Acquired von Willebrand Disease Associated with Mantle Cell Lymphoma

Abstract

We present a rare case of acquired von Willebrand syndrome (AVWS) caused by a mantle cell lymphoma. A 61-year-old male suffered from recurrent bleeding symptoms since a few months. Initially, physical examination was normal. von Willebrand factor antigen (VWF:Ag) level and factor VIII activity (FVIII:C) were low (0.31 IU/ml and 0.43 IU/ml, resp.). Ristocetin cofactor activity (VWF:RCo) was 0.09 IU/ml, and collagen binding activity (VWF:CB) was 0.10 IU/ml. VWF:RCo/VWF:Ag ratio was 0.29, and RIPA value was normal. Highest molecular weight VWF multimers were absent. A diagnosis of von Willebrand Disease (VWD) type 2A was made. However, no genetic mutation was found. No inhibitory antibodies against VWF or factor VIII were detected. A few months later, cervical, axillary, and inguinal lymphadenopathy was found on physical examination. A CT scan confirmed multiple enlarged lymph nodes, and a clonal B-cell population matching a mantle cell lymphoma was detected in the bone marrow. Chemoimmunotherapy resulted in a very good partial remission and concomitantly in a rapid decrease of bleeding problems and complete normalization of FVIII:C and VWF:Ag. The diagnosis of AVWS cannot be rejected by negative mixing studies due to difficulties in the detection of autoantibodies and because of a highly heterogeneous pathogenesis of AVWS. When the suspicion of AVWS is high, an extensive investigation should be performed to find the underlying cause.

Acquired von Willebrand syndrome and lymphoid neoplasms: A review of malignancy management, and propositions of practical recommendations

“…The most important point is that the AWS‐ORR also matched the LRD‐R for most lines of treatment (43 patients, 55 lines of treatment). The median and mean times to normalise VWF levels in LRD were 4.75 and 7.6 months (.2–24 months), respectively 15,40,42,46–48,51–53,55–57 . Several cases described an improvement of bleeding syndrome prior to the biological improvement of AWS 48,51 …”

“…The immunochemotherapy used in some disseminated indolent lymphomas, such as bendamustine‐rituximab, CVP‐rituximab and CHOP‐rituximab was associated with AWS‐ORRs of 66.7% (4/6) 44–49 , 66.7% (2/3) 50,51 and 75% (3/4), respectively 44,46,52,53 . Older drugs, such as chlorambucil, provided an AWS‐ORR of 50% (2/4), 14,54,55 and more recent drugs, such as, showed an AWS‐ORR of 75% (3/4),47 , 51 including one inefficient combination with rituximab 47 .…”

“…(2/3) 50,51 and 75% (3/4), respectively. 44,46,52,53 Older drugs, such as chlorambucil, provided an AWS-ORR of 50% (2/4), 14,54,55 and more recent drugs, such as, showed an AWS-ORR of 75% (3/4),47 , 51 including one inefficient combination with rituximab. 47 Several regimens were only used once in various diseases.…”

“…The median and mean times to normalise VWF levels in LRD were 4.75 and 7.6 months (.2-24 months), respectively. 15,40,42,[46][47][48][51][52][53][55][56][57] Several cases described an improvement of bleeding syndrome prior to the biological improvement of AWS. 48,51 The overall response for AWS was from several months to up to two years after the initial improvement of VWF levels and/or clinical bleeding.…”

Lymphoma‐associated acquired von Willebrand syndrome responsive to splenectomy: A case report

“…With roughly 700 cases reported worldwide (case reports [ 8 , 9 ], registry studies [ 4 ], other observational studies [ 10 ]), treatment is typically focused on the underlying condition and immediate correction of the hemostatic defect in the face of acute bleeding or need for urgent surgery. Such strategies are supported by small observational studies and anecdotal experience.…”