Heparin-Induced Thrombocytopenia (HIT)

Guidelines For Management Of HIT

Management of Suspected HIT

Management of Confirmed HIT

 

Pre-Test Probability Scoring For HIT

The 4T Score

Total Score

• < 3 = low probability of HIT
• 4-5 = intermediate probability of HIT
• > 6 = high probability of HIT

Category	2 points	1 point	0 points
Thrombocytopenia	Platelet count fall > 50% AND platelet nadir > 20 × 109 L−1	Platelet count fall 30-50% AND platelet nadir 10-19 × 109 L−1	Platelet count fall < 30% OR platelet nadir < 10 × 109 L−1
Timing of platelet count fall	Clear onset between days 5 and 10 OR within 1 day of re-exposure after prior  exposure within 30 days	Consistent with days 5–10 fall, but not clear (e.g. missing platelet counts) OR  onset after day 10 OR  within 1 day of re-exposure after prior  exposure 30–100 days ago	Platelet count fall < 4 days AND no heparin exposure within the last 100 days
Thrombosis or other sequelae	New thrombosis (confirmed) OR skin necrosis at heparin injection sites OR acute systemic reaction after intravenous heparin bolus	Progressive or recurrent thrombosis OR non-necrotizing (erythematous) skin lesions OR suspected thrombosis (not proven)	None
Other causes for thrombocytopenia	None apparent	Possible	Definite

Lo GK, Juhl D, Warkentin TE, Sigouin CS, Eichler P, Greinacher A. Evaluation of pretest clinical score (4 T’s) for the diagnosis of heparin-induced thrombocytopenia in two clinical settings. J Thromb Haemost 2006; 4: 759–65.

Score for HIT in Cardiopulmonary Bypass

Total Score

• < 2 = low probability of HIT
• > 2 = high probability of HIT

Variables	Clinical Scenario	Points
Platelet count time course	Pattern A ((Platelet count begins to recover after CPB, but then begins to fall again > 4 days after CPB)	2
	Pattern B (Thrombocytopenia occurs immediately after CPB and persists for > 4 days without recovery)	1
Time from CPB to index date	> 5 days	2
	< 5 days	0
CBP duration	< 118 minutes	1
	> 118 minutes	0

Lillo-Le Louët A, Boutouyrie P, Alhenc-Gelas M, Le Beller C, Gautier I, Aiach M, Lasne D. Diagnostic score for heparin-induced thrombocytopenia after cardiopulmonary bypass. J Thromb Haemost 2004; 2: 1882–8.

HIT Expert Probability (HEP) Score

NOTE:  This scoring has not been prospectively validated and is not yet recommended for clinical use.  Nevertheless, it offers another option for guiding clinical decision-making.

In the initial validation study (referenced above) the following screening cut-offs for total HEP Score were modeled for sensitivity and specificity:

• > 2 = positive for HIT
• < 2 = negative for HIT
  (Sensitivity 1.00 [0.56 – 1.00], Specificity 0.60 [0.45 – 0.75])

• > 5 = positive for HIT
• < 5 = negative for HIT
  (Sensitivity 0.86 [0.42 – 0.99], Specificity 0.88 [0.74-0.96])

Clinical feature	Presentation	Score
Magnitude of fall in platelet count (measured from peak to nadir since heparin exposure)	< 30%	-1
	30-50%	+1
	> 50%	+3
Timing of fall in platelet count	For patients in whom typical onset HIT is suspected:
	Fall begins < 4 days after heparin exposure	-2
	Fall begins 4 days after heparin exposure	+2
	Fall begins 5-10 days after heparin exposure	+3
	Fall begins 11-14 days after heparin exposure	+2
	Fall begins > 14 days after heparin exposure	-1
	For patients with previous heparin exposure in the last 100 days in whom rapid onset HIT is suspected:
	Fall begins < 48 hours after heparin exposure	+2
	Fall begins > 48 hours after heparin exposure	-1
Nadir platelet count	< 20 × 109 L−1	-2
	> 20 × 109 L−1	+2
Thrombosis (select no more than one)	For patients in whom typical onset HIT is suspected:
	New VTE or ATE > 4 days after heparin exposure	+3
	Progression of pre-existing VTE/ATE while receiving heparin	+2
	For patients with previous heparin exposure in the last 100 days in whom rapid onset HIT is suspected:
	New VTE or ATE after heparin exposure	+3
	Progression of pre-existing VTE /ATE while receiving heparin	+2
Skin necrosis	Skin necrosis at subcutaneous heparin injection sites	+3
Acute systemic reaction	Acute systemic reaction after intravenous heparin bolus	+2
Bleeding	Presence of bleeding, petechiae, or extensive bruising	-1
Other causes of thrombocytopenia (select all that apply)	Presence of a chronic thrombocytopenic disorder	-1
	Newly initiated non-heparin med known to cause thrombocytopenia	-2
	Severe infection	-2
	Severe DIC (fibrinogen < 100 mg/dL and D-dimer > 5 mcg/ml)Indwelling intra-arterial device (IABP, VAD, ECMO)	-2
	Cardiopulmonary bypass within previous 96 hrs	-1
	No other apparent cause	+3
VTE=venous thromboembolism; ATE=arterial thromboembolism; DIC=disseminated intravascular coagulation

Cuker A, Arepally G, Crowther MA, Rice L, Datko F, Hook K, Propert KJ, Kuter DJ, Ortel TL, Konkle BA, Cines DB. The HIT Expert Probability (HEP): Score: a novel pre-test probability model for heparin-induced thrombocytopenia based on broad expert opinion. J Thromb Haemost 2010; 8:2642-50.

 

Guidelines for the Use of Bivalirudin in HIT

Bivalirudin Initial Dosing: based on a review of internal data as well as the most recent literature, patients receiving renal replacement therapy are now recommended to start bivalirudin at a rate of 0.05 mg/kg/hr (previously 0.02 mg/kg/hr).

Bivalirudin Dosing Algorithm

Please use the following for the initial dose of bivalirudin in heparin-induced thrombocytopenia (HIT):

Creatinine Clearance (CrCl)	T 1/2	Recommended initial infusion rate (based on total body weight)
>60 ml/min	25 minutes	0.15 mg/kg/hr
30-60 ml/min	34 minutes	0.08 mg/kg/hr
<30 ml/min	57 minutes	0.05 mg/kg/hr
Dialysis-dependent patients (off dialysis)	3-5 hours	0.05 mg/kg/hr*
Dialysis-dependent patients (on dialysis)	(25% clearance by HD filters)	0.05 mg/kg/hr*

Tsu LV and Dager WE. Bivalirudin dosing adjustments for reduced renal function with or without hemodialysis in the management of heparin-induced thrombocytopenia. Ann Pharmacother 2011; 45(10):1185-92.

Runyan CL et al. Correlation of bivalirudin dose with creatinine clearance during treatment of heparin-induced thrombocytopenia. Pharmacotherapy 2011; 31(9):850-6.

Kiser TH et al. Safety, efficacy and dosing requirements of bivalirudin patients with heparin-induced thrombocytopenia. Pharmacotherapy 2008; 28:1115-24

 

Guidelines For The Use Of Argatroban In HIT

Please see the attached document. Note that argatroban is a NONFORMULARY drug at UW Medicine. Bivalirudin is the preferred agent.

Argatroban Guidelines

 

Monitoring Direct Thrombin Inhibitors – DTI Assay

At UWMC, bivalirudin is monitored using the Direct Thrombin Inhibitor (DTI) assay (Plasma-Diluted Thrombin Time).

Used instead of aPTT to monitor injectable DTI therapy. Preferred over aPTT due to better sensitivity, and is not affected by antiphospholipid antibodies. Cost, turn-around time and 24/7 availability at UWMC are similar to aPTT.

• Therapeutic range for DTIs administered by continuous infusion
  • For argatroban: 60-100 seconds
  • For bivalirudin: 60-90 seconds
  • For lepirudin: 90-160 seconds
• Test order code: DTI
• Specimen collection: 3mL or 5mL blue top

Love JE, et al Monitoring direct thrombin inhibitors with a plasma diluted thrombin time. Thromb Haemost. 2007 Jul;98(1):234-42.