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Thromb Haemost 2000; 84(06): 981-988
DOI: 10.1055/s-0037-1614160
Review Article
Schattauer GmbH

Capillary Microscopic and Rheological Dimensions for the Diagnosis of von Willebrand Disease in Comparison to other Haemorrhagic Diatheses

Jürgen K. Koscielny
1   From the Institute for Transfusion Medicine, Medical Faculty Charité, Humboldt-University Berlin, Germany
,
Reinhard Latza
1   From the Institute for Transfusion Medicine, Medical Faculty Charité, Humboldt-University Berlin, Germany
,
Stefan Mürsdorf
,
Christof Mrowietz
2   Department of Clinical Haemostaseology and Transfusion Medicine, University Clinics of the Saarland, Homburg/Saar, Germany
3   Institute for Cardiovascular Research, Dresden, Germany
,
Holger Kiesewetter
1   From the Institute for Transfusion Medicine, Medical Faculty Charité, Humboldt-University Berlin, Germany
,
Ernst Wenzel
2   Department of Clinical Haemostaseology and Transfusion Medicine, University Clinics of the Saarland, Homburg/Saar, Germany
,
Friedrich Jung
2   Department of Clinical Haemostaseology and Transfusion Medicine, University Clinics of the Saarland, Homburg/Saar, Germany
3   Institute for Cardiovascular Research, Dresden, Germany
› Author AffiliationsWe are indebted to Prof. Dr. U. Budde (Hamburg, Germany) for the performance of the multimeric.
Further Information

Publication History

Received 14 October 1999

Accepted after resubmission 06 July 2000

Publication Date:
13 December 2017 (online)

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Summary

It is known that angiodysplasia influence macrocirculation as well as microcirculation in patients with vWD. In the present study it was examined if intravital capillary microscopic dimensions (morphologic and dynamic) in skin (nailfold) in combination with rheologic parameters could give indications for the presence of vWD in patients with haemorrhagic diathesis.

Patients with vWD (n = 100; 92 type 1: definite type 1:78 and possible type 1:14; 8 type 2A) have in comparison to patients with other haemorrhagic diathesis [thrombocytopathy (n = 122), thrombocytopenia (n = 101), severe haemophilia A (n = 50) and severe haemophilia B (n = 20), congenital dysfibrinogenaemia (n = 22), oral anticoagulation with phenprocoumone (n = 112)] and to apparently healthy subjects (n = 100) a significantly increased capillary torquation (median index: 3.5), a venolar and an arteriolar capillary dilatation (median: 16.5 µm; median: 15.1 µm) and the highest part of microscopic bleedings (extravasates) with 40% in the video capillary microscopy as morphological changes. Only the congenital dysfibrinogenaemia appears with a larger dilatation in venolar capillaries (median: 14.5 µm). Microscopic bleedings are much less common in other haemorrhagic diatheses with a frequency between 4% and 13%.

In the vWD a significantly reduced duration of reactive hyperaemia (median: 150 sec). This is the only dynamic change that can be taken as a possible hint for a loss of flexibility within the precapillary vessels. A significantly reduced plasma viscosity (< 1.25 mPas) is typical for the vWD due to the increase of the shear stress in blood plasma because of the reduction of vWF-activities. Changes of the capillary morphology (dilatation, extravasates, capillary torquation) and the hypoplasmaviscosity are most sensitive for the vWD (75%, 65%, 40%, 80%) with a fairly high specifity (up to 93%) and a positive predictive value of 99%.

As a conclusion it seems reasonable to discuss the introduction of video capillary microscopy as a screening test for haemostasiological and angiological centers.

Key words

vWD - haemorrhagic diatheses - capillary microscopy - rheology - microangiopathy
 

  • References

  • 1 Von Willebrand EA. Hereditär Pseudohemofili. Finska Läkarsällskapetes Handl 1926; 67: 7.
    PubMedGoogle Scholar
  • 2 Armand J, Quick PhD. Teleangiectasia: Its Relationship to the Minot-Von Willebrand Syndrome. Am J Med Sci 1967; 11: 585-601.
    PubMedGoogle Scholar
  • 3 O’Brien JR. Familial capillary fragility (Diffuse capillary Teleangiectasia). Proc Int Soc Hematology 1953; 20: 546-8.
    PubMedGoogle Scholar
  • 4 Blackburn EK. Primary capillary haemorrhage (including von Willebrand’s Disease). Brit J Haemat 1961; 07: 239-49.
    CrossrefPubMedGoogle Scholar
  • 5 Koscielny J, Jung F, Kiesewetter H, Franke RP, Radtke H, Wenzel E. Cutaneous microangiopathy in patients with von Willebrand Jürgens syndrome. Clin Hemorheol 1995; 15: 817-23.
    PubMedGoogle Scholar
  • 6 Koscielny J, Jung F, Mrowietz C, Kiesewetter H, Pindur G, Wenzel E. Rheologische und kapillarmikroskopische Größen zur Diagnostik des von- Willebrand-Jürgens-Syndroms. Infusionsther Transfusionsmed 1995; 22: 45-7.
    PubMedGoogle Scholar
  • 7 Koscielny J, Jung F, Seyfert UT, Kiesel J, Groß J, Kiesewetter H, Mrowietz C, Wenzel E. Capillary microscopic findings in patients with von Willebrand-Jürgens syndrome. Ann Hemato 1992; 64: 17.
    PubMedGoogle Scholar
  • 8 Blombäck M, Eneroth P, Andersson O, Anvret M. On laboratory problems in diagnosing mild von Willebrand’s Disease. Am J Hematol 1992; 40: 117-20.
    CrossrefPubMedGoogle Scholar
  • 9 Miller CH, Lenzi R, Breen C. Prevalence of von Willebrand’s disease among U.S. adults. Blood 1989; 70: 377-8.
    PubMedGoogle Scholar
  • 10 Werner E, Broxson E, Tucker E, Giroux D, Shults J, Abshire T. Prevalence of von Willebrand disease in children: Multietnic study. J of Pediatrics 1993; 123: 893-98.
    CrossrefPubMedGoogle Scholar
  • 11 Sadler JE. A revised classification of von Willebrand disease. Thromb Haemost 1994; 71: 520-5.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 12 Budde U, Schneppenheim R, Plendl H, Dent J, Ruggeri ZM, Zimmermann TS. Luminographic detection of von Willebrand Factor multimers in agarose gels and on nitrocellulose membranes. Thromb Haemost 1990; 63: 312-5.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 13 Alström T, Gräsbeck R, Hjelm M, Skandsen S. Recommendations concerning the collection of reference values in clinical chemistry and activity report. Scand J Clin Lab Invest 1975; 35: 1-8.
    CrossrefPubMedGoogle Scholar
  • 14 Jung F, Kiesewetter H, Roggenkamp HG, Nüttgens HP, Ringelstein EB, Gerhards M, Kotitschke G, Wenzel E, Zeller H. Bestimmung der Referenzbereiche rheologischer Parameter: Studie an 653 zufällig ausgewählten Probanden im Kreis Aachen. Klin Wochenschr 1986; 64: 37-43.
    PubMedGoogle Scholar
  • 15 Smith C. Surgicutt: a device for modified template bleeding times. J Med Tech 1986; 03: 229-31.
    PubMedGoogle Scholar
  • 16 Born GVR. Aggregation of blood platelets by adenosine diphosphate and its reversal. Nature 1962; 194: 927-9.
    PubMedGoogle Scholar
  • 17 Entes K, La Duca FM, Tourbaf KD. Flechter factor deficiency, source of variations of the activated partial thromboplastin time test. Amer J Clin Path 1981; 65: 626-30.
    PubMedGoogle Scholar
  • 18 Gruson R, Kernhoff PBA. Diagnostik des von-Willebrand-Jürgens-Syndroms mit Hilfe der quantitativen immunologischen Bestimmung des Faktor VIII-assoziierten Antigens. Dtsch Med Wschr 1974; 99: 1593-7.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 19 Macfarlane DE, Stibbe J, Kirby EP, Zucker MB, Grant RA, McPherson J. A method for assaying von Willebrand factor (Ristocetin cofactor). Thromb Diath Haemorrh 1975; 34: 306-7.
    PubMedGoogle Scholar
  • 20 Clauss A. Gerinnungsphysiologische Schnellmethode zur Bestimmung des Fibrinogens. Acta Haemat 1957; 17: 237-9.
    CrossrefPubMedGoogle Scholar
  • 21 Suchmann AL, Griner PF. Diagnostic uses of activated partial thromboplastin time and prothrombin time. Ann Int Med 1986; 104: 810-2.
    CrossrefPubMedGoogle Scholar
  • 22 Jung F, Seegert A, Roggenkamp HG, Mrowietz C, Nüttgens HP, Kiesewetter H, Zeller H, Müller G. Gleichzeitige Erfassung von Hämatokrit, Erythrozytenaggregation und -desaggregation: Methodik, Qualitätskontrolle und Referenzbereich. Biomed Tech 1987; 32: 117-21.
    CrossrefPubMedGoogle Scholar
  • 23 Jung F, Roggenkamp HG, Ringelstein EB, Schmidt J, Kiesewetter H. Das Kapillarschlauch-Plasmaviskosimeter: Methodik, Qualitätskontrolle und Referenzbereich. Biomed Tech 1985; 30: 239-44.
    CrossrefPubMedGoogle Scholar
  • 24 Jung F, Wappler M, Nüttgens HP, Kiesewetter H, Wolf S, Müller G. Zur Methodik der Videokapillaroskopie: Bestimmung geometrischer und dynamischer Größen. Biomed Tech 1987; 32: 204-13.
    CrossrefPubMedGoogle Scholar
  • 25 Jung F, Toonen H, Mrowietz C, Wolf S, Kiesewetter H, Wenzel E, Gersonde K, Müller G. Fehleranalyse, biologische Einflußfaktoren und Varianz der periunguealen Videokapillaroskopie. Biomed Tech 1990; 35: 195-204.
    PubMedGoogle Scholar
  • 26 Klyscz T, Jünger M, Jung F, Zeintl H. Cap Image – ein neuartiges computergestütztes Videobildanalysesystem für die dynamische Kapillarmikroskopie. Biomed Tech 1997; 42: 168-75.
    CrossrefPubMedGoogle Scholar
  • 27 Schmidt J, Caspary L, von Bierbrauer A, Ehrly A, Jünger M, Jung F, Lawall H. Standardisierung der Nagelfalz-Kapillarmikroskopie in der Routinediagnostik. VASA 1997; 26: 5-10.
    PubMedGoogle Scholar
  • 28 Sachs L. Angewandte Statistik. Springer Verlag; Berlin – Heidelberg – New York: 1984: 1-22.
    CrossrefGoogle Scholar
  • 29 Büttner J. Die Beurteilung des diagnostischen Wertes klinisch-chemischer Untersuchungen. J Clin Chem Biochem 1977; 15: 1-12.
    PubMedGoogle Scholar
  • 30 Galen S, Gambino SR. Norm und Normabweichung klinischer Daten. Gustav Fischer Verlag; Stuttgart: 1979: 4-33.
    Google Scholar
  • 31 Jung F, Waldhausen P, Schwab J, Molter A, Scheffler P, Kiesewetter H, Wenzel E. Einfluß von Naftidrofuryl auf die Mikrozirkulation bei der peripheren arteriellen Verschlußkrankheit. Medwelt 1986; 37: 132-7.
    PubMedGoogle Scholar
  • 32 Birkel L, Scheffler P, Jung F. Untersuchungen zur Wirkung von Dihydroergotamin auf die venöse Makround Mikrostrombahn bei Gefäßgesunden und Patienten mit chronisch venöser Insuffizienz. VASA 1988; 23: 253-6.
    PubMedGoogle Scholar
  • 33 Kiesewetter H, Jung F, Fladung F, Mrowietz C, Wenzel E. Diagnostik und Therapie des Raynaud-Phänomens. Angio 1991; 13: 221-8.
    PubMedGoogle Scholar
  • 34 Bach R, Leicht E, Langer HJ, Hartenstein R, Jung F, Berg G, Schätzer-Klotz D, Bonaventura K, Schieffer H, Weinges KF. Kardiale Funktion und kutane Mikrozirkulation bei Akromegalie. Dtsch med Wschr 1992; 117: 483-9.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 35 Ohlmann P, Jung F, Rosenbaum P, Hummel B, Schäfer P, Schmidt W. Nichtinvasiver Funktionstest zur Überprüfung der Gefäßreagibilität in der Schwangerschaft und bei schwangerschaftsinduzierter Hypertension. Geburtsh Frauenhlk 1992; 52: 327-31.
    PubMedGoogle Scholar
  • 36 Groß J, Seyfert UT, Koscielny J, Wenzel E. Dysfibrinogenämie – Homburg I-VI. In: 22. Hämophilie-Symposium Hamburg 1991. Landbeck G, Scharrer I, Schramm W. Springer-Verlag; Berlin-Heidelberg: 1992: 177-83.
    Google Scholar
  • 37 Kiesewetter H, Körber N, Jung F, Wolf S, Reim M. Die Bedeutung der Fließfähigkeit des Blutes bei diabetischer Retinopathie. In: Diabetische Retinopathie. Lerche W. Schattauer Verlag; Stuttgart: 1984: 25-32.
    Google Scholar
  • 38 Koscielny J, Latza R, Wolf S, Kiesewetter H, Jung F. Early rheological and microcirculatory changes in children with type I diabetes mellitus. Clinical Hemorheology 1998; 19: 139-50.
    PubMedGoogle Scholar
  • 39 Jung F, Kolepke W, Spitzer S, Kiesewetter H, Ruprecht KW, Bach R, Schieffer H, Wenzel E. Primary and secondary microcirculatory disorders in essential hypertension. Clin Investig 1993; 71: 132-8.
    PubMedGoogle Scholar
  • 40 Vlodafsky I, Bar-Shavit R, Ishai-Michaeli R, Bashkin P, Fuchs Z. Extracellular sequestration and release of fibroblast growth factor: a regulatory mechanism?. Tibs 1991; 16: 268-71.
    PubMedGoogle Scholar