PMID- 15030181
OWN - NLM
STAT- MEDLINE
DCOM- 20041129
LR  - 20190818
IS  - 0300-8177 (Print)
IS  - 0300-8177 (Linking)
VI  - 258
IP  - 1-2
DP  - 2004 Mar
TI  - Differential prevalence of anti-heparin-PF4 immunoglobulin subtypes in patients 
      treated with clivarin and heparin: implications in the HIT pathogenesis.
PG  - 163-70
AB  - Heparin-induced thrombocytopenia (HIT) syndrome is a catastrophic complication of 
      heparin therapy that may result in arterial/venous thromboembolic events. The 
      pathophysiology of HIT is mediated by the generation of a functionally and 
      molecularly heterogeneous group of anti-heparin-platelet factor 4 (AHPF4) 
      antibodies that cause platelet/endothelial cell activation/destruction. These 
      AHPF4 antibodies may be of various subtypes and cause differential pathogenic 
      responses during HIT. This study evaluated the differential prevalence and 
      functionality of AHPF4 Ig subtypes (IgA, IgG, and IgM) in plasma samples obtained 
      from clinically suspected HIT patients (n = 111) and two clinical trials. In 
      these trials, a low-molecular-weight heparin, clivarin and unfractionated heparin 
      (UFH) were used to treat deep-vein thrombosis (CORTES) and for prophylaxis of the 
      orthopedic surgery (ECHOS). In the CORTES study, three randomized groups of 
      patients (n = 312-328) received prophylactic treatment with either UFH or 
      clivarin (o.d. or b.i.d.). In the ECHOS study, there were approximately 600 
      patients per group. Citrated plasma samples were analyzed for cumulative 
      IgA/IgG/IgM and individual Ig subtypes of AHPF4 utilizing ELISA. Functionality of 
      the ELISA-positive samples was ascertained by 14C-serotonin release assay. In 
      clinically confirmed HIT patients (and UFH-treated CORTES and ECHOS samples), the 
      Ig subtyping revealed a predominance of IgG AHPF4 antibodies in contrast to the 
      asymptomatic high AHPF4 antibody titers, which were found to be mostly IgM and/or 
      IgA subtypes. In the clivarin-treated patients in both trials, the prevalence of 
      AHPF4 antibodies was found to be lower (2-3 fold, p < 0.01) in comparison to UFH 
      group. In addition, the clivarin-treated patients with positive AHPF4 antibodies 
      were found to be predominantly of the non-functional type and were found in the 
      order of IgM > IgA > IgG Together, these observations demonstrate that 
      ELISA-detectable IgG subtype in UFH-treated patients may be more likely to cause 
      functional/pathologic responses during HIT syndrome. Thus, determination of IgG 
      subtype of AHPF4 antibodies during HIT syndrome may be crucial in the diagnosis; 
      however, the relevance of the pathologically non-functional (IgA and/or IgM) 
      antibodies and the overall mechanism(s) of these HIT-associatied antibodies need 
      further investigation.
FAU - Ahmad, Sarfraz
AU  - Ahmad S
AD  - Loyola University of Chicago, Stritch School of Medicine, Maywood, Illinois, USA. 
      sarfraz.ahmad@flhosp.org
FAU - Untch, Brian
AU  - Untch B
FAU - Haas, Sylvia
AU  - Haas S
FAU - Hoppensteadt, Debra A
AU  - Hoppensteadt DA
FAU - Misselwitz, Frank
AU  - Misselwitz F
FAU - Messmore, Harry L
AU  - Messmore HL
FAU - Walenga, Jeanine M
AU  - Walenga JM
FAU - Fareed, Jawed
AU  - Fareed J
LA  - eng
PT  - Journal Article
PL  - Netherlands
TA  - Mol Cell Biochem
JT  - Molecular and cellular biochemistry
JID - 0364456
RN  - 0 (Anticoagulants)
RN  - 0 (Autoantibodies)
RN  - 0 (Immunoglobulin Isotypes)
RN  - 37270-94-3 (Platelet Factor 4)
RN  - 9005-49-6 (Heparin)
SB  - IM
MH  - Anticoagulants/adverse effects/*immunology/therapeutic use
MH  - *Autoantibodies/blood/immunology
MH  - Female
MH  - Heparin/adverse effects/*immunology/therapeutic use
MH  - Humans
MH  - *Immunoglobulin Isotypes/blood/immunology
MH  - Male
MH  - Orthopedic Procedures/adverse effects
MH  - Platelet Factor 4/*immunology
MH  - Purpura, Thrombocytopenic, Idiopathic/blood/chemically induced/immunology
MH  - Venous Thrombosis/*drug therapy/etiology/immunology
EDAT- 2004/03/20 05:00
MHDA- 2004/12/16 09:00
CRDT- 2004/03/20 05:00
PHST- 2004/03/20 05:00 [pubmed]
PHST- 2004/12/16 09:00 [medline]
PHST- 2004/03/20 05:00 [entrez]
AID - 10.1023/b:mcbi.0000012852.60500.30 [doi]
PST - ppublish
SO  - Mol Cell Biochem. 2004 Mar;258(1-2):163-70. doi: 
      10.1023/b:mcbi.0000012852.60500.30.