CASE REPORT
Scand J Haematol(l979) 22, 305-310
Acquired von Willebrand’s Syndrome and Elders-Danlos Syndrome Presenting with Gastrdntestinal Bleeding VIRGINIA CLOUGH, I. A. MACFARLANE, J. OCONNOR & J. K. WOOD Departments of Haematology and Medicine, Leicester Royal Infirmary, Leicester, England
The clinical and laboratory findings in a patient with severe gastro-intestinal bleeding and the Ehlers-Danlos syndrome are described. Coagulation studies and a lack of history of previous haemorrhage were consistent with a diagnosis of acquired von Willebrand’s syndrome. His response t o treatment with blood transfusion, Factor VIII, cimetidine, tranexamic acid and cyclophosphamide is described. Family studies revealed other members with Ehlers-Danlos syndrome but normal coagulation. Key words: acquired von Willebrand’s syndrome - Ehlers-Danlos syndrome
Accepted for publication January 12, 1979 Correspondence to: D r Virginia Clough, 31, Stonepail Close, Gatley, Manchester, United Kingdom
Von Willebrand’s disease is a hereditary bleeding disorder characterised by a prolonged bleeding time and reduced levels of Factor VIII coagulant activity (Factor VIII:C), Factor VIII related antigen (Factor VIII R:Ag) and Ristocetin cofactor activity (Factor VIII R:RCF) in the plasma. Several examples of acquired von Willebrand’s syndrome (vWS), in patients without a personal or family history of coagulation disturbance, have now been described. It is often associated with immunological or autoimmune disorders such as systemic lupus erythematosus (Simone et a1 1968, Ingram et a1 1971), lymphoma (Handin et a1 1976, Joist et a1 1978), monoclonal gammopathy (Mant et a1 1973, Meyer et a1 1974, Rosborough & Swaim 1978) and
chronic lymphocytic leukaemia (Wautier et a1 1978). The disorder has recently been reviewed by Meyer (1977). We describe in this report a further example of acquired vWS in a patient with Ehlers-Danlos syndrome (EDS). The coexistence of the two syndromes led to his presentation with life threatening gastrointestinal haemorrhage. Coagulation studies and management are described. MATERIALS AND METHODS Routine haematological tests were perfarmed according t o the methods described by Dacie & Lewis (1975). Coagulation studies were performed on blood taken into 3.13 % trisodium citrate (9 parts blood to 1 part citrate). The reference plasma consisted of pooled fresh plasma from 20 normal donors. Platelet-rich plasma and platelet-
0036-553W79/04030546 $02.50/0@ 1979 Munksgaard, Copenhagen
306
V. CLOUGH, I. A. MACFARLANE, J. OCONNOR & J. K. WOOD TABLE 1 Coagulation studies (controls and normal ranges given in brackets)
I Bleeding time Partial thromboplastin time (kaolin) Factor VIII:C Factor VIII R:Ag Factor VIII inhibitors Factor VIII R:RFC Platelet aggregation with ADP Collagen Ristocetin poor plasma from both the patient’s plasma and reference plasma were prepared by the method described by Dacie & Lewis (1975). Bleeding time was performed by the method of Ivy et a1 (1935). Factor VIII coagulant activity (Factor V1II:C) was performed by the method of Biggs et a1 (1935). 1 unit of Factor VIII:C is defined as the amount present in 1 ml of reference plasma. Factor VIII related antigen (Factor VIII R:Ag) was measured by the Laurell technique of rocket immunoelectrophoresis (Laurell 1966). 1 unit of Factor VIII R:Ag is defined as the amount present in 1 ml of reference plasma. Factor VIII antibody was measured by the method of Biggs & Bidwell (1959). 1 unit of antibody is defined as the amount that will destroy 0.75 units of Factor VIII:C after 1 h of incubation. Ristocetin cofactor activity (Factor VIII R: RCF) was assayed quantitatively by the method of Weiss et a1 (1973). 1 unit of Factor VIII R: RCF is defined as the amount present in 1 ml of reference plasma. Platelet aggregation was performed by the turbidometric method of Born (1962). ADP (Boehringer Mannheim Comp., Lewes, East SUSsex, England), collagen (Stago Laboratories, Asnikres, France) and Ristocetin (Lunbeck Limited, Luton, Bedfordshire, England) were used as aggregating agents and used as described in Dacie & Lewis (1975). CASE REPORT A 72-year-old Caucasian man presented as an emergency with a 2-week history of melaena.
At presentation January 1977
I
January 1978
16 min (
Scand J Haematol(l979) 22, 305-310
Acquired von Willebrand’s Syndrome and Elders-Danlos Syndrome Presenting with Gastrdntestinal Bleeding VIRGINIA CLOUGH, I. A. MACFARLANE, J. OCONNOR & J. K. WOOD Departments of Haematology and Medicine, Leicester Royal Infirmary, Leicester, England
The clinical and laboratory findings in a patient with severe gastro-intestinal bleeding and the Ehlers-Danlos syndrome are described. Coagulation studies and a lack of history of previous haemorrhage were consistent with a diagnosis of acquired von Willebrand’s syndrome. His response t o treatment with blood transfusion, Factor VIII, cimetidine, tranexamic acid and cyclophosphamide is described. Family studies revealed other members with Ehlers-Danlos syndrome but normal coagulation. Key words: acquired von Willebrand’s syndrome - Ehlers-Danlos syndrome
Accepted for publication January 12, 1979 Correspondence to: D r Virginia Clough, 31, Stonepail Close, Gatley, Manchester, United Kingdom
Von Willebrand’s disease is a hereditary bleeding disorder characterised by a prolonged bleeding time and reduced levels of Factor VIII coagulant activity (Factor VIII:C), Factor VIII related antigen (Factor VIII R:Ag) and Ristocetin cofactor activity (Factor VIII R:RCF) in the plasma. Several examples of acquired von Willebrand’s syndrome (vWS), in patients without a personal or family history of coagulation disturbance, have now been described. It is often associated with immunological or autoimmune disorders such as systemic lupus erythematosus (Simone et a1 1968, Ingram et a1 1971), lymphoma (Handin et a1 1976, Joist et a1 1978), monoclonal gammopathy (Mant et a1 1973, Meyer et a1 1974, Rosborough & Swaim 1978) and
chronic lymphocytic leukaemia (Wautier et a1 1978). The disorder has recently been reviewed by Meyer (1977). We describe in this report a further example of acquired vWS in a patient with Ehlers-Danlos syndrome (EDS). The coexistence of the two syndromes led to his presentation with life threatening gastrointestinal haemorrhage. Coagulation studies and management are described. MATERIALS AND METHODS Routine haematological tests were perfarmed according t o the methods described by Dacie & Lewis (1975). Coagulation studies were performed on blood taken into 3.13 % trisodium citrate (9 parts blood to 1 part citrate). The reference plasma consisted of pooled fresh plasma from 20 normal donors. Platelet-rich plasma and platelet-
0036-553W79/04030546 $02.50/0@ 1979 Munksgaard, Copenhagen
306
V. CLOUGH, I. A. MACFARLANE, J. OCONNOR & J. K. WOOD TABLE 1 Coagulation studies (controls and normal ranges given in brackets)
I Bleeding time Partial thromboplastin time (kaolin) Factor VIII:C Factor VIII R:Ag Factor VIII inhibitors Factor VIII R:RFC Platelet aggregation with ADP Collagen Ristocetin poor plasma from both the patient’s plasma and reference plasma were prepared by the method described by Dacie & Lewis (1975). Bleeding time was performed by the method of Ivy et a1 (1935). Factor VIII coagulant activity (Factor V1II:C) was performed by the method of Biggs et a1 (1935). 1 unit of Factor VIII:C is defined as the amount present in 1 ml of reference plasma. Factor VIII related antigen (Factor VIII R:Ag) was measured by the Laurell technique of rocket immunoelectrophoresis (Laurell 1966). 1 unit of Factor VIII R:Ag is defined as the amount present in 1 ml of reference plasma. Factor VIII antibody was measured by the method of Biggs & Bidwell (1959). 1 unit of antibody is defined as the amount that will destroy 0.75 units of Factor VIII:C after 1 h of incubation. Ristocetin cofactor activity (Factor VIII R: RCF) was assayed quantitatively by the method of Weiss et a1 (1973). 1 unit of Factor VIII R: RCF is defined as the amount present in 1 ml of reference plasma. Platelet aggregation was performed by the turbidometric method of Born (1962). ADP (Boehringer Mannheim Comp., Lewes, East SUSsex, England), collagen (Stago Laboratories, Asnikres, France) and Ristocetin (Lunbeck Limited, Luton, Bedfordshire, England) were used as aggregating agents and used as described in Dacie & Lewis (1975). CASE REPORT A 72-year-old Caucasian man presented as an emergency with a 2-week history of melaena.
At presentation January 1977
I
January 1978
16 min (
