Willebrand-Juergens Syndrome

This article describes human disease. For von Willebrand disease in veterinary medicine, see there.

Classification according to ICD-10
D68.0	Willebrand-Juergens Syndrome
ICD-10 online (WHO version 2019)

The von Willebrand's disease ( vWD , including Von Willebrand syndrome ) is the most common congenital bleeding diathesis (bleeding), in which the activity of factor VIII carrier protein, and Von Willebrand Factor called, is reduced. As a result, normal blood clotting can be disrupted. The disease can also be completely symptom-free.

Common forms of treatment are the drugs desmopressin or blood coagulation factor VIII concentrate.

Origin of the term

The syndrome is named after the Finnish doctor Erik Adolf von Willebrand (1870–1949) and the German doctor Rudolf Jürgens (1898–1961).

Epidemiology

Von Willebrand-Jürgens syndrome is the most common inherited bleeding disease. The prevalence is estimated at 800 / 100,000 people, with only 12.5 / 100,000 people having significant symptoms. Severe Von Willebrand-Juergens syndrome is very rare and affects less than 0.3 / 100,000 people. Acquired forms are described, but very rare. The inheritance is usually autosomal - dominant , but the severe forms and some subtypes are inherited as an autosomal recessive trait. Men and women are affected roughly equally.

etiology

It is a group of hemorrhagic diatheses , the commonality of which is an inherited quantitative or qualitative defect of the Von Willebrand factor (abbreviated VWF). A distinction is made between three different types of the disease, in which the VWF is either produced less (types I and II) or not at all (type III in 5% of cases). Both the primary (cellular) hemostasis and the secondary (plasmatic) hemostasis are impaired by the impaired platelet adhesion. The latter is due to the function of VWF as a carrier protein for factor VIII. A lack of factor VIII (antihemophilia A factor) leads to a lack of positive feedback and to the non-formation of the complex of endogenous factors for the activation of factor X. Both points lead thus to a symptom similar to haemophilia A.

Rarely acquired forms of Von Willebrand-Jürgens syndrome usually appear as a concomitant disease

• Among other things, for heart valve defects , especially aortic stenosis ,
• in the context of some autoimmune diseases , for example IgA vasculitis , and
• in diseases of the lymphatic system, such as malignant lymphoma ,

or as a side effect of therapy with valproic acid .

Classification

The vWS is basically one of the coagulopathies (diseases of (plasmatic) coagulation), although it also influences the cellular cascade and its clinical appearance is more like a hybrid between plasmatic and corpuscular hemostasis disorder.

Von Willebrand-Jürgens syndrome occurs in three forms.

Type 1

Type 1 of Von Willebrand-Jürgens syndrome has a quantitative deficiency of the Von Willebrand factor . 60–80% of the cases correspond to type 1. Clinically, however, most patients show mild symptoms. An almost normal life is possible. Anomalies arise from the tendency of those affected to bleeding for a long time and to bleeding after surgery, the formation of large-scale hematomas and frequent menorrhagia in women affected.

Type 1 autosomal - dominant inherited that penetrance is variable.

Type 2

Type 2 of Von Willebrand-Jürgens syndrome is inherited as an autosomal dominant trait and is found in around 15% of those affected. The presence of qualitative defects of the Von Willebrand factor is characteristic . A distinction is made between the sub-forms 2A, 2B, 2M and 2N. Type 2A is the most common among them.

Type 3

The clinically most severe, but also the rarest form of Von Willebrand-Juergens syndrome is type 3. Those affected have homozygous or compound heterozygous mutations of the vWF gene. This results in a complete absence or a strong reduction (<5%) of the vWF. Type 3 is inherited as an autosomal recessive trait.

clinic

The clinical symptoms are not uniform. A suspicion should arise with the following symptoms:

• increased bleeding tendency
• severe recurrent epistaxis (nosebleeds)
• Tendency to develop large-area hematomas
• long and profuse bleeding even after minor surgical interventions (e.g. tooth extraction )
• Menorrhagia
• Bleeding in the joints ( hemarthrosis )

Diagnosis

Von Willebrand syndrome is diagnosed clinically and using laboratory methods. The diagnosis includes the documentation of past bleeding (bleeding anamnesis), the recording of similar symptoms and diseases in the family and in ancestors (family anamnesis) as well as blood tests . Bleeding scores are a structured way of recording bleeding in a patient's history. They generally correlate with the severity of Von Willebrand syndrome. Type 3 patients have the highest bleeding scores, type 2 medium and type 1 patients the lowest scores.

There is no genetic test that can confirm the most common Von Willebrand syndrome type 1.

Standard blood coagulation tests are usually in the normal range. Any deviations there (with the exception of the a PTT, which is occasionally changed in the vWS ) indicate a different bleeding disorder or additional diseases; Appropriate patient history and physical examination required. The number of blood platelets may be increased in cases of Von Willebrand syndrome type 2B.

The first laboratory tests to include or exclude Von Willebrand syndrome should be:

1. Von Willebrand factor: risocetin cofactor activity
2. Von Willebrand factor antigen
3. Factor VIII activity

The results of the various blood tests are a continuum; they can only be viewed together. Various other physiological states and variants in certain genes (for example ABO, STXBP5, CLEC4M) can change the amount of the Von Willebrand factor in the blood.

Differential diagnoses

Differential diagnoses include other acquired or inherited bleeding tendencies, as well as the possibility that the person has no tendency to bleed at all.

• Mild haemophilia A.
• Hereditary thrombocytopathies ( Bernard-Soulier syndrome , platelet-type (pseudo) vWS)
• Acquired Von Willebrand Syndrome (Acquired Von Willebrand Factor Dysfunction)

therapy

Long-term therapy is usually not necessary. Medicines containing acetylsalicylic acid (such as aspirin) should be avoided , as these additionally inhibit platelet function. Excessive menstrual bleeding can be regulated with a hormonal contraceptive with a higher progestagen content.

The administration of desmopressin is recommended before surgical interventions . After a short desmopressin infusion, the concentration of the Von Willebrand factor increases by up to five times.

Desmopressin does not work in type 2 B. In these and other cases with no effect, the substitution of the Von Willebrand factor and, in acute cases, the administration of activated factor VII or factor VIII.

In type 3 trauma, a Von Willebrand factor / blood coagulation factor VIII preparation is administered in most cases, or it is prophylactically substituted at regular intervals (2–5 days).

literature

• WL Nichols, MB Hultin, AH James, MJ Manco ‐ Johnson, RR Mongomery, TL Ortel, ME Rick, JE Sadler, M. Weinstein, BP Yawn: von Willebrand disease (VWD): evidence ‐ based diagnosis and management guidelines, the National Heart, Lung, and Blood Institute (NHLBI) Expert Panel report (USA) . In: Haemophilia . tape 14 , no. 2 , February 28, 2008, doi : 10.1111 / j.1365-2516.2007.01643.x , PMID 18315614 (English).

Individual evidence

1. ↑ ^{a b} Ute Krause: Von Willebrand-Jürgens Syndrome (vWS). In: Pschyrembel online - pschyrembel.de. Walter de Gruyter GmbH, July 2018, accessed on May 16, 2020 . 
2. ^ Rudolf Juergens. In: whonamedit.com. Whonamedit? - A dictionary of medical eponyms, accessed May 16, 2020 . 
3. ↑ Erik Adolf von Willebrand. In: whonamedit.com. Whonamedit? - A dictionary of medical eponyms, accessed May 16, 2020 . 
4. ↑ Ruchika Sharma, Veronica H. Flood: Advances in the diagnosis and treatment of disease Von Willebrand . In: Blood . tape 130 , no. 22 , November 30, 2017, p. 2386 - 2391 , doi : 10.1182 / blood-2017-05-782029 , PMID 29187375 (English, review).
5. ↑ Yvonne V. Sanders, Karin Fijnvandraat, Johan Boender, Evelien P. Mauser ‐ Bunschoten, Johanna G. van der Bom, Joke de Meris, Frans J. Smiers, Bernd Granzen, Paul Brons, Rienk YJ Tamminga, Marjon H. Cnossen, Frank WG Leebeek, The WiN Study Group: Bleeding spectrum in children with moderate or severe von Willebrand disease: Relevance of pediatric-specific bleeding. In: American journal of hematology . tape 90 , no. 12 , September 16, 2015, doi : 10.1002 / ajh.24195 , PMID 26375306 (English).
6. ^ J. Evan Sadler: Von Willebrand disease type 1: a diagnosis in search of a disease . In: Blood . tape 101 , no. 6 , 2003, p. 2089 - 2093 , doi : 10.1182 / blood-2002-09-2892 , PMID 12411289 (English).
7. ↑ ^{a b c} W. L. Nichols, MB Hultin, AH James, MJ Manco ‐ Johnson, RR Mongomery, TL Ortel, ME Rick, JE Sadler, M. Weinstein, BP Yawn: von Willebrand disease (VWD): evidence ‐ based diagnosis and management guidelines, the National Heart, Lung, and Blood Institute (NHLBI) Expert Panel report (USA) . In: Haemophilia . tape 14 , no. 2 , February 28, 2008, doi : 10.1111 / j.1365-2516.2007.01643.x , PMID 18315614 (English).
8. ↑ Karl C Desch: Regulation of plasma von Willebrand factor. [version 1; peer review: 3 approved] . In: F1000Research . 7 (F1000 Faculty Rev), No. 96 , 2018, doi : 10.12688 / f1000research.13056.1 , PMID 29416854 (English, review).

This article is about a health issue. It is not used for self-diagnosis and does not replace a diagnosis by a doctor. Please note the information on health issues !