Blood & Lymphoreticular

Disseminated intravascular coagulation: recognition and management

Clinical Overview and When to Suspect DIC

— Tissue factor exposure → thrombin burst → fibrin deposition in microvasculature → consumption of platelets, fibrinogen, factors V/VIII → secondary fibrinolysis → bleeding.

— Result: a patient who is paradoxically clotting and bleeding at the same time.

— Oozing from IV sites, surgical wounds, mucosa, or catheter insertions

— New thrombocytopenia + prolonged PT/aPTT + low fibrinogen + elevated D-dimer

— Acrocyanosis, purpura fulminans, or new organ dysfunction (AKI, ARDS, delirium)

— Sepsis (especially gram-negative; #1 cause overall)

— Trauma (crush injury, burns, head injury — brain is tissue-factor rich)

— Obstetric: amniotic fluid embolism, placental abruption, retained products, HELLP, severe preeclampsia

— Malignancy: APL (M3 AML) — classic boards trigger; mucin-secreting adenocarcinomas (pancreas, gastric, prostate) → chronic DIC/Trousseau

— Toxins/envenomation, transfusion reactions, severe pancreatitis, heat stroke, giant hemangioma (Kasabach-Merritt)

— Acute (sepsis, AFE, APL): overt bleeding dominant, labs markedly abnormal

— Chronic (malignancy): compensated, thrombosis dominant (Trousseau migratory thrombophlebitis), labs subtler

Board pearl: On Step 3, if a septic ICU patient suddenly oozes from three line sites with platelets 60k, fibrinogen 90, INR 1.9, and D-dimer >10× — call it DIC and treat the underlying cause first, blood products second. DIC is never a primary diagnosis — always hunt the trigger.

Step 3 management: Order ISTH DIC score components (platelets, PT, fibrinogen, D-dimer) at recognition and trend q6–12h during active resuscitation.

Definition: Disseminated intravascular coagulation (DIC) is an acquired syndrome of systemic intravascular activation of coagulation, leading to simultaneous microvascular thrombosis and consumptive coagulopathy with bleeding.

Pathophysiology in one breath:

Always think DIC when a critically ill patient develops:

Top precipitating conditions (memorize):

Acute vs chronic DIC:

Presentation Patterns and Key History

— Fever, hypotension, tachypnea, altered mentation; often gram-negative bacteremia, meningococcemia (with purpura fulminans), or post-splenectomy pneumococcal sepsis

— Bleeding develops 24–72 h into ICU course as cytokine storm matures

— Amniotic fluid embolism: sudden hypoxia, hypotension, cardiovascular collapse during labor or immediately postpartum, followed by torrential hemorrhage

— Placental abruption: painful vaginal bleeding + rigid uterus + fetal distress

— HELLP/severe preeclampsia: RUQ pain, headache, hypertension, hemolysis

— Retained dead fetus syndrome: chronic low-grade DIC weeks after intrauterine fetal demise

— APL (AML M3): young/middle-aged adult with pancytopenia, gum bleeding, hematuria, and DIC labs — start ATRA immediately, do not wait for cytogenetics

— Trousseau syndrome: migratory superficial thrombophlebitis in pancreatic/gastric adenocarcinoma; recurrent VTE despite warfarin → switch to LMWH

— Bleeding: oozing IV/wound sites, petechiae, hematuria, GI bleed, intracranial hemorrhage

— Thrombosis: digital ischemia, AKI, ARDS, delirium, DVT/PE

— Organ failure: oliguria, hypoxia, confusion, jaundice

Key distinction: Isolated thrombocytopenia + bleeding in a hospitalized patient without coagulopathy = think HIT, ITP, drug-induced, not DIC. DIC needs both platelet drop and coagulation factor consumption (low fibrinogen, prolonged PT).

Board pearl: A postpartum patient with sudden dyspnea, hypotension, seizure, then uterine hemorrhage = amniotic fluid embolism with DIC until proven otherwise. Mortality is high; activate massive transfusion protocol.

CCS pearl: In the simulated case, the first orders are "IV access ×2, type and cross 6 units, CBC, PT/INR, aPTT, fibrinogen, D-dimer, peripheral smear" — order them before specialty consults.

History is driven by the precipitant — DIC rarely walks in the door alone. Anchor your stem-reading on these patterns:

Septic DIC (most common):

Obstetric DIC — high yield:

Trauma/burn DIC: massive transfusion, crush injury, TBI ("brain TF release"), >40% TBSA burns

Malignancy-associated:

Symptom triad to elicit:

Physical Exam Findings (and Hemodynamic Assessment)

— Petechiae on dependent surfaces and pressure points

— Ecchymoses at venipuncture, BP cuff, ECG lead, and surgical sites

— Purpura fulminans: retiform purpura progressing to hemorrhagic bullae and skin necrosis — classic in meningococcemia and protein C deficiency

— Acrocyanosis and digital gangrene (symmetric peripheral gangrene) from microvascular occlusion of fingers, toes, nose, ears — often despite palpable pulses

— Pulmonary: hypoxia, bilateral crackles → ARDS picture

— Renal: oliguria, rising Cr → AKI

— CNS: focal deficits, seizures, coma

— Hepatic: jaundice, RUQ tenderness

— GI: ileus, bloody stools

— Vitals: hypotension, narrow pulse pressure, tachycardia, tachypnea

— Cap refill >3 s, mottling (Mottling score ≥2 portends mortality)

— Bedside echo if AFE suspected: acute RV failure, severe pulmonary hypertension

Key distinction: Purpura fulminans in DIC vs calciphylaxis vs warfarin-induced skin necrosis — all retiform purpura. Context (sepsis vs ESRD vs day 3–5 of warfarin without bridge) and protein C levels distinguish them.

Board pearl: Symmetric peripheral gangrene with palpable pulses in a septic ICU patient = DIC with microvascular thrombosis. Do not rush to vascular surgery — manage DIC and shock first; many digits demarcate and self-amputate.

Step 3 management: Document skin findings with photo or detailed map at admission and reassess q12h; rapid progression of purpura mandates ICU escalation.

General appearance: ill-appearing, often febrile, tachycardic, hypotensive; mental status changes from microvascular cerebral thrombi or hypoperfusion.

Skin — the most visually diagnostic system:

Mucosal bleeding: gingival oozing, epistaxis, hematuria, hemoptysis, melena/hematochezia

Sites of recent instrumentation: persistent oozing from central line, A-line, Foley, intubation trauma, surgical drains is a near-pathognomonic clue

Organ-specific signs of microthrombosis:

Hemodynamic assessment:

Obstetric exam: uterine atony/tone, lochia volume, expulsion of clots; abdominal rigidity in abruption.

Diagnostic Workup — Initial Labs

— CBC with platelets and smear: thrombocytopenia (often 50–100k, falling trend more important than absolute number); smear shows schistocytes (microangiopathic hemolysis), though fewer than in TTP/HUS

— PT/INR and aPTT: both prolonged from factor consumption; PT often more deranged early (factor VII shortest half-life)

— Fibrinogen: low (<200 mg/dL concerning; <100 critical). Caveat: fibrinogen is an acute-phase reactant — a "normal" fibrinogen in septic DIC may actually be inappropriately low; trending matters

— D-dimer / fibrin degradation products: markedly elevated (usually >5× upper limit)

— Peripheral smear: schistocytes, decreased platelets, polychromasia

— Haptoglobin ↓, LDH ↑, indirect bilirubin ↑ (microangiopathic hemolysis)

— Antithrombin and protein C levels ↓ (consumed) — prognostic

— Type and screen/crossmatch, fibrin monomers if available

— Platelets: >100 = 0, 50–100 = 1, <50 = 2

— Elevated fibrin marker (D-dimer): no rise = 0, moderate = 2, strong = 3

— PT prolongation: <3 s = 0, 3–6 s = 1, >6 s = 2

— Fibrinogen: >100 = 0, <100 = 1

— Score ≥5 = overt DIC; <5 = suggestive, repeat in 24–48 h

— Blood cultures ×2, urine culture, CXR, lactate, procalcitonin

— β-hCG in any reproductive-age female

— Tumor markers/imaging if malignancy suspected

— Toxicology if envenomation

Board pearl: D-dimer is the most sensitive but least specific; fibrinogen <100 is the most specific DIC lab. A normal D-dimer essentially rules out DIC.

CCS pearl: Order the DIC panel q6h during active resuscitation; trending fibrinogen and platelets guides product replacement and signals response to source control.

Core DIC panel (order all four at recognition and serially):

Supportive labs:

ISTH overt DIC score (memorize the components):

Underlying cause workup (parallel, not sequential):

Diagnostic Workup — Advanced and Confirmatory Studies

— TTP: ADAMTS13 activity <10% with inhibitor; pentad rarely complete — pursue plasma exchange empirically if MAHA + thrombocytopenia + normal PT/aPTT

— HIT: 4Ts score → PF4 ELISA → serotonin release assay; normal fibrinogen, isolated thrombocytopenia, recent heparin exposure

— HUS: Shiga toxin assay, stool culture for E. coli O157:H7, or atypical HUS workup (complement)

— Liver failure coagulopathy: factor VIII is normal or elevated in liver disease but LOW in DIC (key discriminator — VIII is not made in liver and is consumed in DIC)

— Vitamin K deficiency: isolated PT prolongation, normal fibrinogen, normal platelets

— HELLP: LFTs, schistocytes, in pregnant patient with hypertension

— CT abdomen/pelvis: malignancy, abruption, retained products, pancreatitis

— CT head: if altered mental status or new focal deficit (rule out ICH)

— CTA chest: PE vs AFE workup

— Bedside US: free fluid, uterine clot

— Peripheral smear: hypergranular promyelocytes, Auer rods, faggot cells

— Confirm with PML-RARA FISH or RT-PCR for t(15;17)

— Do not wait for confirmation — start ATRA immediately at suspicion

Key distinction: TTP vs DIC — both have thrombocytopenia and schistocytes, but PT/aPTT and fibrinogen are normal in TTP. This single distinction guides therapy (PLEX vs DIC management) and is one of the highest-yield USMLE Step 3 hematology discriminations.

Board pearl: Factor VIII level — normal/high in liver disease, low in DIC — is the classic boards-favorite tiebreaker when both PT and aPTT are prolonged.

DIC is a clinical-laboratory diagnosis; there is no single confirmatory test. Goals of advanced testing: (1) exclude mimics, (2) identify trigger, (3) guide therapy.

Rule out key mimics with targeted tests:

Thromboelastography (TEG/ROTEM): increasingly used in trauma and obstetric hemorrhage — distinguishes hyperfibrinolysis from factor deficiency from platelet dysfunction; guides targeted product replacement.

Imaging when indicated:

For suspected APL (high-yield):

Risk Stratification and Management Logic

— (1) Treat the underlying cause — antibiotics for sepsis, delivery for obstetric DIC, ATRA for APL, surgical source control for trauma. DIC will not resolve until the trigger is addressed.

— (2) Supportive hemostatic therapy — replace what is consumed only if bleeding or high bleeding risk (pre-procedure, neurosurgical).

— Bleeding-dominant phenotype (obstetric, trauma, post-op, APL): aggressive product replacement; avoid anticoagulants

— Thrombotic-dominant phenotype (chronic DIC, Trousseau, purpura fulminans): consider therapeutic anticoagulation (LMWH preferred)

— Asymptomatic lab abnormalities only: treat underlying disease; do not transfuse based on numbers alone

— Platelets <50k + bleeding (or <20k without bleeding, <100k if CNS bleed/neurosurgery) → platelet transfusion

— Fibrinogen <150 mg/dL with bleeding (or <200 in obstetric hemorrhage) → cryoprecipitate or fibrinogen concentrate

— INR >1.5 with bleeding → FFP 10–15 mL/kg

— Hb <7 (or <8 with cardiac disease) → pRBC

— Score ≥5 correlates with mortality up to 40–80%

— Trending score predicts response better than single value

— Confirmed VTE, purpura fulminans, chronic DIC with thrombosis dominant

— Avoid in active bleeding, recent CNS bleed, or platelets <50k without correction

Step 3 management: Do not transfuse a non-bleeding DIC patient just because the platelets are 40k or INR is 1.8 — treat the trigger, monitor, and reserve products for active bleeding or planned invasive procedures.

Board pearl: The mantra is "treat the patient, not the lab." Boards punish reflexive FFP and platelet transfusion in stable, non-bleeding DIC.

Two pillars, always, in this order:

Risk-stratify by clinical phenotype:

Transfusion thresholds in DIC (memorize):

ISTH score for prognosis:

Anticoagulation indications:

Pharmacotherapy — First-Line Regimens

— Sepsis: broad-spectrum antibiotics within 1 hour of recognition (Surviving Sepsis bundle), source control, fluid resuscitation 30 mL/kg crystalloid, norepinephrine first-line vasopressor

— APL: ATRA (all-trans retinoic acid) 45 mg/m²/day divided BID + arsenic trioxide (or anthracycline in high-risk) — start at suspicion, before cytogenetic confirmation

— Obstetric: delivery is definitive; uterotonics (oxytocin, methylergonovine, carboprost, misoprostol), tranexamic acid within 3 h of postpartum hemorrhage onset

— Malignancy-associated chronic DIC (Trousseau): LMWH (enoxaparin 1 mg/kg SC BID) — warfarin fails in Trousseau

— FFP 10–15 mL/kg if INR >1.5 with bleeding

— Cryoprecipitate 10 units (or fibrinogen concentrate 4 g) if fibrinogen <150 with bleeding; goal >150–200

— Platelets 1 apheresis unit if <50k with bleeding; goal >50k

— pRBC to Hb >7 (>8 if cardiac/CNS)

— Tranexamic acid (TXA): strong evidence in trauma (CRASH-2) within 3 h and postpartum hemorrhage (WOMAN trial)

— Contraindicated in DIC from APL (worsens microthrombi) and in upper urinary tract bleeding

— LMWH for thrombotic-phenotype DIC, Trousseau, purpura fulminans

— Therapeutic heparin infusion if VTE confirmed and bleeding controlled

— PCC (4-factor) if life-threatening bleed on warfarin contributing

— Antithrombin and recombinant thrombomodulin — used in Japan, not standard US care

— Activated protein C withdrawn from market (PROWESS-SHOCK negative)

Board pearl: In suspected APL, start ATRA before bone marrow biopsy results return — early ATRA reduces fatal hemorrhage. Hold tranexamic acid; combination risks fatal thrombosis.

Step 3 management: Order TXA 1 g IV over 10 min, then 1 g over 8 h, for trauma or PPH presenting within 3 hours.

Underlying-cause-directed therapy (the real treatment):

Blood product replacement (bleeding or pre-procedure only):

Antifibrinolytics:

Anticoagulation:

Specific factor concentrates:

Procedures and Invasive Management

— Surgical: drain abscesses, debride necrotic tissue, evacuate retained products of conception, control trauma hemorrhage with damage-control surgery

— Interventional radiology: uterine artery embolization for refractory PPH, splenic/hepatic artery embolization for trauma

— Obstetric: emergent delivery for abruption, AFE, severe HELLP; B-Lynch suture, intrauterine balloon tamponade, peripartum hysterectomy as last resort

— Activate when anticipated need >10 units pRBC in 24 h or hemorrhagic shock

— 1:1:1 ratio of pRBC : FFP : platelets (PROPPR trial)

— Add cryoprecipitate every 6 units pRBC to keep fibrinogen >150–200

— Calcium gluconate 1 g IV every 4 units of product (citrate chelation)

— Goal: temp >36°C, pH >7.2, ionized Ca >1.1, fibrinogen >150

— Avoid subclavian (non-compressible) in coagulopathic patient — prefer femoral or ultrasound-guided IJ

— Correct platelets to >50k and INR <1.5 before non-emergent line placement

— Lumbar puncture, epidural: platelets >50k, INR <1.5, fibrinogen >100

— Neurosurgery: platelets >100k

— Do not give recombinant factor VIIa routinely — increases arterial thrombosis without mortality benefit

— Do not transfuse to "normalize" labs in stable non-bleeding patient

— Do not start prophylactic heparin in actively bleeding DIC patient — consider mechanical DVT prophylaxis (SCDs) instead

CCS pearl: When you activate MTP in CCS, order in packages ("MTP package 1: 6 pRBC, 6 FFP, 1 apheresis platelets, 10 cryo") and reassess vitals/labs after each package — that mirrors real trauma bay choreography.

Board pearl: Femoral central line in a coagulopathic, bleeding patient is the boards-correct choice — compressible site, lowest mechanical complication risk.

Source control is therapy:

Massive transfusion protocol (MTP):

Central access and lines:

Procedural prophylaxis thresholds:

Avoid these traps:

Special Populations — Elderly and Renal/Hepatic Impairment

— Higher baseline comorbidity → lower physiologic reserve; sepsis-associated DIC carries 60–80% mortality in patients >75

— Atypical sepsis presentation: hypothermia, delirium, falls — may delay DIC recognition

— Higher risk of transfusion-associated circulatory overload (TACO) → transfuse pRBC slowly (1 unit over 2–4 h), pre-furosemide if cardiac history

— Polypharmacy: review for anticoagulants, antiplatelets, SSRIs that worsen bleeding

— Discuss goals of care early — DIC in advanced age often signals end-stage disease trajectory

— Uremia adds platelet dysfunction independent of count → consider DDAVP 0.3 mcg/kg IV for uremic bleeding

— LMWH accumulates in CrCl <30 → use unfractionated heparin infusion instead, or dose-reduce enoxaparin to 1 mg/kg daily with anti-Xa monitoring

— Citrate from massive transfusion is renally cleared — monitor ionized calcium closely

— AKI from DIC microthrombi often requires CRRT in ICU

— Liver disease coagulopathy mimics DIC: prolonged PT/aPTT, low platelets (splenic sequestration), low fibrinogen in advanced cirrhosis

— Discriminator: Factor VIII is normal/elevated in liver disease, low in DIC; fibrinogen drops late in cirrhosis

— Avoid FFP "to correct INR" in stable cirrhotic without bleeding — increases portal pressure and bleeding risk

— Vitamin K 10 mg IV/SC if nutritionally deficient or on antibiotics — quick test for reversible component

— Lower transfusion thresholds for organ-vulnerable patients (cardiac, CNS)

— Reassess all anticoagulant and antiplatelet medications

Key distinction: Cirrhosis vs DIC — both have low platelets, prolonged PT, sometimes low fibrinogen, and elevated D-dimer. Factor VIII level and clinical trajectory (acute deterioration vs chronic stable) separate them.

Step 3 management: In the elderly DIC patient, document a code status conversation within 24 h of admission — high mortality makes this a quality metric.

Elderly:

Renal impairment:

Hepatic impairment:

Both populations:

Special Populations — Pregnancy and Pediatrics

— Amniotic fluid embolism (AFE): sudden cardiopulmonary collapse during labor/delivery → DIC in 80%. Management: ACLS, immediate delivery if antepartum, MTP, supportive ICU care. Mortality 20–60%.

— Placental abruption: painful bleeding + rigid uterus + fetal distress. Deliver emergently; type and cross; MTP if hemodynamically unstable.

— HELLP syndrome: delivery is definitive; magnesium for seizure prophylaxis; antihypertensives (labetalol, hydralazine, nifedipine); steroids if <34 weeks for fetal lung maturity

— Retained dead fetus syndrome: chronic low-grade DIC if IUFD retained >4 weeks; deliver and consider heparin if severe coagulopathy

— Postpartum hemorrhage: uterotonics → TXA within 3 h → balloon → embolization → hysterectomy

— Septic abortion: broad-spectrum antibiotics + uterine evacuation

— Neonatal DIC: sepsis (group B strep, E. coli), severe asphyxia, NEC, congenital infection (TORCH). Often presents with petechiae, pulmonary hemorrhage, IVH.

— Purpura fulminans neonatal: consider homozygous protein C or S deficiency — give protein C concentrate and FFP, then long-term anticoagulation

— Pediatric sepsis: meningococcemia is the classic boards trigger for pediatric DIC with purpura fulminans

— Weight-based product dosing: pRBC 10–15 mL/kg, FFP 10–15 mL/kg, platelets 10 mL/kg, cryo 5–10 mL/kg

Board pearl: A neonate with purpura fulminans within hours of birth and no infectious source = homozygous protein C deficiency until proven otherwise.

Step 3 management: For obstetric hemorrhage with DIC, the answer is almost always deliver the fetus and placenta + uterotonics + TXA + MTP, not "watchful waiting."

Pregnancy — obstetric DIC is a top USMLE scenario:

Pregnancy-specific labs: fibrinogen is physiologically elevated to 400–600 mg/dL at term — a "normal" 250 in a bleeding parturient is dangerously low. Use pregnancy-adjusted thresholds: replace cryo to keep fibrinogen >200.

Pediatrics:

Complications and Adverse Outcomes

— Intracranial hemorrhage (highest mortality contributor)

— Massive GI bleeding, pulmonary hemorrhage, retroperitoneal hematoma

— Surgical site bleeding requiring re-exploration

— Compartment syndrome from intramuscular bleeding

— AKI from glomerular microthrombi → may require RRT

— ARDS from pulmonary microthrombi and inflammatory injury

— Symmetric peripheral gangrene → digit/limb amputation

— Hepatic dysfunction, cholestasis, ischemic hepatitis

— Adrenal hemorrhage (Waterhouse-Friderichsen) in meningococcemia → adrenal insufficiency requiring hydrocortisone

— Stroke, mesenteric ischemia, MI from large-vessel thrombosis

— TACO (volume overload): more common in elderly, cardiac patients → slow infusion, diuretics

— TRALI (transfusion-related acute lung injury): bilateral infiltrates within 6 h, non-cardiogenic → supportive care, report to blood bank

— Hypocalcemia from citrate (in massive transfusion) → tetany, prolonged QT; replace with calcium gluconate

— Hyperkalemia from older pRBC units; dilutional thrombocytopenia and coagulopathy worsen DIC

— Hypothermia from rapid infusion → use blood warmers

— Acute hemolytic reaction from ABO mismatch — fever, back pain, hemoglobinuria

— Chronic kidney disease post-AKI

— Post-ICU syndrome, PTSD, functional decline

— Critical illness myopathy/neuropathy

— Limb loss requiring rehabilitation and prosthetics

Key distinction: TACO vs TRALI — both cause respiratory distress during/after transfusion. TACO: elevated BNP, JVD, responds to diuretics. TRALI: normal BNP, no volume overload, supportive care only.

Board pearl: Mortality in overt DIC is driven more by the underlying disease (sepsis, malignancy, trauma) than by the coagulopathy itself — which is why source control trumps factor replacement.

Step 3 management: Monitor ionized calcium every 4 units of blood product in MTP and replace aggressively — citrate toxicity is reversible and easily missed.

Hemorrhagic complications:

Thrombotic complications:

Transfusion-related complications:

Long-term sequelae:

When to Escalate Care — ICU, Consultation, and Triage

— Hemodynamic instability requiring vasopressors

— Respiratory failure or ARDS

— Active major bleeding requiring MTP

— Need for CRRT, mechanical ventilation, or invasive monitoring

— Rapidly progressing purpura fulminans

— ISTH score ≥5 with organ dysfunction

— Hematology: all overt DIC, especially if APL or atypical course

— Critical care/intensivist: as above

— Surgery/trauma: source control needs, debridement, vascular complications

— OB/GYN: any pregnant or postpartum patient

— Maternal-fetal medicine: complex obstetric DIC

— Oncology: suspected malignancy, urgent ATRA for APL

— Infectious disease: atypical sepsis, resistant organisms

— Nephrology: AKI requiring CRRT

— Blood bank/transfusion medicine: MTP, refractory bleeding, antibody complications

— Palliative care: prognosis discussions in elderly or end-stage disease

— Transfer to tertiary center if no MTP capability, no IR, no specialty support

— Stabilize first: airway, hemorrhage control, type-specific blood, communicate labs and products given

— Use EMTALA-compliant transfer protocols

— Off vasopressors >24 h

— No active bleeding ×24 h

— Trending labs: platelets rising, fibrinogen >200, INR <1.5, D-dimer falling

— Underlying cause controlled

CCS pearl: In the simulated case, order ICU transfer simultaneously with initial resuscitation — do not wait for labs to "declare" the patient sick. The clock penalizes delayed escalation.

Step 3 management: Document a structured handoff (SBAR) at every transition: ED → ICU, ICU → floor, hospital → SNF. Transitions of care are a top Step 3 patient-safety theme.

Board pearl: A pregnant patient with suspected AFE goes to ICU with OB and anesthesia at bedside, not to the regular postpartum floor.

ICU admission criteria (essentially all overt DIC):

Consultations to obtain early:

Transfer considerations:

Step-down/floor criteria (when DIC resolves):

Key Differentials — Same-Category (Coagulopathy) Causes

— Pentad: MAHA, thrombocytopenia, fever, neuro changes, renal dysfunction (rarely all 5)

— ADAMTS13 <10% with inhibitor

— Normal PT, aPTT, fibrinogen — the key discriminator from DIC

— Treatment: plasma exchange (PLEX) + steroids + caplacizumab; do NOT transfuse platelets unless life-threatening bleed

— Children with bloody diarrhea (Shiga toxin, E. coli O157:H7)

— Atypical HUS in adults — complement dysregulation, treat with eculizumab

— Normal coagulation studies; AKI prominent

— Platelets drop 30–50% from baseline 5–10 days after heparin start (or within hours if prior exposure)

— Thrombosis without bleeding; normal PT/aPTT/fibrinogen

— 4Ts score → PF4 ELISA → SRA confirms

— Stop ALL heparin (including flushes); start argatroban or bivalirudin

— Isolated thrombocytopenia, often <30k, otherwise well patient

— Normal coagulation; diagnosis of exclusion

— Treat with steroids, IVIG, or anti-D if Rh+

— Prolonged PT, low platelets, factor VIII normal/high, fibrinogen preserved until late

— Often "balanced" coagulopathy — bleeding and clotting risk both elevated

— Isolated PT prolongation initially, then aPTT; normal fibrinogen and platelets

— Reverse with vitamin K ± PCC for life-threatening bleed

— Isolated aPTT prolongation; mixing study fails to correct in inhibitor

Key distinction: Memorize this single line — DIC = low platelets + prolonged PT/aPTT + low fibrinogen + high D-dimer. TTP/HUS/HIT/ITP all have normal PT/aPTT/fibrinogen. Liver disease has normal factor VIII.

Board pearl: A post-op cardiac patient on heparin with new thrombosis and platelet drop is HIT, not DIC, until 4Ts and PF4 say otherwise.

Thrombotic thrombocytopenic purpura (TTP):

Hemolytic uremic syndrome (HUS):

Heparin-induced thrombocytopenia (HIT):

Immune thrombocytopenia (ITP):

Liver disease coagulopathy:

Vitamin K deficiency / warfarin effect:

Hemophilia or acquired factor inhibitor:

Key Differentials — Other-Category Causes

— Sepsis can cause mild thrombocytopenia, transaminitis, and elevated D-dimer without meeting ISTH overt criteria — "sepsis-induced coagulopathy" (SIC) is the precursor; treat the sepsis, monitor for progression

— Dilutional thrombocytopenia and factor deficiency from large-volume resuscitation

— Overlaps with DIC in trauma — both can coexist

— Use 1:1:1 ratio and TXA to prevent

— Multi-organ thrombosis in days; positive antiphospholipid antibodies

— Treat with anticoagulation, steroids, plasmapheresis, IVIG, rituximab

— Defibrination syndrome mimics DIC; treat with antivenom

— Both DIC and hyperfibrinolysis; ATRA is lifesaving

— Hemolysis, elevated LFTs, low platelets — overlaps with DIC but classically has normal PT/aPTT unless DIC supervenes; delivery is treatment

— Hypoglycemia, hyperammonemia, coagulopathy from hepatic synthetic failure plus DIC — delivery and supportive care

— Quinine, vancomycin, linezolid, GP IIb/IIIa inhibitors — isolated platelet drop; stop drug

— Inflammation, hemoconcentration, then dilution-coagulopathy and DIC; aggressive fluid resuscitation per Parkland formula plus monitoring

— Endothelial injury → DIC; rapid cooling is first-line treatment

Key distinction: CAPS vs DIC — CAPS has antiphospholipid antibodies (lupus anticoagulant, anti-cardiolipin, anti-β2GP1), is dominated by thrombosis, and responds to anticoagulation + immunosuppression rather than blood product replacement.

Board pearl: When the stem mentions a young woman with recurrent miscarriages, prior DVT, and now multi-organ thrombosis with thrombocytopenia, think CAPS, not DIC — and anticoagulate, do not transfuse platelets.

Severe sepsis without overt DIC:

Massive transfusion-induced coagulopathy:

Catastrophic antiphospholipid syndrome (CAPS):

Snake envenomation (e.g., rattlesnake):

Acute promyelocytic leukemia (APL) — overlap with DIC:

HELLP syndrome:

Acute fatty liver of pregnancy:

Drug-induced thrombocytopenia:

Severe burns:

Heatstroke and hyperthermia:

Secondary Prevention, Discharge Planning, and Long-Term Care

— Underlying trigger controlled (source-controlled infection, completed APL induction, delivered placenta, surgical hemostasis confirmed)

— DIC labs normalized or near-normal for >48 h

— No active bleeding, hemodynamically stable, off vasopressors

— Tolerating enteral nutrition, ambulating with PT clearance

— If DVT/PE occurred during DIC course: anticoagulate for at least 3 months (LMWH preferred if active cancer; DOAC or warfarin otherwise)

— Cancer-associated VTE: LMWH or edoxaparin/rivaroxaban/apixaban per CHEST/ASCO guidelines

— Mechanical DVT prophylaxis (SCDs) and early ambulation during hospitalization

— APL: completion of consolidation and maintenance ATRA/arsenic for ~2 years; PCR monitoring for MRD; survivorship clinic

— Sepsis survivors: post-sepsis syndrome screening (cognition, physical function, depression); pneumococcal and influenza vaccination if indicated

— Obstetric: Rh immunoglobulin if indicated; contraception counseling; follow-up at 1–2 weeks postpartum then 6 weeks; assess for postpartum depression

— Malignancy-associated: oncology follow-up, ongoing LMWH for Trousseau

— Restart home anticoagulants/antiplatelets only when bleeding risk acceptable and provider-coordinated

— Avoid NSAIDs if recent bleeding

— Pneumococcal, influenza, COVID vaccines after recovery

— Smoking cessation, alcohol reduction, glycemic control

— Mental health screening — ICU survivors have 20–40% PTSD/depression rates

— Advance directive update during recovery

Step 3 management: A patient discharged after DIC + VTE should leave with a written anticoagulation plan, follow-up appointment within 1 week, and clear bleeding-precaution education — these are testable transition-of-care elements.

Board pearl: Cancer patients with DIC who develop VTE go home on LMWH or a DOAC, not warfarin — Trousseau is famous for warfarin failure.

Discharge readiness criteria:

Anticoagulation considerations at discharge:

Disease-specific long-term plans:

Medication reconciliation:

Lifestyle and counseling:

Follow-Up, Monitoring, and Rehabilitation

— 1 week post-discharge: PCP or hospitalist-led visit; review labs (CBC, BMP, coags), medication reconciliation, wound checks

— 2–4 weeks: specialist follow-up (hematology, oncology, OB, ID as relevant)

— 3 months: reassess anticoagulation duration if VTE occurred; repeat imaging if residual thrombus concern

— 6 months: functional reassessment, mental health screen, vaccination catch-up

— CBC weekly for 2–4 weeks then monthly until stable

— Anticoagulation monitoring: anti-Xa for LMWH in renal impairment, INR for warfarin

— Renal function if AKI occurred — nephrology referral if eGFR <60 persists at 3 months (acute kidney disease → CKD pathway)

— APL: PCR for PML-RARA every 3 months during maintenance

— PT/OT for ICU-acquired weakness — early mobilization in hospital, structured rehab after

— Inpatient rehab facility vs SNF vs home health based on functional assessment

— Prosthetics and amputation rehab for purpura fulminans survivors

— Pulmonary rehab if ARDS sequelae

— Cognitive rehab for post-ICU cognitive impairment

— Bleeding precautions: soft toothbrush, electric razor, avoid contact sports, MedicAlert bracelet

— Recognize recurrence signs: unexplained bruising, mucosal bleeding, leg swelling, dyspnea

— Pregnancy planning if obstetric DIC: preconception consult, MFM for next pregnancy

— Genetic counseling if hereditary thrombophilia identified (e.g., protein C/S deficiency)

— Sepsis bundles, MTP protocols, and DIC scoring as hospital quality metrics

— Readmission within 30 days is a CMS measure — robust discharge planning reduces it

Step 3 management: Schedule the 1-week post-discharge visit before the patient leaves the hospital and confirm the appointment with the patient verbally — this is a Joint Commission transition-of-care safety standard.

Board pearl: Post-ICU syndrome (cognitive, physical, mental health) affects up to 50% of survivors — screen at every follow-up visit during the first year.

Outpatient follow-up cadence:

Lab monitoring after discharge:

Rehabilitation:

Counseling topics:

Quality and value-based care:

Ethical, Legal, and Patient Safety Considerations

— Document discussion of risks (infection, TRALI, TACO, hemolytic reactions, alloimmunization) and alternatives

— Jehovah's Witness patients: explore acceptable alternatives — cell salvage, erythropoietin, IV iron, TXA, factor concentrates (recombinant, derived from plasma fractions some accept), tolerate lower Hb. Document patient's specific wishes in writing; respect autonomy even if life-threatening. In minor children, court order may override parental refusal for life-saving transfusion.

— In emergencies with incapacitated patient and no surrogate, implied consent allows transfusion

— Overt DIC carries 40–80% mortality; early palliative care consultation appropriate

— Address resuscitation status, intubation preferences, surrogate decision-maker before deterioration when possible

— Withdrawal-of-care decisions require surrogate involvement, ethics committee if conflict

— Transition-of-care errors: missed anticoagulation restart, unclear follow-up, medication reconciliation failures

— Wrong blood transfusion: two-person verification at bedside is a Joint Commission Universal Protocol

— Communication breakdowns between ED → ICU → floor → outpatient

— Diagnostic anchoring: missing TTP or HIT by labeling everything as "DIC"

— Lab error: heparin contamination of samples, hemolyzed specimens

— Suspected non-accidental trauma in pediatric DIC patient — mandated child abuse report

— Maternal mortality reporting for obstetric DIC deaths

— Adverse transfusion reactions reported to blood bank and FDA (per hemovigilance)

— Informed consent for research protocols (e.g., novel anticoagulants) — patient must have capacity; surrogate consent allowed for life-threatening conditions with appropriate IRB waivers

— Health disparities: minority and uninsured patients have worse sepsis and DIC outcomes — address access and bias

Step 3 management: A Jehovah's Witness woman with postpartum DIC refusing blood requires immediate hematology + ethics + anesthesia huddle, written documentation of her acceptable interventions, and aggressive use of TXA, fibrinogen concentrate, factor concentrates, cell salvage, and uterine artery embolization to avoid transfusion.

Informed consent for blood products:

Goals of care and end-of-life:

Patient safety pitfalls (high-yield Step 3):

Mandatory reporting and legal:

Research and equity:

High-Yield Associations and Rapid-Fire Clinical Facts

Board pearl: If a stem mentions a 30-year-old with gum bleeding, easy bruising, pancytopenia, low fibrinogen, high D-dimer, and "promyelocytes with multiple Auer rods" — answer start ATRA now, then confirm PML-RARA.

Step 3 management: When you see "fibrinogen 80, platelets 40, INR 2.5, D-dimer 12,000" in a septic patient — diagnose DIC, treat sepsis, transfuse only if bleeding.

APL (AML M3) → t(15;17), PML-RARA, Auer rods, faggot cells, ATRA + arsenic, avoid TXA

Meningococcemia → purpura fulminans + Waterhouse-Friderichsen (adrenal hemorrhage)

Trousseau syndrome → migratory superficial thrombophlebitis + pancreatic adenocarcinoma → LMWH, not warfarin

Amniotic fluid embolism → sudden cardiopulmonary collapse + DIC during labor

Placental abruption → painful bleeding + rigid uterus + DIC

HELLP → hemolysis + elevated LFTs + low platelets in preeclamptic patient → deliver

Retained dead fetus → chronic DIC if >4 weeks

Neonatal purpura fulminans → homozygous protein C deficiency

Kasabach-Merritt → giant hemangioma + DIC/thrombocytopenia in infants

Snake envenomation (rattlesnake) → defibrination syndrome → antivenom

Factor VIII normal/high in liver disease, low in DIC

D-dimer = most sensitive; fibrinogen <100 = most specific for DIC

ISTH score ≥5 = overt DIC

MTP ratio = 1:1:1 (pRBC:FFP:platelets)

TXA within 3 hours for trauma (CRASH-2) and PPH (WOMAN trial)

Calcium gluconate every 4 units of product in MTP (citrate chelation)

TTP = normal PT/aPTT/fibrinogen; treat with PLEX

HIT = platelet drop 5–10 days into heparin, thrombosis without bleeding; stop heparin, start argatroban

TACO = volume overload; TRALI = non-cardiogenic pulmonary edema within 6 h

DDAVP for uremic bleeding (platelet dysfunction in CKD)

Avoid recombinant factor VIIa routinely — arterial thrombosis risk

Sepsis is the #1 cause of DIC overall

Brain is most TF-rich organ → severe TBI causes DIC

Board Question Stem Patterns

— Stem: 68M with gram-negative bacteremia, day 3 ICU. Oozing from central line, BP 80/50, plt 45, INR 2.1, fibrinogen 95, D-dimer >10,000.

— Answer: Treat sepsis (antibiotics, fluids, source control); transfuse platelets/FFP/cryo for active bleeding.

— Stem: 32F with epistaxis, fatigue, WBC 1.5, plt 30, smear with Auer rods.

— Answer: Start ATRA immediately, then confirm t(15;17) PML-RARA.

— Stem: 28F G3P3 sudden hypotension, hypoxia, seizure during labor; then uterine hemorrhage with INR 2.5, fibrinogen 80.

— Answer: Amniotic fluid embolism with DIC; ACLS, MTP, deliver if antepartum, ICU.

— Stem: 65M with pancreatic mass, recurrent DVT on warfarin INR 2.3.

— Answer: Trousseau syndrome; switch to LMWH.

— Stem: Plt 20, schistocytes, normal PT/aPTT/fibrinogen, neuro changes, AKI.

— Answer: TTP; start plasma exchange, do not transfuse platelets.

— Stem: Post-CABG day 7, platelets dropped from 250 to 80, new DVT, normal coags.

— Answer: HIT; stop heparin, start argatroban; send PF4.

— Stem: Cirrhotic with prolonged PT, low platelets, mildly low fibrinogen.

— Answer: Check factor VIII (normal in liver disease, low in DIC).

— Stem: Newborn with retiform purpura within hours of birth, no infection.

— Answer: Homozygous protein C deficiency; give protein C concentrate + FFP.

— Stem: 30F refusing blood products.

— Answer: TXA, fibrinogen concentrate, cell salvage, uterine artery embolization; respect autonomy.

— Stem: After 6 units pRBC, tetany, prolonged QT, ionized Ca 0.7.

— Answer: Calcium gluconate IV.

Board pearl: When two answers seem reasonable (e.g., transfuse FFP vs treat underlying cause), Step 3 almost always rewards treating the underlying trigger first unless the patient is exsanguinating.

Step 3 management: On CCS, type the exact order phrases — "tranexamic acid 1 g IV," "FFP 4 units," "platelets 1 apheresis unit" — partial credit favors specificity.

Pattern 1 — Septic ICU patient with new oozing:

Pattern 2 — Young adult with bleeding gums and pancytopenia:

Pattern 3 — Postpartum collapse:

Pattern 4 — Recurrent VTE on warfarin in cancer patient:

Pattern 5 — Distinguishing TTP from DIC:

Pattern 6 — HIT mimicking DIC:

Pattern 7 — Liver disease vs DIC:

Pattern 8 — Neonatal purpura fulminans:

Pattern 9 — Jehovah's Witness with PPH:

Pattern 10 — Massive transfusion citrate toxicity:

One-Line Recap

DIC is an acquired consumptive coagulopathy with simultaneous microvascular thrombosis and bleeding, always triggered by an underlying disease (sepsis, trauma, obstetric catastrophe, malignancy/APL) — and the cornerstone of management is rapid identification, aggressive treatment of the trigger, and judicious blood product support guided by bleeding, not by lab numbers alone.

Board pearl: Treat the patient, not the lab — and always hunt the trigger.

Step 3 management: Anchor every DIC question on the trio: identify trigger, control trigger, replace products only for bleeding or planned procedures — and you will answer 90% of stems correctly.

Recognition: thrombocytopenia + prolonged PT/aPTT + low fibrinogen + elevated D-dimer in a critically ill patient with bleeding from multiple sites or organ dysfunction; calculate ISTH score (≥5 = overt DIC).

Triggers to memorize: sepsis (#1), trauma/TBI, obstetric (AFE, abruption, HELLP, retained fetus), malignancy (APL → ATRA emergently; Trousseau → LMWH not warfarin), envenomation, transfusion reactions.

Management priorities: (1) treat the underlying cause — antibiotics, source control, delivery, ATRA, debridement; (2) supportive — platelets <50k + bleeding, fibrinogen <150 + bleeding (cryoprecipitate), INR >1.5 + bleeding (FFP), pRBC for Hb <7; (3) TXA within 3 h for trauma/PPH; (4) consider LMWH for thrombotic phenotype or Trousseau.

Avoid pitfalls: don't transfuse stable non-bleeding patients to "correct numbers"; distinguish DIC from TTP (normal PT/aPTT/fibrinogen → PLEX), HIT (4Ts, stop heparin), and liver disease (factor VIII normal/high); recognize that mortality is driven by the underlying disease, not the coagulopathy itself.