© 2014 Wiley Periodicals, Inc.
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Post-Transfusion Purpura Following Cardiac Surgery Tolga Demir, M.D.,* Mazlum Sahin, M.D.,y Helin El, M.D.,y and Husnu Sezer, M.D.* *Department of Cardiovascular Surgery, Beylikduzu Kolan Hospital, Istanbul, Turkey; and yDepartment of Cardiovascular Surgery, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey ABSTRACT Post-transfusion purpura (PTP) is a rare disorder characterized by severe thrombocytopenia developing after a blood component transfusion. Ninety percent of the reported cases are women. In this article, we present a case of PTP in a male patient who underwent coronary artery bypass grafting and discuss its management. doi: 10.1111/jocs.12462 (J Card Surg 2015;30:253–255)
Post-transfusion purpura (PTP) is a rare transfusion reaction, characterized by sudden and severe thrombocytopenia occurring approximately one week after the transfusion. Ninety percent of the reported cases are women.1 This is an alloimmune thrombocytopenia against human platelet antigen (HPA) in platelets. These patients produce anti-HPA alloantibodies against transfused HPAs, which paradoxically destroy recipients platelets. The majority of the reported cases (90%) involve anti-HPA-1a antibodies.2 There is a pre-acquired sensitivity in most of the cases. Heavy platelet destruction occurs when HPA positive blood is given to a HPA negative person. The diagnosis is confirmed by demonstrating that the patient’s serum contains antibodies to platelet-specific antigens. Immediate treatment should be initiated due to severe hemorrhagic complications.1,2 In patients with thrombocytopenia PTP can easily be misdiagnosed as heparin-induced thrombocytopenia (HIT). The degree of thrombocytopenia is important to raise the awareness of this transfusion complication. Making the right diagnosis is of vital importance for further management.1–3 We report a case of PTP occurring in a male patient following cardiac surgery. PATIENT PROFILE Institutional Review Board approval was obtained to present this case. A 73-year-old male was admitted
Conflict of interest: The authors acknowledge no conflict of interest in the submission. Address for correspondence: Tolga Demir, M.D., Adnan Kahveci Mah, Osmanli Cad, No. 23, Gurpinar, 34528 Beylikduzu, Istanbul, Turkey. Fax: þ90-212-855-75-70; e-mail: [email protected]
with angina. He had a past medical history of hypertension, type II diabetes mellitus, and duodenal ulcer surgery requiring two units of red blood cell transfusions. A 12-lead electrocardiogram at rest was normal, but he had ischemic ST-T changes on a treadmill exercise test. Cardiac catheterization demonstrated severe two-vessel coronary artery disease with critical stenosis of the proximal left anterior descending (LAD) and osteal right coronary arteries (RCA). The left ventricular ejection fraction was well preserved. The preoperative EuroSCORE II was 1.14%. He was scheduled for elective coronary artery bypass grafting. Preoperatively, the blood count and biochemical tests were within normal limits. The platelet count was 164 109/L. Under cardiopulmonary bypass the LAD and distal RCA were bypassed using the left internal mammary artery and saphenous vein grafts respectively. During the operation, two units of red blood cells were transfused. The early postoperative course was uneventful and platelet counts on the 1st, 2nd, and 4th postoperative days were measured as 135, 163, 132 (109/L), respectively. On the 7th postoperative day the platelet count was 9 109/L. On the next day, the number of platelets dropped to 3 109/L. The patient showed no signs of any bleeding. The patient was initially misdiagnosed as HIT since the severe thrombocytopenia appeared a week after administration of heparin during cardiopulmonary bypass. However, the very low platelet count, history of recent blood transfusion, and lack of thrombotic complications led us to suspect the diagnosis of PTP. On the 10th postoperative day platelet antibodies identification was performed using enzymelinked immunosorbent assay (ELISA) and antibodies against HPA-1a were detected. This confirmed the
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Figure 1. Serial platelet counts demonstrating the response to IVIG therapy. IVIG, Intravenous immunoglobulin.
diagnosis of PTP and high dose intravenous immunoglobulin (IVIG) treatment 2 g kg1 day1 was instituted for five days. The number of platelets started to increase after four days of treatment. On the 20th postoperative day the platelet count had recovered to 59.3 109/L, and the patient was discharged. On the 40th day, the platelet count rose to 163 109/L (Fig. 1). During this time the patient did not develop any hemorrhagic complications related to thrombocytopenia. DISCUSSION PTP is a rare disorder, characterized by sudden and severe thrombocytopenia caused by alloantibodies specific to platelet antigens. The antibody against the human platelet alloantigen HPA-1a is responsible for most of the cases. This condition appears in patients pre-exposed and sensitized to HPA-1a antigens via pregnancy or recent blood product transfusion. HPA-1a positive blood transfusion causes a secondary immune response and the recipient’s platelets are rapidly destroyed approximately seven days following transfusion.1 Its incidence is approximately 1:50.000 to 100.000 following blood transfusions and occurs more commonly in multiparous women. The mortality rate of PTP is 10% to 20%. Despite the absence of randomized studies about PTP IVIG has been used as the first line therapy with one or two doses of 1 to 2 g kg1 day1. Eighty five of patients have positive results with this treatment.2 Corticosteroids and plasmapheresis have been proven beneficial and can be used if IVIG fails to improve platelet counts.4,5 Over 90% of the documented cases of PTP are women. In 1998 Walker et al. reported three cases of PTP occurring after cardiac surgery. All of them were female.6 The most critical complications of PTP are intracranial, gastrointestinal, and urinary system bleeding.1 A study involving 71 patients diagnosed with PTP, showed that five of the patients died of intracranial bleeding.7 Another study by Kroll et al. found that one of 34 patients died of intracranial bleeding. All of them were female. The same study reported that 16 patients had melana and hematuria, which developed between two and seven days.8
J CARD SURG 2015;30:253–255
There are several etiologic factors associated with thrombocytopenia, which may be seen after cardiac surgery. Besides secondary thrombocytopenia related to hemodulution and platelet consumption, the most common one is heparin-induced thrombocytopenia (HIT) with an overall frequency of about 2%.3,9 PTP and HIT are two immune syndromes causing thrombocytopenia with some clinical similarities.1 A rapid and deep platelet count fall that begins 5 to 10 days after cardiac surgery is very suggestive of HIT. In HIT platelet counts rarely fall below 20 109/L. A more pronounced thrombocytopenia usually below 15 109/L is characteristic for PTP. The differential diagnosis between them on clinical grounds alone is still difficult. The final diagnosis is based on identification of antibodies against HPAs. However, detection of anti-HPA antibodies is time-consuming and not widely available. Therefore serologic testing to assist in ruling out HIT (especially the heparin/platelet factor 4 ELISA and the serotonin release assay) may also be helpful in distinguishing between HIT and PTP.1 The treatment of HIT is to prevent thrombotic complications by inhibiting thrombin. This, however, can induce severe hemorrhage in a patient with PTP. Therefore misdiagnosis of this syndrome might lead to the wrong treatment and a fatal outcome.1,2 The differential diagnosis between PTP and HIT was discussed by Lubenow et al.1 According to their study, the platelet count for PTP is generally below 15 109/L and for HIT it is above 20 109/L. This suggests that the correct diagnosis may be based on the degree of thrombocytopenia. In our patient, HIT was suspected initially, however the history of recent blood transfusion and the degree of thrombocytopenia suggested the correct diagnosis of PTP. In severe cases when PTP was suspected Shtalrid et al.2 recommends starting treatment with IVIG even before laboratory confirmation has been received. Our case emphasizes the importance of being alert to the possibility of PTP in patients presented with isolated thrombocytopenia after cardiac surgery. REFERENCES 1. Lubenow N, Eichler P, Albrecht D, et al: Very low platelet counts in post-transfusion purpura falsely diagnosed as heparin induced thrombocytopenia. Report of four cases and review of literature. Thromb Res 2000;100:115– 125. 2. Shtalrid M, Shvidel L, Vorst E, et al: Post-transfusion purpura: A challenging diagnosis. Isr Med Assoc J 2006;8: 672–674. 3. Warkentin TE, Greinacher A: Heparin-induced thrombocytopenia and cardiac surgery. Ann Thorac Surg 2003;76: 2121–2131. 4. Rankin JS, Stratton CW: Efficacy of immunomodulation in the treatment of profound thrombocytopenia after adult cardiac surgery. J Thorac Cardiovasc Surg 2014;147:808– 815. 5. Puig N, Sayas MJ, Montoro JA, et al: Post-transfusion purpura as the main manifestation of a trilineal transfusion reaction, responsive to steroids: Flow-cytometric investigation of granulocyte and platelet antibodies. Ann Hematol 1991;62:232–234.
J CARD SURG 2015;30:253–255
DEMIR, ET AL. POST-TRANSFUSION PURPURA FOLLOWING CARDIAC SURGERY
6. Weisberg LJ, Linker CA: Prednisone therapy of posttransfusion purpura. Ann Intern Med 1984;100:76–77. 7. Walker WS, Yap PL, Kilpatrick DC, et al: Post-transfusion purpura following open heart surgery: Management by high dose intravenous immunoglobulin infusion. Blut 1988;57:323–327. Mueller-Eckhardt C. Post-transfusion purpura. Br J Haematol 1986;64:419–424.
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8. Kroll H, Kiefel V, Mueller-Eckhardt C: Clinical and serologic studies in 34 patients with post-transfusion purpura. Beitr Infusionsther 1992;30:403–407. 9. Vonderheide RH, Thadhani R, Kuter DJ: Association of thrombocytopenia with the use of intra-aortic balloon pumps. Am J Med 1998;105:27–32.
Copyright of Journal of Cardiac Surgery is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
253
PERIOPERATIVE MANAGEMENT_____________________________________________________
Post-Transfusion Purpura Following Cardiac Surgery Tolga Demir, M.D.,* Mazlum Sahin, M.D.,y Helin El, M.D.,y and Husnu Sezer, M.D.* *Department of Cardiovascular Surgery, Beylikduzu Kolan Hospital, Istanbul, Turkey; and yDepartment of Cardiovascular Surgery, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey ABSTRACT Post-transfusion purpura (PTP) is a rare disorder characterized by severe thrombocytopenia developing after a blood component transfusion. Ninety percent of the reported cases are women. In this article, we present a case of PTP in a male patient who underwent coronary artery bypass grafting and discuss its management. doi: 10.1111/jocs.12462 (J Card Surg 2015;30:253–255)
Post-transfusion purpura (PTP) is a rare transfusion reaction, characterized by sudden and severe thrombocytopenia occurring approximately one week after the transfusion. Ninety percent of the reported cases are women.1 This is an alloimmune thrombocytopenia against human platelet antigen (HPA) in platelets. These patients produce anti-HPA alloantibodies against transfused HPAs, which paradoxically destroy recipients platelets. The majority of the reported cases (90%) involve anti-HPA-1a antibodies.2 There is a pre-acquired sensitivity in most of the cases. Heavy platelet destruction occurs when HPA positive blood is given to a HPA negative person. The diagnosis is confirmed by demonstrating that the patient’s serum contains antibodies to platelet-specific antigens. Immediate treatment should be initiated due to severe hemorrhagic complications.1,2 In patients with thrombocytopenia PTP can easily be misdiagnosed as heparin-induced thrombocytopenia (HIT). The degree of thrombocytopenia is important to raise the awareness of this transfusion complication. Making the right diagnosis is of vital importance for further management.1–3 We report a case of PTP occurring in a male patient following cardiac surgery. PATIENT PROFILE Institutional Review Board approval was obtained to present this case. A 73-year-old male was admitted
Conflict of interest: The authors acknowledge no conflict of interest in the submission. Address for correspondence: Tolga Demir, M.D., Adnan Kahveci Mah, Osmanli Cad, No. 23, Gurpinar, 34528 Beylikduzu, Istanbul, Turkey. Fax: þ90-212-855-75-70; e-mail: [email protected]
with angina. He had a past medical history of hypertension, type II diabetes mellitus, and duodenal ulcer surgery requiring two units of red blood cell transfusions. A 12-lead electrocardiogram at rest was normal, but he had ischemic ST-T changes on a treadmill exercise test. Cardiac catheterization demonstrated severe two-vessel coronary artery disease with critical stenosis of the proximal left anterior descending (LAD) and osteal right coronary arteries (RCA). The left ventricular ejection fraction was well preserved. The preoperative EuroSCORE II was 1.14%. He was scheduled for elective coronary artery bypass grafting. Preoperatively, the blood count and biochemical tests were within normal limits. The platelet count was 164 109/L. Under cardiopulmonary bypass the LAD and distal RCA were bypassed using the left internal mammary artery and saphenous vein grafts respectively. During the operation, two units of red blood cells were transfused. The early postoperative course was uneventful and platelet counts on the 1st, 2nd, and 4th postoperative days were measured as 135, 163, 132 (109/L), respectively. On the 7th postoperative day the platelet count was 9 109/L. On the next day, the number of platelets dropped to 3 109/L. The patient showed no signs of any bleeding. The patient was initially misdiagnosed as HIT since the severe thrombocytopenia appeared a week after administration of heparin during cardiopulmonary bypass. However, the very low platelet count, history of recent blood transfusion, and lack of thrombotic complications led us to suspect the diagnosis of PTP. On the 10th postoperative day platelet antibodies identification was performed using enzymelinked immunosorbent assay (ELISA) and antibodies against HPA-1a were detected. This confirmed the
254
DEMIR, ET AL. POST-TRANSFUSION PURPURA FOLLOWING CARDIAC SURGERY
Figure 1. Serial platelet counts demonstrating the response to IVIG therapy. IVIG, Intravenous immunoglobulin.
diagnosis of PTP and high dose intravenous immunoglobulin (IVIG) treatment 2 g kg1 day1 was instituted for five days. The number of platelets started to increase after four days of treatment. On the 20th postoperative day the platelet count had recovered to 59.3 109/L, and the patient was discharged. On the 40th day, the platelet count rose to 163 109/L (Fig. 1). During this time the patient did not develop any hemorrhagic complications related to thrombocytopenia. DISCUSSION PTP is a rare disorder, characterized by sudden and severe thrombocytopenia caused by alloantibodies specific to platelet antigens. The antibody against the human platelet alloantigen HPA-1a is responsible for most of the cases. This condition appears in patients pre-exposed and sensitized to HPA-1a antigens via pregnancy or recent blood product transfusion. HPA-1a positive blood transfusion causes a secondary immune response and the recipient’s platelets are rapidly destroyed approximately seven days following transfusion.1 Its incidence is approximately 1:50.000 to 100.000 following blood transfusions and occurs more commonly in multiparous women. The mortality rate of PTP is 10% to 20%. Despite the absence of randomized studies about PTP IVIG has been used as the first line therapy with one or two doses of 1 to 2 g kg1 day1. Eighty five of patients have positive results with this treatment.2 Corticosteroids and plasmapheresis have been proven beneficial and can be used if IVIG fails to improve platelet counts.4,5 Over 90% of the documented cases of PTP are women. In 1998 Walker et al. reported three cases of PTP occurring after cardiac surgery. All of them were female.6 The most critical complications of PTP are intracranial, gastrointestinal, and urinary system bleeding.1 A study involving 71 patients diagnosed with PTP, showed that five of the patients died of intracranial bleeding.7 Another study by Kroll et al. found that one of 34 patients died of intracranial bleeding. All of them were female. The same study reported that 16 patients had melana and hematuria, which developed between two and seven days.8
J CARD SURG 2015;30:253–255
There are several etiologic factors associated with thrombocytopenia, which may be seen after cardiac surgery. Besides secondary thrombocytopenia related to hemodulution and platelet consumption, the most common one is heparin-induced thrombocytopenia (HIT) with an overall frequency of about 2%.3,9 PTP and HIT are two immune syndromes causing thrombocytopenia with some clinical similarities.1 A rapid and deep platelet count fall that begins 5 to 10 days after cardiac surgery is very suggestive of HIT. In HIT platelet counts rarely fall below 20 109/L. A more pronounced thrombocytopenia usually below 15 109/L is characteristic for PTP. The differential diagnosis between them on clinical grounds alone is still difficult. The final diagnosis is based on identification of antibodies against HPAs. However, detection of anti-HPA antibodies is time-consuming and not widely available. Therefore serologic testing to assist in ruling out HIT (especially the heparin/platelet factor 4 ELISA and the serotonin release assay) may also be helpful in distinguishing between HIT and PTP.1 The treatment of HIT is to prevent thrombotic complications by inhibiting thrombin. This, however, can induce severe hemorrhage in a patient with PTP. Therefore misdiagnosis of this syndrome might lead to the wrong treatment and a fatal outcome.1,2 The differential diagnosis between PTP and HIT was discussed by Lubenow et al.1 According to their study, the platelet count for PTP is generally below 15 109/L and for HIT it is above 20 109/L. This suggests that the correct diagnosis may be based on the degree of thrombocytopenia. In our patient, HIT was suspected initially, however the history of recent blood transfusion and the degree of thrombocytopenia suggested the correct diagnosis of PTP. In severe cases when PTP was suspected Shtalrid et al.2 recommends starting treatment with IVIG even before laboratory confirmation has been received. Our case emphasizes the importance of being alert to the possibility of PTP in patients presented with isolated thrombocytopenia after cardiac surgery. REFERENCES 1. Lubenow N, Eichler P, Albrecht D, et al: Very low platelet counts in post-transfusion purpura falsely diagnosed as heparin induced thrombocytopenia. Report of four cases and review of literature. Thromb Res 2000;100:115– 125. 2. Shtalrid M, Shvidel L, Vorst E, et al: Post-transfusion purpura: A challenging diagnosis. Isr Med Assoc J 2006;8: 672–674. 3. Warkentin TE, Greinacher A: Heparin-induced thrombocytopenia and cardiac surgery. Ann Thorac Surg 2003;76: 2121–2131. 4. Rankin JS, Stratton CW: Efficacy of immunomodulation in the treatment of profound thrombocytopenia after adult cardiac surgery. J Thorac Cardiovasc Surg 2014;147:808– 815. 5. Puig N, Sayas MJ, Montoro JA, et al: Post-transfusion purpura as the main manifestation of a trilineal transfusion reaction, responsive to steroids: Flow-cytometric investigation of granulocyte and platelet antibodies. Ann Hematol 1991;62:232–234.
J CARD SURG 2015;30:253–255
DEMIR, ET AL. POST-TRANSFUSION PURPURA FOLLOWING CARDIAC SURGERY
6. Weisberg LJ, Linker CA: Prednisone therapy of posttransfusion purpura. Ann Intern Med 1984;100:76–77. 7. Walker WS, Yap PL, Kilpatrick DC, et al: Post-transfusion purpura following open heart surgery: Management by high dose intravenous immunoglobulin infusion. Blut 1988;57:323–327. Mueller-Eckhardt C. Post-transfusion purpura. Br J Haematol 1986;64:419–424.
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8. Kroll H, Kiefel V, Mueller-Eckhardt C: Clinical and serologic studies in 34 patients with post-transfusion purpura. Beitr Infusionsther 1992;30:403–407. 9. Vonderheide RH, Thadhani R, Kuter DJ: Association of thrombocytopenia with the use of intra-aortic balloon pumps. Am J Med 1998;105:27–32.
Copyright of Journal of Cardiac Surgery is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
