Ann Hematol DOI 10.1007/s00277-014-2223-9
ORIGINAL ARTICLE
Outcomes of platelet transfusion in patients with thrombotic thrombocytopenic purpura: a retrospective case series study Amy Zhou & Rohtesh S. Mehta & Roy E. Smith
Received: 13 June 2014 / Accepted: 25 September 2014 # Springer-Verlag Berlin Heidelberg 2014
Abstract Current guidelines advise against the transfusion of platelets in patients with thrombotic thrombocytopenic purpura (TTP) except in cases of life-threatening hemorrhage. We conducted a retrospective medical chart review to examine the outcomes of patients with TTP who received platelet transfusion at our institution from September 2002 to September 2012. A search for “thrombotic thrombocytopenic purpura” in the discharge summary identified 233 patients, out of which only 15 patients had TTP and received platelet transfusion. Primary outcomes were death due to any cause, myocardial infarction, ischemic stroke, coma, seizure, or worsening neurologic status within 24 h of platelet transfusion. Secondary outcomes included bleeding and worsening thrombocytopenia. No adverse outcomes occurred within 24 h of platelet transfusion. Two patients experienced bleeding following renal biopsy despite having platelet counts of greater than 50,000/μl and receiving one pack of pooled platelets prior to the procedures. The response to transfusion was variable. In general, platelet transfusion was not detrimental in this population; however, the efficacy is uncertain.
Keywords Thrombotic thrombocytopenic purpura . Platelet transfusion . Thrombocytopenia
Introduction Thrombotic thrombocytopenic purpura (TTP) is a disorder resulting from deficiency of plasma ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) characterized by consumptive thrombocytopenia, microangiopathic hemolytic anemia, fever, renal dysfunction, and neurologic impairment. Current guidelines advise against the transfusion of platelets in patients with TTP except in cases of severe bleeding [1]. These recommendations are based on a small number of case reports describing worsening neurologic outcomes or mortality within hours of platelet transfusion; however, the patients in these reports did not receive plasma exchange prior to or during platelet transfusion [2–6]. Some recent studies, however, have described no adverse outcomes in patients with TTP who received platelet transfusion [7–10]. The present conflicting observational evidence and lack of level I evidence in this matter poses a dilemma for clinicians treating patients with TTP. This is especially relevant in cases with moderate to severe thrombocytopenia that require surgical procedures or more commonly central venous catheter placement for plasma exchange. In this case series, we sought to examine the outcomes of patients with TTP who received platelet transfusion at a tertiary care center.
Methods A. Zhou (*) Department of Hematology and Medical Oncology, Washington University in St. Louis, 660 S. Euclid Ave., Campus Box 8056, St. Louis, MO 63110, USA e-mail: [email protected] R. S. Mehta : R. E. Smith Department of Hematology and Medical Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
Study design We conducted a retrospective medical chart review including the time frame of 10 years (September 2002 to September 2012). The study was approved for exemption by the Institutional Review Board (IRB) at the University of Pittsburgh Medical Center. Patients with a diagnosis of TTP were
Ann Hematol
identified using a Boolean search expression in the Medical Archival System (MARS) for “thrombotic thrombocytopenic purpura” within existing discharge summaries. Two hundred thirty three patients were identified using this method for further review. The primary investigator (PI) reviewed the medical charts of the 233 patients in the Cerner Powerchart electronic medical record system and identified 37 patients who had received at least one platelet transfusion during any of their hospital admissions. Of these, 22 were excluded as they either did not have a diagnosis of TTP or did not have active TTP during the hospital admission based on the final diagnosis rendered by the treating physician. Data were collected on the remaining 15 patients by systematic chart review. The diagnosis of TTP is primarily based on the final diagnosis made by the treating physician as reported in the discharge summary. Baseline patient characteristics such as age, gender, race, and pertinent medical history such as reason for admission, thrombotic events within the previous 30 days of admission, including deep venous thrombosis (DVT), pulmonary embolism (PE), cerebral vascular accidents (CVA), or acute coronary syndromes (ACS), and past medical history of any active malignancy, HIV, systemic lupus erythematosus (SLE), and active medications including immunosuppressive agents, antiplatelet therapy, or chemotherapy were reviewed along with pertinent laboratory data including ADAMTS13 activity level, LDH, haptoglobin, total bilirubin, and pre- and posttransfusion platelet counts. The initial date of diagnosis of TTP, date and time of platelet transfusion, reason for platelet transfusion, and units of platelets transfused were also obtained. Our primary outcome was a composite of death due to any cause, myocardial infarction (MI), ischemic stroke, coma, seizure, or worsening neurologic status within 24 h of platelet transfusion. Secondary outcomes included bleeding of any severity or worsening thrombocytopenia. The period of 24 h was chosen based on the assumption that adverse events directly related to platelet products should occur immediately or within a few hours of platelet transfusion as described in prior case reports [2–5].
Results
Outcomes There were no adverse outcomes related to the transfusion within 24 h of platelet transfusion for all 15 patients.
Primary outcomes Death Patients 1 and 2 died during or shortly following their hospital admission, but neither within 24 h of platelet transfusion. Patient 1 had a prolonged hospital course requiring intensive care unit (ICU) management and died from worsening acidemia in the setting of a perforated peri-diverticular abscess requiring emergent exploratory laparotomy and colostomy 40 days from the time of his last platelet transfusion. Patient 2 died from an acute subarachnoid hemorrhage 18 days from her last platelet transfusion. CVA, seizure, and coma Patients 8, 9, 10, and 12 were diagnosed with an acute stroke or TIA within 30 days of their TTP diagnosis, but none within 24 h following a platelet transfusion. Patient 8 presented with left-sided weakness and had an acute right central sulcus infarct on admission. Patient 9 presented with seizure, altered mental status, and left-sided hemi-parasthesias to an outside hospital and she was diagnosed with a left vertebral artery dissection and a left parietooccipital ischemic stroke on admission. Patient 10 had a possible transient ischemic attack (TIA) approximately a month prior to her hospital admission, but did not suffer any adverse neurological events during the admission. Patient 12 was found to have a dilated right pupil during his hospital admission and underwent imaging which revealed a right upper midbrain and thalamic infarct which occurred 4 days prior to his first platelet transfusion. Patient 15 was transferred from an outside facility following coronary artery bypass (CABG) and mitral valve repair for management of thrombocytopenia. She had received platelet transfusions at the outside hospital, but the number of units transfused and the time of the last transfusion was unknown. She was found to have an asymptomatic subdural hematoma with acute and chronic features on imaging within 24 h of being transferred to our facility. She did not have any neurological events related to platelet transfusions during her hospital course at our institution.
Patient characteristics The median age was 53 (range 32 to 79 years); two thirds were female and the majority were Caucasian (87 %). Three patients (20 %) had a current or prior history of malignancy and one had a prior history of autologous stem cell transplantation. Two patients had SLE. Detailed baseline characteristics are summarized in Table 1. Admission laboratory data are summarized in Table 2.tgroup1
MI There were no ACS events reported within 24 h of platelet transfusion for any of the patients. Patient 9 presented to an outside hospital with chest pain and she was diagnosed with an inferior wall MI prior to transfer to our institution. There was no report of her receiving platelet transfusion at the outside institution prior to transfer. Patients 2 and 5 had a known coronary artery disease and were on antiplatelet therapy prior to their admission and TTP diagnosis. None of these
70, F, Caucasian
31, F, Caucasian
34, F, Caucasian 44, F, AfricanAmerican 32, F, Caucasian
37, F, AfricanAmerican 59, F, Caucasian
66, F, Caucasian
36, F, Caucasian
79, M, Caucasian 73, M, Caucasian
66, M, Caucasian 62, F, Caucasian 74, F, Caucasian
2
3
4 5
7
9
10
11 12
13 14 15
Left vertebral artery dissection and inferior wall MI diagnosed during admission Possible TIA less than a month prior to admission No DVT and right upper midbrain and right thalamic infarct diagnosed during admission No No CABG and atrial thrombus, subdural hematoma which occurred prior to transfer to our facility
Acute right central sulcus infarct (CVA) during admission
No
No
No No
No No
No
No
No
No
No
No No
No
No
No
No No No
No No
No
No
Yes
No
No
No Yes
No
No
No
No No Yes, malignancy
No No
No
No
Yes, SLE/ myelodysplastic syndrome
No
Yes, pregnancy
No Yes, SLE
No
Yes, APS/Factor V Leiden No
HIV Diagnosis Diagnosis of positive of SLE hypercoagulable disorder
Mantle cell lymphoma No No No History of breast No cancer
No No
No
History of cervical cancer, myelodysplastic syndrome No
No
No
No No
No
No
No
Malignancy
No No No
No No
No
No
Yes, Plaquenil
No
No
Yes, mycophenolate mofetil/ tacrolimus No No
No
No
Immunosuppressive therapy
No
No
No No No
No No
No
No
No
No
No No No
No No
No
No
No
No
No No Yes, No clopidogrel No No
No
3/16/2012 7/1/2011 8/8/2008
3/11/2012 4/27/2010
3/17/2011
2/8/2009
12/27/ 2009
12/27/ 2009 8/31/2010
7/8/2012 3/12/2010
2/23/2010
12/8/2010
6/10/2004
Active Date of chemotherapy TTP diagnosis
Yes, No clopidogrel
No
Antiplatelet therapy
APS antiphospholipid syndrome, AML acute myeloid leukemia, CLL chronic lymphocytic leukemia, CAD coronary artery disease, TIA transient ischemic attack, CABG coronary artery bypass graft
8
6
No
43, M, Caucasian
1
CAD, but unknown if within 30 days of admission No
DVT/PE, ACS, or CVA within 30 days of TTP diagnosis
Patient Age, sex, and race
Table 1 Patient characteristics and pertinent medical history
Ann Hematol
Ann Hematol Table 2 Admission laboratory data
Table 3 Platelet counts pre- and posttransfusion
Patient
ADAMTS13 activity (%)
LDH (Units/L)
Haptoglobin (mg/dL)
Total bilirubin (mg/dL)
1 2 3 4 5 6 7 8 9
88* 49 39 N/A 81* 20 12 N/A 18
2770 190 321 1114 878 326 50 975 445
ORIGINAL ARTICLE
Outcomes of platelet transfusion in patients with thrombotic thrombocytopenic purpura: a retrospective case series study Amy Zhou & Rohtesh S. Mehta & Roy E. Smith
Received: 13 June 2014 / Accepted: 25 September 2014 # Springer-Verlag Berlin Heidelberg 2014
Abstract Current guidelines advise against the transfusion of platelets in patients with thrombotic thrombocytopenic purpura (TTP) except in cases of life-threatening hemorrhage. We conducted a retrospective medical chart review to examine the outcomes of patients with TTP who received platelet transfusion at our institution from September 2002 to September 2012. A search for “thrombotic thrombocytopenic purpura” in the discharge summary identified 233 patients, out of which only 15 patients had TTP and received platelet transfusion. Primary outcomes were death due to any cause, myocardial infarction, ischemic stroke, coma, seizure, or worsening neurologic status within 24 h of platelet transfusion. Secondary outcomes included bleeding and worsening thrombocytopenia. No adverse outcomes occurred within 24 h of platelet transfusion. Two patients experienced bleeding following renal biopsy despite having platelet counts of greater than 50,000/μl and receiving one pack of pooled platelets prior to the procedures. The response to transfusion was variable. In general, platelet transfusion was not detrimental in this population; however, the efficacy is uncertain.
Keywords Thrombotic thrombocytopenic purpura . Platelet transfusion . Thrombocytopenia
Introduction Thrombotic thrombocytopenic purpura (TTP) is a disorder resulting from deficiency of plasma ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) characterized by consumptive thrombocytopenia, microangiopathic hemolytic anemia, fever, renal dysfunction, and neurologic impairment. Current guidelines advise against the transfusion of platelets in patients with TTP except in cases of severe bleeding [1]. These recommendations are based on a small number of case reports describing worsening neurologic outcomes or mortality within hours of platelet transfusion; however, the patients in these reports did not receive plasma exchange prior to or during platelet transfusion [2–6]. Some recent studies, however, have described no adverse outcomes in patients with TTP who received platelet transfusion [7–10]. The present conflicting observational evidence and lack of level I evidence in this matter poses a dilemma for clinicians treating patients with TTP. This is especially relevant in cases with moderate to severe thrombocytopenia that require surgical procedures or more commonly central venous catheter placement for plasma exchange. In this case series, we sought to examine the outcomes of patients with TTP who received platelet transfusion at a tertiary care center.
Methods A. Zhou (*) Department of Hematology and Medical Oncology, Washington University in St. Louis, 660 S. Euclid Ave., Campus Box 8056, St. Louis, MO 63110, USA e-mail: [email protected] R. S. Mehta : R. E. Smith Department of Hematology and Medical Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
Study design We conducted a retrospective medical chart review including the time frame of 10 years (September 2002 to September 2012). The study was approved for exemption by the Institutional Review Board (IRB) at the University of Pittsburgh Medical Center. Patients with a diagnosis of TTP were
Ann Hematol
identified using a Boolean search expression in the Medical Archival System (MARS) for “thrombotic thrombocytopenic purpura” within existing discharge summaries. Two hundred thirty three patients were identified using this method for further review. The primary investigator (PI) reviewed the medical charts of the 233 patients in the Cerner Powerchart electronic medical record system and identified 37 patients who had received at least one platelet transfusion during any of their hospital admissions. Of these, 22 were excluded as they either did not have a diagnosis of TTP or did not have active TTP during the hospital admission based on the final diagnosis rendered by the treating physician. Data were collected on the remaining 15 patients by systematic chart review. The diagnosis of TTP is primarily based on the final diagnosis made by the treating physician as reported in the discharge summary. Baseline patient characteristics such as age, gender, race, and pertinent medical history such as reason for admission, thrombotic events within the previous 30 days of admission, including deep venous thrombosis (DVT), pulmonary embolism (PE), cerebral vascular accidents (CVA), or acute coronary syndromes (ACS), and past medical history of any active malignancy, HIV, systemic lupus erythematosus (SLE), and active medications including immunosuppressive agents, antiplatelet therapy, or chemotherapy were reviewed along with pertinent laboratory data including ADAMTS13 activity level, LDH, haptoglobin, total bilirubin, and pre- and posttransfusion platelet counts. The initial date of diagnosis of TTP, date and time of platelet transfusion, reason for platelet transfusion, and units of platelets transfused were also obtained. Our primary outcome was a composite of death due to any cause, myocardial infarction (MI), ischemic stroke, coma, seizure, or worsening neurologic status within 24 h of platelet transfusion. Secondary outcomes included bleeding of any severity or worsening thrombocytopenia. The period of 24 h was chosen based on the assumption that adverse events directly related to platelet products should occur immediately or within a few hours of platelet transfusion as described in prior case reports [2–5].
Results
Outcomes There were no adverse outcomes related to the transfusion within 24 h of platelet transfusion for all 15 patients.
Primary outcomes Death Patients 1 and 2 died during or shortly following their hospital admission, but neither within 24 h of platelet transfusion. Patient 1 had a prolonged hospital course requiring intensive care unit (ICU) management and died from worsening acidemia in the setting of a perforated peri-diverticular abscess requiring emergent exploratory laparotomy and colostomy 40 days from the time of his last platelet transfusion. Patient 2 died from an acute subarachnoid hemorrhage 18 days from her last platelet transfusion. CVA, seizure, and coma Patients 8, 9, 10, and 12 were diagnosed with an acute stroke or TIA within 30 days of their TTP diagnosis, but none within 24 h following a platelet transfusion. Patient 8 presented with left-sided weakness and had an acute right central sulcus infarct on admission. Patient 9 presented with seizure, altered mental status, and left-sided hemi-parasthesias to an outside hospital and she was diagnosed with a left vertebral artery dissection and a left parietooccipital ischemic stroke on admission. Patient 10 had a possible transient ischemic attack (TIA) approximately a month prior to her hospital admission, but did not suffer any adverse neurological events during the admission. Patient 12 was found to have a dilated right pupil during his hospital admission and underwent imaging which revealed a right upper midbrain and thalamic infarct which occurred 4 days prior to his first platelet transfusion. Patient 15 was transferred from an outside facility following coronary artery bypass (CABG) and mitral valve repair for management of thrombocytopenia. She had received platelet transfusions at the outside hospital, but the number of units transfused and the time of the last transfusion was unknown. She was found to have an asymptomatic subdural hematoma with acute and chronic features on imaging within 24 h of being transferred to our facility. She did not have any neurological events related to platelet transfusions during her hospital course at our institution.
Patient characteristics The median age was 53 (range 32 to 79 years); two thirds were female and the majority were Caucasian (87 %). Three patients (20 %) had a current or prior history of malignancy and one had a prior history of autologous stem cell transplantation. Two patients had SLE. Detailed baseline characteristics are summarized in Table 1. Admission laboratory data are summarized in Table 2.tgroup1
MI There were no ACS events reported within 24 h of platelet transfusion for any of the patients. Patient 9 presented to an outside hospital with chest pain and she was diagnosed with an inferior wall MI prior to transfer to our institution. There was no report of her receiving platelet transfusion at the outside institution prior to transfer. Patients 2 and 5 had a known coronary artery disease and were on antiplatelet therapy prior to their admission and TTP diagnosis. None of these
70, F, Caucasian
31, F, Caucasian
34, F, Caucasian 44, F, AfricanAmerican 32, F, Caucasian
37, F, AfricanAmerican 59, F, Caucasian
66, F, Caucasian
36, F, Caucasian
79, M, Caucasian 73, M, Caucasian
66, M, Caucasian 62, F, Caucasian 74, F, Caucasian
2
3
4 5
7
9
10
11 12
13 14 15
Left vertebral artery dissection and inferior wall MI diagnosed during admission Possible TIA less than a month prior to admission No DVT and right upper midbrain and right thalamic infarct diagnosed during admission No No CABG and atrial thrombus, subdural hematoma which occurred prior to transfer to our facility
Acute right central sulcus infarct (CVA) during admission
No
No
No No
No No
No
No
No
No
No
No No
No
No
No
No No No
No No
No
No
Yes
No
No
No Yes
No
No
No
No No Yes, malignancy
No No
No
No
Yes, SLE/ myelodysplastic syndrome
No
Yes, pregnancy
No Yes, SLE
No
Yes, APS/Factor V Leiden No
HIV Diagnosis Diagnosis of positive of SLE hypercoagulable disorder
Mantle cell lymphoma No No No History of breast No cancer
No No
No
History of cervical cancer, myelodysplastic syndrome No
No
No
No No
No
No
No
Malignancy
No No No
No No
No
No
Yes, Plaquenil
No
No
Yes, mycophenolate mofetil/ tacrolimus No No
No
No
Immunosuppressive therapy
No
No
No No No
No No
No
No
No
No
No No No
No No
No
No
No
No
No No Yes, No clopidogrel No No
No
3/16/2012 7/1/2011 8/8/2008
3/11/2012 4/27/2010
3/17/2011
2/8/2009
12/27/ 2009
12/27/ 2009 8/31/2010
7/8/2012 3/12/2010
2/23/2010
12/8/2010
6/10/2004
Active Date of chemotherapy TTP diagnosis
Yes, No clopidogrel
No
Antiplatelet therapy
APS antiphospholipid syndrome, AML acute myeloid leukemia, CLL chronic lymphocytic leukemia, CAD coronary artery disease, TIA transient ischemic attack, CABG coronary artery bypass graft
8
6
No
43, M, Caucasian
1
CAD, but unknown if within 30 days of admission No
DVT/PE, ACS, or CVA within 30 days of TTP diagnosis
Patient Age, sex, and race
Table 1 Patient characteristics and pertinent medical history
Ann Hematol
Ann Hematol Table 2 Admission laboratory data
Table 3 Platelet counts pre- and posttransfusion
Patient
ADAMTS13 activity (%)
LDH (Units/L)
Haptoglobin (mg/dL)
Total bilirubin (mg/dL)
1 2 3 4 5 6 7 8 9
88* 49 39 N/A 81* 20 12 N/A 18
2770 190 321 1114 878 326 50 975 445
