Highlights
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The risk of thrombotic complications increases with the severity of COVID-19.
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Thromboprophylaxis is recommended for hospitalised patients, but the effectiveness of this, and the incidence of thrombotic events in patients managed in the intensive care unit (ICU) is unknown.
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In 28 studies assessing 2928 critically-ill patients with COVID-19 on the ICU, the incidence of thrombotic events was 34%, but studies employing systematic screening reported a significantly higher incidence of venous thrombosis compared to those relying on clinical suspicion alone (56.3% vs. 11.0%, p < 0.001), despite anticoagulant thromboprophylaxis.
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Consideration should be given to systematic screening and increased dose anticoagulant thromboprophylaxis in patients with COVID-19 on the ICU.
Introduction
Methods
Search strategy
Study selection
Data extraction
Outcome measures
Risk of bias within individual studies
Statistical analysis
Results
Search results
Study and patient characteristics
Patient demographics and treatments | Mean (SD), Median (IQR) or patients with characteristic/total patients with this characteristic documented or n(%) | % of total patients who have this variable documented | Number of studies reporting on this demographic (Specific references in brackets) |
---|---|---|---|
Age (years) | 59.9(14.1), 62(56–66), 70(62–80), 63(53–71), 64(12), 68(51.5–74.5), 61(16), 59(13), 61(55–69), 62.2(8.6), 61(55–70), 65(range:32–97), 59(49–66), 64.5(11.8), 61(14), 62(53–69), 57(49–64), 61.7(15.8), 45(26–66), 68(11), 59(50–61), 50(43–62), 64(57–71) | 1788/2928 (61%) | |
Male | 1291/1879 (69%) | 1879/2928 (64%) | |
Diabetes | 426/1393 (31%) | 1393/2928 (48%) | |
Obesity | 146/392 (37%) | 392/2928 (14%) | |
Body mass index (kg/m2) | 29.5(29.3–32.4), 30.2(25.5–33.5), 34.8(11.8), 31.4(9.0), 30(26–35), 28(24–34), 30.3(5.4), 27(24–29), 28 (25–32), 28(25–32), 30.3(5.7), 27.5(4.6), 27.8(25.1–33.9), 31(27–36) | 942/2928 (32%) | |
Hypertension | 498/1021 (49%) | 1021/2928 (35%) | |
Cardiovascular disease | 281/1393 (20%) | 1393/2928 (48%) | |
Cerebrovascular disease | 39/708 (6%) | 708/2928 (24%) | |
Atrial fibrillation | 21/287 (7%) | 287/2928 (10%) | |
Renal replacement therapy | 147/834 (18%) | 834/2928 (28%) | |
ECMO | 67/529 (13%) | 529/2928 (18%) |
Type of thrombosis | Incidence of thrombotic complication in total patient cohort (n = 2929) | Incidence of event in patients not routinely screened for DVT | Incidence of event in patients routinely screened for DVT | Comparison of the incidence of thrombosis with screening vs. without screening |
---|---|---|---|---|
DVT | 431/2671 (16.1%) | 256/2328 (11.0%) | 151/268 (56.3%) | 56.3% vs. 11.0% (p < 0.001) |
PE | 325/2580 (12.6%) | 277/2298 (12.1%) | 37/207 (17.9%) | 17.9% vs. 12.6% (p = 0.009) |
CVA | 52/1736 (3.0%) | 52/1736 (3.0%) | NA | NA |
MI | 137/1736 (8.0%) | 137/1736 (8.0%) | NA | NA |
Line thrombosis | 13/574 (2.3%) | 13/574 (2.3%) | NA | NA |
Limb or Mesenteric ischaemia | 39/1566 (2.5%) | 39/1566 (2.5%) | NA | NA |
Oxygenator thrombosis (ECMO) | 13/48 (27.1%) | 13/48 (27.1%) | NA | NA |
Circuit thrombosis (RRT) | 28/29 (96.6%) | 28/29 (96.6%) | NA | NA |
Baseline VTE prophylaxis and anticoagulation
Study | Total no. patients | Age mean (SD) or median (IQR) | Gender | Diabetes n (%) | BMI mean (SD) or median (IQR) | Patients on ECMO n (%) | Patients on thromboprophylaxis on admission n (%) | Type of thromboprophylaxis | Patients on therapeutic anticoagulation n (%) | Routine screening for VTE | Patients with any venous thrombotic complications n (%) | Patients with PE n (%) | Patients with DVT n (%) | Other thrombotic complicationsn (%) | Patients with arterial thrombotic events (%) | Patients with any reported thrombotic events n (%) |
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Piazza et al. [36] | 170 | 61.7 (15.8) | M 106 (62%) | 66/170 (39) | 30.3 (5.7) | NA | 89% | LMWH UFH Rivaroxaban | NA | No | 46/170 (27) | 3/170 (2) | 39/170 (23) | Catheter/device-related thrombosis: 30/39 (77) Catheter/device-related arterial thrombosis: 11/170 (7) | 14/170 (8) | 60 (35) |
Longhitano et al. [32] | 62 | NA | NA | NA | NA | NA | 100% | Enoxaparin 100U/kg/24 h > 80 kg: Enoxaparin 5000U b.i.d | 0 (0) | No | 12/62 (19) | 11/62 (18) | 4/62 (6) | NA | NA | 12/62 (19) |
Shah et al. [52] | 187 | 57 (49–64) | M 124 (66%) | 54/187 (30) | 28 (25–32) | 5 (3) | 151/187 (81) | LMWH UFH | 27/187 (14) | No | 56/187 (30) | 42/187 (23%) | 22/187 (12) | Extracorporeal circuit disruption: 23 (12) | 25/187 (13) | 81/187 (43%) |
Bilaloglu et al. [41] | 829 | NA | NA | NA | NA | NA | ‘Most received thromboprophylaxis’ | NA | NA | No | 113/829 (14) | 52/829 (6) | 78/829 (9) | Limb ischaemia, renal and splenic infarcts, PVT: 18/829 (2) | 154/829 (19) | 224/829 (29) |
Bemtgen et al. [40] | 11 | 59 (50–61) | M 7 (64%) | NA | 27.8 (25.1–33.9) | 11 (100) | UFH on ECMO | UFH on ECMO (argatroban if HIT) | 11/11 | No | NA | NA | NA | Extracorporeal circuit disruption: 7/11 (64) | NA | 7/11 (64) |
Yuriditsky et al. [51] | 64 | 64 (57–71) | M 46 (72%) | NA | NA | NA | 9/64 (14) | Enoxaparin UFH | 55/64 (86) | No | 20/64 (31) | 1/64 (2) | 19/64 (30) | Clot in transit in RV: 1/64 (2) | NA | 20/64 (31) |
Hekimian et al. [35] | 51 | NA | NA | NA | NA | NA | NA | NA | NA | No | 8/51 (16) | 8/51 (16) | NA | NA | NA | 8/51 (16) |
Cui et al. [33] | 81 | 59.9 (14.1) | M 37 (46%) | 8/81 (10) | NA | NA | NA | NA | NA | No | 20/81 (25) | NA | 20/81 (25) | NA | 20/81 (25) | |
Helms et al. [38] | 150 | 63 (53–71) | M 122 (81%) | 30/150 (20) | NA | 12/150 (8) | 105/150 (70) | LMWH: 4,000 IU/day UFH: 5–8 U/kg/h | 45/150 (30) | No | 59/150 (39) | 25/150 (17) | 3/150 (2) | Circuit thrombosis (RRT): 28/29 (97); ECMO pump thrombosis: 3/12 (25) | 4/150 (3) | 63/150 (42) |
184 | 64 (12) | M 139 (76%) | NA | NA | NA | 167/184 (91) (all others receiving full anticoagulation) | Nadroparin (dose dependent on patient weight and recruiting site) | 17/184 (9) | No | 68/184 (37) | 65/184 (35) | 1/184 (0.5) | Catheter related thrombosis: 2/184 (1) | 7/184 (4) | 75/184 (41) | |
Poissy et al. [34] | 107 | NA | NA | NA | NA | NA | NA | LMWH or UFH | NA | No | 24/107 (22) | 22/107 (21) | 5/107 (5) | NA | NA | 24/107 (22) |
Thomas et al..[37] | 63 | 59 (13) | M 44(70%) | NA | NA | NA | 63/63 (100) | Dalteparin | NA | No | 6/63 (10) | 5/63 (8) | 0/63 (0) | Line thrombosis: 1/51 (2) | 2/63 (3) | 8/63 (13) |
Lodigiani et al. [53] | 61 | 61 (55–69) | M 49 (80%) | 11/61 (18) | Obesity: 28% | NA | 59/61 (97) | LMWH | 2/61 (3) | No | 4/61 (7) | 2/61 (3) | 1/61 (2) | Line thrombosis:1/61 (2) | 4/61 (7) | 8/61 (13) |
Beyls et al. [39] | 12 | 62 (56–66) | M 10 (83%) | NA | 29.5 (29.3 – 32.4) | 12/12 (100) | UFH on ECMO | UFH on ECMO | 12/12 (100) | No | 10/12 (83) | 1/12 (8) | 6/12 (50) | Cannula thrombosis 2/12 (17); ECMO Oxygenator thrombosis 1/12 (8) | NA | 10/12 (83) |
Maatman et al. [56] | 109 | 61 (16) | M 62 (57%) | 43/109 (39) | 34.8 (11.8) | NA | 102/109 (94) | UFH: 5,000 IU S/C t.d.s. Enoxaparin: 40 mg S/C o.d. or 30 mg S/C b.i.d | 7/109 (6) | No | 31/109 (28) | 5/109 (5) | 29/109 (27) | Line thrombosis:5/109 (5) | NA | 31/109 (28) |
Fraissé et al. [54] | 92 | 61 (55–70) | M 73 (79%) | 35/92 (38) | 30 (26–35) | NA | 43/92 (47) | LMWH | 49/92 (53) | No | 31/92 (34) | 25/92 (27) | 12/92 (13) | NA | 8/92 (9) | 37/92 (42) |
Al Samkari et al. [55] | 144 | 65 (32–97) | M 93 (65%) | 58/144 (40) | Obesity 62 (43%) | NA | 124/144 (86) | Unknown | 18/144 (13) | No | 11/144 (8) | NA | NA | Line thrombosis 2/144 (1); Circuit thrombosis (RRT): 8/12 (67) | 8/144 (6) | 26/144 (18) |
Hippensteel et al. [59] | 91 | NA | M 53 (58%) | 28/91 (31) | NA | 0/91 (0) | NA | Unknown | At start: none; later 24 anticoagulated for AF (n = 4) or unconfirmed VTE/hypercoagulability (n = 20) | No | 24/91 (26) | 5/91 (6) | 11/91 (12) | Internal jugular vein thrombus 8 (9) | NA | 24/91 (26) |
Desborough et al. [57] | 66 | 59 (49–66) | M 48 (73%) | 27/66 (41) | 28 (24–34) | 8/66 (27) | 55/66 (83) | Dalteparin (adjusted to weight and renal function) | 11/66 (17) | No | 10 / 66 (15) | 5/66 (8) | 6/66 (9) | NA | NA | 10/66 (15) |
Middeldorp et al. [30] | 75 | 62 (10) | M 58 (77%) | NA | 27 (24–29) | NA | 68/75 (91) | Nadroparin with weight adjustment. Dose increased mid-study for ICU patients | 7 (9.3) | Screening in 38/ 75 (51%) patients | 35/75 (47) | 11/75 (15) | 24/75 (32) | NA | NA | 35/75 (47) |
Parzy et al. [24] | 13 | 50 (43–62) | M 9 (70%) | 2/13 (15) | 31 (27–36) | 13/13 (100) | UFH on ECMO | UFH on ECMO (argatroban if HIT) | 11/11 (100) | Yes (Contrast CT) | 13/13 (100) | 3/13 (23) | 11/13 (85) | Oxygenator thrombosis: 1/13 (8) centrifugal pump thrombosis: 1/13 (8) | NA | 13/13 (100) |
Mak et al. [23] | 51 | 45 (26–66) | M 38 (75%) | NA | NA | 51 (100) | NA | NA | NA | Yes (CTPA) | NA | 18/51 (35) | NA | NA | NA | 18/51 (35) |
Longchamp et al. [22] | 25 | 68 (11) | 16 (64%) | 1 (4) | 27.5 (4.6) | NA | 23/25 (92) | Enoxaparin (according to weight) UFH | 2/25 (8) | Yes | 8/25 (32) | 5/25 (20) | 6/25 (24) | NA | NA | 8/25 (32) |
Voicu et al. [27] | 92 | 62 (53–69) | M 66 (72%) | 30 (33) | 28 (25–32) | NA | 68 (74) | LMWH UFH | 24 (26) | Yes | 48/92 (52) | 5/92 (5) | 44/92 (48) | NA | NA | 48/92 (52) |
Criel et al. [29] | 30 | 64.5 (11.8) | M 20 (67%) | 5/30 (17) | 30.3 (5.4) | 0/30 (0) | 30/30 | Exoxaparin 40 mg × 2 (or 60 mg × 2 if weight > 100 kg) | 0/30 (0) | Yes | 4/30 (13) | NA | 4/30 (13) | NA | NA | 4/30 (13) |
Llitjos et al. [26] | 26 | 68 (51.5–74.5) | M 20 (77%) | NA | 30.2 (25.5 – 33.5) | 2/26 (8) | 8/26 (31) | LMWH | 18/26 (69) | Yes | 24/26 (92) | 6/26 (23) | 18/26 (69) | NA | NA | 24/26 (92) |
Ren et al. [28] | 48 | 70 (62–80) | M 26 (54%) | 13/48 (27) | NA | NA | 47/48 (98) | LMWH | 0/48 (0) | Yes | 41/48 (85) | NA | 41/48 (85) | NA | NA | 41/48 (85) |
Nahum et al. [25] | 34 | 62.2 (8.6) | M 25 (74%) | 15/34 (44) | 31.4 (9.0) | 4/34 (12) | 34/34 (100) | Unknown | 0/34 (0) | Yes | 27/34 (79) | NA | 27/34 (79) | NA | NA | 27/34 (79) |