Heparin induced thrombocytopenia in critically ill: Diagnostic dilemmas and management conundrums

Table 1 4T score as studied by Lo et al[38]

Points (0, 1, or 2 for each of 4 categories: maximum possible score = 8)
	2	1	0
Thrombocytopenia	> 50% fall or platelet nadir ≥ 20 × 109/L	30%-50% fall or platelet count 10-19 × 109/L	Fall < 30% or platelet nadir < 10 × 109/L
Timing of fall in platelet count	Clear onset between day 5-101; or less than 1 d (if history of heparin exposure within 30 d)	Consistent with d 5-10 fall, but not clear (e.g., missing platelet counts) or onset of thrombocytopenia after d10 or fall ≤ 1 d (prior heparin exposure 30-100 d ago)	Platelet count fall < 4 d without recent heparin exposure
Thrombosis or other sequelae (e.g., Skin lesions)	New thrombosis; skin necrosis; acute systemic reaction post unfractionated heparin bolus	Progressive or recurrent thrombosis; erythematous skin lesions; suspected thrombosis not yet proven	None
Other cause of thrombocytopenia	None apparent	Possible other cause is evident	Definite
4T score: 6-8 = High; 4-5 = Intermediate; 0-3 = Low

¹5-10 d after exposure to heparin or low molecular weight heparin.

Table 2 Characteristics of various assays for heparin induced thrombocytopenia syndrome

	4T score ≤3[73-76]	ELISA[77]	IgG specific ELISA[77]	OD cut off≥1.0[78]	Heparin confirmation step for IgG specific ELISA[79]	Serotonin release assay[80]	Whole bloodimpedenceAggregometry[44]
Sensitivity	-	100%	100%	80%	94%	100%	90.3%-93.6%
Specificity	-	81%	89%	85%	90%-93%	95%-97%	89%-96%
PPV	-	28%	40%	42%	45%	NA	84.4%-94.8%
NPV	100%	100%	100%	84%	99.50%	NA	-

PPV: Positve predictive value; NPV: Negative predictive value; NA: Not applicable as serotonin release assay is the gold standard assay for diagnosis of heparin induced thrombocytopenia syndrome.

Table 3 Characteristics of alternative anticoagulants

Drug	Route of elimination	Plasma half life	Monitoring	Interaction of antibodies with HITS antibodies	Antidote
Lepirudin	Renal	60 min, up to 200 h in anuric patients[81,82]	aPTT (1.5-2 times baseline) ACT on CPB ECT (Not affected by presence of VKAs or UFH)	None	None ?Haemofiltration[47]
Desirudin	Renal	2-3 h	None	None	None
Danaparoid	Renal	24 h	Anti-Xa activity (0.5-0.8 U/mL)	Possible, but very rare	None
Argatroban	Hepatic	40-50 min	aPTT (1.5-3 times baseline) ACT on CPB	None	None
Bivalirudin	Enzymatic 80% (Thrombin), renal 20%	25 min	aPTT (1.5-2.5 times baseline) ACT on CPB	None	None ?Haemofiltration[52]
Fondaparinux	Renal	17-20 h	None, Anti Xa levels with renal impairment	Case reports only[45,61,62]	None

aPTT: Activated partial thromboplastin time; ACT: Activated clotting time; ECT: Ecarin clotting time; CPB: Cardiopulmonary bypass; HITS: Heparin induced thrombocytopenia syndrome; UFH: Unfractionated heparin.

Table 4 Dosage and availability of anticoagulation agents for heparin induced thrombocytopenia syndrome

Drug	Bolus	Dosage	Dosage in renal impairment	Dosage in hepatic impairment	Availability in Australia
Lepirudin	Only if life or limb threatening thrombosis. 0.4 mg/kg iv	0.1-0.15 mg/kg per hour	Cr. Cl. 45-60: 50% of original infusion rate. Cr. Cl. 30-44: 30% of original infusion rate. Cr. Cl. 15-29: 15% of original infusion rate according to body weight. Avoid if Cr. Cl. Lower or use 0.005 mg/kg per hour if on haemofiltration	No change	Discontinued
Desirudin	None	15-30 mg sc bd. Limited data	Not recommended given paucity of data	No change	Not available
Danaparoid	IV according to body weight. < 60 kg: 1500 U; 60-75 kg: 2250 U; 75-90 kg: 3000 U; > 90 kg: 3750 U	400 U/h IV × 4 h followed by 300 U/h IV × 4 h followed by 200 U/h iv	Reduce dose by 30% and monitor antiXa activity	No change	Available
Bivalirudin	None	0.15-0.2 mg/kg per minute	Cr. Cl 10-29: 0.06 mg/kg per minute; Cr. Cl < 10: 0.015 mg/kg per minute iv	No change	Available
Fondaparinux	None	< 50 kg: 5 mg sc; 50-100 kg: 7.5 mg sc; > 100 kg: 10 mg sc	Cr. Cl 30-50: monitor closely. Cr. Cl < 30: Contraindicated	No change	Available
Argatroban	None	2 mcg/kg per minute iv	No change	0.5 mcg/kg per minute	Not available

Cr. Cl.: Creatinine clearance in mL/min; sc: Subcutaneous; iv: Intravenous.