DIC

**Pathophysiology** - Massive release of tissue factor (TF) or other procoagulant substances activates the extrinsic pathway (factor VII) → excess thrombin generation → fibrin deposition in small vessels. - Microthrombi cause end-organ ischemia (kidney, brain, lungs, adrenals, skin) and microangiopathic hemolytic anemia (MAHA, schistocytes) as RBCs shear on fibrin strands. - Consumption of platelets, fibrinogen, and factors V and VIII → bleeding. - Thrombin activates plasmin → fibrinolysis → fibrin degradation products (FDPs) and D-dimer, which further impair clotting. - Endogenous anticoagulants (antithrombin, protein C/S) are depleted.

**Common causes (mnemonic: STOP Making Thrombi)** - **S**epsis (especially gram-negative; endotoxin and cytokines such as TNF-α and IL-1 induce TF on monocytes and endothelium) - **T**rauma (especially head injury/brain tissue, which is TF-rich), burns - **O**bstetric complications: amniotic fluid embolism, abruptio placentae, retained dead fetus, HELLP/eclampsia - **P**ancreatitis - **M**alignancy: acute promyelocytic leukemia (AML M3, t(15;17), PML-RARα; granules release procoagulants) and mucin-secreting adenocarcinomas (pancreas, lung, GI) - Transfusion reactions (ABO mismatch), snake venom, heatstroke, giant hemangioma (Kasabach-Merritt), aortic aneurysm

**Clinical features** - Bleeding: oozing from IV sites and surgical wounds, petechiae, ecchymoses, hematuria, GI bleeding. - Thrombosis: acral cyanosis, purpura fulminans, gangrene, AKI, ARDS, altered mental status. - Chronic DIC (malignancy, Trousseau syndrome) tends to be thrombotic rather than hemorrhagic.

**Labs** - ↑ PT and ↑ aPTT (factor consumption) - ↓ Platelets - ↓ Fibrinogen - ↑ D-dimer and FDPs (most sensitive; D-dimer is nonspecific on its own) - ↑ Bleeding time - Peripheral smear: schistocytes and helmet cells - Factor VIII is low in DIC. This distinguishes it from liver disease, where factor VIII is normal or ↑ because it is made by endothelium.

**Differentials commonly tested** - TTP/HUS: MAHA and thrombocytopenia but normal PT/aPTT and fibrinogen. - Liver disease: ↑PT, but normal factor VIII and no consumptive pattern. - Vitamin K deficiency or warfarin: ↑PT, but normal platelets and normal D-dimer. - HELLP: pregnancy-associated, with elevated LFTs, and usually normal coagulation studies early.

**Management** 1. **Treat the underlying cause** (antibiotics for sepsis, delivery of the fetus or placenta, ATRA for APL). This is the most important step. 2. Supportive care with blood products only for active bleeding or high bleeding risk: platelets, FFP (replaces factors), cryoprecipitate (replaces fibrinogen). 3. Heparin is reserved for predominantly thrombotic DIC (for example, purpura fulminans or arterial or venous thromboembolism). It is generally avoided in patients who are bleeding. 4. Antifibrinolytics (tranexamic acid) are generally contraindicated because they risk worsening microvascular thrombosis. They are considered only in severe hyperfibrinolytic bleeding, such as some APL cases.

**High-yield pearls** - DIC is never a primary disease. Always look for the trigger. - DIC is a consumptive coagulopathy, so both clotting and bleeding occur. - Obstetric DIC is often acute and fulminant, from tissue factor release (amniotic fluid embolism, abruption). - APL + DIC is treated with all-trans retinoic acid (ATRA), which induces differentiation of promyelocytes. - Waterhouse-Friderichsen syndrome (meningococcemia with adrenal hemorrhage) is a classic DIC association. - ISTH scoring: platelet count, D-dimer/FDP, PT prolongation, and fibrinogen; a score of 5 or more is consistent with overt DIC.