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The use of porcine factor viii in the treatment of patients with acquired hemophilia: The United Kingdom experience
The Use of Porcine Factor VIII in the Treatment of Patients With Acquired Hemophilia: The United Kingdom Experience ANNE
E.
MORRISON,
M.D.,
CHRISTOPHER
A. LUDLAM, M.D., Edinburgh,
Data have been collected by questionnaire on 15 acute bleeding episodes in 12 patients with acquired hemophilia, treated with porcine factor VIII (FVIII). The median initial antihuman FVIII inhibitor level was 40 Bethesda Units (BU)/ml, whereas that against porcine was 1 BU/ml. The mean initial dose of porcine FVIII infused was 54 pg/kg, which resulted in a rise of 0.57 IU/mL in the FVIII concentration. Therapy was continued for a mean of 8.5 days, during which time the average number of infusions was 11. Clinical response was rated as good or excellent in 82% of recipients. Side effects were uncommon; only one patient experienced a severe reaction. Following therapy, no increase in antihuman antibody levels was noted; increased levels of antiporcine antibody was detected in only two patients. One patient bled on three further occasions and was successfully retreated with porcine FVIII. Porcine FVIII is a safe and clinically effective treatment for bleeding episodes in acquired hemophilia and should be considered as first-line therapy for patients with low antiportine FVIII levels.
.%ot/and, United Kingdom
A
cquired hemophilia is a rare disorder characterized by the spontaneous development of an antibody to the plasma coagulation factor VIII (FVIII). The management of such patients is not well established and a variety of therapeutic options have been used. As any incliviclual clinician is unlikely to treat many patients with acquired hemophilia, it is difficult to establish optimum therapeutic regimens. In an attempt to determine the role of porcine FVIII in the treatment of such patients, we undertook a survey of patients with acquired hemophilia in the United Kingdom. We obtained data on 12 patients with acquirecl hemophilia who had been treated with porcine FVIII for 15 bleecling episodes. We report here details of these patients and their responses to such treatment.
PATIENTSAND METHODS Information about patients with acquired hemophilia treated with porcine FVIII concentrate was obtained from published cases [l-41, and the manufacturers (Porton Speywood Limitecl, ‘Wrexham, Wales, U.K.). The clinicians responsible for the patients were contacted and invited to complete a questionnaire to give patient and treatment details. Patients
The patients were treated at eight centers within the United Kingdom. Details of the patients and their underlying diagnoses are given in Tables I ancl II. Bleeding Episodes
Of the 12 patients, 11 hacl a single bleeding episode and one re-bled on three further occasions. Details of the hemorrhagic episodes are given in Table III; the commonest sites were into muscles, skin, and urinary tract, although there were also major gastrointestinal and psoas muscle hemorrhages. Bleeding occurrecl at multiple sites in 40% of the patients. From the Department of Haematology, Royal Infirmary, Edinburgh, Scotland, United Kingdom. Requests for reprints should be addressed to A. E. Morrison, M.D., Department Of Haematology. Royal Infirmary. Edinburgh, Scotland, United Kingdom.
Human Blood Products
Prior to the use of porcine FVIII, eight patients received other blood products (Table IV). Several
November 4,
1991 The American Journal of Medicine
Volume 91 (suppl
5A)
5A-23s
SYMPOSIUM
ON ACQUIRED FVIII INHIBlTORS I MORRISON and LUDLAM
“‘;:I
Number of patients (makfemale)
TABLEII Associated Conditions No. of Patients (%)
Mean Age
3 I251 3 (251
56
Connective tkue or autoimmune disease Pregnancy associated Other/unknown
ii
6 (50)
patients received therapy.
treatment
Immunosuppressive
Therapy
with more than one
In addition to therapy with blood and blood products, 10 patients (83%) received immunosuppressive therapy. Cyclophosphamide and steroids were the most commonly used drugs (Table V>. The varying length of follow-up preclucles assessment of whether immunosuppressive therapy resulted in the disappearance of the inhibitor.
RESULTS Clinical Response
TABLEIll BleedingManifestations Site Muscle ’ Postoperative Skin Hemahuia Intra.abdominal Other
No. of Patients
%
3
20
4 (n = 15)
TABLEIV Blood Products Prior to Porcine Factor VIII Product
No. of Patients
Fresh frozen plasma Cryoprecipitate Red cell concentrate Human FVIII Prothrombin complex
%
:
1:
: 1
:: 5 (n = 20)
TABLEV
No. of Patients Cyclophosphamide Steroids IV IgG Azathioprine Plasmapheresis Vincristine Desmopressin Oral antifibrinoiytic
%
6 :z :
I1
:
1:
1 4
: 15 in = 27l
Side Effects to Porcine Factor VIII
TABLEVI Clinical Response No. of Patients
EF 5A-24s
%
2
Fair None
: 0
Total
11
November 4, 1991
Clinicians were asked to grade the response to treatment with porcine FVIII as none, fair, good, or excellent. An excellent response was defined as a dramatic response with abrupt pain relief and unequivocal reduction in joint or bleed site size within 8 hours; a good response as pain relief or reduction in bleed site size that was delayed or required more than one infusion of porcine FVIII; a fair response was a probable or slight beneficial response. Of the 11 patients in whom it was possible to determine the response to porcine FVIII therapy, nine (82%) had a good or excellent response and two (18%) had a fair response. No patient had no response to porcine FVIII therapy (Table VI). The two patients who had a fair response to treatment developed acquired hemophilia associated with pregnancy. The first, an l&year-old, required hysterectomy for persistent postpartum bleeding, which continued postoperatively. She received treatment with multiple blood products (fresh frozen plasma, cryoprecipitate, human FVIII, concentrated red cells, and platelets), desmopressin, immunosuppression, and an oral antifibrinolytic. She was treated for 4 days with porcine FVIII resulting in temporary cessation of the bleeding. She later re-bled and despite further blood product therapy, not including porcine FVIII, died. The second patient was a 36-year-old woman with von Willebrand’s disease who also developed acquirecl hemophilia postpartum. She was treated with porcine FVIII for 14 days for postpartum bleeding and recovered fully.
The American Journal of Medicine
ii 18 0
Only one patient had a major anaphylactic response to treatment with porcine FVIII that led to therapy being discontinued. One patient had a minor reaction (rigor and back pain) to the infusions, but clicl not require interruption of therapy. The reaction was abolished’ by treatment with hydrocortisone and chlorpheniramine. The remaining 10 patients had no adverse reaction to porcine Volume 91 (suppl 5A)
FVIII therapy. No patient developed thrombocytopenia while being treated with porcine FVIII. Inhibitor Response to Porcine FVlll Treatment
Initial median antihuman inhibitor levels were 40 BU/mL with a range 5-108 BU/mL. After approximately 1 month of therapy, antihuman inhibitor levels were assessed at a median level of 16 BU/mL with a range 1-112 BU/mL. The median presentation antiporcine inhibitor level was 1 BU/mL, range Cl-lo, and at follow-up post-treatment the median antiporcine inhibitor level was 6 BU/mL. Two patients showed a rise in porcine inhibitor level of 10 BU/mL or more. Re-bleeding Episodes
One patient, a 67-year-old man, re-bled on three subsequent occasions and was successfully retreated with porcine FVIII. He was re-treated with a dose of porcine FVIII equivalent to his initial dose and on each occasion the porcine FVIII was as effective as it had been initially.
COMMENT Acquired hemophilia is a rare disorder being cliagnosed. in 0.2-l per million population per annum and is caused by the development of an autoantibody against FVIII. These antibodies are almost always IgG ancl, although some inter-species crossreactivity can be demonstrated, are much more active against human than animal FVIII [5]. There is a recognized association between acquired hemophilia and a number of diseases, particularly those with an autoimmune basis. These inclucle rheumatoid arthritis [63 and other connective tissue cliseases, inflammatory bowel disease [7,8], malignancy, skin diseases such as pemphigus, drug treatment (particularly penicillin), and multiple sclerosis [91. Acquired hemophilia may also occur postpartum, but in the majority of cases, as in this study, no underlying cause can be found [lO,ll]. Patients with acquired hemophilia may present with spontaneous bleeds into muscles or joints, ecchymoses, hematuria, or persistent bleeding postoperatively or following minor trauma. Retroperitoneal hemorrhage is not uncommon, but may present particular difficulties in diagnosis and is frequently fatal [lo, 121. In one survey of 215 patients with acquired hemophilia, 37% experienced serious bleeding, and in 40 (19%) of these patients, death was attributecl, directly or indirectly, to the presence of the inhibitor to FVIII [ll]. As acute bleeding episodes in patients with acquired hemophilia are a source of considerable morbidity and mortality, an effective treatment is required. A number of therapeutic options are used, as may be seen from this and November
other studies [6,7,10,11,13]. In general, transfused human FVIII is inactivated by the circulating autoantibody although higher than normal doses may be effective in some cases. Prothrombin complex concentrates (PCCs) have also been used in the treatment of patients with antibodies to FVIII. Difficulties in monitoring the response to treatment and concern about the side effects of such concentrates,. in particular the development of disseminated intravascular coagulation and thrombosis (which. have been reported in noninhibitor patients treated with PCCs), have tended to limit their use [14,151. The low level of interspecies cross-reactivity of the FVIII antibody led to the use of porcine FVIII to treat patients with congenital hemophilia A with allo-antibodies. Polyelectrolyte fractionated porcine FVIII (Hyate:C; Porton Products Limited) has been available since 1980 and has been used successfully to treat both congenital hemophiliacs with inhibitors and patients with acquired hemophilia [1,13,21,22]. Prolonged and repeated courses have been administerecl without loss of effect; other side effects previously associated with porcine FVIII treatment-such as thrombocytopenia, anaphylactic reactions, and anamnestic response to treatment-have been reported only rarely [1,2,81. It is of particular interest to note that there was very little antibody reactivity against porcine FVIII in the cases reported in this study. The median anti-human FVIII level was 35 BU/mL, whereas against porcine FVIII it was only 1 BUI mL. Although this low level of cross-reactivity between human and porcine FVIII may be a universal feature of acquired hemophilia, it should be notecl that the patients may have been treated because they had low anti-porcine titers. Thus the patients reported in this study are a self-selected group who may not be representative of all patients with acquired hemophilia. The results of this survey of porcine FVIII concentrate support the conclusions of other reviews [131 that this treatment is safe and clinically effective therapy in the treatment of bleeding due to acquirecl hemophilia. It shoulcl be noted that the patients reported here may be a selected group who were treated with porcine FVIII because they had very low inhibitor levels against this therapeutic concentrate. This study, however, clearly demonstrates that in patients with acquired hemophilia the anti-porcine inhibitor shoulcl be measured when the patient first presents, and if low, porcine FVIII concentrate should be considered as possible firstline therapy.
CONTRIBUTORS The fottowing investigators contributed to this survey: AL. Bloom. B. Calvin. Kernoff. CA. Ludlam. V.E. Mitchell. E.E Mayne, G. Savidge, DA. Taberner. 4, 1991
The American
Journal
of Medicine
Volume
91 (suppl
5A)
P.&A
5A-25s
SYMPOSIUM
ON ACQUIRED FVlll INHIBITORS /MORRISON
and LUDLAM
REFERENCES 1. Kemoff PB, Thomas ND, Lilley PA, Matthews KB, Goldman E. Tuddenham EG. Clinical experience with polyelectrolytefractionated porcine factor VIII concentrate in the treatment of hemophiliacs with antibodies to factor VIII. Blood 1984; 63: 31-41. 2 Erskine JG, Davidson JF. Anaphylactic reaction to low-molecularweight porcine factor VIII concentrates. Br Med J pin Res) 1981; 282: 2011-2. * 3. Moreau P, PineauVincent F, Laneelle D. Acquired FVIII inhibitor in an 80 year old lady, the benefit of porcine factor VIII therapy. Proceedings of the XVIII International Congress of the World Federation of Haemophilia 1988: Madrid, Spain; 109. (Abstract 162) 4. Treble NJ, Dasani H. Amputation for pseudotumour in acquired haemophilia. 8r Med J pin Res) 1984; 289: 1349-50. 5. Shulman NR, Hirschman RI. Acquired haemophilia. Trans Assoc Am Physicians 1969; 82: 388-97. 6. Soriano RM. Matthews JM. Guerado.Parra E. Acquired haemophilia and rheumatoid arthritis. Br J kheumatol 1987; 26: 381-3. 7. Waddell CC, Ashton CM, Brown Jk Use of porcine Factor VIII concentrate. (Letter]. JAMA 1985; 253: 344. 8. Weston-Smith SG, Revel1 P. Lawrie AS, Holland IJ, Savidge GF. The rapid development of an IgM inhibitor of porcine factor VIII in a patient with acquired haemophilia. 8r J Haematol 1990; 75: 434-6. 9. Hoyle C. Ludlam CA Acquired factor VIII inhibitor associated with multiple sclerosis, successfully treaded with porcine factor VIII. Thromb Haemost 1987; 57: 233. 10. Lottenberg R, Kentro T8, Kitchens C’S Acquired hemophilia. A natural history study of 16 patients with factor VIII inhibitors receiving little or no therapy. Arch Intern Med 1987: 147: 1077-81.
5A-26s
November 4, 1991
The American Journal of Medicine
11. Green D, Lechner K. A survey of 215 nonhemophilic Factor VIII. Thromb Haemost 1981; 45: 200-3.
patients
with inhibltors
to
12. Roy V, Tillyer mL, Colvin ET. Acute abdominal pain due to an acquired disorder of coagulation. Br Med J pin Res) 1988; 296: 1460-1460. 13. Brettler DB. Forsberg AD, Levine PH, et al. The use of porcine factor VIII concentrate (Hyate:C) in the treatment of patients with inhibitor antibodies to factor VIII. A multicenter US experience. Arch Intern Med 1989; 149: 1381-1385. 14. Blatt PM, Lundblad RL. Kingdon HS, McLean G, Roberts HR. Thrombogenic materials in prothrombin complex concentrates. Ann Intern Med 1974: 81: 766-70. 15. Davey RI. Shashasty GG, Rath CE. Acute coagulopathy following infusion of prothrombin complex concentrates. Am J Med 1976; 60: 719-22. 16. Bidwell E. The purification of antihaemophilic globulin from animal plasma. Br J Haematol 1955; 1: 386-9. 17. MacFarlane RG, Mallam PC, Witts U. Surgery in haemophilia, the use of animal antihaemophllic globulins and human plasma in thirteen cases. Lancet 1957; 2: 251-9. 18. Kernoff PB. The clinical use of porcine factor VIII. Prog Clin Biol Res 1990; 324: 47-56. 19. Evans RJ, Austen DE. Assay and characterization of the factor in porcine and bovine plasma which aggregates human platelets. Br J Haematol 1977; 36: 117-26. 20. Johnson AL MacDonald VE, Semar M. Preparation of the major plasma fractions by solidphase polyelectrolytes. J Lab Clin Med 1978; 92(Z): 194-210. 21. Ciavarella N. Antoncecchi S. Ranieri P. Efficay of porcine factor VIII in the management of haemophiliacs with inhibitors. Br J Haematol 1984; 58: 641-8. 22. Hultin MB. Hennessey J. The use of polyelectrolytefractionated porcine factor VIII in the treatment of a spontaneously acquired inhibitor to factor VIII. Thromb Res 1989; 55: 51-6.
Volume 91 (suppl 5A)
E.
MORRISON,
M.D.,
CHRISTOPHER
A. LUDLAM, M.D., Edinburgh,
Data have been collected by questionnaire on 15 acute bleeding episodes in 12 patients with acquired hemophilia, treated with porcine factor VIII (FVIII). The median initial antihuman FVIII inhibitor level was 40 Bethesda Units (BU)/ml, whereas that against porcine was 1 BU/ml. The mean initial dose of porcine FVIII infused was 54 pg/kg, which resulted in a rise of 0.57 IU/mL in the FVIII concentration. Therapy was continued for a mean of 8.5 days, during which time the average number of infusions was 11. Clinical response was rated as good or excellent in 82% of recipients. Side effects were uncommon; only one patient experienced a severe reaction. Following therapy, no increase in antihuman antibody levels was noted; increased levels of antiporcine antibody was detected in only two patients. One patient bled on three further occasions and was successfully retreated with porcine FVIII. Porcine FVIII is a safe and clinically effective treatment for bleeding episodes in acquired hemophilia and should be considered as first-line therapy for patients with low antiportine FVIII levels.
.%ot/and, United Kingdom
A
cquired hemophilia is a rare disorder characterized by the spontaneous development of an antibody to the plasma coagulation factor VIII (FVIII). The management of such patients is not well established and a variety of therapeutic options have been used. As any incliviclual clinician is unlikely to treat many patients with acquired hemophilia, it is difficult to establish optimum therapeutic regimens. In an attempt to determine the role of porcine FVIII in the treatment of such patients, we undertook a survey of patients with acquired hemophilia in the United Kingdom. We obtained data on 12 patients with acquirecl hemophilia who had been treated with porcine FVIII for 15 bleecling episodes. We report here details of these patients and their responses to such treatment.
PATIENTSAND METHODS Information about patients with acquired hemophilia treated with porcine FVIII concentrate was obtained from published cases [l-41, and the manufacturers (Porton Speywood Limitecl, ‘Wrexham, Wales, U.K.). The clinicians responsible for the patients were contacted and invited to complete a questionnaire to give patient and treatment details. Patients
The patients were treated at eight centers within the United Kingdom. Details of the patients and their underlying diagnoses are given in Tables I ancl II. Bleeding Episodes
Of the 12 patients, 11 hacl a single bleeding episode and one re-bled on three further occasions. Details of the hemorrhagic episodes are given in Table III; the commonest sites were into muscles, skin, and urinary tract, although there were also major gastrointestinal and psoas muscle hemorrhages. Bleeding occurrecl at multiple sites in 40% of the patients. From the Department of Haematology, Royal Infirmary, Edinburgh, Scotland, United Kingdom. Requests for reprints should be addressed to A. E. Morrison, M.D., Department Of Haematology. Royal Infirmary. Edinburgh, Scotland, United Kingdom.
Human Blood Products
Prior to the use of porcine FVIII, eight patients received other blood products (Table IV). Several
November 4,
1991 The American Journal of Medicine
Volume 91 (suppl
5A)
5A-23s
SYMPOSIUM
ON ACQUIRED FVIII INHIBlTORS I MORRISON and LUDLAM
“‘;:I
Number of patients (makfemale)
TABLEII Associated Conditions No. of Patients (%)
Mean Age
3 I251 3 (251
56
Connective tkue or autoimmune disease Pregnancy associated Other/unknown
ii
6 (50)
patients received therapy.
treatment
Immunosuppressive
Therapy
with more than one
In addition to therapy with blood and blood products, 10 patients (83%) received immunosuppressive therapy. Cyclophosphamide and steroids were the most commonly used drugs (Table V>. The varying length of follow-up preclucles assessment of whether immunosuppressive therapy resulted in the disappearance of the inhibitor.
RESULTS Clinical Response
TABLEIll BleedingManifestations Site Muscle ’ Postoperative Skin Hemahuia Intra.abdominal Other
No. of Patients
%
3
20
4 (n = 15)
TABLEIV Blood Products Prior to Porcine Factor VIII Product
No. of Patients
Fresh frozen plasma Cryoprecipitate Red cell concentrate Human FVIII Prothrombin complex
%
:
1:
: 1
:: 5 (n = 20)
TABLEV
No. of Patients Cyclophosphamide Steroids IV IgG Azathioprine Plasmapheresis Vincristine Desmopressin Oral antifibrinoiytic
%
6 :z :
I1
:
1:
1 4
: 15 in = 27l
Side Effects to Porcine Factor VIII
TABLEVI Clinical Response No. of Patients
EF 5A-24s
%
2
Fair None
: 0
Total
11
November 4, 1991
Clinicians were asked to grade the response to treatment with porcine FVIII as none, fair, good, or excellent. An excellent response was defined as a dramatic response with abrupt pain relief and unequivocal reduction in joint or bleed site size within 8 hours; a good response as pain relief or reduction in bleed site size that was delayed or required more than one infusion of porcine FVIII; a fair response was a probable or slight beneficial response. Of the 11 patients in whom it was possible to determine the response to porcine FVIII therapy, nine (82%) had a good or excellent response and two (18%) had a fair response. No patient had no response to porcine FVIII therapy (Table VI). The two patients who had a fair response to treatment developed acquired hemophilia associated with pregnancy. The first, an l&year-old, required hysterectomy for persistent postpartum bleeding, which continued postoperatively. She received treatment with multiple blood products (fresh frozen plasma, cryoprecipitate, human FVIII, concentrated red cells, and platelets), desmopressin, immunosuppression, and an oral antifibrinolytic. She was treated for 4 days with porcine FVIII resulting in temporary cessation of the bleeding. She later re-bled and despite further blood product therapy, not including porcine FVIII, died. The second patient was a 36-year-old woman with von Willebrand’s disease who also developed acquirecl hemophilia postpartum. She was treated with porcine FVIII for 14 days for postpartum bleeding and recovered fully.
The American Journal of Medicine
ii 18 0
Only one patient had a major anaphylactic response to treatment with porcine FVIII that led to therapy being discontinued. One patient had a minor reaction (rigor and back pain) to the infusions, but clicl not require interruption of therapy. The reaction was abolished’ by treatment with hydrocortisone and chlorpheniramine. The remaining 10 patients had no adverse reaction to porcine Volume 91 (suppl 5A)
FVIII therapy. No patient developed thrombocytopenia while being treated with porcine FVIII. Inhibitor Response to Porcine FVlll Treatment
Initial median antihuman inhibitor levels were 40 BU/mL with a range 5-108 BU/mL. After approximately 1 month of therapy, antihuman inhibitor levels were assessed at a median level of 16 BU/mL with a range 1-112 BU/mL. The median presentation antiporcine inhibitor level was 1 BU/mL, range Cl-lo, and at follow-up post-treatment the median antiporcine inhibitor level was 6 BU/mL. Two patients showed a rise in porcine inhibitor level of 10 BU/mL or more. Re-bleeding Episodes
One patient, a 67-year-old man, re-bled on three subsequent occasions and was successfully retreated with porcine FVIII. He was re-treated with a dose of porcine FVIII equivalent to his initial dose and on each occasion the porcine FVIII was as effective as it had been initially.
COMMENT Acquired hemophilia is a rare disorder being cliagnosed. in 0.2-l per million population per annum and is caused by the development of an autoantibody against FVIII. These antibodies are almost always IgG ancl, although some inter-species crossreactivity can be demonstrated, are much more active against human than animal FVIII [5]. There is a recognized association between acquired hemophilia and a number of diseases, particularly those with an autoimmune basis. These inclucle rheumatoid arthritis [63 and other connective tissue cliseases, inflammatory bowel disease [7,8], malignancy, skin diseases such as pemphigus, drug treatment (particularly penicillin), and multiple sclerosis [91. Acquired hemophilia may also occur postpartum, but in the majority of cases, as in this study, no underlying cause can be found [lO,ll]. Patients with acquired hemophilia may present with spontaneous bleeds into muscles or joints, ecchymoses, hematuria, or persistent bleeding postoperatively or following minor trauma. Retroperitoneal hemorrhage is not uncommon, but may present particular difficulties in diagnosis and is frequently fatal [lo, 121. In one survey of 215 patients with acquired hemophilia, 37% experienced serious bleeding, and in 40 (19%) of these patients, death was attributecl, directly or indirectly, to the presence of the inhibitor to FVIII [ll]. As acute bleeding episodes in patients with acquired hemophilia are a source of considerable morbidity and mortality, an effective treatment is required. A number of therapeutic options are used, as may be seen from this and November
other studies [6,7,10,11,13]. In general, transfused human FVIII is inactivated by the circulating autoantibody although higher than normal doses may be effective in some cases. Prothrombin complex concentrates (PCCs) have also been used in the treatment of patients with antibodies to FVIII. Difficulties in monitoring the response to treatment and concern about the side effects of such concentrates,. in particular the development of disseminated intravascular coagulation and thrombosis (which. have been reported in noninhibitor patients treated with PCCs), have tended to limit their use [14,151. The low level of interspecies cross-reactivity of the FVIII antibody led to the use of porcine FVIII to treat patients with congenital hemophilia A with allo-antibodies. Polyelectrolyte fractionated porcine FVIII (Hyate:C; Porton Products Limited) has been available since 1980 and has been used successfully to treat both congenital hemophiliacs with inhibitors and patients with acquired hemophilia [1,13,21,22]. Prolonged and repeated courses have been administerecl without loss of effect; other side effects previously associated with porcine FVIII treatment-such as thrombocytopenia, anaphylactic reactions, and anamnestic response to treatment-have been reported only rarely [1,2,81. It is of particular interest to note that there was very little antibody reactivity against porcine FVIII in the cases reported in this study. The median anti-human FVIII level was 35 BU/mL, whereas against porcine FVIII it was only 1 BUI mL. Although this low level of cross-reactivity between human and porcine FVIII may be a universal feature of acquired hemophilia, it should be notecl that the patients may have been treated because they had low anti-porcine titers. Thus the patients reported in this study are a self-selected group who may not be representative of all patients with acquired hemophilia. The results of this survey of porcine FVIII concentrate support the conclusions of other reviews [131 that this treatment is safe and clinically effective therapy in the treatment of bleeding due to acquirecl hemophilia. It shoulcl be noted that the patients reported here may be a selected group who were treated with porcine FVIII because they had very low inhibitor levels against this therapeutic concentrate. This study, however, clearly demonstrates that in patients with acquired hemophilia the anti-porcine inhibitor shoulcl be measured when the patient first presents, and if low, porcine FVIII concentrate should be considered as possible firstline therapy.
CONTRIBUTORS The fottowing investigators contributed to this survey: AL. Bloom. B. Calvin. Kernoff. CA. Ludlam. V.E. Mitchell. E.E Mayne, G. Savidge, DA. Taberner. 4, 1991
The American
Journal
of Medicine
Volume
91 (suppl
5A)
P.&A
5A-25s
SYMPOSIUM
ON ACQUIRED FVlll INHIBITORS /MORRISON
and LUDLAM
REFERENCES 1. Kemoff PB, Thomas ND, Lilley PA, Matthews KB, Goldman E. Tuddenham EG. Clinical experience with polyelectrolytefractionated porcine factor VIII concentrate in the treatment of hemophiliacs with antibodies to factor VIII. Blood 1984; 63: 31-41. 2 Erskine JG, Davidson JF. Anaphylactic reaction to low-molecularweight porcine factor VIII concentrates. Br Med J pin Res) 1981; 282: 2011-2. * 3. Moreau P, PineauVincent F, Laneelle D. Acquired FVIII inhibitor in an 80 year old lady, the benefit of porcine factor VIII therapy. Proceedings of the XVIII International Congress of the World Federation of Haemophilia 1988: Madrid, Spain; 109. (Abstract 162) 4. Treble NJ, Dasani H. Amputation for pseudotumour in acquired haemophilia. 8r Med J pin Res) 1984; 289: 1349-50. 5. Shulman NR, Hirschman RI. Acquired haemophilia. Trans Assoc Am Physicians 1969; 82: 388-97. 6. Soriano RM. Matthews JM. Guerado.Parra E. Acquired haemophilia and rheumatoid arthritis. Br J kheumatol 1987; 26: 381-3. 7. Waddell CC, Ashton CM, Brown Jk Use of porcine Factor VIII concentrate. (Letter]. JAMA 1985; 253: 344. 8. Weston-Smith SG, Revel1 P. Lawrie AS, Holland IJ, Savidge GF. The rapid development of an IgM inhibitor of porcine factor VIII in a patient with acquired haemophilia. 8r J Haematol 1990; 75: 434-6. 9. Hoyle C. Ludlam CA Acquired factor VIII inhibitor associated with multiple sclerosis, successfully treaded with porcine factor VIII. Thromb Haemost 1987; 57: 233. 10. Lottenberg R, Kentro T8, Kitchens C’S Acquired hemophilia. A natural history study of 16 patients with factor VIII inhibitors receiving little or no therapy. Arch Intern Med 1987: 147: 1077-81.
5A-26s
November 4, 1991
The American Journal of Medicine
11. Green D, Lechner K. A survey of 215 nonhemophilic Factor VIII. Thromb Haemost 1981; 45: 200-3.
patients
with inhibltors
to
12. Roy V, Tillyer mL, Colvin ET. Acute abdominal pain due to an acquired disorder of coagulation. Br Med J pin Res) 1988; 296: 1460-1460. 13. Brettler DB. Forsberg AD, Levine PH, et al. The use of porcine factor VIII concentrate (Hyate:C) in the treatment of patients with inhibitor antibodies to factor VIII. A multicenter US experience. Arch Intern Med 1989; 149: 1381-1385. 14. Blatt PM, Lundblad RL. Kingdon HS, McLean G, Roberts HR. Thrombogenic materials in prothrombin complex concentrates. Ann Intern Med 1974: 81: 766-70. 15. Davey RI. Shashasty GG, Rath CE. Acute coagulopathy following infusion of prothrombin complex concentrates. Am J Med 1976; 60: 719-22. 16. Bidwell E. The purification of antihaemophilic globulin from animal plasma. Br J Haematol 1955; 1: 386-9. 17. MacFarlane RG, Mallam PC, Witts U. Surgery in haemophilia, the use of animal antihaemophllic globulins and human plasma in thirteen cases. Lancet 1957; 2: 251-9. 18. Kernoff PB. The clinical use of porcine factor VIII. Prog Clin Biol Res 1990; 324: 47-56. 19. Evans RJ, Austen DE. Assay and characterization of the factor in porcine and bovine plasma which aggregates human platelets. Br J Haematol 1977; 36: 117-26. 20. Johnson AL MacDonald VE, Semar M. Preparation of the major plasma fractions by solidphase polyelectrolytes. J Lab Clin Med 1978; 92(Z): 194-210. 21. Ciavarella N. Antoncecchi S. Ranieri P. Efficay of porcine factor VIII in the management of haemophiliacs with inhibitors. Br J Haematol 1984; 58: 641-8. 22. Hultin MB. Hennessey J. The use of polyelectrolytefractionated porcine factor VIII in the treatment of a spontaneously acquired inhibitor to factor VIII. Thromb Res 1989; 55: 51-6.
Volume 91 (suppl 5A)