scholarly journals Defects in Primary Hemostasis and Acquired Von Willebrand Disease As Cause of Bleeding in Patients with Multiple Myeloma

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3540-3540
Author(s):  
Clemens Hinterleitner ◽  
Klaus Peter Kreisselmeier ◽  
Ann Christin Pecher ◽  
Katja C. Weisel ◽  
Lothar Kanz ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Von Willebrand Disease ◽  
Bleeding Complications ◽  
Bleeding Events ◽  
Primary Hemostasis ◽  
Acquired Von Willebrand Disease ◽  
Serum Free Light Chain ◽  
Closure Time ◽  
Von Willebrand ◽  
Support Research

Abstract Introduction. Paraproteinemia has been associated with both thromboembolic and bleeding complications. Previous retrospective analyses and case reports report on a direct correlation of serum immunoglobulin levels (especially IgM and IgA) with critical bleeding events. Underlying mechanisms include interference with platelet function, immune thrombocytopenia, clotting factor deficiencies, and acquired von Willebrand disease (AVWD). Methods. Laboratory data, including qualitative and quantitative analyses of von Willebrand Factor (vWF), collagen binding assay (CBA) and PFA-100 closure time from 132 patients with diagnosis of multiple myeloma between 2003 and 2015 were retrieved, and cases were retrospectively evaluated for bleeding complications. Coagulation abnormalities were correlated with clinical history and disease parameters. Results. 70 out of 132 patients (53%) displayed bleeding complications including multiple hematomas (n=41), epistaxis (n=10), or perioperative bleeding (n=9). Bleeding vs. non-bleeding patients showed no differences regarding age, gender, previous chemotherapy, or immunoglobulin isotypes. Special coagulation lab results of patients with bleeding events are shown in table 1. Table 1. Pathological coag labs in 70 patients with bleeding Normal Abnormal Sensitivity(95% CI) Specificity(95% CI) PPV*(95% CI) NPV*(95% CI) PLT (<50x103/µl) 70 0 0 1 0 0.47 (0.38-0.56) PT, aPTT 68 2 0.06 (0.02-0.1) 0.95 (0.85-0.99) 0.57 (0.2-0.88) 0.47 (0.38-0.56) vWF:Ag or RCoF 64 6 0.09 (0.04-0.18) 0.95 (0.86-0.99) 0.67 (0.3-0.9) 0.48 (0.39-0.9) PFA-100 27 43 0.61 (0.49-0.73) 0.97 (0.88-0.99) 0.96 (0.84-99) 0.69 (0.58-0.78) CBA/vWF 45 25 0.35 (0.25-0.48) 0.98 (0.9-0.99) 0.96 (0.78-1) 0.58 (0.48-0.67) PFA-100 or CBA/vWF 52 18 0.74 (0.62-0.84) 0.95 (0.86-0.99) 0.94 (0.84-1) 0.76 (0.65-0.85) *PPV = positive predictive value, NPV = negative predictive value Serum free light-chain, but not complete Ig paraprotein levels were significantly associated with bleeding events (p<0.001), prolonged PFA-100 closure time (p<0.001), and pathological CBA/vWF-ratio (p<0.05). Conclusions. Bleeding events were most commonly due to defects of primary hemostasis. Global coagulation tests as well as vWF:Ag and RCo were insufficient in predicting bleeding. When the results of both PFA-100 and CBA/vWF-ratio were considered, 74% of the bleeding patients could be detected. We suggest that both PFA-100 and CBA/vWF-ratio should be determined in patients with multiple myeloma and signs of bleeding in order to rule out AVWD with sufficient sensitivity. Serum free light-chain levels were correlated with hemorrhage and detectable AVWD. Therefore, free Ig light-chains may play a role in the pathophysiology of bleeding. Disclosures Weisel: Janssen Pharmaceuticals: Consultancy, Honoraria, Other: Travel Support, Research Funding; Noxxon: Consultancy; Onyx: Consultancy, Honoraria; Novartis: Other: Travel Support; Celgene: Consultancy, Honoraria, Other: Travel Support, Research Funding; Amgen: Consultancy, Honoraria, Other: Travel Support; BMS: Consultancy, Honoraria, Other: Travel Support.

Acquired von Willebrand disease and multiple myeloma

2014 ◽  
Vol 25 (8) ◽  
pp. 890-893 ◽  
Author(s):  
Ning Jin ◽  
Farah F. Salahuddin ◽  
John A. Nesbitt
Keyword(s):  
Multiple Myeloma ◽  
Von Willebrand Disease ◽  
Acquired Von Willebrand Disease ◽  
Von Willebrand

A Tiered Management Program To Conserve Replacement Therapy Resources for a Rural Population of Women with Type 2M von Willebrand Disease during Labor and Delivery.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3961-3961
Author(s):  
John T. Salter ◽  
Amy D. Shapiro ◽  
Matt Sulkin ◽  
Meadow Heiman ◽  
Anne Greist ◽  
...  
Keyword(s):  
Risk Stratification ◽  
Replacement Therapy ◽  
Post Partum ◽  
Von Willebrand Disease ◽  
Bleeding Complications ◽  
Platelet Glycoprotein ◽  
Close Monitoring ◽  
Bleeding Events ◽  
Excessive Bleeding ◽  
Von Willebrand

Abstract Introduction: Type 2M Von Willebrand Disease (VWD) results from a mutation in the Von Willebrand factor (VWF) gene resulting in decreased or absent binding to platelet glycoprotein Ib. Bleeding episodes in type 2M VWD are variable, but can be severe or life-threatening; effective treatment requires administration of exogenous normal VWF. Pregnant women with type 2M VWD require close monitoring to prevent adverse bleeding events. Following a fatal post-partum hemorrhage in a woman from a large kindred with type 2M VWD, routine prophylactic doses of VWF were administered both pre- and postpartum to women with this disorder. This population is uninsured and utilized product is donated for their care. To determine if the amount of VWF could be safely reduced, a tiered risk stratification and replacement therapy program was developed to manage women with type 2M vWD during labor, delivery and the peuperium. We report the results of this tiered risk stratification in terms of the total product utilized and the rate of bleeding experienced. Methods: Between Jan–Mar 2007, we followed 7 Amish women from a large kindred with type 2M VWD (mutation 4120 C--&gt;T on exon 28). This rural community has limited access to sophisticated hematologic monitoring and is uninsured. Women were risk stratified into 1 of 3 tiers (T) based on their personal or immediate family history of bleeding with childbirth. A nurse provided peripartum monitoring via home visits on postpartum days 1, 3, 5, 10 with a portable hematocrit (Hct) machine. Women in T1 were at lowest risk and given VWF replacement only in the event of excessive bleeding or postpartum Hct &lt;30; T2 (intermediate risk) were given a single prophylactic VWF replacement dose immediately prior to delivery then monitored as T1; T3 received prophylactic VWF dose immediately prior to delivery, at 12 hours postpartum, then monitored by serial Hct per the other tiers. Women requiring Cesarean section were placed into T3 but treated with further VWF replacement due to the surgical intervention. Results: The 7 women fell into the following tiers; T1: 4; T2: 2; T3: 1. Of the 4 women in T1, none experienced excessive bleeding and no VWF therapy was required. In the 2 women in T2, there were no bleeding events requiring additional VWF. Postpartum Hct remained &gt;30 on all evaluations in T1 and 2. One woman was delivered by elective caesarean section for complicated twin pregnancy, and given VWF prior to surgery and once daily for three consecutive postoperative days. She had no bleeding complications, and maintained Hct &gt;30. Compared with the prior method of required pre- and post-partum prophylactic VWF administration regardless of tier or Hct, this pilot protocol safely decreased VWF usage in women assigned to T1 and 2 without adverse bleeding outcome or the need for transfusion. Conclusions: Women with type 2M VWD can be safely managed with a tiered risk stratification system and close postpartum clinical/Hct monitoring that utilizes conservative VWF replacement. For T1 and 2 this lead to a reduction in VWF administration of 83% compared with the prior method of mandatory pre- and postpartum VWF administration. This further translated into a substantial cost savings while still achieving safe hemostatic outcomes. Women at highest risk continue to receive prophylactic VWF pre- and postpartum to prevent serious hemorrhagic events.

Acquired von willebrand disease in multiple myeloma secondary to absorption of von willebrand factor by plasma cells

1990 ◽  
Vol 35 (2) ◽  
pp. 114-117 ◽  
Author(s):  
C. Richard ◽  
M. A. Cuadrado ◽  
M. Prieto ◽  
J. Batlle ◽  
M. Flópez Fernández ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Von Willebrand Factor ◽  
Plasma Cells ◽  
Von Willebrand Disease ◽  
Acquired Von Willebrand Disease ◽  
Von Willebrand ◽  
Willebrand Factor

Management of High Haemorragic Risk Surgery: A Case of Acquired von Willebrand Disease (AVWD).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3950-3950
Author(s):  
Giovanni Mostarda ◽  
Anna Maria Cafro ◽  
Teresa Maria Caimi ◽  
Rosaria Redaelli ◽  
Anna Rosa Corno ◽  
...  
Keyword(s):  
Therapeutic Option ◽  
Reference Interval ◽  
Underlying Disease ◽  
Von Willebrand Disease ◽  
Bleeding Complications ◽  
High Dose ◽  
Laboratory Findings ◽  
Acquired Von Willebrand Disease ◽  
Before And After ◽  
Von Willebrand

Abstract Introduction: Acquired von Willebrand Disease (AVWD) is a rare bleeding disorder occurring in patients with haematological malignancies, solid tumours, immunological and cardiovascular disorders and monoclonal gammopathy of undetermined significance (MGUS). Several pathogenetic mechanisms have been proposed to explain acquired von Willebrand factor (VWF) defect including autoantibodies. Muco-cutaneous bleeding and laboratory findings are similar to those of the congenital VWD. Several approaches have been attempted to correct haemostatic abnormalities with the aim to control bleeding diathesis or to prevent bleeding during surgery. Desmopressin, plasma-derived FVIII/VWF concentrates, intravenous high dose immunoglobulin (HDIg) are the most commonly used. The efficacy of therapy is not predictable and has to be tested before surgery or invasive procedures. In several cases more than one therapeutic option is required. Case report. The patient was a 64-years-old woman with IgGλ-MGUS. Because of persistent uterine bleeding a neoplasia was suspected. The pre-operative coagulative screening showed a prolonged aPTT with markedly reduced levels of FVIII and VWF-related activities (Table 1). VWF multimeric analysis evidenced loss of high and intermediate molecular weight multimers. Patient’s personal and familial history was negative for bleeding and VWF level was normal in other family members. Desmopressin administration (s.c.0.3 μg/kg) obtained a rapid but transient correction of plasma VWF-related parameters, with a return to baseline levels within 6 hours. HDIg intravenous infusion (1 g/kg/day for two consecutive days) led to stable normalization of VWF:RCo, VWF:Ag and FVIII for at least 7 days (Table 1). A laparoscopic hystero-annessiectomy was performed after two-day HDIg infusion: no bleeding complications were observed in the peri-operative period. Histological diagnosis was endometrial hyperplasia. During the two-months follow-up no haemorrhagic episodes were reported. Comments: In AVWD the correction of laboratory abnormalities is crucial to prevent bleeding in patient undergoing high haemorrhagic risk surgery. The choice among therapeutic options is empirical and depends on underlying disease and clinical setting. The efficacy has to be verified. In our patient HDIg infusion obtained a sustained normalisation of VWF-related parameters and prevented bleeding during surgery and in the post-operative period. Table 1. Patient’s laboratory parameters before and after treatment with HDIg VWF-related parameters Reference interval basal +1* +5* +7* *days after HDIg infusion aPTT (R) 1.73 1.21 1.21 1.27 &lt;1.19 VWF:RCo (U/dL) &lt;8 59 56 50 46-118 VWF:Ag (U/dL) 11 66 91 85 43-145 FVIII (U/dL) 14 96 85 96 51-164

scholarly journals How I treat gastrointestinal bleeding in congenital and acquired von Willebrand disease

Blood ◽  
2020 ◽  
Vol 136 (10) ◽  
pp. 1125-1133
Author(s):  
Eugenia Biguzzi ◽  
Simona Maria Siboni ◽  
Flora Peyvandi
Keyword(s):  
Case Reports ◽  
Endoscopic Examination ◽  
Von Willebrand Disease ◽  
High Dose ◽  
Gi Bleeding ◽  
Bleeding Events ◽  
Acquired Von Willebrand Syndrome ◽  
Emergency Situations ◽  
Acquired Von Willebrand Disease ◽  
Von Willebrand

Abstract Gastrointestinal (GI) bleeding is distinctive of severe von Willebrand disease (VWD), generally arising in older patients; in most cases, blood transfusion and hospitalization are required. The presence of arteriovenous malformations is often described when endoscopic examinations are performed. Patients with congenital type 3, 2A, and 2B are those most frequently affected by this symptom, possibly due to the loss of high-molecular-weight multimers of von Willebrand factor (VWF). GI bleeding can also occur in patients affected by acquired von Willebrand syndrome. Endoscopic examination of the GI tract is necessary to exclude ulcers and polyps or cancer as possible causes of GI bleeding. In congenital VWD, prophylaxis with VWF/factor VIII concentrates is generally started after GI-bleeding events, but this therapy is not always successful. Iron supplementation must be prescribed to avoid chronic iron deficiency. Possible rescue therapies (high-dose statins, octreotide, thalidomide, lenalidomide, and tamoxifen) were described in a few case reports and series; however, surgery may be necessary in emergency situations or if medical treatment fails to stop bleeding. In this article, we present several clinical cases that highlight the clinical challenges of these patients and possible strategies for their long-term management.

scholarly journals Multiple myeloma and acquired von Willebrand disease: a combined cause of preanalytical interference causing gel formation?

2017 ◽  
Vol 55 (1) ◽  
pp. 181-184
Author(s):  
Natividad RicoRios ◽  
Louise Bowles ◽  
Ruth M Ayling
Keyword(s):  
Multiple Myeloma ◽  
Total Protein ◽  
Protein Concentration ◽  
Fibrin Clot ◽  
Von Willebrand Disease ◽  
Gel Formation ◽  
Total Protein Concentration ◽  
Acquired Von Willebrand Disease ◽  
Clotting Disorder ◽  
Von Willebrand

We report a patient with acquired von Willebrand disease, associated with multiple myeloma. At one stage in his illness, we were unable to analyse a sample sent in a serum separator tube, due to the presence of a gel within the separated serum layer. We suggest this was due to anomalous position of the gel because of the density of the sample caused by its high total protein concentration, exacerbated by fibrin strand formation because of inhibition of appropriate fibrin clot formation secondary to clotting disorder.

Evaluation of the Abnormal Platelet Function in von Willebrand Disease by the Blood Filtration Test

1996 ◽  
Vol 76 (03) ◽  
pp. 460-468 ◽  
Author(s):  
Francesco I Pareti ◽  
Marco Cattaneo ◽  
Luca Carpinelli ◽  
Maddalena L Zighetti ◽  
Caterina Bressi ◽  
...  
Keyword(s):  
Platelet Function ◽  
Relevant Information ◽  
Von Willebrand Disease ◽  
Type I ◽  
Cumulative Number ◽  
Primary Hemostasis ◽  
Normal Platelet ◽  
Filter Test ◽  
Type 3 ◽  
Von Willebrand

SummaryWe have evaluated platelet function in different subtypes of von Willebrand disease (vWD) by pushing blood through the capillarysized channels of a glass filter. Patients, including those with type IIB vWD, showed lower than normal platelet retention and increased cumulative number of blood drops passing through the filter as a function of time. In contrast, shear-induced platelet aggregation, measured in the cone-and-plate viscometer, was paradoxically increased in type IIB patients. Treatment with l-desamino-8-D-arginine vasopressin (DDAVP) tended to normalize the filter test in patients with type I-platelet normal and type I-platelet low vWD, but infusion of a factor VUI/von Willebrand factor (vWF) concentrate lacking the largest vWF multimers was without effect in type 3 patients. Experiments with specific monoclonal antibodies demonstrated that the A1 and A3 domains of vWF, as well as the glycoproteins Ibα and Ilb-IIIa on platelets, are required for platelet retention in the filter. Thus, the test may reflect vWF function with regard to both platelet adhesion and aggregation under high shear stress, and provide relevant information on mechanisms involved in primary hemostasis.

scholarly journals Acquired von Willebrand disease caused by an autoantibody selectively inhibiting the binding of von Willebrand factor to collagen

Blood ◽  
1994 ◽  
Vol 84 (10) ◽  
pp. 3378-3384 ◽  
Author(s):  
PJ van Genderen ◽  
T Vink ◽  
JJ Michiels ◽  
MB van 't Veer ◽  
JJ Sixma ◽  
...  
Keyword(s):  
Von Willebrand Factor ◽  
Binding Activity ◽  
Von Willebrand Disease ◽  
Low Grade ◽  
Bleeding Tendency ◽  
Glycoprotein Ib ◽  
Acquired Von Willebrand Disease ◽  
Recurrent Epistaxis ◽  
Von Willebrand ◽  
Willebrand Factor

Abstract An 82-year-old man with a low-grade malignant non-Hodgkin lymphoma and an IgG3 lambda monoclonal gammopathy presented a recently acquired bleeding tendency, characterized by recurrent epistaxis, easy bruising, and episodes of melena, requiring packed red blood cell transfusions. Coagulation studies showed a von Willebrand factor (vWF) defect (Ivy bleeding time, > 15 minutes; vWF antigen [vWF:Ag], 0.08 U/mL; ristocetin cofactor activity [vWF:RCoF], < 0.05 U/mL; collagen binding activity [vWF:CBA], 0.01 U/mL; absence of the high molecular weight multimers of vWF on multimeric analysis). Mixing experiments suggested the presence of an inhibitor directed against the vWF:CBA activity of vWF without significantly inhibiting the FVIII:C, vWF:Ag, and vWF:RCoF activities. The inhibitor was identified as an antibody of the IgM class by immunoabsorption of vWF and inhibitor-vWF complexes from the plasma of the patient. Subsequent immunoprecipitation experiments using recombinant fragments of vWF showed that the inhibitor reacted with both the glycoprotein Ib binding domain (amino acids [aa] 422–826) and the A3 (aa 909–1112) domain of vWF, but not with the A2 (aa 716–908) or D4 (aa 1183–1535) domains. We conclude that the IgM autoantibody inhibits the vWF:CBA activity by reacting with an epitope present on both the glycoprotein Ib and A3 domains of vWF.

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