American Journal of Hematology 6: 149-153 (1979)
Immune Thrombocytopenic Purpura in Hodgkin Disease Kamran Hassidim, Robert McMillan, Michael S. Conjalka, and John Morrison Division of Hematology and Oncology, Scripps Clinic and Research Foundation, La Jolla, California (K. H., R.M., M.S.C.), and the Department of Internal Medicine and Clinical Investigation Center, Naval Regional Medical Center, San Diego (J.M.)
Immune thrombocytopenic purpura is rarely seen in Hodgkin disease and the presence of platelet-associated antibody has not been previously reported in these patients. A patient with Hodgkin disease is described who developed a destructive thrombocytopenia demonstrated by shortened platelet survival. In conjunction with his thrombocytopenia, he had marked elevation of platelet-associated immunoglobulin G levels (nanograms IgG per 1O9 platelets: 1 5,187 prior to splenectomy and 7 1,130 and 8 1,900 after surgery). Mean values (+ SD) of control subjects averaged 1,975 ? 381 and four patients with Hodgkin disease and normal platelet counts had levels ranging from 1,581 t o 4,011. We suggest that this patient had immune-mediated thrombocytopenia; whether the increase in platelet-associated immunoglobulin G was due t o antiplatelet antibody or to adsorbed or phagocytosed immune complexes cannot be demonstrated by these studies. The platelet-associated immunoglobulin G test may be useful in evaluating these patients. Key words: ITP, Hodgkin disease, antiplatelet antibody
INTRODUCTION
Immune thrombocytopenic purpura (ITP) is seen rarely in patients with Hodgkin disease. In the few reported cases that suggested immune-mediated platelet destruction, the immunologic nature of this phenomenon was not documented [l-41. We recently encountered a patient with Hodgkin disease who developed a destructive thrombocytopenia in conjunction with an elevation of platelet-associated immunoglobulin G (PAIgG). To the best of our knowledge, this is the first report of such an association.
Received for publication August 25, 1978; accepted December 30, 1978. Reprint requests to Dr. Kamran Hassidim, Division of Hematology and Oncology, Scripps Clinic and Research Foundation, La Jolla, CA 92037.
0361-8609/79/0602-Ol49$01.40 @ 1979 Alan R. Liss, Inc.
150
Case Reports: Hassidim et al
CASE REPORT
A 55-year-old white man presented with fever, chills, and weght loss in March 1976. Physical examination revealed bilateral cervical, left supraclavicular, and right axillary lymphadenopathy with hepatosplenomegaly. Laboratory data included a hemoglobin level of 7.2 gm/dl and hematocrit value of 23 ~ 0 1 %The . white blood cell count was 2,6OO/cu mm with 44% lymphocytes, 23% neutrophils, 28% band forms, and 5% monocytes. The platelet count was 223,OOO/cu mm and the reticulocyte count was 1.7%. The Coombs’ test results were negative. Chest films revealed hilar adenopathy. Biopsy of a cervical lymph node showed Hodgkin disease, lymphocyte-depleted type (Lukes-Butler). Involvement of bone marrow was seen on biopsy. The patient was staged anatomically as stage IVB. Treatment with chemotherapy was initiated, consisting of six courses of CytoxanB),Vincristine, Prednisone, and Procarbazine (COPP), followed by three courses of Adriamycin, Bleomycin, VelbanB, and DTIC (ABVD). All symptoms and signs of Hodgkin disease disappeared and the patient remained asymptomatic for six months. In July 1977 lymphadenopathy and hepatosplenomegaly reappeared; the patient was given three more courses of COPP and he again responded. In November 1977, he was admitted to the hospital because of rectal bleeding and hemoptysis. He had no recent drug ingestion or chemical exposure. On admission vital signs were normal; multiple echymoses and petechiae were noted. There was no lymphadenopathy or hepatosplenomegaly, although there was a mass palpable in the upper abdomen. Neurologic examination was normal. The hemoglobin level was 7.2 gm/dl and hematocrit value was 24 ~ 0 1 %The . white blood cell count was 5,2OO/cu mm with 79% neutrophils, 11% lymphocytes, 7%band forms, and 3% monocytes. The platelet count was 4,OOO/cu mm. The blood smear showed some anisocytosis and poikilocytosis of red blood cells, toxic granulation in the granulocytes, and markedly decreased platelets. The prothrombin time was 12.4 seconds (control 12.7 seconds); the partial thromboplastin time was 32.5 seconds (control 42.5 seconds); the fibrinogen was 3 12 mg% (normal range 147-33 5) and the protamine sulfate test was negative. Bone marrow aspiration revealed granulocytic hyperplasia and a marked increase in megakaryocytes. The serum alkaline phosphatase was increased to 350 munits/ml (normal values are 30-120 munits/ml). The Coombs’ test and antinuclear antibody were negative. Serum immune complexes were not increased. The chest films were normal. Multiple retroperitoneal masses consistent with lymphadenopathy and a mass 5 cm in diameter at the junction of the right and left lobe of the liver were seen on an abdominal computerized axial tomography scan. On the basis of the above clinical and laboratory data, a diagnosis of immune thrombocytopenic purpura in association with Hodgkin disease was tentatively made. The patient was given 100 mg of prednisone daily and one injection of 2 mg vincristine intravenously. Due to progressive anemia and bleeding from mucosal surfaces, two units of packed red cells and 16 units of platelet concentrates were transfused. Four hours after platelet transfusion, the patient’s platelet count had returned to pretransfusion levels. During the next eight days, he was supported with multiple blood transfusions with packed red cells. He received no further platelet transfusions and his platelet count remained unchanged in spite of therapy. The platelet-asssociated immunoglobulin G value was measured and it was found to be elevated (see below). On day 9, the patient complained of abdominal pain and his abdomen was markedly distended. An exploratory laparotomy was performed and a massive hemoperitoneurn was found, as well as enlarged
Case Reports: ITP in Hodgkin Disease
151
paraaortic lymph nodes and masses in the body of the pancreas and liver parenchyma. Splenectomy was done and biopsies of the liver and pancreas were obtained. Hodglun disease, lymphocyte-depleted type, was noted in the liver, spleen, pancreas and paraaortic lymph nodes. Postoperatively the patient received high doses of corticosteroids intravenously and was again started on COPP chemotherapy. He received daily transfusions with platelet concentrates as therapy for continued bleeding; however, in spite of this his platelet count remained unchanged atless than 5,OOO/cu mm. On day 17, he developed aphasia and right hemiplegia. His neurologic condition deteriorated and he died on the 20th hospital day. Permission for autopsy was not granted. MATERIALS AND METHODS
PAIgC values were measured as previously reported [5] except that the platelets were washed mechanically six times in 0.05 M citrate buffer (PH 6.2) rather than by gel fdtration. After washing, PAIgC was assayed using the Fab-anti Fab method [5]. Control values (nanograms IgG per lo9 platelets) using this washing technique were somewhat higher than those obtained with gel filtration (mean k SD of 1,975 k 381 compared to 1,231 k 424). RESULTS
Table I summarizes our results. The mean (5 SD) PAIgG value (nanograms IgC per lo9 platelets) for 17 normal subjects was 1,975 381 and for 19 adults with chronic
*
TABLE 1. Platelet-Associated IgG Levels in Patients With Hodgkin Disease and in Control Subjects ~
Patient
Clinical stage
1. HD - I T P ~
IVB, active
Hodgkin therapya Platelet count (per cu mm) None
PAIgG (ng lgG/109 platelets)
4,000 (presplenectomy)
15,187
2,000 (day 4, postsplenectomy)
71,130
4,000 (day 11, postsplenectomy)
81,900
2. HD
11, active
None
264,000
4,011
3. HD
IVA, responding
MOPP
430,000
2,114
4. HD
IVB, active
None
450,000
2,107
5 . HD
IVB, responding
LP
320,000
1,581
Controls (17 subjects)
1,975 f 381
Chronic ITP (19 patients)
4,711
* 3,025
aMOPP) nitrogen mustard, vincristine, prednisolone and procarbazine; LP) leukeran and prednisone. bHD) Hodgkin disease; ITP) immune thrombocytopenia purpura.
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Case Reports: Hassidim et a1
immune thrombocytopenic purpura (ITP) was 4,711 5 3,025 [ 5 ] .The PAIgG values of four patients with Hodgkin disease who were not thrombocytopenic ranged from 1,581 to 4,011. The patient’s PAIgG value of 15,187 ng IgG per lo9 platelets prior t o splenectomy was markedly elevated when compared either to the control subjects, chronic ITP patients, or the four nonthrombocytopenic patients with Hodgkin disease; postsplenectomy values were even more increased, with levels of 71,130 and 81,900 obtained 4 and 11 days after surgery, respectively. COMMENTS
Thrombocytopenic purpura is commonly seen in Hodgkin disease as a result of bone marrow failure due to the disease or secondary to treatment with chemotherapy or radiation therapy. Less frequently encountered in Hodgkin disease is thrombocytopenia with the features of immune thrombocytopenic purpura. This entity is characterized by documented intravascular destruction of platelets and the presence of normal or increased numbers of megakaryocytes in the bone marrow. In one recent review [4], only ten cases of immune thrombocytopenia with Hodgkin disease were found in the literature. In 1960 Doan [ l ] reported four cases of Hodgkin disease in his review of 381 cases of ITP; they were not classified by histologic type. In 1972 Rudders et a1 [2] reported three cases of immune thrombocytopenia associated with Hodgkin disease, two patients with mixed cellularity, and one patient with nodular sclerosis. Jones, in 1973 [3], reported two cases of nodular sclerosing-type Hodgkin disease with immune thrombocytopenia. He emphasized the uncommon occurrence of autoimmune disorders in Hodgkin disease and noted that only 2% of patients with this disease have associated autoimmune hemolytic anemia or immune thrombocytopenia during the course of their disease. Julia and Miller in 1976 [4] reported a patient with mixed-cell Hodgkin disease who developed immune thrombocytopenia. In this patient, the serum was tested for antiplatelet antibody using a complement fixation method; negative results were obtained. Our patient satisfies the criteria for immune thrombocytopenia in Hodgkin disease. A destructive thrombocytopenia was documented by the failure of transfused platelets to circulate and the increased numbers of megakaryocytes in the bone marrow. The markedly elevated PAIgC levels provide support for immune-mediated destruction of platelets. Three possible explanations for the increase of PAIgC levels must be considered: 1) an antibody against a platelet autoantigen, 2) an antibody against a tenaciously adsorbed antigen, or 3) adsorbed or phagocytosed immune complexes. Presently available assays do not allow us to differentiate between these possibilities, although we feel the third possibility is most likely. Longmire and co-workers [6] have shown, in patients with Hodgkin disease, the presence of antibodies that bind t o lymphocytes and destroy them. If this mechanism were ongoing in this patient, it could explain the severe lymphocyte depletion as well as the presence of immune complexes that could adsorb to or be phagocytosed by the platelets. The markedly elevated PAIgC levels are most consistent with this hypothesis, since similarly high levels have been noted in other diseases that are presumed to have circulating complexes (eg, systemic lupus erythematosus, vasculitis), whereas patients with chronic ITP, a disease thought due to a platelet autoantigen, have less elevated PAIgG values for a given platelet count (Table I) [7] . The absence of demonstrable circulating immune complexes does not rule out this possibility. On the
Case Reports: ITP in Hodgkin Disease
153
other hand, if the antibody against lymphocytes in Hodgkin disease is an autoantibody, it might suggest that antibody against other autoantigens (platelets) could also develop. Further studies will be required to settle this issue. ACKNOWLEDGMENTS
This study was supported in part by Public Health Service grant AM-16 125, REFERENCES 1. Doan CA, Bouroncle BA, Wiseman BK: Idiopathic and secondary thrombocytopenic purpura Clinical study and evaluation of 381 cases over a period of 28 years. Ann Intern Med 53:861, 1960. 2. Rudders RA, Aisenberg AC, Schiller AL: Hodgkin’s disease presenting as “idiopathic” thrombocytopenic purpura. Cancer 30:220, 1972. 3. Jones SE: Autoimmune disorders and malignant lymphoma. Cancer 31: 1032, 1973. 4. Julia A, Miller SP: Idiopathic thrombocytopenic purpura in Hodgkin’s disease after splenectomy. Am J Hematol 1:115,1976. 5. Luiken GA, McMillan R, Lightsey AL, et al: Platelet-associated IgG in immune thrombocytopenic purpura. Blood 50:317, 1977. 6. Longmire RL, Ryan S, McMillan R: Antibody-dependent lymphocytotoxicity induced by immunoglobulin G from Hodgkin’s disease splenic lymphocytes. Science 199:71, 1978. 7. McMillan R, Yelenosky RJ, Bakich MJ, Schulman I, Lightsey AL: Platelet-associated IgG - an assay for immune-mediated thrombocytopenia. In Day HJ, Holmsen H, Zucker MB (eds): “Proceedings of Workshop on Platelets: The Significance of Platelet Function Tests in the Evaluation of Hemostatic and Thrombotic Tendencies.” DHEW Publication No. (NIH) 78-1087. Washington, DC: Government Printing Office, p 598.
Immune Thrombocytopenic Purpura in Hodgkin Disease Kamran Hassidim, Robert McMillan, Michael S. Conjalka, and John Morrison Division of Hematology and Oncology, Scripps Clinic and Research Foundation, La Jolla, California (K. H., R.M., M.S.C.), and the Department of Internal Medicine and Clinical Investigation Center, Naval Regional Medical Center, San Diego (J.M.)
Immune thrombocytopenic purpura is rarely seen in Hodgkin disease and the presence of platelet-associated antibody has not been previously reported in these patients. A patient with Hodgkin disease is described who developed a destructive thrombocytopenia demonstrated by shortened platelet survival. In conjunction with his thrombocytopenia, he had marked elevation of platelet-associated immunoglobulin G levels (nanograms IgG per 1O9 platelets: 1 5,187 prior to splenectomy and 7 1,130 and 8 1,900 after surgery). Mean values (+ SD) of control subjects averaged 1,975 ? 381 and four patients with Hodgkin disease and normal platelet counts had levels ranging from 1,581 t o 4,011. We suggest that this patient had immune-mediated thrombocytopenia; whether the increase in platelet-associated immunoglobulin G was due t o antiplatelet antibody or to adsorbed or phagocytosed immune complexes cannot be demonstrated by these studies. The platelet-associated immunoglobulin G test may be useful in evaluating these patients. Key words: ITP, Hodgkin disease, antiplatelet antibody
INTRODUCTION
Immune thrombocytopenic purpura (ITP) is seen rarely in patients with Hodgkin disease. In the few reported cases that suggested immune-mediated platelet destruction, the immunologic nature of this phenomenon was not documented [l-41. We recently encountered a patient with Hodgkin disease who developed a destructive thrombocytopenia in conjunction with an elevation of platelet-associated immunoglobulin G (PAIgG). To the best of our knowledge, this is the first report of such an association.
Received for publication August 25, 1978; accepted December 30, 1978. Reprint requests to Dr. Kamran Hassidim, Division of Hematology and Oncology, Scripps Clinic and Research Foundation, La Jolla, CA 92037.
0361-8609/79/0602-Ol49$01.40 @ 1979 Alan R. Liss, Inc.
150
Case Reports: Hassidim et al
CASE REPORT
A 55-year-old white man presented with fever, chills, and weght loss in March 1976. Physical examination revealed bilateral cervical, left supraclavicular, and right axillary lymphadenopathy with hepatosplenomegaly. Laboratory data included a hemoglobin level of 7.2 gm/dl and hematocrit value of 23 ~ 0 1 %The . white blood cell count was 2,6OO/cu mm with 44% lymphocytes, 23% neutrophils, 28% band forms, and 5% monocytes. The platelet count was 223,OOO/cu mm and the reticulocyte count was 1.7%. The Coombs’ test results were negative. Chest films revealed hilar adenopathy. Biopsy of a cervical lymph node showed Hodgkin disease, lymphocyte-depleted type (Lukes-Butler). Involvement of bone marrow was seen on biopsy. The patient was staged anatomically as stage IVB. Treatment with chemotherapy was initiated, consisting of six courses of CytoxanB),Vincristine, Prednisone, and Procarbazine (COPP), followed by three courses of Adriamycin, Bleomycin, VelbanB, and DTIC (ABVD). All symptoms and signs of Hodgkin disease disappeared and the patient remained asymptomatic for six months. In July 1977 lymphadenopathy and hepatosplenomegaly reappeared; the patient was given three more courses of COPP and he again responded. In November 1977, he was admitted to the hospital because of rectal bleeding and hemoptysis. He had no recent drug ingestion or chemical exposure. On admission vital signs were normal; multiple echymoses and petechiae were noted. There was no lymphadenopathy or hepatosplenomegaly, although there was a mass palpable in the upper abdomen. Neurologic examination was normal. The hemoglobin level was 7.2 gm/dl and hematocrit value was 24 ~ 0 1 %The . white blood cell count was 5,2OO/cu mm with 79% neutrophils, 11% lymphocytes, 7%band forms, and 3% monocytes. The platelet count was 4,OOO/cu mm. The blood smear showed some anisocytosis and poikilocytosis of red blood cells, toxic granulation in the granulocytes, and markedly decreased platelets. The prothrombin time was 12.4 seconds (control 12.7 seconds); the partial thromboplastin time was 32.5 seconds (control 42.5 seconds); the fibrinogen was 3 12 mg% (normal range 147-33 5) and the protamine sulfate test was negative. Bone marrow aspiration revealed granulocytic hyperplasia and a marked increase in megakaryocytes. The serum alkaline phosphatase was increased to 350 munits/ml (normal values are 30-120 munits/ml). The Coombs’ test and antinuclear antibody were negative. Serum immune complexes were not increased. The chest films were normal. Multiple retroperitoneal masses consistent with lymphadenopathy and a mass 5 cm in diameter at the junction of the right and left lobe of the liver were seen on an abdominal computerized axial tomography scan. On the basis of the above clinical and laboratory data, a diagnosis of immune thrombocytopenic purpura in association with Hodgkin disease was tentatively made. The patient was given 100 mg of prednisone daily and one injection of 2 mg vincristine intravenously. Due to progressive anemia and bleeding from mucosal surfaces, two units of packed red cells and 16 units of platelet concentrates were transfused. Four hours after platelet transfusion, the patient’s platelet count had returned to pretransfusion levels. During the next eight days, he was supported with multiple blood transfusions with packed red cells. He received no further platelet transfusions and his platelet count remained unchanged in spite of therapy. The platelet-asssociated immunoglobulin G value was measured and it was found to be elevated (see below). On day 9, the patient complained of abdominal pain and his abdomen was markedly distended. An exploratory laparotomy was performed and a massive hemoperitoneurn was found, as well as enlarged
Case Reports: ITP in Hodgkin Disease
151
paraaortic lymph nodes and masses in the body of the pancreas and liver parenchyma. Splenectomy was done and biopsies of the liver and pancreas were obtained. Hodglun disease, lymphocyte-depleted type, was noted in the liver, spleen, pancreas and paraaortic lymph nodes. Postoperatively the patient received high doses of corticosteroids intravenously and was again started on COPP chemotherapy. He received daily transfusions with platelet concentrates as therapy for continued bleeding; however, in spite of this his platelet count remained unchanged atless than 5,OOO/cu mm. On day 17, he developed aphasia and right hemiplegia. His neurologic condition deteriorated and he died on the 20th hospital day. Permission for autopsy was not granted. MATERIALS AND METHODS
PAIgC values were measured as previously reported [5] except that the platelets were washed mechanically six times in 0.05 M citrate buffer (PH 6.2) rather than by gel fdtration. After washing, PAIgC was assayed using the Fab-anti Fab method [5]. Control values (nanograms IgG per lo9 platelets) using this washing technique were somewhat higher than those obtained with gel filtration (mean k SD of 1,975 k 381 compared to 1,231 k 424). RESULTS
Table I summarizes our results. The mean (5 SD) PAIgG value (nanograms IgC per lo9 platelets) for 17 normal subjects was 1,975 381 and for 19 adults with chronic
*
TABLE 1. Platelet-Associated IgG Levels in Patients With Hodgkin Disease and in Control Subjects ~
Patient
Clinical stage
1. HD - I T P ~
IVB, active
Hodgkin therapya Platelet count (per cu mm) None
PAIgG (ng lgG/109 platelets)
4,000 (presplenectomy)
15,187
2,000 (day 4, postsplenectomy)
71,130
4,000 (day 11, postsplenectomy)
81,900
2. HD
11, active
None
264,000
4,011
3. HD
IVA, responding
MOPP
430,000
2,114
4. HD
IVB, active
None
450,000
2,107
5 . HD
IVB, responding
LP
320,000
1,581
Controls (17 subjects)
1,975 f 381
Chronic ITP (19 patients)
4,711
* 3,025
aMOPP) nitrogen mustard, vincristine, prednisolone and procarbazine; LP) leukeran and prednisone. bHD) Hodgkin disease; ITP) immune thrombocytopenia purpura.
152
Case Reports: Hassidim et a1
immune thrombocytopenic purpura (ITP) was 4,711 5 3,025 [ 5 ] .The PAIgG values of four patients with Hodgkin disease who were not thrombocytopenic ranged from 1,581 to 4,011. The patient’s PAIgG value of 15,187 ng IgG per lo9 platelets prior t o splenectomy was markedly elevated when compared either to the control subjects, chronic ITP patients, or the four nonthrombocytopenic patients with Hodgkin disease; postsplenectomy values were even more increased, with levels of 71,130 and 81,900 obtained 4 and 11 days after surgery, respectively. COMMENTS
Thrombocytopenic purpura is commonly seen in Hodgkin disease as a result of bone marrow failure due to the disease or secondary to treatment with chemotherapy or radiation therapy. Less frequently encountered in Hodgkin disease is thrombocytopenia with the features of immune thrombocytopenic purpura. This entity is characterized by documented intravascular destruction of platelets and the presence of normal or increased numbers of megakaryocytes in the bone marrow. In one recent review [4], only ten cases of immune thrombocytopenia with Hodgkin disease were found in the literature. In 1960 Doan [ l ] reported four cases of Hodgkin disease in his review of 381 cases of ITP; they were not classified by histologic type. In 1972 Rudders et a1 [2] reported three cases of immune thrombocytopenia associated with Hodgkin disease, two patients with mixed cellularity, and one patient with nodular sclerosis. Jones, in 1973 [3], reported two cases of nodular sclerosing-type Hodgkin disease with immune thrombocytopenia. He emphasized the uncommon occurrence of autoimmune disorders in Hodgkin disease and noted that only 2% of patients with this disease have associated autoimmune hemolytic anemia or immune thrombocytopenia during the course of their disease. Julia and Miller in 1976 [4] reported a patient with mixed-cell Hodgkin disease who developed immune thrombocytopenia. In this patient, the serum was tested for antiplatelet antibody using a complement fixation method; negative results were obtained. Our patient satisfies the criteria for immune thrombocytopenia in Hodgkin disease. A destructive thrombocytopenia was documented by the failure of transfused platelets to circulate and the increased numbers of megakaryocytes in the bone marrow. The markedly elevated PAIgC levels provide support for immune-mediated destruction of platelets. Three possible explanations for the increase of PAIgC levels must be considered: 1) an antibody against a platelet autoantigen, 2) an antibody against a tenaciously adsorbed antigen, or 3) adsorbed or phagocytosed immune complexes. Presently available assays do not allow us to differentiate between these possibilities, although we feel the third possibility is most likely. Longmire and co-workers [6] have shown, in patients with Hodgkin disease, the presence of antibodies that bind t o lymphocytes and destroy them. If this mechanism were ongoing in this patient, it could explain the severe lymphocyte depletion as well as the presence of immune complexes that could adsorb to or be phagocytosed by the platelets. The markedly elevated PAIgC levels are most consistent with this hypothesis, since similarly high levels have been noted in other diseases that are presumed to have circulating complexes (eg, systemic lupus erythematosus, vasculitis), whereas patients with chronic ITP, a disease thought due to a platelet autoantigen, have less elevated PAIgG values for a given platelet count (Table I) [7] . The absence of demonstrable circulating immune complexes does not rule out this possibility. On the
Case Reports: ITP in Hodgkin Disease
153
other hand, if the antibody against lymphocytes in Hodgkin disease is an autoantibody, it might suggest that antibody against other autoantigens (platelets) could also develop. Further studies will be required to settle this issue. ACKNOWLEDGMENTS
This study was supported in part by Public Health Service grant AM-16 125, REFERENCES 1. Doan CA, Bouroncle BA, Wiseman BK: Idiopathic and secondary thrombocytopenic purpura Clinical study and evaluation of 381 cases over a period of 28 years. Ann Intern Med 53:861, 1960. 2. Rudders RA, Aisenberg AC, Schiller AL: Hodgkin’s disease presenting as “idiopathic” thrombocytopenic purpura. Cancer 30:220, 1972. 3. Jones SE: Autoimmune disorders and malignant lymphoma. Cancer 31: 1032, 1973. 4. Julia A, Miller SP: Idiopathic thrombocytopenic purpura in Hodgkin’s disease after splenectomy. Am J Hematol 1:115,1976. 5. Luiken GA, McMillan R, Lightsey AL, et al: Platelet-associated IgG in immune thrombocytopenic purpura. Blood 50:317, 1977. 6. Longmire RL, Ryan S, McMillan R: Antibody-dependent lymphocytotoxicity induced by immunoglobulin G from Hodgkin’s disease splenic lymphocytes. Science 199:71, 1978. 7. McMillan R, Yelenosky RJ, Bakich MJ, Schulman I, Lightsey AL: Platelet-associated IgG - an assay for immune-mediated thrombocytopenia. In Day HJ, Holmsen H, Zucker MB (eds): “Proceedings of Workshop on Platelets: The Significance of Platelet Function Tests in the Evaluation of Hemostatic and Thrombotic Tendencies.” DHEW Publication No. (NIH) 78-1087. Washington, DC: Government Printing Office, p 598.
