- Email: [email protected]
Relapsing post-transfusion purpura. A preventable disease
Relapsing Post-Transfusion Purpura A Preventable Disease
JAMES L. BUDD, M.D. SUSAN E. WIEGERS, M.D. JAMES M. O’HARA, MD. Rochester,
New
York
Post-transfusion purpura is an isoimmune disorder that can recur It unrecognized. A 56-year-old woman is described who had her third episode of post-transfusion purpura 17 years after her last exposure to the inciting antigen. Clinical and immunologic features are reviewed, and specific preventive measures are proposed. Post-transfusion purpura is a syndrome characterized by sudden, profound thrombocytopenia and bleeding, occurring five to 12 days after transfusion of products containing platelet antigens. The syndrome may recur if unrecognized, but effective prevention is available. The following case demonstrates susceptibility to multiple relapses and stresses the importance of more vigorous preventive measures
in these patients. CASE REPORT
From Strong Memorial Hospital, University of Rochester School of Medicine and Dentistry, Rochester, New York. Requests for reprints should be addressed to Dr. James L. Budd, Department of Medicine, Strong Memorial Hospital, 601 Elmwood Avenue, Rochester, New York 14642. Manuscript accepted April 20. 1964.
In 1960, a 33-year-old woman, gravida IV, para IV, had her first episode of thrombocytopenic purpura six days after gastrojejunostomy and blood transfusion. Platelet count of 10,000/mm3 was associated with diffuse petechiae, ecchymoses, hematuria, melena, and a fall in hematocrit to 27 percent. The syndrome resolved within two weeks during prednisone therapy. A second episode occurred in 1966, eight days after a transfusion for menorrhagia. Platelet count fell to 3,000/mm3, and fever, oral mucosal ecchymoses, petechial rash, and vaginal bleeding were noted. Serologic study demonstrated antiplatelet antibody with PI*’ specificity, and autologous platelets after recovery lacked PI*’ antigen. Bleeding resolved and the platelet count recovered by eight days without specific treatment. In 1968, hysterectomy and transfusion with a banked unit of her own blood were uncomplicated. In March 1983, the patient’s gastrojejunostomy required revision. Two units of blood were transfused postoperatively. She presented 10 days later with fulminant thrombocytopenic purpura. Temperature was 39.8’F. Multiple ecchymoses and petechiae covered her skin and oral mucosa. Epistaxis, hematemesis, melena, and incisional bleeding at the recent operative site were noted. Platelet count was 4,000/mm3 and prothrombin time, partial thromboplastin time, and fibrinogen level were normal. Platelet transfusion was begun but interrupted because of rigors and hypotension. Administration of high-dose corticosteroids and aminocaproic acid was begun, but by eight hours the patient was again hypotensive with a hematocrit of 23 percent. Despite cross-matching difficulties, two units of washed red blood cells were infused, and a 4,400 cc plasma exchange was performed. Bleeding stopped within
12 hours
and
the platelet
count
rose
steadily,
normalizing
by the third
day after exchange. Treatment with steroids was rapidly tapered, and the patient recovered unevenffully. Immunoassay again demonstrated high-titer anti-PI*’
antibody
in the acute-phase
February 1985
plasma.
The American Journal of Medlclne
Volume 78
381
RELAPSING
POST-TRANSFUSION
F’UPFURA-BUDD
ET AL
COMMENTS
Since Shulman and associates [l] defined this syndrome in 196 1, at least 42 well-documented cases of post-transfusion purpura have been reported. Most were in women with previous sensitizing pregnancies or transfusions, who lacked PIA antigen. Three men with post-transfusion purpura and two PIA’-positive cases have been described. Serologic studies demonstrated isoantibody directed against the PIA antigen, a platelet antigen present in 97 percent of the general population. The mechanism of autologous platelet destruction by such antibodies remains unclear [l-3]. Thrombocytopenia is severe, and significant bleeding complications are common. Full recovery is expected within flve to 60 days, with or without treatment, although four hemorrhagic deaths have been reported. Plasma exchange appears the most effective means of preventing serious bleeding complications. A single exchange is usually followed by resolution of hemorrhage and rise in platelet count within 46 hours. Immunoglobulin infusion may be effective if apheresis is poorly tolerated or unavailable [4]. Corticosteroid administration remains of unproved value, although a recent report suggests efficacy in one case [ 51. Transfusion with blood products containing PIA1antigen is commonly necessary during the acute phase of post-transfusion purpura. Reactions to such transfusions are frequent and may be severe after platelet transfusion. However, antibody titer decay and time to recovery of platelet count are unaffected, and transfusion should not be withheld if clinically indicated. Susceptibility to relapse upon antigen re-exposure is unpredictable. Reports of uneventful transfusions at
up to 10 years after the initial episode [l] suggest a refractory period. However, relapse upon m-exposure at 20 months is also reported [6]. The observed refractory period has been explained by neutralization and removal of infused antigen by persisting isoantibody before an anamnestic response can occur [7]. Persistence of significant antibody titers for more than a year has been noted [6]. After a variable period, antibody titer fails below a critical protective level, and patients then become susceptible to recurrent posttransfusion purpura. Our case illustrates the potential for multiple recurrences and a vigorous anamnestic response up to 17 years after the last antigen exposure. Although measurement of antibody titer might provide an index of protection, susceptibility to recurrence remains unpredictable in the individual case. Preventive measures in these patients thus become critically important. We would suggest that all such patients wear medical alert bracelets. Certainly, ail subsequent transfusions shoukf be with PIA’-negative blood products following an acute episode of post-transfusion purpura. Siblings should be screened as potential donors and autoiogous units banked if feasible. Platelet antigen typing is not generally available, and thus donor screening should be performed by a regional research laboratory as soon as a case of post-transfusion purpura is identified. Through such measures, cases such as ours can be readily avoided. ACKNOWLEDGMENT
All platelet antigen and antibody typing was performed by N. Raphael Shulman, M.D., National Institutes of Health, Bethesda, Maryland.
REFERENCES 1.
2.
3. 4.
362
Shulrnan NR, Aster RH, Leitner A, Hiller MC: Immunoreactions involving platelets. V. Post-transfusion purpura due to a complement-fixing antibody against a genetically controlled platelet antigen. J Clin Invest 1981; 40: 1597-1820. Kickler TS, Ness PM, Bell WI?: Ability of PIA’-negative platelets to acquire PIA specificity from plasma obtained from stored blood (abstr). Blood 1982; 80 (suppl): 179a. Morrison FS. Mollison PL: Post-transfusion purpura. N Engl J Med 1988; 275: 243-248. Muelfer-Eckhardt C, Kuenzlen E, Thilo-Korner D, Pralle H: Highdose intravenous immunoglobulin for post-transfusion
February 1985
The Amerkan
Journal of Medkine
5. 8.
7.
8.
Volume 78
purpura (letter). N Engl J Med 1983; 308: 287. Welsbarg LJ. Linker CA: Prednll therapy of post-transfusll purpura. Ann Intern Med 1984; 100: 78-77. Soulier J. Patereau C, Gobert N. Achach P. Muller J: Posttransfusional immurologic Wopenia. A case report. Vox Sang 1979; 37: 21-29. 8hulman NR, Jordan JV: Platelet immunology. In: Colman RW, Hirsh J, Marder VJ, Salzman EW, eds. Hemostasis and thrombosis. Philadelphia: JB Lippincott. 1982; 290-298. Lau P, Sholtis CM, Aster RH: Post-transfusion purpura. An enigma of alloimmunization. Am J Hematol 1980; 9: 331-
338.
JAMES L. BUDD, M.D. SUSAN E. WIEGERS, M.D. JAMES M. O’HARA, MD. Rochester,
New
York
Post-transfusion purpura is an isoimmune disorder that can recur It unrecognized. A 56-year-old woman is described who had her third episode of post-transfusion purpura 17 years after her last exposure to the inciting antigen. Clinical and immunologic features are reviewed, and specific preventive measures are proposed. Post-transfusion purpura is a syndrome characterized by sudden, profound thrombocytopenia and bleeding, occurring five to 12 days after transfusion of products containing platelet antigens. The syndrome may recur if unrecognized, but effective prevention is available. The following case demonstrates susceptibility to multiple relapses and stresses the importance of more vigorous preventive measures
in these patients. CASE REPORT
From Strong Memorial Hospital, University of Rochester School of Medicine and Dentistry, Rochester, New York. Requests for reprints should be addressed to Dr. James L. Budd, Department of Medicine, Strong Memorial Hospital, 601 Elmwood Avenue, Rochester, New York 14642. Manuscript accepted April 20. 1964.
In 1960, a 33-year-old woman, gravida IV, para IV, had her first episode of thrombocytopenic purpura six days after gastrojejunostomy and blood transfusion. Platelet count of 10,000/mm3 was associated with diffuse petechiae, ecchymoses, hematuria, melena, and a fall in hematocrit to 27 percent. The syndrome resolved within two weeks during prednisone therapy. A second episode occurred in 1966, eight days after a transfusion for menorrhagia. Platelet count fell to 3,000/mm3, and fever, oral mucosal ecchymoses, petechial rash, and vaginal bleeding were noted. Serologic study demonstrated antiplatelet antibody with PI*’ specificity, and autologous platelets after recovery lacked PI*’ antigen. Bleeding resolved and the platelet count recovered by eight days without specific treatment. In 1968, hysterectomy and transfusion with a banked unit of her own blood were uncomplicated. In March 1983, the patient’s gastrojejunostomy required revision. Two units of blood were transfused postoperatively. She presented 10 days later with fulminant thrombocytopenic purpura. Temperature was 39.8’F. Multiple ecchymoses and petechiae covered her skin and oral mucosa. Epistaxis, hematemesis, melena, and incisional bleeding at the recent operative site were noted. Platelet count was 4,000/mm3 and prothrombin time, partial thromboplastin time, and fibrinogen level were normal. Platelet transfusion was begun but interrupted because of rigors and hypotension. Administration of high-dose corticosteroids and aminocaproic acid was begun, but by eight hours the patient was again hypotensive with a hematocrit of 23 percent. Despite cross-matching difficulties, two units of washed red blood cells were infused, and a 4,400 cc plasma exchange was performed. Bleeding stopped within
12 hours
and
the platelet
count
rose
steadily,
normalizing
by the third
day after exchange. Treatment with steroids was rapidly tapered, and the patient recovered unevenffully. Immunoassay again demonstrated high-titer anti-PI*’
antibody
in the acute-phase
February 1985
plasma.
The American Journal of Medlclne
Volume 78
381
RELAPSING
POST-TRANSFUSION
F’UPFURA-BUDD
ET AL
COMMENTS
Since Shulman and associates [l] defined this syndrome in 196 1, at least 42 well-documented cases of post-transfusion purpura have been reported. Most were in women with previous sensitizing pregnancies or transfusions, who lacked PIA antigen. Three men with post-transfusion purpura and two PIA’-positive cases have been described. Serologic studies demonstrated isoantibody directed against the PIA antigen, a platelet antigen present in 97 percent of the general population. The mechanism of autologous platelet destruction by such antibodies remains unclear [l-3]. Thrombocytopenia is severe, and significant bleeding complications are common. Full recovery is expected within flve to 60 days, with or without treatment, although four hemorrhagic deaths have been reported. Plasma exchange appears the most effective means of preventing serious bleeding complications. A single exchange is usually followed by resolution of hemorrhage and rise in platelet count within 46 hours. Immunoglobulin infusion may be effective if apheresis is poorly tolerated or unavailable [4]. Corticosteroid administration remains of unproved value, although a recent report suggests efficacy in one case [ 51. Transfusion with blood products containing PIA1antigen is commonly necessary during the acute phase of post-transfusion purpura. Reactions to such transfusions are frequent and may be severe after platelet transfusion. However, antibody titer decay and time to recovery of platelet count are unaffected, and transfusion should not be withheld if clinically indicated. Susceptibility to relapse upon antigen re-exposure is unpredictable. Reports of uneventful transfusions at
up to 10 years after the initial episode [l] suggest a refractory period. However, relapse upon m-exposure at 20 months is also reported [6]. The observed refractory period has been explained by neutralization and removal of infused antigen by persisting isoantibody before an anamnestic response can occur [7]. Persistence of significant antibody titers for more than a year has been noted [6]. After a variable period, antibody titer fails below a critical protective level, and patients then become susceptible to recurrent posttransfusion purpura. Our case illustrates the potential for multiple recurrences and a vigorous anamnestic response up to 17 years after the last antigen exposure. Although measurement of antibody titer might provide an index of protection, susceptibility to recurrence remains unpredictable in the individual case. Preventive measures in these patients thus become critically important. We would suggest that all such patients wear medical alert bracelets. Certainly, ail subsequent transfusions shoukf be with PIA’-negative blood products following an acute episode of post-transfusion purpura. Siblings should be screened as potential donors and autoiogous units banked if feasible. Platelet antigen typing is not generally available, and thus donor screening should be performed by a regional research laboratory as soon as a case of post-transfusion purpura is identified. Through such measures, cases such as ours can be readily avoided. ACKNOWLEDGMENT
All platelet antigen and antibody typing was performed by N. Raphael Shulman, M.D., National Institutes of Health, Bethesda, Maryland.
REFERENCES 1.
2.
3. 4.
362
Shulrnan NR, Aster RH, Leitner A, Hiller MC: Immunoreactions involving platelets. V. Post-transfusion purpura due to a complement-fixing antibody against a genetically controlled platelet antigen. J Clin Invest 1981; 40: 1597-1820. Kickler TS, Ness PM, Bell WI?: Ability of PIA’-negative platelets to acquire PIA specificity from plasma obtained from stored blood (abstr). Blood 1982; 80 (suppl): 179a. Morrison FS. Mollison PL: Post-transfusion purpura. N Engl J Med 1988; 275: 243-248. Muelfer-Eckhardt C, Kuenzlen E, Thilo-Korner D, Pralle H: Highdose intravenous immunoglobulin for post-transfusion
February 1985
The Amerkan
Journal of Medkine
5. 8.
7.
8.
Volume 78
purpura (letter). N Engl J Med 1983; 308: 287. Welsbarg LJ. Linker CA: Prednll therapy of post-transfusll purpura. Ann Intern Med 1984; 100: 78-77. Soulier J. Patereau C, Gobert N. Achach P. Muller J: Posttransfusional immurologic Wopenia. A case report. Vox Sang 1979; 37: 21-29. 8hulman NR, Jordan JV: Platelet immunology. In: Colman RW, Hirsh J, Marder VJ, Salzman EW, eds. Hemostasis and thrombosis. Philadelphia: JB Lippincott. 1982; 290-298. Lau P, Sholtis CM, Aster RH: Post-transfusion purpura. An enigma of alloimmunization. Am J Hematol 1980; 9: 331-
338.