Unfractionated heparin versus low molecular weight heparins for avoiding heparin‐induced thrombocytopenia in postoperative patients

Daniela R Junqueira; Liliane M Zorzela; Edson Perini

doi:10.1002/14651858.CD007557.pub3

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Figure 1

Flow diagram

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Figure 2

Flowchart illustrating the recruitment of the participants included in and extracted from the study reported by Levine 1991 and Warkentin 2003

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Figure 3

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies

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Figure 4

Risk of bias summary: review authors' judgements about each risk of bias item for each included study

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$Comparison 1 Low molecular weight heparin (LMWH) versus unfractionated heparin (UFH), Outcome 1 Heparin‐induced thrombocytopenia (HIT).$

Analysis 1.1

Comparison 1 Low molecular weight heparin (LMWH) versus unfractionated heparin (UFH), Outcome 1 Heparin‐induced thrombocytopenia (HIT).

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$Comparison 1 Low molecular weight heparin (LMWH) versus unfractionated heparin (UFH), Outcome 2 HIT in people undergoing major surgical procedures.$

Analysis 1.2

Comparison 1 Low molecular weight heparin (LMWH) versus unfractionated heparin (UFH), Outcome 2 HIT in people undergoing major surgical procedures.

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$Comparison 1 Low molecular weight heparin (LMWH) versus unfractionated heparin (UFH), Outcome 3 HIT complicated by venous thromboembolism.$

Analysis 1.3

Comparison 1 Low molecular weight heparin (LMWH) versus unfractionated heparin (UFH), Outcome 3 HIT complicated by venous thromboembolism.

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Summary of findings for the main comparison. Is unfractionated heparin (UFH) use better than low molecular weight heparin (LMWH) use to avoid heparin‐induced thrombocytopenia?

Is unfractionated heparin (UFH) use better than low molecular weight heparin (LMWH) use to avoid heparin‐induced thrombocytopenia?
Patient or population: people undergoing surgical procedures and treated with UFH or LMWH for prophylaxis of thrombotic events lasting at least 5 days Setting: hospital Intervention: LMWH Comparison: UFH
Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	№ of participants (studies)	Quality of the evidence (GRADE)	Comments
	Risk with UFH	Risk with LMWH
Heparin‐induced thrombocytopenia (HIT) Follow‐up: range 10 days to 14 days, or until discharge	Study population		RR 0.23 (0.07 to 0.73)	1398 (3 RCTs)	⊕⊕⊝⊝ Low^{1, 2}
	22 per 1000	5 per 1000 (2 to 16)
HIT in people undergoing major surgical procedures Follow‐up: range 10 days to 14 days, or until discharge	Study population		RR 0.22 (0.06 to 0.75)	586 (2 RCTs)	⊕⊕⊝⊝ Low^{1, 2}
	48 per 1000	11 per 1000 (3 to 36)
HIT complicated by venous thromboembolism Follow‐up: range 10 days to 14 days, or until discharge	Study population		RR 0.22 (0.06 to 0.84)	1398 (3 RCTs)	⊕⊕⊝⊝ Low^{1, 2}
	17 per 1000	4 per 1000 (1 to 14)
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI) CI: Confidence interval; HIT: heparin‐induced thrombocytopenia;LMWH: low molecular weight heparin; RR: Risk ratio; UFH: unfractionated heparin
GRADE Working Group grades of evidence High quality: We are very confident that the true effect lies close to that of the estimate of the effect Moderate quality: We are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different Low quality: Our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect Very low quality: We have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect
¹Downgraded by one level due to high risk and unclear risk of bias in the domains: selection bias, performance bias, detection and attrition bias. ²Downgraded by one level due to imprecision: small number of events and due to the fact that trials included in the analysis were underpowered to detect HIT.

Summary of findings for the main comparison. Is unfractionated heparin (UFH) use better than low molecular weight heparin (LMWH) use to avoid heparin‐induced thrombocytopenia?

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Table 1. Details of the dose, type of medication used and length of follow‐up

Study ID	UFH	Number of participants	Dose	LMWH	Number of participants	Dose	Treatment duration	Time point when plasma samples were obtained for HIT‐IgG antibodies test	Laboratory test for HIT
Warkentin 2003	Standard calcium heparin	192	7500 U sc twice daily	Enoxaparin	170	30 mg sc twice daily	Started 12 h‐24 h after surgery and continued for 14 days or until discharge if it occurred sooner	At least 1 plasma sample obtained on postoperative day 7 or later	SRA, with confirmatory investigation for the presence of functional antibodies of IgG class
Lubenow 2010a	Standard UFH	289	5000 U SC 3 times daily	Certoparin	272	3000 anti‐factor Xa U sc once daily	Started immediately after admission and continued until day 10 or until discharge. After day 10 all participants received LMWH	Obtained on admission, at discharge (if before day 10) and between days 10 and 14	Anti‐platelet factor 4/heparin for immunoglobulin IgG class and platelet‐activating antibodies in the HIPA test
PROTECT 2011	Standard UFH	238	5000 U sc twice daily	Dalteparin	237	5000 U once daily	At least 5 days of heparin in the ICU	Data were collected daily in the ICU	Commercially available platelet factor 4 ELISA and SRA
ELISA: enzyme‐linked immunosorbent assay HIPA: heparin‐induced platelet activation h: hours HIT: heparin‐induced thrombocytopenia ICU: intensive care unit LMWH: low molecular weight heparin mg: milligrams sc: subcutaneously SRA: serotonin release assay U: units UFH: unfractionated heparin

Table 1. Details of the dose, type of medication used and length of follow‐up

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Comparison 1. Low molecular weight heparin (LMWH) versus unfractionated heparin (UFH)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Heparin‐induced thrombocytopenia (HIT) Show forest plot	3	1398	Risk Ratio (M‐H, Fixed, 95% CI)	0.23 [0.07, 0.73]

2 HIT in people undergoing major surgical procedures Show forest plot	2	586	Risk Ratio (M‐H, Fixed, 95% CI)	0.22 [0.06, 0.75]

3 HIT complicated by venous thromboembolism Show forest plot	3	1398	Risk Ratio (M‐H, Fixed, 95% CI)	0.22 [0.06, 0.84]

Comparison 1. Low molecular weight heparin (LMWH) versus unfractionated heparin (UFH)

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