Thrombin generation and heparin-induced thrombocytopenia.
BACKGROUND
Heparin-induced thrombocytopenia (HIT) is a severe complication of heparin therapy. IgG antibodies targeting the platelet factor 4-heparin complex activate platelets and generate microparticles with procoagulant activity.


OBJECTIVE
To determine whether the thrombin generation assay is capable of detecting procoagulant activity induced by patient platelet-poor plasma (PPP) in donor platelet-rich plasma (PRP).


METHODS
We explored two groups of patients; group 1 (n = 23): patients with a positive clinical and biological diagnosis of HIT; group 2 (n = 25): patients with a negative clinical and biological diagnosis of HIT. Mixtures of donor PRP and patient PPP (1:1) were incubated either with unfractionated heparin 0.2 U mL(-1) or with physiological saline. Thrombin generation was assessed by calibrated thrombinography. The effect of heparin on the mixtures was evaluated according to the ratio of the values with and without heparin (wH/woH) of the five thrombogram parameters.


RESULTS
With low heparin concentrations, plasma of group 1 activates donor platelets and generates procoagulant activity. A set of three ratios outside the cut-off values corresponds to the 'HIT thrombogram profile', characterized by a highly specific aspect of the thrombogram wH in relation to the thrombogram woH. None of the group 2 patients presented a HIT thrombogram profile. The results of thrombinography correlate well with the results of the platelet aggregation test.


CONCLUSIONS
Our studies illustrate the central paradox of HIT, namely enhancement of thrombin generation in the presence of heparin. The HIT thrombogram profile as it is defined in this study can detect the procoagulant activity of HIT IgG antibodies.
Tardy-Poncet
B
B
CHU Saint-Etienne, Hôpital Nord, Laboratoire d'Hématologie, Saint-Etienne, France.
Piot
M
M
Chapelle
C
C
France
G
G
Campos
L
L
Garraud
O
O
Decousus
H
H
Mismetti
P
P
Tardy
B
B
D001792:Blood Platelets / Q000378:metabolism; D005260:Female; D006493:Heparin / Q000009:adverse effects* / Q000737:chemistry; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry; D008297:Male; D015539:Platelet Activation; D010974:Platelet Aggregation; D010978:Platelet Factor 4 / Q000378:metabolism; D053657:Platelet-Rich Plasma / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry; D013917:Thrombin / Q000737:chemistry; D013921:Thrombocytopenia / Q000139:chemically induced*; D013925:Thromboplastin
D007074:Immunoglobulin G; D011994:Recombinant Proteins; D010978:Platelet Factor 4; D006493:Heparin; D013925:Thromboplastin; D013917:Thrombin