Introduction:

• It is a life-threatening complication of exposure to heparin that occurs regardless of dose, schedule, or route of administration.

Classification:2 types:

• Type I
  • Non immune mediated- Caused due to binding of heparin to platelet GPIIb-IIIa
  • Transient fall in platelet count
  • Discontinuation of heparin is not needed.
• Type II
  • Immune mediated
  • Unless told otherwise Heparin induced thrombocytopenia means HIT-2

Epidemiology:

• Seen in 2-6% of patients on conventional heparin and 0.2% of patients on LMWH
• Common with IV, than SC administration
• Common in females
• Common with bovine, than porcine heparin
• Risk is higher in surgical patients than medical patients
• Generally seen 4-5 days after starting heparin

Pathogenesis:

Platelet factor 4 is secreted by platelets, which normally binds to exogenous heparin and inactivates it.

↓

Production of IgG antibodies that bind to platelet factor 4-heparin complex 

(In case of unfractionated heparin these complexes are multimeric and they elicit higher immune response)

↓

HIT antibodies activate platelets and also endothelial cells

↓

Promotion of tissue factor expression and thrombin generation

↓

Thrombotic events

• Also, these antibodies target platelets, leading to their accelerated clearance from circulation, which causes thrombocytopenia
• Note: Only minority of patients who develop PF4/Heparin antibodies develop clinically evident HIT.

Clinical Features:

• Thrombosis- 
  • Seen in 50% patients who develop HIT
  • DVT/ Pulmonary embolism 
  • Rarely arterial thrombosis- Stroke/ MI/ Limb ischemia
• Skin lesions
• Adrenal hemorrhage
• Warfarin induced skin necrosis

Investigations:

• Platelet count- Moderately reduced (50,000- 70,000/cmm)
• Immuno-assay for PF4-Heparin complex- Positive
• Heparin induced platelet aggregation test- Test is done using radiolabeled serotonin- Release of serotonin indicates platelet activation 

Criteria for Diagnosis:

4 T Clinical scoring system

• Low- No need for further testing. Continue heparin if indicated.
• Intermediate and high
  • Immediately stop heparin
  • Start treatment without waiting for confirmatory tests
  • Do Immuno-assay for PF4-Heparin complex/ HIPA test for confirmation of diagnosis of heparin induced thrombocytopenia.

Pretreatment Work-up:

• History
• Examination
• Hemoglobin
• TLC, DLC
• Platelet count
• Peripheral smear
• LFT: Bili- T/D  SGPT:    SGOT:Albumin:    Globulin:
• Creatinine
• Electrolytes: Na:     K:      Ca:    Mg:                                  PO4:  
• LDH
• HIV:
• HBsAg:
• HCV:

Treatment:

• Discontinue all forms of heparin (including LMWH) including heparin coated catheters and flushes 
• Start non-heparin anticoagulation
  • As patients with HIT have thrombosis/ are high risk of thrombosis and also need treatment for condition for which heparin was started
  • Avoid in patients who have active bleeding
  • Agents that may be used
    • Inj. Fondaparinux- 5mg- SC-OD
    • Argatroban/ Rivaroxaban
  • Continue till recovery of thrombocytopenia (Usually takes 7 days) and then add oral anticoagulation (Warfarin or NOACs)
• If warfarin is already started, administer vitamin K. 
• Do not use Warfarin in acute setting, as it can lead to venous limb gangrene and thrombosis, due to depletion of protein C and protein S. Start only after platelet count is >1,50,000/cmm. Stop fondaparinux after achieving therapeutic INR.
• Continue anticoagulation for 3 months for patients with thrombotic complication and for 4 weeks for patients without thrombotic complication.
• Only if bleeding occurs- Transfuse platelets (Avoid using prophylactic platelets transfusions)
• If possible, delay surgery till patient is antibody negative.

Monitoring After Treatment/ Follow-up:

• Patients once diagnosed with HIT (by specific antibody tests) must avoid all forms of heparin for lifetime. 
• Use fondaparinux if required.
• For cardiac surgeries, heparin can used if negative for HIT antibodies and after 100 days of episode of HIT.

Prevention:

• Use LMWH instead of heparin wherever possible
• Limit thromboprophylaxis with heparin to the period of high thrombotic risk.
• Monitor platelet counts every 2-3 days for patients who are receiving heparin from day 4 to day 14 or until heparin is stopped, whichever occurs first.
• Eliminate use of heparin flushes for maintaining patency of catheter lines 
• VTE in patient with history of HIT- Use fondaparinux in full therapeutic doses, until transition to VKA can be achieved.