. 2022 Aug 20;62(10):2117–2136. doi: 10.1111/trf.17064

TABLE 4.

Grading of Recommendations Assessment, Development and Evaluation evidence profile

Certainty assessment							No. of patients		Effect		Certainty	Importance
No. of studies	Study design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	Prophylactic platelet transfusion	No prophylaxis	Relative (95% CI)	Absolute (95% CI)	Certainty	Importance
All‐cause mortality (low risk of bias trials only) ^a
1	Randomized trials	Not serious	Not serious	Not serious	Very serious ^b	None	4/298 (1.3%)	5/300 (1.7%)	RR 0.81 (0.22 to 2.97)	3 fewer per 1.000 (from 13 fewer to 33 more)	⊕⊕◯◯ Low	Critical
All‐cause mortality (all trials) ^a
5	Randomized trials	Serious ^c	Not serious ^d	Not serious ^e	Very serious ^f	None	27/714 (3.8%)	21/684 (3.1%)	RR 1.00 (0.59 to 1.69)	0 fewer per 1.000 (from 13 fewer to 21 more)	⊕◯◯◯ Very low	Critical
Proportion of participants with at least one episode of clinically important bleeding ^a
5	Randomized trials	Serious ^g	Serious ^h	Not serious ⁱ	Serious ^j	None	218/647 (33.7%)	284/629 (45.2%)	RR 0.70 (0.53 to 0.92)	135 fewer per 1.000 (from 212 fewer to 36 fewer)	⊕◯◯◯ Very low	Important
Days with clinically important bleeding ^a
2	Randomized trials	Serious ^k	Serious ^l	Not serious ^m	Not serious ⁿ	None	Stanworth 2013 reported a MD (95% CI) in number of days with clinically important bleeding of 0.5 (0.1–0.9) days fewer in the prophylaxis group versus the no prophylaxis group. Murphy 1982 reported a mean of 1.9 days with clinically important bleeding in the prophylaxis group versus 2.2 days in the no prophylaxis group.				⊕⊕◯◯ Low	Important
Proportion of participants with at least one nosocomial infection ^a
1	Randomized trials	Serious ^o	Not serious	Not serious ^p	Very serious ^q	None	14/466 (3.0%)	16/453 (3.5%)	RR 0.89 (0.40 to 1.97)	4 fewer per 1.000 (from 21 fewer to 34 more)	⊕◯◯◯ Very low	Important
Proportion of participants with at least one venous or arterial thromboembolism ^a —not reported
—	—	—	—	—	—	—	—	—	—	—	—	Important
Proportion of participants with at least one transfusion‐related adverse event ^a
3	Randomized trials	Serious ^r	Serious ^s	Not serious ^t	Very serious ^u	None	35/660 (5.3%)	27/650 (4.2%)	RR 2.54 (0.27 to 23.61)	64 more per 1.000 (from 30 fewer to 939 more)	⊕◯◯◯ Very low	Important
Days alive without the use of life support ^a —not reported
—	—	—	—	—	—	—	—	—	—	—	—	Important
Length of hospital stay ^a
3	Randomized trials	Serious ^v	Serious ^w	Not serious ^e	Not serious ^x	None	We were able to meta‐analyze data from Lye 2017 and Wandt 2012 which showed a MD (97.5% CI) in length of hospital stay of 0.23 days fewer (0.60 fewer to 0.13 more) in the prophylaxis group versus the no prophylaxis group. Stanworth 2013 reported the median (IQR) days to be 12 (9–18) versus 12 (9–18) in the prophylaxis group (n = 298) and no prophylaxis group (n = 300) respectively.				⊕⊕◯◯ Low	Important
Quality of life ^a —not reported
—	—	—	—	—	—	—	—	—	—	—	—	Important

Abbreviations: CI, confidence interval; IQR, interquartile range; MD, mean difference; RR, relative risks.

^{^a}

All outcomes were assessed at longest follow‐up.

^{^b}

Only one trial was included. There were very few events and CI around effect estimate includes substantial benefit and harm. Trial sequential analysis (TSA) could not be performed as the accrued information size (AIS) of 598 patients only corresponds to 0.59% of the required information size (RIS) of 102,293 patients. Thus, we rated down two levels.

^{^c}

Effect estimates in trials at overall low risk of bias versus trials at some concerns or high risk of bias does not seem to differ. However, there are very few events and CI a broad making judgment difficult. Only one trial was at overall low risk of bias and trials at some concerns or high risk of bias contributed with 84% of the weight in the meta‐analysis. Thus, we rated down one level.

^{^d}

We detected no statistical heterogeneity, I ² = 0% (p = .91), D ² = 0%. The Clinical Diversity in Meta‐analyses (CDIM) score was 11 corresponding to “low” clinical diversity. Thus, we did not to rate down for inconsistency.

^{^e}

Only trials conducted in the hematological and infectious disease ward setting contributed to the meta‐analysis. Results may not be applicable to other hospitalized patient populations (i.e., surgical patients, critically ill patients, neonates), but as the all trials reported on the defined patient population, we did not to rate down for indirectness.

^{^f}

The meta‐analysis included very few events and the CI around both the relative and absolute effect estimates include substantial benefit and harm. TSA could not be performed as the AIS of 1398 patients only corresponds to 2.0% of the RIS of 52,950 patients. Thus, we rated down two levels.

^{^g}

All trials were at some concerns or high for risk of bias. We chose to rate down one level as there is no information from low risk of bias trials and as it is thus impossible to estimate the effects of risk of bias.

^{^h}

We detected substantial statistical heterogeneity; I ² = 59% (p = .04), D ² = 72%. The CDIM score was 17 corresponding to moderate clinical heterogeneity. However, all effect estimates favored prophylaxis. Thus, we rated down one level.

^ⁱ

Only trials conducted in the hematological and infectious disease ward setting contributed to the meta‐analysis. Results may not be applicable to other hospitalized patient populations (i.e., surgical patients, critically ill patients, neonates), but as all trials reported on the defined patient population, we did not to rate down for indirectness.

^{^j}

TSA highlighted that the AIS of 1276 patients corresponds to 13.4% of the RIS of 9546 patients. The TSA adjusted CI: 0.26 to 1.87 includes both substantial benefit and harm corresponding to 334 fewer to 388 more per 1000 patients. As the D ² = 72% is high, the TSA adjusted CIs are broadened when using a random effects model. As we already rated down one level for inconsistency, we chose to only rate down one level for imprecision.

^{^k}

The trials was at some concerns or high risk of bias. We chose to rate down one level as there is no information from low risk of bias trials and as it is thus impossible to estimate the effects of risk of bias.

^{^l}

The CDIM score was 15 corresponding to moderate clinical diversity. Considering this and the sparsity of data, we chose to rate down one level.

^{^m}

The trials only reported on hematological patients for this outcome and results may not be applicable to other hospitalized patient populations (i.e., surgical patients, critically ill patients, children, neonates), but as the trials reported on the defined patient population, we chose not to rate down for indirectness.

^ⁿ

TSA (assuming alfa of 5% and a beta of 0.1 and a clinically relevant difference in means of 1 day) was redundant as more than 100% of the RIS of 261 had been obtained. Thus, we did not rate down.

^{^o}

The trial was at some concerns for risk of bias. We chose to rate down one level as there is no information from low risk of bias trials and as it is thus impossible to estimate the effects of risk of bias.

^{^p}

The trial reported on hematological patients for this outcome and results may not be applicable to other hospitalized patient populations (i.e., surgical patients, critically ill patients, children, neonates), but as the trials reported on the defined patient population, we chose not to rate down for indirectness.

^{^q}

TSA (assuming alfa of 5% and a beta of 0.1 and a clinically relevant risk reduction or increase of 15%) could not be performed as only 1.23% of the RIS of 48,730 patients had been accrued Therefore, we rate down two levels.

^{^r}

All trials were at some concerns for risk of bias. We chose to rate down one level as there is no information from low risk of bias trials and as it is thus impossible to estimate the effects of risk of bias.

^{^s}

We detected substantial statistical heterogeneity; I ² = 60% (p = .08), D ² = 94%. CDIM tool yielded a score of 13 corresponding to moderate clinical diversity. We chose to rate down one level.

^{^t}

Only trials conducted in the hematological and infectious disease ward setting contributed to the meta‐analysis. Results may not be applicable to other hospitalized patient populations (i.e., surgical patients, critically ill patients, neonates), but as all trials reported on the defined patient population, we did not to rate down for indirectness.

^{^u}

This analysis included very few events and CI around both the relative and absolute estimates of effect include substantial benefit and harm. TSA could not be performed as the AIS of 1310 patients only corresponds to 0.2% of the RIS of 73,050 patients. We chose to rate down two levels.

^{^v}

^{^w}

We observed no statistical heterogeneity I ² = 0%, D ² = 0% in the meta‐analysis which did not include the data from Stanworth 2013 because of different statistical summary data used (median, IQR). However, the CDIM tool yielded a score of 12 corresponding to moderate diversity. We chose to rate down one level.

^{^x}

TSA could not be performed as the RIS of 238 patients had already been accumulated within any of the two included trials.