A Primer on TTP and DIC

TTP and DIC both present with thrombocytopenia and organ injury, but the pattern of clotting versus bleeding points in different directions. TTP is a primary thrombotic microangiopathy with severe hemolysis, while DIC is a secondary consumptive coagulopathy driven by an underlying illness.

Differentiating TTP from DIC

• Shared high-acuity presentation: Both disorders usually announce themselves with a sick, ill-appearing patient, low platelets, and evolving organ damage; isolated thrombocytopenia in a well patient should push you toward another diagnosis.
• Thrombotic versus hemorrhagic pattern: TTP tends to be more thrombotic, causing confusion, stroke, and renal injury from microvascular occlusion, while DIC more often declares itself with bleeding from IV sites, mucosa, or diffuse oozing.
• Core coagulation panel clues: The fastest separator is the lab pattern: TTP often has normal INR, PTT, and fibrinogen, whereas DIC typically shows prolonged coagulation studies with low fibrinogen and a striking D-dimer.
• LDH out of proportion: A markedly elevated LDH, often more than 2 to 3 times normal and out of proportion to the LFT bump, is a classic TTP clue because it reflects both hemolysis and tissue ischemia.
• Peripheral smear hallmark: Schistocytes plus thrombocytopenia anchor the diagnosis of thrombotic microangiopathy and should sharply raise concern for TTP, especially when paired with MAHA and neurologic symptoms. We get into the smear-and-lab pattern recognition in the episode.

TTP pathophysiology and treatment

• ADAMTS13 failure mechanism: TTP is driven by loss of ADAMTS13 activity, usually from an acquired autoimmune inhibitor, leaving ultra-large von Willebrand multimers free to trigger spontaneous platelet aggregation.
• Classic but incomplete pentad: The historical pentad is MAHA, thrombocytopenia, fever, renal failure, and neurologic findings, but waiting for all five is a mistake because most patients do not present with the full set.
• Younger abrupt presentation: TTP often affects younger adults, especially women, and tends to arrive over days with fatigue, bruising, abdominal pain, confusion, and abrupt hematologic deterioration.
• Plasma exchange mainstay: Untreated TTP is essentially universally fatal, and plasma exchange is the key therapy because it removes the inhibitor and replenishes ADAMTS13 rather than just replacing blood products.
• Platelet transfusion caution: Avoid platelets in TTP unless bleeding is catastrophic, because adding platelets can worsen the underlying microthrombotic process; the temporizing bridge when exchange is delayed is covered in the chapter.

DIC pathophysiology and treatment

• Secondary thrombin storm: DIC is a disease-induced coagulopathy caused by uncontrolled thrombin generation, producing simultaneous clot formation, factor consumption, and secondary fibrinolysis.
• Underlying trigger search: DIC is almost always secondary to another critical illness such as sepsis, major trauma, cancer, certain drugs, or obstetric catastrophe, so finding the driver is part of the resuscitation.
• Treat cause and coagulopathy: Management runs on two tracks at once: control the precipitating disease while supporting the coagulopathy, because correcting labs alone will not stop ongoing consumptive injury.
• Magic four components: The transfusion backbone is platelets, fibrinogen replacement, FFP, and pRBCs, each used according to bleeding and laboratory deficits rather than reflexively giving everything to everyone.
• Anticoagulation exception: Routine anticoagulation is generally avoided in DIC, but there are thrombotic phenotypes where that instinct changes. We walk through that bedside distinction in the podcast.

References:

1. Page EE, et al. Thrombotic thrombocytopenic purpura: diagnostic criteria, clinical features, and long-term outcomes from 1995 through 2015. Blood Adv. 2017 Apr 6;1(10):590-600. PMID: 29296701.

2. Wada H, et al; The Scientific Standardization Committee on DIC of the International Society on Thrombosis Haemostasis. Guidance for diagnosis and treatment of DIC from harmonization of the recommendations from three guidelines. J Thromb Haemost. 2013 Feb 4. PMID: 23379279.

3. Rock GA, et al. Comparison of plasma exchange with plasma infusion in the treatment of thrombotic thrombocytopenic purpura. Canadian Apheresis Study Group. N Engl J Med. 1991 Aug 8;325(6)