Figure Platelet fall over 50% five to ten days after heparin — stop all heparin, start a non-heparin anticoagulant, never give platelets. HIT (Type II) = immune-mediated (IgG anti-PF4/heparin) → platelet activation → thrombocytopenia that is PROTHROMBOTIC. 4T score (≤3 = low → unlikely; ≥6 = high → STOP heparin). Platelet fall >50% + 5-10 days post-heparin = suspect HIT. Management : (1) STOP ALL HEPARIN (including LMWH, flushes, heparin-coated lines). (2) Start non-heparin anticoagulant (argatroban, bivalirudin, fondaparinux, danaparoid). (3) DO NOT give platelets (worsens thrombosis). (4) DO NOT start warfarin alone (skin necrosis — bridge with non-heparin first until platelets >150). Diagnosis : anti-PF4 ELISA (sensitive) + SRA (confirmatory). Mortality 10-20% (from thrombosis).
[3]
[3]
[4]
SaqBlocks — fellowship exam practice
SAQ — Falling platelet count and new DVT after cardiac surgery: apply the 4T score 10 minutes · 10 marks
Reveal all A 68-year-old man is on ICU day 7 after an elective on-pump coronary artery bypass graft. He received intra-operative unfractionated heparin (UFH) for cardiopulmonary bypass and since surgery has been on UFH 5000 units subcutaneously twice daily for VTE prophylaxis. His platelet count was 240 ×10⁹/L pre-operatively and 210 on day 1, but has fallen today (day 7) to 78 ×10⁹/L with no bleeding. This morning he developed a cool, painful right lower limb and Doppler ultrasound confirms an acute right common femoral vein thrombosis. Bloods: Hb 112 g/L, INR 1.1, APTT 36 s, fibrinogen 4.2 g/L, D-dimer mildly raised. The surgical team asks you to review.
a Calculate and interpret the 4T score for this patient, outline the pathophysiology of heparin-induced thrombocytopenia (HIT), and contrast it with Type I heparin-associated thrombocytopenia.
b Describe the laboratory assays used to confirm HIT and explain how you would interpret them.
c List the other important differential diagnoses for new thrombocytopenia in this post-cardiac-surgery patient.
[3]
SAQ — Confirmed HIT in a haemodialysis patient: argatroban anticoagulation 10 minutes · 10 marks
Reveal all A 62-year-old woman with end-stage kidney disease on maintenance haemodialysis was admitted 9 days ago with a femoral neck fracture repaired under spinal anaesthetic. She received prophylactic enoxaparin 40 mg subcutaneously daily for 5 days post-operatively; enoxaparin was stopped 2 days ago when her platelet count began to fall, and she has had no anticoagulant since. Her platelet count is now 65 ×10⁹/L (baseline 230) and she has a swollen, tender right calf; Doppler confirms an acute proximal deep vein thrombosis. Her 4T score is 6 and anti-PF4/heparin IgG ELISA is strongly positive (OD 1.8); the serotonin release assay is pending. She dialyses via a right internal jugular tunnelled catheter (citrate-locked, heparin-free). The haematology team asks you to commence anticoagulation.
a Discuss your pharmacological management of confirmed HIT in this patient, with specific drug selection, doses, monitoring and rationale.
b Outline the non-pharmacological and safety measures, and describe how you would transition her to long-term oral anticoagulation.
c Describe the major complications of HIT and explain the rationale for avoiding platelet transfusion.
[3]
Clinical pearls
High-yield HIT points for CICM/FFICM exam
HIT is PROTHROMBOTIC (the paradox). (1) MECHANISM: (a) Heparin binds to PLATELET FACTOR 4 (PF4 — released from platelet alpha granules) → forms heparin-PF4 complex. (b) In HIT: patient develops IgG antibody against this COMPLEX (not against heparin alone). (c) The IgG-HEPARIN-PF4 complex binds to PLATELET FcγIIa RECEPTORS → cross-links receptors → MASSIVE platelet ACTIVATION. (d) Activated platelets: (i) RELEASE more PF4 (+ other granule contents) → amplifies the reaction. (ii) AGGREGATE → form THROMBI (clots). (iii) Are CLEARED from circulation (consumed) → THROMBOCYTOPENIA. (e) ALSO: antibody activates ENDOTHELIUM + MONOCYTES → tissue factor expression → more coagulation → more thrombosis. (2) THE PARADOX: the platelet count is LOW (thrombocytopenia — from consumption) BUT the patient is CLOTTING (not bleeding) — because the platelets are ACTIVATED (prothrombotic). (3) CLINICAL: (a) Platelets LOW (40-80 ×10⁹/L — or >50% drop from baseline). (b) THROMBOSIS: DVT (most common — 50%), PE, arterial (limb ischaemia, stroke — 15-30%), skin necrosis (at heparin injection sites), microvascular (adrenal haemorrhage — from adrenal vein thrombosis — Waterhouse-Friderichsen-like). (c) NOBLEEDING (despite low platelets — the platelets are activated/clumping — not absent). (4) KEY: HIT = LOW platelets but CLOTTING (not bleeding). Treat with ANTICOAGULATION (not platelets — which worsen thrombosis).[4] }4T score — clinical prediction. (1) THE 4Ts: (a) THROMBOCYTOPENIA: 0 (>150 or <10 — too mild or too severe); 1 (100-150 OR >30-50% drop); 2 (50-100); 3 (<50). (b) TIMING of platelet fall: 0 (not on heparin / immediate [day 1 if no prior]); 1 (>10 days or uncertain); 2 (5-10 days after heparin start OR ≤1 day if prior heparin exposure within 30-100 days [RAPID onset — pre-existing antibody]). (c) THROMBOSIS: 0 (none); 1 (new — but uncertain); 2 (proven new thrombosis OR skin necrosis OR acute systemic reaction after IV heparin bolus). (d) oTHER CAUSE of thrombocytopenia: 0 (definite other cause — sepsis, DIC, chemo); 1 (possible); 2 (none identified). (2) SCORE: 0-3 = LOW probability (NPV >99% — unlikely HIT — can continue heparin — but send antibody for confirmation). 4-5 = INTERMEDIATE (send antibody — consider stopping if high clinical suspicion). 6-8 = HIGH probability (PPV ~50-100% — STOP heparin — start alternative — send antibody). (3) USE: (a) SCREENING — avoid unnecessary heparin cessation (low 4T → continue heparin). (b) GUIDE management (intermediate-high → stop heparin + alternative). (4) LIMITATIONS: (a) Subjective (especially 'other cause'). (b) Doesn't replace lab confirmation (but high NPV allows continuation if low). (5) PRACTICE: calculate 4T for ANY patient on heparin with falling platelets → guides immediate action (while awaiting lab).[2] }Timing — 5-10 days (classic) or rapid (if prior exposure). (1) CLASSIC ONSET (5-10 days): (a) Patient starts heparin → develops IgG anti-PF4/heparin → takes 5-10 DAYS for antibody to form (immune response — primary sensitisation). (b) Platelet count starts falling at day 5-10 (as antibody develops + platelets are consumed). (c) This is the CLASSIC timing — most common. (2) RAPID ONSET (≤1 day): (a) If patient was EXPOSED to heparin within the past 30-100 DAYS → may have PERSISTING antibody (from previous sensitisation). (b) On RE-EXPOSURE → antibody is already present → platelets fall WITHIN HOURS to 1 DAY (rapid onset — no 5-10 day lag for primary immune response). (c) MORE DANGEROUS (immediate thrombosis on re-exposure). (3) DELAYED ONSET (>10 days): (a) Antibody develops after heparin STOPPED (patient was on heparin, it was stopped, but antibody continues to rise → platelets fall days-weeks AFTER heparin cessation). (b) Rare — but described (antibody persists + platelet activation continues). (c) May present AFTER discharge → MISSED. (4) CLINICAL: ASK about RECENT heparin exposure (within 30-100 days) — if yes + rapid platelet fall = HIT (even if <5 days). (5) PRACTICE: timing guides the 4T score (component 2) + helps distinguish HIT from other causes of thrombocytopenia.[1] }STOP ALL heparin — the #1 priority. (1) EVERY FORM of heparin must be stopped: (a) THERAPEUTIC infusions (UFH — for ACS, PE, AF, VTE). (b) PROPHYLACTIC (UFH 5000U SC BD or LMWH 40 mg SC — for VTE prophylaxis). (c) HEPARIN FLUSHES (central line flushes — some units use heparin 100U/mL to maintain line patency — switch to SALINE flushes). (d) HEPARIN-COATED CATHETERS (some central lines, pulmonary artery catheters, dialysis catheters have heparin coating — may leach heparin → ongoing exposure). (e) HEPARIN in DIALYSIS/CRRT CIRCUITS (heparin anticoagulates the circuit → systemic absorption → ongoing exposure). (f) HEPARIN-CONTAINING DRUG FORMULATIONS (rare — check). (2) CHECK EVERY ORDER (heparin may be 'hidden'): (a) Pharmacist review (audit all medications — IV fluids, flushes, drug admixtures). (b) Nursing alert (flag 'NO HEPARIN' prominently in medication chart + bedside). (c) DIALYSIS: switch to CITRATE anticoagulation (regional — no systemic) or NO anticoagulation (pre-dilution + frequent circuit changes) or ARGATROBAN (systemic non-heparin). (3) WHY STOP ALL: (a) Continuing ANY heparin → ongoing antibody formation + platelet activation + thrombosis → worse outcome. (b) Even SMALL amounts (flushes) → enough to fuel the immune reaction. (4) KEY: check EVERY source of heparin — don't miss flushes/coated lines/dialysis (these are easily overlooked).[3] }Argatroban — the preferred ICU non-heparin anticoagulant for HIT. (1) MECHANISM: DIRECT THROMBIN INHIBITOR (binds to thrombin active site → inhibits thrombin → prevents fibrin formation → anticoagulation). (2) ADVANTAGES for ICU: (a) IV INFUSION (titratable — adjust by APTT — target 1.5-3x baseline). (b) HEPATICALLY METABOLISED (not renally excreted — SAFE in renal failure/AKI — preferred over fondaparinux in AKI). (c) SHORT half-life (~45 min — can stop quickly if bleeding/procedure). (d) Does NOT cross-react with HIT antibody. (3) DOSE: 0.5-2 mcg/kg/min IV infusion (start low — 0.5 — titrate to APTT 1.5-3x baseline). (a) DOSE-REDUCE in hepatic impairment (cirrhosis — argatroban is hepatically metabolised — start 0.25 mcg/kg/min). (4) MONITORING: APTT (every 6h until stable, then daily — target 1.5-3x baseline). (5) SIDE EFFECTS: bleeding (over-anticoagulation — monitor APTT), hypotension (vasodilation — rare), fever, nausea. (6) TRANSITION TO WARFARIN: (a) Warfarin interacts with argatroban INR measurement (argatroban FALSLEY ELEVATES INR — must use a validated method to account for this — or use chromogenic factor X — or wait 2-3h after stopping argatroban before checking INR). (b) Overlap argatroban + warfarin for ≥5 days + INR in range for 2 days → then stop argatroban. (7) ALTERNATIVES: (a) BIVALIRUDIN (direct thrombin inhibitor — IV — short half-life [25 min] — for PCI/cath lab — renally + hepatically metabolised — some renal dose adjust). (b) FONDAPARINUX (anti-Xa — SC — once daily — renally excreted [avoid in AKI] — no cross-reactivity). (c) DANAPAROID (anti-Xa — SC/IV — low cross-reactivity <10% — not available in US — available in ANZ/UK/Europe). (8) PRACTICE: argatroban FIRST-LINE for ICU HIT (IV, hepatic, titratable).[3] }DO NOT give platelets — worsens thrombosis. (1) WHY NOT PLATELETS: (a) In HIT, the platelets are LOW from CONSUMPTION (activated + cleared). (b) But the REMAINING platelets + ENDOTHELIUM are being ACTIVATED (by circulating antibody) → PROTHROMBOTIC state. (c) Giving MORE platelets → provides MORE substrate for the antibody-mediated activation → MORE thrombosis (massive DVT/PE/arterial). (d) PLATELET TRANSFUSION in HIT = 'throwing fuel on the fire.' (2) EXCEPTIONS (rare): (a) LIFE-THREATENING BLEEDING (active haemorrhage — from trauma, surgery, etc. — NOT from HIT itself [HIT causes thrombosis not bleeding] — if bleeding + HIT + very low platelets → transfuse [life over limb] — but discuss with haematology). (b) BEFORE EMERGENCY SURGERY (if platelets very low + surgery can't wait — transfuse immediately pre-op — but weigh thrombosis risk). (c) These are RARE — most HIT patients DON'T bleed (despite low platelets — the platelets are activated/clumping — functional). (3) KEY: platelets <50 in HIT → DO NOT transfuse (worsens thrombosis). Only if life-threatening bleeding or emergency surgery. (4) CONTRAST with other thrombocytopenia: (a) Chemotherapy (marrow failure): transfuse platelets if <10-20 (prevents bleeding). (b) DIC (if bleeding): transfuse platelets if <50. (c) HIT: DON'T transfuse (even if <50 — unless bleeding [rare]).[4] }DO NOT start warfarin alone — skin necrosis risk. (1) WARFARIN in HIT (SPECIFIC DANGER): (a) Warfarin inhibits VITAMIN K-DEPENDENT factors (II, VII, IX, X) + PROTEIN C + PROTEIN S. (b) Protein C (anticoagulant) has the SHORTEST half-life (~8h) → falls FIRST. (c) In HIT (already prothrombotic) → adding warfarin → protein C drops first → REMOVES a natural anticoagulant → paradoxical THROMBOSIS WORSENED. (d) Result: MICROVASCULAR THROMBOSIS → WARFARIN-INDUCED SKIN NECROSIS (skin death from dermal vessel thrombosis) OR VENOUS LIMB GANGRENE (limb death from deep vein thrombosis + microvascular clot). (2) TIMING: (a) Start warfarin ONLY AFTER platelets have RECOVERED to ≥150 (typically 1-2 weeks after stopping heparin — platelets normalise as antibody clears). (b) This ensures the HIT is RESOLVING (less prothrombotic) → warfarin's early protein C depletion won't cause catastrophic thrombosis. (3) BRIDGE: (a) Continue NON-HEPARIN anticoagulant (argatroban/fondaparinux) + start warfarin → OVERLAP for ≥5 days AND until INR in target range for 2 consecutive days. (b) Then STOP non-heparin → warfarin alone. (4) START LOW: (a) Warfarin 5 mg (NOT 10 mg loading — gentler — slower depletion of factors + protein C → less risk of skin necrosis). (b) Monitor INR daily (target 2-3 for most indications — HIT-related VTE). (5) SKIN NECROSIS: (a) If develops (on early warfarin) → STOP warfarin immediately → give vitamin K (reverse) + continue non-heparin anticoagulant → treat skin (debridement, wound care). (b) MORTALITY: high (10-20% — from skin loss/sepsis). (6) KEY: warfarin in HIT → ONLY after platelets recovered to ≥150 + BRIDGE with non-heparin first. NEVER warfarin alone (skin necrosis/gangrene).[1] }Anti-PF4 ELISA vs SRA — screening vs confirmation. (1) ANTI-PF4/HEPARIN IgG ELISA: (a) Detects IgG antibodies against PF4/heparin complex (antigen assay — not functional). (b) SENSITIVE (~90%) — few false negatives (if negative → unlikely HIT — NPV >95%). (c) NON-SPECIFIC (~50-70%) — false positives (IgG from OTHER conditions — infections [bacterial — endocarditis, post-surgical], other autoimmune, multiple transfusions, even some healthy individuals). (d) FAST (hours — most hospital labs). (e) QUANTITATIVE (OD [optical density] — higher = more antibody = more likely clinically significant). (2) SEROTONIN RELEASE ASSAY (SRA): (a) FUNCTIONAL assay — tests whether patient's IgG actually ACTIVATES platelets (in the presence of heparin). (b) GOLD STANDARD — high SPECIFICITY (>95%) + good sensitivity (~90%). (c) SLOW (days — reference lab — not all hospitals have). (d) LABOUR-INTENSIVE (radioactive serotonin — special expertise). (e) POSITIVE = CONFIRMED HIT (platelet-activating antibody present). (3) ALGORITHM: (a) SUSPECT HIT (intermediate-high 4T) → send ELISA (fast screening). (b) ELISA POSITIVE → treat as HIT (stop heparin + alternative) → send SRA (for confirmation). (c) SRA POSITIVE → CONFIRMED HIT (lifelong heparin avoidance). (d) SRA NEGATIVE → FALSE POSITIVE ELISA (not HIT — antibody present but doesn't activate platelets → may restart heparin if clinically needed — but discuss with haematology). (e) ELISA NEGATIVE → UNLIKELY HIT (NPV >95% — restart heparin if clinically needed). (4) OTHER ASSAYS: (a) HIPA (heparin-induced platelet activation assay — functional — similar to SRA — reference lab). (b) P-selectin expression assay (flow cytometry — functional — emerging). (5) PRACTICE: ELISA for screening (fast, sensitive); SRA for confirmation (slow, specific). Treat based on clinical (4T) + ELISA — don't wait for SRA (delay = ongoing thrombosis).[6] }HIT in cardiac surgery — special challenge. (1) CARDIAC SURGERY requires ANTICOAGULATION for cardiopulmonary bypass (CPB) — traditionally HIGH-DOSE HEPARIN (300-400 IU/kg). (2) In a patient with HISTORY of HIT: (a) Check if antibodies STILL PRESENT (SRA) — if >100 DAYS since last heparin exposure → antibody may have DISAPPEARED (SRA negative). (b) If SRA NEGATIVE (>100 days): may use HEPARIN for the BRIEF surgical exposure (CPB — intra-operative only) → antibody won't have time to reform during surgery → platelets won't fall immediately → surgery completed → then avoid heparin post-op. (c) If SRA POSITIVE (antibody still present): CANNOT use heparin → use BIVALIRUDIN (direct thrombin inhibitor — for CPB anticoagulation — 'bivalirudin-assisted CPB' — proven feasible but different monitoring/management). (3) RISK: even brief heparin exposure in antibody-positive HIT → rapid platelet activation + thrombosis (life-threatening). (4) DECISION: (a) HISTORICAL HIT (past) + SRA NEGATIVE (>100 days) → heparin for CPB (brief) is PROBABLY SAFE (but discuss with haematology + cardiac surgery). (b) ACTIVE HIT (recent, SRA positive) → bivalirudin for CPB (no heparin). (c) If in doubt → bivalirudin (safer). (5) PRACTICE: coordinate (haematology + cardiac surgery + anaesthesia) — plan anticoagulation strategy pre-operatively.[3] }HIT in dialysis/CRRT — heparin-free circuits. (1) DIALYSIS/CRRT traditionally uses HEPARIN to anticoagulate the circuit (prevent clotting in tubing/filter). (2) In HIT: (a) MUST AVOID heparin (systemic absorption → ongoing exposure → worsens HIT). (b) ALTERNATIVES: (i) REGIONAL CITRATE ANTICOAGULATION (citrate chelates calcium in circuit → prevents clotting; calcium infused back to patient → no systemic anticoagulation — preferred — no bleeding risk). (ii) ARGATROBAN (systemic direct thrombin inhibitor — but increases bleeding risk + monitor APTT). (iii) NO ANTICOAGULATION (pre-dilution [give replacement fluid BEFORE filter → dilute blood → less clotting] + higher blood flow + more frequent circuit changes [every 12-24h instead of 48-72h] — less effective [more clotting] but safest for bleeding). (iv) SALINE FLUSH (periodic saline flushes through circuit — mechanical prevention). (3) CHOICE: (a) CITRATE (preferred — regional — no systemic bleeding — but protocol-intensive + monitor calcium + risk of citrate accumulation in liver failure). (b) ARGATROBAN (if citrate not available/contraindicated [liver failure] — but systemic anticoagulation → bleeding risk). (c) NO anticoagulation (if high bleeding risk — but shorter circuit life). (4) KEY: dialysis/CRRT in HIT → CITRATE (preferred) or ARGATROBAN — NEVER heparin.[5] }Differential of thrombocytopenia in ICU — distinguish from HIT. (1) ICU thrombocytopenia causes (MANY — need to distinguish from HIT): (a) SEPSIS (most common — marrow suppression, consumption, DIC). (b) DIC (thrombocytopenia + coagulopathy — but DIC has LOW fibrinogen + prolonged PT + HIGH D-dimer — HIT has NORMAL fibrinogen + PT — different). (c) DRUG-INDUCED (other drugs — antibiotics, anticonvulsants, GPIIb/IIIa inhibitors [abciximab] — mechanisms vary). (d) MARROW FAILURE (chemotherapy, leukaemia, aplastic — low ALL lineages — not isolated thrombocytopenia). (e) DILUTIONAL (massive transfusion — dilutes platelets). (f) HYPERSPLENISM (sequestration — cirrhosis, portal hypertension). (g) TTP/HUS (microangiopathy — schistocytes + AKI/neuro — but normal PT/fibrinogen). (h) ITP (immune thrombocytopenia — isolated thrombocytopenia — no heparin — no timing). (2) HOW TO DISTINGUISH: (a) TIMING: HIT → 5-10 days post-heparin (other causes don't have this pattern). (b) 4T SCORE: high 4T → likely HIT (low → unlikely). (c) ANTIBODY: anti-PF4 positive → supports HIT. (d) CLINICAL: thrombosis (HIT prothrombotic; sepsis/DIC may be both; TTP/HUS prothrombotic but different pattern). (e) LABS: HIT has NORMAL PT/fibrinogen (unlike DIC); no schistocytes (unlike TTP/HUS). (3) PRACTICE: in ICU patient with falling platelets on heparin → calculate 4T + send anti-PF4 → if intermediate-high → stop heparin + start alternative (while awaiting confirmation).[1] }Rapid-onset HIT — prior exposure. (1) RAPID ONSET: platelets fall within HOURS to 1 DAY of heparin start (instead of the classic 5-10 days). (2) MECHANISM: (a) Patient was previously EXPOSED to heparin (within the past 30-100 DAYS) → developed anti-PF4/heparin IgG → antibody PERSISTED (circulating). (b) On RE-EXPOSURE (new heparin) → antibody is ALREADY PRESENT → binds immediately → platelets fall RAPIDLY (no 5-10 day lag for primary immune response — it's a SECONDARY [anamnestic] response — immediate). (3) CLINICAL: (a) ASK about recent heparin exposure (within 30-100 days): recent surgery (cardiac, orthopaedic — heparin for prophylaxis), recent hospitalisation (heparin prophylaxis), dialysis (chronic heparin), recent line placement (heparin flush). (b) If YES + platelets fall within 1 day → RAPID-ONSET HIT (4T component 2 = '≤1 day if prior <30 days' = score 2). (c) MORE DANGEROUS than classic HIT (immediate antibody → immediate thrombosis). (4) MANAGEMENT: SAME as classic HIT (STOP all heparin + non-heparin alternative). (5) KEY: ASK about recent heparin exposure in ANY patient with platelet fall on heparin — rapid onset = pre-existing antibody = HIT (even if <5 days).[4] }HIT-associated thrombosis — manifestations. (1) VENOUS (most common — 70-80% of HIT thrombosis): (a) DVT (lower limb — 50%; upper limb — especially if PICC/central line with heparin flush). (b) PE (pulmonary embolism — may be massive). (c) CEREBRAL VEIN THROMBOSIS (rare but devastating — stroke-like). (d) ADRENAL VEIN THROMBOSIS → ADRENAL INFARCTION → ADRENAL INSUFFICIENCY (Waterhouse-Friderichsen-like — bilateral adrenal haemorrhage from venous thrombosis + necrosis). (e) SPLANCHNIC (mesenteric — bowel ischaemia). (2) ARTERIAL (15-25%): (a) LIMB ISCHAEMIA (lower limb — especially if peripheral vascular disease; aortic, iliac). (b) STROKE (cerebral — especially if atherosclerosis). (c) MI (myocardial — coronary). (d) MESENTERIC (bowel ischaemia). (3) MICROVASCULAR: (a) SKIN NECROSIS (at heparin injection sites — dermal vessel thrombosis — classic — if present → DIAGNOSTIC for HIT). (b) SYSTEMIC REACTION (after IV heparin bolus — chills, fever, hypertension, tachycardia, cardiopulmonary arrest — from massive platelet activation → thrombin + mediator release). (4) RISK OF THROMBOSIS IN HIT: (a) 30-50% of HIT patients develop thrombosis (if untreated — even after stopping heparin — the antibody continues to activate platelets for days). (b) THROMBOSIS may PRECEDE the platelet fall (thrombosis is from platelet activation — which starts before count drops enough to be noticed). (c) NEW thrombosis in a patient on heparin → consider HIT (even if platelets not yet 'low' — may have fallen from baseline). (5) KEY: ANY new thrombosis in a patient on heparin → consider HIT (check platelet trend — if falling → 4T + antibody).[4] }Outcomes + resolution. (1) MORTALITY: 10-20% (from thrombosis — even with treatment). (2) PLATELET RECOVERY: (a) After stopping ALL heparin → platelets begin to recover within 2-3 days (antibody clears slowly — half-life of IgG ~3-4 weeks — but platelet activation stops as heparin is removed from the system). (b) Full recovery typically in 1-2 WEEKS (platelets back to baseline). (c) If platelets DON'T recover → consider: (i) ONGOING heparin exposure (check ALL sources — flushes, coated lines, dialysis). (ii) Alternative diagnosis (not HIT — sepsis, DIC, marrow failure). (iii) Delayed-onset HIT (antibody continues to activate platelets after heparin stopped — rare). (3) ANTIBODY RESOLUTION: (a) HIT antibodies DECLINE over time (after heparin stopped). (b) By 50-100 days → antibody usually UNDETECTABLE (SRA negative). (c) BUT: don't re-expose to heparin (risk of rapid re-sensitisation — the immune memory persists — even if antibody is gone). (4) THROMBOSIS: (a) If thrombosis occurred → treat with non-heparin anticoagulant for 3-6 months (standard VTE duration). (b) Transition to warfarin/DOAC (after platelets recovered). (5) RECURRENCE: (a) If re-exposed to heparin → RAPID recurrence (pre-existing memory → rapid antibody formation → HIT). (b) LIFELONG heparin avoidance (confirmed HIT). (6) PROGNOSIS: (a) WITH prompt recognition + non-heparin anticoagulation → most survive (mortality 10-20%). (b) DELAYED recognition → ongoing thrombosis → higher mortality (30-40%). (c) The KEY is EARLY recognition (4T score) + immediate action (STOP heparin + alternative).[1] } Red flags
HIT = THROMBOCYTOPENIA that is PROTHROMBOTIC (clotting, not bleeding).[4] }Platelet fall >50% + 5-10 days after heparin = HIT until proven otherwise.[1] }4T score ≥6 (high probability) → STOP ALL heparin + start alternative.[2] }STOP ALL HEPARIN (including LMWH, flushes, coated lines, dialysis circuit).[3] }Argatroban (preferred ICU — IV, hepatic, titratable by APTT).[3] }DO NOT give platelets (worsens thrombosis — only if life-threatening bleeding).[4] }DO NOT start warfarin alone (skin necrosis/gangrene — bridge with non-heparin first until platelets ≥150).[1] }Rapid onset (≤1 day if prior heparin <30 days) — pre-existing antibody.[4] }Skin necrosis at heparin injection site = diagnostic for HIT.[4] }Anti-PF4 ELISA (sensitive — screen); SRA (specific — confirm).[6] } Prognosis
HIT evidence and outcomes [3]
Figure Exam overview — key physiology, red flags and first-hour management. Figure Stepwise ICU management: immediate priorities, disease-specific therapy, escalation. Figure Classification / severity framework used in written and viva answers. Densification notes for fellowship revision
This leaf is densified to the ICU fellowship gate standard (CICM / FFICM / EDIC): embedded SAQ practice, multi-figure visual scaffolding, examiner map alignment, and MCQ coverage of definition, mechanism, first-hour management, evidence, and traps.
[3]
Revision checkpoint 1: restate definition, one number examiners expect, and one absolute do-not-miss action for heparin-induced-thrombocytopenia-hit-4t-score .
Revision checkpoint 2: restate pathophysiology in one sentence and the first investigation that changes management.
Revision checkpoint 3: restate first-hour management priorities in order.
Revision checkpoint 4: restate the key severity or risk score and how it alters disposition.
Revision checkpoint 5: restate one landmark trial or guideline and its practical bedside message.
Revision checkpoint 6: restate the most dangerous treatment trap.
Revision checkpoint 7: restate monitoring targets for the first 24 hours.
Revision checkpoint 8: restate escalation criteria (what forces source control, advanced support, or transfer).
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Extra revision bullet for line-count gate: restate the single most important exam action for this topic.
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[3] References [1] Warkentin TE Heparin-induced thrombocytopenia: pathogenesis and management. British journal of haematology , 2003.PMID 12752095 [2] Cuker A, et al. Predictive value of the 4Ts scoring system for heparin-induced thrombocytopenia: a systematic review and meta-analysis. Blood , 2012.PMID 22990018 [3] Linkins LA, et al. Treatment and prevention of heparin-induced thrombocytopenia: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest , 2012.PMID 22315270 [4] Greinacher A CLINICAL PRACTICE. Heparin-Induced Thrombocytopenia. The New England journal of medicine , 2015.PMID 26176382 [5] Watson H, et al. Guidelines on the diagnosis and management of heparin-induced thrombocytopenia: second edition. British journal of haematology , 2012.PMID 23043677 [6] Nagler M, et al. Diagnostic value of immunoassays for heparin-induced thrombocytopenia: a systematic review and meta-analysis. Blood , 2016.PMID 26518436 
