In a letter to the editor in The New England Journal of Medicine, Salmasi et al described identification of monoclonal gammopathy of thrombotic significance (MGTS) in a patient with coronary artery disease and its successful treatment with daratumumab, bortezomib, and dexamethasone (DVd).
As stated by the investigators: “… MGTS is a recently described highly prothrombotic neoplastic condition characterized by monoclonal anti–platelet factor 4 (PF4) antibodies…. Here, we describe the use of plasma cell–directed therapy to eradicate an MGTS antibody.”
Key Points
A 67-year-old male patient receiving aspirin for coronary artery disease presented with thrombocytopenia, with a platelet count of 38,000/mm3, and mesenteric ischemia associated with extensive splanchnic vein thrombosis. He underwent resection of the small bowel; heparin worsened the splanchnic vein thrombosis, leading to additional resection. Testing confirmed heparin-induced thrombocytopenia, and his treatment was subsequently switched to argatroban. The patient then developed bilateral deep vein thrombosis and pulmonary embolism, leading to cardiac arrest and resuscitation.
Additional testing showed the patient had a monoclonal gammopathy of undetermined significance (MGUS), with IgG lambda of 0.2 g/dL. Treatment was switched to daily fondaparinux before discharge.
The patient exhibited persistent positive heparin-induced thrombocytopenia testing, MGUS, and thrombocytopenia, with bone marrow biopsy indicating 5% lambda-restricted plasma cells. Despite adherence to aspirin and fondaparinux treatment, he developed a cerebrovascular accident due to acute occlusion of the right middle cerebral and internal carotid arteries and underwent thrombectomy and stent placement, with clopidogrel added to the treatment regimen.
Investigation of antibody light chains from the MGUS and isolated anti–PF4 antibody showed monoclonality in both cases; the identical molecular masses of the MGUS and anti–PF4 antibody suggested they were synonymous. The finding was supported by the observed ability of the immune-enriched anti–PF4 antibody to bind PF4-polyanion complexes and activate PF4-treated platelets.
Given recurrent life-threatening thrombosis, plasma cell–directed therapy with DVd was initiated. After three cycles of DVd, analysis showed negative results on heparin-induced thrombocytopenia testing and undetectable MGUS protein. After completion of the third cycle, the patient had a fall that led to intracranial hemorrhage likely associated with concomitant anticoagulation and antiplatelet therapy. The patient received treatment with platelet transfusions and andexanet alfa, with no subsequent thrombosis; treatment was then de-escalated to aspirin and prophylactic fondaparinux. DVd therapy resulted in complete platelet recovery, with the most recent platelet count being 214,000/mm3 at 46 days after platelet transfusion.
As stated by the investigators: “In this study, we found that myeloma therapy provided substantial benefit in a patient with MGTS, a highly prothrombotic disorder in which anticoagulation and antiplatelet therapy may be inadequate.”
Giselle Salmasi, MD, of Stanford University Medical Center, is the corresponding author of The New England Journal of Medicine article.
Disclosure: The work was supported by a grant from the National Institutes of Health. For full disclosures of the study authors, visit www.nejm.org.
