Clinical analysis of six cases of multiple myeloma first presenting with coagulopathy

Abstract

This is a retrospective study on six multiple myeloma patients with upfront coagulopathy and bleeding. A detailed description and analysis of clinical characteristics, coagulation factor deficiencies, treatments and outcome of those six multiple myeloma patients are presented. All six patients presented with significant bleeding. One patient was detected with single factor X deficiency and another with single factor VII (FVII) deficiency, whereas four other patients had complex factor deficiencies. The time from symptom presentation to diagnosis ranged from 3 to 10 months. After correct diagnosis and coagulation factor supplementation, those patients were treated with bortezomib/adriamycin/dexamethasone (PAD) or melphalan/dexamethasone/thalidomide (MTD) regimen. It took 29-71 days (median time 46 days) to completely correct coagulation factor deficiencies since the start of therapy for multiple myeloma. Multiple myeloma patients with acquired bleeding disorders may present with large, deep and multiple sites of haematoma or other types of significant bleeding, which may affect bone marrow examination in some of the cases. Patients may be easily misdiagnosed. The routine examinations of erythrocyte sedimentation rate, serum immunoglobulins and blood urine light chain are the key to diagnosis, hence requiring the treating physician to think broadly and look for traits suggesting myeloma as the underlying cause.

Factor X Deficiency Caused by Nonsecretory Myeloma Successfully Corrected with Bortezomib: A Case Report and Review of the Literature

“…It is worthy to discuss the role of novel agents such as bortezomib, which is associated with high response rates for MM, in improving coagulation dysfunction. According to the literature, a median of 46 days (range 29-71 days) was required to completely correct coagulation factor deficiency with combined chemotherapy of bortezomib/adriamycin/dexamethasone or melphalan/dexamethasone/thalidomide in secretory myeloma with coagulation dysfunction [2]. The regimen of PCD was the inducing regimen for this patient.…”

“…Altered coagulation factors in MM have been occasionally reported in the literature. Hu et al [2] described 6 cases of MM with coagulation factor deficiency, 1 case with isolated factor X deficiency, 1 with isolated factor VII deficiency, and the other 4 with combined factor deficiency. The paraproteins were 1 with IgG-κ, 1 with IgA-κ, 2 with IgA-λ, and the other 2 with light chain.…”

“…The diagnosis of nonsecretory myeloma, which accounts for 3% of all patients with MM, is based on the absence of detectable M-protein in serum and urine [1]. Upfront coagulopathy and bleeding in patients with secretory MM is accompanied by deficiencies of single or complex coagulation factors [2]. However, cases of nonsecretory myeloma complicated with coagulation factor deficiency are not reported.…”

Acquired Isolated Factor VII Deficiency in Plasma Cell Dyscrasias: A Brief Presentation of Two Plasma-Cell-Leukemia-Related Cases and Review of Literature

“…Seven cases of acquired isolated FVII deficiency associated with plasma cell disorders (MM/PCL and/or AL amyloidosis) are reported in the literature [ 12 , 13 , 14 , 15 , 16 ], including the two personal cases here described, and one patient with combined FVII and FX deficiency [ 17 ]. The analysis also includes a patient taken from our case records with AL amyloidosis and isolated PT prolongation, whose abnormality resolved immediately after splenectomy for splenic rupture, but who was not specifically tested for FVII activity.…”

“…The failure to attain a hematologic response and, thus, to prevent new amyloid deposition in tissues translated into persistent and uncontrolled bleeding diathesis with fatal outcomes in two cases, including our personal case of pPCL [ 14 ]. On the other hand, in patients responsive to specific treatment, the time for FVII to recover to normal levels was reported to be 30–46 days, concomitant with therapeutic response [ 13 , 16 ] in two patients diagnosed with MM, and with no reported significant hepatosplenomegaly or documented amyloidosis. It is plausible that in patients with hepatosplenic amyloidosis, particularly in the presence of massive organomegaly, the clearance of factor-binding amyloid deposits and the subsequent correction of coagulation may take a prolonged time with negative impact on prognosis.…”