presents with anemia, thrombocytopenia, and neutropenia. Unlike in DIC, hemolysis and coagulation are not typical features.

Bullet Summary:
Diffuse intravascular coagulation is caused by infectious or inflammatory activation of the clotting cascade, leading to a consumptive coagulopathy with microangiopathic hemolytic anemia and classic laboratory evidence of thrombocytopenia, prolonged PT/PTT, elevated D-dimer, and “schistocyte” red blood cells (RBCs) on peripheral blood smear.