Table 1.
VTE and coagulation abnormalities in CAR T-cell patients
| Summary of VTE and coagulation abnormalities and management | Value |
|---|---|
| Prior recent VTE (within 6 mo) before CAR T-cell infusion * | 28/121 (23) |
| DVT alone | 17 |
| PE alone | 1 |
| DVT + PE | 7 |
| Other VTE (splenic/mesenteric) | 3 (2/1) |
| Patients who had AC held after CAR T-cell infusion | 16/28 (57) |
| Median platelet count when AC held after CAR T-cell infusion (range), ×103/μL | 54 (39-116) |
| Median days after infusion when AC held (range) | 5 (2-7) |
| Median platelet count when AC resumed after initial interruption (range), ×103/μL | 66 (54-213) |
| Patients with recurrent thrombosis when AC was held | 2/16 |
| New diagnosis of VTE between day 0 and day 100 after CAR T-cell infusion | 16/148 (11) |
| DVT | 8/16 |
| Upper extremity (all catheter-associated)† | 4/8 |
| Lower extremity | 4/8 |
| PE | 4/16 |
| Others (mesenteric/cerebral/renal) thrombosis | 4/16 |
| Asymptomatic/incidental new VTE | 5/16 (31) |
| Patients who had AC held after initiation/patients initiating AC‡ | 5/12 (42) |
| Median platelet count when AC was held (range), ×103/μL | 53 (39-202) |
| Median days after initiation when AC was held (range) | 5 (3-10) |
| Patients who had AC resumed after initial interruption§ | 2/5 |
| Patients with serum fibrinogen measured between day 0 and day 100 ‖ | 31 |
| Nadir serum fibrinogen level <100 mg/dL | 9/31 |
| Nadir serum fibrinogen level 100-200 mg/dL | 6/31 |
| Nadir serum fibrinogen level >200 mg/dL | 16/31 |
| Days to reach nadir serum fibrinogen after infusion, median (range)¶ | 11 (5-27) |
| Abnormal PT or PTT in patients with hypofibrinogenemia # | 6/15 |
| PT only | 4 |
| PTT + PT | 2 |
| Patients receiving cryoprecipitate ** | 8 |
| Median no. of prepooled units used per patient (range) | 2 (1-5) |
| Median days to first cryoprecipitate use after infusion (range) | 9 (6-18) |
| Median days to last cryoprecipitate use after infusion (range) | 14 (9-29) |
| Patients receiving fresh frozen plasma | 1 |
| No. of fresh frozen plasma units used | 3 |
Values are n or n/N (%), unless otherwise noted. AC, anticoagulation; DVT, deep vein thrombosis; PE, pulmonary embolism; PT, prothrombin time; PTT, partial thromboplastin time.
Patients who received CAR T-cell therapy on clinical trial (N = 27) were excluded for “prior recent” VTE as this was a trial exclusion criterion.
None of the catheter-associated VTEs was associated with local or bloodstream infections.
Initial anticoagulation for new VTE was low-molecular-weight heparin (n = 6), unfractionated heparin (n = 2), rivaroxaban (n = 2), dabigatran (n = 1), and apixaban (n = 1).
Platelet count (×103/μL) when AC resumed was 55 and 61, respectively, in these 2 patients.
Reasons for checking serum fibrinogen levels included minor bleeding (n = 4), workup for anemia and/or thrombocytopenia (n = 10), workup for elevated international normalized ratio and/or PTT (n = 2), workup for possible hemophagocytic lymphohistiocytosis (n = 4), workup during severe CRS or neurotoxicity (n = 4), patient on anticoagulation (n = 3), screening workup for postrelapse clinical trial (n = 1), and unknown (n = 3).
Days postinfusion the fibrinogen level was first measured: median (range), 7 (0-45). Number of days the level was measured between day 0 and day 100: median (range), 3 (1-32).
Patients with PT or PTT levels that were above the normal range at the time of nadir fibrinogen in patients experiencing a fibrinogen level <200 mg/dL.
Reasons for giving cryoprecipitate (all patients had serum fibrinogen levels <100 mg/dL) included concomitant severe CRS (n = 1), minor bleeding (n = 1), transient decrease in hemoglobin without an identifiable bleeding source (n = 1), elevated PT/PTT without overt DIC (n = 1), and low fibrinogen level without other reason(s) (n = 4).