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. 2025 Jul 17;393(3):306-309.
doi: 10.1056/NEJMc2506014.

Monoclonal Anti-Platelet Factor 4 Antibodies in Recurrent Pregnancy Loss

Natalie R Bavli  1 , Adam J Kanack  2 , Yoshito Nishimura  2 , Noah P Splinter  2 , Emily E Mauch  2 , Alessandra J Ainsworth  2 , Ravi Sarode  1 , Robert D McBane 2nd  2 , Mindy C Kohlhagen  2 , David Murray  2 , Dong Chen  2 , Rajiv K Pruthi  2 , Anand Padmanabhan  2
Affiliations

Monoclonal Anti-Platelet Factor 4 Antibodies in Recurrent Pregnancy Loss

Natalie R Bavli et al. N Engl J Med. .
No abstract available

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Figures

Figure 1.
Figure 1.. Clinical course, laboratory correlates, and research testing of the two patients.
(A) The elapsed time from the first spontaneous abortion (SAB) is displayed. Available platelet counts are displayed as black circles. (B) PF4-dependent P-selectin expression (PEA) testing results are displayed for the patient’s sample in the following testing conditions: Buffer-treated platelets, PF4-treated platelets, PF4-treated platelets with high concentration of unfractionated heparin (UFH, 100 U/mL), PF4-treated platelets with an isotype control (IC) murine monoclonal antibody, or PF4-treated platelets with the FcgammaRIIa-blocking murine monoclonal antibody IV.3. PF4-dependent activation was inhibited by high concentrations of heparin and FcλRIIa blockade. NC- negative (healthy donor) control; HIT- HIT positive control. (C) Displayed are LC-ESI-QTOF MS light chain +11 distributions of the immunoglobulin light chains isolated from patient serum or (D) anti-PF4 antibodies affinity-purified from patient serum. Purple represents the distribution of all λ-containing Ig’s, orange represents the +11 m/z distribution of all κ-containing Ig’s, and blue represents the +11 m/z light chain distribution of all κ and λ light chains associated with an IgG heavy chain. The number listed above the peaks indicates the deconvoluted weight (Daltons) of the monoclonal anti-PF4 antibody. The x-axis shows the deconvoluted weight, and the y-axis shows the relative abundance of each identified peak. (E) Diagnostic testing results of a VITT ELISA utilizing uncomplexed PF4 as an antigenic target for Patient 1 (blue) are compared to the results from a negative (healthy donor) control sample (NC) or a known Ad26.COV2.S-associated VITT antibody (VITT). (F) Patient 2’s historical platelet counts until hospital admission are displayed as black circles. The pink overlay denotes platelet counts below the normal reference range (150 × 103/μL). (G) The LC-ESI-QTOF MS light chain +11 distributions of the immunoglobulin light chains isolated from patient serum or (H) anti-PF4 antibodies affinity-purified from patient serum are displayed. Purple represents the distribution of all λ-containing Ig’s, orange represents the +11 m/z distribution of all κ-containing Ig’s and blue represents the +11 m/z light chain distribution of all κ and λ light chains associated with an IgG heavy chain. The number listed above the peaks indicates the deconvoluted weight (Daltons) of the monoclonal anti-PF4 antibody. The x-axis shows the deconvoluted weight, and the y-axis shows the relative abundance of each identified peak. (I) Diagnostic testing results of a VITT ELISA utilizing uncomplexed PF4 as an antigenic target for Patient 2 (blue) are compared to the results from a negative (healthy donor) control sample (NC) or a known Ad26.COV2.S-associated VITT antibody (VITT). LMWH - low molecular weight heparin; DTI - direct thrombin inhibitor; SAB- spontaneous abortion.
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References

    1. Kanack AJ, Schaefer JK, Sridharan M, et al. Monoclonal gammopathy of thrombotic/thrombocytopenic significance. Blood 2023;141(14):1772–1776. DOI: 10.1182/blood.2022018797. - DOI - PMC - PubMed
    1. Salmasi G, Murray DL, Padmanabhan A. Myeloma Therapy for Monoclonal Gammopathy of Thrombotic Significance. N Engl J Med 2024;391(6):570–571. DOI: 10.1056/NEJMc2406453. - DOI - PMC - PubMed
    1. Kanack AJ, Leung N, Padmanabhan A. Diagnostic Complexity in Monoclonal Gammopathy of Thrombotic Significance. N Engl J Med 2024;391(20):1961–1963. DOI: 10.1056/NEJMc2409428. - DOI - PMC - PubMed
    1. Samuelson Bannow B, Warad DM, Jones CG, et al. A prospective, blinded study of a PF4-dependent assay for HIT diagnosis. Blood 2021;137(8):1082–1089. DOI: 10.1182/blood.2020008195. - DOI - PMC - PubMed
    1. Kanack AJ, Singh B, George G, et al. Persistence of Ad26.COV2.S-associated vaccine-induced immune thrombotic thrombocytopenia (VITT) and specific detection of VITT antibodies. Am J Hematol 2022;97(5):519–526. DOI: 10.1002/ajh.26488. - DOI - PMC - PubMed

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