Quantification of the relationship between desmopressin concentration and Von Willebrand factor in Von Willebrand disease type 1: A pharmacodynamic study.

INTRODUCTION: Desmopressin can be used to prevent bleeding in von Willebrand disease (VWD), but the relationship between desmopressin and von Willebrand factor activity (VWF:Act) has yet to be quantified. AIM: To quantify the relationship between desmopressin dose, its plasma concentration and the VWF:Act response in type 1 VWD patients. METHODS: Forty-seven VWD patients (median age 25 years, IQR: 19-37; median body weight 71 kg, IQR: 59-86) received an IV desmopressin dose of .3 mcg/kg. In total, 177 blood samples were available for analysis. We developed an integrated population pharmacokinetic-pharmacodynamic (PK-PD) model using nonlinear mixed effect modelling. Subsequently, we performed Monte Carlo simulations to investigate the efficacy of the current dosing regimen. RESULTS: A one-compartment PK model best described the time profile of the desmopressin concentrations. In the PD turnover model, the relationship between desmopressin plasma concentration and release of VWF:Act from the vascular endothelium was best described with an Emax model. Typically, VWF:Act increased 452% with an EC50 of .174 ng/ml. Simulations demonstrated that after .3 mcg/kg desmopressin intravenously, >90% patients with a VWF:Act baseline of ≥.20 IU/mL attain a VWF:Act >.5 IU/ml up to ≥4 h after administration. A capped dose of 30 mcg was sufficient in patients weighing over 100 kg. CONCLUSION: The relationship between desmopressin and VWF:Act was quantified in a PK-PD model. The simulations provide evidence that recently published international guidelines advising an intravenous desmopressin dose of .3 mcg/kg with a capped dose of 30 mcg > 100 kg gives a sufficient desmopressin response.

Use of Tranexamic Acid for the Treatment of Mittelschmerz in a Patient with Type 1 von Willebrand Disease and Recurrent Hemorrhagic Cysts.

BACKGROUND: Tranexamic acid reduces blood loss in patients with bleeding diatheses and is used in a number of gynaecologic and non-gynaecologic conditions CASE: We discuss the case of a 27-year-old woman with type 1 von Willebrand disease, who presented with a two-year history of severe mittelschmerz secondary to recurrent hemorrhagic cysts. The patient refused oral contraception and reported that traditional analgesia did not significantly alleviate symptoms. We theorized that the underlying von Willebrand disease compounded the degree of hemorrhage into her recurrent cysts. As such, a trial of mid-cycle tranexamic acid was offered, which drastically improved her symptoms. CONCLUSION: We report that the use of mid-cycle tranexamic acid in patients with recurrent haemorrhagic cysts can lower ovulation-associated pain.

Clinical significance of slightly reduced von Willebrand factor activity.

Von Willebrand disease (VWD) is the most common congenital bleeding disorder, with a clinical presentation of mucocutaneous and surgical bleeding varying from mild to severe. It is inherited in an autosomal dominant or autosomal recessive manner. The disease is caused by quantitative or qualitative deficiency of the von Willebrand factor (VWF) and is classified as type 1, 2 (2A, 2B, 2M, 2N), and 3. Although type 1 VWD is the most common form of VWD, the f ormal cutoff for diagnosis remains a subject of debate. In our paper, we present results of studies regarding the clinical and laboratory importance of a new type of bleeding disorder called low VWF. The new guidelines for VWD diagnosis and management suggested that patients with historically type 1 VWD should be divided into 2 subsets: type 1 VWD with a VWF antigen level (VWF:Ag) of less than 30 IU/dl or less than 40 IU/dl, in which about 80% of patients exhibited VWF gene mutations, and low VWF with a VWF:Ag level of 30 to 50 IU/dl or 40 to 50 IU/dl, in which the causative mutation is detected in merely 40% of patients and in most families, inheritance is not dependent on the locus of VWF on chromosome 12. Previously, moderately reduced VWF levels (30-50 IU/dl) were considered a risk factor for bleeding, but not a true bleeding disorder, and this condition was named low VWF. Recently, it was documented in a large group of patients with type 1 VWD and low VWF that bleeding score does not correlate with VWF:Ag and bleeding symptoms in type 1 VWD (<30 IU/dl) and low VWF can change from infrequent and moderate to severe bleeds. Because the plasma concentration of VWF depends on many physiological and pathological factors that may mask the diagnosis of VWD, separation of the group of patients with low VWF (30-50 IU/dl) from those with type 1 VWD may delay or prevent them from receiving appropriate treatment. Diagnosis of VWD in each case, particularly those with a slight decrease in VWF (30-50 IU/dl), should be based primarily on the clinical manifestations and family history of hemorrhagic diathesis.

von Willebrand factor and factor VIII levels after desmopressin are associated with bleeding phenotype in type 1 VWD.

The bleeding phenotype of patients with type 1 von Willebrand disease (VWD) is very heterogeneous. We hypothesized that this heterogeneity may partly be explained by variability in response of von Willebrand factor (VWF) and factor VIII (FVIII) levels to stress during hemostatic challenges. We therefore investigated whether VWF and FVIII levels after administration of desmopressin, which mimic in vivo hemostatic response during hemostatic challenges, explain the heterogeneity in bleeding phenotype of patients with type 1 VWD. We performed a retrospective cohort study in 122 patients with type 1 VWD. All patients received a test dose of desmopressin shortly after diagnosis. Patients' mean age was 47 ± 14 years, and the mean Tosetto bleeding score was 10 ± 7. Higher FVIII activity during the complete time course after desmopressin administration (1, 3, and 5-6 hours), and higher VWF and FVIII levels combined at 3 hours after desmopressin administration, were associated with a lower bleeding score: ß = -0.9 (-1.7; -0.1) and ß = -1.2 (-1.9; -0.5), respectively, adjusted for age, sex, body mass index (BMI), and comorbidities. Patients with FVIII activity in the highest quartile 3 hours after desmopressin administration had a much lower bleeding score compared with patients in the other 3 quartiles (ß = -5.1 [-8.2; -2.0]) and also had a lower chance of an abnormal bleeding score (odds ratio = 0.2 [0.1-0.5]), both adjusted for age, sex, BMI, and comorbidities. In conclusion, VWF and FVIII levels after desmopressin administration, which mimic hemostatic response to hemostatic challenges, are associated with the bleeding phenotype of patients with type 1 VWD. This may partly explain the variability in bleeding phenotype of these patients.

Quantitative analysis of desmopressin (DDAVP) response in adult patients with type 1 von Willebrand disease.

INTRODUCTION: Patients with Type 1 von Willebrand disease (VWD) have reduced amounts of von Willebrand factor (VWF) in their blood. Desmopressin (DDAVP) has been used to raise the blood levels of VWF in these patients. However, not all patients with Type 1 VWD are known to respond to DDAVP therapy. We sought to compare the levels of Factor VIII, VWF antigen (VWF:Ag), VWF ristocetin cofactor (VWF:RCo), and fibrinogen at different time points after administration of DDAVP. METHODS: A retrospective analysis was conducted at a single institution on 89 patients with Type 1 VWD who received a single intravenous dose of 0.3 µg/kg DDAVP. Levels of Factor VIII, VWF:Ag, VWF:RCo, and fibrinogen were measured before and then 30, 60, 90, and 120 minutes after completion of DDAVP administration. RESULTS: Median levels of Factor VIII, VWF:Ag, and VWF:RCo were significantly elevated (P < 0.001) at 30 (175 IU/dL, 111 IU/dL, 127 IU/dL), 60 (218 IU/dL, 138 IU/dL, 139 IU/dL), and 90 (212 IU/dL, 134 IU/dL, 130 IU/dL) minutes time points when compared to their respective baseline values (71 IU/dL, 54 IU/dL, 54 IU/dL). At 60 minutes, 96% of subjects were responders, but three subjects failed to respond at any time point. CONCLUSION: Measurement of levels of Factor VIII, VWF:Ag, and VWF:RCo, optimally at 60 minutes after the DDAVP infusion, is sufficient to confirm a patient as a responder in a DDAVP challenge test. Curtailing the number of time points of measurement will result in significant savings in cost and time to patients and their providers.

Evaluation of a microfluidic flow assay to screen for von Willebrand disease and low von Willebrand factor levels.

Essentials von Willebrand factor (VWF) function is shear stress dependent. Platelet accumulation in a microfluidic assay correlates with VWF levels. The microfluidic assay discriminates type 1 von Willebrand disease from healthy controls. The microfluidic flow assay detects responses to therapeutic intervention (DDAVP). SUMMARY: Background von Willebrand disease (VWD) is a mucocutaneous bleeding disorder with a reported prevalence of 1 in 10 000. von Willebrand factor (VWF) function and platelet adhesion are regulated by hemodynamic forces that are not integrated into most current clinical assays. Objective We evaluated whether a custom microfluidic flow assay (MFA) can screen for deficiencies in VWF in patients presenting with mucocutaneous bleeding. Methods Whole blood from individuals with mucocutaneous bleeding was assayed in a custom MFA. Results Thirty-two patients with type 1 VWD (10/32) or reported mucocutaneous bleeding were enrolled. The platelet adhesion velocity (r = 0.5978 for 750 s-1 and 0.6895 for 1500 s-1 ) and the maximum platelet surface area coverage (r = 0.5719 for 750 s-1 and 0.6633 for 1500 s-1 ) in the MFA correlated with VWF levels. Furthermore, the platelet adhesion velocity at 750 s-1 (type 1 VWD, mean 0.0009761, 95% confidence interval [CI] 0.0003404-0.001612; control, mean 0.003587, 95% CI 0.002455-0.004719) and at 1500 s-1 (type 1 VWD, mean 0.0003585, 95% CI 0.00003914-0.0006778; control, mean 0.003132, 95% CI 0.001565-0.004699) differentiated type 1 VWD from controls. Maximum platelet surface area coverage at 750 s-1 (type 1 VWD, mean 0.1831, 95% CI 0.03816-0.3281; control, mean 0.6755, 95% CI 0.471-0.88) and at 1500 s-1 (type 1 VWD, mean 0.07873, 95% CI 0.01689-0.1406; control, mean 0.6432, 95% CI 0.3607-0.9257) also differentiated type 1 VWD from controls. We also observed an improvement in platelet accumulation after 1-desamino-8-d-arginine vasopressin (DDAVP) treatment at 1500 s-1 (pre-DDAVP, mean 0.4784, 95% CI 0.1777-0.7791; post-DDAVP, mean 0.8444, 95% CI 0.7162-0.9726). Conclusions These data suggest that this approach can be used as a screening tool for VWD.

Advances in the diagnosis and treatment of Von Willebrand disease.

Von Willebrand disease (VWD) is the most common inherited bleeding disorder, yet diagnosis and management remain challenging. Development and use of bleeding assessment tools allows for improved stratification of which patients may require further assessment and which patients are most likely to require treatment of their VWD. New options for laboratory assessment of von Willebrand factor (VWF) activity include a new platelet-binding assay, the VWF:GPIbM, which is subject to less variability than the ristocetin cofactor activity assay, and collagen-binding assays that provide insight into a different function of VWF. Genetic testing may be helpful in some cases where a type 2 VWD variant is suspected but is usually not helpful in type 1 VWD. Finally, treatment options for VWD are reviewed, including the use of recombinant VWF. Despite these advances, still more work is required to improve diagnosis, treatment, and quality of life for affected patients.

Revascularization Operation for Moyamoya Disease with Concurrent von Willebrand Disease.

BACKGROUND: Although extracranial-intracranial (EC-IC) bypass is an effective treatment strategy for symptomatic moyamoya disease, surgeons need to be cautious regarding the possibility of postoperative hemorrhagic complications in patients with a concurrent coagulation disorder. Here, we describe a case of EC-IC bypass for moyamoya disease concurrent with von Willebrand disease type 1. CASE DESCRIPTION: Following perioperative replacement of the von Willebrand factor, the patient showed an uneventful and uncomplicated clinical course. CONCLUSION: This is the first reported case of EC-IC bypass being performed for moyamoya disease in a patient with concurrent von Willebrand disease. We emphasize the importance of appropriate management with replacement of the von Willebrand factor during the perioperative period to avoid hemorrhagic complications.

Haemostatic patterns and bleeding scores of a genetically characterised Italian family with combined haemophilia A and type 1 von Willebrand disease.

: We report on the coinheritance of mild haemophilia A and type 1 von Willebrand disease (VWD) in a genetically characterized Italian family. The proband is a 56-year-old man carrying both the c.2167G>A mutation in the factor VIII (FVIII) gene (responsible for p.A723T substitution) and the c.4751A>G mutation (p.Y1584C) in the von Willebrand factor (VWF) gene. His FVIII and VWF levels were 9.8 and 43.2 IU/dl, respectively. His bleeding symptoms included mucocutaneous bleeding, haemarthrosis, and muscle haematomas. Using the bleeding assessment tool, a questionnaire currently employed in diagnosing VWD, the patient had a bleeding score of 27 as compared with the 10.2 ±â€Š3.4 found in patients with mild-to-moderate haemophilia A, and 0-3 in normal men. One of the proband's two daughters (both obligate carriers of haemophilia A) also harboured the VWF p.Y1584C mutation. Her FVIII and VWF levels were 45.9 and 54 IU/dl, respectively, and her bleeding score was slightly higher than normal for women (6 vs. 0-5). The other daughter had a normal bleeding score, and so did the proband's father (with type 1 VWD) and mother (haemophilia A carrier). Discrepancies between haemostatic patterns and bleeding symptoms in cases of haemophilia A, as seen in our patient, suggest the need to search for other coagulation defects, especially involving VWF, which is the carrier of FVIII. Although the presence of a VWF mutation significantly exacerbates the haemorrhagic complications in patients with mild haemophilia A, it has only mild effects on haemophilia A carriers.

Desmopressin responsiveness at a capped dose of 15  µg in type 1 von Willebrand disease and mild hemophilia A.

Desmopressin (DDAVP) is commonly used in the treatment of patients with type 1 von Willebrand disease (VWD) and mild hemophilia A. A patient's responsiveness to DDAVP based on a 0.3  µg/kg dose determines future therapeutic efficacy of the drug. The aim of the study was to determine whether a capped dose of 15 µg subcutaneous DDAVP is able to achieve the same level of DDAVP responsiveness as previously reported. This is a retrospective chart review of patients from 1995 to 2013 in adults and children with type 1 VWD and hemophilia A weighing more than 50 kg. Levels of factor VIII, ristocetin cofactor, and von Willebrand factor antigen were measured before and after 1 h of administration of 15 µg of DDAVP. In patients with type 1 VWD, the complete response rate was 82.5% with a partial response rate of 12.5% and 5% nonresponders. In patients with mild hemophilia A, the complete response rate was 53.8% with a partial response rate of 38.5% and 7.7% nonresponders. These results using a capped 15-µg dose of DDAVP are similar to previously published reports using the 0.3-µg/kg dose.

Similarity in joint and mucous bleeding syndromes in type 2N von Willebrand disease and severe hemophilia A coexisting with type 1 von Willebrand disease in two Chinese pedigrees.

In this study, we investigated the molecular basis of two unrelated Chinese patients with hemostatic disorders. The proband of the first family had severe hemophilia A (HA) coexisting with type 1 von Willebrand disease (VWD) and the proband of the second family had type 2N VWD. Both probands had similar phenotypes, which included joint and mucosal bleeding, very low factor VIII (FVIII) activity (FVIII:C), and moderate reductions in VWF antigen (VWF:Ag) and VWF ristocetin cofactor activity (VWF:Rco), as well as a normal multimeric pattern. One FVIII mutation and three VWF mutations were identified: FVIII p.R446* and VWF heterozygous p.E216K mutations were detected in proband 1 and compound heterozygosity of VWF mutations (p.R816W and c.1911delC) in proband 2. Transient expression studies in HEK293T cells proved that R816W mutation abolished the binding of FVIII to VWF and slightly impaired protein synthesis and secretion; 1911delC mutation mainly impaired VWF protein synthesis and secretion. These results provided insight into the possible pathogenic mechanism of type 2N VWD in Chinese patients carrying these mutations.

Response to low-dose desmopressin by a subcutaneous route in children with type 1 von Willebrand disease.

OBJECTIVE: The primary objective of this study was to determine responses to low-dose desmopressin (DDAVP) by a subcutaneous route in children with type 1 VWD. METHODS: This study analyzed responses to low doses of DDAVP administered by a subcutaneous route to 14 children between the ages of 3 and 16 with type 1 VWD and a personal and familial history of bleeding. At 0 (baseline) and 1 hour (initial response) after the subcutaneous injection of DDAVP, the vital signs were assessed and blood samples were obtained for VWD panel determinations (VWF:Ag, VWF:RCo, FVIII:C levels, and Col/Epi, Col/ADP). At 4 hours (sustained response), only Col/Epi and Col/ADP were assessed. RESULTS: The DDAVP mean (min-max range, µg/kg) based on the patient's weight was 0.15 (0.12-0.18). Laboratory values mean (min-max range in U/dl) baseline for VWF:RCo, VWF:Ag, and FVIII:C were 28 (20-36), 34 (25-42), and 40 (29-48), respectively. After a subcutaneous administration, the laboratory values mean (min-max range in U/dl(-1)) achieved for 1 hour for VWF:RCo, VWF:Ag, and FVIII:C were 109 (72-144), 132 (88-166), and 151 (96-198), respectively. PFA 100(®) CT (Col/Epi <134 seconds and Col/ADP <110 seconds) returned to normal values at 1 and 4 hours after a subcutaneous administration. CONCLUSION: Subcutaneous low-dose DDAVP therapy is at least effective as 0.3 µg/kg intravenous therapy for children with type 1 VWD. This study shows that a wider use of DDAVP should be promoted, especially in developing countries.

Increased amounts of von Willebrand factor are bound to microparticles after infusion of desmopressin.

Effects of desmopressin (DDAVP) in platelet disorders and primary haemostasis cannot be attributed solely to the increase in FVIII/VWF (von Willebrand factor), as VWF/FVIII concentrates have no effect in these circumstances. Microparticles (MP) can support haemostasis by expression of phospholipids, tissue factor and VWF on their surface. We hypothesized that significant amounts of VWF are bound to MP after DDAVP administration and that consequently depletion of MP should influence VWF:Ag and VWF:RCo plasma levels. Platelet-poor plasma was either obtained well from healthy controls or before and after DDAVP administration from patients with von Willebrand's disease (type 1 or possible type 1) or patients with other bleeding disorders as controls. Concentrations of MP and VWF parameters were determined before and after MP depletion by different methods (magnetic bead selection, plasma microfiltration, ultracentrifugation). Platelet MP and VWF-bearing MP were significantly increased after DDAVP. MP depletion by magnetic bead selection led to a significant reduction in VWF:Ag (-18.0%) and VWF:RCo (-27.7%) plasma levels without changes in VWF multimer composition. As results were similar for DDAVP control subjects, the amount of VWF bound to circulating microparticles was significantly higher after DDAVP administration compared with healthy controls (reduction -11.7%). DDAVP leads to a release of microparticles and increases the amount of VWF bound to microparticles which might explain the clinical efficacy of DDAVP in platelet disorders.

Common management issues in pediatric patients with mild bleeding disorders.

Type 1 von Willebrand disease and mild platelet function defects are among the most common disorders seen by pediatric hematologists. The management and prevention of bleeding in these patients can be challenging, as there are limited published data to guide clinical practice, and a complete lack of randomized clinical trials. Desmopressin (DDAVP) and antifibrinolytics are the mainstays of treatment in these patients, yet the optimal dosing and timing of these agents to prevent or resolve bleeding, while minimizing adverse side effects, is sometimes unclear. DDAVP-induced hyponatremia is a particularly under-recognized complication in children with bleeding disorders who undergo surgery. Clinicians need to be aware of local measures that are equally important in treating problems such as epistaxis and surgical bleeding. This review will discuss the published literature and provide practical suggestions regarding four common management issues in the care of children and adolescents with mild bleeding disorders: epistaxis, heavy menstrual bleeding, dental extractions, and tonsillectomy.

Haemostasis prophylaxis using single dose desmopressin acetate and extended use epsilon aminocaproic acid for adenotonsillectomy in patients with type 1 von Willebrand disease.

In patients with confirmed or suspected type 1 von Willebrand disease (VWD), adenotonsillectomy has been reported to be associated with a rate of peri-operative hemorrhage between 8 and 23%. Desmopressin acetate (DDAVP, 1-deamino 8-D arginine- vasopressin) is the treatment of choice for type 1 patients with baseline von Willebrand factor levels of 10 IU/dL or greater. DDAVP is generally well tolerated; however, severe hyponatremia and seizures have been reported in young children less than 2 years of age, limiting its use in this age group. Antifibrinolytic therapy plays an important adjunctive role in the effective treatment of mucocutaneous bleeding, particularly in the oropharynx where the salivary concentration of fibrinolytic enzymes is high. During the past 10 years, we treated 6 pediatric patients with mild/moderate type 1 VWD undergoing an adenotonsillar procedure at our institution with the same hemostatic regimen consisting of one single dose of DDAVP and an extended use of EACA. In this small case series, the above mentioned prophylactic treatment regimen was both well tolerated and efficacious in controlling hemorrhage. Furthermore, DDAVP-related complications were avoided in a pediatric population with a higher risk of developing them.

[Desmopressin parenteral in patients with VWD1, VWD 2A and thrombocytopathy]. / Desmopressin parenteral bei VWD1, VWD 2A und Thrombozytopathie. Biologische und klinische Ansprechbarkeit.

UNLABELLED: Desmopressin (DDAVP, Minirin® parenteral), which induces the release of von-Willebrand factor from endogenous stores, is indicated in von Willebrand disease type 1 (VWD 1). In the present study effectiveness of DDAVP was tested and side effects were recorded in patients with VWD 1, von Willebrand disease type 2 (VWD 2) or thrombocytopathy (TCP). PATIENTS, METHODS: Subjects were analysed prior to and after Minirin parenteral infusion (0.4 µg/kg body weight (b.w.) over 60 minutes) for partial thromboplastin time (PTT, seconds), ADP/epinephrine triggered platelet-function analyzer (PFA-100) occlusion time (seconds), factor VIII activity (FVIII, %), VWF as ristocetin cofactor activity (VWF:RCo, %) and VWF antigen (VWF:Ag, %). Side effects of DDAVP during operative interventions were recorded per questionnaires by the patients. RESULTS: The mean ± standard deviation dose (n = 165 patients) of Minirin parenteral administered was 0.37 ± 0.02 µg/kg b.w., most often upcoming dental operations (57%) necessitated testing. Coagulation parameters of patients with VWD 1 or TCP normalised in almost all patients, but only in approximately 50% of patients with VWD 2 respectively. Appraisal of effectiveness of Minirin parenteral as good was 96% in case of VWD 1 and 95 % in case of TCP. During minor surgeries (n = 23) in 91% of the patients no complications and in 2 patients (9%) postoperative haemorrhages without need for further interventions occurred, but 83% of the patients reported adverse reactions in the questionnaires, although Minirin parenteral was well tolerated by all patients during DDAVP efficacy tests. CONCLUSION: Desmopressin is well tolerated and affective in patients with VWD 1 and thrombocytopathy.

Bleeding tendency and efficacy of anti-haemorrhagic treatments in patients with type 1 von Willebrand disease and increased von Willebrand factor clearance.

Accelerated clearance of von Willebrand factor (VWF) has been recently identified as a major pathophysiologic mechanism inducing low VWF in some patients with von Willebrand disease (VWD). The frequency of bleeding and the best treatment of these patients have never been evaluated prospectively in large series of patients. It was the aim of the present study to prospectively evaluate clinical events of 60 heterozygous patients with VWD Vicenza (VWD-VI) carrying R1205H VWF mutation and 23 with C1130F mutation, both characterised by markedly increased VWF clearance. During 71 months of follow-up, 65% of patients with VWD-VI and 61% with C1130F required treatment. The rate of spontaneous bleeding requiring consultation/treatment was 7.5/100 patients-year in patients with C1130F mutation vs. 1.9/100 patients-year in those with R1205H (p=0.004). This difference persisted also by multivariate analysis adjusted for sex, age and blood group (hazard ratio [HR]=3.3 for C1130F, 95% confidence interval [CI] 1.16-9.27) and females were at greater risk of bleeding (HR=3, 95%CI 1.01-9.93) because of menorrhagia. Only 3/15 (20 %) women in fertile age with VWD-VI compared to 8/9 (89 %) with C1130F mutation required consultation/treatment for menorrhagia (iron supplementation, combined oral contraceptives, tranexamic acid). Almost all dental extractions, minor surgeries and deliveries occurring during follow-up were successfully managed with desmopressin. Major surgery required factor VIII/VWF concentrates, but a few cases benefited from desmopressin. In conclusion, similar to patients with type 1 VWD, also in patients with increased VWF clearance desmopressin maintains a major therapeutic role.

An evaluation of the DDAVP infusion test with PFA-100 and vWF activity assays to distinguish vWD types in children.

von Willebrand disease (vWD) is classified into partial (type 1), qualitative (type 2), and total deficiency (type 3).The aims of the study were to evaluate prospectively the potency of the DDAVP infusion test together with von Willebrand factor (vWF) ristocetin cofactor (vWF:RCo), vWF antigen (vWF:Ag), factor VIII coagulant activity (FVIII:C), and platelet function analyzer (PFA)-100 to distinguish vWD types. Genetic analysis and multimeric analysis of vWF was not applied. We classified the 112 patients and 47 healthy children phenotypically according to the laboratory test results and bleeding severity score. PFA-100 closure times (CT), FVIII:C, vWF:RCo, vWF:Ag, ristocetin-induced platelet aggregation (RIPA), and the response of FVIII:C and vWF parameters to desmopressin (DDAVP) were used to define types 1, 2, and 3 vWD. Type 1 vWD is mild in 34 cases (vWF:RCo % 40-55), moderate in 29 (vWF:RCo %27-40), severe type 1 vWD or nonclassical type 2 vWD in 12 cases (vWF:RCo % 4-16), and type 2 vWD in 23 cases (vWF:RCo %4-38).The response to DDAVP of vWF parameters is normal in all patients with mild/moderate type 1 vWD, 6 patients with severe type 1 vWD or nonclassical type 2 vWD and 11 patients with type 2 vWD. In conclusion, this study showed that measurement of vWF:RCo, vWF:Ag, FVIII:C, and PFA-100 parameters can differentiate vWD types but not severe type 1 vWD or nonclassical type 2 vWD. In the differentiation of severe type 1 vWD and nonclassical type 2 vWD, DDAVP response may be used.