Morbidity and mortality of patients with haemophilia in Germany 2007/2008

SummarySince 1978 an annual multicentric survey regarding the epidemiology of patients suffering of haemophilia is performed with support of haemophilia treating centres of any size. Again the actual compilation is resting upon a broad database returning to over 30 years of inquiry well representing both the actual and retrospective status of mortality. Prompted was exclusively information about patients with haemophilia A, B and von Willebrand disease. In particular anonymous data concerning the last 12 months about number of treated patients, type and severity of illness, HIV-status and detailed information about causes of death was inquired. This data was merged with existing data and analyzed statistically. In the 2007/2008 survey, a total

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Hämophilie-Patienten in Deutschland 2008/2009

Hämostaseologie ◽

10.1055/s-0037-1619060 ◽

2010 ◽

Vol 30 (S 01) ◽

pp. S9-S14 ◽

Cited By ~ 2

Author(s):

H. Krebs ◽

W. Schramm ◽

Keyword(s):

Age Distribution ◽

Severity Of Illness ◽

Von Willebrand Disease ◽

Hiv Status ◽

Mortality And Morbidity ◽

Increase Risk ◽

Risk Of Progression ◽

Severe Liver Disease ◽

Hcv Coinfection ◽

Von Willebrand

SummarySince 1978 an annual multicentric survey regarding the epidemiology of patients suffering of haemophilia is performed with support of hemophilia treating centres of any size. Again the actual compilation is resting upon a broad database returning to over 30 years of inquiry well representing both the actual and retrospective status of mortality. Prompted was exclusively information about patients with haemo philia A, B and von Willebrand disease. In particular anonymous data concerning the last 12 months about number of treated patients, type and severity of illness, HIV-status and detailed information about causes of death was inquired. This data was merged with existing data and analyzed statistically. In the 2008/2009 survey, a total number of 9101 patients with bleeding disorders have been reported from 66 participating centres. Despite mortality from HIV in patients with haemophilia is keeping on decreasing, HIV still remains an important factor as an HIV/HCV coinfection seems to increase risk of progression of severe liver disease. Age structure in our patients has been shifting significantly over the last decades bringing age distribution into line with the entire population. This has to be considered assessing mortality and morbidity.

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Morbidität und Mortalität der Hämo philie-Patienten in Deutschland

Hämostaseologie ◽

10.1055/s-0037-1619768 ◽

2012 ◽

Vol 32 (S 01) ◽

pp. S5-S11 ◽

Cited By ~ 1

Author(s):

A. Rieger ◽

W. Schramm ◽

Keyword(s):

Moving Average ◽

Severity Of Illness ◽

Von Willebrand Disease ◽

Hiv Status ◽

Increase Risk ◽

Risk Of Progression ◽

Severe Liver Disease ◽

Hcv Coinfection ◽

Von Willebrand ◽

First Time

SummarySince 1982 an annual multicentric survey regarding the epidemiology of patients suffering of haemophilia is performed with support of haemophilia treating centres of any size. Again, the actual compilation is resting upon a broad database returning to over 30 years of inquiry well representing both the actual and retrospective status of mortality. Prompted was exclusively information about patients with haemophilia A, B and von Willebrand disease. In particular anonymous data concerning the preceeding 12 months about number of treated patients, type and severity of illness, HIV-status and detailed information about causes of death was inquired. This data was merged with existing data and analysed statistically. In the 2009/2010 survey, a total number of 9448 patients with bleeding disorders have been reported from 47 participating centres. Despite mortality from HIV in patients with haemophilia is keeping on decreasing, HIV still remains an important factor as an HIV/HCV coinfection seems to increase risk of progression of severe liver disease. In the actual investigation the findings of the foundation “Humanitäre Hilfe für durch Blutpro-dukte HIV-infizierte Personen” were compared for the first time to our data. Time trends were visualised with a moving average. Our investigation has a smaller number of deceased patients, but contains consistent data.

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Characterisation of Type 2N von Willebrand Disease Using Phenotypic and Molecular Techniques

Thrombosis and Haemostasis ◽

10.1055/s-0038-1650401 ◽

1996 ◽

Vol 75 (06) ◽

pp. 959-964 ◽

Cited By ~ 27

Author(s):

I M Nesbitt ◽

A C Goodeve ◽

A M Guilliatt ◽

M Makris ◽

F E Preston ◽

...

Keyword(s):

Direct Sequencing ◽

Von Willebrand Disease ◽

Molecular Techniques ◽

Haemophilia A ◽

Binding Region ◽

Gene Encoding ◽

Covalently Linked ◽

Von Willebrand ◽

Willebrand Factor

Summaryvon Willebrand factor (vWF) is a multimeric glycoprotein found in plasma non covalently linked to factor VIII (FVIII). Type 2N von Willebrand disease (vWD) is caused by a mutation in the vWF gene that results in vWF with a normal multimeric pattern, but with reduced binding to FVIII.We have utilised methods for the phenotypic and genotypic detection of type 2N vWD. The binding of FVIII to vWF in 69 patients, 36 with type 1 vWD, 32 with mild haemophilia A and one possible haemophilia A carrier with low FVIII levels was studied. Of these, six were found to have reduced binding (five type 1 vWD, one possible haemophilia A carrier), DNA was extracted from these patients and exons 18-23 of the vWF gene encoding the FVIII binding region of vWF were analysed. After direct sequencing and chemical cleavage mismatch detection, a Thr28Met mutation was detected in two unrelated individuals, one of whom appears to be a compound heterozygote for the mutation and a null allele. No mutations were found in the region of the vWF gene encoding the FVIII binding region of vWF in the other four patients

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Clinical assessment of efficacy and safety of DDAVP

Hämostaseologie ◽

10.1055/s-0037-1619106 ◽

2010 ◽

Vol 30 (S 01) ◽

pp. S172-S175 ◽

Cited By ~ 8

Author(s):

W. Miesbach ◽

S. Krekeler ◽

O. Dück ◽

B. Llugaliu ◽

G. Asmelash ◽

...

Keyword(s):

Blood Pressure ◽

Adverse Reactions ◽

Fluid Intake ◽

Von Willebrand Disease ◽

Haemophilia A ◽

Efficacy And Safety ◽

Drug Reactions ◽

Clinical Routine ◽

Von Willebrand ◽

Mild Haemophilia

SummaryThe efficacy of DDAVP (1-deamino-8-D-argi-nine-vasopressin, desmopressin) in mild haemophilia A and von Willebrand disease (VWD) has been established and the use of this well tolerated drug has become clinical routine. In case of increased fluid intake and based on very rarely occurring hyponatraemia, the indication of administration of DDAVP intravenously (i. v.) has to be performed diligently in elderly patients and in children below the age of five years. Aim, patients: Due to clinical practice we were interested in finding prospective parameter potentially correlating with adverse reactions of DDAVP and initiated this study. From 2007 to 2008, we included 49 patients suspicious to suffer from mild haemophilia A (n = 1) or VWD (n = 48) and investigated efficacy and safety of DDAVP after intravenous administration (mean: 0.29 ± 0.032 μg/kg body weight). They underwent clinical and laboratory investigation and were questioned with regard to potential adverse reactions immediately and three days after administration of DDAVP.: Results, conclusion: Most adverse reactions were mild and no serious adverse drug reactions were either observed or reported by the subjects. We identified significant changes of heart rate, blood pressure and leucocytes after conduct of the DDAVP test. The value of these findings has to be investigated in later prospective randomized studies. Further research on identification of prospective parameter is currently ongoing.

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Haemophilia Registry of the Medical Committee of the Swiss Haemophilia Society

Hämostaseologie ◽

10.1055/s-0037-1619794 ◽

2013 ◽

Vol 33 (S 01) ◽

pp. S10-S14

Author(s):

N. von der Weid

Keyword(s):

Young Patients ◽

Von Willebrand Disease ◽

Haemophilia A ◽

Factor Level ◽

On Demand ◽

Level Data ◽

The Usa ◽

Per Capita ◽

Von Willebrand ◽

Yearly Data

SummaryThe Haemophilia Registry of the Swiss Haemophilia Society is currently more than 12 years old. We present here the data as from October 31st, 2012. Registered are patients with haemophilia A and B, von Willebrand disease with VWF : R-Co < 10% and other rare factor deficiencies. For this latter group, inclusion in the Registry depends on the clinical relevance of the bleeding disorder, not on the factor level. Data come directly from the Swiss haemophilia reference and treatment centers and should be updated once a year. Currently 967 patients are registered, the majority (587) presenting with haemophilia A. Disease severity is graded according to ISTH criteria. Basic epidemiological findings are similar to those from larger registries in Europe, Canada or the USA.More that 60% of persons with haemophilia in Switzerland are treated on-demand, with the exception of young patients (<20 years) who present an 80 to 90% rate of prophylactic therapy. Nevertheless, global use of factor concentrates went continuously up over the last decade and reaches now 5.52 Units per capita, still a low value compared to other high-income European countries. A recent survey of the Registry shows that treaters’ compliance with yearly data updates is insufficient; measures will be undertaken in 2013 to enhance data quality.

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Increased Von Willebrand Factor Antigen Clearance in Type 1 Von Willebrand Disease: Investigation of Relationship with ABO Blood Group and Tyr1584Cys Polymorphism.

Blood ◽

10.1182/blood.v104.11.256.256 ◽

2004 ◽

Vol 104 (11) ◽

pp. 256-256 ◽

Cited By ~ 1

Author(s):

Carolyn M. Millar ◽

Anne F. Riddell ◽

Peter V. Jenkins ◽

Christine A. Lee ◽

Simon A. Brown

Keyword(s):

Blood Group ◽

Von Willebrand Factor ◽

Von Willebrand Disease ◽

Abo Blood Group ◽

Haemophilia A ◽

Significant Difference ◽

Von Willebrand ◽

Willebrand Factor ◽

Increased Susceptibility

Abstract Type 1 von Willebrand disease (VWD) is a heterogeneous bleeding disorder in which genetic modifying factors, including ABO blood group, contribute towards the variability in von Willebrand factor (VWF) levels. Recent findings have reported an increased incidence of the Tyr1584Cys polymorphism in the VWF-A2 domain of patients with type 1 VWD. Presence of Cys1584 has been shown to cause increased intracellular retention of VWF, as well as lead to increased susceptibility of VWF to proteolysis by the metalloprotease ADAMTS13. An increased susceptibility to proteolysis by ADAMTS13 has also been demonstrated in the VWF of blood group O individuals. We have investigated the relationship between increased VWF antigen (VWF:Ag) clearance, ABO blood group and the presence of the Tyr1584Cys polymorphism in a group of patients with type 1 VWD. The VWF:Ag half-life (VWF:Ag t1/2) was prospectively evaluated in 45 patients with type 1 VWD, which included three families of two or more first-degree relatives. Median VWF:Ag level was 36.0iu/dl (range 4–50iu/dl); median VWF ristocetin cofactor activity (VWF:RCo) level was 35.0iu/dl (range 3–52iu/dl) and VWF:RCo/VWF:Ag ratio 0.97 (range 0.70–1.37). A normal multimeric pattern was demonstrated in all patients. 25 (55.5%) and 20 (44.5%) of the patients were of blood groups O and A respectively. The control group comprised eight patients with haemophilia A. VWF:Ag levels were measured over a 6 hour period following the administration of intravenous DDAVP. VWF:Ag t1/2 was calculated using the formula: C(t)=C0e−k.t, where C(t)=plasma [VWF:Ag] as a function of time; C0=[VWF:Ag] at time zero; e=base for natural logarithms; k=first order rate constant for the elimination phase (ß phase); t=time. The median value of the VWF:Ag t1/2 in the VWD group was 4.1 hours (95% C.I. 3.2–4.9h) and in the haemophilia A group 9.5 hours (95% C.I. 5.3–19h). This represents a significant difference in VWF:Ag t1/2 between the two groups (p<0.05). However, within the VWD patient group, there was no significant difference between the median VWF:Ag t1/2 values of patients of blood group O and those of blood group A (p>0.05). Within the three families, two affected family members of the same ABO blood group were studied and a concordant reduction in the VWF:Ag t1/2s was found in these subjects. To date, 24 of the VWD patients have been genotyped for the A/G polymorphism at nucleotide 24/1282 in the VWF gene, encoding a Tyr1584Cys polymorphism. The heterozygous presence of the G allele encoding Cys 1282 was demonstrated in one patient. The frequency of this polymorphism in normal and type 1 VWD individuals has been reported to be ~1% and 14% respectively. The median VWF:Ag t1/2 value of the 23 homozygous Tyr1584 patients was 3.4 hours (95% C.I. 3.2–4.8h), representative of the whole VWD group. The VWF:Ag t1/2 in the heterozygous patient was 4.8 hours. The finding of increased plasma VWF:Ag clearance as reflected by a reduction in VWF:Ag half-life in a significant number of patients with type 1 VWD, suggests that increased VWF:Ag clearance may be a contributory factor in the aetiology of type 1 VWD. However, this study suggests there is no relationship between increased VWF:Ag clearance and ABO blood group. Furthermore, the Tyr1584Cys polymorphism is not a major determinant of VWF:Ag clearance within this group of type 1 VWD patients.

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Long-Term Outcome after Joint Bleeds in Von Willebrand Disease Compared to Haemophilia A: A Post Hoc Analysis

Thrombosis and Haemostasis ◽

10.1055/s-0038-1670704 ◽

2018 ◽

Vol 118 (10) ◽

pp. 1690-1700 ◽

Cited By ~ 1

Author(s):

Karin van Galen ◽

Merel Timmer ◽

Piet de Kleijn ◽

Frank Leebeek ◽

Wouter Foppen ◽

...

Keyword(s):

Von Willebrand Disease ◽

Haemophilia A ◽

Term Outcome ◽

Long Term Outcome ◽

Post Hoc Analysis ◽

Joint Health ◽

Post Hoc ◽

Type 3 ◽

Von Willebrand

AbstractLong-term outcome after joint bleeds in von Willebrand disease (VWD) (von Willebrand factor activity ≤ 30 IU/dL) could differ from moderate or severe haemophilia A (HA) (factor VIII [FVIII] 1–5 IU/dL or FVIII < 1 IU/dL). We performed a post hoc analysis on Haemophilia Joint Health Score (HJHS, 0–124), X-ray Pettersson scores (PS, 0–13/joint) and the Haemophilia Activities List (HAL, 0–100), using multivariable regression to adjust for age (rate ratio [RR] or odds ratio [OR] [95% confidence interval]). We included 48 VWD (median age, 47 years, type 3 VWD, n = 19), 39 moderate HA (median, 39 years) and 59 severe HA patients (median, 25 years) with documented joint bleeds. VWD patients suffered repeated bleeding (lifetime > 5/joint) less often than moderate and severe HA patients (52% vs. 77% vs. 98%). HJHS and PS in VWD were similar to moderate HA (median HJHS 5 vs. 6, RR 0.9 [0.5–1.4] and PS > 3 of ≥ 1 joint OR 0.3 [0.1–1.4]), but better than in severe HA patients (median HJHS 5 vs. 9, RR 1.8 [1.1–2.9]; PS > 3 in any joint OR 0.1 [0.0–0.3]). Self-reported limitations in activities were comparable across VWD, moderate HA (HAL score < 95: 67% vs. 49%; OR 1.4 [0.5–3.6]) and young adults with severe HA (67% vs. 48%; OR 1.7 [0.7–4.4]). Despite fewer joint bleeds, joint outcome after joint bleeds was similar in VWD and moderate HA patients. Type 3 VWD patients had worst joint outcome, comparable to younger intensively treated severe HA patients. Limitations in activities occurred as often in VWD as in both moderate and severe HA.

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The Effect of DDAVP Infusion on Thrombin Generation in Platelet-rich Plasma of von Willebrand Type 1 and in Mild Haemophilia A Patients

Thrombosis and Haemostasis ◽

10.1055/s-0037-1614080 ◽

2000 ◽

Vol 84 (10) ◽

pp. 638-642 ◽

Cited By ~ 32

Author(s):

Irene Keularts ◽

K. Hamulyak ◽

H.C. Hemker ◽

Suzette Béguin

Keyword(s):

Factor Viii ◽

Thrombin Generation ◽

Platelet Rich Plasma ◽

Von Willebrand Disease ◽

Clotting Factor ◽

Haemophilia A ◽

The Individual ◽

Von Willebrand ◽

Mild Haemophilia

SummaryIn von Willebrand disease (vWD) type 1 and mild haemophilia A patients we studied the effect of an infusion of DDAVP (0.3 µg/kg body weight) on thrombin generation in platelet-rich plasma (PRP) and platelet-poor plasma (PPP). Baseline thrombin generation in PRP was diminished both in the haemophilia A and vWD patients. It was normal in vWD plasma when sufficient procoagulant phospholipids were present, either via adding phospholipid vesicles to PPP or via scrambling of the platelet membrane with ionomycin in PRP. In haemophilia A plasma, thrombin generation did not normalize by providing procoagulant phospholipids. Treatment with DDAVP temporarily restored thrombin generation in PRP to normal in both diseases.To investigate the individual roles of von Willebrand factor (vWF) and factor VIII, we also studied the effect of factor VIII infusion on thrombin generation in a severe haemophilia patient. It appears that at a fixed normal vWF concentration, <25% factor VIII is sufficient for normal thrombin generation in PRP. At a sufficient factor VIII concentration, however, thrombin generation is still lower than normal in vWD patients; ∼40% of vWF is required for half-normal thrombin generation in PRP.It thus appears that vWF is also a clotting factor, in the sense that it is required for normal thrombin generation. This underlines the importance of the interaction between coagulation and the platelets in normal haemostasis. Thrombin generation in PRP appears to be a suitable test to reflect the combined function.

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Dokumentation in der Hämophilietherapie mit Unterstützung des Deutschen Hämophilieregisters

Hämostaseologie ◽

10.1055/s-0037-1619079 ◽

2010 ◽

Vol 30 (S 01) ◽

pp. S62-S64

Author(s):

J. Hesse ◽

M. Heiden ◽

R. Seitz ◽

W. Schramm ◽

B. Haschberger

Keyword(s):

Data Processing ◽

Coagulation Factor ◽

Patient Data ◽

Von Willebrand Disease ◽

Haemophilia A ◽

Haemophilia B ◽

Factor Deficiency ◽

Coagulation Factor Deficiency ◽

Von Willebrand ◽

Paul Ehrlich

SummaryThe DHR (Deutsches Hämophilieregister, German Haemophilia Register) records patient data on haemophilia A, haemophilia B, von Willebrand disease, and other coagulation factor deficiency disorders. The DHR has been online since 2009. The participation in the DHR leads to additional administrative workload for the hospitals and physicians, but provides many advantages as well: A standard of documentation will be developed to give evidence for the hospitals. They may use their own data as well as with new possibilities for data processing at any time. Reports in accordance with Section 21 TFG (Transfusionsgesetz, German Transfusion Act) are compiled automatically and transmitted to the Paul-Ehrlich-Institut. The DHR may support the searching for patients fulfilling the requirements for participation in a study.

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