• Immune-mediated prothrombotic disorder occurring in patients on unfractioned heparin (UFH) or low molecular weight heparin (LMWH)
• If left untreated, associated with a 6% daily risk of thrombosis, amputation, or death 
• Identify early, stop heparin and substitute alternative anticoagulation
• Over-diagnosis may cause harm due to unnecessary replacement of heparin by infrequently used, non-heparin anticoagulants
• Despite thrombocytopenia, bleeding in HIT is uncommon

• Inform all patients that HIT is a possible complication of heparin therapy
  
  • UFH > LMWH risk
  • Surgical > medical > obstetric risk
• Before starting heparin in all patients, check baseline platelet count 
• Post-operative and cardiopulmonary bypass patients who have been exposed to heparin in the previous 100 days, check platelet count 24 hr after starting any type of heparin/UFH

Patients requiring routine monitoring for HIT (incidence >1%)

• Post-operative patients including obstetric cases receiving UFH 
• Post-cardiopulmonary bypass patients receiving LMWH

Monitor platelet count at least every other day

• From days 4-14 of heparin treatment or until heparin is stopped
  
  • if heparin is stopped for surgery, the day of restarting becomes day zero for the timing

The following patients do not require routine monitoring for HIT (incidence <1%)

• Post-operative patients (other than cardiopulmonary bypass patients) receiving LMWH 
• Medical patients and obstetric patients receiving LMWH

Clinical features of HIT

• Consider HIT in a patient treated with heparin who has a platelet count fall of >30% and/or any of the following
  
  • skin necrosis at sites of heparin injection
  • venous and/or arterial thrombosis
  • anaphylactoid response (cardiorespiratory, neurological or unusual symptoms) within 30 min of systemic heparin infusion
  • extension of previous thrombosis
  • adrenal haemorrhage

HIT suspected

• Perform pre-test probability scoring for HIT using the 4T score

Pre-test probability scoring for HIT (four Ts)

Pre-test probability score

Add score for each clinical category maximum score = 8
6-8 = High (~50% probability of HIT)
4-5 = Intermediate (~10% probability of HIT)
0-3 = Low (<<1% probability of HIT)

Patients with low 4T score (0−3)

• Probability of HIT <<1%
• HIT excluded - continue heparin 
• HIT antibody testing usually not required
• Contact haemostasis team regarding work up of alternative causes of thrombocytopenia and role of HIT antibody testing

Intermediate (4−5) or high (6−8) pre-test probability of HIT on 4T score

• Stop heparin immediately 
  
  • including line locks and flushes; remove any heparin coated lines
• Start alternative anticoagulant, usually at full treatment dose 
  
  • see Non-heparin anticoagulants in heparin induced thrombocytopenia guideline

Do not start warfarin

• Risk of skin necrosis
• If warfarin already started: 
  
  • omit further doses and 
  • give a single dose of vitamin K1 (phytomenadione) 5 mg by slow IV injection 
  • while introducing alternative anticoagulation

HIT antibody testing

• Do not order in patients with 4T score of 0-3
• Obtain blood sample for HIT antibody testing
  
  • 6 mL clotted (red top) sample required
  • complete HIT request form with 4T score and send with blood sample
  • contact blood bank when sending sample
• If in doubt, contact the haemostasis team
• Discuss all HIT antibody results with consultant haematologist 

Platelet transfusion is relatively contraindicated

• Discuss patients with bleeding or a need for urgent procedures with the haemostasis team

• Prefer DOACs for clinically stable HIT patients (with or without thrombosis) at low to average bleeding risk
• Use is off licence but supported by major international guidelines
• Apply the same contraindications to their use in the treatment of acute VTE in determining their appropriateness for patients with HIT
• Rivaroxaban has been most studied in this area. If contraindicated, discuss alternative DOAC with a consultant haematologist 

Rivaroxaban

• HIT with thrombosis: dose is 15 mg twice daily for 21 days then 20 mg once daily
• HIT without thrombosis: dose is 15 mg twice daily until platelet count >150 x 10⁹/L then 20 mg once daily
• All doses to be taken with food

Switching from argatroban or fondaparinux to DOAC

Argatroban

• Stop infusion and start DOAC 2 hr after discontinuation

Fondaparinux

• Start DOAC 24 hr after last dose of fondaparinux

Switching from argatroban to warfarin

• Do not give warfarin until platelet count is >150 x 10⁹/L 
  
  • if commenced too early, risk of warfarin induced skin necrosis and gangrene
• When assessing warfarin effect, remember argatroban prolongs INR 
• Ask anticoagulation team for advice

Starting warfarin

• Start warfarin at 3 mg/day and monitor INR daily 
• When INR is >4.0 for 2 days, stop argatroban infusion and check INR after 4 hr 
• If INR >2 no further argatroban required 
  If INR <2 restart argatroban infusion and adjust warfarin dose with advice 

Switching from fondaparinux to warfarin

• Do not give warfarin until the platelet count is >150 x 10⁹/L 
  
  • if commenced too early, risk of warfarin induced skin necrosis and gangrene 
• Start warfarin 3-5 mg daily (avoid large loading doses)
• Check INR daily - fondaparinux does not interfere with INR 
• When INR >2 for 2 consecutive days, discontinue fondaparinux 

• After HIT associated with a thrombotic complication, give therapeutic anticoagulation for 3 months 
• HIT without a thrombotic complication requires anticoagulation for 4 weeks. Discuss with haemostasis team

• Avoid all forms of heparin and use an alternative anticoagulant
• Discuss with a haematologist if severe renal failure or planned cardiac surgery

• Platelet recovery in HIT usually occurs within 1 week of stopping heparin
• Screen all patients with HIT for asymptomatic proximal deep vein thrombosis
  
  • by bilateral lower-extremity compression ultrasonography 
• Screen all patients with an upper limb central line for asymptomatic DVT by an upper-extremity ultrasonography in the limb with the catheter 
• In patients with an additional indication for antiplatelet therapy (e.g. recent PCI), decide on the balance of bleeding and thrombosis risk whether to continue antiplatelet therapy alongside anticoagulation 

• Document HIT in patient notes and electronic records (iPortal alert)
• Refer all patients being discharged on anticoagulation to the anticoagulation team 
• Refer all patients to thrombosis clinic even if no thrombosis has developed

Inform patient and GP

• If given UFH or LMWH in the 100 days after HIT, increased risk of thrombosis 
• If patient requires anticoagulation with heparin after more than 100 days, seek advice from haemostasis team
• Document HIT in discharge letter
• Ask GP to monitor platelet count where appropriate (see Monitoring above)