Baseline characteristics of the studies included in the systematic review
| Reference . | Study design . | PCC type and dose . | Cointerventions, no. (%) . | No. of patients receiving FXa inhibitor who received PCC . | FXa inhibitor . | Indication for FXa inhibitor, no. (%) . | Follow-up duration, d . | Inclusion criteria . | Exclusion criteria . | Major bleeding definition . | Bleeding type . |
|---|---|---|---|---|---|---|---|---|---|---|---|
| 34 | Prospective | Type unspecified, dose range, 18-47 IU/kg | FFP alone, 2 (33); FFP and RBCs, 1 (17) | 6 | Rivaroxaban | Atrial fibrillation, 4 (67); VTE, 2 (33) | 90 | Planned anticoagulation for at least 3 months; indications included atrial fibrillation, DVT, PE, and others; age older than 18 years; written informed consent; and availability for follow-up by telephone visits | No exclusion criteria applied | ISTH criteria for major bleeding | ICH, 2; upper gastrointestinal bleeding, 2; intraoperative bleeding, 1; spontaneous hemothorax, 1 |
| 35 | Retrospective | Kcentra, mean dose 3177 U (range, 2124-4770 U) | Platelets, 3 (17) | 18 | Rivaroxaban, 16 patients; apixaban, 2 patients | Atrial fibrillation alone, 14 (78); atrial fibrillation and DVT, 1 (5.5); atrial fibrillation and mechanical aortic valve replacement, 1 (5.5); mechanical aortic valve replacement, 1 (5.5); lupus anticoagulant, 1 (5.5) | 90 | Preinjury use of direct oral FXa inhibitors and diagnosis of either spontaneous ICH or blunt traumatic brain injury with evidence of ICH on initial noncontrast CT scan | Patients who had received FFP | Patients with ICH | ICH |
| 36 | Retrospective | Profilnine, median dose 40 U/kg | FFP alone, 1 (33.3); FFP and RBCs, 1 (33.3); FFP, platelets, and intravenous iron, 1 (33.3) | 3 | Rivaroxaban | Atrial fibrillation, 2 (66.7); DVT prophylaxis after hip replacement, 1 (33.3) | 180 | Age 18 years or older; hemorrhage during admission in those who had received dabigatran or rivaroxaban before this event | If hemorrhage was attributed to other agents or if the etiology of the event was determined to be surgical or caused by other medical conditions | Major bleeding, ISTH criteria; life-threatening bleeding, any fatal bleeding; symptomatic ICH; decrease in hemoglobin ≥50 g/L; ≥4 units of RBCs transfused; required inotropes or surgery | ICH,1; upper gastrointestinal bleeding, 2 |
| 37 | Retrospective | Beriplex, dose unspecified | FFP and recombinant FVIIa, 1 (17) | 3 | Rivaroxaban | Atrial fibrillation, 5 (83.3); stents and tachyarrythmia, 1 (16.7) | 90 | Patients receiving anticoagulation therapy with rivaroxaban or dabigatran 3 days before ICH | NA | Patients with ICH | ICH |
| 39 | Prospective | Octaplex or beriplex, median 2000 U (range, 1500-2000 U) | Tranexamic acid, 56 (67); RBCs, 12 (14) before PCC and 18 (21) after PCC; FFP, 5 (6) before PCC and 8 (9.5) after PCC; platelets, 10 (12) after PCC; recombinant FVIIa, 1 (1) | 84 | Rivaroxaban, 45; apixaban, 39 | Atrial fibrillation alone, 63 (75); VTE alone, 18 (21); atrial fibrillation and VTE, 3 (4) | 30 | Needed treatment with PCC to manage acute and active major bleeding while receiving rivaroxaban or apixaban | Do not resuscitate order, reduced hemoglobin without source of bleeding, perioperative reversal of rivaroxaban or apixaban, acute coronary syndrome or ischemic stroke during the past 30 days if they received other hemostatic agents (recombinant FVIIa or activated PCC) | ISTH criteria for major bleeding | ICH, 59; gastrointestinal , 13; visceral, 5; genitourinary, 4; musculoskeletal, 3 |
| 40 | Prospective | Freeze-dried human blood coagulation FIX complex, median 1000 U (range, 1000-1125 U) | RBCs and FFP, 1 (0.1) | 9 | Rivaroxaban, 7; apixaban, 2 | Atrial fibrillation, 9 (100) | Median 9 (range,6-28) | Patients who developed major bleeding while taking NOAC medication and who subsequently received PCC administration were prospectively enrolled | Patients who were judged ineligible for PCC use by physicians in charge or who declined written informed consent were excluded | ISTH criteria for major bleeding | ICH, 8; gastrointestinal, 1 |
| 41 | Retrospective | Type unspecified, median dose of rivaroxban, 2000 U (IQR, 1500-2600 U); apixaban, 2400 U (IQR, 1500-3000 U) | Rivaroxaban, platelets, 5 (4.5); FFP, 2 (1.8); apixaban, platelets, 2 (9.5); FFP, 1 (4.8); tranexamic acid, 1 (4.8) | 94 (total of 146 in the study) | Rivaroxaban, 81; apixaban, 13 | Unspecified | 90 | Patients were treated with a DOAC at onset of ICH | ICH as a result of secondary etiologies such as ICH related to trauma, tumor, arteriovenous malformation, aneurysmal subarachnoid hemorrhage, acute thrombolysis, or other coagulopathies | Patients with ICH | ICH |
| 42 | Retrospective | Kcentra, 10 received 50 U/kg, 2 received 35 U/kg, and 2 received 25 U/kg | Unspecified; excluded patients who received FFP | 14 | Rivaroxaban and apixaban; breakdown was not specified | Atrial fibrillation, 12 (86); VTE, 3 (21); CVA, 2 (14); no. of patients with concomitant indications was not specified | 30 | If they were age 18 years or older and were admitted with traumatic or nontraumatic oral anticoagulant–associated ICH | Patients who received 4F-PCC without traumatic or nontraumatic oral anticoagulant–associated ICH | Patients with ICH | ICH |
| 38 | Prospective | Octaplex or beriplex, mean dose, 2072 U, 2000 U for 54 patients; dose violations from protocol for 12 patients, 2 received 1000 U, 3 received 1500 U, 1 received 2500 U, 4 received 3000 U, 1 received 3500 U, and 1 received 4200 U | Tranexamic acid, 17 (26); transfusions after PCC, second dose PCC, 2 (3); 1 received 1000 U and 1 received 2000 U; RBCs 1-8 units, 13 (20); platelets (1-3 apheresis or pooled units), 8 (12); cryoprecipitate, 1 (2) | 66 | Rivaroxaban, 37; apixaban, 29 | Atrial fibrillation alone, 54 (82); VTE alone, 8 (13); atrial fibrillation and VTE, 2 (3); ischemic stroke, 1 (2) | 30 | Received infusion per local hospital protocol with PCC (2000 U) for major bleeding on treatment with rivaroxaban or apixaban; did not receive other hemostatic agents including plasma, platelets, activated PCC, or recombinant FVIIa before PCC was administered (antifibrinolytic drugs and local hemostatic agents were allowed); written consent provided | Do not resuscitate orders given before treatment with PCC because of the severity of bleeding; reduction of hemoglobin without evidence of source of bleeding; acute coronary syndrome or ischemic stroke during the past 30 days | ISTH criteria for major bleeding | ICH, 36; gastrointestinal, 16; retroperitoneal, 3; intramuscular, 2; intraspinal, 2; other, 7 with one each of intra-abdominal, pelvic, vaginal, hematuria, hemothorax, chest tube wounds, or carotid artery injury |
| 43 | Retrospective | Kcentra, 22 received 25 U/kg, 16 received 50 U/kg, 2 received 25-50 U/kg, 1 received >50 U/kg | FFP, 3 (6.9) | 43 | Rivaroxaban, 21; apixaban, 22 | Atrial fibrillation, 30 (69.8); VTE, 9 (20.9); atrial fibrillation and VTE, 3 (7.0); lower extremity venous bypass graft 1 (2.3) | 90 | If the patients received 4F-PCC for reversing rivaroxaban, apixaban, or edoxaban for emergency surgery or invasive procedures, or during episodes of major bleeding | If they received 4F-PCC for purposes other than reversing FXa inhibitors or if they were younger than age 18 years | Major bleeding defined as bleeding with hemodynamic instability, decrease in hemoglobin of 2 g/dL, or bleeding requiring blood transfusion | Gastrointestinal bleeding, 17 (39.5); intracranial hemorrhage (nontraumatic), 9 (20.9); intracranial hemorrhage (traumatic), 7 (16.3); trauma, 5 (14.0); other, 5 (11.6) |
| Reference . | Study design . | PCC type and dose . | Cointerventions, no. (%) . | No. of patients receiving FXa inhibitor who received PCC . | FXa inhibitor . | Indication for FXa inhibitor, no. (%) . | Follow-up duration, d . | Inclusion criteria . | Exclusion criteria . | Major bleeding definition . | Bleeding type . |
|---|---|---|---|---|---|---|---|---|---|---|---|
| 34 | Prospective | Type unspecified, dose range, 18-47 IU/kg | FFP alone, 2 (33); FFP and RBCs, 1 (17) | 6 | Rivaroxaban | Atrial fibrillation, 4 (67); VTE, 2 (33) | 90 | Planned anticoagulation for at least 3 months; indications included atrial fibrillation, DVT, PE, and others; age older than 18 years; written informed consent; and availability for follow-up by telephone visits | No exclusion criteria applied | ISTH criteria for major bleeding | ICH, 2; upper gastrointestinal bleeding, 2; intraoperative bleeding, 1; spontaneous hemothorax, 1 |
| 35 | Retrospective | Kcentra, mean dose 3177 U (range, 2124-4770 U) | Platelets, 3 (17) | 18 | Rivaroxaban, 16 patients; apixaban, 2 patients | Atrial fibrillation alone, 14 (78); atrial fibrillation and DVT, 1 (5.5); atrial fibrillation and mechanical aortic valve replacement, 1 (5.5); mechanical aortic valve replacement, 1 (5.5); lupus anticoagulant, 1 (5.5) | 90 | Preinjury use of direct oral FXa inhibitors and diagnosis of either spontaneous ICH or blunt traumatic brain injury with evidence of ICH on initial noncontrast CT scan | Patients who had received FFP | Patients with ICH | ICH |
| 36 | Retrospective | Profilnine, median dose 40 U/kg | FFP alone, 1 (33.3); FFP and RBCs, 1 (33.3); FFP, platelets, and intravenous iron, 1 (33.3) | 3 | Rivaroxaban | Atrial fibrillation, 2 (66.7); DVT prophylaxis after hip replacement, 1 (33.3) | 180 | Age 18 years or older; hemorrhage during admission in those who had received dabigatran or rivaroxaban before this event | If hemorrhage was attributed to other agents or if the etiology of the event was determined to be surgical or caused by other medical conditions | Major bleeding, ISTH criteria; life-threatening bleeding, any fatal bleeding; symptomatic ICH; decrease in hemoglobin ≥50 g/L; ≥4 units of RBCs transfused; required inotropes or surgery | ICH,1; upper gastrointestinal bleeding, 2 |
| 37 | Retrospective | Beriplex, dose unspecified | FFP and recombinant FVIIa, 1 (17) | 3 | Rivaroxaban | Atrial fibrillation, 5 (83.3); stents and tachyarrythmia, 1 (16.7) | 90 | Patients receiving anticoagulation therapy with rivaroxaban or dabigatran 3 days before ICH | NA | Patients with ICH | ICH |
| 39 | Prospective | Octaplex or beriplex, median 2000 U (range, 1500-2000 U) | Tranexamic acid, 56 (67); RBCs, 12 (14) before PCC and 18 (21) after PCC; FFP, 5 (6) before PCC and 8 (9.5) after PCC; platelets, 10 (12) after PCC; recombinant FVIIa, 1 (1) | 84 | Rivaroxaban, 45; apixaban, 39 | Atrial fibrillation alone, 63 (75); VTE alone, 18 (21); atrial fibrillation and VTE, 3 (4) | 30 | Needed treatment with PCC to manage acute and active major bleeding while receiving rivaroxaban or apixaban | Do not resuscitate order, reduced hemoglobin without source of bleeding, perioperative reversal of rivaroxaban or apixaban, acute coronary syndrome or ischemic stroke during the past 30 days if they received other hemostatic agents (recombinant FVIIa or activated PCC) | ISTH criteria for major bleeding | ICH, 59; gastrointestinal , 13; visceral, 5; genitourinary, 4; musculoskeletal, 3 |
| 40 | Prospective | Freeze-dried human blood coagulation FIX complex, median 1000 U (range, 1000-1125 U) | RBCs and FFP, 1 (0.1) | 9 | Rivaroxaban, 7; apixaban, 2 | Atrial fibrillation, 9 (100) | Median 9 (range,6-28) | Patients who developed major bleeding while taking NOAC medication and who subsequently received PCC administration were prospectively enrolled | Patients who were judged ineligible for PCC use by physicians in charge or who declined written informed consent were excluded | ISTH criteria for major bleeding | ICH, 8; gastrointestinal, 1 |
| 41 | Retrospective | Type unspecified, median dose of rivaroxban, 2000 U (IQR, 1500-2600 U); apixaban, 2400 U (IQR, 1500-3000 U) | Rivaroxaban, platelets, 5 (4.5); FFP, 2 (1.8); apixaban, platelets, 2 (9.5); FFP, 1 (4.8); tranexamic acid, 1 (4.8) | 94 (total of 146 in the study) | Rivaroxaban, 81; apixaban, 13 | Unspecified | 90 | Patients were treated with a DOAC at onset of ICH | ICH as a result of secondary etiologies such as ICH related to trauma, tumor, arteriovenous malformation, aneurysmal subarachnoid hemorrhage, acute thrombolysis, or other coagulopathies | Patients with ICH | ICH |
| 42 | Retrospective | Kcentra, 10 received 50 U/kg, 2 received 35 U/kg, and 2 received 25 U/kg | Unspecified; excluded patients who received FFP | 14 | Rivaroxaban and apixaban; breakdown was not specified | Atrial fibrillation, 12 (86); VTE, 3 (21); CVA, 2 (14); no. of patients with concomitant indications was not specified | 30 | If they were age 18 years or older and were admitted with traumatic or nontraumatic oral anticoagulant–associated ICH | Patients who received 4F-PCC without traumatic or nontraumatic oral anticoagulant–associated ICH | Patients with ICH | ICH |
| 38 | Prospective | Octaplex or beriplex, mean dose, 2072 U, 2000 U for 54 patients; dose violations from protocol for 12 patients, 2 received 1000 U, 3 received 1500 U, 1 received 2500 U, 4 received 3000 U, 1 received 3500 U, and 1 received 4200 U | Tranexamic acid, 17 (26); transfusions after PCC, second dose PCC, 2 (3); 1 received 1000 U and 1 received 2000 U; RBCs 1-8 units, 13 (20); platelets (1-3 apheresis or pooled units), 8 (12); cryoprecipitate, 1 (2) | 66 | Rivaroxaban, 37; apixaban, 29 | Atrial fibrillation alone, 54 (82); VTE alone, 8 (13); atrial fibrillation and VTE, 2 (3); ischemic stroke, 1 (2) | 30 | Received infusion per local hospital protocol with PCC (2000 U) for major bleeding on treatment with rivaroxaban or apixaban; did not receive other hemostatic agents including plasma, platelets, activated PCC, or recombinant FVIIa before PCC was administered (antifibrinolytic drugs and local hemostatic agents were allowed); written consent provided | Do not resuscitate orders given before treatment with PCC because of the severity of bleeding; reduction of hemoglobin without evidence of source of bleeding; acute coronary syndrome or ischemic stroke during the past 30 days | ISTH criteria for major bleeding | ICH, 36; gastrointestinal, 16; retroperitoneal, 3; intramuscular, 2; intraspinal, 2; other, 7 with one each of intra-abdominal, pelvic, vaginal, hematuria, hemothorax, chest tube wounds, or carotid artery injury |
| 43 | Retrospective | Kcentra, 22 received 25 U/kg, 16 received 50 U/kg, 2 received 25-50 U/kg, 1 received >50 U/kg | FFP, 3 (6.9) | 43 | Rivaroxaban, 21; apixaban, 22 | Atrial fibrillation, 30 (69.8); VTE, 9 (20.9); atrial fibrillation and VTE, 3 (7.0); lower extremity venous bypass graft 1 (2.3) | 90 | If the patients received 4F-PCC for reversing rivaroxaban, apixaban, or edoxaban for emergency surgery or invasive procedures, or during episodes of major bleeding | If they received 4F-PCC for purposes other than reversing FXa inhibitors or if they were younger than age 18 years | Major bleeding defined as bleeding with hemodynamic instability, decrease in hemoglobin of 2 g/dL, or bleeding requiring blood transfusion | Gastrointestinal bleeding, 17 (39.5); intracranial hemorrhage (nontraumatic), 9 (20.9); intracranial hemorrhage (traumatic), 7 (16.3); trauma, 5 (14.0); other, 5 (11.6) |
CT, computed tomography; CVA, cerebrovascular accident; DVT, deep vein thrombosis; IQR, interquartile range; NA, not available; NOAC, novel oral anticoagulant; PE, pulmonary embolism; RBC, red blood cell.